TY - JOUR
T1 - Disruption of the atrophy-based functional network in multiple sclerosis is associated with clinical disability
T2 - Validation of a meta-analytic model in resting-state functional MRI
AU - Chiang, Florence L.
AU - Feng, Max
AU - Romero, Rebecca S.
AU - Price, Larry
AU - Franklin, Crystal G.
AU - Deng, Shengwen
AU - Gray, Jodie P.
AU - Yu, Fang F.
AU - Tantiwongkosi, Bundhit
AU - Huang, Susie Y.
AU - Fox, Peter T.
N1 - Funding Information:
ticle: institution received grants from National Institutes of Health and Radiological Society of North America. Activities not related to the present article: disclosed no relevant relationships. Other relationships: filed patent with U.S. Patent Office. M.F. disclosed no relevant relationships. R.S.R. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: is a consultant for BSM, Viela Bio, and Genentech. Other relationships: disclosed no relevant relationships. L.P. disclosed no relevant relationships. C.G.F. disclosed no relevant relationships. S.D. disclosed no relevant relationships. J.P.G. disclosed no relevant relationships. F.F.Y. disclosed no relevant relationships. B.T. disclosed no relevant relationships. S.Y.H. Activities related to the present article: institution received grant from National Institutes of Health (NIH). Activities not related to the present article: institution has grants/grants pending with Siemens Healthineers; has received payment for lectures including service on speakers bureaus from Siemens Healthineers. Other relationships: disclosed no relevant relationships. P.T.F. Activities related to the present article: institution received grants from NIH and National Institute of Mental Health. Activities not related to the present article: is a consultant for NIH Center for Scientific Review; receives payment from Wiley as editor in chief of Human Brain Mapping; has grants/grants pending with NIH, U.S. Department of Defense, U.S. Department of Veterans Affairs, and Michael J. Fox Foundation; filed patent with U.S. Patent Office; has received reimbursement from various institutions for travel, accommodations, and meeting expenses. Other relationships: receives payment as a licensee of intellectual property.
Funding Information:
Supported by the National Institutes of Health (grant nos. R01MH074457, R25EB16631, P41EB030006, and K23NS096056) and Radiological Society of North America (grant no. RR1826).
Publisher Copyright:
© RSNA, 2021
PY - 2021/4
Y1 - 2021/4
N2 - Background: In multiple sclerosis (MS), gray matter (GM) atrophy exhibits a specific pattern, which correlates strongly with clinical disability. However, the mechanism of regional specificity in GM atrophy remains largely unknown. Recently, the network degeneration hypothesis (NDH) was quantitatively defined (using coordinate-based meta-analysis) as the atrophy-based functional network (AFN) model, which posits that localized GM atrophy in MS is mediated by functional networks. Purpose: To test the NDH in MS in a data-driven manner using the AFN model to direct analyses in an independent test sample. Materials and Methods: Model fit testing was conducted with structural equation modeling, which is based on the computation of semipartial correlations. Model verification was performed in coordinate-based data of healthy control participants from the BrainMap database (https://www.brainmap.org). Model validation was conducted in prospectively acquired resting-state functional MRI in participants with relapsing-remitting MS who were recruited between September 2018 and January 2019. Correlation analyses of model fit indices and volumetric measures with Expanded Disability Status Scale (EDSS) scores and disease duration were performed. Results: Model verification of healthy control participants included 80 194 coordinates from 9035 experiments. Model verification in healthy control data resulted in excellent model fit (root mean square error of approximation, 0.037; 90% CI: 0.036, 0.039). Twenty participants (mean age, 36 years 6 9 [standard deviation]; 12 women) with relapsing-remitting MS were evaluated. Model validation in resting-state functional MRI in participants with MS resulted in deviation from optimal model fit (root mean square error of approximation, 0.071; 90% CI: 0.070, 0.072), which correlated with EDSS scores (r = 0.68; P = .002). Conclusion: The atrophy-based functional network model predicts functional network disruption in multiple sclerosis (MS), thereby supporting the network degeneration hypothesis. On resting-state functional MRI scans, reduced functional network integrity in participants with MS had a strong positive correlation with clinical disability.
AB - Background: In multiple sclerosis (MS), gray matter (GM) atrophy exhibits a specific pattern, which correlates strongly with clinical disability. However, the mechanism of regional specificity in GM atrophy remains largely unknown. Recently, the network degeneration hypothesis (NDH) was quantitatively defined (using coordinate-based meta-analysis) as the atrophy-based functional network (AFN) model, which posits that localized GM atrophy in MS is mediated by functional networks. Purpose: To test the NDH in MS in a data-driven manner using the AFN model to direct analyses in an independent test sample. Materials and Methods: Model fit testing was conducted with structural equation modeling, which is based on the computation of semipartial correlations. Model verification was performed in coordinate-based data of healthy control participants from the BrainMap database (https://www.brainmap.org). Model validation was conducted in prospectively acquired resting-state functional MRI in participants with relapsing-remitting MS who were recruited between September 2018 and January 2019. Correlation analyses of model fit indices and volumetric measures with Expanded Disability Status Scale (EDSS) scores and disease duration were performed. Results: Model verification of healthy control participants included 80 194 coordinates from 9035 experiments. Model verification in healthy control data resulted in excellent model fit (root mean square error of approximation, 0.037; 90% CI: 0.036, 0.039). Twenty participants (mean age, 36 years 6 9 [standard deviation]; 12 women) with relapsing-remitting MS were evaluated. Model validation in resting-state functional MRI in participants with MS resulted in deviation from optimal model fit (root mean square error of approximation, 0.071; 90% CI: 0.070, 0.072), which correlated with EDSS scores (r = 0.68; P = .002). Conclusion: The atrophy-based functional network model predicts functional network disruption in multiple sclerosis (MS), thereby supporting the network degeneration hypothesis. On resting-state functional MRI scans, reduced functional network integrity in participants with MS had a strong positive correlation with clinical disability.
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U2 - 10.1148/RADIOL.2021203414
DO - 10.1148/RADIOL.2021203414
M3 - Article
C2 - 33529135
AN - SCOPUS:85103473286
SN - 0033-8419
VL - 299
SP - 159
EP - 166
JO - Radiology
JF - Radiology
IS - 1
ER -