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Objective: We employed diffusion-weighted magnetic resonance spectroscopy (DW-MRS), which allows to measure in vivo the diffusion properties of metabolites, to explore the functional neuro-axonal damage and the ongoing energetic dysregulation in multiple sclerosis (MS). Methods: Twenty-five patients with MS and 18 healthy controls (HC) underwent conventional magnetic resonance imaging (MRI) and DW-MRS. The apparent diffusion coefficient (ADC) of total N-acetyl-aspartate (tNAA) and creatine–phosphocreatine (tCr) were measured in the parietal normal-appearing white matter (NAWM) and in the thalamic grey matter (TGM). Multiple regressions were used to compare metabolite ADCs between groups and to explore clinical correlations. Results: In patients compared with HCs, we found a reduction in ADC(tNAA) in the TGM, reflecting functional and structural neuro-axonal damage, and in ADC(tCr) in both NAWM and TGM, possibly reflecting a reduction in energy supply in neurons and glial cells. Metabolite ADCs did not correlate with tissue atrophy, lesional volume or metabolite concentrations, while in TGM metabolite ADCs correlated with clinical scores. Conclusion: DW-MRS showed a reduction in tCr diffusivity in the normal-appearing brain of patients with MS, which might reflect a state of ongoing energy dysregulation affecting neurons and/or glial cells. Reversing this energy dysregulation before neuro-axonal degeneration arises may become a key objective in future neuroprotective strategies. [ABSTRACT FROM AUTHOR]

Diffusion-weighted MRS (DWS) of brain metabolites enables the study of cell-specific alterations in tissue microstructure by probing the diffusion of intracellular metabolites. In particular, the diffusion properties of neuronal N-acetylaspartate (NAA), typically co-measured with N-acetylaspartyl glutamate (NAAG) (NAA + NAAG = tNAA), have been shown to be sensitive to intraneuronal/axonal damage in pathologies such as stroke and multiple sclerosis. Lacking, so far, are empirical assessments of the reproducibility of DWS measures across time and subjects, as well as a systematic investigation of the optimal acquisition parameters for DWS experiments, both of which are sorely needed for clinical applications of the method. In this study, we acquired comprehensive single-volume DWS datasets of the human corpus callosum at 3T and 7T. We investigated the inter- and intra-subject variability of empirical and modeled diffusion properties of tNAA [ Davg(tNAA) and Dmodel(tNAA), respectively]. Subsequently, we used a jackknife-like resampling approach to explore the variance of these properties in partial data subsets reflecting different total scan durations. The coefficients of variation ( CV) and repeatability coefficients ( CR) for Davg(tNAA) and Dmodel(tNAA) were calculated for both 3T and 7T, with overall lower variability in the 7T results. Although this work is limited to the estimation of the diffusion properties in the corpus callosum, we show that a careful choice of diffusion-weighting conditions at both field strengths allows the accurate measurement of tNAA diffusion properties in clinically relevant experimental time. Based on the resampling results, we suggest optimized acquisition schemes of 13-min duration at 3T and 10-min duration at 7T, whilst retaining low variability ( CV ≈ 8%) for the tNAA diffusion measures. Power calculations for the estimation of Dmodel(tNAA) and Davg(tNAA) based on the suggested schemes show that less than 21 subjects per group are sufficient for the detection of a 10% effect between two groups in case-control studies. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

