White Matter Fraction Research Articles

Conservation of structural brain connectivity in people with multiple sclerosis

ABSTRACT Multiple sclerosis (MS) is a neurodegenerative disease that affects the central nervous system. Structures affected in MS include the corpus callosum, connecting the hemispheres. Studies have shown that in mammalian brains, structural connectivity is organized according to a conservation principle, an inverse relationship between intra- and interhemispheric connectivity. The aim of this study was to replicate this conservation principle in subjects with MS and to explore how the disease interacts with it. A multicentric dataset has been analyzed including 513 people with MS and 208 healthy controls from seven different centers. Structural connectivity was quantified through various connectivity measures, and graph analysis was used to study the behavior of intra- and interhemispheric connectivity. The association between the intra- and the interhemispheric connectivity showed a similar strength for healthy controls (r = 0.38, p < 0.001) and people with MS (r = 0.35, p < 0.001). Intrahemispheric connectivity was associated with white matter fraction (r = 0.48, p < 0.0001), lesion volume (r = −0.44, p < 0.0001), and the Symbol Digit Modalities Test (r = 0.25, p < 0.0001). Results show that this conservation principle seems to hold for people with MS. These findings support the hypothesis that interhemispheric connectivity decreases at higher cognitive decline and disability levels, while intrahemispheric connectivity increases to maintain the balance.

Single-shot diffusion trace spectroscopic imaging using radial echo planar trajectories.

Demonstrate the feasibility and evaluate the performance of single-shot diffusion trace-weighted radial echo planar spectroscopic imaging (Trace DW-REPSI) for quantifying the trace ADC in phantom and in vivo using a 3T clinical scanner. Trace DW-REPSI datasets were acquired in 10 phantom and 10 healthy volunteers, with a maximum b-value of 1601 s/mm2 and diffusion time of 10.75 ms. The self-navigation properties of radial acquisitions were used for corrections of shot-to-shot phase and frequency shift fluctuations of the raw data. In vivo trace ADCs of total NAA (tNAA), total creatine (tCr), and total choline (tCho) extrapolated to pure gray and white matter fractions were compared, as well as trace ADCs estimated in voxels within white or gray matter-dominant regions. Trace ADCs in phantom show excellent agreement with reported values, and in vivo ADCs agree well with the expected differences between gray and white matter. For tNAA, tCr, and tCho, the trace ADCs extrapolated to pure gray and white matter ranged from 0.18-0.27 and 0.26-0.38 μm2/ms, respectively. In sets of gray and white matter-dominant voxels, the values ranged from 0.21 to 0.27 and 0.24 to 0.31 μm2/ms, respectively. The overestimated trace ADCs from this sequence can be attributed to the short diffusion time. This study presents the first demonstration of the single-shot diffusion trace-weighted spectroscopic imaging sequence using radial echo planar trajectories. The Trace DW-REPSI sequence could provide an estimate of the trace ADC in a much shorter scan time compared to conventional approaches that require three separate measurements.

Intrinsic and extrinsic contributors to subregional thalamic volume loss in multiple sclerosis.

To evaluate the intrinsic and extrinsic microstructural factors contributing to atrophy within individual thalamic subregions in multiple sclerosis using in vivo high-gradient diffusion MRI. In this cross-sectional study, 41 people with multiple sclerosis and 34 age and sex-matched healthy controls underwent 3T MRI with up to 300 mT/m gradients using a multi-shell diffusion protocol consisting of eight b-values and diffusion time of 19 ms. Each thalamus was parcellated into 25 subregions for volume determination and diffusion metric estimation. The soma and neurite density imaging model was applied to obtain estimates of intra-neurite, intra-soma, and extra-cellular signal fractions for each subregion and within structurally connected white matter trajectories and cortex. Multiple sclerosis-related volume loss was more pronounced in posterior/medial subregions than anterior/ventral subregions. Intra-soma signal fraction was lower in multiple sclerosis, reflecting reduced cell body density, while the extra-cellular signal fraction was higher, reflecting greater extra-cellular space, both of which were observed more in posterior/medial subregions than anterior/ventral subregions. Lower intra-neurite signal fraction in connected normal-appearing white matter and lower intra-soma signal fraction of structurally connected cortex were associated with reduced subregional thalamic volumes. Intrinsic and extrinsic microstructural measures independently related to subregional volume with heterogeneity across atrophy-prone thalamic nuclei. Extrinsic microstructural alterations predicted left anteroventral, intrinsic microstructural alterations predicted bilateral medial pulvinar, and both intrinsic and extrinsic factors predicted lateral geniculate and medial mediodorsal volumes. Our results might be reflective of the involvement of anterograde and retrograde degeneration from white matter demyelination and cerebrospinal fluid-mediated damage in subregional thalamic volume loss.

