2025
Otuya, David O; Liu, Zhongyu; Joseph, Reny; Hanafy, Mohammed A; Vijaykumar, Kadambari; Stanford, Denise; Raju, S Vamsee; Baker, Elizabeth H; Rowe, Steven M; Tearney, Guillermo J; Solomon, George M
Toward in vivo bronchoscopic functional CFTR assessment using a short circuit current measurement probe Journal Article
In: Am J Physiol Lung Cell Mol Physiol, vol. 328, no. 2, pp. L313โL320, 2025, ISSN: 1522-1504.
@article{pmid39601216,
title = {Toward in vivo bronchoscopic functional CFTR assessment using a short circuit current measurement probe},
author = {David O Otuya and Zhongyu Liu and Reny Joseph and Mohammed A Hanafy and Kadambari Vijaykumar and Denise Stanford and S Vamsee Raju and Elizabeth H Baker and Steven M Rowe and Guillermo J Tearney and George M Solomon},
doi = {10.1152/ajplung.00137.2024},
issn = {1522-1504},
year = {2025},
date = {2025-02-01},
journal = {Am J Physiol Lung Cell Mol Physiol},
volume = {328},
number = {2},
pages = {L313--L320},
abstract = {The epithelial lining of luminal organs provides an immune barrier against external factors and regulates the transport of nutrients, ions, and water into the body. Several conditions are associated with the breakdown or dysfunction of the epithelial lining. Short circuit current () measurement using a bulky, expensive, and hard-to-deploy system known as the Ussing chamber is the gold standard for evaluation of epithelial transport function but requires tissue excision. We demonstrated the ability of the probe to measure in normal wild type (WT) versus reduced cystic fibrosis transmembrane conductance regulator (CFTR) function knockout (KO) rats as a relevant animal model for testing ion channel function. We have conducted short circuit current measurements in animal models in vivo for studying cystic fibrosis transmembrane conductance regulator (CFTR) and ion channel restoration.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The epithelial lining of luminal organs provides an immune barrier against external factors and regulates the transport of nutrients, ions, and water into the body. Several conditions are associated with the breakdown or dysfunction of the epithelial lining. Short circuit current () measurement using a bulky, expensive, and hard-to-deploy system known as the Ussing chamber is the gold standard for evaluation of epithelial transport function but requires tissue excision. We demonstrated the ability of the probe to measure in normal wild type (WT) versus reduced cystic fibrosis transmembrane conductance regulator (CFTR) function knockout (KO) rats as a relevant animal model for testing ion channel function. We have conducted short circuit current measurements in animal models in vivo for studying cystic fibrosis transmembrane conductance regulator (CFTR) and ion channel restoration.
2024
Kelly, Paul; VanBuskirk, Kelley; Coomes, David; Mouksassi, Samer; Smith, Gerald; Jamil, Zehra; Hossain, Md Shabab; Syed, Sana; Marie, Chelsea; Tarr, Phillip I; Sullivan, Peter B; Petri, William A; Denno, Donna M; Ahmed, Tahmeed; Mahfuz, Mustafa; Ali, S Asad; Moore, Sean R; Ndao, I Malick; Tearney, Guillermo J; Yilmaz, รmer H; Raghavan, Shyam S; Moskaluk, Christopher A; and, Ta-Chiang Liu
In: Am J Clin Nutr, vol. 120 Suppl 1, pp. S15โS30, 2024, ISSN: 1938-3207.
@article{pmid39300660,
title = {Histopathology underlying environmental enteric dysfunction in a cohort study of undernourished children in Bangladesh, Pakistan, and Zambia compared with United States children},
author = {Paul Kelly and Kelley VanBuskirk and David Coomes and Samer Mouksassi and Gerald Smith and Zehra Jamil and Md Shabab Hossain and Sana Syed and Chelsea Marie and Phillip I Tarr and Peter B Sullivan and William A Petri and Donna M Denno and Tahmeed Ahmed and Mustafa Mahfuz and S Asad Ali and Sean R Moore and I Malick Ndao and Guillermo J Tearney and รmer H Yilmaz and Shyam S Raghavan and Christopher A Moskaluk and Ta-Chiang Liu and },
doi = {10.1016/j.ajcnut.2024.02.028},
issn = {1938-3207},
year = {2024},
date = {2024-09-01},
journal = {Am J Clin Nutr},
volume = {120 Suppl 1},
pages = {S15--S30},
abstract = {BACKGROUND: Environmental enteric dysfunction (EED) is an asymptomatic intestinal disorder associated with growth impairment, delayed neurocognitive development, and impaired oral vaccine responses.nnOBJECTIVES: We set out to develop and validate a histopathologic scoring system on duodenal biopsies from a cohort study of children with growth failure in Bangladesh, Pakistan, and Zambia ("EED") with reference to biopsies from United States children with no clinically reported histologic pathology (referred to hereafter as "normal") or celiac disease.nnMETHODS: Five gastrointestinal pathologists evaluated 745 hematoxylin and eosin slide images from 291 children with EED (mean age: 1.6 y) and 66 United States children (mean age: 6.8 y). Histomorphologic features (i.e., villus/crypt architecture, goblet cells, epithelial and lamina propria acute/chronic inflammation, Brunner's glands, Paneth cells, epithelial detachment, enterocyte injury, and foveolar metaplasia) were used to score each histopathologic slide. Generalized estimating equations were used to determine differences between EED, normal, and celiac disease, and receiver operating characteristic curves were used to assess predictive value.nnRESULTS: Biopsies from the duodenal bulb showed higher intramucosal Brunner's gland scores and lower intraepithelial lymphocyte scores than from the second or third parts of the duodenum (D2/3), so only D2/3 were included in the final analysis. Although 7 parameters differed significantly between EED and normal biopsies in regression models, only 5 (blunted villus architecture, increased intraepithelial lymphocytosis, goblet cell depletion, Paneth cell depletion, and reduced intramucosal Brunner's glands) were required to create a total score percentage (TSP-5) that correctly identified EED against normal biopsies (AUC: 0.992; 95% CI: 0.983, 0.998). Geographic comparisons showed more severe goblet cell depletion in Bangladesh and more marked intraepithelial lymphocytosis in Pakistan.nnCONCLUSIONS: This scoring system involving 5 histologic parameters demonstrates very high discrimination between EED and normal biopsies, indicating that this scoring system can be applied with confidence to studies of intestinal biopsies in EED.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: Environmental enteric dysfunction (EED) is an asymptomatic intestinal disorder associated with growth impairment, delayed neurocognitive development, and impaired oral vaccine responses.nnOBJECTIVES: We set out to develop and validate a histopathologic scoring system on duodenal biopsies from a cohort study of children with growth failure in Bangladesh, Pakistan, and Zambia (“EED”) with reference to biopsies from United States children with no clinically reported histologic pathology (referred to hereafter as “normal”) or celiac disease.nnMETHODS: Five gastrointestinal pathologists evaluated 745 hematoxylin and eosin slide images from 291 children with EED (mean age: 1.6 y) and 66 United States children (mean age: 6.8 y). Histomorphologic features (i.e., villus/crypt architecture, goblet cells, epithelial and lamina propria acute/chronic inflammation, Brunner’s glands, Paneth cells, epithelial detachment, enterocyte injury, and foveolar metaplasia) were used to score each histopathologic slide. Generalized estimating equations were used to determine differences between EED, normal, and celiac disease, and receiver operating characteristic curves were used to assess predictive value.nnRESULTS: Biopsies from the duodenal bulb showed higher intramucosal Brunner’s gland scores and lower intraepithelial lymphocyte scores than from the second or third parts of the duodenum (D2/3), so only D2/3 were included in the final analysis. Although 7 parameters differed significantly between EED and normal biopsies in regression models, only 5 (blunted villus architecture, increased intraepithelial lymphocytosis, goblet cell depletion, Paneth cell depletion, and reduced intramucosal Brunner’s glands) were required to create a total score percentage (TSP-5) that correctly identified EED against normal biopsies (AUC: 0.992; 95% CI: 0.983, 0.998). Geographic comparisons showed more severe goblet cell depletion in Bangladesh and more marked intraepithelial lymphocytosis in Pakistan.nnCONCLUSIONS: This scoring system involving 5 histologic parameters demonstrates very high discrimination between EED and normal biopsies, indicating that this scoring system can be applied with confidence to studies of intestinal biopsies in EED.
Tufaro, Vincenzo; Jaffer, Farouc A; Serruys, Patrick W; Onuma, Yoshinobu; van der Steen, Antonius F W; Stone, Gregg W; Muller, James E; Marcu, Laura; Soest, Gijs Van; Courtney, Brian K; Tearney, Guillermo J; Bourantas, Christos V
Emerging Hybrid Intracoronary Imaging Technologies and Their Applications in Clinical Practice andย Research Journal Article
In: JACC Cardiovasc Interv, vol. 17, no. 17, pp. 1963โ1979, 2024, ISSN: 1876-7605.
@article{pmid39260958,
title = {Emerging Hybrid Intracoronary Imaging Technologies and Their Applications in Clinical Practice andย Research},
author = {Vincenzo Tufaro and Farouc A Jaffer and Patrick W Serruys and Yoshinobu Onuma and Antonius F W van der Steen and Gregg W Stone and James E Muller and Laura Marcu and Gijs Van Soest and Brian K Courtney and Guillermo J Tearney and Christos V Bourantas},
doi = {10.1016/j.jcin.2024.07.007},
issn = {1876-7605},
year = {2024},
date = {2024-09-01},
journal = {JACC Cardiovasc Interv},
volume = {17},
number = {17},
pages = {1963--1979},
abstract = {Intravascular ultrasound and optical coherence tomography are used with increasing frequency for the care of coronary patients and in research studies. These imaging tools can identify culprit lesions in acute coronary syndromes, assess coronary stenosis severity, guide percutaneous coronary intervention (PCI), and detect vulnerable plaques and patients. However, they have significant limitations that have stimulated the development of multimodality intracoronary imaging catheters, which provide improvements in assessing vessel wall pathology and guiding PCI. Prototypes combining 2 or even 3 imaging probes with complementary attributes have been developed, and several multimodality systems have already been used in patients, with near-infrared spectroscopy intravascular ultrasound-based studies showing promising results for the identification of high-risk plaques. Moreover, postmortem histology studies have documented that hybrid imaging catheters can enable more accurate characterization of plaque morphology than standalone imaging. This review describes the evolution in the field of hybrid intracoronary imaging; presents the available multimodality catheters; andย discusses their potential role in PCI guidance, vulnerable plaque detection, and the assessment of endovascular devices and emerging pharmacotherapies targeting atherosclerosis.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Intravascular ultrasound and optical coherence tomography are used with increasing frequency for the care of coronary patients and in research studies. These imaging tools can identify culprit lesions in acute coronary syndromes, assess coronary stenosis severity, guide percutaneous coronary intervention (PCI), and detect vulnerable plaques and patients. However, they have significant limitations that have stimulated the development of multimodality intracoronary imaging catheters, which provide improvements in assessing vessel wall pathology and guiding PCI. Prototypes combining 2 or even 3 imaging probes with complementary attributes have been developed, and several multimodality systems have already been used in patients, with near-infrared spectroscopy intravascular ultrasound-based studies showing promising results for the identification of high-risk plaques. Moreover, postmortem histology studies have documented that hybrid imaging catheters can enable more accurate characterization of plaque morphology than standalone imaging. This review describes the evolution in the field of hybrid intracoronary imaging; presents the available multimodality catheters; andย discusses their potential role in PCI guidance, vulnerable plaque detection, and the assessment of endovascular devices and emerging pharmacotherapies targeting atherosclerosis.
Lever, Jacelyn E Peabody; Turner, K Brett; Fernandez, Courtney M; Leung, Hui Min; Hussain, Shah Saddad; Shei, Ren-Jay; Lin, Vivian Y; Birket, Susan E; Chu, Kengyeh K; Tearney, Guillermo J; Rowe, Steven M; Solomon, George M
Metachrony drives effective mucociliary transport via a calcium-dependent mechanism Journal Article
In: Am J Physiol Lung Cell Mol Physiol, vol. 327, no. 3, pp. L282โL292, 2024, ISSN: 1522-1504.
@article{pmid38860289,
title = {Metachrony drives effective mucociliary transport via a calcium-dependent mechanism},
author = {Jacelyn E Peabody Lever and K Brett Turner and Courtney M Fernandez and Hui Min Leung and Shah Saddad Hussain and Ren-Jay Shei and Vivian Y Lin and Susan E Birket and Kengyeh K Chu and Guillermo J Tearney and Steven M Rowe and George M Solomon},
doi = {10.1152/ajplung.00392.2023},
issn = {1522-1504},
year = {2024},
date = {2024-09-01},
journal = {Am J Physiol Lung Cell Mol Physiol},
volume = {327},
number = {3},
pages = {L282--L292},
abstract = {The mucociliary transport apparatus is critical for maintaining lung health via the coordinated movement of cilia to clear mucus and particulates. A metachronal wave propagates across the epithelium when cilia on adjacent multiciliated cells beat slightly out of phase along the proximal-distal axis of the airways in alignment with anatomically directed mucociliary clearance. We hypothesized that metachrony optimizes mucociliary transport (MCT) and that disruptions of calcium signaling would abolish metachrony and decrease MCT. We imaged bronchi from human explants and ferret tracheae using micro-optical coherence tomography (ยตOCT) to evaluate airway surface liquid depth (ASL), periciliary liquid depth (PCL), cilia beat frequency (CBF), MCT, and metachrony in situ. We developed statistical models that included covariates of MCT. Ferret tracheae were treated with BAPTA-AM (chelator of intracellular Ca), lanthanum chloride (nonpermeable Cachannel competitive antagonist), and repaglinide (inhibitor of calaxin) to test calcium dependence of metachrony. We demonstrated that metachrony contributes to mucociliary transport of human and ferret airways. MCT was augmented in regions of metachrony compared with nonmetachronous regions by 48.1%, = 0.0009 or 47.5%, < 0.0020 in humans and ferrets, respectively. PCL and metachrony were independent contributors to MCT rate in humans; ASL, CBF, and metachrony contribute to ferret MCT rates. Metachrony can be disrupted by interference with calcium signaling including intracellular, mechanosensitive channels, and calaxin. Our results support that the presence of metachrony augments MCT in a calcium-dependent mechanism. We developed a novel imaging-based analysis to detect coordination of ciliary motion and optimal coordination, a process called metachrony. We found that metachrony is key to the optimization of ciliary-mediated mucus transport in both ferret and human tracheal tissue. This process appears to be regulated through calcium-dependent mechanisms. This study demonstrates the capacity to measure a key feature of ciliary coordination that may be important in genetic and acquired disorders of ciliary function.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The mucociliary transport apparatus is critical for maintaining lung health via the coordinated movement of cilia to clear mucus and particulates. A metachronal wave propagates across the epithelium when cilia on adjacent multiciliated cells beat slightly out of phase along the proximal-distal axis of the airways in alignment with anatomically directed mucociliary clearance. We hypothesized that metachrony optimizes mucociliary transport (MCT) and that disruptions of calcium signaling would abolish metachrony and decrease MCT. We imaged bronchi from human explants and ferret tracheae using micro-optical coherence tomography (ยตOCT) to evaluate airway surface liquid depth (ASL), periciliary liquid depth (PCL), cilia beat frequency (CBF), MCT, and metachrony in situ. We developed statistical models that included covariates of MCT. Ferret tracheae were treated with BAPTA-AM (chelator of intracellular Ca), lanthanum chloride (nonpermeable Cachannel competitive antagonist), and repaglinide (inhibitor of calaxin) to test calcium dependence of metachrony. We demonstrated that metachrony contributes to mucociliary transport of human and ferret airways. MCT was augmented in regions of metachrony compared with nonmetachronous regions by 48.1%, = 0.0009 or 47.5%, < 0.0020 in humans and ferrets, respectively. PCL and metachrony were independent contributors to MCT rate in humans; ASL, CBF, and metachrony contribute to ferret MCT rates. Metachrony can be disrupted by interference with calcium signaling including intracellular, mechanosensitive channels, and calaxin. Our results support that the presence of metachrony augments MCT in a calcium-dependent mechanism. We developed a novel imaging-based analysis to detect coordination of ciliary motion and optimal coordination, a process called metachrony. We found that metachrony is key to the optimization of ciliary-mediated mucus transport in both ferret and human tracheal tissue. This process appears to be regulated through calcium-dependent mechanisms. This study demonstrates the capacity to measure a key feature of ciliary coordination that may be important in genetic and acquired disorders of ciliary function.
Harris, Elex S; McIntire, Hannah J; Mazur, Marina; Schulz-Hildebrandt, Hinnerk; Leung, Hui Min; Tearney, Guillermo J; Krick, Stefanie; Rowe, Steven M; Barnes, Jarrod W
Reduced sialylation of airway mucin impairs mucus transport by altering the biophysical properties of mucin Journal Article
In: Sci Rep, vol. 14, no. 1, pp. 16568, 2024, ISSN: 2045-2322.
@article{pmid39019950,
title = {Reduced sialylation of airway mucin impairs mucus transport by altering the biophysical properties of mucin},
author = {Elex S Harris and Hannah J McIntire and Marina Mazur and Hinnerk Schulz-Hildebrandt and Hui Min Leung and Guillermo J Tearney and Stefanie Krick and Steven M Rowe and Jarrod W Barnes},
doi = {10.1038/s41598-024-66510-2},
issn = {2045-2322},
year = {2024},
date = {2024-07-01},
journal = {Sci Rep},
volume = {14},
number = {1},
pages = {16568},
abstract = {Mucus stasis is a pathologic hallmark of muco-obstructive diseases, including cystic fibrosis (CF). Mucins, the principal component of mucus, are extensively modified with hydroxyl (O)-linked glycans, which are largely terminated by sialic acid. Sialic acid is a negatively charged monosaccharide and contributes to the biochemical/biophysical properties of mucins. Reports suggest that mucin sialylation may be altered in CF; however, the consequences of reduced sialylation on mucus clearance have not been fully determined. Here, we investigated the consequences of reduced sialylation on the charge state and conformation of the most prominent airway mucin, MUC5B, and defined the functional consequences of reduced sialylation on mucociliary transport (MCT). Reduced sialylation contributed to a lower charged MUC5B form and decreased polymer expansion. The inhibition of total mucin sialylation de novo impaired MCT in primary human bronchial epithelial cells and rat airways, and specific ฮฑ-2,3 sialylation blockade was sufficient to recapitulate these findings. Finally, we show that ST3 beta-galactoside alpha-2,3-sialyltransferase (ST3Gal1) expression is downregulated in CF and partially restored by correcting CFTR via Elexacaftor/Tezacaftor/Ivacaftor treatment. Overall, this study demonstrates the importance of mucin sialylation in mucus clearance and identifies decreased sialylation by ST3Gal1 as a possible therapeutic target in CF and potentially other muco-obstructive diseases.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Mucus stasis is a pathologic hallmark of muco-obstructive diseases, including cystic fibrosis (CF). Mucins, the principal component of mucus, are extensively modified with hydroxyl (O)-linked glycans, which are largely terminated by sialic acid. Sialic acid is a negatively charged monosaccharide and contributes to the biochemical/biophysical properties of mucins. Reports suggest that mucin sialylation may be altered in CF; however, the consequences of reduced sialylation on mucus clearance have not been fully determined. Here, we investigated the consequences of reduced sialylation on the charge state and conformation of the most prominent airway mucin, MUC5B, and defined the functional consequences of reduced sialylation on mucociliary transport (MCT). Reduced sialylation contributed to a lower charged MUC5B form and decreased polymer expansion. The inhibition of total mucin sialylation de novo impaired MCT in primary human bronchial epithelial cells and rat airways, and specific ฮฑ-2,3 sialylation blockade was sufficient to recapitulate these findings. Finally, we show that ST3 beta-galactoside alpha-2,3-sialyltransferase (ST3Gal1) expression is downregulated in CF and partially restored by correcting CFTR via Elexacaftor/Tezacaftor/Ivacaftor treatment. Overall, this study demonstrates the importance of mucin sialylation in mucus clearance and identifies decreased sialylation by ST3Gal1 as a possible therapeutic target in CF and potentially other muco-obstructive diseases.
Liu, Guigen; Ahn, Sebastian W; Kang, Jeon Woong; Bhagavatula, Sharath; Matthew, Destiny; Martin, Samantha; Marlin, Courtney; So, Peter T C; Tearney, Guillermo J; Jonas, Oliver
Two-site microendoscopic imaging probe for simultaneous three-dimensional imaging at two anatomic locations in tissues Journal Article
In: Opt Lett, vol. 49, no. 12, pp. 3312โ3315, 2024, ISSN: 1539-4794.
@article{pmid38875608,
title = {Two-site microendoscopic imaging probe for simultaneous three-dimensional imaging at two anatomic locations in tissues},
author = {Guigen Liu and Sebastian W Ahn and Jeon Woong Kang and Sharath Bhagavatula and Destiny Matthew and Samantha Martin and Courtney Marlin and Peter T C So and Guillermo J Tearney and Oliver Jonas},
doi = {10.1364/OL.525945},
issn = {1539-4794},
year = {2024},
date = {2024-06-01},
journal = {Opt Lett},
volume = {49},
number = {12},
pages = {3312--3315},
abstract = {Systems that can image in three dimensions at cellular resolution and across different locations within an organism may enable insights into complex biological processes, such as immune responses, for which a single location measurement may be insufficient. In this Letter, we describe an in vivo two-site imaging probe (TIP) that can simultaneously image two anatomic sites with a maximum separation of a few centimeters. The TIP consists of two identical bendable graded index (GRIN) lenses and is demonstrated by a two-photon two-color fluorescence imaging system. Each GRIN lens has a field of view of 162โร162โร170โ
ยตm, a nominal numerical aperture of 0.5, a magnification of 0.7, and working distances of 0.2โ
mm in air for both ends. A blind linear unmixing algorithm is applied to suppress bleedthrough between channels. We use this system to successfully demonstrate two-site two-photon two-color imaging of two biomedically relevant samples, i.e., (1) a mixture of two autofluorescent anti-cancer drugs and (2) a live hybrid tumor consisting of two spectrally distinct fluorescent cell lines.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Systems that can image in three dimensions at cellular resolution and across different locations within an organism may enable insights into complex biological processes, such as immune responses, for which a single location measurement may be insufficient. In this Letter, we describe an in vivo two-site imaging probe (TIP) that can simultaneously image two anatomic sites with a maximum separation of a few centimeters. The TIP consists of two identical bendable graded index (GRIN) lenses and is demonstrated by a two-photon two-color fluorescence imaging system. Each GRIN lens has a field of view of 162โร162โร170โ
ยตm, a nominal numerical aperture of 0.5, a magnification of 0.7, and working distances of 0.2โ
mm in air for both ends. A blind linear unmixing algorithm is applied to suppress bleedthrough between channels. We use this system to successfully demonstrate two-site two-photon two-color imaging of two biomedically relevant samples, i.e., (1) a mixture of two autofluorescent anti-cancer drugs and (2) a live hybrid tumor consisting of two spectrally distinct fluorescent cell lines.
Ikegami, Ryutaro; Piao, Zhonglie; Iglesias, Juan F; Pilgrim, Thomas; Ha, Khanh; McCarthy, Jason R; Castellanos, Maria I; Kassab, Mohamad B; Albagdadi, Mazen S; Mauskapf, Adam; Spicer, Graham; Kandzari, David E; Edelman, Elazer R; Libby, Peter; Heg, Dik; Joner, Michael; Tearney, Guillermo J; Jaffer, Farouc A
Ultrathin-strut versus thin-strut stent healing and outcomes in preclinical and clinical subjects Journal Article
In: EuroIntervention, vol. 20, no. 10, pp. e669โe680, 2024, ISSN: 1969-6213.
@article{pmid38776143,
title = {Ultrathin-strut versus thin-strut stent healing and outcomes in preclinical and clinical subjects},
author = {Ryutaro Ikegami and Zhonglie Piao and Juan F Iglesias and Thomas Pilgrim and Khanh Ha and Jason R McCarthy and Maria I Castellanos and Mohamad B Kassab and Mazen S Albagdadi and Adam Mauskapf and Graham Spicer and David E Kandzari and Elazer R Edelman and Peter Libby and Dik Heg and Michael Joner and Guillermo J Tearney and Farouc A Jaffer},
doi = {10.4244/EIJ-D-23-00563},
issn = {1969-6213},
year = {2024},
date = {2024-05-01},
journal = {EuroIntervention},
volume = {20},
number = {10},
pages = {e669--e680},
abstract = {BACKGROUND: Compared with thin-strut durable-polymer drug-eluting stents (DP-DES), ultrathin-strut biodegradable-polymer sirolimus-eluting stents (BP-SES) improve stent-related clinical outcomes in patients undergoing percutaneous coronary intervention (PCI). Reduced stent strut thickness is hypothesised to underlie these benefits, but this conjecture remains unproven.nnAIMS: We aimed to assess the impact of strut thickness on stent healing and clinical outcomes between ultrathin-strut and thin-strut BP-SES.nnMETHODS: First, we performed a preclinical study of 8 rabbits implanted with non-overlapping thin-strut (diameter/thickness 3.5 mm/80 ฮผm) and ultrathin-strut (diameter/thickness 3.0 mm/60 ฮผm) BP-SES in the infrarenal aorta. On day 7, the rabbits underwent intravascular near-infrared fluorescence optical coherence tomography (NIRF-OCT) molecular-structural imaging of fibrin deposition and stent tissue coverage, followed by histopathological analysis. Second, we conducted an individual data pooled analysis of patients enrolled in the BIOSCIENCE and BIOSTEMI randomised PCI trials treated with ultrathin-strut (n=282) or thin-strut (n=222) BP-SES. The primary endpoint was target lesion failure (TLF) at 1-year follow-up, with a landmark analysis at 30 days.nnRESULTS: NIRF-OCT image analyses revealed that ultrathin-strut and thin-strut BP-SES exhibited similar stent fibrin deposition (p=0.49) and percentage of uncovered stent struts (p=0.63). Histopathological assessments corroรborated these findings. In 504 pooled randomised trial patients, TLF rates were similar for those treated with ultrathin-strut or thin-strut BP-SES at 30-day (2.5% vs 1.8%; p=0.62) and 1-year follow-up (4.3% vs 4.7%; p=0.88).nnCONCLUSIONS: Ultrathin-strut and thin-strut BP-SES demonstrate similar early arterial healing profiles and 30-day and 1-year clinical outcomes.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: Compared with thin-strut durable-polymer drug-eluting stents (DP-DES), ultrathin-strut biodegradable-polymer sirolimus-eluting stents (BP-SES) improve stent-related clinical outcomes in patients undergoing percutaneous coronary intervention (PCI). Reduced stent strut thickness is hypothesised to underlie these benefits, but this conjecture remains unproven.nnAIMS: We aimed to assess the impact of strut thickness on stent healing and clinical outcomes between ultrathin-strut and thin-strut BP-SES.nnMETHODS: First, we performed a preclinical study of 8 rabbits implanted with non-overlapping thin-strut (diameter/thickness 3.5 mm/80 ฮผm) and ultrathin-strut (diameter/thickness 3.0 mm/60 ฮผm) BP-SES in the infrarenal aorta. On day 7, the rabbits underwent intravascular near-infrared fluorescence optical coherence tomography (NIRF-OCT) molecular-structural imaging of fibrin deposition and stent tissue coverage, followed by histopathological analysis. Second, we conducted an individual data pooled analysis of patients enrolled in the BIOSCIENCE and BIOSTEMI randomised PCI trials treated with ultrathin-strut (n=282) or thin-strut (n=222) BP-SES. The primary endpoint was target lesion failure (TLF) at 1-year follow-up, with a landmark analysis at 30 days.nnRESULTS: NIRF-OCT image analyses revealed that ultrathin-strut and thin-strut BP-SES exhibited similar stent fibrin deposition (p=0.49) and percentage of uncovered stent struts (p=0.63). Histopathological assessments corroรborated these findings. In 504 pooled randomised trial patients, TLF rates were similar for those treated with ultrathin-strut or thin-strut BP-SES at 30-day (2.5% vs 1.8%; p=0.62) and 1-year follow-up (4.3% vs 4.7%; p=0.88).nnCONCLUSIONS: Ultrathin-strut and thin-strut BP-SES demonstrate similar early arterial healing profiles and 30-day and 1-year clinical outcomes.
