Measuring Brain Tissue Integrity during 4 Years Using Diffusion Tensor Imaging

Abstract

Background and Purpose DTI is an MRI measure of brain tissue integrity. Little is known regarding the long term longitudinal evolution of lesional and non-lesional tissue DTI parameters in multiple sclerosis. Materials and Methods Twenty-one patients with multiple sclerosis were imaged for up to 48 months after starting natalizumab therapy. Gadolinium-enhancing lesions at baseline, chronic T2 lesions, and normal-appearing white matter were followed longitudinally. T2 lesions were sub classified as black holes and non-black holes. Within each region of interest, the average values of DTI metrics were derived using Analysis of Functional Neuroimaging Software. The longitudinal trend in DTI metrics was estimated using a mixed-model regression analysis. Results A significant increase was observed for axial diffusivity (p <0.001) in gadolinium enhancing lesions and chronic T2 lesions over 4 years. No significant change in radial diffusivity either in normal appearing white matter or lesional tissue was observed. Evolution of axial diffusivity was different in gadolinium enhancing lesions (p <0.001) and chronic T2 lesions (p=0.02) when compared with normal appearing white matter. Conclusion An increase in axial diffusion in both gadolinium enhancing lesions and T2 lesions may relate to the complex evolution of chronically demyelinated brain tissue. Pathological changes in normal appearing white matter are likely more subtle than in lesional tissue and may explain stability of these measures using DTI.

Diffusion tensor imaging and disability progression in multiple sclerosis: A 4‐year follow‐up study

“…Similar to our observation, serial DTI study using tractography showed significant longitudinal change in DTI metrics in the supratentorial brain and the CC of the MS cohort with different disease phenotypes (Harrison et al, 2011). However, such temporal DTI evolution was not observed in a recent ROI-based MS study including natalizumab-treated patients (Ontaneda et al, 2017). In another study in early RRMS with a 2-year follow-up, the rate of change in diffusivity characteristics assessed by a histogram-based whole-brain analysis did not correlate with disability progression expressed by an EDSS increase, which confirms our results (Rashid et al, 2008).…”

“…Previously, decreased FA and increased RD mostly in the CC of MS were observed in a 2-year longitudinal study (Harrison et al, 2011). In contrast, no changes in diffusivity were observed in the NAWM of MS over 2-4 years (Ontaneda et al, 2017;Rashid et al, 2008). Moreover, few studies with a short (1-2 years) follow-up have applied a regional and whole-brain DTI analysis to longitudinal measurements of diffusivity aiming to evaluate the prognostic value of DTI in the assessment of disability progression in MS (Rashid et al, 2008;Samann et al, 2012;Schmierer et al, 2004).…”

Evidence for Progressive Microstructural Damage in Early Multiple Sclerosis by Multi-Shell Diffusion Magnetic Resonance Imaging

“…Recent DTI findings reported significant axial diffusivity changes, which may be compatible with severe demyelination and axonal loss in WM lesions, but not in NAWM, of patients with MS over a longer observation period (4 years) as compared to the follow-up period in our study [11]. However, DTI radial and axial diffusivity are influenced by the underlying fiber architecture and specifically by the amount of crossing fibers present in the voxel [13,34], whereas the CHARMED model is specifically designed to explicitly model multiple fibers populations in a voxel.…”

“…A few studies have consistently reported deterioration of WM microstructure in lesions over a 1-2 year follow-up period [8,9]. However, mixed results have been obtained with DTI in NAWM [10,11]. This is most likely due to the fact that DTI-derived indices are sensitive to tissue alterations but lack specificity (Beaulieu, 2002), and DTI parameters strongly depends on the local fibre geometry, posing challenges for the interpretation of the observed changes [12,13].…”

The Role of Advanced Magnetic Resonance Imaging Techniques in Multiple Sclerosis Clinical Trials

“…Active lesions with increased RD in 1 study suggested more severe demyelination and predicted the development of T1 hypointensities [49]. Another study found increased AD in active lesions, and the authors speculated glial recruitment may have been responsible [50]. Interestingly, the T2 rim in the periphery of a lesion has significantly higher RD compared with AD, suggesting relative axonal preservation [48].…”