Browsing by Subject "Diffusion magnetic resonance imaging"
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Item Blood-Based Markers of Neuronal Injury in Adult-Onset Myotonic Dystrophy Type 1(Frontiers Media, 2022-01-20) van der Plas, Ellen; Long, Jeffrey D.; Koscik, Timothy R.; Magnotta, Vincent; Monckton, Darren G.; Cumming, Sarah A.; Gottschalk, Amy C.; Hefti, Marco; Gutmann, Laurie; Nopoulos, Peggy C.; Neurology, School of MedicineIntroduction: The present study had four aims. First, neuronal injury markers, including neurofilament light (NF-L), total tau, glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase (UCH-L1), were compared between individuals with and without adult-onset myotonic dystrophy type 1 (DM1). Second, the impact of age and CTG repeat on brain injury markers was evaluated. Third, change in brain injury markers across the study period was quantified. Fourth, associations between brain injury markers and cerebral white matter (WM) fractional anisotropy (FA) were identified. Methods: Yearly assessments, encompassing blood draws and diffusion tensor imaging on a 3T scanner, were conducted on three occasions. Neuronal injury markers were quantified using single molecule array (Simoa). Results: The sample included 53 patients and 70 controls. NF-L was higher in DM1 patients than controls, with individuals in the premanifest phases of DM1 (PreDM1) exhibiting intermediate levels ( χ 2 ( 2 ) = 38.142, P < 0.001). Total tau was lower in DM1 patients than controls (Estimate = -0.62, 95% confidence interval [CI] -0.95: -0.28, P < 0.001), while GFAP was elevated in PreDM1 only (Estimate = 30.37, 95% CI 10.56:50.19, P = 0.003). Plasma concentrations of UCH-L1 did not differ between groups. The age by CTG interaction predicted NF-L: patients with higher estimated progenitor allelege length (ePAL) had higher NF-L at a younger age, relative to patients with lower CTG repeat; however, the latter exhibited faster age-related change (Estimate = -0.0021, 95% CI -0.0042: -0.0001, P = 0.045). None of the markers changed substantially over the study period. Finally, cerebral WM FA was significantly associated with NF-L (Estimate = -42.86, 95% CI -82.70: -3.02, P = 0.035). Interpretation: While NF-L appears sensitive to disease onset and severity, its utility as a marker of progression remains to be determined. The tau assay may have low sensitivity to tau pathology associated with DM1.Item Have clinicians adopted the use of brain MRI for patients with TIA and minor stroke?(American Academy of Neurology, 2017-01-17) Chaturvedi, Seemant; Ofner, Susan; Baye, Fitsum; Myers, Laura J.; Phipps, Mike; Sico, Jason J.; Damush, Teresa; Miec, Edward; Reeves, Mat; Johanning, Jason; Williams, Linda S.; Arling, Greg; Cheng, Eric; Yu, Zhangsheng; Bravata, Dawn; Biostatistics, School of Public HealthBACKGROUND: Use of MRI with diffusion-weighted imaging (DWI) can identify infarcts in 30%-50% of patients with TIA. Previous guidelines have indicated that MRI-DWI is the preferred imaging modality for patients with TIA. We assessed the frequency of MRI utilization and predictors of MRI performance. METHODS: A review of TIA and minor stroke patients evaluated at Veterans Affairs hospitals was conducted with regard to medical history, use of diagnostic imaging within 2 days of presentation, and in-hospital care variables. Chart abstraction was performed in a subset of hospitals to assess clinical variables not available in the administrative data. RESULTS: A total of 7,889 patients with TIA/minor stroke were included. Overall, 6,694 patients (84.9%) had CT or MRI, with 3,396/6,694 (50.7%) having MRI. Variables that were associated with increased odds of CT performance were age >80 years, prior stroke, history of atrial fibrillation, heart failure, coronary artery disease, anxiety, and low hospital complexity, while blood pressure >140/90 mm Hg and high hospital complexity were associated with increased likelihood of MRI. Diplopia (87% had MRI, p = 0.03), neurologic consultation on the day of presentation (73% had MRI, p < 0.0001), and symptom duration of >6 hours (74% had MRI, p = 0.0009) were associated with MRI performance. CONCLUSIONS: Within a national health system, about 40% of patients with TIA/minor stroke had MRI performed within 2 days. Performance of MRI appeared to be influenced by several patient and facility-level variables, suggesting that there has been partial acceptance of the previous guideline that endorsed MRI for patients with TIA.Item Hippocampal-subfield microstructures and their relation to plasma biomarkers in Alzheimer's disease(Oxford University Press, 2022) Shahid, Syed Salman; Wen, Qiuting; Risacher, Shannon L.; Farlow, Martin R.; Unverzagt, Frederick W.; Apostolova, Liana G.; Foroud, Tatiana M.; Zetterberg, Henrik; Blennow, Kaj; Saykin, Andrew J.; Wu, Yu-Chien; Neurology, School of