Ali, Ziad A; Dager, Antonio; Zรบรฑiga, Mauricio; Fonseca, Jaime; Arana, Camilo; Chamiรฉ, Daniel; Hill, Jonathan M; Madder, Ryan D; Muller, James E; Simonton, Charles A; Tearney, Guillermo J; Stone, Gregg W
First-in-Human Experience With a Novel Multimodality DeepOCT-NIRS Intracoronary Imaging System Journal Article
In: J Soc Cardiovasc Angiogr Interv, vol. 3, no. 4, pp. 101344, 2024, ISSN: 2772-9303.
@article{pmid39130176,
title = {First-in-Human Experience With a Novel Multimodality DeepOCT-NIRS Intracoronary Imaging System},
author = {Ziad A Ali and Antonio Dager and Mauricio Zรบรฑiga and Jaime Fonseca and Camilo Arana and Daniel Chamiรฉ and Jonathan M Hill and Ryan D Madder and James E Muller and Charles A Simonton and Guillermo J Tearney and Gregg W Stone},
doi = {10.1016/j.jscai.2024.101344},
issn = {2772-9303},
year = {2024},
date = {2024-04-01},
journal = {J Soc Cardiovasc Angiogr Interv},
volume = {3},
number = {4},
pages = {101344},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Vijaykumar, Kadambari; Leung, Hui Min; Barrios, Amilcar; Wade, Justin; Hathorne, Heather Y; Nichols, David P; Tearney, Guillermo J; Rowe, Steven M; Solomon, George M
In: Heliyon, vol. 10, no. 8, pp. e29188, 2024, ISSN: 2405-8440.
@article{pmid38681615b,
title = {Longitudinal improvements in clinical and functional outcomes following initiation of elexacaftor/tezacaftor/ivacaftor in patients with cystic fibrosis},
author = {Kadambari Vijaykumar and Hui Min Leung and Amilcar Barrios and Justin Wade and Heather Y Hathorne and David P Nichols and Guillermo J Tearney and Steven M Rowe and George M Solomon},
doi = {10.1016/j.heliyon.2024.e29188},
issn = {2405-8440},
year = {2024},
date = {2024-04-01},
journal = {Heliyon},
volume = {10},
number = {8},
pages = {e29188},
abstract = {BACKGROUND: Use of elexacaftor/tezacaftor/ivacaftor (ETI) for treatment of cystic fibrosis (CF) has resulted in unprecedented clinical improvements necessitating development of outcome measures for monitoring disease course. Intranasal micro-optical coherence tomography (ฮผOCT) has previously helped detect and characterize mucociliary abnormalities in patients with CF. This study was done to determine if ฮผOCT can define the effects of ETI on nasal mucociliary clearance and monitor changes conferred to understand mechanistic effects of CFTR modulators beyond CFTR activation.nnMETHODS: 26 subjects, with at least 1 F508del mutation were recruited and followed at baseline (visit 1), +1 month (visit 2) and +6 months (visit 4) following initiation of ETI therapy. Clinical outcomes were computed at visits 1, 2 and 4. Intranasal ฮผOCT imaging and functional metrics analysis including mucociliary transport rate (MCT) estimation were done at visits 1 and 2.nnRESULTS: Percent predicted forced expiratory volume in 1ย s (ppFEV) showed a significant increase of +10.9ย % at visit 2, which sustained at visit 4 (+10.6ย %). Sweat chloride levels significantly decreased by -36.6ย mmol/L and -41.3ย mmol/L at visits 2 and 4, respectively. ฮผOCT analysis revealed significant improvement in MCT rate (2.8ย ยฑย 1.5, visit 1 vs 4.0ย ยฑย 1.5ย mm/min, visit 2; Pย =ย 0.048).nnCONCLUSIONS: Treatment with ETI resulted in significant and sustained clinical improvements over 6 months. Functional improvements in MCT rate were evident within a month after initiation of ETI therapy indicating that ฮผOCT imaging is sensitive to the treatment effect of HEMT and suggests improved mucociliary transport as a probable mechanism of action underlying the clinical benefits.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: Use of elexacaftor/tezacaftor/ivacaftor (ETI) for treatment of cystic fibrosis (CF) has resulted in unprecedented clinical improvements necessitating development of outcome measures for monitoring disease course. Intranasal micro-optical coherence tomography (ฮผOCT) has previously helped detect and characterize mucociliary abnormalities in patients with CF. This study was done to determine if ฮผOCT can define the effects of ETI on nasal mucociliary clearance and monitor changes conferred to understand mechanistic effects of CFTR modulators beyond CFTR activation.nnMETHODS: 26 subjects, with at least 1 F508del mutation were recruited and followed at baseline (visit 1), +1 month (visit 2) and +6 months (visit 4) following initiation of ETI therapy. Clinical outcomes were computed at visits 1, 2 and 4. Intranasal ฮผOCT imaging and functional metrics analysis including mucociliary transport rate (MCT) estimation were done at visits 1 and 2.nnRESULTS: Percent predicted forced expiratory volume in 1ย s (ppFEV) showed a significant increase of +10.9ย % at visit 2, which sustained at visit 4 (+10.6ย %). Sweat chloride levels significantly decreased by -36.6ย mmol/L and -41.3ย mmol/L at visits 2 and 4, respectively. ฮผOCT analysis revealed significant improvement in MCT rate (2.8ย ยฑย 1.5, visit 1 vs 4.0ย ยฑย 1.5ย mm/min, visit 2; Pย =ย 0.048).nnCONCLUSIONS: Treatment with ETI resulted in significant and sustained clinical improvements over 6 months. Functional improvements in MCT rate were evident within a month after initiation of ETI therapy indicating that ฮผOCT imaging is sensitive to the treatment effect of HEMT and suggests improved mucociliary transport as a probable mechanism of action underlying the clinical benefits.
Schulz-Hildebrandt, Hinnerk; Spasic, Svetolik; Hou, Fang; Ting, Kuan-Chung; Batts, Shelley; Tearney, Guillermo; Stankovic, Konstantina M
Dynamic micro-optical coherence tomography enables structural and metabolic imaging of the mammalian cochlea Journal Article
In: Front Mol Neurosci, vol. 17, pp. 1436837, 2024, ISSN: 1662-5099.
@article{pmid39449964,
title = {Dynamic micro-optical coherence tomography enables structural and metabolic imaging of the mammalian cochlea},
author = {Hinnerk Schulz-Hildebrandt and Svetolik Spasic and Fang Hou and Kuan-Chung Ting and Shelley Batts and Guillermo Tearney and Konstantina M Stankovic},
doi = {10.3389/fnmol.2024.1436837},
issn = {1662-5099},
year = {2024},
date = {2024-01-01},
journal = {Front Mol Neurosci},
volume = {17},
pages = {1436837},
abstract = {Sensorineural hearing loss (SNHL) is caused by damage to the mechanosensory hair cells and auditory neurons of the cochlea. The development of imaging tools that can directly visualize or provide functional information about a patient's cochlear cells is critical to identify the pathobiological defect and determine the cells' receptiveness to emerging SNHL treatments. However, the cochlea's small size, embedded location within dense bone, and sensitivity to perturbation have historically precluded high-resolution clinical imaging. Previously, we developed micro-optical coherence tomography (ฮผOCT) as a platform for otologic imaging in animal models and human cochleae. Here we report on advancing ฮผOCT technology to obtain simultaneously acquired and co-localized images of cell viability/metabolic activity through dynamic ฮผOCT (DฮผOCT) imaging of intracellular motion. DฮผOCT obtains cross-sectional images of ATP-dependent movement of intracellular organelles and cytoskeletal polymerization by acquiring sequential ฮผOCT images and computing intensity fluctuation frequency metrics on a pixel-wise basis. Using a customized benchtop DฮผOCT system, we demonstrate the detailed resolution of anatomical and metabolic features of cells within the organ of Corti, via an apical cochleostomy, in freshly-excised adult mouse cochleae. Further, we show that DฮผOCT is capable of capturing rapid changes in cochlear cell metabolism following an ototoxic insult to induce cell death and actin stabilization. Notably, as few as 6 frames can be used to reconstruct cochlear DฮผOCT images with sufficient detail to discern individual cells and their metabolic state. Taken together, these results motivate future development of a DฮผOCT imaging probe for cellular and metabolic diagnosis of SNHL in humans.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Sensorineural hearing loss (SNHL) is caused by damage to the mechanosensory hair cells and auditory neurons of the cochlea. The development of imaging tools that can directly visualize or provide functional information about a patient’s cochlear cells is critical to identify the pathobiological defect and determine the cells’ receptiveness to emerging SNHL treatments. However, the cochlea’s small size, embedded location within dense bone, and sensitivity to perturbation have historically precluded high-resolution clinical imaging. Previously, we developed micro-optical coherence tomography (ฮผOCT) as a platform for otologic imaging in animal models and human cochleae. Here we report on advancing ฮผOCT technology to obtain simultaneously acquired and co-localized images of cell viability/metabolic activity through dynamic ฮผOCT (DฮผOCT) imaging of intracellular motion. DฮผOCT obtains cross-sectional images of ATP-dependent movement of intracellular organelles and cytoskeletal polymerization by acquiring sequential ฮผOCT images and computing intensity fluctuation frequency metrics on a pixel-wise basis. Using a customized benchtop DฮผOCT system, we demonstrate the detailed resolution of anatomical and metabolic features of cells within the organ of Corti, via an apical cochleostomy, in freshly-excised adult mouse cochleae. Further, we show that DฮผOCT is capable of capturing rapid changes in cochlear cell metabolism following an ototoxic insult to induce cell death and actin stabilization. Notably, as few as 6 frames can be used to reconstruct cochlear DฮผOCT images with sufficient detail to discern individual cells and their metabolic state. Taken together, these results motivate future development of a DฮผOCT imaging probe for cellular and metabolic diagnosis of SNHL in humans.
Nishimiya, Kensuke; Sharma, Gargi; Singh, Kanwarpal; Ahsen, Osman O; Gardecki, Joseph A; Tearney, Guillermo J
Imaging human coronary cholesterol/urate crystals with cross-polarized micro-optical coherence tomography Journal Article
In: Front Cardiovasc Med, vol. 11, pp. 1433227, 2024, ISSN: 2297-055X.
@article{pmid39529973,
title = {Imaging human coronary cholesterol/urate crystals with cross-polarized micro-optical coherence tomography},
author = {Kensuke Nishimiya and Gargi Sharma and Kanwarpal Singh and Osman O Ahsen and Joseph A Gardecki and Guillermo J Tearney},
doi = {10.3389/fcvm.2024.1433227},
issn = {2297-055X},
year = {2024},
date = {2024-01-01},
journal = {Front Cardiovasc Med},
volume = {11},
pages = {1433227},
abstract = {INTRODUCTION: Birefringent crystals such as monosodium-urate (MSU) and cholesterol crystals (CC) likely contribute to the progression of coronary artery disease (CAD) due to their potential to exacerbate inflammation through inflammatory cytokine activation. Here, we present cross-polarized micro-optical coherence tomography (CP-ยตOCT) for visualizing individual birefringent crystals in human coronary arteries.nnMETHODS AND RESULTS: Human cadaver coronary arteries with a history of CAD with or without gout were dissected for CP-ยตOCT imaging. Specimens were processed for histological identification of birefringence under polarization light microscopy (PLM). CP-ยตOCT visualized needle-crystals that appeared as long projections in orthogonal planes, and PLM confirmed that CP-ยตOCT-delineated needle-crystals demonstrated negative birefringence. The needle-crystals were dissolved after immersion in uricase (โ<โ0.05), and thus were MSU. CP-ยตOCT was three-dimensionally volume-rendered for counting MSU and CCs in 79 regions of interest sized [750 ()โรโ500 ()โรโ400 () ยตm]. Crystal counts were normalized by the total coronary length utilized. The relationship between CP-ยตOCT-delineated MSU counts and those seen in corresponding histology, and the difference in coronary MSU amongst gout vs. non-gout patients was analyzed. CP-ยตOCT-delineated MSU counts were significantly correlated with MSU counted by PLM-based histology (โ=โ0.98, โ<โ0.01), and with histology-derived intimal thickening (โ=โ0.51, โ<โ0.01). MSU and CCs were both significantly greater in gout patients compared with non-gout patients (โ<โ0.05).nnDISCUSSION: These results demonstrate a significant increase in CP-ยตOCT-delineated crystals in gout vs. non-gout patients, suggesting that this technology can be used to improve our understanding of crystal-driven coronary pathogenesis.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
INTRODUCTION: Birefringent crystals such as monosodium-urate (MSU) and cholesterol crystals (CC) likely contribute to the progression of coronary artery disease (CAD) due to their potential to exacerbate inflammation through inflammatory cytokine activation. Here, we present cross-polarized micro-optical coherence tomography (CP-ยตOCT) for visualizing individual birefringent crystals in human coronary arteries.nnMETHODS AND RESULTS: Human cadaver coronary arteries with a history of CAD with or without gout were dissected for CP-ยตOCT imaging. Specimens were processed for histological identification of birefringence under polarization light microscopy (PLM). CP-ยตOCT visualized needle-crystals that appeared as long projections in orthogonal planes, and PLM confirmed that CP-ยตOCT-delineated needle-crystals demonstrated negative birefringence. The needle-crystals were dissolved after immersion in uricase (โ<โ0.05), and thus were MSU. CP-ยตOCT was three-dimensionally volume-rendered for counting MSU and CCs in 79 regions of interest sized [750 ()โรโ500 ()โรโ400 () ยตm]. Crystal counts were normalized by the total coronary length utilized. The relationship between CP-ยตOCT-delineated MSU counts and those seen in corresponding histology, and the difference in coronary MSU amongst gout vs. non-gout patients was analyzed. CP-ยตOCT-delineated MSU counts were significantly correlated with MSU counted by PLM-based histology (โ=โ0.98, โ<โ0.01), and with histology-derived intimal thickening (โ=โ0.51, โ<โ0.01). MSU and CCs were both significantly greater in gout patients compared with non-gout patients (โ<โ0.05).nnDISCUSSION: These results demonstrate a significant increase in CP-ยตOCT-delineated crystals in gout vs. non-gout patients, suggesting that this technology can be used to improve our understanding of crystal-driven coronary pathogenesis.
2023
Cho, Do-Yeon; Zhang, Shaoyan; Skinner, Daniel; Koch, Connor G; Smith, Metta J; Lim, Dong-Jin; Grayson, Jessica W; Tearney, Guillermo J; Rowe, Steven M; Woodworth, Bradford A
Red ginseng aqueous extract improves mucociliary transport dysfunction and histopathology in CF rat airways Journal Article
In: J Cyst Fibros, vol. 22, no. 6, pp. 1113โ1119, 2023, ISSN: 1873-5010.
@article{pmid37704464b,
title = {Red ginseng aqueous extract improves mucociliary transport dysfunction and histopathology in CF rat airways},
author = {Do-Yeon Cho and Shaoyan Zhang and Daniel Skinner and Connor G Koch and Metta J Smith and Dong-Jin Lim and Jessica W Grayson and Guillermo J Tearney and Steven M Rowe and Bradford A Woodworth},
doi = {10.1016/j.jcf.2023.09.002},
issn = {1873-5010},
year = {2023},
date = {2023-11-01},
journal = {J Cyst Fibros},
volume = {22},
number = {6},
pages = {1113--1119},
abstract = {BACKGROUND: We previously discovered that Korean red ginseng aqueous extract (RGAE) potentiates the TMEM16A channel, improved mucociliary transport (MCT) parameters in CF nasal epithelia in vitro, and thus could serve as a therapeutic strategy to rescue the MCT defect in cystic fibrosis (CF) airways. The hypothesis of this study is that RGAE can improve epithelial Cl secretion, MCT, and histopathology in an in-vivo CF rat model.nnMETHODS: Seventeen 4-month old CFTR rats were randomly assigned to receive daily oral control (saline, nย =ย 9) or RGAE (Ginsenosides 0.4mg/kg/daily, nย =ย 8) for 4 weeks. Outcomes included nasal Cl secretion measured with the nasal potential difference (NPD), functional microanatomy of the trachea using micro-optical coherence tomography, histopathology, and immunohistochemical staining for TMEM16a.nnRESULTS: RGAE-treated CF rats had greater mean NPD polarization with UTP (controlย =ย -5.48 +/- 2.87 mV, RGAEย =ย -9.49 +/- 2.99ย mV, pย <ย 0.05), indicating, at least in part, potentiation of UTP-mediated Cl secretion through TMEM16A. All measured tracheal MCT parameters (airway surface liquid, periciliary liquid, ciliary beat frequency, MCT) were significantly increased in RGAE-treated CF rats with MCT exhibiting a 3-fold increase (control, 0.45+/-0.31 vs. RGAE, 1.45+/-0.66 mm/min, pย <ย 0.01). Maxillary mucosa histopathology was markedly improved in RGAE-treated cohort (reduced intracellular mucus, goblet cells with no distention, and shorter epithelial height). TMEM16A expression was similar between groups.nnCONCLUSION: RGAE improves TMEM16A-mediated transepithelial Cl secretion, functional microanatomy, and histopathology in CF rats. Therapeutic strategies utilizing TMEM16A potentiators to treat CF airway disease are appropriate and provide a new avenue for mutation-independent therapies.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: We previously discovered that Korean red ginseng aqueous extract (RGAE) potentiates the TMEM16A channel, improved mucociliary transport (MCT) parameters in CF nasal epithelia in vitro, and thus could serve as a therapeutic strategy to rescue the MCT defect in cystic fibrosis (CF) airways. The hypothesis of this study is that RGAE can improve epithelial Cl secretion, MCT, and histopathology in an in-vivo CF rat model.nnMETHODS: Seventeen 4-month old CFTR rats were randomly assigned to receive daily oral control (saline, nย =ย 9) or RGAE (Ginsenosides 0.4mg/kg/daily, nย =ย 8) for 4 weeks. Outcomes included nasal Cl secretion measured with the nasal potential difference (NPD), functional microanatomy of the trachea using micro-optical coherence tomography, histopathology, and immunohistochemical staining for TMEM16a.nnRESULTS: RGAE-treated CF rats had greater mean NPD polarization with UTP (controlย =ย -5.48 +/- 2.87 mV, RGAEย =ย -9.49 +/- 2.99ย mV, pย <ย 0.05), indicating, at least in part, potentiation of UTP-mediated Cl secretion through TMEM16A. All measured tracheal MCT parameters (airway surface liquid, periciliary liquid, ciliary beat frequency, MCT) were significantly increased in RGAE-treated CF rats with MCT exhibiting a 3-fold increase (control, 0.45+/-0.31 vs. RGAE, 1.45+/-0.66 mm/min, pย <ย 0.01). Maxillary mucosa histopathology was markedly improved in RGAE-treated cohort (reduced intracellular mucus, goblet cells with no distention, and shorter epithelial height). TMEM16A expression was similar between groups.nnCONCLUSION: RGAE improves TMEM16A-mediated transepithelial Cl secretion, functional microanatomy, and histopathology in CF rats. Therapeutic strategies utilizing TMEM16A potentiators to treat CF airway disease are appropriate and provide a new avenue for mutation-independent therapies.
Ahmed, Mona E; Hakim, Diaa; Stone, Peter H
The plaque hypothesis: understanding mechanisms of plaque progression and destabilization, and implications for clinical management Journal Article
In: Curr Opin Cardiol, vol. 38, no. 6, pp. 496โ503, 2023, ISSN: 1531-7080.
@article{pmid37767898,
title = {The plaque hypothesis: understanding mechanisms of plaque progression and destabilization, and implications for clinical management},
author = {Mona E Ahmed and Diaa Hakim and Peter H Stone},
doi = {10.1097/HCO.0000000000001077},
issn = {1531-7080},
year = {2023},
date = {2023-11-01},
journal = {Curr Opin Cardiol},
volume = {38},
number = {6},
pages = {496--503},
abstract = {PURPOSE OF REVIEW: Major adverse cardiac events (MACE) typically arise from nonflow-limiting coronary artery disease and not from flow-limiting obstructions that cause ischemia. This review elaborates the current understanding of the mechanism(s) for plaque development, progression, and destabilization and how identification of these high-risk features can optimally inform clinical management.nnRECENT FINDINGS: Advanced invasive and noninvasive coronary imaging and computational postprocessing enhance an understanding of pathobiologic/pathophysiologic features of coronary artery plaques prone to destabilization and MACE. Early investigations of high-risk plaques focused on anatomic and biochemical characteristics (large plaque burden, severe luminal obstruction, thin cap fibroatheroma morphology, and large lipid pool), but more recent studies underscore that additional factors, particularly biomechanical factors [low endothelial shear stress (ESS), high ESS gradient, plaque structural stress, and axial plaque stress], provide the critical incremental stimulus acting on the anatomic substrate to provoke plaque destabilization. These destabilizing features are often located in areas distant from the flow-limiting obstruction or may exist in plaques without any flow limitation. Identification of these high-risk, synergistic plaque features enable identification of plaques prone to destabilize regardless of the presence or absence of a severe obstruction (Plaque Hypothesis).nnSUMMARY: Local plaque topography, hemodynamic patterns, and internal plaque constituents constitute high-risk features that may be located along the entire course of the coronary plaque, including both flow-limiting and nonflow-limiting regions. For coronary interventions to have optimal clinical impact, it will be critical to direct their application to the plaque area(s) at highest risk.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
PURPOSE OF REVIEW: Major adverse cardiac events (MACE) typically arise from nonflow-limiting coronary artery disease and not from flow-limiting obstructions that cause ischemia. This review elaborates the current understanding of the mechanism(s) for plaque development, progression, and destabilization and how identification of these high-risk features can optimally inform clinical management.nnRECENT FINDINGS: Advanced invasive and noninvasive coronary imaging and computational postprocessing enhance an understanding of pathobiologic/pathophysiologic features of coronary artery plaques prone to destabilization and MACE. Early investigations of high-risk plaques focused on anatomic and biochemical characteristics (large plaque burden, severe luminal obstruction, thin cap fibroatheroma morphology, and large lipid pool), but more recent studies underscore that additional factors, particularly biomechanical factors [low endothelial shear stress (ESS), high ESS gradient, plaque structural stress, and axial plaque stress], provide the critical incremental stimulus acting on the anatomic substrate to provoke plaque destabilization. These destabilizing features are often located in areas distant from the flow-limiting obstruction or may exist in plaques without any flow limitation. Identification of these high-risk, synergistic plaque features enable identification of plaques prone to destabilize regardless of the presence or absence of a severe obstruction (Plaque Hypothesis).nnSUMMARY: Local plaque topography, hemodynamic patterns, and internal plaque constituents constitute high-risk features that may be located along the entire course of the coronary plaque, including both flow-limiting and nonflow-limiting regions. For coronary interventions to have optimal clinical impact, it will be critical to direct their application to the plaque area(s) at highest risk.
Cho, Do-Yeon; Zhang, Shaoyan; Skinner, Daniel; Koch, Connor G; Smith, Metta J; Lim, Dong-Jin; Grayson, Jessica W; Tearney, Guillermo J; Rowe, Steven M; Woodworth, Bradford A
Red ginseng aqueous extract improves mucociliary transport dysfunction and histopathology in CF rat airways Journal Article
In: J Cyst Fibros, vol. 22, no. 6, pp. 1113โ1119, 2023, ISSN: 1873-5010.
