Widespread Disruptions of White Matter in Familial Multiple Sclerosis: DTI and NODDI Study

Abstract

Diffusion tensor imaging (DTI) is a noninvasive, quantitative MRI technique that measures white matter (WM) integrity. Many brain dimensions are heritable, including white matter integrity measured with DTI. Family studies are valuable to provide insights into the interactive effects of non-environmental factors on multiple sclerosis (MS). To examine the contribution of familial factors to the diffusion signals across WM microstructure, we performed DTI and calculated neurite orientation dispersion plus density imaging (NODDI) diffusion parameters in two patient groups comprising familial and sporadic forms of multiple sclerosis and their unaffected relatives. We divided 111 subjects (49 men and 62 women: age range 19–60) into three groups conforming to their MS history. The familial MS group included 30 participants (patients; n = 16, healthy relatives; n = 14). The sporadic group included 41 participants (patients; n = 10, healthy relatives; n = 31). Forty age-matched subjects with no history of MS in their families were defined as the control group. To study white matter integrity, two methods were employed: one for calculating the mean of DTI, FA, and MD parameters on 18 tracts using Tracts Constrained by Underlying Anatomy (TRACULA) and the other for whole brain voxel-based analysis using tract-based spatial statistics (TBSS) on NDI and ODI parameters derived from NODDI and DTI parameters. Voxel-based analysis showed considerable changes in FA, MD, NDI, and ODI in the familial group when compared with the control group, reflecting widespread impairment of white matter in this group. The analysis of 18 tracts with TRACULA revealed increased MD and FA reduction in more tracts (left and right ILF, UNC, and SLFT, forceps major and minor) in familial MS patients vs. the control group. There were no significant differences between the patient groups. We found no consequential changes in healthy relatives of both patient groups in voxel-based and tract analyses. Considering the multifactorial etiology of MS, familial studies are of great importance to clarify the effects of certain predisposing factors on demyelinating brain pathology.

Neurite Orientation Dispersion and Density Imaging in Multiple Sclerosis: A Systematic Review

“…Thalamic radiation changes were also observed, as NDI of left anterior and posterior thalamic radiation was reduced 29,34 . Two of these studies also reported specific pathways, including the corpus callosum, with increased ODI 27,29 . Hagiwara et al and Kato et al focused on the ISOVF of several NAWM tracts 31,33 .…”

“…Participants were age‐matched in four studies, 24,28,37,39 sex‐matched in one study 36 . Meanwhile, 15 studies controlled for both age and gender 16,18,23,26,27,29–31,33–35,40–43 …”

“…A total of five studies included in the present systematic review assessed microstructural changes in specific NAWM regions 27,29,31,33,34 (Table 2). The corpus callosum, corticospinal tract, and superior longitudinal fasciculus were the most consistent brain regions exhibiting reduced NDI 27,29,34 . Thalamic radiation changes were also observed, as NDI of left anterior and posterior thalamic radiation was reduced 29,34 .…”

Effects of 3-month CPAP therapy on brain structure in obstructive sleep apnea: A diffusion tensor imaging study

“…DTI can analyze the dispersion movement of water molecules in tissues in three-dimensional space and non-invasively observe the changes in WM structure and fiber bundles in the brain ( 15 ), which is used to study the pathophysiological changes in the early brain ( 16 ). Based on the advantages of voxel and trajectory analysis, tract-based spatial statistics (TBSS) has been widely applied in studies of various neurological diseases, such as Parkinson's disease ( 17 ), chronic spinal cord injury in children ( 18 ), multiple sclerosis ( 19 ), schizophrenia ( 20 ), and preoperative evaluation of tumor ( 21 ). Macey et al ( 22 ) showed that OSA is more likely to damage WM fibers (bilateral cingulate, right terminal striatum) in women, and this differential damage helps explain the sex differences in symptoms, particularly anxiety and depression.…”

Disrupted topological properties of the structural brain network in patients with cerebellar infarction on different sides are associated with cognitive impairment

“…Diffusion imaging technology (DTI) can noninvasively display brain network connectivity and functional status without exogenous stimulation or tasks. It has been widely used in the study of neuropsychiatric diseases, such as Alzheimer's disease, multiple sclerosis, and schizophrenia ( 6 – 8 ). As mentioned earlier, the cerebellum may be involved in the coordination of cognitive functions through cerebellar fiber circuits.…”