Age-stratified Assessment of Brain Volumetric Segmentation on the Indian Population Using Quantitative Magnetic Resonance Imaging.

Automated methods for quantifying brain tissue volumes have gained clinical interest for their objective assessment of neurological diseases. This study aimed to establish reference curves for brain volumes and fractions in the Indian population using Synthetic MRI (SyMRI), aquantitative imaging technique providing multiple contrast-weighted images through fast postprocessing. The study included acohort of 314 healthy individuals aged 15-65years from multiple hospitals/centers across India. The SyMRI-quantified brain volumes and fractions, including brain parenchymal fraction (BPF), gray matter fraction (GMF), white matter fraction (WMF), and myelin. Normative age-stratified quantification curves were created based on the obtained data. The results showed significant differences in brain volumes between the sexes, but not after normalization by intracranial volume. The findings provide normative data for the Indian population and can be used for comparative analysis of brain structure values. Furthermore, our data indicate that the use of fractions rather than absolute volumes in normative curves, such as BPF, GMF, and WMF, can mitigate sex and population differences as they account for individual differences in head size or brain volume.

Diffusion MRI approaches for investigating microstructural complexity in a rat model of traumatic brain injury

Our study explores the potential of conventional and advanced diffusion MRI techniques including diffusion tensor imaging (DTI), and single-shell 3-tissue constrained spherical deconvolution (SS3T-CSD) to investigate complex microstructural changes following severe traumatic brain injury in rats at a chronic phase. Rat brains after sham-operation or lateral fluid percussion (LFP) injury were scanned ex vivo in a 9.4 T scanner. Our region-of-interest-based approach of tensor-, and SS3T-CSD derived fixel-, 3-tissue signal fraction maps were sensitive to changes in both white matter (WM) and grey matter (GM) areas. Tensor-based measures, such as fractional anisotropy (FA) and radial diffusivity (RD), detected more changes in WM and GM areas as compared to fixel-based measures including apparent fiber density (AFD), peak FOD amplitude and primary fiber bundle density, while 3-tissue signal fraction maps revealed distinct changes in WM, GM, and phosphate-buffered saline (PBS) fractions highlighting the complex tissue microstructural alterations post-trauma. Track-weighted imaging demonstrated changes in track morphology including reduced curvature and average pathlength distal from the primary lesion in severe TBI rats. In histological analysis, changes in the diffusion MRI measures could be associated to decreased myelin density, loss of myelinated axons, and increased cellularity, revealing progressive microstructural alterations in these brain areas five months after injury. Overall, this study highlights the use of combined conventional and advanced diffusion MRI measures to obtain more precise insights into the complex tissue microstructural alterations in chronic phase of severe brain injury.

Abstract 126: Genetic Analyses Of Oral Health And Neuroimaging Markers Of Brain Health In Persons Without Stroke

