Decoding Diffusivity in Multiple Sclerosis: Analysis of Optic Radiation Lesional and Non-Lesional White Matter

Abstract

ObjectivesDiffusion tensor imaging (DTI) has been suggested as a new promising tool in MS that may provide greater pathological specificity than conventional MRI, helping, therefore, to elucidate disease pathogenesis and monitor therapeutic efficacy. However, the pathological substrates that underpin alterations in brain tissue diffusivity are not yet fully delineated. Tract-specific DTI analysis has previously been proposed in an attempt to alleviate this problem. Here, we extended this approach by segmenting a single tract into areas bound by seemingly similar pathological processes, which may better delineate the potential association between DTI metrics and underlying tissue damage.MethodSeveral compartments were segmented in optic radiation (OR) of 50 relapsing-remitting MS patients including T2 lesions, proximal and distal parts of fibers transected by lesion and fibers with no discernable pathology throughout the entire length of the OR.ResultsAsymmetry analysis between lesional and non-lesional fibers demonstrated a marked increase in Radial Diffusivity (RD), which was topographically limited to focal T2 lesions and potentially relates to the lesional myelin loss. A relative elevation of Axial Diffusivity (AD) in the distal part of the lesional fibers was observed in a distribution consistent with Wallerian degeneration, while diffusivity in the proximal portion of transected axons remained normal. A moderate, but significant elevation of RD in OR non-lesional fibers was strongly associated with the global (but not local) T2 lesion burden and is probably related to microscopic demyelination undetected by conventional MRI.ConclusionThis study highlights the utility of the compartmentalization approach in elucidating the pathological substrates of diffusivity and demonstrates the presence of tissue-specific patterns of altered diffusivity in MS, providing further evidence that DTI is a sensitive marker of tissue damage in both lesions and NAWM. Our results suggest that, at least within the OR, parallel and perpendicular diffusivities are affected by tissue restructuring related to distinct pathological processes.

Cerebral Mitochondrial Microangiopathy Leads to Leukoencephalopathy in Mitochondrial Neurogastrointestinal Encephalopathy

“…29 Similarly, in patients with relapsing-remitting multiple sclerosis, tract-specific DTI analysis of the optic radiations showed selective increases in RD only within the T2 lesions and, therefore, related to local myelin disruption. 30 The absence of demyelination at postmortem examination in one of our patients with MNGIE as well as in the other 2 previously reported cases 14 points to increased intramyelin water content as the most likely explanation for prominent or selective radial diffusivity found in brain white matter structures in our patients. A negative correlation between N-acetylaspartate concentration and mean diffusivity values within the same white matter volume was demonstrated, supporting the hypothesis of a dilution effect as the basis of the metabolite concentration reduction, possibly affecting neuronal cells, because no correlation was observed between any other metabolite concentration expressed in either neural or glial cells and any DTI metrics.…”

Diffusion tensor imaging for multilevel assessment of the visual pathway: possibilities for personalized outcome prediction in autoimmune disorders of the central nervous system

“…In this study, a linear regression model was employed that, apart from lesion volume, also included disease duration, age, gender, and a history of ON. The model explained 38% of the observed increase in RD in non-lesional fibers and demonstrated a significant effect of T2 lesion volume outside of the OR and, to a lesser extent, disease duration and history of ON on RD [91]. The same investigators reported significant associations between mfVEP latency delay and increased ORspecific T2 lesion volume.…”

“…One study reported regional RD elevation in the OR parts that were affected by OR-specific white matter lesions corroborating the role of RD as a potential marker for demyelination [91]. A significant elevation of RD in OR non-lesional fibers that correlated with increased global but not focal T2 lesion volume was found, possibly indicating OR fiber damage to be related to the overall burden of brain inflammatory activity [91]. In this study, a linear regression model was employed that, apart from lesion volume, also included disease duration, age, gender, and a history of ON.…”

“…These results were consistently interpreted as a consequence of anterograde and retrograde axonal degeneration due to inflammatory lesional impact within the OR [115,118]. One study reported regional RD elevation in the OR parts that were affected by OR-specific white matter lesions corroborating the role of RD as a potential marker for demyelination [91]. A significant elevation of RD in OR non-lesional fibers that correlated with increased global but not focal T2 lesion volume was found, possibly indicating OR fiber damage to be related to the overall burden of brain inflammatory activity [91].…”

Metabolites predict lesion formation and severity in relapsing-remitting multiple sclerosis

“…28 The Glu increase during the pre-lesional period was strongly correlated with the AD increase, which is generally deemed to relate to axonal injury. 4,5,[29][30][31] The early pathological changes discussed above may therefore be indicative of the extent of eventual axonal damage within newly developing WM lesions in MS. Moreover, a stronger increase of Glu in pre-lesional WM was also associated with higher subsequent lesion volumes.…”