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Original article (peer-reviewed)

Journal Neuroimage
Volume (Issue) 202
Page(s) 116075
Title of proceedings Neuroimage
DOI 10.1016/j.neuroimage.2019.116075

Open Access

Type of Open Access Green OA Embargo (Freely available via Repository after an embargo)


PURPOSE:To demonstrate that oscillating gradient spin-echo sequences can be combined with diffusion-weighted magnetic resonance spectroscopy even on clinical MR systems to study human brain at short diffusion times to provide apparent diffusion coefficients (ADCs) sensitive to a narrower cellular length scale than pulsed gradient spin-echo sequences at long diffusion time. METHODS:Measurements were performed on a 3T MR system using a semiLaser sequence with diffusion-weighting realized by oscillating and pulsed gradient modules, encoding diffusion times <10 ms and >50 ms, respectively. Metabolite-cycling was included to measure metabolites and water simultaneously. The sequence was tested in a phantom and in a parieto-occipital cerebral region of interest with mixed gray/white matter content of 6 subjects. The water reference was used for phase, frequency, and eddy-current correction as well as motion compensation. ADCs were estimated by 1D sequential and 2D simultaneous fitting. RESULTS:Measurements in the phantom established that both sequences yield equal ADCs, independent of diffusion time, as expected for free diffusion. In contrast, on average over multiple metabolites in vivo metabolite diffusion was found to be 1.9 times faster at short (8.3 ms) than at long (155 ms) diffusion times. The difference in ADC was found to be statistically significant for the creatines, cholines, N-acetylaspartate, N-acetylaspartylglutamate, myo-inositol, scyllo-inositol, glutamate, glutamine and taurine. The water ADC was measured to be 1.3 times larger at short than at long diffusion time. CONCLUSION:It is demonstrated that application of oscillating gradients in diffusion-weighted MRS is feasible on clinical MR systems to establish the dependence of ADCs on diffusion times in humans. The initial results largely confirm earlier reports for mice' and rats' brain at short and long diffusion times. ADCs representing diffusion at short and ultra-short diffusion times are of interest to probe cellular or subcellular changes in disease. The presented methodology may thus open the door for investigation of pathophysiological changes in cell-specific microcellular structures in human cohorts.