Browsing by Subject "White matter"
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Item Advanced Modeling of Longitudinal Spectroscopy Data(2014) Kundu, Madan Gopal; Harezlak, Jaroslaw; Randolph, Timothy W.; Sarkar, Jyotirmoy; Steele, Gregory K.; Yiannoutsos, Constantin T.Magnetic resonance (MR) spectroscopy is a neuroimaging technique. It is widely used to quantify the concentration of important metabolites in a brain tissue. Imbalance in concentration of brain metabolites has been found to be associated with development of neurological impairment. There has been increasing trend of using MR spectroscopy as a diagnosis tool for neurological disorders. We established statistical methodology to analyze data obtained from the MR spectroscopy in the context of the HIV associated neurological disorder. First, we have developed novel methodology to study the association of marker of neurological disorder with MR spectrum from brain and how this association evolves with time. The entire problem fits into the framework of scalar-on-function regression model with individual spectrum being the functional predictor. We have extended one of the existing cross-sectional scalar-on-function regression techniques to longitudinal set-up. Advantage of proposed method includes: 1) ability to model flexible time-varying association between response and functional predictor and (2) ability to incorporate prior information. Second part of research attempts to study the influence of the clinical and demographic factors on the progression of brain metabolites over time. In order to understand the influence of these factors in fully non-parametric way, we proposed LongCART algorithm to construct regression tree with longitudinal data. Such a regression tree helps to identify smaller subpopulations (characterized by baseline factors) with differential longitudinal profile and hence helps us to identify influence of baseline factors. Advantage of LongCART algorithm includes: (1) it maintains of type-I error in determining best split, (2) substantially reduces computation time and (2) applicable even observations are taken at subject-specific time-points. Finally, we carried out an in-depth analysis of longitudinal changes in the brain metabolite concentrations in three brain regions, namely, white matter, gray matter and basal ganglia in chronically infected HIV patients enrolled in HIV Neuroimaging Consortium study. We studied the influence of important baseline factors (clinical and demographic) on these longitudinal profiles of brain metabolites using LongCART algorithm in order to identify subgroup of patients at higher risk of neurological impairment.Item Age Effects and Sex Differences in Human Brain White Matter of Young to Middle-Aged Adults: A DTI, NODDI, and q-Space Study(Elsevier, 2016-03) Kodiweera, Chandana; Alexander, Andrew L.; Andrew L., Jaroslaw; McAllister, Thomas W.; Wu, Yu-Chien; Department of Biostatistics, Richard M. Fairbanks School of Public HealthMicrostructural changes in human brain white matter of young to middle-aged adults were studied using advanced diffusion Magnetic Resonance Imaging (dMRI). Multiple shell diffusion-weighted data were acquired using the Hybrid Diffusion Imaging (HYDI). The HYDI method is extremely versatile and data were analyzed using Diffusion Tensor Imaging (DTI), Neurite Orientation Dispersion and Density Imaging (NODDI), and q-space imaging approaches. Twenty-four females and 23 males between 18 and 55years of age were included in this study. The impact of age and sex on diffusion metrics were tested using least squares linear regressions in 48 white matter regions of interest (ROIs) across the whole brain and adjusted for multiple comparisons across ROIs. In this study, white matter projections to either the hippocampus or the cerebral cortices were the brain regions most sensitive to aging. Specifically, in this young to middle-aged cohort, aging effects were associated with more dispersion of white matter fibers while the tissue restriction and intra-axonal volume fraction remained relatively stable. The fiber dispersion index of NODDI exhibited the