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MarrowQuant Across Aging and Aplasia: A Digital Pathology Workflow for Quantification of Bone Marrow Compartments in Histological Sections

The bone marrow (BM) exists heterogeneously as hematopoietic/red or adipocytic/yellow marrow depending on skeletal location, age, and physiological condition. Mouse models and patients undergoing radio/chemotherapy or suffering acute BM failure endure rapid adipocytic conversion of the marrow microe...

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Autores principales: Tratwal, Josefine, Bekri, David, Boussema, Chiheb, Sarkis, Rita, Kunz, Nicolas, Koliqi, Tereza, Rojas-Sutterlin, Shanti, Schyrr, Frédérica, Tavakol, Daniel Naveed, Campos, Vasco, Scheller, Erica L., Sarro, Rossella, Bárcena, Carmen, Bisig, Bettina, Nardi, Valentina, de Leval, Laurence, Burri, Olivier, Naveiras, Olaia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7542184/
https://www.ncbi.nlm.nih.gov/pubmed/33071956
http://dx.doi.org/10.3389/fendo.2020.00480
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author Tratwal, Josefine
Bekri, David
Boussema, Chiheb
Sarkis, Rita
Kunz, Nicolas
Koliqi, Tereza
Rojas-Sutterlin, Shanti
Schyrr, Frédérica
Tavakol, Daniel Naveed
Campos, Vasco
Scheller, Erica L.
Sarro, Rossella
Bárcena, Carmen
Bisig, Bettina
Nardi, Valentina
de Leval, Laurence
Burri, Olivier
Naveiras, Olaia
author_facet Tratwal, Josefine
Bekri, David
Boussema, Chiheb
Sarkis, Rita
Kunz, Nicolas
Koliqi, Tereza
Rojas-Sutterlin, Shanti
Schyrr, Frédérica
Tavakol, Daniel Naveed
Campos, Vasco
Scheller, Erica L.
Sarro, Rossella
Bárcena, Carmen
Bisig, Bettina
Nardi, Valentina
de Leval, Laurence
Burri, Olivier
Naveiras, Olaia
author_sort Tratwal, Josefine
collection PubMed
description The bone marrow (BM) exists heterogeneously as hematopoietic/red or adipocytic/yellow marrow depending on skeletal location, age, and physiological condition. Mouse models and patients undergoing radio/chemotherapy or suffering acute BM failure endure rapid adipocytic conversion of the marrow microenvironment, the so-called “red-to-yellow” transition. Following hematopoietic recovery, such as upon BM transplantation, a “yellow-to-red” transition occurs and functional hematopoiesis is restored. Gold Standards to estimate BM cellular composition are pathologists' assessment of hematopoietic cellularity in hematoxylin and eosin (H&E) stained histological sections as well as volumetric measurements of marrow adiposity with contrast-enhanced micro-computerized tomography (CE-μCT) upon osmium-tetroxide lipid staining. Due to user-dependent variables, reproducibility in longitudinal studies is a challenge for both methods. Here we report the development of a semi-automated image analysis plug-in, MarrowQuant, which employs the open-source software QuPath, to systematically quantify multiple bone components in H&E sections in an unbiased manner. MarrowQuant discerns and quantifies the areas occupied by bone, adipocyte ghosts, hematopoietic cells, and the interstitial/microvascular compartment. A separate feature, AdipoQuant, fragments adipocyte ghosts in H&E-stained sections of extramedullary adipose tissue to render adipocyte area and size distribution. Quantification of BM hematopoietic cellularity with MarrowQuant lies within the range of scoring by four independent pathologists, while quantification of the total adipocyte area in whole bone sections compares with volumetric measurements. Employing our tool, we were able to develop a standardized map of BM hematopoietic cellularity and adiposity in mid-sections of murine C57BL/6 bones in homeostatic conditions, including quantification of the highly predictable red-to-yellow transitions in the proximal section of the caudal tail and in the proximal-to-distal tibia. Additionally, we present a comparative skeletal map induced by lethal irradiation, with longitudinal quantification of the “red-to-yellow-to-red” transition over 2 months in C57BL/6 femurs and tibiae. We find that, following BM transplantation, BM adiposity inversely correlates with kinetics of hematopoietic recovery and that a proximal to distal gradient is conserved. Analysis of in vivo recovery through magnetic resonance imaging (MRI) reveals comparable kinetics. On human trephine biopsies MarrowQuant successfully recognizes the BM compartments, opening avenues for its application in experimental, or clinical contexts that require standardized human BM evaluation.