Background: Oral health is a modifiable risk factor for stroke. However, the role of oral health in the brain health of clinically asymptomatic persons remains understudied. We hypothesize that genetically-determined poor oral health leads to worse neuroimaging brain health profiles in persons without stroke. Methods: We conducted a two-sample Mendelian Randomization (MR) study. As instruments, we used 105 genetic variants known to be associated (p<5x10 -8 ) with a composite of caries, dentures and missing teeth in the GLIDE Consortium. In stroke-free participants enrolled in the UK Biobank, we tested for association between these genetic variants and white matter hyperintensity volume (natural log-transformed), fraction anisotropy and mean diffusivity. For the last two neuroimaging traits, we evaluated the first principal component of measurements obtained across 48 brain regions. Results: Our primary analysis using the inverse variance-weighted MR method indicated that genetically-increased risk of poor oral health was associated with: (1) higher burden of silent cerebrovascular disease, as represented by higher volumes of white matter hyperintensities (beta=0.24, SE=0.07 p-value=0.001), and (2) increased microstructural damage, as represented by lower fractional anisotropy (beta=-2.53, SE=0.38; p=1x10 -9 ) and higher mean diffusivity (beta=3.42, SE=0.41; p=2x10 -11 ). Sensitivity analyses identified horizontal pleiotropy in our primary results, but an outlier-corrected analysis confirmed all three initial results (all p-values <0.001, Table 1). Conclusion: Among persons without stroke, genetically-determined poor oral health is associated with worse neuroimaging brain health profiles. Because gene-disease associations are immune to confounding, our results indicate that this association is causal. Early treatment of poor oral health may lead to significant brain health benefits, even in persons without stroke.

Estimation of white matter hyperintensities with synthetic MRI myelin volume fraction in patients with multiple sclerosis and non-multiple-sclerosis white matter hyperintensities: A pilot study among the Indian population

<abstract><sec> <title>AIM</title> <p>Synthetic MRI (SyMRI) works on the MDME sequence, which acquires the relaxation properties of the brain and helps to measure the accurate tissue properties in 6 minutes. The aim of this study was to evaluate the synthetic MRI (SyMRI)-generated myelin (MyC) to white matter (WM) ratio, the WM fraction (WMF), MyC partial maps performing normative brain volumetry to investigate MyC loss in multiple sclerosis (MS) patients with white-matter hyperintensites (WMHs) and non-MS patients with WMHs in a clinical setting.</p> </sec><sec> <title>MATERIALS and METHODS</title> <p>Synthetic MRI images were acquired from 15 patients with MS, and from 15 non-MS patients on a 3T MRI scanner (Discovery MR750w; GE Healthcare; Milwaukee, USA) using MAGiC, a customized version of SyntheticMR's SyMRI® IMAGE software marketed by GE Healthcare under a license agreement. Fast multi-delay multi-echo acquisition was performed with a 2D axial pulse sequence with different combinations of echo time (TEs) and saturation delay times. The total image acquisition time was 6 minutes. SyMRI image analysis was done using SyMRI software (SyMRI Version: 11.3.6; Synthetic MR, Linköping, Sweden). SyMRI data were used to generate the MyC partial maps and WMFs to quantify the signal intensities of test group and control group, andcontrol group , and their mean values were recorded. All patients also underwent conventional diffusion-weighted imaging, i.e., T1w and T2w imaging.</p> </sec><sec> <title>RESULTS</title> <p>The results showed that the WMF was significantly lower in the test group than in the control group (38.8% vs 33.2%, p < 0.001). The Mann-Whitney U nonparametric t-test revealed a significant difference in the mean myelin volume between the test group and the control group (158.66 ± 32.31 vs. 138.29 ± 29.28, p = 0.044). Also, there were no significant differences in the gray matter fraction and intracranial volume between the test group and the control group.</p> </sec><sec> <title>CONCLUSIONS</title> <p>We observed MyC loss in test group using quantitative SyMRI. Thus, myelin loss in MS patients can be quantitatively evaluated using SyMRI.</p> </sec></abstract>

Exploring the effect of glatiramer acetate on cerebral gray matter atrophy in multiple sclerosis

