Fixel-Based Analysis Effectively Identifies White Matter Tract Degeneration in Huntington's Disease.
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ABSTRACT:
SUBMITTER: Oh SL
PROVIDER: S-EPMC8473742 | biostudies-literature | 2021
REPOSITORIES: biostudies-literature
Publications
Fixel-Based Analysis Effectively Identifies White Matter Tract Degeneration in Huntington's Disease.
Oh Sher Li SL Chen Chiung-Mei CM Wu Yih-Ru YR Valdes Hernandez Maria M Tsai Chih-Chien CC Cheng Jur-Shan JS Chen Yao-Liang YL Wu Yi-Ming YM Lin Yu-Chun YC Wang Jiun-Jie JJ
Frontiers in neuroscience 20210913
Microstructure damage in white matter might be linked to regional and global atrophy in Huntington's Disease (HD). We hypothesize that degeneration of subcortical regions, including the basal ganglia, is associated with damage of white matter tracts linking these affected regions. We aim to use fixel-based analysis to identify microstructural changes in the white matter tracts. To further assess the associated gray matter damage, diffusion tensor-derived indices were measured from regions of int ...[more]
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Project description:Diffusion MRI has provided insight into the widespread structural connectivity changes that characterize epilepsies. Although syndrome-specific white matter abnormalities have been demonstrated, studies to date have predominantly relied on statistical comparisons between patient and control groups. For diffusion MRI techniques to be of clinical value, they should be able to detect white matter microstructural changes in individual patients. In this study, we apply an individualized approach to a technique known as fixel-based analysis, to examine fibre-tract-specific abnormalities in individuals with epilepsy. We explore the potential clinical value of this individualized fixel-based approach in epilepsy patients with differing syndromic diagnoses. Diffusion MRI data from 90 neurologically healthy control participants and 10 patients with epilepsy (temporal lobe epilepsy, progressive myoclonus epilepsy, and Dravet Syndrome, malformations of cortical development) were included in this study. Measures of fibre density and cross-section were extracted for all participants across brain white matter fixels, and mean values were computed within select tracts-of-interest. Scanner harmonized and normalized data were then used to compute Z-scores for individual patients with epilepsy. White matter abnormalities were observed in distinct patterns in individual patients with epilepsy, both at the tract and fixel level. For patients with specific epilepsy syndromes, the detected white matter abnormalities were in line with expected syndrome-specific clinical phenotypes. In patients with lesional epilepsies (e.g. hippocampal sclerosis, periventricular nodular heterotopia, and bottom-of-sulcus dysplasia), white matter abnormalities were spatially concordant with lesion location. This proof-of-principle study demonstrates the clinical potential of translating advanced diffusion MRI methodology to individual-patient-level use in epilepsy. This technique could be useful both in aiding diagnosis of specific epilepsy syndromes, and in localizing structural abnormalities, and is readily amenable to other neurological disorders. We have included code and data for this study so that individualized white matter changes can be explored robustly in larger cohorts in future work.
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Project description:BackgroundEnd-stage renal disease (ESRD) patients on maintenance haemodialysis (HD) often have damage to brain white matter (WM) and cognitive impairment. However, whether this damage is caused by maintenance HD or renal dysfunction is unclear. Herein we investigate the natural progression of WM damage in patients with ESRD and the effects of HD on WM using tract-based spatial statistics (TBSS) and fixel-based analysis (FBA).MethodsEighty-one ESRD patients, including 41 with no dialysis (ND) and 40 on HD, and 46 healthy controls (HCs) were enrolled in this study. The differences in WM among the three groups [ESRD patients with HD (ESRD-HD), ESRD patients without HD (ESRD-ND) and HCs] were analysed using TBSS and FBA. Pairwise comparison was then used to compare the differences in WM between two groups. The relationships between WM and neurocognitive assessments/clinical data were analysed in ESRD patients with and without HD.ResultsThe damage to WM in ESRD-ND and ESRD-HD appeared around the lateral ventricles in TBSS, while FBA reflected that the changes had extended to adjacent WM in the anterior hemisphere, with a larger region in ESRD-HD compared with ESRD-ND and the brainstem was also widely affected in ESRD-HD. The Montreal Cognitive Assessment (MoCA) scores were lower in the ESRD-HD group. RD in the body of the corpus callosum were negatively correlated with MoCA scores in both groups. Fiber density and cross-section (FDC) in the left thalamo-prefrontal projection (T_PREFL) and left and right cingulum (CGL and CGR) were positively correlated with MoCA scores in both groups. Creatinine (Cr) was positively correlated with FDC in some frontal projection fibres in the striatum and thalamus, CG and fronto-pontine tract and was positively correlated with FD mainly in premotor projection fibres in the striatum and thalamus in the ESRD-HD group. Cr was negatively correlated with mean and radial diffusivity in regions of the corona radiata in the ESRD-ND group.ConclusionsFBA is more sensitive in detecting differences between ESRD patients and HCs. When ESRD patients receive maintenance HD, the degree of WM damage may not be aggravated, but the range of damaged WM may be expanded, especially in the anterior hemisphere and brainstem. Some of these changes in the anterior hemisphere may contribute to cognitive decline.