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spelling pubmed-75421842020-10-16 MarrowQuant Across Aging and Aplasia: A Digital Pathology Workflow for Quantification of Bone Marrow Compartments in Histological Sections Tratwal, Josefine Bekri, David Boussema, Chiheb Sarkis, Rita Kunz, Nicolas Koliqi, Tereza Rojas-Sutterlin, Shanti Schyrr, Frédérica Tavakol, Daniel Naveed Campos, Vasco Scheller, Erica L. Sarro, Rossella Bárcena, Carmen Bisig, Bettina Nardi, Valentina de Leval, Laurence Burri, Olivier Naveiras, Olaia Front Endocrinol (Lausanne) Endocrinology The bone marrow (BM) exists heterogeneously as hematopoietic/red or adipocytic/yellow marrow depending on skeletal location, age, and physiological condition. Mouse models and patients undergoing radio/chemotherapy or suffering acute BM failure endure rapid adipocytic conversion of the marrow microenvironment, the so-called “red-to-yellow” transition. Following hematopoietic recovery, such as upon BM transplantation, a “yellow-to-red” transition occurs and functional hematopoiesis is restored. Gold Standards to estimate BM cellular composition are pathologists' assessment of hematopoietic cellularity in hematoxylin and eosin (H&E) stained histological sections as well as volumetric measurements of marrow adiposity with contrast-enhanced micro-computerized tomography (CE-μCT) upon osmium-tetroxide lipid staining. Due to user-dependent variables, reproducibility in longitudinal studies is a challenge for both methods. Here we report the development of a semi-automated image analysis plug-in, MarrowQuant, which employs the open-source software QuPath, to systematically quantify multiple bone components in H&E sections in an unbiased manner. MarrowQuant discerns and quantifies the areas occupied by bone, adipocyte ghosts, hematopoietic cells, and the interstitial/microvascular compartment. A separate feature, AdipoQuant, fragments adipocyte ghosts in H&E-stained sections of extramedullary adipose tissue to render adipocyte area and size distribution. Quantification of BM hematopoietic cellularity with MarrowQuant lies within the range of scoring by four independent pathologists, while quantification of the total adipocyte area in whole bone sections compares with volumetric measurements. Employing our tool, we were able to develop a standardized map of BM hematopoietic cellularity and adiposity in mid-sections of murine C57BL/6 bones in homeostatic conditions, including quantification of the highly predictable red-to-yellow transitions in the proximal section of the caudal tail and in the proximal-to-distal tibia. Additionally, we present a comparative skeletal map induced by lethal irradiation, with longitudinal quantification of the “red-to-yellow-to-red” transition over 2 months in C57BL/6 femurs and tibiae. We find that, following BM transplantation, BM adiposity inversely correlates with kinetics of hematopoietic recovery and that a proximal to distal gradient is conserved. Analysis of in vivo recovery through magnetic resonance imaging (MRI) reveals comparable kinetics. On human trephine biopsies MarrowQuant successfully recognizes the BM compartments, opening avenues for its application in experimental, or clinical contexts that require standardized human BM evaluation. Frontiers Media S.A. 2020-09-24 /pmc/articles/PMC7542184/ /pubmed/33071956 http://dx.doi.org/10.3389/fendo.2020.00480 Text en Copyright © 2020 Tratwal, Bekri, Boussema, Sarkis, Kunz, Koliqi, Rojas-Sutterlin, Schyrr, Tavakol, Campos, Scheller, Sarro, Bárcena, Bisig, Nardi, de Leval, Burri and Naveiras. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Endocrinology
Tratwal, Josefine
Bekri, David
Boussema, Chiheb
Sarkis, Rita
Kunz, Nicolas
Koliqi, Tereza
Rojas-Sutterlin, Shanti
Schyrr, Frédérica
Tavakol, Daniel Naveed
Campos, Vasco
Scheller, Erica L.
Sarro, Rossella
Bárcena, Carmen
Bisig, Bettina
Nardi, Valentina
de Leval, Laurence
Burri, Olivier
Naveiras, Olaia
MarrowQuant Across Aging and Aplasia: A Digital Pathology Workflow for Quantification of Bone Marrow Compartments in Histological Sections
title MarrowQuant Across Aging and Aplasia: A Digital Pathology Workflow for Quantification of Bone Marrow Compartments in Histological Sections
title_full MarrowQuant Across Aging and Aplasia: A Digital Pathology Workflow for Quantification of Bone Marrow Compartments in Histological Sections
title_fullStr MarrowQuant Across Aging and Aplasia: A Digital Pathology Workflow for Quantification of Bone Marrow Compartments in Histological Sections
title_full_unstemmed MarrowQuant Across Aging and Aplasia: A Digital Pathology Workflow for Quantification of Bone Marrow Compartments in Histological Sections
title_short MarrowQuant Across Aging and Aplasia: A Digital Pathology Workflow for Quantification of Bone Marrow Compartments in Histological Sections
title_sort marrowquant across aging and aplasia: a digital pathology workflow for quantification of bone marrow compartments in histological sections
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7542184/
https://www.ncbi.nlm.nih.gov/pubmed/33071956
http://dx.doi.org/10.3389/fendo.2020.00480
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