MedicineHippocampal subfields exhibit differential vulnerabilities to Alzheimer's disease-associated pathology including abnormal accumulation of amyloid-β deposition and neurofibrillary tangles. These pathological processes extensively impact on the structural and functional interconnectivities of the subfields and may explain the association between hippocampal dysfunction and cognitive deficits. In this study, we investigated the degree of alterations in the microstructure of hippocampal subfields across the clinical continuum of Alzheimer's disease. We applied a grey matter-specific multi-compartment diffusion model (Cortical-Neurite orientation dispersion and density imaging) to understand the differential effects of Alzheimer's disease pathology on the hippocampal subfield microstructure. A total of 119 participants were included in this cross-sectional study. Participants were stratified into three categories, cognitively normal (n = 47), mild cognitive impairment (n = 52), and Alzheimer's disease (n = 19). Diffusion MRI, plasma biomarkers and neuropsychological test scores were used to determine the association between the microstructural integrity and Alzheimer's disease-associated molecular indicators and cognition. For Alzheimer's disease-related plasma biomarkers, we studied amyloid-β, total tau and neurofilament light; for Alzheimer's disease-related neuropsychological tests, we included the Trail Making Test, Rey Auditory Verbal Learning Test, Digit Span and Montreal Cognitive Assessment. Comparisons between cognitively normal subjects and those with mild cognitive impairment showed significant microstructural alterations in the hippocampal cornu ammonis (CA) 4 and dentate gyrus region, whereas CA 1-3 was the most sensitive region for the later stages in the Alzheimer's disease clinical continuum. Among imaging metrics for microstructures, the volume fraction of isotropic diffusion for interstitial free water demonstrated the largest effect size in between-group comparisons. Regarding the plasma biomarkers, neurofilament light appeared to be the most sensitive biomarker for associations with microstructural imaging findings in CA4-dentate gyrus. CA 1-3 was the subfield which had stronger correlations between cognitive performance and microstructural metrics. Particularly, poor performance on the Rey Auditory Verbal Learning Test and Montreal Cognitive Assessment was associated with decreased intracellular volume fraction. Overall, our findings support the value of tissue-specific microstructural imaging for providing pathologically relevant information manifesting in the plasma biomarkers and neuropsychological outcomes across various stages of Alzheimer's disease.Item Longitudinal diffusion changes in prodromal and early HD: Evidence of white-matter tract deterioration(Wiley, 2017-03) Shaffer, Joseph J.; Ghayoor, Ali; Long, Jeffrey D.; Kim, Regina Eun-Young; Lourens, Spencer; O’Donnell, Lauren J.; Westin, Carl-Fredrik; Rathi, Yogesh; Magnotta, Vincent; Paulsen, Jane S.; Johnson, Hans J.; Biostatistics, School of Public HealthINTRODUCTION: Huntington's disease (HD) is a genetic neurodegenerative disorder that primarily affects striatal neurons. Striatal volume loss is present years before clinical diagnosis; however, white matter degradation may also occur prior to diagnosis. Diffusion-weighted imaging (DWI) can measure microstructural changes associated with degeneration that precede macrostructural changes. DWI derived measures enhance understanding of degeneration in prodromal HD (pre-HD). METHODS: As part of the PREDICT-HD study, N = 191 pre-HD individuals and 70 healthy controls underwent two or more (baseline and 1-5 year follow-up) DWI, with n = 649 total sessions. Images were processed using cutting-edge DWI analysis methods for large multicenter studies. Diffusion tensor imaging (DTI) metrics were computed in selected tracts connecting the primary motor, primary somato-sensory, and premotor areas of the cortex with the subcortical caudate and putamen. Pre-HD participants were divided into three CAG-Age Product (CAP) score groups reflecting clinical diagnosis probability (low, medium, or high probabilities). Baseline and longitudinal group differences were examined using linear mixed models. RESULTS: Cross-sectional and longitudinal differences in DTI measures were present in all three CAP groups compared with controls. The high CAP group was most affected. CONCLUSIONS: This is the largest longitudinal DWI study of pre-HD to date. Findings showed DTI differences, consistent with white matter degeneration, were present up to a decade before predicted HD diagnosis. Our findings indicate a unique role for disrupted connectivity between the premotor area and the putamen, which may be closely tied to the onset of motor symptoms in HD. Hum Brain Mapp 38:1460-1477, 2017. © 2017 Wiley Periodicals, Inc.