most pronounced sensitivity to aging. In addition, changes of the DTI indices in this aging cohort were correlated mostly with the fiber dispersion index rather than the intracellular volume fraction of NODDI or the q-space measurements. While men and women did not differ in the aging rate, men tend to have higher intra-axonal volume fraction than women. This study demonstrates that advanced dMRI using a HYDI acquisition and compartmental modeling of NODDI can elucidate microstructural alterations that are sensitive to age and sex. Finally, this study provides insight into the relationships between DTI diffusion metrics and advanced diffusion metrics of NODDI model and q-space imaging.Item Alzheimer's Disease and Small Vessel Disease Differentially Affect White Matter Microstructure(Wiley, 2024) Tranfa, Mario; Lorenzini, Luigi; Collij, Lyduine E.; Vállez García, David; Ingala, Silvia; Pontillo, Giuseppe; Pieperhoff, Leonard; Maranzano, Alessio; Wolz, Robin; Haller, Sven; Blennow, Kaj; Frisoni, Giovanni; Sudre, Carole H.; Chételat, Gael; Ewers, Michael; Payoux, Pierre; Waldman, Adam; Martinez-Lage, Pablo; Schwarz, Adam J.; Ritchie, Craig W.; Wardlaw, Joanna M.; Domingo Gispert, Juan; Brunetti, Arturo; Mutsaerts, Henk J. M. M.; Meije Wink, Alle; Barkhof, Frederik; Radiology and Imaging Sciences, School of MedicineObjective: Alzheimer's disease (AD) and cerebral small vessel disease (cSVD), the two most common causes of dementia, are characterized by white matter (WM) alterations diverging from the physiological changes occurring in healthy aging. Diffusion tensor imaging (DTI) is a valuable tool to quantify WM integrity non-invasively and identify the determinants of such alterations. Here, we investigated main effects and interactions of AD pathology, APOE-ε4, cSVD, and cardiovascular risk on spatial patterns of WM alterations in non-demented older adults. Methods: Within the prospective European Prevention of Alzheimer's Dementia study, we selected 606 participants (64.9 ± 7.2 years, 376 females) with baseline cerebrospinal fluid samples of amyloid β1-42 and p-Tau181 and MRI scans, including DTI scans. Longitudinal scans (mean follow-up time = 1.3 ± 0.5 years) were obtained in a subset (n = 223). WM integrity was assessed by extracting fractional anisotropy and mean diffusivity in relevant tracts. To identify the determinants of WM disruption, we performed a multimodel inference to identify the best linear mixed-effects model for each tract. Results: AD pathology, APOE-ε4, cSVD burden, and cardiovascular risk were all associated with WM integrity within several tracts. While limbic tracts were mainly impacted by AD pathology and APOE-ε4, commissural, associative, and projection tract integrity was more related to cSVD burden and cardiovascular risk. AD pathology and cSVD did not show any significant interaction effect. Interpretation: Our results suggest that AD pathology and cSVD exert independent and spatially different effects on WM microstructure, supporting the role of DTI in disease monitoring and suggesting independent targets for preventive medicine approaches.Item Anterior Cingulate Cortex Metabolites and White Matter Microstructure: A Multimodal Study of Emergent Alcohol Use Disorder(Springer, 2021) Grecco, Gregory G.; Chumin, Evgeny J.; Dzemidzic, Mario; Cheng, Hu; Finn, Peter; Newman, Sharlene; Dydak, Ulrike; Yoder, Karmen K.; Radiology and Imaging Sciences, School of MedicineMultimodal imaging is increasingly used to address neuropathology associated with alcohol use disorder (AUD). Few studies have investigated relationships between metabolite concentrations and white matter (WM) integrity; currently, there are no such data in AUD. In this preliminary study, we used complementary neuroimaging techniques, magnetic resonance spectroscopy (MRS), and diffusion weighted imaging (DWI), to study AUD neurophysiology. We tested for relationships between metabolites in the dorsal anterior cingulate cortex (dACC) and adjacent WM microstructure in young adult AUD and control (CON) subjects. Sixteen AUD and fourteen CON underwent whole-brain DWI and MRS of the dACC. Outcomes were dACC