MRI in multiple sclerosis: progress in in-vivo pathobiology.

Area of Science:

• Neuroimaging
• Neurology
• Pathobiology

Background:

• Magnetic resonance imaging (MRI) has evolved beyond diagnostics for multiple sclerosis (MS).
• MRI now investigates in-vivo MS pathobiology, including blood-brain barrier dysfunction, demyelination, neuroaxonal loss, glial activation, and network disruption.
• Emerging evidence challenges the traditional inflammation-driven MS model, highlighting the role of central nervous system-intrinsic mechanisms.

Purpose of the Study:

• To review recent advances in MRI techniques for investigating MS.
• To discuss how advanced MRI markers reveal complex pathobiological processes in MS.
• To support a unified model of MS integrating inflammatory, metabolic, and neurodegenerative aspects.

Main Methods:

• Review of advanced magnetic resonance imaging (MRI) techniques and biomarkers.
• Analysis of conventional versus advanced MRI findings in multiple sclerosis (MS).
• Integration of imaging evidence with current understanding of MS pathobiology.

Main Results:

• Conventional MRI markers (e.g., enhancing lesions) reflect focal inflammation.
• Advanced MRI reveals diffuse vulnerability, chronic active lesions, meningeal inflammation, metabolic dysfunction, and network failure.
• These advanced biomarkers link focal pathology to chronic, smoldering, and neurodegenerative processes.

Conclusions:

• MRI supports a unified MS model where inflammatory, metabolic, and neurodegenerative mechanisms interact.
• Mechanistic MRI biomarkers allow for patient stratification and prognosis.
• Advanced MRI provides sensitive outcome measures for novel MS therapies, advancing precision medicine.