Radiology - Research Publications
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ItemSeven-tesla quantitative magnetic resonance spectroscopy of glutamate, γ-aminobutyric acid, and glutathione in the posterior cingulate cortex/precuneus in patients with epilepsy(WILEY, 2020-12)OBJECTIVE: The posterior cingulate cortex (PCC)/precuneus is a key hub of the default mode network, whose function is known to be altered in epilepsy. Glutamate and γ-aminobutyric acid (GABA) are the main excitatory and inhibitory neurotransmitters in the central nervous system, respectively. Glutathione (GSH) is the most important free radical scavenging compound in the brain. Quantification of these molecules by magnetic resonance spectroscopy (MRS) up to 4 T is limited by overlapping resonances from other molecules. In this study, we used ultra-high-field (7 T) MRS to quantify their concentrations in patients with different epilepsy syndromes. METHODS: Nineteen patients with temporal lobe epilepsy (TLE) and 16 with idiopathic generalized epilepsy (IGE) underwent magnetic resonance imaging scans using a 7-T research scanner. Single-voxel (8 cm3 ) MRS, located in the PCC/precuneus, was acquired via stimulated echo acquisition mode. Their results were compared to 10 healthy volunteers. RESULTS: Mean concentrations of glutamate, GABA, and the glutamate/GABA ratio did not differ between the IGE, TLE, and healthy volunteer groups. The mean ± SD concentration of GSH was 1.9 ± 0.3 mmol·L-1 in healthy controls, 2.0 ± 0.2 mmol·L-1 in patients with TLE, and 2.2 ± 0.4 mmol·L-1 in patients with IGE. One-way analysis of variance with post hoc Tukey-Kramer test revealed a significant difference in the concentration of GSH between patients with IGE and controls (P = .03). Short-term seizure freedom in patients with epilepsy was predicted by an elevated concentration of glutamate in the PCC/precuneus (P = .01). In patients with TLE, the concentration of GABA declined with age (P = .03). SIGNIFICANCE: Patients with IGE have higher concentrations of GSH in the PCC/precuneus than healthy controls. There is no difference in the concentrations of glutamate and GABA, or their ratio, in the PCC/precuneus between patients with IGE, patients with TLE, and healthy controls. Measuring the concentration of glutamate in the PCC/precuneus may assist with predicting drug response.
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ItemNo Preview AvailableAssociation Between Cognitive Function and Clustered Cardiovascular Risk of Metabolic Syndrome in Older Adults at Risk of Cognitive Decline(SPRINGER FRANCE, 2020-03)OBJECTIVES: Metabolic syndrome (MetS) represents a cluster of obesity and insulin resistance-related comorbidities. Abdominal obesity, hypertension, elevated triglyceride and glucose levels are components of MetS and may have a negative effect on cognitive function, but few cognitive studies have examined the combined risk severity. We sought to determine which specific cognitive abilities were associated with MetS in older adults at risk of cognitive decline. DESIGN: Cross-sectional study. PARTICIPANTS: 108 AIBL Active participants with memory complaints and at least one cardiovascular risk factor. MEASUREMENTS: Cardiovascular parameters and blood tests were obtained to assess metabolic syndrome criteria. The factors of MetS were standardized to obtain continuous z-scores. A battery of neuropsychological tests was used to evaluate cognitive function. RESULTS: Higher MetS z-scores were associated with poorer global cognition using ADAS-cog (adjusted standardized beta=0.26, SE 0.11, p<0.05) and higher Trail Making B scores (adjusted beta=0.23, SE 0.11, p<0.05). Higher MetS risk was related to lower cognitive performance. CONCLUSION: Combined risk due to multiple risk factors in MetS was related to lower global cognitive performance and executive function. A higher MetS risk burden may point to opportunities for cognitive testing in older adults as individuals may experience cognitive changes.
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ItemResting-state functional connectivity and quantitation of glutamate and GABA of the PCC/precuneus by magnetic resonance spectroscopy at 7T in healthy individuals(PUBLIC LIBRARY SCIENCE, 2020-12-29)The default mode network (DMN) is the main large-scale network of the resting brain and the PCC/precuneus is a major hub of this network. Glutamate and GABA (γ-amino butyric acid) are the main excitatory and inhibitory neurotransmitters in the CNS, respectively. We studied glutamate and GABA concentrations in the PCC/precuneus via magnetic resonance spectroscopy (MRS) at 7T in relation to age and correlated them with functional connectivity between this region and other DMN nodes in ten healthy right-handed volunteers ranging in age between 23-68 years. Mean functional connectivity of the PCC/precuneus to the other DMN nodes and the glutamate/GABA ratio significantly correlated with age (r = 0.802, p = 0.005 and r = 0.793, p = 0.006, respectively) but not with each other. Glutamate and GABA alone did not significantly correlate with age nor with functional connectivity within the DMN. The glutamate/GABA ratio and functional connectivity of the PCC/precuneus are, therefore, independent age-related biomarkers of the DMN and may be combined in a multimodal pipeline to study DMN alterations in various disease states.
