The Role of T1-Weighted Derived Measures of Neurodegeneration for Assessing Disability Progression in Multiple Sclerosis

Abstract

IntroductionMultiple sclerosis (MS) is characterised by the accumulation of permanent neurological disability secondary to irreversible tissue loss (neurodegeneration) in the brain and spinal cord. MRI measures derived from T1-weighted image analysis (i.e., black holes and atrophy) are correlated with pathological measures of irreversible tissue loss. Quantifying the degree of neurodegeneration in vivo using MRI may offer a surrogate marker with which to predict disability progression and the effect of treatment. This review evaluates the literature examining the association between MRI measures of neurodegeneration derived from T1-weighted images and disability in MS patients.MethodsA systematic PubMed search was conducted in January 2017 to identify MRI studies in MS patients investigating the relationship between “black holes” and/or atrophy in the brain and spinal cord, and disability. Results were limited to human studies published in English in the previous 10 years.ResultsA large number of studies have evaluated the association between the previous MRI measures and disability. These vary considerably in terms of study design, duration of follow-up, size, and phenotype of the patient population. Most, although not all, have shown that there is a significant correlation between disability and black holes in the brain, as well as atrophy of the whole brain and grey matter. The results for brain white matter atrophy are less consistently positive, whereas studies evaluating spinal cord atrophy consistently showed a significant correlation with disability. Newer ways of measuring atrophy, thanks to the development of segmentation and voxel-wise methods, have allowed us to assess the involvement of strategic regions of the CNS (e.g., thalamus) and to map the regional distribution of damage. This has resulted in better correlations between MRI measures and disability and in the identification of the critical role played by some CNS structures for MS clinical manifestations.ConclusionThe evaluation of MRI measures of atrophy as predictive markers of disability in MS is a highly active area of research. At present, measurement of atrophy remains within the realm of clinical studies, but its utility in clinical practice has been recognized and barriers to its implementation are starting to be addressed.

Brain atrophy in multiple sclerosis: mechanisms, clinical relevance and treatment options

“…Clinical symptoms and signs do not usually correlate with changes seen on conventional MRI measures (the "clinical-MRI paradox") [81,82]. Whole brain atrophy, on the other hand, has a significant imaging association with physical disability as measured by Expanded Disability Status Scale (EDSS) score [83][84][85][86][87][88]. In a longitudinal study, whole brain (WB) and cortical atrophy as well as other MRI related metrics such as the enlargement of ventricular CSF spaces have been associated with disability progression over a 10 year follow up [89].…”

Spatial distribution of white matter degenerative lesions and cognitive dysfunction in relapsing-remitting multiple sclerosis patients

“…In previous studies, the incidence of black holes explained disharmonious cognitive and emotional processing in MS [27]. The location of degenerative white matter lesions can be associated with subsequent development of atrophy in distant brain regions [28][29][30][31].…”

Gray matter network reorganization in multiple sclerosis from 7‐Tesla and 3‐Tesla MRI data

“…Increased SNR and CNR result in data with higher spatial resolution and improved visualization of fine contrast differences, 14 leading to reduced partial volume effects and clearer tissue boundary differentiation 11 . The latter attribute is key for the precise estimation of cortical thickness (CT), a common and reliable measure of GM tissue loss in studies tracking neurodegeneration in MS 15‐18 . Regional variations in tissue integrity are further captured by GM/white matter (WM) contrast (GWc), a measure of tissue‐contrast intensity differences between the boundaries of GM and WM.…”