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Unraveling Microstructural and Macrostructural Brain Age Dynamics in Multiple Sclerosis.

Xinjie Chen1,2,3, Po-Jui Lu1,2,3, Mario Ocampo-Pineda1,2,3

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Quantitative MRI (qMRI) combined with conventional MRI improves brain age prediction in multiple sclerosis (MS). This brain-predicted age difference (brain-PAD) can track MS progression, disability, and neuroinflammation.

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Area of Science:

  • Neuroimaging
  • Biomarkers
  • Neurodegeneration

Background:

  • Multiple sclerosis (MS) involves neurodegeneration influenced by disease pathology and aging.
  • Conventional MRI shows structural changes, while quantitative MRI (qMRI) measures microstructural alterations.
  • Combining MRI techniques may clarify aging-pathology interactions in MS disability.

Purpose of the Study:

  • To assess the added value of qMRI in predicting brain age differences (brain-PAD) in MS.
  • To investigate associations between brain-PAD, clinical disability, and neuroinflammation biomarkers.
  • To determine if integrated MRI models improve brain age prediction over morphometry or qMRI alone.

Main Methods:

  • Analysis of cross-sectional and longitudinal morphometry data from 1,353 MS patients and 3,462 healthy controls (HCs).
  • Analysis of cross-sectional qMRI data from 169 MS patients and 378 HCs.
  • Machine learning models used to estimate brain-PAD from morphometric and qMRI data; associations with clinical and biomarker data were assessed.

Main Results:

  • Integrated morphometry and qMRI models yielded the best brain age prediction performance (mean absolute error: 5.73).
  • Morphometry-based brain-PAD correlated with disability, neurofilament light chain, and glial fibrillary acidic protein.
  • qMRI-based brain-PAD correlated with white matter lesion count and paramagnetic rim lesion volume.

Conclusions:

  • Integrating qMRI enhances the accuracy of brain age prediction in MS.
  • Brain-PAD derived from integrated MRI serves as a valuable imaging biomarker.
  • This approach can quantify MS-associated aging and monitor disease progression, disability, and neuroinflammation.