We present a method for the robust and accurate estimation of brain metabolite transverse relaxation times ( T2) from multiple spin-echo data acquired with a single-shot Carr-Purcell-Meiboom-Gill (CPMG) spectroscopic sequence. Each acquired echo consists of a small number of complex time-domain data points. The amplitudes of the spectral components in each echo are calculated by solving a set of linear equations in which previously estimated frequencies and linewidths serve as prior information. These priors are obtained from a short MRS experiment in which a large number of time-domain data points are acquired, and are subsequently estimated using linear prediction with singular value decomposition (LPSVD) processing. We show that this process can be used to accurately and rapidly measure the T2 values for the main singlet resonances in single-volume MRS measurements in the brain. The proposed method can be generalized to any set of MRS experiments comprising repeated measurements of amplitude changes, e.g. as a function of an experimental parameter, such as TE, inversion time or diffusion weighting. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Sensitive and specific in vivo measures of axonal damage, an important determinant of clinical status in multiple sclerosis (MS), might greatly benefit prognostication and therapy assessment. Diffusion tensor spectroscopy (DTS) combines features of diffusion tensor imaging and magneticresonancespectroscopy, allowingmeasurementofthediffusionpropertiesofintracellular,cell-type-specificmetabolites. As such,itmaybe sensitive to disruption of tissue microstructure within neurons. In this cross-sectional pilot study, diffusion of the neuronal metabolite N-acetylaspartate (NAA) was measured in the human normal-appearing corpus callosum on a 7 tesla MRI scanner, comparing 15 MS patients and 14 healthy controls. We found that NAA parallel diffusivity is lower in MS (p=0.030) and inversely correlated with both water parallel diffusivity (p=0.020) and clinical severity (p=0.015). Interpreted in the context of previous experiments, our findings provide preliminary evidence that DTS can distinguish axonopathy from other processes such as inflammation, edema, demyelination, and gliosis. By detecting reduced diffusion of NAA parallel to axons in white matter, DTS may thus be capable of distinguishing axonal disruption in MS in the setting of increased parallel diffusion of water, which is commonly observed in MS but pathologically nonspecific. [ABSTRACT FROM AUTHOR]

Abstract: The rhesus monkey is a useful model for examining age-related effects on the brain, because of the extensive neuroanatomical homology between the monkey and the human brain, the tight control for neurological diseases as well as the possibility of obtaining relevant behavioral data and post-mortem tissue for histological analyses. Here, proton magnetic resonance spectroscopy (1H-MRS) was used together with high-resolution anatomical MRI images to carefully assess regional concentrations of brain metabolites in a group of 20 rhesus monkeys. In an anterior volume of interest (VOI) that covered frontal and prefrontal areas, significant positive correlations of myo-inositol and of total creatine concentrations with age were detected, whereas N-acetyl aspartate (NAA) and choline compounds (Cho) were not significantly correlated with age. In an occipito-parietal VOI, all metabolites showed no statistically significant age-dependent trend. Strong correlations were found between NAA concentration and gray matter fraction in the VOIs as well as between choline compounds and white matter fraction. [Copyright &y& Elsevier]

Presents information on a study which examined the H2...O distribution in a live rat brain using proton-detected magnetic resonance imaging. Theoretical background of the study; Materials and methods; Results; Conclusions.