Background and purposeCerebral gray matter (GM) atrophy is a proposed measure of neuroprotection in multiple sclerosis (MS). Glatiramer acetate (GA) limits clinical relapses, MRI lesions, and whole brain atrophy in relapsing-remitting MS (RRMS). The effect of GA on GM atrophy remains unclear. We assessed GM atrophy in patients with RRMS starting GA therapy in comparison to a cohort of patients with clinically benign RRMS (BMS). Design/methodsWe studied 14 patients at GA start [age (mean ± SD) 44.2 ± 7.0 years, disease duration (DD) 7.2 ± 6.4 years, Expanded Disability Status Scale score (EDSS) (median,IQR) 1.0,2.0] and 6 patients with BMS [age 43.0 ± 6.1 years, DD 18.1 ± 8.4 years, EDSS 0.5,1.0]. Brain MRI was obtained at baseline and one year later (both groups) and two years later in all patients in the GA group except one who was lost to follow-up. Semi-automated algorithms assessed cerebral T2 hyperintense lesion volume (T2LV), white matter fraction (WMF), GM fraction (GMF), and brain parenchymal fraction (BPF). The exact Wilcoxon-Mann-Whitney test compared the groups. The Wilcoxon signed rank test assessed longitudinal changes within groups. ResultsDuring the first year, MRI changes did not differ significantly between groups (p > 0.15). Within the BMS group, WMF and BPF decreased during the first year (p = 0.03). Within the GA group, there was no significant change in MRI measures during each annual period (p > 0.05). Over two years, the GA group had a significant increase in T2LV and decrease in WMF (p < 0.05), while GMF and BPF remained stable (p > 0.05). MRI changes in brain volumes (GMF or WMF) in the first year in the GA group were not significantly different from those in the BMS group (p > 0.5). ConclusionsIn this pilot study with a small sample size, patients with RRMS started on GA did not show significant GM or whole brain atrophy over 2 years, resembling MS patients with a clinically benign disease course.

Association between brain volume and disability over time in multiple sclerosis.

Most previous multiple sclerosis (MS) brain atrophy studies using MS impact scale 29 (MSIS-29) or symbol digit modalities test (SDMT) have been cross-sectional with limited sets of clinical outcomes. To investigate which brain and lesion volume metrics show the strongest long-term associations with the expanded disability status scale (EDSS), SDMT, and MSIS-29, and whether MRI-clinical associations vary with age. We acquired MRI and clinical data from a real-world Swedish MS cohort. FreeSurfer and SPM Lesion Segmentation Tool were used to obtain brain parenchymal, cortical and subcortical grey matter, thalamic and white matter fractions as well as T1- and T2-lesion volumes. Mixed-effects and rolling regression models were used in the statistical analyses. We included 989 persons with MS followed for a median of 9.3 (EDSS), 10.1 (SDMT), and 9.3 (MSIS-29) years, respectively. In a cross-sectional analysis, the strength of the associations of the MRI metrics with the EDSS and MSIS-29 was found to drastically increase after 40-50 years of age. Low baseline regional grey matter fractions were associated with longitudinal increase of EDSS and physical MSIS-29 scores and decrease in SDMT scores and these atrophy measures were stronger predictors than the lesion volumes. The strength of MRI-clinical associations increase with age. Grey matter volume fractions are stronger predictors of long-term disability measures than lesion volumes.

Spinal cord grey matter atrophy in Multiple Sclerosis clinical practice

PurposeSeveral studies have indicated the relevance of spinal cord grey matter atrophy for Multiple Sclerosis (MS) related disability. This work aimed at evaluating feasibility and clinical relevance of MRI-derived estimations of spinal cord grey matter atrophy in clinical practice. MethodsA convenience sample of MS patients (n=48) and healthy controls (HC, n=11) was scanned using brain sagittal 3D T1w (MPRAGE) and transverse T2w-FLAIR, and transverse single-slice spinal cord 2D heavily T1w (PSIR: phase-sensitive inversion recovery) sequences. An experienced technician with neuroradiological supervision used a semiautomated thresholding method implemented in JIM software on PSIR sequences to obtain cross-sectional area (CSA) of the spinal canal (CSAcanal), whole cord (CSAcord), grey (CSAgm) and white matter (CSAwm) at C2-C3. MPRAGE and T2w-FLAIR sequences were used to obtain brain parenchymal, grey and white matter fractions (BPF, GMF and WMF) using the Statistical Parametric Mapping software. Appropriate statistical tests were used before and after age and sex adjustment. ResultsCSAgm and CSAwm could be obtained in all HC, but only 18 patients (37.5%) due to presence of lesions at C2-C3. Significant univariate associations between EDSS and BPF (rho =−0.376, p=0.015), GMF (rho =−0.287, p=0.069), CSAcanal (rho =−0.310, p=0.049), CSAcord (rho =−0.533 p<0.001) and CSAgm (rho =−0.511, p=0.062) were detected. After age/sex adjustment trends were observed for CSAcanal and CSAcord. ConclusionIn a clinical practice setting, relevance of spinal cord grey matter is confirmed, but cervical cord lesions could greatly hamper its application. Clinical associations with disability have been observed and seem stronger for spinal cord than for brain atrophy measures.

