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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Nature Portfolio
2017
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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) |
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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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