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ItemNetwork-based atrophy modeling in the common epilepsies: A worldwide ENIGMA study(AMER ASSOC ADVANCEMENT SCIENCE, 2020-11)Epilepsy is increasingly conceptualized as a network disorder. In this cross-sectional mega-analysis, we integrated neuroimaging and connectome analysis to identify network associations with atrophy patterns in 1021 adults with epilepsy compared to 1564 healthy controls from 19 international sites. In temporal lobe epilepsy, areas of atrophy colocalized with highly interconnected cortical hub regions, whereas idiopathic generalized epilepsy showed preferential subcortical hub involvement. These morphological abnormalities were anchored to the connectivity profiles of distinct disease epicenters, pointing to temporo-limbic cortices in temporal lobe epilepsy and fronto-central cortices in idiopathic generalized epilepsy. Negative effects of age on atrophy further revealed a strong influence of connectome architecture in temporal lobe, but not idiopathic generalized, epilepsy. Our findings were reproduced across individual sites and single patients and were robust across different analytical methods. Through worldwide collaboration in ENIGMA-Epilepsy, we provided deeper insights into the macroscale features that shape the pathophysiology of common epilepsies.
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ItemReproducibility of Glutamate, Glutathione, and GABA Measurementsin vivoby Single-Voxel STEAM Magnetic Resonance Spectroscopy at 7-Tesla in Healthy Individuals(FRONTIERS MEDIA SA, 2020-09-15)BACKGROUND AND PURPOSE: Derangements in brain glutamate, glutathione, and γ-amino butyric acid (GABA) are implicated in a range of neurological disorders. Reliable methods to measure these compounds non-invasively in vivo are needed. We evaluated the reproducibility of their measurements in brain regions involved in the default mode network using quantitative MRS at 7-Tesla in healthy individuals. METHODS: Ten right-handed healthy volunteers underwent 7-Tesla MRI scans on 2 separate days, not more than 2 weeks apart. On each day two scanning sessions took place, with a re-positioning break in between. High-resolution isotropic anatomical scans were acquired prior to each scan, followed by single-voxel 1H-MRS using the STEAM pulse sequence on an 8 mL midline cubic voxel, positioned over the posterior cingulate and precuneus regions. Concentrations were corrected for partial-volume effects. RESULTS: Maximal Cramér-Rao lower bounds for glutamate, glutathione, and GABA were 2.0, 8.0, and 14.0%, respectively. Mean coefficients of variation within sessions were 5.9 ± 4.8%, 9.3 ± 7.6%, and 11.5 ± 8.8%, and between sessions were 4.6 ± 4.5%, 8.3 ± 5.7%, and 9.2 ± 8.7%, respectively. The mean (±SD) Dice's coefficient for voxel overlap was 90 ± 4% within sessions and 86 ± 7% between sessions. CONCLUSION: Glutamate, glutathione, and GABA can be reliably quantified using STEAM MRS at 7-Tesla from the posterior cingulate and precuneus cortices of healthy human subjects. STEAM MRS at 7-Tesla may be used to study the metabolic behavior of this important resting-state hub in various disease states.
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ItemBaseline White Matter Is Associated With Physical Fitness Change in Preclinical Alzheimer's Disease(FRONTIERS MEDIA SA, 2020-04-29)White matter (WM) microstructure is a sensitive marker to distinguish individuals at risk of Alzheimer's disease. The association of objective physical fitness (PF) measures and WM microstructure has not been explored and mixed results reported with physical activity (PA). Longitudinal studies of WM with PA and PF measures have had limited investigation. This study explored the relationship between objective PF measures over 24-months with "normal-appearing" WM microstructure. Data acquired on magnetic resonance imaging was used to measure "normal-appearing" WM microstructure at baseline and 24-months. Clinical variables such as cognitive and blood-based measures were collected longitudinally. Also, as part of the randomized controlled trial of a PA, extensive measures of PA and fitness were obtained over the 24 months. Bilateral corticospinal tracts (CST) and the corpus callosum showed a significant association between PF performance over 24-months and baseline WM microstructural measures. There was no significant longitudinal effect of the intervention or PF performance over 24-months. Baseline WM microstructural measures were significantly associated with PF performance over 24-months in this cohort of participants with vascular risk factors and at risk of Alzheimer's disease with distinctive patterns for each PF test.