White Matter but not Gray Matter Volumes Are Associated with Cognition in Community-Dwelling Chinese Populations.

Few studies have investigated the association between cognition and brain volume associated with cerebral small vessel disease (CSVD). We investigated the association between cognition and brain volume and neuroimaging markers of CSVD in a community-dwelling population. Participants (n = 993, age≥35 years) from the community-based Shunyi Study were included to investigate the association between neuroimaging markers and cognition cross-sectionally. Magnetic resonance imaging markers included brain volume measurements of the total cerebrum, white matter, gray matter, and CSVD imaging markers. Cognitive performance was assessed using neuropsychological tests of the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Fuld Object Memory, digit span, Trail Making Test (TMT)-A, and TMT-B. For brain volume measurement, subcortical white matter fraction was positively associated with MMSE score (β= 0.034, p = 0.0062) and MoCA score (β= 0.034, p = 0.0174), and negatively associated with TMT-A and TMT-B completion time (β= -2.319, p = 0.0002; β= -2.827, p = 0.0073, respectively). For evaluation of CSVD imaging markers, the presence of lacunes was positively associated with TMT-B completion time (β= 17.241, p = 0.0028). In community-dwelling populations, reduced white matter volumes, as a consequence of aging and vascular damage, are associated with worse global cognition and executive function. Our findings provide potential insights into the correlation between cognition and CSVD-associated subcortical white matter injury.

Does obesity exacerbate brain lesion volume and atrophy in patients with multiple sclerosis?

BackgroundObesity is common among patients with multiple sclerosis (pwMS) and has been shown to exacerbate central inflammation, a key factor in disease progression. The purpose of this cross-sectional study is to examine the possible relationships between obesity, as measured by body mass index (BMI), and MS-related brain changes in atrophy and lesion volume, as measured from MRI, in a large, representative sample of pwMS. MethodsBMI and MRI data, along with demographic and disease variables, were acquired from the Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS) registry. Unadjusted and adjusted partial correlations, controlling for gender, race, age, education level, MS phenotype, disability and disease duration, examined the associations between BMI and MRI outcomes, which included brain parenchymal fraction, white matter fraction, gray matter fraction, thalamic volume, and T2 lesion volume. ResultsThe sample consisted of 3,046 pwMS. Unadjusted and adjusted BMI-MRI correlations accounted for between 0.4% and 2.0% of shared variance (R2). When considering the relationship between MRI outcomes and BMI category (normal weight, overweight, obese), multiple regression analyses continued to show minimal association, with BMI category accounting for no more than 1.5% of shared variance. ConclusionsNo clinically meaningful associations were found between BMI and MRI outcomes in this large, representative sample of MS patients, regardless of demographics and disease variables. These unexpected negative results will require replication with a longitudinal design using more precise measures of obesity.

Age-Related Changes in Relaxation Times, Proton Density, Myelin, and Tissue Volumes in Adult Brain Analyzed by 2-Dimensional Quantitative Synthetic Magnetic Resonance Imaging.

