Pathways to clinical CLARITY: volumetric analysis of irregular, soft, and heterogeneous tissues in development and disease

Abstract Three-dimensional tissue-structural relationships are not well captured by typical thin-section histology, posing challenges for the study of tissue physiology and pathology. Moreover, while recent progress has been made with intact methods for clearing, labeling, and imaging whole organs s...

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Autores principales: Brian Hsueh, Vanessa M. Burns, Philip Pauerstein, Katherine Holzem, Li Ye, Kristin Engberg, Ai-Chi Wang, Xueying Gu, Harini Chakravarthy, H. Efsun Arda, Gregory Charville, Hannes Vogel, Igor R. Efimov, Seung Kim, Karl Deisseroth
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Publicado: Nature Portfolio 2017
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Acceso en línea:https://doaj.org/article/b005b26d2af84e9196f1657c71463209
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spelling oai:doaj.org-article:b005b26d2af84e9196f1657c714632092021-12-02T12:30:51ZPathways to clinical CLARITY: volumetric analysis of irregular, soft, and heterogeneous tissues in development and disease10.1038/s41598-017-05614-42045-2322https://doaj.org/article/b005b26d2af84e9196f1657c714632092017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05614-4https://doaj.org/toc/2045-2322Abstract Three-dimensional tissue-structural relationships are not well captured by typical thin-section histology, posing challenges for the study of tissue physiology and pathology. Moreover, while recent progress has been made with intact methods for clearing, labeling, and imaging whole organs such as the mature brain, these approaches are generally unsuitable for soft, irregular, and heterogeneous tissues that account for the vast majority of clinical samples and biopsies. Here we develop a biphasic hydrogel methodology, which along with automated analysis, provides for high-throughput quantitative volumetric interrogation of spatially-irregular and friable tissue structures. We validate and apply this approach in the examination of a variety of developing and diseased tissues, with specific focus on the dynamics of normal and pathological pancreatic innervation and development, including in clinical samples. Quantitative advantages of the intact-tissue approach were demonstrated compared to conventional thin-section histology, pointing to broad applications in both research and clinical settings.Brian HsuehVanessa M. BurnsPhilip PauersteinKatherine HolzemLi YeKristin EngbergAi-Chi WangXueying GuHarini ChakravarthyH. Efsun ArdaGregory CharvilleHannes VogelIgor R. EfimovSeung KimKarl DeisserothNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-16 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Brian Hsueh
Vanessa M. Burns
Philip Pauerstein
Katherine Holzem
Li Ye
Kristin Engberg
Ai-Chi Wang
Xueying Gu
Harini Chakravarthy
H. Efsun Arda
Gregory Charville
Hannes Vogel
Igor R. Efimov
Seung Kim
Karl Deisseroth
Pathways to clinical CLARITY: volumetric analysis of irregular, soft, and heterogeneous tissues in development and disease
description Abstract Three-dimensional tissue-structural relationships are not well captured by typical thin-section histology, posing challenges for the study of tissue physiology and pathology. Moreover, while recent progress has been made with intact methods for clearing, labeling, and imaging whole organs such as the mature brain, these approaches are generally unsuitable for soft, irregular, and heterogeneous tissues that account for the vast majority of clinical samples and biopsies. Here we develop a biphasic hydrogel methodology, which along with automated analysis, provides for high-throughput quantitative volumetric interrogation of spatially-irregular and friable tissue structures. We validate and apply this approach in the examination of a variety of developing and diseased tissues, with specific focus on the dynamics of normal and pathological pancreatic innervation and development, including in clinical samples. Quantitative advantages of the intact-tissue approach were demonstrated compared to conventional thin-section histology, pointing to broad applications in both research and clinical settings.
format article
author Brian Hsueh
Vanessa M. Burns
Philip Pauerstein
Katherine Holzem
Li Ye
Kristin Engberg
Ai-Chi Wang
Xueying Gu
Harini Chakravarthy
H. Efsun Arda
Gregory Charville
Hannes Vogel
Igor R. Efimov
Seung Kim
Karl Deisseroth
author_facet Brian Hsueh
Vanessa M. Burns
Philip Pauerstein
Katherine Holzem
Li Ye
Kristin Engberg
Ai-Chi Wang
Xueying Gu
Harini Chakravarthy
H. Efsun Arda
Gregory Charville
Hannes Vogel
Igor R. Efimov
Seung Kim
Karl Deisseroth
author_sort Brian Hsueh
title Pathways to clinical CLARITY: volumetric analysis of irregular, soft, and heterogeneous tissues in development and disease
title_short Pathways to clinical CLARITY: volumetric analysis of irregular, soft, and heterogeneous tissues in development and disease
title_full Pathways to clinical CLARITY: volumetric analysis of irregular, soft, and heterogeneous tissues in development and disease
title_fullStr Pathways to clinical CLARITY: volumetric analysis of irregular, soft, and heterogeneous tissues in development and disease
title_full_unstemmed Pathways to clinical CLARITY: volumetric analysis of irregular, soft, and heterogeneous tissues in development and disease
title_sort pathways to clinical clarity: volumetric analysis of irregular, soft, and heterogeneous tissues in development and disease
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/b005b26d2af84e9196f1657c71463209
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