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.
Highlights
Multiple sclerosis (MS) is a complex disease of the CNS, characterized by inflammation, demyelination, neuro-axonal loss and gliosis
Asymmetry 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 moderate, but significant elevation of RD in optic radiation (OR) non-lesional fibers was strongly associated with the global T2 lesion burden and is probably related to microscopic demyelination undetected by conventional MRI
Summary
Multiple sclerosis (MS) is a complex disease of the CNS, characterized by inflammation, demyelination, neuro-axonal loss and gliosis. While RD is considerably lower than diffusivity parallel to the fibers (Axial Diffusivity, AD), resulting in high fractional anisotropy (FA), demyelination can significantly “modulate” this relationship [2]. This has prompted speculation that RD may potentially be used as a marker of myelination [3][4][5]. A strong association between AD and axonal pathology, described in earlier animal models [7] has not been corroborated in a recent post-mortem study [8]. Clinical studies of diffusivity are difficult to validate since histological correlations are not feasible and proof of specificity of the diffusion measure in question can only be indirectly deduced
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