Diffusion Tensor MRI Reveals Chronic Alterations in White Matter Despite the Absence of a Visible Ischemic Lesion on Conventional MRI

Abstract

Background and Purpose-The impact of stroke on white matter is poorly described in preclinical investigations mainly based on rodents with a low white (WM)/gray matter ratio. Using diffusion tensor imaging, we evaluated WM alterations and correlated them with sensorimotor deficits after stroke in the marmoset, a nonhuman primate that displays a WM/gray matter ratio close to that of humans. Methods-Marmosets underwent a transient brain ischemia (3-hour). Eight serial MRI examinations were made during ischemia and up to 45 days after reperfusion. The sensorimotor deficits were evaluated weekly over 45 days. To assess WM alterations, the SD of the angle of the first eigenvector projection was calculated in the cortex and in the internal and external capsules. The fiber-tracking approach was used to measure the number and the length of bundles. Results-Changes in the apparent diffusion coefficient and the fractional anisotropy values were similar during the temporal evolution of the lesion in the marmoset model of ischemia to that reported in patients with stroke. Despite an absence of visible lesions on T2-MRI and diffusion tensor imaging at the chronic stage, diffusion tensor MRI evidenced alterations in WM by the increase in the standard deviation of the angle of the first eigenvector projection in the cortex, internal and external capsules, and the decrease in the number of bundles of fibers tracked. The disruption of WM was strongly correlated with the chronic sensorimotor deficits. Conclusions-Despite an absence of a visible ischemic lesion at the chronic stage, diffusion tensor MRI revealed disorganization of WM, which probably underlies the persistence of functional deficits.

Local Diffusion Homogeneity (LDH): An Inter-Voxel Diffusion MRI Metric for Assessing Inter-Subject White Matter Variability

“…In addition, the inter-voxel metric measuring the standard deviation of the angle of the first eigenvector projection within a neighborhood revealed WM abnormalities in the chronic phases of ischemia. In this study, the FA/MD metrics failed to uncover any WM differences [20]. Together, these reports and the current study suggest that the inter-voxel indices (e.g., LDH) may be applied when no significant results are found by assessing FA/MD.…”

“…In addition, a recent nonhuman primate study applied another inter-voxel index that measures the standard deviation of the angle of the first eigenvector projection within a neighborhood. This study demonstrated WM abnormalities during the chronic stage of induced cerebral ischemia [20]. Intriguingly, the studies that have applied both inter- and intra-voxel indices (e.g., FA and MD) have shown discrepant results between the indices.…”

Reduced local diffusion homogeneity as a biomarker for temporal lobe epilepsy

“…Only a few intervoxel measures have been developed, [14,15] and all are based on the diffusion tensor model. Hence, these studies are all limited by the problematic assumption that a simple Gaussian profile can be applied to water diffusion in complex anatomical structures.…”

Quantitative molecular assessment of chimerism across tissues in marmosets and tamarins

“…Recently, marmoset models have been developed for dengue virus infection [7], smallpox [8], and Karposi's sarcoma [9]. In neuroscience research, marmoset models have been developed recently for the study of temporal lobe epilepsy [10] as well as stroke and ischemia [11]. These join the more established models of Parkinson's disease [12], Huntington's disease [13], Alzheimer's disease [14] and multiple sclerosis [15].…”