@article{pmid37704464,
title = {Red ginseng aqueous extract improves mucociliary transport dysfunction and histopathology in CF rat airways},
author = {Do-Yeon Cho and Shaoyan Zhang and Daniel Skinner and Connor G Koch and Metta J Smith and Dong-Jin Lim and Jessica W Grayson and Guillermo J Tearney and Steven M Rowe and Bradford A Woodworth},
doi = {10.1016/j.jcf.2023.09.002},
issn = {1873-5010},
year = {2023},
date = {2023-11-01},
journal = {J Cyst Fibros},
volume = {22},
number = {6},
pages = {1113--1119},
abstract = {BACKGROUND: We previously discovered that Korean red ginseng aqueous extract (RGAE) potentiates the TMEM16A channel, improved mucociliary transport (MCT) parameters in CF nasal epithelia in vitro, and thus could serve as a therapeutic strategy to rescue the MCT defect in cystic fibrosis (CF) airways. The hypothesis of this study is that RGAE can improve epithelial Cl secretion, MCT, and histopathology in an in-vivo CF rat model.nnMETHODS: Seventeen 4-month old CFTR rats were randomly assigned to receive daily oral control (saline, nย =ย 9) or RGAE (Ginsenosides 0.4mg/kg/daily, nย =ย 8) for 4 weeks. Outcomes included nasal Cl secretion measured with the nasal potential difference (NPD), functional microanatomy of the trachea using micro-optical coherence tomography, histopathology, and immunohistochemical staining for TMEM16a.nnRESULTS: RGAE-treated CF rats had greater mean NPD polarization with UTP (controlย =ย -5.48 +/- 2.87 mV, RGAEย =ย -9.49 +/- 2.99ย mV, pย <ย 0.05), indicating, at least in part, potentiation of UTP-mediated Cl secretion through TMEM16A. All measured tracheal MCT parameters (airway surface liquid, periciliary liquid, ciliary beat frequency, MCT) were significantly increased in RGAE-treated CF rats with MCT exhibiting a 3-fold increase (control, 0.45+/-0.31 vs. RGAE, 1.45+/-0.66 mm/min, pย <ย 0.01). Maxillary mucosa histopathology was markedly improved in RGAE-treated cohort (reduced intracellular mucus, goblet cells with no distention, and shorter epithelial height). TMEM16A expression was similar between groups.nnCONCLUSION: RGAE improves TMEM16A-mediated transepithelial Cl secretion, functional microanatomy, and histopathology in CF rats. Therapeutic strategies utilizing TMEM16A potentiators to treat CF airway disease are appropriate and provide a new avenue for mutation-independent therapies.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: We previously discovered that Korean red ginseng aqueous extract (RGAE) potentiates the TMEM16A channel, improved mucociliary transport (MCT) parameters in CF nasal epithelia in vitro, and thus could serve as a therapeutic strategy to rescue the MCT defect in cystic fibrosis (CF) airways. The hypothesis of this study is that RGAE can improve epithelial Cl secretion, MCT, and histopathology in an in-vivo CF rat model.nnMETHODS: Seventeen 4-month old CFTR rats were randomly assigned to receive daily oral control (saline, nย =ย 9) or RGAE (Ginsenosides 0.4mg/kg/daily, nย =ย 8) for 4 weeks. Outcomes included nasal Cl secretion measured with the nasal potential difference (NPD), functional microanatomy of the trachea using micro-optical coherence tomography, histopathology, and immunohistochemical staining for TMEM16a.nnRESULTS: RGAE-treated CF rats had greater mean NPD polarization with UTP (controlย =ย -5.48 +/- 2.87 mV, RGAEย =ย -9.49 +/- 2.99ย mV, pย <ย 0.05), indicating, at least in part, potentiation of UTP-mediated Cl secretion through TMEM16A. All measured tracheal MCT parameters (airway surface liquid, periciliary liquid, ciliary beat frequency, MCT) were significantly increased in RGAE-treated CF rats with MCT exhibiting a 3-fold increase (control, 0.45+/-0.31 vs. RGAE, 1.45+/-0.66 mm/min, pย <ย 0.01). Maxillary mucosa histopathology was markedly improved in RGAE-treated cohort (reduced intracellular mucus, goblet cells with no distention, and shorter epithelial height). TMEM16A expression was similar between groups.nnCONCLUSION: RGAE improves TMEM16A-mediated transepithelial Cl secretion, functional microanatomy, and histopathology in CF rats. Therapeutic strategies utilizing TMEM16A potentiators to treat CF airway disease are appropriate and provide a new avenue for mutation-independent therapies.
Yuan, Feng; Gasser, Grace N; Lemire, Evan; Montoro, Daniel T; Jagadeesh, Karthik; Zhang, Yan; Duan, Yifan; Ievlev, Vitaly; Wells, Kristen L; Rotti, Pavana G; Shahin, Weam; Winter, Michael; Rosen, Bradley H; Evans, Idil; Cai, Qian; Yu, Miao; Walsh, Susan A; Acevedo, Michael R; Pandya, Darpan N; Akurathi, Vamsidhar; Dick, David W; Wadas, Thaddeus J; Joo, Nam Soo; Wine, Jeffrey J; Birket, Susan; Fernandez, Courtney M; Leung, Hui Min; Tearney, Guillermo J; Verkman, Alan S; Haggie, Peter M; Scott, Kathleen; Bartels, Douglas; Meyerholz, David K; Rowe, Steven M; Liu, Xiaoming; Yan, Ziying; Haber, Adam L; Sun, Xingshen; Engelhardt, John F
Transgenic ferret models define pulmonary ionocyte diversity and function Journal Article
In: Nature, vol. 621, no. 7980, pp. 857โ867, 2023, ISSN: 1476-4687.
@article{pmid37730992c,
title = {Transgenic ferret models define pulmonary ionocyte diversity and function},
author = {Feng Yuan and Grace N Gasser and Evan Lemire and Daniel T Montoro and Karthik Jagadeesh and Yan Zhang and Yifan Duan and Vitaly Ievlev and Kristen L Wells and Pavana G Rotti and Weam Shahin and Michael Winter and Bradley H Rosen and Idil Evans and Qian Cai and Miao Yu and Susan A Walsh and Michael R Acevedo and Darpan N Pandya and Vamsidhar Akurathi and David W Dick and Thaddeus J Wadas and Nam Soo Joo and Jeffrey J Wine and Susan Birket and Courtney M Fernandez and Hui Min Leung and Guillermo J Tearney and Alan S Verkman and Peter M Haggie and Kathleen Scott and Douglas Bartels and David K Meyerholz and Steven M Rowe and Xiaoming Liu and Ziying Yan and Adam L Haber and Xingshen Sun and John F Engelhardt},
doi = {10.1038/s41586-023-06549-9},
issn = {1476-4687},
year = {2023},
date = {2023-09-01},
journal = {Nature},
volume = {621},
number = {7980},
pages = {857--867},
abstract = {Speciation leads to adaptive changes in organ cellular physiology and creates challenges for studying rare cell-type functions that diverge between humans and mice. Rare cystic fibrosis transmembrane conductance regulator (CFTR)-rich pulmonary ionocytes exist throughout the cartilaginous airways of humans, but limited presence and divergent biology in the proximal trachea of mice has prevented the use of traditional transgenic models to elucidate ionocyte functions in the airway. Here we describe the creation and use of conditional genetic ferret models to dissect pulmonary ionocyte biology and function by enabling ionocyte lineage tracing (FOXI1-Cre::ROSA-TG), ionocyte ablation (FOXI1-KO) and ionocyte-specific deletion of CFTR (FOXI1-Cre::CFTR). By comparing these models with cystic fibrosis ferrets, we demonstrate that ionocytes control airway surface liquid absorption, secretion, pH and mucus viscosity-leading to reduced airway surface liquid volume and impaired mucociliary clearance in cystic fibrosis, FOXI1-KO and FOXI1-Cre::CFTR ferrets. These processes are regulated by CFTR-dependent ionocyte transport of Cl and HCO. Single-cell transcriptomics and in vivo lineage tracing revealed three subtypes of pulmonary ionocytes and a FOXI1-lineage common rare cell progenitor for ionocytes, tuft cells and neuroendocrine cells during airway development. Thus, rare pulmonary ionocytes perform critical CFTR-dependent functions in the proximal airway that are hallmark features of cystic fibrosis airway disease. These studies provide a road map for using conditional genetics in the first non-rodent mammal to address gene function, cell biology and disease processes that have greater evolutionary conservation between humans and ferrets.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Speciation leads to adaptive changes in organ cellular physiology and creates challenges for studying rare cell-type functions that diverge between humans and mice. Rare cystic fibrosis transmembrane conductance regulator (CFTR)-rich pulmonary ionocytes exist throughout the cartilaginous airways of humans, but limited presence and divergent biology in the proximal trachea of mice has prevented the use of traditional transgenic models to elucidate ionocyte functions in the airway. Here we describe the creation and use of conditional genetic ferret models to dissect pulmonary ionocyte biology and function by enabling ionocyte lineage tracing (FOXI1-Cre::ROSA-TG), ionocyte ablation (FOXI1-KO) and ionocyte-specific deletion of CFTR (FOXI1-Cre::CFTR). By comparing these models with cystic fibrosis ferrets, we demonstrate that ionocytes control airway surface liquid absorption, secretion, pH and mucus viscosity-leading to reduced airway surface liquid volume and impaired mucociliary clearance in cystic fibrosis, FOXI1-KO and FOXI1-Cre::CFTR ferrets. These processes are regulated by CFTR-dependent ionocyte transport of Cl and HCO. Single-cell transcriptomics and in vivo lineage tracing revealed three subtypes of pulmonary ionocytes and a FOXI1-lineage common rare cell progenitor for ionocytes, tuft cells and neuroendocrine cells during airway development. Thus, rare pulmonary ionocytes perform critical CFTR-dependent functions in the proximal airway that are hallmark features of cystic fibrosis airway disease. These studies provide a road map for using conditional genetics in the first non-rodent mammal to address gene function, cell biology and disease processes that have greater evolutionary conservation between humans and ferrets.
Yuan, Feng; Gasser, Grace N; Lemire, Evan; Montoro, Daniel T; Jagadeesh, Karthik; Zhang, Yan; Duan, Yifan; Ievlev, Vitaly; Wells, Kristen L; Rotti, Pavana G; Shahin, Weam; Winter, Michael; Rosen, Bradley H; Evans, Idil; Cai, Qian; Yu, Miao; Walsh, Susan A; Acevedo, Michael R; Pandya, Darpan N; Akurathi, Vamsidhar; Dick, David W; Wadas, Thaddeus J; Joo, Nam Soo; Wine, Jeffrey J; Birket, Susan; Fernandez, Courtney M; Leung, Hui Min; Tearney, Guillermo J; Verkman, Alan S; Haggie, Peter M; Scott, Kathleen; Bartels, Douglas; Meyerholz, David K; Rowe, Steven M; Liu, Xiaoming; Yan, Ziying; Haber, Adam L; Sun, Xingshen; Engelhardt, John F
Transgenic ferret models define pulmonary ionocyte diversity and function Journal Article
In: Nature, vol. 621, no. 7980, pp. 857โ867, 2023, ISSN: 1476-4687.
@article{pmid37730992b,
title = {Transgenic ferret models define pulmonary ionocyte diversity and function},
author = {Feng Yuan and Grace N Gasser and Evan Lemire and Daniel T Montoro and Karthik Jagadeesh and Yan Zhang and Yifan Duan and Vitaly Ievlev and Kristen L Wells and Pavana G Rotti and Weam Shahin and Michael Winter and Bradley H Rosen and Idil Evans and Qian Cai and Miao Yu and Susan A Walsh and Michael R Acevedo and Darpan N Pandya and Vamsidhar Akurathi and David W Dick and Thaddeus J Wadas and Nam Soo Joo and Jeffrey J Wine and Susan Birket and Courtney M Fernandez and Hui Min Leung and Guillermo J Tearney and Alan S Verkman and Peter M Haggie and Kathleen Scott and Douglas Bartels and David K Meyerholz and Steven M Rowe and Xiaoming Liu and Ziying Yan and Adam L Haber and Xingshen Sun and John F Engelhardt},
doi = {10.1038/s41586-023-06549-9},
issn = {1476-4687},
year = {2023},
date = {2023-09-01},
journal = {Nature},
volume = {621},
number = {7980},
pages = {857--867},
abstract = {Speciation leads to adaptive changes in organ cellular physiology and creates challenges for studying rare cell-type functions that diverge between humans and mice. Rare cystic fibrosis transmembrane conductance regulator (CFTR)-rich pulmonary ionocytes exist throughout the cartilaginous airways of humans, but limited presence and divergent biology in the proximal trachea of mice has prevented the use of traditional transgenic models to elucidate ionocyte functions in the airway. Here we describe the creation and use of conditional genetic ferret models to dissect pulmonary ionocyte biology and function by enabling ionocyte lineage tracing (FOXI1-Cre::ROSA-TG), ionocyte ablation (FOXI1-KO) and ionocyte-specific deletion of CFTR (FOXI1-Cre::CFTR). By comparing these models with cystic fibrosis ferrets, we demonstrate that ionocytes control airway surface liquid absorption, secretion, pH and mucus viscosity-leading to reduced airway surface liquid volume and impaired mucociliary clearance in cystic fibrosis, FOXI1-KO and FOXI1-Cre::CFTR ferrets. These processes are regulated by CFTR-dependent ionocyte transport of Cl and HCO. Single-cell transcriptomics and in vivo lineage tracing revealed three subtypes of pulmonary ionocytes and a FOXI1-lineage common rare cell progenitor for ionocytes, tuft cells and neuroendocrine cells during airway development. Thus, rare pulmonary ionocytes perform critical CFTR-dependent functions in the proximal airway that are hallmark features of cystic fibrosis airway disease. These studies provide a road map for using conditional genetics in the first non-rodent mammal to address gene function, cell biology and disease processes that have greater evolutionary conservation between humans and ferrets.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Speciation leads to adaptive changes in organ cellular physiology and creates challenges for studying rare cell-type functions that diverge between humans and mice. Rare cystic fibrosis transmembrane conductance regulator (CFTR)-rich pulmonary ionocytes exist throughout the cartilaginous airways of humans, but limited presence and divergent biology in the proximal trachea of mice has prevented the use of traditional transgenic models to elucidate ionocyte functions in the airway. Here we describe the creation and use of conditional genetic ferret models to dissect pulmonary ionocyte biology and function by enabling ionocyte lineage tracing (FOXI1-Cre::ROSA-TG), ionocyte ablation (FOXI1-KO) and ionocyte-specific deletion of CFTR (FOXI1-Cre::CFTR). By comparing these models with cystic fibrosis ferrets, we demonstrate that ionocytes control airway surface liquid absorption, secretion, pH and mucus viscosity-leading to reduced airway surface liquid volume and impaired mucociliary clearance in cystic fibrosis, FOXI1-KO and FOXI1-Cre::CFTR ferrets. These processes are regulated by CFTR-dependent ionocyte transport of Cl and HCO. Single-cell transcriptomics and in vivo lineage tracing revealed three subtypes of pulmonary ionocytes and a FOXI1-lineage common rare cell progenitor for ionocytes, tuft cells and neuroendocrine cells during airway development. Thus, rare pulmonary ionocytes perform critical CFTR-dependent functions in the proximal airway that are hallmark features of cystic fibrosis airway disease. These studies provide a road map for using conditional genetics in the first non-rodent mammal to address gene function, cell biology and disease processes that have greater evolutionary conservation between humans and ferrets.
Zhang, Yihan; Lin, Tian; Leung, Hui Min; Zhang, Cheng; Wilson-Mifsud, Brittany; Feldman, Michael B; Puel, Anne; Lanternier, Fanny; Couderc, Louis-Jean; Danion, Francois; Catherinot, Emilie; Salvator, Hรฉlรจne; Tcherkian, Colas; Givel, Claire; Xu, Jie; Tearney, Guillermo J; Vyas, Jatin M; Li, Hu; Hurley, Bryan P; Mou, Hongmei
STAT3 mutation-associated airway epithelial defects in Job syndrome Journal Article
In: J Allergy Clin Immunol, vol. 152, no. 2, pp. 538โ550, 2023, ISSN: 1097-6825.
@article{pmid36638921,
title = {STAT3 mutation-associated airway epithelial defects in Job syndrome},
author = {Yihan Zhang and Tian Lin and Hui Min Leung and Cheng Zhang and Brittany Wilson-Mifsud and Michael B Feldman and Anne Puel and Fanny Lanternier and Louis-Jean Couderc and Francois Danion and Emilie Catherinot and Hรฉlรจne Salvator and Colas Tcherkian and Claire Givel and Jie Xu and Guillermo J Tearney and Jatin M Vyas and Hu Li and Bryan P Hurley and Hongmei Mou},
doi = {10.1016/j.jaci.2022.12.821},
issn = {1097-6825},
year = {2023},
date = {2023-08-01},
journal = {J Allergy Clin Immunol},
volume = {152},
number = {2},
pages = {538--550},
abstract = {BACKGROUND: Job syndrome is a disease of autosomal dominant hyper-IgE syndrome (AD-HIES). Patients harboring STAT3 mutation are particularly prone to airway remodeling and airway infections.nnOBJECTIVES: Airway epithelial cells play a central role as the first line of defense against pathogenic infection and express high levels of STAT3. This study thus interrogates how AD-HIES STAT3 mutations impact the physiological functions of airway epithelial cells.nnMETHODS: This study created human airway basal cells expressing 4 common AD-HIES STAT3 mutants (R382W, V463del, V637M, and Y657S). In addition, primary airway epithelial cells were isolated from a patient with Job syndrome who was harboring a STAT3-S560del mutation and from mice harboring a STAT3-V463del mutation. Cell proliferation, differentiation, barrier function, bacterial elimination, and innate immune responses to pathogenic infection were quantitatively analyzed.nnRESULTS: STAT3 mutations reduce STAT3 protein phosphorylation, nuclear translocation, transcription activity, and protein stability in airway basal cells. As a consequence, STAT3-mutated airway basal cells give rise to airway epithelial cells with abnormal cellular composition and loss of coordinated mucociliary clearance. Notably, AD-HIES STAT3 airway epithelial cells are defective in bacterial killing and fail to initiate vigorous proinflammatory responses and neutrophil transepithelial migration in response to an experimental model of Pseudomonas aeruginosa infection.nnCONCLUSIONS: AD-HIES STAT3 mutations confer numerous abnormalities to airway epithelial cells in cell differentiation and host innate immunity, emphasizing their involvement in the pathogenesis of lung complications in Job syndrome. Therefore, therapies must address the epithelial defects as well as the previously noted immune cell defects to alleviate chronic infections in patients with Job syndrome.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: Job syndrome is a disease of autosomal dominant hyper-IgE syndrome (AD-HIES). Patients harboring STAT3 mutation are particularly prone to airway remodeling and airway infections.nnOBJECTIVES: Airway epithelial cells play a central role as the first line of defense against pathogenic infection and express high levels of STAT3. This study thus interrogates how AD-HIES STAT3 mutations impact the physiological functions of airway epithelial cells.nnMETHODS: This study created human airway basal cells expressing 4 common AD-HIES STAT3 mutants (R382W, V463del, V637M, and Y657S). In addition, primary airway epithelial cells were isolated from a patient with Job syndrome who was harboring a STAT3-S560del mutation and from mice harboring a STAT3-V463del mutation. Cell proliferation, differentiation, barrier function, bacterial elimination, and innate immune responses to pathogenic infection were quantitatively analyzed.nnRESULTS: STAT3 mutations reduce STAT3 protein phosphorylation, nuclear translocation, transcription activity, and protein stability in airway basal cells. As a consequence, STAT3-mutated airway basal cells give rise to airway epithelial cells with abnormal cellular composition and loss of coordinated mucociliary clearance. Notably, AD-HIES STAT3 airway epithelial cells are defective in bacterial killing and fail to initiate vigorous proinflammatory responses and neutrophil transepithelial migration in response to an experimental model of Pseudomonas aeruginosa infection.nnCONCLUSIONS: AD-HIES STAT3 mutations confer numerous abnormalities to airway epithelial cells in cell differentiation and host innate immunity, emphasizing their involvement in the pathogenesis of lung complications in Job syndrome. Therefore, therapies must address the epithelial defects as well as the previously noted immune cell defects to alleviate chronic infections in patients with Job syndrome.
Hakim, Diaa; Pinilla-Echeverri, Natalia; Coskun, Ahmet U; Pu, Zhongyue; Kajander, Olli A; Rupert, Deborah; Maynard, Charles; Cefalo, Nicholas; Siasos, Gerasimos; Papafaklis, Michail I; Kostas, Stefanu; Michalis, Lampros K; Jolly, Sanjit; Mehta, Shamir R; Sheth, Tej; Croce, Kevin; Stone, Peter H
The role of endothelial shear stress, shear stress gradient, and plaque topography in plaque erosion Journal Article
In: Atherosclerosis, vol. 376, pp. 11โ18, 2023, ISSN: 1879-1484.
@article{pmid37257352,
title = {The role of endothelial shear stress, shear stress gradient, and plaque topography in plaque erosion},
author = {Diaa Hakim and Natalia Pinilla-Echeverri and Ahmet U Coskun and Zhongyue Pu and Olli A Kajander and Deborah Rupert and Charles Maynard and Nicholas Cefalo and Gerasimos Siasos and Michail I Papafaklis and Stefanu Kostas and Lampros K Michalis and Sanjit Jolly and Shamir R Mehta and Tej Sheth and Kevin Croce and Peter H Stone},
doi = {10.1016/j.atherosclerosis.2023.05.013},
issn = {1879-1484},
year = {2023},
date = {2023-07-01},
journal = {Atherosclerosis},
volume = {376},
pages = {11--18},
abstract = {BACKGROUND AND AIMS: Plaque erosion is a common underlying cause of acute coronary syndromes. The role of endothelial shear stress (ESS) and endothelial shear stress gradient (ESSG) in plaque erosion remains unknown. We aimed to determine the role of ESS metrics and maximum plaque slope steepness in plaques with erosion versus stable plaques.nnMETHODS: This analysis included 46 patients/plaques from TOTAL and COMPLETE trials and Brigham and Women's Hospital's database who underwent angiography and OCT. Plaques were divided into those with erosion (nย =ย 24) and matched stable coronary plaques (nย =ย 22). Angiographic views were used to generate a 3-D arterial reconstruction, with centerlines merged from angiography and OCT pullback. Local ESS metrics were assessed by computational fluid dynamics. Among plaque erosions, the up- and down-slope (ฮ lumen area/frame) was calculated for each culprit plaque.nnRESULTS: Compared with stable plaque controls, plaques with an erosion were associated with higher max ESS (8.3ย ยฑย 4.8 vs. 5.0ย ยฑย 1.9ย Pa, pย = 0.02) and max ESSG any direction (9.2ย ยฑย 7.5 vs. 4.3ย ยฑย 3.11ย Pa/mm, pย =ย 0.005). Proximal erosion was associated with a steeper plaque upslope while distal erosion with a steeper plaque downslope. Max ESS and Max ESSG any direction were independent factors in the development of plaque erosion (OR 1.32, 95%CI 1.06-1.65, p =ย 0.014; OR 1.22, 95% CI 1.03-1.45, pย =ย 0.009, respectively).nnCONCLUSIONS: In plaques with similar luminal stenosis, plaque erosion was strongly associated with higher ESS, ESS gradients, and plaque slope as compared with stable plaques. These data support that ESS and slope metrics play a key role in the development of plaque erosion and may help prognosticate individual plaques at risk for future erosion.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND AND AIMS: Plaque erosion is a common underlying cause of acute coronary syndromes. The role of endothelial shear stress (ESS) and endothelial shear stress gradient (ESSG) in plaque erosion remains unknown. We aimed to determine the role of ESS metrics and maximum plaque slope steepness in plaques with erosion versus stable plaques.nnMETHODS: This analysis included 46 patients/plaques from TOTAL and COMPLETE trials and Brigham and Women’s Hospital’s database who underwent angiography and OCT. Plaques were divided into those with erosion (nย =ย 24) and matched stable coronary plaques (nย =ย 22). Angiographic views were used to generate a 3-D arterial reconstruction, with centerlines merged from angiography and OCT pullback. Local ESS metrics were assessed by computational fluid dynamics. Among plaque erosions, the up- and down-slope (ฮ lumen area/frame) was calculated for each culprit plaque.nnRESULTS: Compared with stable plaque controls, plaques with an erosion were associated with higher max ESS (8.3ย ยฑย 4.8 vs. 5.0ย ยฑย 1.9ย Pa, pย = 0.02) and max ESSG any direction (9.2ย ยฑย 7.5 vs. 4.3ย ยฑย 3.11ย Pa/mm, pย =ย 0.005). Proximal erosion was associated with a steeper plaque upslope while distal erosion with a steeper plaque downslope. Max ESS and Max ESSG any direction were independent factors in the development of plaque erosion (OR 1.32, 95%CI 1.06-1.65, p =ย 0.014; OR 1.22, 95% CI 1.03-1.45, pย =ย 0.009, respectively).nnCONCLUSIONS: In plaques with similar luminal stenosis, plaque erosion was strongly associated with higher ESS, ESS gradients, and plaque slope as compared with stable plaques. These data support that ESS and slope metrics play a key role in the development of plaque erosion and may help prognosticate individual plaques at risk for future erosion.
Albers, Suki; Allen, Elizabeth C; Bharti, Nikhil; Davyt, Marcos; Joshi, Disha; Perez-Garcia, Carlos G; Santos, Leonardo; Mukthavaram, Rajesh; Delgado-Toscano, Miguel Angel; Molina, Brandon; Kuakini, Kristen; Alayyoubi, Maher; Park, Kyoung-Joo Jenny; Acharya, Grishma; Gonzalez, Jose A; Sagi, Amit; Birket, Susan E; Tearney, Guillermo J; Rowe, Steven M; Manfredi, Candela; Hong, Jeong S; Tachikawa, Kiyoshi; Karmali, Priya; Matsuda, Daiki; Sorscher, Eric J; Chivukula, Pad; Ignatova, Zoya
Engineered tRNAs suppress nonsense mutations in cells and in vivo Journal Article
In: Nature, vol. 618, no. 7966, pp. 842โ848, 2023, ISSN: 1476-4687.