Quantitative synthetic magnetic resonance imaging (MRI) enables the determination of fundamental tissue properties, namely, T1 and T2 relaxation times and proton density (PD), in a single scan. Myelin estimation and brain segmentation based on these quantitative values can also be performed automatically. This study aimed to reveal the changes in tissue characteristics and volumes of the brain according to age and provide age-specific reference values obtained by quantitative synthetic MRI. This was a prospective study of healthy subjects with no history of brain diseases scanned with a multidynamic multiecho sequence for simultaneous measurement of relaxometry of T1, T2, and PD. We performed myelin estimation and brain volumetry based on these values. We performed volume-of-interest analysis on both gray matter (GM) and white matter (WM) regions for T1, T2, PD, and myelin volume fraction maps. Tissue volumes were calculated in the whole brain, producing brain parenchymal volume, GM volume, WM volume, and myelin volume. These volumes were normalized by intracranial volume to a brain parenchymal fraction, GM fraction, WM fraction, and myelin fraction (MyF). We examined the changes in the mean regional quantitative values and segmented tissue volumes according to age. We analyzed data of 114 adults (53 men and 61 women; median age, 66.5 years; range, 21-86 years). T1, T2, and PD values showed quadratic changes according to age and stayed stable or decreased until around 60 years of age and increased thereafter. Myelin volume fraction showed a reversed trend. Brain parenchymal fraction and GM fraction decreased throughout all ages. The approximation curves showed that WM fraction and MyF gradually increased until around the 40s to 50s and decreased thereafter. A significant decline in MyF was first noted in the 60s age group (Tukey test, P < 0.001). Our study showed changes according to age in tissue characteristic values and brain volumes using quantitative synthetic MRI. The reference values for age demonstrated in this study may be useful to discriminate brain disorders from healthy brains.

Optical coherence tomography measures correlate with brain and spinal cord atrophy and multiple sclerosis disease-related disability.

Both optical coherence tomography (OCT) and magnetic resonance imaging (MRI) volumetric measures have been postulated as potential biomarkers of multiple sclerosis (MS)-related disability. The aim of the study was to investigate the association between OCT and brain volume and spinal cord area (SCA) parameters in patients with relapsing MS and to assess their independent associations with disability. This was a cross-sectional analysis of 90 patients with MS who underwent OCT and MRI examination. Values of peripapillary retinal nerve fibre layer (pRNFL), ganglion cell/inner plexiform layer (GCIPL) and inner nuclear layer of eyes without previous optic neuritis were obtained. SCA and brain parenchymal fraction (BPF), grey and white matter fractions were obtained. Multivariable regression analyses were conducted with disability as dependent variable. Lower pRNFL thickness and lower GCIPL volume as well as lower BPF, grey matter fraction and SCA were associated with a longer disease duration and a higher Expanded Disability Status Scale score. Lower pRNFL thickness and GCIPL volumes were associated with lower BPF and SCA. In the multivariable logistic regression analyses, pRNFL thickness and GCIPL volume outperformed MRI in predicting disability. The OCT measures correlate with brain and spinal cord atrophy and appear more closely associated with disability than MRI volumetric measures.

Late onset multiple sclerosis - multiparametric MRI characteristics.

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) with heterogenic character. Typical age of onset is between 20 and 35 years. Clinically definite multiple sclerosis (CDMS) can occur also in patients older than 50 years. This type of MS is called Late Onset Multiple Sclerosis (LOMS). Until now, the differences in clinical course, type of first symptoms, and prognosis of LOMS have not been well established. Also the MRI characteristics of patients with LOMS have not been determined. Neither conventional nor nonconventional MRI features are known to be typical for LOMS. To investigate the MRI characteristics of LOMS patients based on conventional and non-conventional techniques. Twenty patients with LOMS were included in the study and 17 patients with typical onset of MS (TOMS) served as a comparative group. The two groups were matched in terms of disease duration and EDSS score. Conventional (T1- and T2-weighted images) and non-conventional (magnetization transfer images, proton magnetic resonance spectroscopy) MRI techniques were performed in all participants. Parameters from both techniques were compared between LOMS and TOMS groups. Patients with late onset of MS had lower Brain Parenchyma Fraction (BPF) (p < 0.001) and Grey Matter Fraction (GMF) values (p = 0.008) than the TOMS group. There was no statistical differences in White Matter Fraction (WMF) values between the groups (p = 0.572). Patients with LOMS and TOMS statistically differed in the peak height (p = 0.018), peak location (p < 0.001), and MTR mean value (p < 0.001). Patients with LOMS manifested lower concentrations of NAA+NAAG and NAA+NAAG/Cr than patients with TOMS (p = 0.009 and p < 0.001 respectively). No statistical difference was found between the groups in terms of mean mIn (p = 0.346) and mean GPC+PCh (p = 0.563). We did not find a statistical difference in T1- and T2- lesion load (p = 0.1, p = 0.3 respectively) although T1/T2 lesion ratio was higher in the LOMS group. MRI parameters in patients with LOMS differed significantly from those obtained from the TOMS group. Our results, which indicate that in LOMS patients brain tissue damage is more advanced than in TOMS patients, may contribute to a better understanding of the heterogeneity of MS.