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| S-EPMC8799636 | biostudies-literature
Project description:IntroductionDisruption to white matter pathways is an important contributor to the pathogenesis of Parkinson's disease. Fixel-based analysis has recently emerged as a useful fiber-specific tool for examining white matter structure. In this longitudinal study, we used Fixel-based analysis to investigate white matter changes occurring over time in patients with Parkinson's disease.MethodsFifty patients with idiopathic Parkinson's disease (27 men and 23 women; mean age: 61.8 ± 6.1 years), were enrolled. Diffusion-weighted imaging and clinical examinations were performed at three different time points (baseline, first follow-up [after a mean of 24±2 months], and second follow-up [after a mean of 40 ± 3 months]). Additional 76 healthy control subjects (38 men and 38 women; mean age: 62.3 ± 5.5 years) were examined at baseline. The following fixel-based metrics were obtained: fiber density (FD), fiber bundle cross-section (FC), and a combined measure of both (FDC). Paired comparisons of metrics between three different time points were performed in patients. Linear regression was implemented between longitudinal changes of fixel-based metrics and the corresponding modifications in clinical parameters. A family-wise error corrected p < 0.05 was considered statistically significant.Results and discussionsEarly degeneration in the splenium of corpus callosum was identified as a typical alteration of Parkinson's disease over time. At follow-up, we observed significant FDC reductions compared with baseline in white matter, noticeably in corpus callosum; tapetum; cingulum, posterior thalamic radiation, corona radiata, and sagittal stratum. We also identified significant FC decreases that reflected damage to white matter structures involved in Parkinson's disease -related pathways. Fixel-based metrics were found to relate with a deterioration of 39-item Parkinson's Disease Questionnaire, Unified Parkinson's Disease Rating Scale and activity of daily living. A Parkinson's disease -facilitated aging effect was observed in terms of white matter disruption.ConclusionThis study provides a thorough fixel-based profile of longitudinal white matter alterations occurring in patients with Parkinson's disease and new evidence of FC as an important role in white matter degeneration in this setting.
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Project description:BackgroundWhite matter (WM) tract alterations are early signs of cognitive impairment in Parkinson disease (PD) patients. Fixel-based analysis (FBA) has advantages over traditional diffusion tensor imaging in managing complex and crossing fibers. We used FBA to measure fiber-specific changes in patients with PD mild cognitive impairment (PD-MCI) and PD normal cognition (PD-NC).MethodsSeventy-one patients with PD without dementia were included: 39 PD-MCI and 32 PD-NC. All underwent diffusion-weighted imaging, clinical examinations, and tests to evaluate their cognitive function globally and in five cognitive domains. FBA was used to investigate fiber-tract alterations and compare PD-MCI with PD-NC subjects. Correlations with each cognitive test were analyzed.ResultsPatients with PD-MCI were significantly older (p = 0.044), had a higher male-to-female ratio (P = 0.006) and total Unified Parkinson's Disease Rating Scale score (P = 0.001). All fixel-based metrics were significantly reduced within the body of the corpus callosum and superior corona radiata in PD-MCI patients (family-wise error-corrected P value < 0.05) compared with PD-NC patients. The cingulum, superior longitudinal fasciculi, and thalamocortical circuit exhibited predominantly fiber-bundle cross-section (FC) changes. In regression analysis, reduced FC values in cerebellar circuits were associated with poor motor function in PD-MCI patients and poor picture-naming ability in PD-NC patients.ConclusionsPD-MCI patients have significant WM alterations compared with PD-NC patients. FBA revealed these changes in various bundle tracts, helping us to better understand specific WM changes that are functionally implicated in PD cognitive decline. FBA is potentially useful in detecting early cognitive decline in PD.
| S-EPMC11399627 | biostudies-literature
Project description:Aging is associated with widespread alterations in cerebral white matter (WM). Most prior studies of age differences in WM have used diffusion tensor imaging (DTI), but typical DTI metrics (e.g., fractional anisotropy; FA) can reflect multiple neurobiological features, making interpretation challenging. Here, we used fixel-based analysis (FBA) to investigate age-related WM differences observed using DTI in a sample of 45 older and 25 younger healthy adults. Age-related FA differences were widespread but were strongly associated with differences in multi-fiber complexity (CX), suggesting that they reflected differences in crossing fibers in addition to structural differences in individual fiber segments. FBA also revealed a frontolimbic locus of age-related effects and provided insights into distinct microstructural changes underlying them. Specifically, age differences in fiber density were prominent in fornix, bilateral anterior internal capsule, forceps minor, body of the corpus callosum, and corticospinal tract, while age differences in fiber cross section were largest in cingulum bundle and forceps minor. These results provide novel insights into specific structural differences underlying major WM differences associated with aging.
| S-EPMC8440891 | biostudies-literature
Project description:BackgroundNeuropsychiatric symptoms in Huntington's disease (HD) are often evident prior to clinical diagnosis. Apathy is highly correlated with disease progression, while depression and irritability occur at different stages of the disease, both before and after clinical onset. Little is understood about the neural bases of these neuropsychiatric symptoms and to what extent those neural bases are analogous to neuropsychiatric disorders in the general population.ObjectiveWe used Diffusion Tensor Imaging (DTI) to investigate structural connectivity between brain regions and any putative microstructural changes associated with depression, apathy and irritability in HD.MethodsDTI data were collected from 39 premanifest and 45 early-HD participants in the Track-HD study and analysed using whole-brain Tract-Based Spatial Statistics. We used regression analyses to identify white matter tracts whose structural integrity (as measured by fractional anisotropy, FA) was correlated with HADS-depression, PBA-apathy or PBA-irritability scores in gene-carriers and related to cumulative probability to onset (CPO).ResultsFor those with the highest CPO, we found significant correlations between depression scores and reduced FA in the splenium of the corpus callosum. In contrast, those with lowest CPO demonstrated significant correlations between irritability scores and widespread FA reductions. There was no significant relationship between apathy and FA throughout the whole brain.ConclusionsWe demonstrate that white matter changes associated with both depression and irritability in HD occur at different stages of disease progression concomitant with their clinical presentation.
| S-EPMC4684097 | biostudies-literature