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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 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 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].Item Effects of acute alcohol exposure and chronic alcohol use on neurite orientation dispersion and density imaging (NODDI) parameters(Springer, 2023) Yoder, Karmen K.; Chumin, Evgeny J.; Mustafi, Sourajit M.; Kolleck, Kelly A.; Halcomb, Meredith E.; Hile, Karen L.; Plawecki, Martin H.; O’Connor, Sean J.; Dzemidzic, Mario; Wu, Yu‑Chien; Radiology and Imaging Sciences, School of MedicineRationale: Little is known about how acute and chronic alcohol exposure may alter the in vivo membrane properties of neurons. Objectives: We employed neurite orientation dispersion and density imaging (NODDI) to examine acute and chronic effects of alcohol exposure on neurite density. Methods: Twenty-one healthy social drinkers (CON) and thirteen nontreatment-seeking individuals with alcohol use disorder (AUD) underwent a baseline multi-shell diffusion magnetic resonance imaging (dMRI) scan. A subset (10 CON, 5 AUD) received dMRI during intravenous infusions of saline and alcohol during dMRI. NODDI parametric images included orientation dispersion (OD), isotropic volume fraction (ISOVF), and corrected intracellular volume fraction (cICVF). Diffusion tensor imaging metrics of fractional anisotropy and mean, axial, and radial diffusivity (FA, MD, AD, RD) were also computed. Average parameter values were extracted from white matter (WM) tracts defined by the Johns Hopkins University atlas. Results: There were group differences in FA, RD, MD, OD, and cICVF, primarily in the corpus callosum. Both saline and alcohol had effects on AD and cICVF in WM tracts proximal to the striatum, cingulate, and thalamus. This is the first work to indicate that acute fluid infusions may alter WM properties, which are conventionally believed to be insensitive to acute pharmacological challenges. It also suggests that the NODDI approach may be sensitive to transient changes in WM. The next steps should include determining if the effect on neurite density differs with solute or osmolality, or both, and translational studies to assess how alcohol and osmolality affect the efficiency of neurotransmission.Item Effects of chemotherapy on aging white matter microstructure: a longitudinal diffusion tensor imaging study(Elsevier, 2020-03) Chen, Bihong T.; Ye, Ningrong; Wong, Chi Wah; Patel, Sunita K.; Jin, Taihao; Sun, Can-Lan; Rockne, Russell C.; Kim, Heeyoung; Root, James C.; Saykin, Andrew J.; Ahles, Tim A.; Holodny, Andrei I.; Prakash, Neal; Mortimer, Joanne; Sedrak, Mina S.; Waisman, James; Yuan, Yuan; Li, Daneng; Vazquez, Jessica; Katheria, Vani; Dale, William; Medicine, School of MedicineObjective: We aimed to use diffusion tensor imaging (DTI) to detect alterations in white matter microstructure in older patients with breast cancer receiving chemotherapy. Methods: We recruited women age ≥60 years with stage I-III breast cancer (chemotherapy [CT] group; n = 19) to undergo two study assessments: at baseline and within one month after chemotherapy. Each assessment consisted of a brain magnetic resonance imaging scan with DTI and neuropsychological (NP) testing using the National Institutes of Health (NIH) Toolbox Cognition Battery. An age- and sex-matched group of healthy controls (HC, n = 14) underwent the same assessments at matched intervals. Four DTI parameters (fractional anisotropy [FA], mean diffusivity [MD], axial diffusivity [AD], and radial diffusivity [RD]) were calculated and correlated with NP testing scores. Results: For CT group but not HCs, we detected statistically significant increases in MD and RD in the genu of the corpus callosum from time point 1 to time point 2 at p < 0.01, effect size:0.3655 and 0.3173, and 95% confidence interval: from 0.1490 to 0.5821, and from 0.1554 to 0.4792, for MD and RD respectively. AD values increased for the CT group and decreased for the HC group over time, resulting in significant between-group differences (p = 0.0056, effect size:1.0215, 95% confidence interval: from 0.2773 to 1.7657). There were no significant correlations between DTI parameters and NP scores (p > 0.05). Conclusions: We identified alterations in white matter microstructures in older women with breast cancer undergoing chemotherapy. These findings may potentially serve as neuroimaging biomarkers for identifying cognitive impairment in older adults with cancer.Item Effects of White-Matter Tract Length in Sport-Related Concussion: A Tractography Study from the NCAA-DoD CARE Consortium(Mary Ann Liebert, 2022) Mustafi, Sourajit M.; Yang, Ho-Ching; Harezlak, Jaroslaw; Meier, Timothy B.; Brett, Benjamin L.; Giza, Christopher C.; Goldman, Joshua; Guskiewicz, Kevin M.; Mihalik, Jason P.; LaConte, Stephen M.; Duma, Stefan M.; Broglio, Steven P.; McCrea, Michael A.; McAllister, Thomas W.; Wu, Yu-Chien; Radiology and Imaging Sciences, School of MedicineSport-related concussion (SRC) is an important public health issue. White-matter alterations after SRC are widely studied by neuroimaging approaches, such as diffusion magnetic resonance imaging (MRI). Although the exact anatomical location of the alterations may differ, significant white-matter alterations are commonly observed in long fiber tracts, but are never proven. In the present study, we performed streamline tractography to characterize the association between tract length and white-matter microstructural alterations after SRC. Sixty-eight collegiate athletes diagnosed with acute concussion (24–48 h post-injury) and 64 matched contact-sport controls were included in this study. The athletes underwent diffusion tensor imaging (DTI) in 3.0 T MRI scanners across three study sites. DTI metrics were used for tract-based spatial statistics to map white-matter regions-of-interest (ROIs) with significant group differences. Whole-brain white-mater streamline tractography was performed to extract “affected” white-matter streamlines (i.e., streamlines passing through the identified ROIs). In the concussed athletes, streamline counts and DTI metrics of the affected white-matter fiber tracts were summarized and compared with unaffected white-matter tracts across tract length in the same participant. The affected white-matter tracts had a high streamline count at length of 80–100 mm and high length-adjusted affected ratio for streamline length longer than 80 mm. DTI mean diffusivity was higher in the affected streamlines longer than 100 mm with significant associations with the Brief Symptom Inventory score. Our findings suggest that long fibers in the brains of collegiate athletes are more vulnerable to acute SRC with higher mean diffusivity and a higher affected ratio compared with the whole distribution.
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