January-February 2018

Imaging Gray Matter Damage in Multiple Sclerosis

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Massimo Filippi

Over the past 3 decades, many pathologic and imaging studies1–4 have supported the notion that gray matter (GM) involvement is a critical feature in the progression of MS. Importantly, GM damage has been shown to be clinically relevant because it helps to explain some of the clinical manifestations of MS, including cognitive impairment, depression, and fatigue,5 and is also a predictor of the long-term evolution of the disease.6

Different pathologic features have been seen in the GM of patients with MS. Focal lesions have been shown to involve the cortex and deep GM nuclei, as well as the cerebellar cortex and GM of the spinal cord. Cortical lesions (CLs) have been classified according to their location in the cortex with respect to the white matter (WM) interface and pial surface.7 Extensive subpial demyelination has been proposed as the distinctive hallmark of MS.8 GM pathology also includes neuronal injury, synaptic and dendritic abnormalities, and Wallerian and transsynaptic degeneration.9,10

Consistent with pathologic observations, many MRI studies have shown a marked involvement of the GM in MS, with focal lesions, “diffuse” tissue abnormalities, and irreversible tissue loss (ie, atrophy). Despite the significant efforts made to improve characterization of the type and extent of GM damage in patients with MS, most GM lesions remain undetected by current MR techniques, and there is an urgent need to develop new MR sequences and postprocessing procedures capable of accurately quantifying GM involvement, as highlighted by the papers selected for this Digest.

A postmortem MRI and histopathology study of 27 formalin-fixed coronal hemispheric brain sections from 15 patients with MS11 showed that, at 7T, T2-weighted and T2*-weighted sequences have a similar sensitivity in detecting CLs, allowing the retrospective identification of more than 80% of CLs. However, without histopathologic information, 84% of CLs still … more »


Juxtacortical Lesions and Cortical Thinning in Multiple Sclerosis

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Deborah Pareto

We are very interested in investigating the relationship between MRI-derived biomarkers and clinical outcomes in MS, particularly early in the disease evolution, when an accurate prediction of long-term prognosis is crucial to better plan therapeutic interventions. Our final goal is to establish a more complete … more »


Cortical Perfusion Alteration in Normal-Appearing Gray Matter Is Most Sensitive to Disease Progression in Relapsing-Remitting Multiple Sclerosis


Parsa Hojjat

Gray matter involvement in MS has been demonstrated in numerous recent studies. However, because of the limited resolution of existing structural imaging techniques, widespread quantification of gray matter damage and the corresponding impact on cognition has been limited. Perfusion imaging has been shown to enable the … more »


Modeling the Relationship among Gray Matter Atrophy, Abnormalities in Connecting White Matter, and Cognitive Performance in Early Multiple Sclerosis

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Amy Kuceyeski

MS is a complicated disease that has a heterogeneous presentation and progression. We believe that quantitative methods, including machine learning, may allow researchers to shed light on the relationship among white matter lesions, gray matter atrophy, and cognitive/physical impairments over the course of the disease. … more »