Brain cell structure and function reflect neurodevelopment, plasticity, and aging; and changes can help flag pathological processes such as neurodegeneration and neuroinflammation. Accurate and quantitative methods to noninvasively disentangle cellular structural features are needed and are a substantial focus of brain research. Diffusion-weighted MRS (dMRS) gives access to diffusion properties of endogenous intracellular brain metabolites that are preferentially located inside specific brain cell populations. Despite its great potential, dMRS remains a challenging technique on all levels: from the data acquisition to the analysis, quantification, modeling, and interpretation of results. These challenges were the motivation behind the organization of the Lorentz Center workshop on "Best Practices & Tools for Diffusion MR Spectroscopy" held in Leiden, the Netherlands, in September 2021. During the workshop, the dMRS community established a set of recommendations to execute robust dMRS studies. This paper provides a description of the steps needed for acquiring, processing, fitting, and modeling dMRS data, and provides links to useful resources., (© 2023 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Objective: We employed diffusion-weighted magnetic resonance spectroscopy (DW-MRS), which allows to measure in vivo the diffusion properties of metabolites, to explore the functional neuro-axonal damage and the ongoing energetic dysregulation in multiple sclerosis (MS)., Methods: Twenty-five patients with MS and 18 healthy controls (HC) underwent conventional magnetic resonance imaging (MRI) and DW-MRS. The apparent diffusion coefficient (ADC) of total N-acetyl-aspartate (tNAA) and creatine-phosphocreatine (tCr) were measured in the parietal normal-appearing white matter (NAWM) and in the thalamic grey matter (TGM). Multiple regressions were used to compare metabolite ADCs between groups and to explore clinical correlations., Results: In patients compared with HCs, we found a reduction in ADC(tNAA) in the TGM, reflecting functional and structural neuro-axonal damage, and in ADC(tCr) in both NAWM and TGM, possibly reflecting a reduction in energy supply in neurons and glial cells. Metabolite ADCs did not correlate with tissue atrophy, lesional volume or metabolite concentrations, while in TGM metabolite ADCs correlated with clinical scores., Conclusion: DW-MRS showed a reduction in tCr diffusivity in the normal-appearing brain of patients with MS, which might reflect a state of ongoing energy dysregulation affecting neurons and/or glial cells. Reversing this energy dysregulation before neuro-axonal degeneration arises may become a key objective in future neuroprotective strategies.

Cortical hyperexcitability due to enhanced glutamatergic activity has been implicated in migraine pathophysiology but direct evidence is lacking. Here we assessed glutamate levels and intracellular mobility of glutamate in the visual cortex of migraineurs in-between attacks. We included 50 migraineurs (23 with aura and 27 without aura) and 24 age- and gender-matched non-headache controls. We used proton magnetic resonance spectroscopy (1H-MRS) and diffusion weighted spectroscopy at 7 T with a single volume of interest (2 × 2 × 3 cm) located in the primary and secondary visual cortex. For 1H-MRS we used a semi-LASER sequence with water referencing for absolute quantification. For diffusion weighted spectroscopy we used an adapted PRESS sequence with gradients applied in three directions and two different gradient amplitudes. Between-group differences were evaluated using analysis of covariance with the grey matter fraction in the volume of interest as covariate and post hoc comparisons with Bonferroni correction. Glutamate concentrations differed between groups (P = 0.047) and were higher in migraineurs without aura (mean ± standard deviation: 7.02 ± 0.50 mM) compared to controls (mean ± standard deviation: 6.40 ± 0.78 mM, P = 0.042). The apparent diffusion coefficient of glutamate was similar among groups (P = 0.129) suggesting similar inter- and intracellular mobility of glutamate in all three study groups. No differences were observed for concentrations and diffusion constants of other metabolites. The present study suggests that interictal glutamate levels are increased in the visual cortex of migraineurs without aura, supporting the hypothesis of cortical hyperexcitability in migraine., (© The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Aim: To evaluate brain involvement in quiescent Crohn's disease (CD) patients with fatigue using quantitative magnetic resonance imaging (MRI)., Methods: Multiple MRI techniques were used to assess cerebral changes in 20 quiescent CD patients with fatigue (defined with at least 6 points out of an 11-point numeric rating scale compared with 17 healthy age and gender matched controls without fatigue. Furthermore, mental status was assessed by cognitive functioning, based on the neuropsychological inventory including the different domains global cognitive functioning, memory and executive functioning and in addition mood and quality of life scores. Cognitive functioning and mood status were correlated with MRI findings in the both study groups., Results: Reduced glutamate + glutamine (Glx = Glu + Gln) concentrations ( P = 0.02) and ratios to total creatine ( P = 0.02) were found in CD patients compared with controls. Significant increased Cerebral Blood Flow ( P = 0.05) was found in CD patients (53.08 ± 6.14 mL/100 g/min) compared with controls (47.60 ± 8.62 mL/100 g/min). CD patients encountered significantly more depressive symptoms ( P < 0.001). Cognitive functioning scores related to memory ( P = 0.007) and executive functioning ( P = 0.02) were lower in CD patients and both scores showed correlation with depression and anxiety. No correlation was found subcortical volumes between CD patients and controls in the T 1 -weighted analysis. In addition, no correlation was found between mental status and MRI findings., Conclusion: This work shows evidence for perfusion, neurochemical and mental differences in the brain of CD patients with fatigue compared with healthy controls., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interest to disclose.

