TY - JOUR
T1 - Development of a standardized histopathology scoring system using machine learning algorithms for intervertebral disc degeneration in the mouse model—An ORS spine section initiative
AU - Melgoza, Itzel Paola
AU - Chenna, Srish S.
AU - Tessier, Steven
AU - Zhang, Yejia
AU - Tang, Simon Y.
AU - Ohnishi, Takashi
AU - Novais, Emanuel José
AU - Kerr, Geoffrey J.
AU - Mohanty, Sarthak
AU - Tam, Vivian
AU - Chan, Wilson C.W.
AU - Zhou, Chao Ming
AU - Zhang, Ying
AU - Leung, Victor Y.
AU - Brice, Angela K.
AU - Séguin, Cheryle A.
AU - Chan, Danny
AU - Vo, Nam
AU - Risbud, Makarand V.
AU - Dahia, Chitra L.
N1 - Funding Information:
Support to Chitra L. Dahia for this work was provided by the Starr Foundation, S & L Marx Foundation, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) of the National Institutes of Health (NIH) Grant Number R01 AR065530, R01 AR077145 and NIH grant number S10 OD026763. Makarand V. Risbud is supported by NIAMS grants R01 AR064733, R01 AR055655, R01 AR074813. Contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of NIAMS or NIH. Part of this work was supported by the Research Grants Council (RGC) of Hong Kong; GRF17126319 and E‐HKU703/18 provided to Danny Chan, and GRF17126518 to Victor Y. Leung.
Funding Information:
National Institute of Arthritis and Musculoskeletal and Skin Diseases, Grant/Award Numbers: R01 AR055655, R01 AR064733, R01 AR074813, R01AR065530, R01AR077145; NIH Office of the Director, Grant/Award Number: S10OD026763; Research Grant Council of Hong Kong, Grant/Award Numbers: GRF17126518, GRF17126319; RGC European Union—Hong Kong Research and Innovation Cooperation Co‐funding Mechanism, Grant/Award Number: E‐HKU703/18; Hong Kong Research Grants Council, Grant/Award Number: T12‐708/12N; S & L Marx Foundation; Starr Foundation Funding information
Publisher Copyright:
© 2021 The Authors. JOR Spine published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.
PY - 2021/6
Y1 - 2021/6
N2 - Mice have been increasingly used as preclinical model to elucidate mechanisms and test therapeutics for treating intervertebral disc degeneration (IDD). Several intervertebral disc (IVD) histological scoring systems have been proposed, but none exists that reliably quantitate mouse disc pathologies. Here, we report a new robust quantitative mouse IVD histopathological scoring system developed by building consensus from the spine community analyses of previous scoring systems and features noted on different mouse models of IDD. The new scoring system analyzes 14 key histopathological features from nucleus pulposus (NP), annulus fibrosus (AF), endplate (EP), and AF/NP/EP interface regions. Each feature is categorized and scored; hence, the weight for quantifying the disc histopathology is equally distributed and not driven by only a few features. We tested the new histopathological scoring criteria using images of lumbar and coccygeal discs from different IDD models of both sexes, including genetic, needle-punctured, static compressive models, and natural aging mice spanning neonatal to old age stages. Moreover, disc sections from common histological preparation techniques and stains including H&E, SafraninO/Fast green, and FAST were analyzed to enable better cross-study comparisons. Fleiss's multi-rater agreement test shows significant agreement by both experienced and novice multiple raters for all 14 features on several mouse models and sections prepared using various histological techniques. The sensitivity and specificity of the new scoring system was validated using artificial intelligence and supervised and unsupervised machine learning algorithms, including artificial neural networks, k-means clustering, and principal component analysis. Finally, we applied the new scoring system on established disc degeneration models and demonstrated high sensitivity and specificity of histopathological scoring changes. Overall, the new histopathological scoring system offers the ability to quantify histological changes in mouse models of disc degeneration and regeneration with high sensitivity and specificity.
AB - Mice have been increasingly used as preclinical model to elucidate mechanisms and test therapeutics for treating intervertebral disc degeneration (IDD). Several intervertebral disc (IVD) histological scoring systems have been proposed, but none exists that reliably quantitate mouse disc pathologies. Here, we report a new robust quantitative mouse IVD histopathological scoring system developed by building consensus from the spine community analyses of previous scoring systems and features noted on different mouse models of IDD. The new scoring system analyzes 14 key histopathological features from nucleus pulposus (NP), annulus fibrosus (AF), endplate (EP), and AF/NP/EP interface regions. Each feature is categorized and scored; hence, the weight for quantifying the disc histopathology is equally distributed and not driven by only a few features. We tested the new histopathological scoring criteria using images of lumbar and coccygeal discs from different IDD models of both sexes, including genetic, needle-punctured, static compressive models, and natural aging mice spanning neonatal to old age stages. Moreover, disc sections from common histological preparation techniques and stains including H&E, SafraninO/Fast green, and FAST were analyzed to enable better cross-study comparisons. Fleiss's multi-rater agreement test shows significant agreement by both experienced and novice multiple raters for all 14 features on several mouse models and sections prepared using various histological techniques. The sensitivity and specificity of the new scoring system was validated using artificial intelligence and supervised and unsupervised machine learning algorithms, including artificial neural networks, k-means clustering, and principal component analysis. Finally, we applied the new scoring system on established disc degeneration models and demonstrated high sensitivity and specificity of histopathological scoring changes. Overall, the new histopathological scoring system offers the ability to quantify histological changes in mouse models of disc degeneration and regeneration with high sensitivity and specificity.
KW - aging
KW - degeneration
KW - pre-clinical models
KW - structure-function relationships
UR - http://www.scopus.com/inward/record.url?scp=85110396260&partnerID=8YFLogxK
U2 - 10.1002/jsp2.1164
DO - 10.1002/jsp2.1164
M3 - Article
C2 - 34337338
AN - SCOPUS:85110396260
VL - 4
JO - JOR Spine
JF - JOR Spine
SN - 2572-1143
IS - 2
M1 - e1164
ER -