title: Reproducibility and optimization of in vivo human diffusion-weighted MRS of the corpus callosum at 3 T and 7 T.
abstract: 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.
authors.affiliation: Translational Neuroradiology Unit (NINDS), National Institutes of Health, Bethesda, MD, USA.|Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Emily T
authors.initials: ET
authors.lastname: Wood
authors.affiliation: C. J. Gorter Center for High Field MRI, Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Ayse Ece
authors.initials: AE
authors.lastname: Ercan
authors.affiliation: Institut du Cerveau et de la Moelle épinière - ICM, Centre for NeuroImaging Research - CENIR, Paris, France.|Sorbonne Universités, UPMC Paris 06, Inserm UMR S 1127, CNRS UMR 7225, Paris, France.
authors.forename: Francesca
authors.initials: F
authors.lastname: Branzoli
authors.affiliation: C. J. Gorter Center for High Field MRI, Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Andrew
authors.initials: A
authors.lastname: Webb
authors.affiliation: Translational Neuroradiology Unit (NINDS), National Institutes of Health, Bethesda, MD, USA.
authors.forename: Pascal
authors.initials: P
authors.lastname: Sati
authors.affiliation: Translational Neuroradiology Unit (NINDS), National Institutes of Health, Bethesda, MD, USA.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Reich
authors.affiliation: C. J. Gorter Center for High Field MRI, Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Itamar
authors.initials: I
authors.lastname: Ronen
mesh_terms: D000328:Adult; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000032:analysis; D003337:Corpus Callosum / Q000033:anatomy & histology* / Q000737:chemistry*; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007089:Image Enhancement / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D057054:Molecular Imaging / Q000379:methods; D011829:Radiation Dosage; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014018:Tissue Distribution
chemical_list: D001224:Aspartic Acid; C000179:N-acetylaspartate
keywords: diffusion-weighted MRS; inter-subject variability; intra-subject variability; power calculations; white matter