@article{pmid37258671b,
title = {Engineered tRNAs suppress nonsense mutations in cells and in vivo},
author = {Suki Albers and Elizabeth C Allen and Nikhil Bharti and Marcos Davyt and Disha Joshi and Carlos G Perez-Garcia and Leonardo Santos and Rajesh Mukthavaram and Miguel Angel Delgado-Toscano and Brandon Molina and Kristen Kuakini and Maher Alayyoubi and Kyoung-Joo Jenny Park and Grishma Acharya and Jose A Gonzalez and Amit Sagi and Susan E Birket and Guillermo J Tearney and Steven M Rowe and Candela Manfredi and Jeong S Hong and Kiyoshi Tachikawa and Priya Karmali and Daiki Matsuda and Eric J Sorscher and Pad Chivukula and Zoya Ignatova},
doi = {10.1038/s41586-023-06133-1},
issn = {1476-4687},
year = {2023},
date = {2023-06-01},
journal = {Nature},
volume = {618},
number = {7966},
pages = {842--848},
abstract = {Nonsense mutations are the underlying cause of approximately 11% of all inherited genetic diseases. Nonsense mutations convert a sense codon that is decoded by tRNA into a premature termination codon (PTC), resulting in an abrupt termination of translation. One strategy to suppress nonsense mutations is to use natural tRNAs with altered anticodons to base-pair to the newly emerged PTC and promote translation. However, tRNA-based gene therapy has not yielded an optimal combination of clinical efficacy and safety and there is presently no treatment for individuals with nonsense mutations. Here we introduce a strategy based on altering native tRNAs intoย efficient suppressor tRNAs (sup-tRNAs) by individually fine-tuning their sequence to the physico-chemical properties of the amino acid that they carry. Intravenous and intratracheal lipid nanoparticle (LNP) administration of sup-tRNA in miceย restored the production of functional proteins with nonsense mutations. LNP-sup-tRNA formulations caused no discernible readthrough at endogenous native stop codons, as determined by ribosome profiling. At clinically important PTCs in the cystic fibrosis transmembrane conductance regulator gene (CFTR), the sup-tRNAs re-established expression and function in cell systems and patient-derived nasal epithelia and restored airway volume homeostasis. These results provide a framework for the development of tRNA-based therapies with a high molecular safety profile and high efficacy in targeted PTC suppression.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Nonsense mutations are the underlying cause of approximately 11% of all inherited genetic diseases. Nonsense mutations convert a sense codon that is decoded by tRNA into a premature termination codon (PTC), resulting in an abrupt termination of translation. One strategy to suppress nonsense mutations is to use natural tRNAs with altered anticodons to base-pair to the newly emerged PTC and promote translation. However, tRNA-based gene therapy has not yielded an optimal combination of clinical efficacy and safety and there is presently no treatment for individuals with nonsense mutations. Here we introduce a strategy based on altering native tRNAs intoย efficient suppressor tRNAs (sup-tRNAs) by individually fine-tuning their sequence to the physico-chemical properties of the amino acid that they carry. Intravenous and intratracheal lipid nanoparticle (LNP) administration of sup-tRNA in miceย restored the production of functional proteins with nonsense mutations. LNP-sup-tRNA formulations caused no discernible readthrough at endogenous native stop codons, as determined by ribosome profiling. At clinically important PTCs in the cystic fibrosis transmembrane conductance regulator gene (CFTR), the sup-tRNAs re-established expression and function in cell systems and patient-derived nasal epithelia and restored airway volume homeostasis. These results provide a framework for the development of tRNA-based therapies with a high molecular safety profile and high efficacy in targeted PTC suppression.
Albers, Suki; Allen, Elizabeth C; Bharti, Nikhil; Davyt, Marcos; Joshi, Disha; Perez-Garcia, Carlos G; Santos, Leonardo; Mukthavaram, Rajesh; Delgado-Toscano, Miguel Angel; Molina, Brandon; Kuakini, Kristen; Alayyoubi, Maher; Park, Kyoung-Joo Jenny; Acharya, Grishma; Gonzalez, Jose A; Sagi, Amit; Birket, Susan E; Tearney, Guillermo J; Rowe, Steven M; Manfredi, Candela; Hong, Jeong S; Tachikawa, Kiyoshi; Karmali, Priya; Matsuda, Daiki; Sorscher, Eric J; Chivukula, Pad; Ignatova, Zoya
Engineered tRNAs suppress nonsense mutations in cells and in vivo Journal Article
In: Nature, vol. 618, no. 7966, pp. 842โ848, 2023, ISSN: 1476-4687.
@article{pmid37258671,
title = {Engineered tRNAs suppress nonsense mutations in cells and in vivo},
author = {Suki Albers and Elizabeth C Allen and Nikhil Bharti and Marcos Davyt and Disha Joshi and Carlos G Perez-Garcia and Leonardo Santos and Rajesh Mukthavaram and Miguel Angel Delgado-Toscano and Brandon Molina and Kristen Kuakini and Maher Alayyoubi and Kyoung-Joo Jenny Park and Grishma Acharya and Jose A Gonzalez and Amit Sagi and Susan E Birket and Guillermo J Tearney and Steven M Rowe and Candela Manfredi and Jeong S Hong and Kiyoshi Tachikawa and Priya Karmali and Daiki Matsuda and Eric J Sorscher and Pad Chivukula and Zoya Ignatova},
doi = {10.1038/s41586-023-06133-1},
issn = {1476-4687},
year = {2023},
date = {2023-06-01},
journal = {Nature},
volume = {618},
number = {7966},
pages = {842--848},
abstract = {Nonsense mutations are the underlying cause of approximately 11% of all inherited genetic diseases. Nonsense mutations convert a sense codon that is decoded by tRNA into a premature termination codon (PTC), resulting in an abrupt termination of translation. One strategy to suppress nonsense mutations is to use natural tRNAs with altered anticodons to base-pair to the newly emerged PTC and promote translation. However, tRNA-based gene therapy has not yielded an optimal combination of clinical efficacy and safety and there is presently no treatment for individuals with nonsense mutations. Here we introduce a strategy based on altering native tRNAs intoย efficient suppressor tRNAs (sup-tRNAs) by individually fine-tuning their sequence to the physico-chemical properties of the amino acid that they carry. Intravenous and intratracheal lipid nanoparticle (LNP) administration of sup-tRNA in miceย restored the production of functional proteins with nonsense mutations. LNP-sup-tRNA formulations caused no discernible readthrough at endogenous native stop codons, as determined by ribosome profiling. At clinically important PTCs in the cystic fibrosis transmembrane conductance regulator gene (CFTR), the sup-tRNAs re-established expression and function in cell systems and patient-derived nasal epithelia and restored airway volume homeostasis. These results provide a framework for the development of tRNA-based therapies with a high molecular safety profile and high efficacy in targeted PTC suppression.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Nonsense mutations are the underlying cause of approximately 11% of all inherited genetic diseases. Nonsense mutations convert a sense codon that is decoded by tRNA into a premature termination codon (PTC), resulting in an abrupt termination of translation. One strategy to suppress nonsense mutations is to use natural tRNAs with altered anticodons to base-pair to the newly emerged PTC and promote translation. However, tRNA-based gene therapy has not yielded an optimal combination of clinical efficacy and safety and there is presently no treatment for individuals with nonsense mutations. Here we introduce a strategy based on altering native tRNAs intoย efficient suppressor tRNAs (sup-tRNAs) by individually fine-tuning their sequence to the physico-chemical properties of the amino acid that they carry. Intravenous and intratracheal lipid nanoparticle (LNP) administration of sup-tRNA in miceย restored the production of functional proteins with nonsense mutations. LNP-sup-tRNA formulations caused no discernible readthrough at endogenous native stop codons, as determined by ribosome profiling. At clinically important PTCs in the cystic fibrosis transmembrane conductance regulator gene (CFTR), the sup-tRNAs re-established expression and function in cell systems and patient-derived nasal epithelia and restored airway volume homeostasis. These results provide a framework for the development of tRNA-based therapies with a high molecular safety profile and high efficacy in targeted PTC suppression.
Nishimiya, Kensuke; Poduval, Radhika K; Tearney, Guillermo J
OCT Emerging Technologies: Coronary Micro-optical Coherence Tomography Journal Article
In: Interv Cardiol Clin, vol. 12, no. 2, pp. 237โ244, 2023, ISSN: 2211-7466.
@article{pmid36922064c,
title = {OCT Emerging Technologies: Coronary Micro-optical Coherence Tomography},
author = {Kensuke Nishimiya and Radhika K Poduval and Guillermo J Tearney},
doi = {10.1016/j.iccl.2023.01.001},
issn = {2211-7466},
year = {2023},
date = {2023-04-01},
journal = {Interv Cardiol Clin},
volume = {12},
number = {2},
pages = {237--244},
abstract = {Optical coherence tomography (OCT) is an imaging modality that is used in a significant number of interventional cardiology procedures. Key structural changes occurring within the vessel wall, including presence of neutrophils, macrophages, monocytes, and vascular smooth muscle cells, are below the resolution of clinical intracoronary OCT. To address this challenge, a new form of OCT with 1 to 2ย ฮผm resolution, termed micro-OCT (ฮผOCT), has been developed. This review article summarizes the ability of ฮผOCT technology to visualize coronary microstructures and discusses its clinical implications.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Optical coherence tomography (OCT) is an imaging modality that is used in a significant number of interventional cardiology procedures. Key structural changes occurring within the vessel wall, including presence of neutrophils, macrophages, monocytes, and vascular smooth muscle cells, are below the resolution of clinical intracoronary OCT. To address this challenge, a new form of OCT with 1 to 2ย ฮผm resolution, termed micro-OCT (ฮผOCT), has been developed. This review article summarizes the ability of ฮผOCT technology to visualize coronary microstructures and discusses its clinical implications.
Ryu, Jiheun; Kang, Dongkyun; Kim, Junyoung; Chung, Anita; Grant, Catriona N; Ryan, Emily; Barrios, Amilcar; Osman, Hany; Tearney, Guillermo J
High-speed reflectance confocal microscopy of human skin at 1251-1342โnm Journal Article
In: Lasers Surg Med, vol. 55, no. 4, pp. 405โ413, 2023, ISSN: 1096-9101.
@article{pmid36924183b,
title = {High-speed reflectance confocal microscopy of human skin at 1251-1342โnm},
author = {Jiheun Ryu and Dongkyun Kang and Junyoung Kim and Anita Chung and Catriona N Grant and Emily Ryan and Amilcar Barrios and Hany Osman and Guillermo J Tearney},
doi = {10.1002/lsm.23652},
issn = {1096-9101},
year = {2023},
date = {2023-04-01},
journal = {Lasers Surg Med},
volume = {55},
number = {4},
pages = {405--413},
abstract = {OBJECTIVES: Reflectance confocal microscopy (RCM) is an imaging method that can noninvasively visualize microscopic features of the human skin. The utility of RCM can be further improved by increasing imaging speed. In this paper, we report high-speed RCM imaging of human skin with a frame rate that is over 10 times faster and an area imaging rate that is 6-9 times faster than those of commercially available RCM devices.nnMETHODS: The higher imaging speed was achieved using a high-speed RCM technique, termed spectrally encoded confocal microscopy (SECM). SECM uses a diffraction grating and a high-speed, wavelength-swept source to conduct confocal imaging at a very high rate. We developed a handheld SECM probe using a scanned-grating approach. The SECM probe was used in conjunction with a wavelength-swept source with a spectral band of 1251-1342โnm.nnRESULTS: The SECM probe achieved high lateral resolution of 1.3-1.6โยตm and an axial resolution of 3.5โยตm. SECM images of the human skin (image sizeโ=โ439โรโ439โยตm ) obtained at 100 frames/s clearly show previously reported RCM features of the human skin in vivo with adequate image quality. The fast imaging speed allowed for the rapid acquisiton of volumetric SECM image data (200 frames covering a depth range of 200โยตm) within 2โs. The use of 1251-1342โnm provided sufficient signal level and contrast required to visualize key cellular morphologic features.nnCONCLUSIONS: These preliminary results demonstrate that high-speed SECM imaging of the human skin at 1251-1342โnm is feasible.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
OBJECTIVES: Reflectance confocal microscopy (RCM) is an imaging method that can noninvasively visualize microscopic features of the human skin. The utility of RCM can be further improved by increasing imaging speed. In this paper, we report high-speed RCM imaging of human skin with a frame rate that is over 10 times faster and an area imaging rate that is 6-9 times faster than those of commercially available RCM devices.nnMETHODS: The higher imaging speed was achieved using a high-speed RCM technique, termed spectrally encoded confocal microscopy (SECM). SECM uses a diffraction grating and a high-speed, wavelength-swept source to conduct confocal imaging at a very high rate. We developed a handheld SECM probe using a scanned-grating approach. The SECM probe was used in conjunction with a wavelength-swept source with a spectral band of 1251-1342โnm.nnRESULTS: The SECM probe achieved high lateral resolution of 1.3-1.6โยตm and an axial resolution of 3.5โยตm. SECM images of the human skin (image sizeโ=โ439โรโ439โยตm ) obtained at 100 frames/s clearly show previously reported RCM features of the human skin in vivo with adequate image quality. The fast imaging speed allowed for the rapid acquisiton of volumetric SECM image data (200 frames covering a depth range of 200โยตm) within 2โs. The use of 1251-1342โnm provided sufficient signal level and contrast required to visualize key cellular morphologic features.nnCONCLUSIONS: These preliminary results demonstrate that high-speed SECM imaging of the human skin at 1251-1342โnm is feasible.
Nishimiya, Kensuke; Poduval, Radhika K; Tearney, Guillermo J
OCT Emerging Technologies: Coronary Micro-optical Coherence Tomography Journal Article
In: Interv Cardiol Clin, vol. 12, no. 2, pp. 237โ244, 2023, ISSN: 2211-7466.
@article{pmid36922064b,
title = {OCT Emerging Technologies: Coronary Micro-optical Coherence Tomography},
author = {Kensuke Nishimiya and Radhika K Poduval and Guillermo J Tearney},
doi = {10.1016/j.iccl.2023.01.001},
issn = {2211-7466},
year = {2023},
date = {2023-04-01},
journal = {Interv Cardiol Clin},
volume = {12},
number = {2},
pages = {237--244},
abstract = {Optical coherence tomography (OCT) is an imaging modality that is used in a significant number of interventional cardiology procedures. Key structural changes occurring within the vessel wall, including presence of neutrophils, macrophages, monocytes, and vascular smooth muscle cells, are below the resolution of clinical intracoronary OCT. To address this challenge, a new form of OCT with 1 to 2ย ฮผm resolution, termed micro-OCT (ฮผOCT), has been developed. This review article summarizes the ability of ฮผOCT technology to visualize coronary microstructures and discusses its clinical implications.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Optical coherence tomography (OCT) is an imaging modality that is used in a significant number of interventional cardiology procedures. Key structural changes occurring within the vessel wall, including presence of neutrophils, macrophages, monocytes, and vascular smooth muscle cells, are below the resolution of clinical intracoronary OCT. To address this challenge, a new form of OCT with 1 to 2ย ฮผm resolution, termed micro-OCT (ฮผOCT), has been developed. This review article summarizes the ability of ฮผOCT technology to visualize coronary microstructures and discusses its clinical implications.
Ryu, Jiheun; Kang, Dongkyun; Kim, Junyoung; Chung, Anita; Grant, Catriona N; Ryan, Emily; Barrios, Amilcar; Osman, Hany; Tearney, Guillermo J
High-speed reflectance confocal microscopy of human skin at 1251-1342โnm Journal Article
In: Lasers Surg Med, vol. 55, no. 4, pp. 405โ413, 2023, ISSN: 1096-9101.
@article{pmid36924183,
title = {High-speed reflectance confocal microscopy of human skin at 1251-1342โnm},
author = {Jiheun Ryu and Dongkyun Kang and Junyoung Kim and Anita Chung and Catriona N Grant and Emily Ryan and Amilcar Barrios and Hany Osman and Guillermo J Tearney},
doi = {10.1002/lsm.23652},
issn = {1096-9101},
year = {2023},
date = {2023-04-01},
journal = {Lasers Surg Med},
volume = {55},
number = {4},
pages = {405--413},
abstract = {OBJECTIVES: Reflectance confocal microscopy (RCM) is an imaging method that can noninvasively visualize microscopic features of the human skin. The utility of RCM can be further improved by increasing imaging speed. In this paper, we report high-speed RCM imaging of human skin with a frame rate that is over 10 times faster and an area imaging rate that is 6-9 times faster than those of commercially available RCM devices.nnMETHODS: The higher imaging speed was achieved using a high-speed RCM technique, termed spectrally encoded confocal microscopy (SECM). SECM uses a diffraction grating and a high-speed, wavelength-swept source to conduct confocal imaging at a very high rate. We developed a handheld SECM probe using a scanned-grating approach. The SECM probe was used in conjunction with a wavelength-swept source with a spectral band of 1251-1342โnm.nnRESULTS: The SECM probe achieved high lateral resolution of 1.3-1.6โยตm and an axial resolution of 3.5โยตm. SECM images of the human skin (image sizeโ=โ439โรโ439โยตm ) obtained at 100 frames/s clearly show previously reported RCM features of the human skin in vivo with adequate image quality. The fast imaging speed allowed for the rapid acquisiton of volumetric SECM image data (200 frames covering a depth range of 200โยตm) within 2โs. The use of 1251-1342โnm provided sufficient signal level and contrast required to visualize key cellular morphologic features.nnCONCLUSIONS: These preliminary results demonstrate that high-speed SECM imaging of the human skin at 1251-1342โnm is feasible.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
OBJECTIVES: Reflectance confocal microscopy (RCM) is an imaging method that can noninvasively visualize microscopic features of the human skin. The utility of RCM can be further improved by increasing imaging speed. In this paper, we report high-speed RCM imaging of human skin with a frame rate that is over 10 times faster and an area imaging rate that is 6-9 times faster than those of commercially available RCM devices.nnMETHODS: The higher imaging speed was achieved using a high-speed RCM technique, termed spectrally encoded confocal microscopy (SECM). SECM uses a diffraction grating and a high-speed, wavelength-swept source to conduct confocal imaging at a very high rate. We developed a handheld SECM probe using a scanned-grating approach. The SECM probe was used in conjunction with a wavelength-swept source with a spectral band of 1251-1342โnm.nnRESULTS: The SECM probe achieved high lateral resolution of 1.3-1.6โยตm and an axial resolution of 3.5โยตm. SECM images of the human skin (image sizeโ=โ439โรโ439โยตm ) obtained at 100 frames/s clearly show previously reported RCM features of the human skin in vivo with adequate image quality. The fast imaging speed allowed for the rapid acquisiton of volumetric SECM image data (200 frames covering a depth range of 200โยตm) within 2โs. The use of 1251-1342โnm provided sufficient signal level and contrast required to visualize key cellular morphologic features.nnCONCLUSIONS: These preliminary results demonstrate that high-speed SECM imaging of the human skin at 1251-1342โnm is feasible.
Karcioglu, Amanda L Silver; Triponez, Frรฉdรฉric; Solรณrzano, Carmen C; Iwata, Ayaka J; Ahmed, Amr H Abdelhamid; Almquist, Martin; Angelos, Peter; Benmiloud, Fares; Berber, Eren; Bergenfelz, Anders; Cha, Jaepyeong; Colaianni, C Alessandra; Davies, Louise; Duh, Quan-Yang; Hartl, Dana; Kandil, Emad; Kim, Wan Wook; Kopp, Peter A; Liddy, Whitney; Mahadevan-Jansen, Anita; Lee, Kang-Dae; Mannstadt, Michael; McMullen, Caitlin P; Shonka, David C; Shin, Jennifer J; Singer, Michael C; Slough, Cristian M; Stack, Brendan C; Tearney, Guillermo; Thomas, Giju; Tolley, Neil; Vidal-Fortuny, Jordi; Randolph, Gregory W
In: JAMA Otolaryngol Head Neck Surg, vol. 149, no. 3, pp. 253โ260, 2023, ISSN: 2168-619X.
@article{pmid36633855b,
title = {Emerging Imaging Technologies for Parathyroid Gland Identification and Vascular Assessment in Thyroid Surgery: A Review From the American Head and Neck Society Endocrine Surgery Section},
author = {Amanda L Silver Karcioglu and Frรฉdรฉric Triponez and Carmen C Solรณrzano and Ayaka J Iwata and Amr H Abdelhamid Ahmed and Martin Almquist and Peter Angelos and Fares Benmiloud and Eren Berber and Anders Bergenfelz and Jaepyeong Cha and C Alessandra Colaianni and Louise Davies and Quan-Yang Duh and Dana Hartl and Emad Kandil and Wan Wook Kim and Peter A Kopp and Whitney Liddy and Anita Mahadevan-Jansen and Kang-Dae Lee and Michael Mannstadt and Caitlin P McMullen and David C Shonka and Jennifer J Shin and Michael C Singer and Cristian M Slough and Brendan C Stack and Guillermo Tearney and Giju Thomas and Neil Tolley and Jordi Vidal-Fortuny and Gregory W Randolph},
doi = {10.1001/jamaoto.2022.4421},
issn = {2168-619X},
year = {2023},
date = {2023-03-01},
journal = {JAMA Otolaryngol Head Neck Surg},
volume = {149},
number = {3},
pages = {253--260},
abstract = {IMPORTANCE: Identification and preservation of parathyroid glands (PGs) remain challenging despite advances in surgical techniques. Considerable morbidity and even mortality result from hypoparathyroidism caused by devascularization or inadvertent removal of PGs. Emerging imaging technologies hold promise to improve identification and preservation of PGs during thyroid surgery.nnOBSERVATION: This narrative review (1) comprehensively reviews PG identification and vascular assessment using near-infrared autofluorescence (NIRAF)-both label free and in combination with indocyanine green-based on a comprehensive literature review and (2) offers a manual for possible implementation these emerging technologies in thyroid surgery.nnCONCLUSIONS AND RELEVANCE: Emerging technologies hold promise to improve PG identification and preservation during thyroidectomy. Future research should address variables affecting the degree of fluorescence in NIRAF, standardization of signal quantification, definitions and standardization of parameters of indocyanine green injection that correlate with postoperative PG function, the financial effect of these emerging technologies on near-term and longer-term costs, the adoption learning curve and effect on surgical training, and long-term outcomes of key quality metrics in adequately powered randomized clinical trials evaluating PG preservation.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
IMPORTANCE: Identification and preservation of parathyroid glands (PGs) remain challenging despite advances in surgical techniques. Considerable morbidity and even mortality result from hypoparathyroidism caused by devascularization or inadvertent removal of PGs. Emerging imaging technologies hold promise to improve identification and preservation of PGs during thyroid surgery.nnOBSERVATION: This narrative review (1) comprehensively reviews PG identification and vascular assessment using near-infrared autofluorescence (NIRAF)-both label free and in combination with indocyanine green-based on a comprehensive literature review and (2) offers a manual for possible implementation these emerging technologies in thyroid surgery.nnCONCLUSIONS AND RELEVANCE: Emerging technologies hold promise to improve PG identification and preservation during thyroidectomy. Future research should address variables affecting the degree of fluorescence in NIRAF, standardization of signal quantification, definitions and standardization of parameters of indocyanine green injection that correlate with postoperative PG function, the financial effect of these emerging technologies on near-term and longer-term costs, the adoption learning curve and effect on surgical training, and long-term outcomes of key quality metrics in adequately powered randomized clinical trials evaluating PG preservation.
Karcioglu, Amanda L Silver; Triponez, Frรฉdรฉric; Solรณrzano, Carmen C; Iwata, Ayaka J; Ahmed, Amr H Abdelhamid; Almquist, Martin; Angelos, Peter; Benmiloud, Fares; Berber, Eren; Bergenfelz, Anders; Cha, Jaepyeong; Colaianni, C Alessandra; Davies, Louise; Duh, Quan-Yang; Hartl, Dana; Kandil, Emad; Kim, Wan Wook; Kopp, Peter A; Liddy, Whitney; Mahadevan-Jansen, Anita; Lee, Kang-Dae; Mannstadt, Michael; McMullen, Caitlin P; Shonka, David C; Shin, Jennifer J; Singer, Michael C; Slough, Cristian M; Stack, Brendan C; Tearney, Guillermo; Thomas, Giju; Tolley, Neil; Vidal-Fortuny, Jordi; Randolph, Gregory W
In: JAMA Otolaryngol Head Neck Surg, vol. 149, no. 3, pp. 253โ260, 2023, ISSN: 2168-619X.
@article{pmid36633855,
title = {Emerging Imaging Technologies for Parathyroid Gland Identification and Vascular Assessment in Thyroid Surgery: A Review From the American Head and Neck Society Endocrine Surgery Section},
author = {Amanda L Silver Karcioglu and Frรฉdรฉric Triponez and Carmen C Solรณrzano and Ayaka J Iwata and Amr H Abdelhamid Ahmed and Martin Almquist and Peter Angelos and Fares Benmiloud and Eren Berber and Anders Bergenfelz and Jaepyeong Cha and C Alessandra Colaianni and Louise Davies and Quan-Yang Duh and Dana Hartl and Emad Kandil and Wan Wook Kim and Peter A Kopp and Whitney Liddy and Anita Mahadevan-Jansen and Kang-Dae Lee and Michael Mannstadt and Caitlin P McMullen and David C Shonka and Jennifer J Shin and Michael C Singer and Cristian M Slough and Brendan C Stack and Guillermo Tearney and Giju Thomas and Neil Tolley and Jordi Vidal-Fortuny and Gregory W Randolph},
doi = {10.1001/jamaoto.2022.4421},
issn = {2168-619X},
year = {2023},
date = {2023-03-01},
journal = {JAMA Otolaryngol Head Neck Surg},
volume = {149},
number = {3},
pages = {253--260},
abstract = {IMPORTANCE: Identification and preservation of parathyroid glands (PGs) remain challenging despite advances in surgical techniques. Considerable morbidity and even mortality result from hypoparathyroidism caused by devascularization or inadvertent removal of PGs. Emerging imaging technologies hold promise to improve identification and preservation of PGs during thyroid surgery.nnOBSERVATION: This narrative review (1) comprehensively reviews PG identification and vascular assessment using near-infrared autofluorescence (NIRAF)-both label free and in combination with indocyanine green-based on a comprehensive literature review and (2) offers a manual for possible implementation these emerging technologies in thyroid surgery.nnCONCLUSIONS AND RELEVANCE: Emerging technologies hold promise to improve PG identification and preservation during thyroidectomy. Future research should address variables affecting the degree of fluorescence in NIRAF, standardization of signal quantification, definitions and standardization of parameters of indocyanine green injection that correlate with postoperative PG function, the financial effect of these emerging technologies on near-term and longer-term costs, the adoption learning curve and effect on surgical training, and long-term outcomes of key quality metrics in adequately powered randomized clinical trials evaluating PG preservation.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
IMPORTANCE: Identification and preservation of parathyroid glands (PGs) remain challenging despite advances in surgical techniques. Considerable morbidity and even mortality result from hypoparathyroidism caused by devascularization or inadvertent removal of PGs. Emerging imaging technologies hold promise to improve identification and preservation of PGs during thyroid surgery.nnOBSERVATION: This narrative review (1) comprehensively reviews PG identification and vascular assessment using near-infrared autofluorescence (NIRAF)-both label free and in combination with indocyanine green-based on a comprehensive literature review and (2) offers a manual for possible implementation these emerging technologies in thyroid surgery.nnCONCLUSIONS AND RELEVANCE: Emerging technologies hold promise to improve PG identification and preservation during thyroidectomy. Future research should address variables affecting the degree of fluorescence in NIRAF, standardization of signal quantification, definitions and standardization of parameters of indocyanine green injection that correlate with postoperative PG function, the financial effect of these emerging technologies on near-term and longer-term costs, the adoption learning curve and effect on surgical training, and long-term outcomes of key quality metrics in adequately powered randomized clinical trials evaluating PG preservation.
