DW-MRS with ultra-strong diffusion gradients

Diffusion-weighted magnetic resonance spectroscopy benefits from the use of ultra-strong gradients. Slow diffusing metabolites necessitate a large range of b-values to accurately model the diffusion properties. Ultra-strong gradients open the possibility of higher b-values and reduced diffusion times, alleviating some of these constraints. We present initial data acquired with DW-PRESS on a 300mT/m gradient Connectom scanner, and introduce the practical considerations associated with ultra-strong gradients

Machine learning based estimation of axonal permeability: validation on cuprizone treated in-vivo mouse model of axonal demyelination

Estimating axonal permeability reliably is extremely important, however not yet achieved because mathematical models that express its relationship to the MR signal accurately are intractable. Recently introduced machine learning based computational model showed to outperforms previous approximate mathematical models. Here we apply and validate this novel method experimentally on a highly controlled in-vivo mouse model of axonal demyelination, and demonstrate for the first time in practice the power of machine learning as a mechanism to construct complex biophysical models for quantitative MRI

Magnetic resonance spectroscopy of isocitrate dehydrogenase mutated gliomas: current knowledge on the neurochemical profile

International audiencePurpose of review Magnetic resonance spectroscopy (MRS) may play a key role for the management of patients with glioma. We highlighted the utility of MRS in the noninvasive diagnosis of gliomas with mutations in isocitrate dehydrogenase (IDH) genes, by providing an overview of the neurochemical alterations observed in different glioma subtypes, as well as during treatment and progression, both in vivo and ex vivo.Recent findings D-2-hydroxyglutarate (2HG) decrease during anticancer treatments was recently shown to be associated with altered levels of other metabolites, including lactate, glutamate and glutathione, suggesting that tumour treatment leads to a metabolic reprogramming beyond 2HG depletion. In combination with 2HG quantification, cystathionine and glycine seem to be the most promising candidates for higher specific identification of glioma subtypes and follow-up of disease progression and response to treatment.Summary The implementation of advanced MRS methods in the routine clinical practice will allow the quantification of metabolites that are not detectable with conventional methods and may enable immediate, accurate diagnosis of gliomas, which is crucial for planning optimal therapeutic strategies and follow-up examinations. The role of different metabolites as predictors of patient outcome still needs to be elucidated

Differentiating between axonal damage and demyelination in healthy aging by combining diffusion-tensor imaging and diffusion-weighted spectroscopy in the human corpus callosum at 7 T

International audienceDiffusion-tensor imaging and single voxel diffusion-weighted magnetic resonance spectroscopy were used at 7T to explore in vivo age-related microstructural changes in the corpus callosum. Sixteen healthy elderly (age range 60–71 years) and 13 healthy younger controls (age range 23–32 years) were included in the study. In healthy elderly, we found lower water fractional anisotropy and higher water mean diffusivity and radial diffusivity in the corpus callosum, indicating the onset of demyelination processes with healthy aging. These changes were not associated with a concomitant significant difference in the cytosolic diffusivity of the intra-axonal metabolite N-acetylaspartate (p = 0.12), the latter representing a pure measure of intra-axonal integrity. It was concluded that the possible intra-axonal changes associated with normal aging processes are below the detection level of diffusion-weighted magnetic resonance spectroscopy in our experiment (e.g., smaller than 10%) in the age range investigated. Lower axial diffusivity of total creatine was observed in the elderly group (p = 0.058), possibly linked to a dysfunction in the energy metabolism associated with a deficit in myelin synthesis

The influence of cystathionine on neurochemical quantification in brain tumor in vivo magnetic resonance spectroscopy

International audiencePurpose: To evaluate the ability of the PRESS sequence (TE = 97 ms, optimized for 2-hydroxyglutarate detection) to detect cystathionine in gliomas and the effect of the omission of cystathionine on the quantification of the full neurochemical profile.Methods: Twenty-three subjects with a glioma were retrospectively included based on the availability of both MEGA-PRESS and PRESS acquisitions at 3T, and the presence of the cystathionine signal in the edited MR spectrum. In eight subjects, the PRESS acquisition was performed also in normal tissue. Metabolite quantification was performed using LCModel and simulated basis sets. The LCModel analysis for the PRESS data was performed with and without cystathionine.Results: All subjects with glioma had detectable cystathionine levels >1 mM with Cramér-Rao lower bounds (CRLB) <15%. The mean cystathionine concentrations were 3.49 ± 1.17 mM for MEGA-PRESS and 2.20 ± 0.80 mM for PRESS data. Cystathionine concentrations showed a significant correlation between the two MRS methods (r = 0.58, p = .004), and it was not detectable in normal tissue. Using PRESS, 19 metabolites were quantified with CRLB <50% for more than half of the subjects. The metabolites that were significantly (p < .0028) and mostly affected by the omission of cystathionine were aspartate, betaine, citrate, γ-aminobutyric acid (GABA), and serine.Conclusions: Cystathionine was detectable by PRESS in all the selected gliomas, while it was not detectable in normal tissue. The omission from the spectral analysis of cystathionine led to severe biases in the quantification of other neurochemicals that may play key roles in cancer metabolism