metabolites, and diffusion tensor metrics of dACC-adjacent WM. Multiple linear regression terms included WM region, group, and region × group for prediction of dACC metabolites. dACC myo-inositol was positively correlated with axial diffusivity in the left anterior corona radiata (p < 0.0001) in CON but not AUD (group effect: p < 0.001; region × group: p < 0.001; Bonferroni-corrected). In the bilateral anterior corona radiata and right genu of the corpus callosum, glutamate was negatively related to mean diffusivity in AUD, but not CON subjects (all model terms: p < 0.05, uncorrected). In AUD subjects, dACC glutamate was negatively correlated with AUD symptom severity. This is likely the first integrative study of cortical metabolites and WM integrity in young individuals with AUD. Differential relationships between dACC metabolites and adjacent WM tract integrity in AUD could represent early consequences of hazardous drinking, and/or novel biomarkers of early-stage AUD. Additional studies are required to replicate these findings, and to determine the behavioral relevance of these results.Item The Association Between Persistent White-Matter Abnormalities and Repeat Injury After Sport-Related Concussion(Frontiers Media, 2020-01-21) Brett, Benjamin L.; Wu, Yu-Chien; Mustafi, Sourajit M.; Saykin, Andrew J.; Koch, Kevin M.; Nencka, Andrew S.; Giza, Christopher C.; Goldman, Joshua; Guskiewicz, Kevin M.; Mihalik, Jason P.; Duma, Stefan M.; Broglio, Steven P.; McAllister, Thomas W.; McCrea, Michael A.; Meier, Timothy B.; Radiology and Imaging Sciences, School of MedicineObjective: A recent systematic review determined that the physiological effects of concussion may persist beyond clinical recovery. Preclinical models suggest that ongoing physiological effects are accompanied by increased cerebral vulnerability that is associated with risk for subsequent, more severe injury. This study examined the association between signal alterations on diffusion tensor imaging following clinical recovery of sport-related concussion in athletes with and without a subsequent second concussion. Methods: Average mean diffusivity (MD) was calculated in a region of interest (ROI) in which concussed athletes (n = 82) showed significantly elevated MD acutely after injury (<48 h), at an asymptomatic time point, 7 days post-return to play (RTP), and 6 months relative to controls (n = 69). The relationship between MD in the identified ROI and likelihood of sustaining a subsequent concussion over a 1-year period was examined with a binary logistic regression (re-injured, yes/no). Results: Eleven of 82 concussed athletes (13.4%) sustained a second concussion within 12 months of initial injury. Mean MD at 7 days post-RTP was significantly higher in those athletes who went on to sustain a repeat concussion within 1 year of initial injury than those who did not (p = 0.048; d = 0.75). In this underpowered sample, the relationship between MD at 7 days post-RTP and likelihood of sustaining a secondary injury approached significance [χ2 (1) = 4.17, p = 0.057; B = 0.03, SE = 0.017; OR = 1.03, CI = 0.99, 1.07]. Conclusions: These preliminary findings raise the hypothesis that persistent signal abnormalities in diffusion imaging metrics at RTP following concussion may be predictive of a repeat concussion. This may reflect a window of cerebral vulnerability or increased susceptibility following concussion, though understanding the clinical significance of these findings requires further study.Item Cerebrovascular disease emerges with age and Alzheimer's disease in adults with Down syndrome(Springer Nature, 2024-05-29) Lao, Patrick; Edwards, Natalie; Flores‑Aguilar, Lisi; Alshikho, Mohamad; Rizvi, Batool; Tudorascu, Dana; Rosas, H. Diana; Yassa, Michael; Christian, Bradley T.; Mapstone, Mark; Handen, Benjamin; Zimmerman, Molly E.; Gutierrez, Jose; Wilcock, Donna; Head, Elizabeth; Brickman, Adam M.; Neurology, School of MedicineAdults with Down syndrome have a genetic form of Alzheimer's disease (AD) and evidence of cerebrovascular disease across the AD continuum, despite few systemic vascular risk factors. The onset and progression