Stone, Peter H; Libby, Peter; Boden, William E
In: JAMA Cardiol, vol. 8, no. 2, pp. 192โ201, 2023, ISSN: 2380-6591.
@article{pmid36515941,
title = {Fundamental Pathobiology of Coronary Atherosclerosis and Clinical Implications for Chronic Ischemic Heart Disease Management-The Plaque Hypothesis: A Narrative Review},
author = {Peter H Stone and Peter Libby and William E Boden},
doi = {10.1001/jamacardio.2022.3926},
issn = {2380-6591},
year = {2023},
date = {2023-02-01},
journal = {JAMA Cardiol},
volume = {8},
number = {2},
pages = {192--201},
abstract = {IMPORTANCE: Recent clinical and imaging studies underscore that major adverse cardiac events (MACE) outcomes are associated not solely with severe coronary obstructions (ischemia hypothesis or stenosis hypothesis), but with the plaque burden along the entire coronary tree. New research clarifies the pathobiologic mechanisms responsible for plaque development/progression/destabilization leading to MACE (plaque hypothesis), but the translation of these insights to clinical management strategies has lagged. This narrative review elaborates the plaque hypothesis and explicates the current understanding of underlying pathobiologic mechanisms, the provocative destabilizing influences, the diagnostic and therapeutic implications, and their actionable clinical management approaches to optimize the management of patients with chronic coronary disease.nnOBSERVATIONS: Clinical trials of management strategies for patients with chronic coronary artery disease demonstrate that while MACE rate increases progressively with the anatomic extent of coronary disease, revascularization of the ischemia-producing obstruction does not forestall MACE. Most severely obstructive coronary lesions often remain quiescent and seldom destabilize to cause a MACE. Coronary lesions that later provoke acute myocardial infarction often do not narrow the lumen critically. Invasive and noninvasive imaging can identify the plaque anatomic characteristics (plaque burden, plaque topography, lipid content) and local hemodynamic/biomechanical characteristics (endothelial shear stress, plaque structural stress, axial plaque stress) that can indicate the propensity of individual plaques to provoke a MACE.nnCONCLUSIONS AND RELEVANCE: The pathobiologic construct concerning the culprit region of a plaque most likely to cause a MACE (plaque hypothesis), which incorporates multiple convergent plaque features, informs the evolution of a new management strategy capable of identifying the high-risk portion of plaque wherever it is located along the course of the coronary artery. Ongoing investigations of high-risk plaque features, coupled with technical advances to enable prognostic characterization in real time and at the point of care, will soon enable evaluation of the entire length of the atheromatous coronary artery and broaden the target(s) of our therapeutic intervention to include all regions of the plaque (both flow limiting and nonflow limiting).},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
IMPORTANCE: Recent clinical and imaging studies underscore that major adverse cardiac events (MACE) outcomes are associated not solely with severe coronary obstructions (ischemia hypothesis or stenosis hypothesis), but with the plaque burden along the entire coronary tree. New research clarifies the pathobiologic mechanisms responsible for plaque development/progression/destabilization leading to MACE (plaque hypothesis), but the translation of these insights to clinical management strategies has lagged. This narrative review elaborates the plaque hypothesis and explicates the current understanding of underlying pathobiologic mechanisms, the provocative destabilizing influences, the diagnostic and therapeutic implications, and their actionable clinical management approaches to optimize the management of patients with chronic coronary disease.nnOBSERVATIONS: Clinical trials of management strategies for patients with chronic coronary artery disease demonstrate that while MACE rate increases progressively with the anatomic extent of coronary disease, revascularization of the ischemia-producing obstruction does not forestall MACE. Most severely obstructive coronary lesions often remain quiescent and seldom destabilize to cause a MACE. Coronary lesions that later provoke acute myocardial infarction often do not narrow the lumen critically. Invasive and noninvasive imaging can identify the plaque anatomic characteristics (plaque burden, plaque topography, lipid content) and local hemodynamic/biomechanical characteristics (endothelial shear stress, plaque structural stress, axial plaque stress) that can indicate the propensity of individual plaques to provoke a MACE.nnCONCLUSIONS AND RELEVANCE: The pathobiologic construct concerning the culprit region of a plaque most likely to cause a MACE (plaque hypothesis), which incorporates multiple convergent plaque features, informs the evolution of a new management strategy capable of identifying the high-risk portion of plaque wherever it is located along the course of the coronary artery. Ongoing investigations of high-risk plaque features, coupled with technical advances to enable prognostic characterization in real time and at the point of care, will soon enable evaluation of the entire length of the atheromatous coronary artery and broaden the target(s) of our therapeutic intervention to include all regions of the plaque (both flow limiting and nonflow limiting).
Li, Qian; Vijaykumar, Kadambari; Phillips, Scott E; Hussain, Shah S; Huynh, Nha V; Fernandez-Petty, Courtney M; Lever, Jacelyn E Peabody; Foote, Jeremy B; Ren, Janna; Campos-Gรณmez, Javier; Daya, Farah Abou; Hubbs, Nathaniel W; Kim, Harrison; Onuoha, Ezinwanne; Boitet, Evan R; Fu, Lianwu; Leung, Hui Min; Yu, Linhui; Detchemendy, Thomas W; Schaefers, Levi T; Tipper, Jennifer L; Edwards, Lloyd J; Leal, Sixto M; Harrod, Kevin S; Tearney, Guillermo J; Rowe, Steven M
Mucociliary transport deficiency and disease progression in Syrian hamsters with SARS-CoV-2 infection Journal Article
In: JCI Insight, vol. 8, no. 1, 2023, ISSN: 2379-3708.
@article{pmid36625345,
title = {Mucociliary transport deficiency and disease progression in Syrian hamsters with SARS-CoV-2 infection},
author = {Qian Li and Kadambari Vijaykumar and Scott E Phillips and Shah S Hussain and Nha V Huynh and Courtney M Fernandez-Petty and Jacelyn E Peabody Lever and Jeremy B Foote and Janna Ren and Javier Campos-Gรณmez and Farah Abou Daya and Nathaniel W Hubbs and Harrison Kim and Ezinwanne Onuoha and Evan R Boitet and Lianwu Fu and Hui Min Leung and Linhui Yu and Thomas W Detchemendy and Levi T Schaefers and Jennifer L Tipper and Lloyd J Edwards and Sixto M Leal and Kevin S Harrod and Guillermo J Tearney and Steven M Rowe},
doi = {10.1172/jci.insight.163962},
issn = {2379-3708},
year = {2023},
date = {2023-01-01},
journal = {JCI Insight},
volume = {8},
number = {1},
abstract = {Substantial clinical evidence supports the notion that ciliary function in the airways is important in COVID-19 pathogenesis. Although ciliary damage has been observed in both in vitro and in vivo models, the extent or nature of impairment of mucociliary transport (MCT) in in vivo models remains unknown. We hypothesize that SARS-CoV-2 infection results in MCT deficiency in the airways of golden Syrian hamsters that precedes pathological injury in lung parenchyma. Micro-optical coherence tomography was used to quantitate functional changes in the MCT apparatus. Both genomic and subgenomic viral RNA pathological and physiological changes were monitored in parallel. We show that SARS-CoV-2 infection caused a 67% decrease in MCT rate as early as 2 days postinfection (dpi) in hamsters, principally due to 79% diminished airway coverage of motile cilia. Correlating quantitation of physiological, virological, and pathological changes reveals steadily descending infection from the upper airways to lower airways to lung parenchyma within 7 dpi. Our results indicate that functional deficits of the MCT apparatus are a key aspect of COVID-19 pathogenesis, may extend viral retention, and could pose a risk factor for secondary infection. Clinically, monitoring abnormal ciliated cell function may indicate disease progression. Therapies directed toward the MCT apparatus deserve further investigation.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Substantial clinical evidence supports the notion that ciliary function in the airways is important in COVID-19 pathogenesis. Although ciliary damage has been observed in both in vitro and in vivo models, the extent or nature of impairment of mucociliary transport (MCT) in in vivo models remains unknown. We hypothesize that SARS-CoV-2 infection results in MCT deficiency in the airways of golden Syrian hamsters that precedes pathological injury in lung parenchyma. Micro-optical coherence tomography was used to quantitate functional changes in the MCT apparatus. Both genomic and subgenomic viral RNA pathological and physiological changes were monitored in parallel. We show that SARS-CoV-2 infection caused a 67% decrease in MCT rate as early as 2 days postinfection (dpi) in hamsters, principally due to 79% diminished airway coverage of motile cilia. Correlating quantitation of physiological, virological, and pathological changes reveals steadily descending infection from the upper airways to lower airways to lung parenchyma within 7 dpi. Our results indicate that functional deficits of the MCT apparatus are a key aspect of COVID-19 pathogenesis, may extend viral retention, and could pose a risk factor for secondary infection. Clinically, monitoring abnormal ciliated cell function may indicate disease progression. Therapies directed toward the MCT apparatus deserve further investigation.
รap, Murat; Torii, Ryo; Onuma, Yoshinobu; Krams, Rob; Bennett, Martin R; Stone, Peter H; Serruys, Patrick W; Bourantas, Christos V
Editorial: Computational modeling for assessing coronary artery pathophysiology Miscellaneous
2023, ISSN: 2297-055X.
@misc{pmid36733302,
title = {Editorial: Computational modeling for assessing coronary artery pathophysiology},
author = {Murat รap and Ryo Torii and Yoshinobu Onuma and Rob Krams and Martin R Bennett and Peter H Stone and Patrick W Serruys and Christos V Bourantas},
doi = {10.3389/fcvm.2023.1113835},
issn = {2297-055X},
year = {2023},
date = {2023-01-01},
journal = {Front Cardiovasc Med},
volume = {10},
pages = {1113835},
keywords = {},
pubstate = {published},
tppubtype = {misc}
}
Hakim, Diaa; Coskun, Ahmet U; Maynard, Charles; Pu, Zhongyue; Rupert, Deborah; Cefalo, Nicholas; Cormier, Michelle; Ahmed, Mona; Earls, James; Jennings, Rob; Croce, Kevin; Mushtaq, Saima; Andreini, Daniele; Conte, Edoardo; Molony, David; Samady, Habib; Min, James K; Stone, Peter H
Endothelial shear stress computed from coronary computed tomography angiography: A direct comparison to intravascular ultrasound Journal Article
In: J Cardiovasc Comput Tomogr, vol. 17, no. 3, pp. 201โ210, 2023, ISSN: 1876-861X.
@article{pmid37076326,
title = {Endothelial shear stress computed from coronary computed tomography angiography: A direct comparison to intravascular ultrasound},
author = {Diaa Hakim and Ahmet U Coskun and Charles Maynard and Zhongyue Pu and Deborah Rupert and Nicholas Cefalo and Michelle Cormier and Mona Ahmed and James Earls and Rob Jennings and Kevin Croce and Saima Mushtaq and Daniele Andreini and Edoardo Conte and David Molony and Habib Samady and James K Min and Peter H Stone},
doi = {10.1016/j.jcct.2023.03.009},
issn = {1876-861X},
year = {2023},
date = {2023-01-01},
journal = {J Cardiovasc Comput Tomogr},
volume = {17},
number = {3},
pages = {201--210},
abstract = {INTRODUCTION: Intravascular ultrasound (IVUS) studies have shown that biomechanical variables, particularly endothelial shear stress (ESS), add synergistic prognostic insight when combined with anatomic high-risk plaque features. Non-invasive risk assessment of coronary plaques with coronary computed tomography angiography (CCTA) would be helpful to enable broad population risk-screening.nnAIM: To compare the accuracy of ESS computation of local ESS metrics by CCTA vs IVUS imaging.nnMETHODS: We analyzed 59 patients from a registry of patients who underwent both IVUS and CCTA for suspected CAD. CCTA images were acquired using either a 64- or 256-slice scanner. Lumen, vessel, and plaque areas were segmented from both IVUS and CCTA (59 arteries, 686 3-mm segments). Images were co-registered and used to generate a 3-D arterial reconstruction, and local ESS distribution was assessed by computational fluid dynamics (CFD) and reported in consecutive 3-mm segments.nnRESULTS: Anatomical plaque characteristics (vessel, lumen, plaque area and minimal luminal area [MLA] per artery) were correlated when measured with IVUS and CCTA: 12.7ย โยฑย โ4.3 vs 10.7ย โยฑย โ4.5ย โmm, rย โ=ย โ0.63; 6.8ย โยฑย โ2.7 vs 5.6ย โยฑย โ2.7ย โmm, rย โ=ย โ0.43; 5.9ย โยฑย โ2.9 vs 5.1ย โยฑย โ3.2ย โmm, rย โ=ย โ0.52; 4.5ย โยฑย โ1.3 vs 4.1ย โยฑย โ1.5ย โmm, rย โ=ย โ0.67 respectively. ESS metrics of local minimal, maximal, and average ESS were also moderately correlated when measured with IVUS and CCTA (2.0ย โยฑย โ1.4 vs 2.5ย โยฑย โ2.6ย โPa rย โ=ย โ0.28; 3.3ย โยฑย โ1.6 vs 4.2ย โยฑย โ3.6ย โPa, rย โ=ย โ0.42; 2.6ย โยฑย โ1.5 vs 3.3ย โยฑย โ3.0ย โPa, rย โ=ย โ0.35, respectively). CCTA-based computation accurately identified the spatial localization of local ESS heterogeneity compared to IVUS, with Bland-Altman analyses indicating that the absolute ESS differences between the two CCTA methods were pathobiologically minor.nnCONCLUSION: Local ESS evaluation by CCTA is possible and similar to IVUS; and is useful for identifying local flow patterns that are relevant to plaque development, progression, and destabilization.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
INTRODUCTION: Intravascular ultrasound (IVUS) studies have shown that biomechanical variables, particularly endothelial shear stress (ESS), add synergistic prognostic insight when combined with anatomic high-risk plaque features. Non-invasive risk assessment of coronary plaques with coronary computed tomography angiography (CCTA) would be helpful to enable broad population risk-screening.nnAIM: To compare the accuracy of ESS computation of local ESS metrics by CCTA vs IVUS imaging.nnMETHODS: We analyzed 59 patients from a registry of patients who underwent both IVUS and CCTA for suspected CAD. CCTA images were acquired using either a 64- or 256-slice scanner. Lumen, vessel, and plaque areas were segmented from both IVUS and CCTA (59 arteries, 686 3-mm segments). Images were co-registered and used to generate a 3-D arterial reconstruction, and local ESS distribution was assessed by computational fluid dynamics (CFD) and reported in consecutive 3-mm segments.nnRESULTS: Anatomical plaque characteristics (vessel, lumen, plaque area and minimal luminal area [MLA] per artery) were correlated when measured with IVUS and CCTA: 12.7ย โยฑย โ4.3 vs 10.7ย โยฑย โ4.5ย โmm, rย โ=ย โ0.63; 6.8ย โยฑย โ2.7 vs 5.6ย โยฑย โ2.7ย โmm, rย โ=ย โ0.43; 5.9ย โยฑย โ2.9 vs 5.1ย โยฑย โ3.2ย โmm, rย โ=ย โ0.52; 4.5ย โยฑย โ1.3 vs 4.1ย โยฑย โ1.5ย โmm, rย โ=ย โ0.67 respectively. ESS metrics of local minimal, maximal, and average ESS were also moderately correlated when measured with IVUS and CCTA (2.0ย โยฑย โ1.4 vs 2.5ย โยฑย โ2.6ย โPa rย โ=ย โ0.28; 3.3ย โยฑย โ1.6 vs 4.2ย โยฑย โ3.6ย โPa, rย โ=ย โ0.42; 2.6ย โยฑย โ1.5 vs 3.3ย โยฑย โ3.0ย โPa, rย โ=ย โ0.35, respectively). CCTA-based computation accurately identified the spatial localization of local ESS heterogeneity compared to IVUS, with Bland-Altman analyses indicating that the absolute ESS differences between the two CCTA methods were pathobiologically minor.nnCONCLUSION: Local ESS evaluation by CCTA is possible and similar to IVUS; and is useful for identifying local flow patterns that are relevant to plaque development, progression, and destabilization.
2022
Araki, Makoto; Park, Seung-Jung; Dauerman, Harold L; Uemura, Shiro; Kim, Jung-Sun; Mario, Carlo Di; Johnson, Thomas W; Guagliumi, Giulio; Kastrati, Adnan; Joner, Michael; Holm, Niels Ramsing; Alfonso, Fernando; Wijns, William; Adriaenssens, Tom; Nef, Holger; Rioufol, Gilles; Amabile, Nicolas; Souteyrand, Geraud; Meneveau, Nicolas; Gerbaud, Edouard; Opolski, Maksymilian P; Gonzalo, Nieves; Tearney, Guillermo J; Bouma, Brett; Aguirre, Aaron D; Mintz, Gary S; Stone, Gregg W; Bourantas, Christos V; Rรคber, Lorenz; Gili, Sebastiano; Mizuno, Kyoichi; Kimura, Shigeki; Shinke, Toshiro; Hong, Myeong-Ki; Jang, Yangsoo; Cho, Jin Man; Yan, Bryan P; Porto, Italo; Niccoli, Giampaolo; Montone, Rocco A; Thondapu, Vikas; Papafaklis, Michail I; Michalis, Lampros K; Reynolds, Harmony; Saw, Jacqueline; Libby, Peter; Weisz, Giora; Iannaccone, Mario; Gori, Tommaso; Toutouzas, Konstantinos; Yonetsu, Taishi; Minami, Yoshiyasu; Takano, Masamichi; Raffel, O Christopher; Kurihara, Osamu; Soeda, Tsunenari; Sugiyama, Tomoyo; Kim, Hyung Oh; Lee, Tetsumin; Higuma, Takumi; Nakajima, Akihiro; Yamamoto, Erika; Bryniarski, Krzysztof L; Vito, Luca Di; Vergallo, Rocco; Fracassi, Francesco; Russo, Michele; Seegers, Lena M; McNulty, Iris; Park, Sangjoon; Feldman, Marc; Escaned, Javier; Prati, Francesco; Arbustini, Eloisa; Pinto, Fausto J; Waksman, Ron; Garcia-Garcia, Hector M; Maehara, Akiko; Ali, Ziad; Finn, Aloke V; Virmani, Renu; Kini, Annapoorna S; Daemen, Joost; Kume, Teruyoshi; Hibi, Kiyoshi; Tanaka, Atsushi; Akasaka, Takashi; Kubo, Takashi; Yasuda, Satoshi; Croce, Kevin; Granada, Juan F; Lerman, Amir; Prasad, Abhiram; Regar, Evelyn; Saito, Yoshihiko; Sankardas, Mullasari Ajit; Subban, Vijayakumar; Weissman, Neil J; Chen, Yundai; Yu, Bo; Nicholls, Stephen J; Barlis, Peter; West, Nick E J; Arbab-Zadeh, Armin; Ye, Jong Chul; Dijkstra, Jouke; Lee, Hang; Narula, Jagat; Crea, Filippo; Nakamura, Sunao; Kakuta, Tsunekazu; Fujimoto, James; Fuster, Valentin; Jang, Ik-Kyung
Optical coherence tomography in coronary atherosclerosis assessment and intervention Journal Article
In: Nat Rev Cardiol, vol. 19, no. 10, pp. 684โ703, 2022, ISSN: 1759-5010.
@article{pmid35449407b,
title = {Optical coherence tomography in coronary atherosclerosis assessment and intervention},
author = {Makoto Araki and Seung-Jung Park and Harold L Dauerman and Shiro Uemura and Jung-Sun Kim and Carlo Di Mario and Thomas W Johnson and Giulio Guagliumi and Adnan Kastrati and Michael Joner and Niels Ramsing Holm and Fernando Alfonso and William Wijns and Tom Adriaenssens and Holger Nef and Gilles Rioufol and Nicolas Amabile and Geraud Souteyrand and Nicolas Meneveau and Edouard Gerbaud and Maksymilian P Opolski and Nieves Gonzalo and Guillermo J Tearney and Brett Bouma and Aaron D Aguirre and Gary S Mintz and Gregg W Stone and Christos V Bourantas and Lorenz Rรคber and Sebastiano Gili and Kyoichi Mizuno and Shigeki Kimura and Toshiro Shinke and Myeong-Ki Hong and Yangsoo Jang and Jin Man Cho and Bryan P Yan and Italo Porto and Giampaolo Niccoli and Rocco A Montone and Vikas Thondapu and Michail I Papafaklis and Lampros K Michalis and Harmony Reynolds and Jacqueline Saw and Peter Libby and Giora Weisz and Mario Iannaccone and Tommaso Gori and Konstantinos Toutouzas and Taishi Yonetsu and Yoshiyasu Minami and Masamichi Takano and O Christopher Raffel and Osamu Kurihara and Tsunenari Soeda and Tomoyo Sugiyama and Hyung Oh Kim and Tetsumin Lee and Takumi Higuma and Akihiro Nakajima and Erika Yamamoto and Krzysztof L Bryniarski and Luca Di Vito and Rocco Vergallo and Francesco Fracassi and Michele Russo and Lena M Seegers and Iris McNulty and Sangjoon Park and Marc Feldman and Javier Escaned and Francesco Prati and Eloisa Arbustini and Fausto J Pinto and Ron Waksman and Hector M Garcia-Garcia and Akiko Maehara and Ziad Ali and Aloke V Finn and Renu Virmani and Annapoorna S Kini and Joost Daemen and Teruyoshi Kume and Kiyoshi Hibi and Atsushi Tanaka and Takashi Akasaka and Takashi Kubo and Satoshi Yasuda and Kevin Croce and Juan F Granada and Amir Lerman and Abhiram Prasad and Evelyn Regar and Yoshihiko Saito and Mullasari Ajit Sankardas and Vijayakumar Subban and Neil J Weissman and Yundai Chen and Bo Yu and Stephen J Nicholls and Peter Barlis and Nick E J West and Armin Arbab-Zadeh and Jong Chul Ye and Jouke Dijkstra and Hang Lee and Jagat Narula and Filippo Crea and Sunao Nakamura and Tsunekazu Kakuta and James Fujimoto and Valentin Fuster and Ik-Kyung Jang},
doi = {10.1038/s41569-022-00687-9},
issn = {1759-5010},
year = {2022},
date = {2022-10-01},
journal = {Nat Rev Cardiol},
volume = {19},
number = {10},
pages = {684--703},
abstract = {Since optical coherence tomography (OCT) was first performed in humans two decades ago, this imaging modality has been widely adopted in research on coronary atherosclerosis and adopted clinically for the optimization of percutaneous coronary intervention. In the past 10 years, substantial advances have been made in the understanding of in vivo vascular biology using OCT. Identification by OCT of culprit plaque pathology could potentially lead to a major shift in the management of patients with acute coronary syndromes. Detection by OCT of healed coronary plaque has been important in our understanding of the mechanisms involved in plaque destabilization and healing with the rapid progression of atherosclerosis. Accurate detection by OCT of sequelae from percutaneous coronary interventions that might be missed by angiography could improve clinical outcomes. In addition, OCT has become an essential diagnostic modality for myocardial infarction with non-obstructive coronary arteries. Insight into neoatherosclerosis from OCT could improve our understanding of the mechanisms of very late stent thrombosis. The appropriate use of OCT depends on accurate interpretation and understanding of the clinical significance of OCT findings. In this Review, we summarize the state of the art in cardiac OCT and facilitate the uniform use of this modality in coronary atherosclerosis. Contributions have been made by clinicians and investigators worldwide with extensive experience in OCT, with the aim that this document will serve as a standard reference for future research and clinical application.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Since optical coherence tomography (OCT) was first performed in humans two decades ago, this imaging modality has been widely adopted in research on coronary atherosclerosis and adopted clinically for the optimization of percutaneous coronary intervention. In the past 10 years, substantial advances have been made in the understanding of in vivo vascular biology using OCT. Identification by OCT of culprit plaque pathology could potentially lead to a major shift in the management of patients with acute coronary syndromes. Detection by OCT of healed coronary plaque has been important in our understanding of the mechanisms involved in plaque destabilization and healing with the rapid progression of atherosclerosis. Accurate detection by OCT of sequelae from percutaneous coronary interventions that might be missed by angiography could improve clinical outcomes. In addition, OCT has become an essential diagnostic modality for myocardial infarction with non-obstructive coronary arteries. Insight into neoatherosclerosis from OCT could improve our understanding of the mechanisms of very late stent thrombosis. The appropriate use of OCT depends on accurate interpretation and understanding of the clinical significance of OCT findings. In this Review, we summarize the state of the art in cardiac OCT and facilitate the uniform use of this modality in coronary atherosclerosis. Contributions have been made by clinicians and investigators worldwide with extensive experience in OCT, with the aim that this document will serve as a standard reference for future research and clinical application.
Araki, Makoto; Park, Seung-Jung; Dauerman, Harold L; Uemura, Shiro; Kim, Jung-Sun; Mario, Carlo Di; Johnson, Thomas W; Guagliumi, Giulio; Kastrati, Adnan; Joner, Michael; Holm, Niels Ramsing; Alfonso, Fernando; Wijns, William; Adriaenssens, Tom; Nef, Holger; Rioufol, Gilles; Amabile, Nicolas; Souteyrand, Geraud; Meneveau, Nicolas; Gerbaud, Edouard; Opolski, Maksymilian P; Gonzalo, Nieves; Tearney, Guillermo J; Bouma, Brett; Aguirre, Aaron D; Mintz, Gary S; Stone, Gregg W; Bourantas, Christos V; Rรคber, Lorenz; Gili, Sebastiano; Mizuno, Kyoichi; Kimura, Shigeki; Shinke, Toshiro; Hong, Myeong-Ki; Jang, Yangsoo; Cho, Jin Man; Yan, Bryan P; Porto, Italo; Niccoli, Giampaolo; Montone, Rocco A; Thondapu, Vikas; Papafaklis, Michail I; Michalis, Lampros K; Reynolds, Harmony; Saw, Jacqueline; Libby, Peter; Weisz, Giora; Iannaccone, Mario; Gori, Tommaso; Toutouzas, Konstantinos; Yonetsu, Taishi; Minami, Yoshiyasu; Takano, Masamichi; Raffel, O Christopher; Kurihara, Osamu; Soeda, Tsunenari; Sugiyama, Tomoyo; Kim, Hyung Oh; Lee, Tetsumin; Higuma, Takumi; Nakajima, Akihiro; Yamamoto, Erika; Bryniarski, Krzysztof L; Vito, Luca Di; Vergallo, Rocco; Fracassi, Francesco; Russo, Michele; Seegers, Lena M; McNulty, Iris; Park, Sangjoon; Feldman, Marc; Escaned, Javier; Prati, Francesco; Arbustini, Eloisa; Pinto, Fausto J; Waksman, Ron; Garcia-Garcia, Hector M; Maehara, Akiko; Ali, Ziad; Finn, Aloke V; Virmani, Renu; Kini, Annapoorna S; Daemen, Joost; Kume, Teruyoshi; Hibi, Kiyoshi; Tanaka, Atsushi; Akasaka, Takashi; Kubo, Takashi; Yasuda, Satoshi; Croce, Kevin; Granada, Juan F; Lerman, Amir; Prasad, Abhiram; Regar, Evelyn; Saito, Yoshihiko; Sankardas, Mullasari Ajit; Subban, Vijayakumar; Weissman, Neil J; Chen, Yundai; Yu, Bo; Nicholls, Stephen J; Barlis, Peter; West, Nick E J; Arbab-Zadeh, Armin; Ye, Jong Chul; Dijkstra, Jouke; Lee, Hang; Narula, Jagat; Crea, Filippo; Nakamura, Sunao; Kakuta, Tsunekazu; Fujimoto, James; Fuster, Valentin; Jang, Ik-Kyung
Optical coherence tomography in coronary atherosclerosis assessment and intervention Journal Article
In: Nat Rev Cardiol, vol. 19, no. 10, pp. 684โ703, 2022, ISSN: 1759-5010.