In vivo diffusion-weighted MRS using semi-LASER in the human brain at 3 T: methodological aspects and clinical feasibility

Diffusion-weighted (DW-) MRS investigates non-invasively microstructural properties of tissue by probing metabolite diffusion in vivo. Despite the growing interest in DW-MRS for clinical applications, little has been published on the reproducibility of this technique. In this study, we explored the optimization of a single-voxel DW-semi-LASER sequence for clinical applications at 3 T, and evaluated the reproducibility of the method under different experimental conditions. DW-MRS measurements were carried out in 10 healthy participants and repeated across three sessions. Metabolite apparent diffusion coefficients (ADCs) were calculated from mono-exponential fits (ADCexp) up to b = 3300 s/mm2, and from the diffusional kurtosis approach (ADCK) up to b = 7300 s/mm2. The inter-subject variabilities of ADCs of N-acetylaspartate + N-acetylaspartylglutamate (tNAA), creatine + phosphocreatine, choline containing compounds, and myo-inositol were calculated in the posterior cingulate cortex (PCC) and in the corona radiata (CR). We explored the effect of physiological motion on the DW-MRS signal and the importance of cardiac gating and peak thresholding to account for signal amplitude fluctuations. Additionally, we investigated the dependence of the intra-subject variability on the acquisition scheme using a bootstrapping resampling method. Coefficients of variation were lower in PCC than CR, likely due to the different sensitivities to motion artifacts of the two regions. Finally, we computed coefficients of repeatability for ADCexp and performed power calculations needed for designing clinical studies. The power calculation for ADCexp of tNAA showed that in the PCC seven subjects per group are sufficient to detect a difference of 5% between two groups with an acquisition time of 4 min, suggesting that ADCexp of tNAA is a suitable marker for disease-related intracellular alteration even in small case–control studies. In the CR, further work is needed to evaluate the voxel size and location that minimize the motion artifacts and variability of the ADC measurements

Diffusion-weighted MR Spectroscopy (DW-MRS) is sensitive to LPS-induced changes in human glial morphometry: a preliminary study

Background Low-dose lipopolysaccharide (LPS) is a well-established experimental method for inducing systemic inflammation and shown by microscopy to activate microglia in rodents. Currently, techniques for in-vivo imaging of glia in humans are limited to TSPO (Translocator protein) PET, which is expensive, methodologically challenging, and has poor cellular specificity. Diffusion-weighted magnetic resonance spectroscopy (DW-MRS) sensitizes MR spectra to diffusion of intracellular metabolites, potentially providing cell-specific information about cellular morphology. In this preliminary study, we applied DW-MRS to measure changes in the apparent diffusion coefficients (ADC) of glial and neuronal metabolites to healthy participants who underwent an LPS administration protocol. We hypothesized that the ADC of glial metabolites will be selectively modulated by LPS-induced glial activation. Methods Seven healthy male volunteers, (mean 25.3 ± 5.9 years) were each tested in two separate sessions once after LPS (1 ng/Kg intravenously) and once after placebo (saline). Physiological responses were monitored during each session and serial blood samples and Profile of Mood States (POMS) completed to quantify white blood cell (WBC), cytokine and mood responses. DW-MRS data were acquired 5-5½ hours after injection from two brain regions: grey matter in the left thalamus, and frontal white matter. Results Body temperature, heart rate, WBC and inflammatory cytokines were significantly higher in the LPS compared to the placebo condition (p < 0.001). The ADC of the glial metabolite choline (tCho) was also significantly increased after LPS administration compared to placebo (p = 0.008) in the thalamus which scaled with LPS-induced changes in POMS total and negative mood (Adj R2 = 0.83; p = 0.004). Conclusions DW-MRS may be a powerful new tool sensitive to glial cytomorphological changes in grey matter induced by systemic inflammation

Multiparametric characterization of white matter alterations in early stage Huntington disease

International audienceHuntington's disease (HD) is a monogenic, fully penetrant neurodegenerative disorder. Widespread white matter damage affects the brain of patients with HD at very early stages of the disease. Fixel-based analysis (FBA) is a novel method to investigate the contribution of individual crossing fibers to the white matter damage and to detect possible alterations in both fiber density and fiber-bundle morphology. Diffusion-weighted magnetic resonance spectroscopy (DW-MRS), on the other hand, quantifies the motion of brain metabolites in vivo, thus enabling the investigation of microstructural alteration of specific cell populations. The aim of this study was to identify novel specific microstructural imaging markers of white matter degeneration in HD, by combining FBA and DW-MRS. Twenty patients at an early stage of HD and 20 healthy controls were recruited in a monocentric study. Using diffusion imaging we observed alterations to the brain microstructure and their morphology in patients with HD. Furthermore, FBA revealed specific fiber populations that were affected by the disease. Moreover, the mean diffusivity of the intra-axonal metabolite N-acetylaspartate, co-measured with N-acetylaspartylglutamate (tNAA), was significantly reduced in the corpus callosum of patients compared to controls. FBA and DW-MRS of tNAA provided more specific information about the biological mechanisms underlying HD and showed promise for early investigation of white matter degeneration in HD