of AD in Down syndrome is highly age-dependent, but it is unknown at what age cerebrovascular disease emerges and what factors influence its severity. In the Alzheimer's Biomarker Consortium-Down Syndrome study (ABC-DS; n = 242; age = 25-72), we estimated the age inflection point at which MRI-based white matter hyperintensities (WMH), enlarged perivascular spaces (PVS), microbleeds, and infarcts emerge in relation to demographic data, risk factors, amyloid and tau, and AD diagnosis. Enlarged PVS and infarcts appear to develop in the early 30s, while microbleeds, WMH, amyloid, and tau emerge in the mid to late 30s. Age-residualized WMH were higher in women, in individuals with dementia, and with lower body mass index. Participants with hypertension and APOE-ε4 had higher age-residualized PVS and microbleeds, respectively. Lifespan trajectories demonstrate a dramatic cerebrovascular profile in adults with Down syndrome that appears to evolve developmentally in parallel with AD pathophysiology approximately two decades prior to dementia symptoms.Item Childhood adversity is associated with longitudinal white matter changes after adulthood trauma(medRxiv, 2025-03-14) Tianyi, Li; Huibregtse, Megan E.; Ely, Timothy D.; van Rooij, Sanne J. H.; Lebois, Lauren A. M.; Webb, E. Kate; Jovanovic, Tanja; House, Stacey L.; Bruce, Steven E.; Murty, Vishnu P.; Beaudoin, Francesca L.; An, Xinming; Neylan, Thomas C.; Clifford, Gari D.; Linnstaedt, Sarah D.; Bollen, Kenneth A.; Rauch, Scott L.; Haran, John P.; Storrow, Alan B.; Lewandowski, Christopher; Musey, Paul I., Jr.; Hendry, Phyllis L.; Sheikh, Sophia; Jones, Christopher W.; Punches, Brittany E.; Hudak, Lauren A.; Pascual, Jose L.; Seamon, Mark J.; Datner, Elizabeth M.; Pearson, Claire; Peak, David A.; Merchant, Roland C.; Domeier, Robert M.; Rathlev, Niels K.; O'Neil, Brian J.; Sergot, Paulina; Sanchez, Leon D.; Sheridan, John F.; Kessler, Ronald C.; Koenen, Karestan C.; Ressler, Kerry J.; McLean, Samuel A.; Stevens, Jennifer S.; Harnett, Nathaniel G.; Emergency Medicine, School of MedicineBackground: Childhood adversity is associated with susceptibility to posttraumatic stress disorder (PTSD) in adulthood. Both PTSD and adverse experiences in childhood are linked to disrupted white matter microstructure, yet the role of white matter as a potential neural mechanism connecting childhood adversity to PTSD remains unclear. The present study investigated the potential moderating role of previous childhood adversity on longitudinal changes in white matter microstructures and posttraumatic stress symptoms following a recent traumatic event in adulthood. Methods: As part of the AURORA Study, 114 recent trauma survivors completed diffusion weighted imaging at 2-weeks and 6-months after exposure. Participants reported on prior childhood adversity and PTSD symptoms at 2-weeks, 6-months, and 12-months post-trauma. We performed both region-of-interest (ROI) and whole-brain correlational tractography analyses to index associations between white matter microstructure changes and prior adversity. Results: Whole-brain correlational tractography revealed that greater childhood adversity moderated the changes in quantitative anisotropy (QA) over time across threat and visual processing tracts including the cingulum bundle and inferior fronto-occipital fasciculus (IFOF). Further, QA changes within cingulum bundle, IFOF, and inferior longitudinal fasciculus were associated with changes in PTSD symptoms between 2-weeks and 6-months. Conclusions: Our findings suggest temporal variability in threat and visual white matter tracts may be a potential neural pathway through which childhood adversity confers risk to PTSD symptoms after adulthood trauma. Future studies should take the temporal properties of white matter into consideration to better understand the neurobiology of childhood adversity and PTSD.Item Cigarette smoking is associated with amplified age-related volume loss in subcortical brain regions(Elsevier, 2017-08-01) Durazzo, Timothy C.; Meyerhoff, Dieter J.; Yoder, Karmen K.; Murray, Donna E.; Radiology and Imaging Sciences, School of MedicineBACKGROUND: Magnetic resonance imaging studies of cigarette smoking-related effects on human brain structure have primarily employed voxel-based morphometry, and the most consistently reported finding was smaller volumes or lower density in anterior frontal regions and the insula. Much less is known about the effects of smoking on subcortical regions. We compared smokers and non-smokers on regional subcortical volumes, and predicted that smokers demonstrate greater age-related volume loss across subcortical regions than non-smokers. METHODS: Non-smokers (n=43) and smokers (n=40), 22-70 years of age, completed a 4T MRI study. Bilateral total subcortical lobar white matter (WM) and subcortical nuclei volumes were quantitated via FreeSurfer. In smokers, associations between smoking severity measures and subcortical volumes were examined. RESULTS: Smokers demonstrated greater age-related volume loss than non-smokers in the bilateral subcortical lobar WM, thalamus, and cerebellar cortex, as well as in the corpus callosum and subdivisions. In smokers, higher pack-years were associated with smaller volumes of the bilateral amygdala, nucleus accumbens, total corpus callosum and subcortical WM. CONCLUSIONS: Results provide novel evidence that chronic smoking in adults is associated with accelerated age-related volume loss in subcortical WM and GM nuclei. Greater cigarette quantity/exposure was related to smaller volumes in regions that also showed greater age-related volume loss in smokers. Findings suggest smoking adversely affected the structural integrity of subcortical brain regions with increasing age and exposure. The greater age-related volume loss in smokers may have implications for cortical-subcortical structural and/or functional connectivity, and response to available smoking cessation interventions.Item Cross-β helical filaments of Tau and TMEM106B in gray and white matter of multiple system tauopathy with presenile dementia(Springer, 2023) Hoq, Md. Rejaul; Bharath, Sakshibeedu R.; Hallinan, Grace I.; Fernandez, Anllely; Vago, Frank S.; Ozcan, Kadir A.; Li, Daoyi; Garringer, Holly J.; Vidal, Ruben; Ghetti, Bernardino; Jiang, Wen; Pathology and Laboratory Medicine, School of MedicineItem Data of NODDI diffusion metrics in the brain and computer simulation of hybrid diffusion imaging (HYDI) acquisition scheme(Elsevier, 2016-06) Kodiweera, Chandana; Wu, Yu-Chien; Department of Radiology and Imaging Sciences, IU School of MedicineThis article provides NODDI diffusion metrics in the brains of 52 healthy participants and computer simulation data to support compatibility of hybrid diffusion imaging (HYDI), "Hybrid diffusion imaging"[1] acquisition scheme in fitting neurite orientation dispersion and density imaging (NODDI) model, "NODDI: practical in vivo neurite orientation dispersion and density imaging of the human brain"[2]. HYDI is an extremely versatile diffusion magnetic resonance imaging (dMRI) technique that enables various analyzes methods using a single diffusion dataset. One of the diffusion data analysis methods is the NODDI computation, which models the brain tissue with three compartments: fast isotropic diffusion (e.g., cerebrospinal fluid), anisotropic hindered diffusion (e.g., extracellular space), and anisotropic restricted diffusion (e.g., intracellular space). The NODDI model produces microstructural metrics in the developing brain, aging brain or human brain with neurologic disorders. The first dataset provided here are the means and standard deviations of NODDI metrics in 48 white matter region-of-interest (ROI) averaging across 52 healthy participants. The second dataset provided here is the computer simulation with initial conditions guided by the first dataset as inputs and gold standard for model fitting. The computer simulation data provide a direct comparison of NODDI indices computed from the HYDI acquisition [1] to the NODDI indices computed from the originally proposed acquisition [2]. These data are related to the accompanying research article "Age Effects and Sex Differences in Human Brain White Matter of Young to Middle-Aged Adults: A DTI, NODDI, and q-Space Study" [3].