@article{pmid35449407,
title = {Optical coherence tomography in coronary atherosclerosis assessment and intervention},
author = {Makoto Araki and Seung-Jung Park and Harold L Dauerman and Shiro Uemura and Jung-Sun Kim and Carlo Di Mario and Thomas W Johnson and Giulio Guagliumi and Adnan Kastrati and Michael Joner and Niels Ramsing Holm and Fernando Alfonso and William Wijns and Tom Adriaenssens and Holger Nef and Gilles Rioufol and Nicolas Amabile and Geraud Souteyrand and Nicolas Meneveau and Edouard Gerbaud and Maksymilian P Opolski and Nieves Gonzalo and Guillermo J Tearney and Brett Bouma and Aaron D Aguirre and Gary S Mintz and Gregg W Stone and Christos V Bourantas and Lorenz Rรคber and Sebastiano Gili and Kyoichi Mizuno and Shigeki Kimura and Toshiro Shinke and Myeong-Ki Hong and Yangsoo Jang and Jin Man Cho and Bryan P Yan and Italo Porto and Giampaolo Niccoli and Rocco A Montone and Vikas Thondapu and Michail I Papafaklis and Lampros K Michalis and Harmony Reynolds and Jacqueline Saw and Peter Libby and Giora Weisz and Mario Iannaccone and Tommaso Gori and Konstantinos Toutouzas and Taishi Yonetsu and Yoshiyasu Minami and Masamichi Takano and O Christopher Raffel and Osamu Kurihara and Tsunenari Soeda and Tomoyo Sugiyama and Hyung Oh Kim and Tetsumin Lee and Takumi Higuma and Akihiro Nakajima and Erika Yamamoto and Krzysztof L Bryniarski and Luca Di Vito and Rocco Vergallo and Francesco Fracassi and Michele Russo and Lena M Seegers and Iris McNulty and Sangjoon Park and Marc Feldman and Javier Escaned and Francesco Prati and Eloisa Arbustini and Fausto J Pinto and Ron Waksman and Hector M Garcia-Garcia and Akiko Maehara and Ziad Ali and Aloke V Finn and Renu Virmani and Annapoorna S Kini and Joost Daemen and Teruyoshi Kume and Kiyoshi Hibi and Atsushi Tanaka and Takashi Akasaka and Takashi Kubo and Satoshi Yasuda and Kevin Croce and Juan F Granada and Amir Lerman and Abhiram Prasad and Evelyn Regar and Yoshihiko Saito and Mullasari Ajit Sankardas and Vijayakumar Subban and Neil J Weissman and Yundai Chen and Bo Yu and Stephen J Nicholls and Peter Barlis and Nick E J West and Armin Arbab-Zadeh and Jong Chul Ye and Jouke Dijkstra and Hang Lee and Jagat Narula and Filippo Crea and Sunao Nakamura and Tsunekazu Kakuta and James Fujimoto and Valentin Fuster and Ik-Kyung Jang},
doi = {10.1038/s41569-022-00687-9},
issn = {1759-5010},
year = {2022},
date = {2022-10-01},
journal = {Nat Rev Cardiol},
volume = {19},
number = {10},
pages = {684--703},
abstract = {Since optical coherence tomography (OCT) was first performed in humans two decades ago, this imaging modality has been widely adopted in research on coronary atherosclerosis and adopted clinically for the optimization of percutaneous coronary intervention. In the past 10 years, substantial advances have been made in the understanding of in vivo vascular biology using OCT. Identification by OCT of culprit plaque pathology could potentially lead to a major shift in the management of patients with acute coronary syndromes. Detection by OCT of healed coronary plaque has been important in our understanding of the mechanisms involved in plaque destabilization and healing with the rapid progression of atherosclerosis. Accurate detection by OCT of sequelae from percutaneous coronary interventions that might be missed by angiography could improve clinical outcomes. In addition, OCT has become an essential diagnostic modality for myocardial infarction with non-obstructive coronary arteries. Insight into neoatherosclerosis from OCT could improve our understanding of the mechanisms of very late stent thrombosis. The appropriate use of OCT depends on accurate interpretation and understanding of the clinical significance of OCT findings. In this Review, we summarize the state of the art in cardiac OCT and facilitate the uniform use of this modality in coronary atherosclerosis. Contributions have been made by clinicians and investigators worldwide with extensive experience in OCT, with the aim that this document will serve as a standard reference for future research and clinical application.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Since optical coherence tomography (OCT) was first performed in humans two decades ago, this imaging modality has been widely adopted in research on coronary atherosclerosis and adopted clinically for the optimization of percutaneous coronary intervention. In the past 10 years, substantial advances have been made in the understanding of in vivo vascular biology using OCT. Identification by OCT of culprit plaque pathology could potentially lead to a major shift in the management of patients with acute coronary syndromes. Detection by OCT of healed coronary plaque has been important in our understanding of the mechanisms involved in plaque destabilization and healing with the rapid progression of atherosclerosis. Accurate detection by OCT of sequelae from percutaneous coronary interventions that might be missed by angiography could improve clinical outcomes. In addition, OCT has become an essential diagnostic modality for myocardial infarction with non-obstructive coronary arteries. Insight into neoatherosclerosis from OCT could improve our understanding of the mechanisms of very late stent thrombosis. The appropriate use of OCT depends on accurate interpretation and understanding of the clinical significance of OCT findings. In this Review, we summarize the state of the art in cardiac OCT and facilitate the uniform use of this modality in coronary atherosclerosis. Contributions have been made by clinicians and investigators worldwide with extensive experience in OCT, with the aim that this document will serve as a standard reference for future research and clinical application.
Otuya, David O; Dechene, Nicholas M; Poshtupaka, Darina; Judson, Seth; Carlson, Camella J; Zemlok, Sarah K; Sevieri, Evan; Choy, Peter; Shore, Rachel E; Leรณn-Peralta, Esmarline De; Cirio, Alissa A; Rihm, Tyler W; Krall, Alexander A; Gavgiotaki, Evangelia; Dong, Jing; Silva, Sarah L; Baillargeon, Aaron; Baldwin, Grace; Gao, Anna H; Jansa, Zachary; Barrios, Amilcar; Ryan, Emily; Bhat, Nitasha G M; Balmasheva, Indira; Chung, Anita; Grant, Catriona N; Bablouzian, Ara L; Beatty, Matthew; Ahsen, Osman O; Zheng, Hui; Tearney, Guillermo J
Passively scanned, single-fiber optical coherence tomography probes for gastrointestinal devices Journal Article
In: Lasers Surg Med, vol. 54, no. 7, pp. 935โ944, 2022, ISSN: 1096-9101.
@article{pmid35708124,
title = {Passively scanned, single-fiber optical coherence tomography probes for gastrointestinal devices},
author = {David O Otuya and Nicholas M Dechene and Darina Poshtupaka and Seth Judson and Camella J Carlson and Sarah K Zemlok and Evan Sevieri and Peter Choy and Rachel E Shore and Esmarline De Leรณn-Peralta and Alissa A Cirio and Tyler W Rihm and Alexander A Krall and Evangelia Gavgiotaki and Jing Dong and Sarah L Silva and Aaron Baillargeon and Grace Baldwin and Anna H Gao and Zachary Jansa and Amilcar Barrios and Emily Ryan and Nitasha G M Bhat and Indira Balmasheva and Anita Chung and Catriona N Grant and Ara L Bablouzian and Matthew Beatty and Osman O Ahsen and Hui Zheng and Guillermo J Tearney},
doi = {10.1002/lsm.23576},
issn = {1096-9101},
year = {2022},
date = {2022-09-01},
journal = {Lasers Surg Med},
volume = {54},
number = {7},
pages = {935--944},
abstract = {BACKGROUND/OBJECTIVES: Optical coherence tomography (OCT) uses low coherence interferometry to obtain depth-resolved tissue reflectivity profiles (M-mode) and transverse beam scanning to create images of two-dimensional tissue morphology (B-mode). Endoscopic OCT imaging probes typically employ proximal or distal mechanical beam scanning mechanisms that increase cost, complexity, and size. Here, we demonstrate in the gastrointestinal (GI) tracts of unsedated human patients, that a passive, single-fiber probe can be used to guide device placement, conduct device-tissue physical contact sensing, and obtain two-dimensional OCT images via M-to-B-mode conversion.nnMATERIALS AND METHODS: We designed and developed ultrasmall, manually scannable, side-ย and forward-viewing single fiber-optic probes that can capture M-mode OCT data. Side-viewing M-mode OCT probes were incorporated into brush biopsy devices designed to harvest the microbiome and forward-viewing M-mode OCT probes were integrated into devices that measure intestinal potential difference (IPD). The M-mode OCT probe-coupled devices were utilized in the GIย tract in six unsedated patients in vivo. M-mode data were converted into B-mode images using an M-to-B-mode conversion algorithm. The effectiveness of physical contact sensing by the M-mode OCT probes was assessed by comparing the variances of the IPD values when the probe was in physical contact with the tissue versus when it was not. The capacity of forward- and side-viewing M-mode OCT probes to produce high-quality B-mode images was compared by computing the percentages of the M-to-B-mode images that showed close contact between the probe and the luminal surface. Passively scanned M-to-B-mode images were qualitatively compared to B-mode images obtained by mechanical scanning OCT tethered capsule endomicroscopy (TCE) imaging devices.nnRESULTS: The incorporation of M-mode OCT probes in these nonendoscopic GI devices safely and effectively enabled M-mode OCT imaging, facilitating real-time device placement guidance and contact sensing in vivo. Results showed that M-mode OCT contact sensing improved the variance of IPD measurements threefold and side-viewing probes increased M-to-B-mode image visibility by 10%. Images of the esophagus, stomach, and duodenum generated by the passively scanned probes and M-to-B-mode conversion were qualitatively superior to B-mode images obtained by mechanically scanning OCT TCE devices.nnCONCLUSION: These results show that passive, single optical fiber OCT probes can be effectively utilized for nonendoscopic device placement guidance, device contact sensing, and two-dimensional morphologic imaging in the human GI tract in vivo. Due to their small size, lower cost, and reduced complexity, these M-mode OCT probes may provide an easier avenue for the incorporation of OCT functionality into endoscopic/nonendoscopic devices.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND/OBJECTIVES: Optical coherence tomography (OCT) uses low coherence interferometry to obtain depth-resolved tissue reflectivity profiles (M-mode) and transverse beam scanning to create images of two-dimensional tissue morphology (B-mode). Endoscopic OCT imaging probes typically employ proximal or distal mechanical beam scanning mechanisms that increase cost, complexity, and size. Here, we demonstrate in the gastrointestinal (GI) tracts of unsedated human patients, that a passive, single-fiber probe can be used to guide device placement, conduct device-tissue physical contact sensing, and obtain two-dimensional OCT images via M-to-B-mode conversion.nnMATERIALS AND METHODS: We designed and developed ultrasmall, manually scannable, side-ย and forward-viewing single fiber-optic probes that can capture M-mode OCT data. Side-viewing M-mode OCT probes were incorporated into brush biopsy devices designed to harvest the microbiome and forward-viewing M-mode OCT probes were integrated into devices that measure intestinal potential difference (IPD). The M-mode OCT probe-coupled devices were utilized in the GIย tract in six unsedated patients in vivo. M-mode data were converted into B-mode images using an M-to-B-mode conversion algorithm. The effectiveness of physical contact sensing by the M-mode OCT probes was assessed by comparing the variances of the IPD values when the probe was in physical contact with the tissue versus when it was not. The capacity of forward- and side-viewing M-mode OCT probes to produce high-quality B-mode images was compared by computing the percentages of the M-to-B-mode images that showed close contact between the probe and the luminal surface. Passively scanned M-to-B-mode images were qualitatively compared to B-mode images obtained by mechanical scanning OCT tethered capsule endomicroscopy (TCE) imaging devices.nnRESULTS: The incorporation of M-mode OCT probes in these nonendoscopic GI devices safely and effectively enabled M-mode OCT imaging, facilitating real-time device placement guidance and contact sensing in vivo. Results showed that M-mode OCT contact sensing improved the variance of IPD measurements threefold and side-viewing probes increased M-to-B-mode image visibility by 10%. Images of the esophagus, stomach, and duodenum generated by the passively scanned probes and M-to-B-mode conversion were qualitatively superior to B-mode images obtained by mechanically scanning OCT TCE devices.nnCONCLUSION: These results show that passive, single optical fiber OCT probes can be effectively utilized for nonendoscopic device placement guidance, device contact sensing, and two-dimensional morphologic imaging in the human GI tract in vivo. Due to their small size, lower cost, and reduced complexity, these M-mode OCT probes may provide an easier avenue for the incorporation of OCT functionality into endoscopic/nonendoscopic devices.
Liu, Guigen; Kang, Jeon Woong; Bhagavatula, Sharath; Ahn, Sebastian W; So, Peter T C; Tearney, Guillermo J; Jonas, Oliver
Bendable long graded index lens microendoscopy Journal Article
In: Opt Express, vol. 30, no. 20, pp. 36651โ36664, 2022, ISSN: 1094-4087.
@article{pmid36258589,
title = {Bendable long graded index lens microendoscopy},
author = {Guigen Liu and Jeon Woong Kang and Sharath Bhagavatula and Sebastian W Ahn and Peter T C So and Guillermo J Tearney and Oliver Jonas},
doi = {10.1364/OE.468827},
issn = {1094-4087},
year = {2022},
date = {2022-09-01},
journal = {Opt Express},
volume = {30},
number = {20},
pages = {36651--36664},
abstract = {Graded index (GRIN) lens endoscopy has broadly benefited biomedical microscopic imaging by enabling accessibility to sites not reachable by traditional benchtop microscopes. It is a long-held notion that GRIN lenses can only be used as rigid probes, which may limit their potential for certain applications. Here, we describe bendable and long-range GRIN microimaging probes for a variety of potential micro-endoscopic biomedical applications. Using a two-photon fluorescence imaging system, we have experimentally demonstrated the feasibility of three-dimensional imaging through a 500-ยตm-diameter and โผ11 cm long GRIN lens subject to a cantilever beam-like deflection with a minimum bend radius of โผ25 cm. Bend-induced perturbation to the field of view and resolution has also been investigated quantitatively. Our development alters the conventional notion of GRIN lenses and enables a range of innovative applications. For example, the demonstrated flexibility is highly desirable for implementation into current and emerging minimally invasive clinical procedures, including a pioneering microdevice for high-throughput cancer drug selection.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Graded index (GRIN) lens endoscopy has broadly benefited biomedical microscopic imaging by enabling accessibility to sites not reachable by traditional benchtop microscopes. It is a long-held notion that GRIN lenses can only be used as rigid probes, which may limit their potential for certain applications. Here, we describe bendable and long-range GRIN microimaging probes for a variety of potential micro-endoscopic biomedical applications. Using a two-photon fluorescence imaging system, we have experimentally demonstrated the feasibility of three-dimensional imaging through a 500-ยตm-diameter and โผ11 cm long GRIN lens subject to a cantilever beam-like deflection with a minimum bend radius of โผ25 cm. Bend-induced perturbation to the field of view and resolution has also been investigated quantitatively. Our development alters the conventional notion of GRIN lenses and enables a range of innovative applications. For example, the demonstrated flexibility is highly desirable for implementation into current and emerging minimally invasive clinical procedures, including a pioneering microdevice for high-throughput cancer drug selection.
Yao, Song; Campbell, Peter T; Ugai, Tomotaka; Gierach, Gretchen; Abubakar, Mustapha; Adalsteinsson, Viktor; Almeida, Jonas; Brennan, Paul; Chanock, Stephen; Golub, Todd; Hanash, Samir; Harris, Curtis; Hathaway, Cassandra A; Kelsey, Karl; Landi, Maria Teresa; Mahmood, Faisal; Newton, Christina; Quackenbush, John; Rodig, Scott; Schultz, Nikolaus; Tearney, Guillermo; Tworoger, Shelley S; Wang, Molin; Zhang, Xuehong; Garcia-Closas, Montserrat; Rebbeck, Timothy R; Ambrosone, Christine B; Ogino, Shuji
Proceedings of the fifth international Molecular Pathological Epidemiology (MPE) meeting Journal Article
In: Cancer Causes Control, vol. 33, no. 8, pp. 1107โ1120, 2022, ISSN: 1573-7225.
@article{pmid35759080,
title = {Proceedings of the fifth international Molecular Pathological Epidemiology (MPE) meeting},
author = {Song Yao and Peter T Campbell and Tomotaka Ugai and Gretchen Gierach and Mustapha Abubakar and Viktor Adalsteinsson and Jonas Almeida and Paul Brennan and Stephen Chanock and Todd Golub and Samir Hanash and Curtis Harris and Cassandra A Hathaway and Karl Kelsey and Maria Teresa Landi and Faisal Mahmood and Christina Newton and John Quackenbush and Scott Rodig and Nikolaus Schultz and Guillermo Tearney and Shelley S Tworoger and Molin Wang and Xuehong Zhang and Montserrat Garcia-Closas and Timothy R Rebbeck and Christine B Ambrosone and Shuji Ogino},
doi = {10.1007/s10552-022-01594-7},
issn = {1573-7225},
year = {2022},
date = {2022-08-01},
journal = {Cancer Causes Control},
volume = {33},
number = {8},
pages = {1107--1120},
abstract = {Cancer heterogeneities hold the key to a deeper understanding of cancer etiology and progression and the discovery of more precise cancer therapy. Modern pathological and molecular technologies offer a powerful set of tools to profile tumor heterogeneities at multiple levels in large patient populations, from DNA to RNA, protein and epigenetics, and from tumor tissues to tumor microenvironment and liquid biopsy. When coupled with well-validated epidemiologic methodology and well-characterized epidemiologic resources, the rich tumor pathological and molecular tumor information provide new research opportunities at an unprecedented breadth and depth. This is the research space where Molecular Pathological Epidemiology (MPE) emerged over a decade ago and has been thriving since then. As a truly multidisciplinary field, MPE embraces collaborations from diverse fields including epidemiology, pathology, immunology, genetics, biostatistics, bioinformatics, and data science. Since first convened in 2013, the International MPE Meeting series has grown into a dynamic and dedicated platform for experts from these disciplines to communicate novel findings, discuss new research opportunities and challenges, build professional networks, and educate the next-generation scientists. Herein, we share the proceedings of the Fifth International MPE meeting, held virtually online, on May 24 and 25, 2021. The meeting consisted of 21 presentations organized into the three main themes, which were recent integrative MPE studies, novel cancer profiling technologies, and new statistical and data science approaches. Looking forward to the near future, the meeting attendees anticipated continuous expansion and fruition of MPE research in many research fronts, particularly immune-epidemiology, mutational signatures, liquid biopsy, and health disparities.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Cancer heterogeneities hold the key to a deeper understanding of cancer etiology and progression and the discovery of more precise cancer therapy. Modern pathological and molecular technologies offer a powerful set of tools to profile tumor heterogeneities at multiple levels in large patient populations, from DNA to RNA, protein and epigenetics, and from tumor tissues to tumor microenvironment and liquid biopsy. When coupled with well-validated epidemiologic methodology and well-characterized epidemiologic resources, the rich tumor pathological and molecular tumor information provide new research opportunities at an unprecedented breadth and depth. This is the research space where Molecular Pathological Epidemiology (MPE) emerged over a decade ago and has been thriving since then. As a truly multidisciplinary field, MPE embraces collaborations from diverse fields including epidemiology, pathology, immunology, genetics, biostatistics, bioinformatics, and data science. Since first convened in 2013, the International MPE Meeting series has grown into a dynamic and dedicated platform for experts from these disciplines to communicate novel findings, discuss new research opportunities and challenges, build professional networks, and educate the next-generation scientists. Herein, we share the proceedings of the Fifth International MPE meeting, held virtually online, on May 24 and 25, 2021. The meeting consisted of 21 presentations organized into the three main themes, which were recent integrative MPE studies, novel cancer profiling technologies, and new statistical and data science approaches. Looking forward to the near future, the meeting attendees anticipated continuous expansion and fruition of MPE research in many research fronts, particularly immune-epidemiology, mutational signatures, liquid biopsy, and health disparities.
Vijaykumar, Kadambari; Leung, Hui Min; Barrios, Amilcar; Fernandez-Petty, Courtney M; Solomon, George M; Hathorne, Heather Y; Wade, Justin D; Monroe, Kathryn; Slaten, Katie Brand; Li, Qian; Leal, Sixto M; Moates, Derek B; Pierce, Hannah M; Olson, Kristian R; Currier, Paul; Foster, Sam; Marsden, Doug; Tearney, Guillermo J; Rowe, Steven M
COVID-19 Causes Ciliary Dysfunction as Demonstrated by Human Intranasal Micro-Optical Coherence Tomography Imaging Journal Article
In: bioRxiv, 2022, ISSN: 2692-8205.
@article{pmid35860227,
title = {COVID-19 Causes Ciliary Dysfunction as Demonstrated by Human Intranasal Micro-Optical Coherence Tomography Imaging},
author = {Kadambari Vijaykumar and Hui Min Leung and Amilcar Barrios and Courtney M Fernandez-Petty and George M Solomon and Heather Y Hathorne and Justin D Wade and Kathryn Monroe and Katie Brand Slaten and Qian Li and Sixto M Leal and Derek B Moates and Hannah M Pierce and Kristian R Olson and Paul Currier and Sam Foster and Doug Marsden and Guillermo J Tearney and Steven M Rowe},
doi = {10.1101/2022.07.08.499336},
issn = {2692-8205},
year = {2022},
date = {2022-07-01},
journal = {bioRxiv},
abstract = {Severe acute respiratory syndrome coronavirus (SARS-CoV-2), causative agent of coronavirus disease 2019 (COVID-19), binds via ACE2 receptors, highly expressed in ciliated cells of the nasal epithelium. Micro-optical coherence tomography (ฮผOCT) is a minimally invasive intranasal imaging technique that can determine cellular and functional dynamics of respiratory epithelia at 1-ฮผm resolution, enabling real time visualization and quantification of epithelial anatomy, ciliary motion, and mucus transport. We hypothesized that respiratory epithelial cell dysfunction in COVID-19 will manifest as reduced ciliated cell function and mucociliary abnormalities, features readily visualized by ฮผOCT. Symptomatic outpatients with SARS-CoV-2 aged โฅ 18 years were recruited within 14 days of symptom onset. Data was interpreted for subjects with COVID-19 (n=13) in comparison to healthy controls (n=8). Significant reduction in functional cilia, diminished ciliary beat frequency, and abnormal ciliary activity were evident. Other abnormalities included denuded epithelium, presence of mucus rafts, and increased inflammatory cells. Our results indicate that subjects with mild but symptomatic COVID-19 exhibit functional abnormalities of the respiratory mucosa underscoring the importance of mucociliary health in viral illness and disease transmission. Ciliary imaging enables investigation of early pathogenic mechanisms of COVID-19 and may be useful for evaluating disease progression and therapeutic response.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Severe acute respiratory syndrome coronavirus (SARS-CoV-2), causative agent of coronavirus disease 2019 (COVID-19), binds via ACE2 receptors, highly expressed in ciliated cells of the nasal epithelium. Micro-optical coherence tomography (ฮผOCT) is a minimally invasive intranasal imaging technique that can determine cellular and functional dynamics of respiratory epithelia at 1-ฮผm resolution, enabling real time visualization and quantification of epithelial anatomy, ciliary motion, and mucus transport. We hypothesized that respiratory epithelial cell dysfunction in COVID-19 will manifest as reduced ciliated cell function and mucociliary abnormalities, features readily visualized by ฮผOCT. Symptomatic outpatients with SARS-CoV-2 aged โฅ 18 years were recruited within 14 days of symptom onset. Data was interpreted for subjects with COVID-19 (n=13) in comparison to healthy controls (n=8). Significant reduction in functional cilia, diminished ciliary beat frequency, and abnormal ciliary activity were evident. Other abnormalities included denuded epithelium, presence of mucus rafts, and increased inflammatory cells. Our results indicate that subjects with mild but symptomatic COVID-19 exhibit functional abnormalities of the respiratory mucosa underscoring the importance of mucociliary health in viral illness and disease transmission. Ciliary imaging enables investigation of early pathogenic mechanisms of COVID-19 and may be useful for evaluating disease progression and therapeutic response.
Kaza, Niroop; Lin, Vivian Y; Stanford, Denise; Hussain, Shah S; Libby, Emily Falk; Kim, Harrison; Borgonovi, Monica; Conrath, Katja; Mutyam, Venkateshwar; Byzek, Stephen A; Tang, Li Ping; Trombley, John E; Rasmussen, Lawrence; Schoeb, Trenton; Leung, Hui Min; Tearney, Guillermo J; Raju, S Vamsee; Rowe, Steven M
Evaluation of a novel CFTR potentiator in COPD ferrets with acquired CFTR dysfunction Journal Article
In: Eur Respir J, vol. 60, no. 1, 2022, ISSN: 1399-3003.
