Browsing by Subject "Creatine"

Now showing 1 - 4 of 4
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    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.
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    Estimating the synaptic density deficit in Alzheimer’s disease using multi-contrast CEST imaging
    (Public Library of Science, 2024-03-14) Shahid, Syed Salman; Dzemidzic, Mario; Butch, Elizabeth R.; Jarvis, Erin E.; Snyder, Scott E.; Wu, Yu-Chien; Radiology and Imaging Sciences, School of Medicine
    In vivo noninvasive imaging of neurometabolites is crucial to improve our understanding of the underlying pathophysiological mechanism in neurodegenerative diseases. Abnormal changes in synaptic organization leading to synaptic degradation and neuronal loss is considered as one of the primary factors driving Alzheimer's disease pathology. Magnetic resonance based molecular imaging techniques such as chemical exchange saturation transfer (CEST) and magnetic resonance spectroscopy (MRS) can provide neurometabolite specific information which may relate to underlying pathological and compensatory mechanisms. In this study, CEST and short echo time single voxel MRS was performed to evaluate the sensitivity of cerebral metabolites to beta-amyloid (Aβ) induced synaptic deficit in the hippocampus of a mouse model of Alzheimer's disease. The CEST based spectra (Z-spectra) were acquired on a 9.4 Tesla small animal MR imaging system with two radiofrequency (RF) saturation amplitudes (1.47 μT and 5.9 μT) to obtain creatine-weighted and glutamate-weighted CEST contrasts, respectively. Multi-pool Lorentzian fitting and quantitative T1 longitudinal relaxation maps were used to obtain metabolic specific apparent exchange-dependent relaxation (AREX) maps. Short echo time (TE = 12 ms) single voxel MRS was acquired to quantify multiple neurometabolites from the right hippocampus region. AREX contrasts and MRS based metabolite concentration levels were examined in the ARTE10 animal model for Alzheimer's disease and their wild type (WT) littermate counterparts (age = 10 months). Using MRS voxel as a region of interest, group-wise analysis showed significant reduction in Glu-AREX and Cr-AREX in ARTE10, compared to WT animals. The MRS based results in the ARTE10 mice showed significant decrease in glutamate (Glu) and glutamate-total creatine (Glu/tCr) ratio, compared to WT animals. The MRS results also showed significant increase in total creatine (tCr), phosphocreatine (PCr) and glutathione (GSH) concentration levels in ARTE10, compared to WT animals. In the same ROI, Glu-AREX and Cr-AREX demonstrated positive associations with Glu/tCr ratio. These results indicate the involvement of neurotransmitter metabolites and energy metabolism in Aβ-mediated synaptic degradation in the hippocampus region. The study also highlights the feasibility of CEST and MRS to identify and track multiple competing and compensatory mechanisms involved in heterogeneous pathophysiology of Alzheimer's disease in vivo.
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    An Investigation of Neurochemical Changes in Chronic Cannabis Users
    (Frontiers Media, 2019-09-19) Newman, Sharlene D.; Cheng, Hu; Martin, Ashley Schnakenberg; Dydak, Ulrike; Dharmadhikari, Shalmali; Hetrick, William; O’Donnell, Brian; Radiology and Imaging Sciences, School of Medicine
    With the legalization of recreational cannabis (CB) the characterization of how it may impact brain chemistry is essential. Magnetic resonance spectroscopy (MRS) was used to examine neurometabolite concentrations in the dorsal anterior cingulate (dACC) in chronic CB users (N = 26; 10 females) and controls (N = 24; 10 females). The concentrations of glutamate (Glu), total creatine (tCr), choline (Cho), total N-acetylaspartate (tNAA), and myo-inositol (mI) were estimated using LCModel. The ANCOVAs failed to show significant differences between controls and CB users. Regression analyses were then performed on the CB group to model each neurometabolite to determine its relationship to monthly CB use, sex, the interaction between CB use and sex. tCr was found to be predicted by both monthly CB use and sex. While the regression model was not significant the relationship between monthly CB use and Glu appears to be modulated by sex with the effect of monthly use (dose) being stronger in males. tNAA failed to show an effect of CB use but did reveal an effect of sex with females showing larger tNAA levels. Although the results presented are preliminary due to the small sample size they do guide future research. The results presented provide direction for further studies as they suggest that dose may significantly influence the observance of CB effects and that those effects may be modulated by sex. Studies with significantly larger sample sizes designed specifically to examine individuals with varying usage as well as sex effects are necessary.
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    Restoring cellular energetics promotes axon regeneration and functional recovery after spinal cord injury
    (Cell Press, 2020-03-03) Han, Qi; Xie, Yuxiang; Ordaz, Josue D.; Huh, Andrew J.; Huang, Ning; Wu, Wei; Liu, Naikui; Chamberlain, Kelly A.; Sheng, Zu-Hang; Xu, Xiao-Ming; Neurological Surgery, School of Medicine
    Axonal regeneration in the central nervous system (CNS) is a highly energy-demanding process. Extrinsic insults and intrinsic restrictions lead to an energy crisis in injured axons, raising the question of whether recovering energy deficits facilitates regeneration. Here, we reveal that enhancing axonal mitochondrial transport by deleting syntaphilin (Snph) recovers injury-induced mitochondrial depolarization. Using three CNS injury mouse models, we demonstrate that Snph-/- mice display enhanced corticospinal tract (CST) regeneration passing through a spinal cord lesion, accelerated regrowth of monoaminergic axons across a transection gap, and increased compensatory sprouting of uninjured CST. Notably, regenerated CST axons form functional synapses and promote motor functional recovery. Administration of the bioenergetic compound creatine boosts CST regenerative capacity in Snph-/- mice. Our study provides mechanistic insights into intrinsic regeneration failure in CNS and suggests that enhancing mitochondrial transport and cellular energetics are promising strategies to promote regeneration and functional restoration after CNS injuries.