Diffusion-weighted MRS (DWS) of brain metabolites enables the study of cell-specific alterations in tissue microstructure by probing the diffusion of intracellular metabolites. In particular, the diffusion properties of neuronal N-acetylaspartate (NAA), typically co-measured with N-acetylaspartyl glutamate (NAAG) (NAA + NAAG = tNAA), have been shown to be sensitive to intraneuronal/axonal damage in pathologies such as stroke and multiple sclerosis. Lacking, so far, are empirical assessments of the reproducibility of DWS measures across time and subjects, as well as a systematic investigation of the optimal acquisition parameters for DWS experiments, both of which are sorely needed for clinical applications of the method. In this study, we acquired comprehensive single-volume DWS datasets of the human corpus callosum at 3 T and 7 T. We investigated the inter- and intra-subject variability of empirical and modeled diffusion properties of tNAA [D(avg) (tNAA) and D(model) (tNAA), respectively]. Subsequently, we used a jackknife-like resampling approach to explore the variance of these properties in partial data subsets reflecting different total scan durations. The coefficients of variation (C(V)) and repeatability coefficients (C(R)) for D(avg) (tNAA) and D(model) (tNAA) were calculated for both 3 T and 7 T, with overall lower variability in the 7 T results. Although this work is limited to the estimation of the diffusion properties in the corpus callosum, we show that a careful choice of diffusion-weighting conditions at both field strengths allows the accurate measurement of tNAA diffusion properties in clinically relevant experimental time. Based on the resampling results, we suggest optimized acquisition schemes of 13-min duration at 3T and 10-min duration at 7 T, whilst retaining low variability (C(V) ≈ 8%) for the tNAA diffusion measures. Power calculations for the estimation of D(model )(tNAA) and D(avg) (tNAA) based on the suggested schemes show that less than 21 subjects per group are sufficient for the detection of a 10% effect between two groups in case-control studies., (Copyright © 2015 John Wiley & Sons, Ltd.)

We present a method for the robust and accurate estimation of brain metabolite transverse relaxation times (T2 ) from multiple spin-echo data acquired with a single-shot Carr-Purcell-Meiboom-Gill (CPMG) spectroscopic sequence. Each acquired echo consists of a small number of complex time-domain data points. The amplitudes of the spectral components in each echo are calculated by solving a set of linear equations in which previously estimated frequencies and linewidths serve as prior information. These priors are obtained from a short MRS experiment in which a large number of time-domain data points are acquired, and are subsequently estimated using linear prediction with singular value decomposition (LPSVD) processing. We show that this process can be used to accurately and rapidly measure the T2 values for the main singlet resonances in single-volume MRS measurements in the brain. The proposed method can be generalized to any set of MRS experiments comprising repeated measurements of amplitude changes, e.g. as a function of an experimental parameter, such as TE, inversion time or diffusion weighting., (Copyright © 2013 John Wiley & Sons, Ltd.)

One of the most important applications of diffusion tensor image (DTI) is the in-vivo investigation of brain white-matter connectivity. However, DTI has difficulties on the reconstruction of axonal fibers. The data that is used to reconstruct the fibers is affected by partial volume effect, particularly at the border between gray and white matter, and the typical voxel size used in the acquisition of the MR images is larger than the characteristic size of the axonal fiber. The proposed vector criterion tracking method uses selective eigenvector interpolation for fiber tracking. As a result, the method produces faster and more stable trajectories with reducing memory consumption, compared to other current methods.