@article{pmid34916262,
title = {Evaluation of a novel CFTR potentiator in COPD ferrets with acquired CFTR dysfunction},
author = {Niroop Kaza and Vivian Y Lin and Denise Stanford and Shah S Hussain and Emily Falk Libby and Harrison Kim and Monica Borgonovi and Katja Conrath and Venkateshwar Mutyam and Stephen A Byzek and Li Ping Tang and John E Trombley and Lawrence Rasmussen and Trenton Schoeb and Hui Min Leung and Guillermo J Tearney and S Vamsee Raju and Steven M Rowe},
doi = {10.1183/13993003.01581-2021},
issn = {1399-3003},
year = {2022},
date = {2022-07-01},
journal = {Eur Respir J},
volume = {60},
number = {1},
abstract = {RATIONALE: The majority of chronic obstructive pulmonary disease (COPD) patients have chronic bronchitis, for which specific therapies are unavailable. Acquired cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction is observed in chronic bronchitis, but has not been proven in a controlled animal model with airway disease. Furthermore, the potential of CFTR as a therapeutic target has not been tested given limitations to rodent models of COPD. Ferrets exhibit cystic fibrosis-related lung pathology when CFTR is absent and COPD with bronchitis following cigarette smoke exposure.nnOBJECTIVES: To evaluate CFTR dysfunction induced by smoking and test its pharmacological reversal by a novel CFTR potentiator, GLPG2196, in a ferret model of COPD with chronic bronchitis.nnMETHODS: Ferrets were exposed for 6โ
months to cigarette smoke to induce COPD and chronic bronchitis and then treated with enteral GLPG2196 once daily for 1โ
month. Electrophysiological measurements of ion transport and CFTR function, assessment of mucociliary function by one-micron optical coherence tomography imaging and particle-tracking microrheology, microcomputed tomography imaging, histopathological analysis and quantification of CFTR protein and mRNA expression were used to evaluate mechanistic and pathophysiological changes.nnMEASUREMENTS AND MAIN RESULTS: Following cigarette smoke exposure, ferrets exhibited CFTR dysfunction, increased mucus viscosity, delayed mucociliary clearance, airway wall thickening and airway epithelial hypertrophy. In COPD ferrets, GLPG2196 treatment reversed CFTR dysfunction, increased mucus transport by decreasing mucus viscosity, and reduced bronchial wall thickening and airway epithelial hypertrophy.nnCONCLUSIONS: The pharmacologic reversal of acquired CFTR dysfunction is beneficial against pathological features of chronic bronchitis in a COPD ferret model.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
RATIONALE: The majority of chronic obstructive pulmonary disease (COPD) patients have chronic bronchitis, for which specific therapies are unavailable. Acquired cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction is observed in chronic bronchitis, but has not been proven in a controlled animal model with airway disease. Furthermore, the potential of CFTR as a therapeutic target has not been tested given limitations to rodent models of COPD. Ferrets exhibit cystic fibrosis-related lung pathology when CFTR is absent and COPD with bronchitis following cigarette smoke exposure.nnOBJECTIVES: To evaluate CFTR dysfunction induced by smoking and test its pharmacological reversal by a novel CFTR potentiator, GLPG2196, in a ferret model of COPD with chronic bronchitis.nnMETHODS: Ferrets were exposed for 6โ
months to cigarette smoke to induce COPD and chronic bronchitis and then treated with enteral GLPG2196 once daily for 1โ
month. Electrophysiological measurements of ion transport and CFTR function, assessment of mucociliary function by one-micron optical coherence tomography imaging and particle-tracking microrheology, microcomputed tomography imaging, histopathological analysis and quantification of CFTR protein and mRNA expression were used to evaluate mechanistic and pathophysiological changes.nnMEASUREMENTS AND MAIN RESULTS: Following cigarette smoke exposure, ferrets exhibited CFTR dysfunction, increased mucus viscosity, delayed mucociliary clearance, airway wall thickening and airway epithelial hypertrophy. In COPD ferrets, GLPG2196 treatment reversed CFTR dysfunction, increased mucus transport by decreasing mucus viscosity, and reduced bronchial wall thickening and airway epithelial hypertrophy.nnCONCLUSIONS: The pharmacologic reversal of acquired CFTR dysfunction is beneficial against pathological features of chronic bronchitis in a COPD ferret model.
Cho, Do-Yeon; Zhang, Shaoyan; Skinner, Daniel F; Lim, Dong Jin; Banks, Catherine; Grayson, Jessica W; Tearney, Guillermo J; Rowe, Steven M; Woodworth, Bradford A
In: Int Forum Allergy Rhinol, vol. 12, no. 5, pp. 690โ698, 2022, ISSN: 2042-6984.
@article{pmid34704673b,
title = {Ivacaftor restores delayed mucociliary transport caused by Pseudomonas aeruginosa-induced acquired cystic fibrosis transmembrane conductance regulator dysfunction in rabbit nasal epithelia},
author = {Do-Yeon Cho and Shaoyan Zhang and Daniel F Skinner and Dong Jin Lim and Catherine Banks and Jessica W Grayson and Guillermo J Tearney and Steven M Rowe and Bradford A Woodworth},
doi = {10.1002/alr.22907},
issn = {2042-6984},
year = {2022},
date = {2022-05-01},
journal = {Int Forum Allergy Rhinol},
volume = {12},
number = {5},
pages = {690--698},
abstract = {BACKGROUND: Abnormal chloride (Cl ) transport dehydrates airway surface liquid (ASL) in sinonasal epithelium leading to mucus stasis and chronic rhinosinusitis. As an experimental epithelium, rabbit tissue provides an excellent representation of human sinus disease, and the rabbit sinusitis model is both established and well suited for therapeutic interventions in vivo. Our objective in this study was to evaluate whether ivacaftor reverses the consequences of Pseudomonas aeruginosa-induced acquired cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction.nnMETHODS: Rabbit nasal cavities were assessed for responsiveness to ivacaftor in vivo (by nasal potential difference [NPD] assay). Rabbit nasal epithelial (RNE) cultures were incubated with an ultrafiltrate of P aeruginosa (PAO1 strain) for 4ย hours and tested for acquired CFTR dysfunction. Markers of mucociliary function, including airway surface liquid depth (ASL), periciliary liquid depth (PCL), ciliary beat frequency (CBF), and mucociliary transport (MCT), were measured by micro-optical coherence tomography (ฮผOCT) after PAO1 and/or ivacaftor incubation.nnRESULTS: Ivacaftor resulted in a significant mean NPD polarization of 21.8 ยฑ 2.1ย mV, which was significantly greater than that seen in the low Cl control (12.9 ยฑ 1.3; pย =ย 0.01). PAO1 exposure induced a state of acquired CFTR dysfunction in rabbit nasal epithelium as measured byย forskolin-stimulated short-circuit current (I ) (control, 37.0 ยฑ 1.1ย ฮผA/cm ; PAO1, 24.4 ยฑ 1.1 ฮผA/cm ;ย pย <ย 0.001). RNE cultures exposed to PAO1 had inhibited mucociliary function, whereas coincubation with ivacaftor restored mucociliary clearance, as measured by ฮผOCT.nnCONCLUSION: In rabbit nasal epithelium, ivacaftor robustly stimulates CFTR-mediated Cl secretion and normalizes ASL and CBF in PAO1-induced acquired CFTR dysfunction. Preclinical testing of CFTR potentiators as therapy for P aeruginosa rabbit sinusitis is planned.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: Abnormal chloride (Cl ) transport dehydrates airway surface liquid (ASL) in sinonasal epithelium leading to mucus stasis and chronic rhinosinusitis. As an experimental epithelium, rabbit tissue provides an excellent representation of human sinus disease, and the rabbit sinusitis model is both established and well suited for therapeutic interventions in vivo. Our objective in this study was to evaluate whether ivacaftor reverses the consequences of Pseudomonas aeruginosa-induced acquired cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction.nnMETHODS: Rabbit nasal cavities were assessed for responsiveness to ivacaftor in vivo (by nasal potential difference [NPD] assay). Rabbit nasal epithelial (RNE) cultures were incubated with an ultrafiltrate of P aeruginosa (PAO1 strain) for 4ย hours and tested for acquired CFTR dysfunction. Markers of mucociliary function, including airway surface liquid depth (ASL), periciliary liquid depth (PCL), ciliary beat frequency (CBF), and mucociliary transport (MCT), were measured by micro-optical coherence tomography (ฮผOCT) after PAO1 and/or ivacaftor incubation.nnRESULTS: Ivacaftor resulted in a significant mean NPD polarization of 21.8 ยฑ 2.1ย mV, which was significantly greater than that seen in the low Cl control (12.9 ยฑ 1.3; pย =ย 0.01). PAO1 exposure induced a state of acquired CFTR dysfunction in rabbit nasal epithelium as measured byย forskolin-stimulated short-circuit current (I ) (control, 37.0 ยฑ 1.1ย ฮผA/cm ; PAO1, 24.4 ยฑ 1.1 ฮผA/cm ;ย pย <ย 0.001). RNE cultures exposed to PAO1 had inhibited mucociliary function, whereas coincubation with ivacaftor restored mucociliary clearance, as measured by ฮผOCT.nnCONCLUSION: In rabbit nasal epithelium, ivacaftor robustly stimulates CFTR-mediated Cl secretion and normalizes ASL and CBF in PAO1-induced acquired CFTR dysfunction. Preclinical testing of CFTR potentiators as therapy for P aeruginosa rabbit sinusitis is planned.
Sheil, Conor J; Wartak, Andreas; Spicer, Graham L C; Tearney, Guillermo J
Extended depth of focus by self-imaging wavefront division with the mirror tunnel Journal Article
In: J Opt Soc Am A Opt Image Sci Vis, vol. 39, no. 4, pp. 711โ725, 2022, ISSN: 1520-8532.
@article{pmid35471398,
title = {Extended depth of focus by self-imaging wavefront division with the mirror tunnel},
author = {Conor J Sheil and Andreas Wartak and Graham L C Spicer and Guillermo J Tearney},
doi = {10.1364/JOSAA.448848},
issn = {1520-8532},
year = {2022},
date = {2022-04-01},
journal = {J Opt Soc Am A Opt Image Sci Vis},
volume = {39},
number = {4},
pages = {711--725},
abstract = {The mirror tunnel is a component used to extend the depth of focus for compact imaging probes used in endoscopic optical coherence tomography (OCT). A fast and accurate method for mirror tunnel probe simulation, characterization, and optimization is needed, with the aim of reconciling wave- and ray-optics simulation methods and providing a thorough description of the physical operating principle of the mirror tunnel. BeamLab software, employing the beam propagation method, was used to explore the parameter space and quantify lateral resolution and depth of focus extension. The lateral resolution performance was found to depend heavily on the metric chosen, implying that care should be taken in the interpretation of optimization and simulation results. Interpreting the mirror tunnel exit face as an extended object gives an understanding of the probe operation, decoupling it from the focusing optics and potentially helping to reduce the parameter space for future optimization.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The mirror tunnel is a component used to extend the depth of focus for compact imaging probes used in endoscopic optical coherence tomography (OCT). A fast and accurate method for mirror tunnel probe simulation, characterization, and optimization is needed, with the aim of reconciling wave- and ray-optics simulation methods and providing a thorough description of the physical operating principle of the mirror tunnel. BeamLab software, employing the beam propagation method, was used to explore the parameter space and quantify lateral resolution and depth of focus extension. The lateral resolution performance was found to depend heavily on the metric chosen, implying that care should be taken in the interpretation of optimization and simulation results. Interpreting the mirror tunnel exit face as an extended object gives an understanding of the probe operation, decoupling it from the focusing optics and potentially helping to reduce the parameter space for future optimization.
Dong, Jing; Grant, Catriona; Vuong, Barry; Nishioka, Norman; Gao, Anna Huizi; Beatty, Matthew; Baldwin, Grace; Baillargeon, Aaron; Bablouzian, Ara; Grahmann, Patricia; Bhat, Nitasha; Ryan, Emily; Barrios, Amilcar; Giddings, Sarah; Ford, Timothy; Beaulieu-Ouellet, Emilie; Hosseiny, Seyed Hamid; Lerman, Irene; Trasischker, Wolfgang; Reddy, Rohith; Singh, Kanwarpal; Gora, Michalina; Hyun, Daryl; Quรฉnรฉhervรฉ, Lucille; Wallace, Michael; Wolfsen, Herbert; Sharma, Prateek; Wang, Kenneth K; Leggett, Cadman L; Poneros, John; Abrams, Julian A; Lightdale, Charles; Leeds, Samantha; Rosenberg, Mireille; Tearney, Guillermo J
Feasibility and Safety of Tethered Capsule Endomicroscopy in Patients With Barrett’s Esophagus in a Multi-Center Study Journal Article
In: Clin Gastroenterol Hepatol, vol. 20, no. 4, pp. 756โ765.e3, 2022, ISSN: 1542-7714.
@article{pmid33549871,
title = {Feasibility and Safety of Tethered Capsule Endomicroscopy in Patients With Barrett's Esophagus in a Multi-Center Study},
author = {Jing Dong and Catriona Grant and Barry Vuong and Norman Nishioka and Anna Huizi Gao and Matthew Beatty and Grace Baldwin and Aaron Baillargeon and Ara Bablouzian and Patricia Grahmann and Nitasha Bhat and Emily Ryan and Amilcar Barrios and Sarah Giddings and Timothy Ford and Emilie Beaulieu-Ouellet and Seyed Hamid Hosseiny and Irene Lerman and Wolfgang Trasischker and Rohith Reddy and Kanwarpal Singh and Michalina Gora and Daryl Hyun and Lucille Quรฉnรฉhervรฉ and Michael Wallace and Herbert Wolfsen and Prateek Sharma and Kenneth K Wang and Cadman L Leggett and John Poneros and Julian A Abrams and Charles Lightdale and Samantha Leeds and Mireille Rosenberg and Guillermo J Tearney},
doi = {10.1016/j.cgh.2021.02.008},
issn = {1542-7714},
year = {2022},
date = {2022-04-01},
journal = {Clin Gastroenterol Hepatol},
volume = {20},
number = {4},
pages = {756--765.e3},
abstract = {BACKGROUND & AIMS: Tethered capsule endomicroscopy (TCE) involves swallowing a small tethered pill that implements optical coherence tomography (OCT) imaging, procuring high resolution images of the whole esophagus. Here, we demonstrate and evaluate the feasibility and safety of TCE and a portable OCT imaging system in patients with Barrett's esophagus (BE) in a multi-center (5-site) clinical study.nnMETHODS: Untreated patients with BE as per endoscopic biopsy diagnosis were eligible to participate in the study. TCE procedures were performed in unsedated patients by either doctors or nurses. After the capsule was swallowed, the device continuously obtained 10-ฮผm-resolution cross-sectional images as it traversed the esophagus. Following imaging, the device was withdrawn through mouth, and disinfected for subsequent reuse. BE lengths were compared to endoscopy findings when available. OCT-TCE images were compared to volumetric laser endomicroscopy (VLE) images from a patient who had undergone VLE on the same day as TCE.nnRESULTS: 147 patients with BE were enrolled across all sites. 116 swallowed the capsule (79%), 95/114 (83.3%) men and 21/33 (63.6%) women (P = .01). High-quality OCT images were obtained in 104/111 swallowers (93.7%) who completed the procedure. The average imaging duration was 5.55 ยฑ 1.92 minutes. The mean length of esophagus imaged per patient was 21.69 ยฑ 5.90 cm. A blinded comparison of maximum extent of BE measured by OCT-TCE and EGD showed a strong correlation (r = 0.77-0.79). OCT-TCE images were of similar quality to those obtained by OCT-VLE.nnCONCLUSIONS: The capabilities of TCE to be used across multiple sites, be administered to unsedated patients by either physicians or nurses who are not expert in OCT-TCE, and to rapidly and safely evaluate the microscopic structure of the esophagus make it an emerging tool for screening and surveillance of BE patients. Clinical trial registry website and trial number: NCT02994693 and NCT03459339.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND & AIMS: Tethered capsule endomicroscopy (TCE) involves swallowing a small tethered pill that implements optical coherence tomography (OCT) imaging, procuring high resolution images of the whole esophagus. Here, we demonstrate and evaluate the feasibility and safety of TCE and a portable OCT imaging system in patients with Barrett’s esophagus (BE) in a multi-center (5-site) clinical study.nnMETHODS: Untreated patients with BE as per endoscopic biopsy diagnosis were eligible to participate in the study. TCE procedures were performed in unsedated patients by either doctors or nurses. After the capsule was swallowed, the device continuously obtained 10-ฮผm-resolution cross-sectional images as it traversed the esophagus. Following imaging, the device was withdrawn through mouth, and disinfected for subsequent reuse. BE lengths were compared to endoscopy findings when available. OCT-TCE images were compared to volumetric laser endomicroscopy (VLE) images from a patient who had undergone VLE on the same day as TCE.nnRESULTS: 147 patients with BE were enrolled across all sites. 116 swallowed the capsule (79%), 95/114 (83.3%) men and 21/33 (63.6%) women (P = .01). High-quality OCT images were obtained in 104/111 swallowers (93.7%) who completed the procedure. The average imaging duration was 5.55 ยฑ 1.92 minutes. The mean length of esophagus imaged per patient was 21.69 ยฑ 5.90 cm. A blinded comparison of maximum extent of BE measured by OCT-TCE and EGD showed a strong correlation (r = 0.77-0.79). OCT-TCE images were of similar quality to those obtained by OCT-VLE.nnCONCLUSIONS: The capabilities of TCE to be used across multiple sites, be administered to unsedated patients by either physicians or nurses who are not expert in OCT-TCE, and to rapidly and safely evaluate the microscopic structure of the esophagus make it an emerging tool for screening and surveillance of BE patients. Clinical trial registry website and trial number: NCT02994693 and NCT03459339.
Kunio, Mie; Gardecki, Joseph A; Watanabe, Kohei; Nishimiya, Kensuke; Verma, Sarika; Jaffer, Farouc A; Tearney, Guillermo J
Histopathological correlation of near infrared autofluorescence in human cadaver coronary arteries Journal Article
In: Atherosclerosis, vol. 344, pp. 31โ39, 2022, ISSN: 1879-1484.
@article{pmid35134654,
title = {Histopathological correlation of near infrared autofluorescence in human cadaver coronary arteries},
author = {Mie Kunio and Joseph A Gardecki and Kohei Watanabe and Kensuke Nishimiya and Sarika Verma and Farouc A Jaffer and Guillermo J Tearney},
doi = {10.1016/j.atherosclerosis.2022.01.012},
issn = {1879-1484},
year = {2022},
date = {2022-03-01},
journal = {Atherosclerosis},
volume = {344},
pages = {31--39},
abstract = {BACKGROUND AND AIMS: Prior coronary optical coherence tomography (OCT)-near infrared auto-fluorescence (NIRAF) imaging data has shown a correlation between high-risk morphological features and NIRAF signal intensity. This study aims to understand the histopathological origins of NIRAF in human cadaver coronary arteries.nnMETHODS: Ex vivo intracoronary OCT-NIRAF imaging was performed on coronary arteries prosected from 23 fresh human cadaver hearts. Arteries with elevated NIRAF were formalin-fixed and paraffin-embedded. Microscopic images of immunostained Glycophorin A (indicating intraplaque hemorrhage) and Sudan Black (indicating ceroid after fixation) stained slides were compared with confocal NIRAF images (ex. 635ย nm, em. 655-755ย nm) from adjacent unstained slides in each section. Different images from the same section were registered via luminal morphology. Confocal NIRAF-positive 45ยฐ sectors were compared to immunohistochemistry and colocalization between NIRAF and intraplaque hemorrhage or ceroid was quantified by Manders' overlap and Dice similarity coefficients.nnRESULTS: Thirty-one coronary arteries from 14 hearts demonstrated โฅ1.5 times higher NIRAF signal than background, and 429 sections were created from them, including 54 sections (12.6%) with high-risk plaques. Within 112 confocal NIRAF-positive 45ยฐ sectors, 65 sectors (58.0%) showed both Glycophorin A-positive and Sudan Black-positive, while 7 sectors (6.3%) and 40 sectors (33.6%) only showed Glycophorin A-positive or Sudan black-positive, respectively. A two-tailed McNemar's test showed that Sudan Black more closely corresponded to confocal NIRAF than Glycophorin A (pย <ย 1.0ย รย 10). NIRAF was also found to spatially associate with both Glycophorin A and Sudan Black, with stronger colocalization between Sudan Black and NIRAF (Manders: 0.19ย ยฑย 0.15 vs. 0.13ย ยฑย 0.14, pย <ย 0.005; Dice: 0.072ย ยฑย 0.096 vs. 0.060ย ยฑย 0.090, pย <ย 0.01).nnCONCLUSIONS: As ceroid associates with oxidative stress and intraplaque hemorrhage is implicated in rapid lesion progression, these results suggest that NIRAF provides additional, complementary information to morphologic imaging that may aid in identifying high-risk coronary plaques via translatable intracoronary OCT-NIRAF imaging.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND AND AIMS: Prior coronary optical coherence tomography (OCT)-near infrared auto-fluorescence (NIRAF) imaging data has shown a correlation between high-risk morphological features and NIRAF signal intensity. This study aims to understand the histopathological origins of NIRAF in human cadaver coronary arteries.nnMETHODS: Ex vivo intracoronary OCT-NIRAF imaging was performed on coronary arteries prosected from 23 fresh human cadaver hearts. Arteries with elevated NIRAF were formalin-fixed and paraffin-embedded. Microscopic images of immunostained Glycophorin A (indicating intraplaque hemorrhage) and Sudan Black (indicating ceroid after fixation) stained slides were compared with confocal NIRAF images (ex. 635ย nm, em. 655-755ย nm) from adjacent unstained slides in each section. Different images from the same section were registered via luminal morphology. Confocal NIRAF-positive 45ยฐ sectors were compared to immunohistochemistry and colocalization between NIRAF and intraplaque hemorrhage or ceroid was quantified by Manders’ overlap and Dice similarity coefficients.nnRESULTS: Thirty-one coronary arteries from 14 hearts demonstrated โฅ1.5 times higher NIRAF signal than background, and 429 sections were created from them, including 54 sections (12.6%) with high-risk plaques. Within 112 confocal NIRAF-positive 45ยฐ sectors, 65 sectors (58.0%) showed both Glycophorin A-positive and Sudan Black-positive, while 7 sectors (6.3%) and 40 sectors (33.6%) only showed Glycophorin A-positive or Sudan black-positive, respectively. A two-tailed McNemar’s test showed that Sudan Black more closely corresponded to confocal NIRAF than Glycophorin A (pย <ย 1.0ย รย 10). NIRAF was also found to spatially associate with both Glycophorin A and Sudan Black, with stronger colocalization between Sudan Black and NIRAF (Manders: 0.19ย ยฑย 0.15 vs. 0.13ย ยฑย 0.14, pย <ย 0.005; Dice: 0.072ย ยฑย 0.096 vs. 0.060ย ยฑย 0.090, pย <ย 0.01).nnCONCLUSIONS: As ceroid associates with oxidative stress and intraplaque hemorrhage is implicated in rapid lesion progression, these results suggest that NIRAF provides additional, complementary information to morphologic imaging that may aid in identifying high-risk coronary plaques via translatable intracoronary OCT-NIRAF imaging.
Lopez, Dan R; Sgroi, Dennis; Krishnamourthy, Savitri; Tearney, Guillermo
Is Real-Time Microscopy on the Horizon? A Brief Review of the Potential Future Directions in Clinical Breast Tumor Microscopy Implementation Journal Article
In: Virchows Arch, vol. 480, no. 1, pp. 211โ227, 2022, ISSN: 1432-2307.
@article{pmid35218378,
title = {Is Real-Time Microscopy on the Horizon? A Brief Review of the Potential Future Directions in Clinical Breast Tumor Microscopy Implementation},
author = {Dan R Lopez and Dennis Sgroi and Savitri Krishnamourthy and Guillermo Tearney},
doi = {10.1007/s00428-022-03300-z},
issn = {1432-2307},
year = {2022},
date = {2022-01-01},
journal = {Virchows Arch},
volume = {480},
number = {1},
pages = {211--227},
abstract = {We will briefly review the current paradigm and some recent developments in the area of clinical breast microscopy, highlighting several promising commercially available, and research-based platforms. Confocal microscopy (reflectance, fluorescence, and spectrally encoded), optical coherence tomography (wide field and full field), stereomicroscopy, open-top light sheet microscopy, microscopy with ultraviolet surface excitation, nonlinear microscopy, Raman scattering microscopy, photoacoustic microscopy, and needle microendoscopy will be discussed. Non-microscopic methods for breast pathology assessment are beyond the scope of this review. These microscopic technologies have to varying degrees the potential for transforming breast cancer care, but in order for any of these to be integrated into clinical practice there are several hurdles to overcome. In our review we will focus on what needs to be done in order for the commercially available technologies to become more established, what the technologies in the research domain need to do in order to reach the commercial realm; and finally, what the field of breast pathology might look like if these technologies were to be widely adopted.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
We will briefly review the current paradigm and some recent developments in the area of clinical breast microscopy, highlighting several promising commercially available, and research-based platforms. Confocal microscopy (reflectance, fluorescence, and spectrally encoded), optical coherence tomography (wide field and full field), stereomicroscopy, open-top light sheet microscopy, microscopy with ultraviolet surface excitation, nonlinear microscopy, Raman scattering microscopy, photoacoustic microscopy, and needle microendoscopy will be discussed. Non-microscopic methods for breast pathology assessment are beyond the scope of this review. These microscopic technologies have to varying degrees the potential for transforming breast cancer care, but in order for any of these to be integrated into clinical practice there are several hurdles to overcome. In our review we will focus on what needs to be done in order for the commercially available technologies to become more established, what the technologies in the research domain need to do in order to reach the commercial realm; and finally, what the field of breast pathology might look like if these technologies were to be widely adopted.
Chowdhury, Mohammed M; Piao, Zhonglie; Albaghdadi, Mazen S; Coughlin, Patrick A; Rudd, James H F; Tearney, Guillermo J; Jaffer, Farouc A
Intravascular Fluorescence Molecular Imaging of Atherosclerosis Journal Article
In: Methods Mol Biol, vol. 2419, pp. 853โ872, 2022, ISSN: 1940-6029.