Big GABA II: Water-referenced edited MR spectroscopy at 25 research sites

Accurate and reliable quantification of brain metabolites measured in vivo using 1H magnetic resonance spectroscopy (MRS) is a topic of continued interest. Aside from differences in the basic approach to quantification, the quantification of metabolite data acquired at different sites and on different platforms poses an additional methodological challenge. In this study, spectrally edited γ-aminobutyric acid (GABA) MRS data were analyzed and GABA levels were quantified relative to an internal tissue water reference. Data from 284 volunteers scanned across 25 research sites were collected using GABA+ (GABA + co-edited macromolecules (MM)) and MM-suppressed GABA editing. The unsuppressed water signal from the volume of interest was acquired for concentration referencing. Whole-brain T1-weighted structural images were acquired and segmented to determine gray matter, white matter and cerebrospinal fluid voxel tissue fractions. Water-referenced GABA measurements were fully corrected for tissue-dependent signal relaxation and water visibility effects. The cohort-wide coefficient of variation was 17% for the GABA + data and 29% for the MM-suppressed GABA data. The mean within-site coefficient of variation was 10% for the GABA + data and 19% for the MM-suppressed GABA data. Vendor differences contributed 53% to the total variance in the GABA + data, while the remaining variance was attributed to site- (11%) and participant-level (36%) effects. For the MM-suppressed data, 54% of the variance was attributed to site differences, while the remaining 46% was attributed to participant differences. Results from an exploratory analysis suggested that the vendor differences were related to the unsuppressed water signal acquisition. Discounting the observed vendor-specific effects, water-referenced GABA measurements exhibit similar levels of variance to creatine-referenced GABA measurements. It is concluded that quantification using internal tissue water referencing is a viable and reliable method for the quantification of in vivo GABA levels.

Association of Retinal Nerve Fiber Layer Thickness With Brain Alterations in the Visual and Limbic Networks in Elderly Adults Without Dementia

The eye is a sensory organ that is easily accessible for imaging techniques, allowing the measurement of the retinal nerve fiber layer (RNFL) thickness. The eye is part of the central nervous system, and its neurons may be susceptible to degeneration; therefore, changes in the RNFL thickness may reflect microstructural and volume alterations in the brain. To explore the association between the peripapillary RNFL thickness and brain alterations in the visual and limbic networks in elderly people without dementia. Cross-sectional analysis of the Three-City/Antioxydants, Lipides Essentiels, Nutrition et Maladies Oculaires (Alienor) Study cohort (April 2009 to December 2010). The dates of analysis were July 2017 to August 2018. The setting was a population-based study in France. The brain volume analysis included 104 participants, and the diffusion tensor imaging analysis included 79 participants. Global RNFL was assessed by spectral-domain optical coherence tomography. Brain volumes were assessed via T1-weighted magnetic resonance imaging by measurement of the global white and gray matter fractions and the hippocampal fraction. Brain microstructural alterations were assessed with diffusion tensor imaging at the level of the posterior thalamic radiations, the limbic system tracts (the fornix and cingulum bundles), and the posterior limb of the internal capsule (control region). Linear regression models adjusted for several confounders were performed. Among a total of 104 participants, the mean (SD) age was 80.8 (3.9) years, and the cohort was 56.7% women (n = 59). The mean (SD) global RNFL thickness was 89.3 (12.9) µm. A thicker RNFL was associated with a greater hippocampal fraction (quantity of increase β = 0.013; 95% CI, 0.001-0.025 per 10-μm increase in the RNFL thickness) and better diffusion tensor imaging variables in the global cingulum (mean diffusivity β = -0.007; 95% CI, -0.015 to -0.000) and the hippocampal part of the cingulum (mean diffusivity β = -0.009; 95% CI, -0.016 to -0.002 and radial diffusivity β = -0.010; 95% CI, -0.018 to -0.002) and the posterior thalamic radiations (fractional anisotropy β = 0.008; 95% CI, 0.000-0.017). No significant associations were found with other magnetic resonance imaging volumes or with other diffusion tensor imaging variables. In particular, there was no significant association with the control region of interest. Results of this study suggest that in elderly individuals without dementia, a thicker RNFL was associated with better magnetic resonance imaging variables both in a region that included the visual pathways and in regions particularly involved in the neurodegenerative processes of Alzheimer disease.

