Metabolic voxel‐based analysis of the complete human brain using fast 3D‐MRSI: Proof of concept in multiple sclerosis

Abstract

Purpose Using optimized fast volumic echo planar spectroscopic imaging (3D-EPSI), we aimed to detect local metabolic abnormalities over the complete human brain in multiple sclerosis patients. Materials and methods Weighted mean combination of two 3D-EPSI covering the whole brain acquired at 3T in AC-PC and AC-PC+15° axial planes was performed to obtain high quality metabolite maps for five metabolites: N-acetyl aspartate (NAA), glutamate+glutamine (Glx), choline (Cho), myo-inositol (m-Ins) and creatine+phosphocreatine (tCr). After spatial normalisation, maps from 19 patients suffering from relapsing-remitting multiple sclerosis were compared to 19 matched controls using statistical mapping analyses to determine the topography of metabolic abnormalities. Probabilistic white matter (WM) T2 lesion maps and grey matter (GM) atrophy maps were also generated. Results Two-group ANOVA (SPM8, p<0.005, FDR corrected p<0.05 at the cluster level with age and sex as confounding covariates) comparing Patients and controls matched for age and sex showed clusters of abnormal metabolite levels with i) decreased NAA (around −15%) and Glx (around 20%) predominantly in GM within prefrontal cortices, motor cortices, bilateral thalami and mesial temporal cortices in line with neuronal/neuro-astrocytic dysfunction, ii) increased m-Ins (around +20%) inside WM T2 lesions and in the normal appearing WM of temporal-occipital lobes suggesting glial activation. Conclusion We demonstrated the ability to map non-invasively over the complete brain - from vertex to cerebellum – with a validated sequence, the metabolic abnormalities associated with MS, for characterizing the topography of pathological processes affecting widespread areas of WM and GM and its functional impact.

Methodological consensus on clinical proton MRS of the brain: Review and recommendations

“…This sequence has been reported to sample, on average, 70% of the brain volume, although with instrumentation‐dependent differences. Recent 3T studies using whole‐brain 3D EPSI have been able to achieve an acquisition time of 18 minutes with a TE of 20 ms, which may be acceptable for clinical trials and some specialized clinical assessments . Shorter scan times are feasible using partial‐brain 3D EPSI …”

“…Recent 3T studies using whole-brain 3D EPSI have been able to achieve an acquisition time of 18 minutes with a TE of 20 ms, which may be acceptable for clinical trials and some specialized clinical assessments. 105 Shorter scan times are feasible using partial-brain 3D EPSI. 100,106 An alternative approach for whole-brain MRSI is to combine medium-resolution EPSI encoding (10-mm isotropic) with OVERPRESS localization and automatically prescribed VSS bands.…”

Fast high‐resolution brain metabolite mapping on a clinical 3T MRI by accelerated H‐FID‐MRSI and low‐rank constrained reconstruction

“…for acquiring whole brain MRSI data in 3D, but at the cost of a lower SNR and longer TE. [50][51][52][53][54] Recent developments in FID-MRSI acquisitions at ultra high fields combined with acceleration techniques are particularly promising due to the high SNR and resolution of the resulting metabolite maps. 2,3,[6][7][8][55][56][57] The method presented in this article is an adaptation of the FID-MRSI approach for lower field strength.…”

CEST MRI with distribution‐based analysis for assessment of early stage disease activity in a mouse model of multiple sclerosis: An initial study

“…MI is often considered a marker of astrocytic activation and proliferation . MI levels were found to be higher in the NAWM of relapse‐remitting MS patients, and of patients with clinically isolated syndrome (the diagnosis of those whose MS status cannot be confirmed using standard criteria), compared with healthy subjects. Cho is generally considered a marker of cell turnover and inflammation that has been reported to be elevated prior to the appearance of a Gd‐enhancing lesion .…”