@article{pmid35238006,
title = {Intravascular Fluorescence Molecular Imaging of Atherosclerosis},
author = {Mohammed M Chowdhury and Zhonglie Piao and Mazen S Albaghdadi and Patrick A Coughlin and James H F Rudd and Guillermo J Tearney and Farouc A Jaffer},
doi = {10.1007/978-1-0716-1924-7_52},
issn = {1940-6029},
year = {2022},
date = {2022-01-01},
journal = {Methods Mol Biol},
volume = {2419},
pages = {853--872},
abstract = {Optical molecular imaging using near-infrared fluorescence (NIRF) light is an emerging high-resolution imaging approach to image a wide range of molecular and cellular species in vivo. Imaging using NIR wavelengths (650-900ย nm) enables deeper photon penetration into tissue and reduced tissue autofluorescence, resulting in higher sensitivity to detect exogenously administered NIR fluorophores (injectable molecular imaging agents). Greater imaging depth of several centimeters is further achievable in the NIR window as blood absorption is as an order of magnitude lower than in the visible range. Furthermore, as optical imaging is routinely performed in the cardiac catheterization laboratory (e.g., optical coherence tomography), intravascular NIRF offers a promising translational approach for clinical coronary and peripheral arterial imaging. To this point, the first human intravascular NIRF imaging study recently demonstrated the ability to detect NIR autofluorescence in patients with coronary atherosclerosis. This study provides a foundation for targeted intravascular NIRF molecular imaging studies in coronary patients. In this chapter, we detail system engineering, imaging agents and translational applications of intravascular NIRF molecular imaging.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Optical molecular imaging using near-infrared fluorescence (NIRF) light is an emerging high-resolution imaging approach to image a wide range of molecular and cellular species in vivo. Imaging using NIR wavelengths (650-900ย nm) enables deeper photon penetration into tissue and reduced tissue autofluorescence, resulting in higher sensitivity to detect exogenously administered NIR fluorophores (injectable molecular imaging agents). Greater imaging depth of several centimeters is further achievable in the NIR window as blood absorption is as an order of magnitude lower than in the visible range. Furthermore, as optical imaging is routinely performed in the cardiac catheterization laboratory (e.g., optical coherence tomography), intravascular NIRF offers a promising translational approach for clinical coronary and peripheral arterial imaging. To this point, the first human intravascular NIRF imaging study recently demonstrated the ability to detect NIR autofluorescence in patients with coronary atherosclerosis. This study provides a foundation for targeted intravascular NIRF molecular imaging studies in coronary patients. In this chapter, we detail system engineering, imaging agents and translational applications of intravascular NIRF molecular imaging.
Li, Qian; Vijaykumar, Kadambari; Philips, Scott E; Hussain, Shah S; Huynh, Van N; Fernandez-Petty, Courtney M; Lever, Jacelyn E Peabody; Foote, Jeremy B; Ren, Janna; Campos-Gรณmez, Javier; Daya, Farah Abou; Hubbs, Nathaniel W; Kim, Harrison; Onuoha, Ezinwanne; Boitet, Evan R; Fu, Lianwu; Leung, Hui Min; Yu, Linhui; Detchemendy, Thomas W; Schaefers, Levi T; Tipper, Jennifer L; Edwards, Lloyd J; Leal, Sixto M; Harrod, Kevin S; Tearney, Guillermo J; Rowe, Steven M
Mucociliary Transport Deficiency and Disease Progression in Syrian Hamsters with SARS-CoV-2 Infection Journal Article
In: bioRxiv, 2022, ISSN: 2692-8205.
@article{pmid35075457,
title = {Mucociliary Transport Deficiency and Disease Progression in Syrian Hamsters with SARS-CoV-2 Infection},
author = {Qian Li and Kadambari Vijaykumar and Scott E Philips and Shah S Hussain and Van N Huynh and Courtney M Fernandez-Petty and Jacelyn E Peabody Lever and Jeremy B Foote and Janna Ren and Javier Campos-Gรณmez and Farah Abou Daya and Nathaniel W Hubbs and Harrison Kim and Ezinwanne Onuoha and Evan R Boitet and Lianwu Fu and Hui Min Leung and Linhui Yu and Thomas W Detchemendy and Levi T Schaefers and Jennifer L Tipper and Lloyd J Edwards and Sixto M Leal and Kevin S Harrod and Guillermo J Tearney and Steven M Rowe},
doi = {10.1101/2022.01.16.476016},
issn = {2692-8205},
year = {2022},
date = {2022-01-01},
journal = {bioRxiv},
abstract = {Substantial clinical evidence supports the notion that ciliary function in the airways plays an important role in COVID-19 pathogenesis. Although ciliary damage has been observed in both and models, consequent impaired mucociliary transport (MCT) remains unknown for the intact MCT apparatus from an model of disease. Using golden Syrian hamsters, a common animal model that recapitulates human COVID-19, we quantitatively followed the time course of physiological, virological, and pathological changes upon SARS-CoV-2 infection, as well as the deficiency of the MCT apparatus using micro-optical coherence tomography, a novel method to visualize and simultaneously quantitate multiple aspects of the functional microanatomy of intact airways. Corresponding to progressive weight loss up to 7 days post-infection (dpi), viral detection and histopathological analysis in both the trachea and lung revealed steadily descending infection from the upper airways, as the main target of viral invasion, to lower airways and parenchymal lung, which are likely injured through indirect mechanisms. SARS-CoV-2 infection caused a 67% decrease in MCT rate as early as 2 dpi, largely due to diminished motile ciliation coverage, but not airway surface liquid depth, periciliary liquid depth, or cilia beat frequency of residual motile cilia. Further analysis indicated that the fewer motile cilia combined with abnormal ciliary motion of residual cilia contributed to the delayed MCT. The time course of physiological, virological, and pathological progression suggest that functional deficits of the MCT apparatus predispose to COVID-19 pathogenesis by extending viral retention and may be a risk factor for secondary infection. As a consequence, therapies directed towards the MCT apparatus deserve further investigation as a treatment modality.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Substantial clinical evidence supports the notion that ciliary function in the airways plays an important role in COVID-19 pathogenesis. Although ciliary damage has been observed in both and models, consequent impaired mucociliary transport (MCT) remains unknown for the intact MCT apparatus from an model of disease. Using golden Syrian hamsters, a common animal model that recapitulates human COVID-19, we quantitatively followed the time course of physiological, virological, and pathological changes upon SARS-CoV-2 infection, as well as the deficiency of the MCT apparatus using micro-optical coherence tomography, a novel method to visualize and simultaneously quantitate multiple aspects of the functional microanatomy of intact airways. Corresponding to progressive weight loss up to 7 days post-infection (dpi), viral detection and histopathological analysis in both the trachea and lung revealed steadily descending infection from the upper airways, as the main target of viral invasion, to lower airways and parenchymal lung, which are likely injured through indirect mechanisms. SARS-CoV-2 infection caused a 67% decrease in MCT rate as early as 2 dpi, largely due to diminished motile ciliation coverage, but not airway surface liquid depth, periciliary liquid depth, or cilia beat frequency of residual motile cilia. Further analysis indicated that the fewer motile cilia combined with abnormal ciliary motion of residual cilia contributed to the delayed MCT. The time course of physiological, virological, and pathological progression suggest that functional deficits of the MCT apparatus predispose to COVID-19 pathogenesis by extending viral retention and may be a risk factor for secondary infection. As a consequence, therapies directed towards the MCT apparatus deserve further investigation as a treatment modality.
Valvo, Veronica; Parietti, Elena; Deans, Kyle; Ahn, Sebastian W; Park, Noel Ruth; Ferland, Benjamin; Thompson, Devon; Dominas, Christine; Bhagavatula, Sharath K; Davidson, Shawn; Jonas, Oliver
In: Front Cell Dev Biol, vol. 10, pp. 1032360, 2022, ISSN: 2296-634X.
@article{pmid36619865,
title = {High-throughput perturbation of metabolite levels in the tumor micro-environment reveals favorable metabolic condition for increased fitness of infiltrated T-cells},
author = {Veronica Valvo and Elena Parietti and Kyle Deans and Sebastian W Ahn and Noel Ruth Park and Benjamin Ferland and Devon Thompson and Christine Dominas and Sharath K Bhagavatula and Shawn Davidson and Oliver Jonas},
doi = {10.3389/fcell.2022.1032360},
issn = {2296-634X},
year = {2022},
date = {2022-01-01},
journal = {Front Cell Dev Biol},
volume = {10},
pages = {1032360},
abstract = {Tumor-infiltrating immune cells experience significant metabolic reprogramming in the tumor microenvironment (TME), and they share similar metabolic pathways and nutrient needs with malignant cells. This positions these cell types in direct nutrient competition in the TME. We currently lack a complete understanding of the similarities, differences, and functional consequences of the metabolic pathways utilized by activated immune cells from different lineages neoplastic cells. This study applies a novel approach using implantable microdevices to expose the tumor to 27 controlled and localized metabolic perturbations in order to perform a systematic investigation into the metabolic regulation of the cellular fitness and persistence between immune and tumor cells directly within the native TME. Our findings identify the most potent metabolites, notably glutamine and arginine, that induce a favorable metabolic immune response in a mammary carcinoma model, and reveal novel insights on less characterized pathways, such as cysteine and glutathione. We then examine clinical samples from cancer patients to confirm the elevation of these pathways in tumor regions that are enriched in activated T cells. Overall, this work provides the first instance of a highly multiplexed competition assay between malignant and immune cells within tumors using a range of localized microdose metabolic perturbations. The approach and findings may be used to potentiate the effects of T cell stimulating immunotherapies on a tumor-specific or personalized basis through targeted enrichment or depletion of specific metabolites.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Tumor-infiltrating immune cells experience significant metabolic reprogramming in the tumor microenvironment (TME), and they share similar metabolic pathways and nutrient needs with malignant cells. This positions these cell types in direct nutrient competition in the TME. We currently lack a complete understanding of the similarities, differences, and functional consequences of the metabolic pathways utilized by activated immune cells from different lineages neoplastic cells. This study applies a novel approach using implantable microdevices to expose the tumor to 27 controlled and localized metabolic perturbations in order to perform a systematic investigation into the metabolic regulation of the cellular fitness and persistence between immune and tumor cells directly within the native TME. Our findings identify the most potent metabolites, notably glutamine and arginine, that induce a favorable metabolic immune response in a mammary carcinoma model, and reveal novel insights on less characterized pathways, such as cysteine and glutathione. We then examine clinical samples from cancer patients to confirm the elevation of these pathways in tumor regions that are enriched in activated T cells. Overall, this work provides the first instance of a highly multiplexed competition assay between malignant and immune cells within tumors using a range of localized microdose metabolic perturbations. The approach and findings may be used to potentiate the effects of T cell stimulating immunotherapies on a tumor-specific or personalized basis through targeted enrichment or depletion of specific metabolites.
2021
Schenk, Merle S; Wartak, Andreas; Buehler, Verena; Zhao, Jie; Tearney, Guillermo J; Birngruber, Reginald; Kassumeh, Stefan
Advances in Imaging of Subbasal Corneal Nerves With Micro-Optical Coherence Tomography Journal Article
In: Transl Vis Sci Technol, vol. 10, no. 13, pp. 22, 2021, ISSN: 2164-2591.
@article{pmid34779835b,
title = {Advances in Imaging of Subbasal Corneal Nerves With Micro-Optical Coherence Tomography},
author = {Merle S Schenk and Andreas Wartak and Verena Buehler and Jie Zhao and Guillermo J Tearney and Reginald Birngruber and Stefan Kassumeh},
doi = {10.1167/tvst.10.13.22},
issn = {2164-2591},
year = {2021},
date = {2021-11-01},
journal = {Transl Vis Sci Technol},
volume = {10},
number = {13},
pages = {22},
abstract = {PURPOSE: To investigate the most peripheral corneal nerve plexus using high-resolution micro-optical coherence tomography (ยตOCT) imaging and to assessย ยตOCT's clinical potential as a screening tool for corneal and systemic diseases.nnMETHODS: An experimental high-resolution (1.5 ร 1.5 ร 1ย ยตm) ยตOCT setup was applied for three-dimensional imaging of the subbasal nerve plexus in nonhuman primates (NHPs) and swine within 3 hours postmortem. Morphologic features of subbasal nerves in ยตOCT were compared to ฮฒ3 tubulin-stained fluorescence confocal microscopy (FCM). Parameters such as nerve density, nerve distribution, and imaging repeatability were evaluated, using semiautomatic image analysis in form of a custom corneal surface segmentation algorithm and NeuronJ.nnRESULTS: Swine and NHP corneas showed the species-specific nerve morphology in both imaging modalities. Most fibers showed a linear course, forming a highly parallel pattern, converging in a vortex with overall nerve densities varying between 9.51 and 24.24 mm/mm2. The repeatability of nerve density quantification of the ยตOCT scans as approximately 88% in multiple image recordings of the same cornea.nnCONCLUSIONS: Compared to the current gold standard of FCM, ยตOCT's larger field of view of currently 1 ร 1 mm increases the conclusiveness of density measurements, which, coupled with ยตOCT's feature of not requiring direct contact, shows promise for future clinical application. The nerve density quantification may be relevant for screening for systemic disease (e.g., peripheral neuropathy).nnTRANSLATIONAL RELEVANCE: Technological advances in OCT technology may enable a quick assessment of corneal nerve density, which could be valuable evaluating ophthalmic and systemic peripheral innervation.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
PURPOSE: To investigate the most peripheral corneal nerve plexus using high-resolution micro-optical coherence tomography (ยตOCT) imaging and to assessย ยตOCT’s clinical potential as a screening tool for corneal and systemic diseases.nnMETHODS: An experimental high-resolution (1.5 ร 1.5 ร 1ย ยตm) ยตOCT setup was applied for three-dimensional imaging of the subbasal nerve plexus in nonhuman primates (NHPs) and swine within 3 hours postmortem. Morphologic features of subbasal nerves in ยตOCT were compared to ฮฒ3 tubulin-stained fluorescence confocal microscopy (FCM). Parameters such as nerve density, nerve distribution, and imaging repeatability were evaluated, using semiautomatic image analysis in form of a custom corneal surface segmentation algorithm and NeuronJ.nnRESULTS: Swine and NHP corneas showed the species-specific nerve morphology in both imaging modalities. Most fibers showed a linear course, forming a highly parallel pattern, converging in a vortex with overall nerve densities varying between 9.51 and 24.24 mm/mm2. The repeatability of nerve density quantification of the ยตOCT scans as approximately 88% in multiple image recordings of the same cornea.nnCONCLUSIONS: Compared to the current gold standard of FCM, ยตOCT’s larger field of view of currently 1 ร 1 mm increases the conclusiveness of density measurements, which, coupled with ยตOCT’s feature of not requiring direct contact, shows promise for future clinical application. The nerve density quantification may be relevant for screening for systemic disease (e.g., peripheral neuropathy).nnTRANSLATIONAL RELEVANCE: Technological advances in OCT technology may enable a quick assessment of corneal nerve density, which could be valuable evaluating ophthalmic and systemic peripheral innervation.
Osborn, Eric A; Ughi, Giovanni J; Verjans, Johan W; Piao, Zhonglie; Gerbaud, Edouard; Albaghdadi, Mazen; Khraishah, Haitham; Kassab, Mohamad B; Takx, Richard A P; Cui, Jie; Mauskapf, Adam; Shen, Changyu; Yeh, Robert W; Klimas, Michael T; Tawakol, Ahmed; Tearney, Guillermo J; Jaffer, Farouc A
Intravascular Molecular-Structural Assessment of Arterial Inflammation in Preclinical Atherosclerosis Progression Miscellaneous
2021, ISSN: 1876-7591.
@misc{pmid34419392b,
title = {Intravascular Molecular-Structural Assessment of Arterial Inflammation in Preclinical Atherosclerosis Progression},
author = {Eric A Osborn and Giovanni J Ughi and Johan W Verjans and Zhonglie Piao and Edouard Gerbaud and Mazen Albaghdadi and Haitham Khraishah and Mohamad B Kassab and Richard A P Takx and Jie Cui and Adam Mauskapf and Changyu Shen and Robert W Yeh and Michael T Klimas and Ahmed Tawakol and Guillermo J Tearney and Farouc A Jaffer},
doi = {10.1016/j.jcmg.2021.06.017},
issn = {1876-7591},
year = {2021},
date = {2021-11-01},
journal = {JACC Cardiovasc Imaging},
volume = {14},
number = {11},
pages = {2265--2267},
keywords = {},
pubstate = {published},
tppubtype = {misc}
}
Yonker, Lael M; Marand, Anika; Muldur, Sinan; Hopke, Alex; Leung, Hui Min; Flor, Denis De La; Park, Grace; Pinsky, Hanna; Guthrie, Lauren B; Tearney, Guillermo J; Irimia, Daniel; Hurley, Bryan P
Neutrophil dysfunction in cystic fibrosis Journal Article
In: J Cyst Fibros, vol. 20, no. 6, pp. 1062โ1071, 2021, ISSN: 1873-5010.
@article{pmid33589340,
title = {Neutrophil dysfunction in cystic fibrosis},
author = {Lael M Yonker and Anika Marand and Sinan Muldur and Alex Hopke and Hui Min Leung and Denis De La Flor and Grace Park and Hanna Pinsky and Lauren B Guthrie and Guillermo J Tearney and Daniel Irimia and Bryan P Hurley},
doi = {10.1016/j.jcf.2021.01.012},
issn = {1873-5010},
year = {2021},
date = {2021-11-01},
journal = {J Cyst Fibros},
volume = {20},
number = {6},
pages = {1062--1071},
abstract = {BACKGROUND: Excessive neutrophil inflammation is the hallmark of cystic fibrosis (CF) airway disease. Novel technologies for characterizing neutrophil dysfunction may provide insight into the nature of these abnormalities, revealing a greater mechanistic understanding and new avenues for CF therapies that target these mechanisms.nnMETHODS: Blood was collected from individuals with CF in the outpatient clinic, CF individuals hospitalized for a pulmonary exacerbation, and non-CF controls. Using microfluidic assays and advanced imaging technologies, we characterized 1) spontaneous neutrophil migration using microfluidic motility mazes, 2) neutrophil migration to and phagocytosis of Staphylococcal aureus particles in a microfluidic arena, 3) neutrophil swarming on Candida albicans clusters, and 4) Pseudomonas aeruginosa-induced neutrophil transepithelial migration using micro-optical coherence technology (ยตOCT).nnRESULTS: Participants included 44 individuals: 16 Outpatient CF, 13 Hospitalized CF, and 15 Non-CF individuals. While no differences were seen with spontaneous migration, CF neutrophils migrated towards S. aureus particles more quickly than non-CF neutrophils (pย <ย 0.05). CF neutrophils, especially Hospitalized CF neutrophils, generated significantly larger aggregates around S. aureus particles over time. Hospitalized CF neutrophils were more likely to have dysfunctional swarming (pย <ย 0.01) and less efficient clearing of C. albicans (pย <ย 0.0001). When comparing trans-epithelial migration towards Pseudomonas aeruginosa epithelial infection, Outpatient CF neutrophils displayed an increase in the magnitude of transmigration and adherence to the epithelium (pย <ย 0.05).nnCONCLUSIONS: Advanced technologies for characterizing CF neutrophil function reveal significantly altered migratory responses, cell-to-cell clustering, and microbe containment. Future investigations will probe mechanistic basis for abnormal responses in CF to identify potential avenues for novel anti-inflammatory therapeutics.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: Excessive neutrophil inflammation is the hallmark of cystic fibrosis (CF) airway disease. Novel technologies for characterizing neutrophil dysfunction may provide insight into the nature of these abnormalities, revealing a greater mechanistic understanding and new avenues for CF therapies that target these mechanisms.nnMETHODS: Blood was collected from individuals with CF in the outpatient clinic, CF individuals hospitalized for a pulmonary exacerbation, and non-CF controls. Using microfluidic assays and advanced imaging technologies, we characterized 1) spontaneous neutrophil migration using microfluidic motility mazes, 2) neutrophil migration to and phagocytosis of Staphylococcal aureus particles in a microfluidic arena, 3) neutrophil swarming on Candida albicans clusters, and 4) Pseudomonas aeruginosa-induced neutrophil transepithelial migration using micro-optical coherence technology (ยตOCT).nnRESULTS: Participants included 44 individuals: 16 Outpatient CF, 13 Hospitalized CF, and 15 Non-CF individuals. While no differences were seen with spontaneous migration, CF neutrophils migrated towards S. aureus particles more quickly than non-CF neutrophils (pย <ย 0.05). CF neutrophils, especially Hospitalized CF neutrophils, generated significantly larger aggregates around S. aureus particles over time. Hospitalized CF neutrophils were more likely to have dysfunctional swarming (pย <ย 0.01) and less efficient clearing of C. albicans (pย <ย 0.0001). When comparing trans-epithelial migration towards Pseudomonas aeruginosa epithelial infection, Outpatient CF neutrophils displayed an increase in the magnitude of transmigration and adherence to the epithelium (pย <ย 0.05).nnCONCLUSIONS: Advanced technologies for characterizing CF neutrophil function reveal significantly altered migratory responses, cell-to-cell clustering, and microbe containment. Future investigations will probe mechanistic basis for abnormal responses in CF to identify potential avenues for novel anti-inflammatory therapeutics.
Schenk, Merle S; Wartak, Andreas; Buehler, Verena; Zhao, Jie; Tearney, Guillermo J; Birngruber, Reginald; Kassumeh, Stefan
Advances in Imaging of Subbasal Corneal Nerves With Micro-Optical Coherence Tomography Journal Article
In: Transl Vis Sci Technol, vol. 10, no. 13, pp. 22, 2021, ISSN: 2164-2591.
@article{pmid34779835,
title = {Advances in Imaging of Subbasal Corneal Nerves With Micro-Optical Coherence Tomography},
author = {Merle S Schenk and Andreas Wartak and Verena Buehler and Jie Zhao and Guillermo J Tearney and Reginald Birngruber and Stefan Kassumeh},
doi = {10.1167/tvst.10.13.22},
issn = {2164-2591},
year = {2021},
date = {2021-11-01},
journal = {Transl Vis Sci Technol},
volume = {10},
number = {13},
pages = {22},
abstract = {PURPOSE: To investigate the most peripheral corneal nerve plexus using high-resolution micro-optical coherence tomography (ยตOCT) imaging and to assessย ยตOCT's clinical potential as a screening tool for corneal and systemic diseases.nnMETHODS: An experimental high-resolution (1.5 ร 1.5 ร 1ย ยตm) ยตOCT setup was applied for three-dimensional imaging of the subbasal nerve plexus in nonhuman primates (NHPs) and swine within 3 hours postmortem. Morphologic features of subbasal nerves in ยตOCT were compared to ฮฒ3 tubulin-stained fluorescence confocal microscopy (FCM). Parameters such as nerve density, nerve distribution, and imaging repeatability were evaluated, using semiautomatic image analysis in form of a custom corneal surface segmentation algorithm and NeuronJ.nnRESULTS: Swine and NHP corneas showed the species-specific nerve morphology in both imaging modalities. Most fibers showed a linear course, forming a highly parallel pattern, converging in a vortex with overall nerve densities varying between 9.51 and 24.24 mm/mm2. The repeatability of nerve density quantification of the ยตOCT scans as approximately 88% in multiple image recordings of the same cornea.nnCONCLUSIONS: Compared to the current gold standard of FCM, ยตOCT's larger field of view of currently 1 ร 1 mm increases the conclusiveness of density measurements, which, coupled with ยตOCT's feature of not requiring direct contact, shows promise for future clinical application. The nerve density quantification may be relevant for screening for systemic disease (e.g., peripheral neuropathy).nnTRANSLATIONAL RELEVANCE: Technological advances in OCT technology may enable a quick assessment of corneal nerve density, which could be valuable evaluating ophthalmic and systemic peripheral innervation.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
PURPOSE: To investigate the most peripheral corneal nerve plexus using high-resolution micro-optical coherence tomography (ยตOCT) imaging and to assessย ยตOCT’s clinical potential as a screening tool for corneal and systemic diseases.nnMETHODS: An experimental high-resolution (1.5 ร 1.5 ร 1ย ยตm) ยตOCT setup was applied for three-dimensional imaging of the subbasal nerve plexus in nonhuman primates (NHPs) and swine within 3 hours postmortem. Morphologic features of subbasal nerves in ยตOCT were compared to ฮฒ3 tubulin-stained fluorescence confocal microscopy (FCM). Parameters such as nerve density, nerve distribution, and imaging repeatability were evaluated, using semiautomatic image analysis in form of a custom corneal surface segmentation algorithm and NeuronJ.nnRESULTS: Swine and NHP corneas showed the species-specific nerve morphology in both imaging modalities. Most fibers showed a linear course, forming a highly parallel pattern, converging in a vortex with overall nerve densities varying between 9.51 and 24.24 mm/mm2. The repeatability of nerve density quantification of the ยตOCT scans as approximately 88% in multiple image recordings of the same cornea.nnCONCLUSIONS: Compared to the current gold standard of FCM, ยตOCT’s larger field of view of currently 1 ร 1 mm increases the conclusiveness of density measurements, which, coupled with ยตOCT’s feature of not requiring direct contact, shows promise for future clinical application. The nerve density quantification may be relevant for screening for systemic disease (e.g., peripheral neuropathy).nnTRANSLATIONAL RELEVANCE: Technological advances in OCT technology may enable a quick assessment of corneal nerve density, which could be valuable evaluating ophthalmic and systemic peripheral innervation.
Osborn, Eric A; Ughi, Giovanni J; Verjans, Johan W; Piao, Zhonglie; Gerbaud, Edouard; Albaghdadi, Mazen; Khraishah, Haitham; Kassab, Mohamad B; Takx, Richard A P; Cui, Jie; Mauskapf, Adam; Shen, Changyu; Yeh, Robert W; Klimas, Michael T; Tawakol, Ahmed; Tearney, Guillermo J; Jaffer, Farouc A
Intravascular Molecular-Structural Assessment of Arterial Inflammation in Preclinical Atherosclerosis Progression Miscellaneous
2021, ISSN: 1876-7591.
@misc{pmid34419392,
title = {Intravascular Molecular-Structural Assessment of Arterial Inflammation in Preclinical Atherosclerosis Progression},
author = {Eric A Osborn and Giovanni J Ughi and Johan W Verjans and Zhonglie Piao and Edouard Gerbaud and Mazen Albaghdadi and Haitham Khraishah and Mohamad B Kassab and Richard A P Takx and Jie Cui and Adam Mauskapf and Changyu Shen and Robert W Yeh and Michael T Klimas and Ahmed Tawakol and Guillermo J Tearney and Farouc A Jaffer},
doi = {10.1016/j.jcmg.2021.06.017},
issn = {1876-7591},
year = {2021},
date = {2021-11-01},
journal = {JACC Cardiovasc Imaging},
volume = {14},
number = {11},
pages = {2265--2267},
keywords = {},
pubstate = {published},
tppubtype = {misc}
}