Association of smoking but not HLA-DRB1*15:01, APOE or body mass index with brain atrophy in early multiple sclerosis

Background: The course of multiple sclerosis (MS) shows substantial inter-individual variability. The underlying determinants of disease severity likely involve genetic and environmental factors. Objective: The aim of this study was to assess the impact of APOE and HLA polymorphisms as well as smoking and body mass index (BMI) in the very early MS course. Methods: Untreated patients (n = 263) with a recent diagnosis of relapsing-remitting (RR) MS or clinically isolated syndrome underwent standardized magnetic resonance imaging (MRI). Genotyping was performed for single-nucleotide polymorphisms (SNPs) rs3135388 tagging the HLA-DRB1*15:01 haplotype and rs7412 (Ɛ2) and rs429358 (Ɛ4) in APOE. Linear regression analyses were applied based on the three SNPs, smoking and BMI as exposures and MRI surrogate markers for disease severity as outcomes. Results: Current smoking was associated with reduced gray matter fraction, lower brain parenchymal fraction and increased cerebrospinal fluid fraction in comparison to non-smoking, whereas no effect was observed on white matter fraction. BMI and the SNPs in HLA and APOE were not associated with structural MRI parameters. Conclusions: Smoking may have an unfavorable effect on the gray matter fraction as a potential measure of MS severity already in early MS. These findings may impact patients’ counseling upon initial diagnosis of MS.

In vivo estimation of transverse relaxation time constant (T2 ) of 17 human brain metabolites at 3T.

The transverse relaxation times T2 of 17 metabolites in vivo at 3T is reported and region specific differences are addressed. An echo-time series protocol was applied to one, two, or three volumes of interest with different fraction of white and gray matter including a total number of 106 healthy volunteers and acquiring a total number of 128 spectra. The data were fitted with the 2D fitting tool ProFit2, which included individual line shape modeling for all metabolites and allowed the T2 calculation of 28 moieties of 17 metabolites. The T2 of 10 metabolites and their moieties have been reported for the first time. Region specific T2 differences in white and gray matter enriched tissue occur in 16 of 17 metabolites examined including single resonance lines and coupled spin systems. The relaxation time T2 is regions specific and has to be considered when applying tissue composition correction for internal water referencing. Magn Reson Med 80:452-461, 2018. © 2018 International Society for Magnetic Resonance in Medicine.

Brain atrophy 15 years after CIS: Baseline and follow-up clinico-radiological correlations

Background: Brain atrophy in multiple sclerosis (MS) patients is present since the very early stages of the disease and it has been related to long-term disability. Objective: To estimate brain volume (BV) at 15 years after a clinically isolated syndrome (CIS) and to evaluate its relationship with disease outcomes. Methods: From a prospective cohort including patients presenting with a CIS, 54 patients with a brain magnetic resonance imaging (MRI) performed 15 years after CIS were included. Brain parenchymal fraction (BPF), grey matter fraction (GMF) and white matter fraction (WMF) at 15-year follow-up were obtained. Regression analyses were conducted to predict BV loss and reaching an Expanded Disability Status Scale (EDSS) of 3.0 in that 15-year period. Results: In multivariable analyses, lower values of BPF and WMF were significantly associated with being male, presenting 3–4 Barkhof criteria at baseline, presenting a second relapse, and with a decision to start treatment. In the multivariable logistic regression analysis, only lower GMF was associated with a greater risk of reaching EDSS 3.0 (odds ratio (OR) = 0.24, p = 0.028). Conclusion: Lower BPF and WMF 15 years after CIS are associated with previous markers of inflammatory disease. Lower GMF 15 years after a CIS is associated with an increased risk of reaching an EDSS of 3.0.