The History of MRI Research in Multiple Sclerosis: A Global Perspective With a Focus on Japan

ABSTRACT Magnetic resonance imaging (MRI) has fundamentally transformed the diagnosis and management of multiple sclerosis (MS) by enabling direct and serial visualization of clinically silent pathology. This review provides a historical overview of MRI research in MS across five distinct phases, highlighting representative findings, with particular emphasis on contributions from Japan within a global context. The pioneering phase established MRI acquisition techniques and characterized typical lesion distribution and early clinico‐radiological relationships. The subsequent brain lesion–focused phase examined T2 lesion and T1 hypointense lesion load, revealing the limited ability of focal lesion measures alone to explain disability and enabling in vivo assessment of cortical lesions using advanced sequences. The early brain atrophy–focused phase introduced automated volumetric analyses, demonstrating that global brain atrophy can be detected over short intervals, may progress despite apparent clinical quiescence, and is closely associated with disability and cognitive impairment. The late brain atrophy–focused phase shifted attention to regional vulnerability, identifying cortical and deep gray matter atrophy as prognostically informative and linking choroid plexus enlargement to future neurodegeneration. Finally, the phase of advanced imaging techniques has expanded assessment of microstructural and myelin integrity in lesions and normal‐appearing tissue and enabled MRI‐based visualization of smoldering disease activity through slowly expanding lesions or paramagnetic rim lesions. Together with concepts such as progression independent of relapse activity, these advances reflect a paradigm shift beyond relapse‐centric models. As relapse frequency declines with potent therapies, sensitive imaging markers of smoldering disease activity and tissue repair will become increasingly important.