Apparent diffusion coefficients of 31P metabolites in the human calf muscle at 7 T.

PURPOSE: In this study, we aimed to measure the apparent diffusion coefficients (ADCs) of major phosphorous metabolites in the human calf muscle at 7 T with a diffusion-weighted (DW)-STEAM sequence. METHODS: A DW-STEAM sequence with bipolar gradients was implemented at 7 T, and DW MR spectra were acquired in three orthogonal directions in the human calf muscle of six healthy volunteers (TE/TM/TR = 15 ms/750 ms/5 s) at three b-values (0, 800, and 1200 s/mm2). Frequency and phase alignments were applied prior to spectral averaging. Averaged DW MR spectra were analyzed with LCModel, and ADCs of 31P metabolites were estimated. RESULTS: Four metabolites (phosphocreatine (PCr), adenosine triphosphate (ATP), inorganic phosphate (Pi) and glycerol phosphorylcholine (GPC)) were quantified at all b-values with mean CRLBs below 10%. The ADC values of PCr, ATP, Pi, and GPC were (0.24 ± 0.02, 0.15 ± 0.04, 0.43 ± 0.14, 0.40 ± 0.09) × 10-3 mm2/s, respectively. CONCLUSION: The ADCs of four 31P metabolites were successfully measured in the human calf muscle at 7 T, among which those of ATP, Pi and GPC were reported for the first time in humans. This study paves the way to investigate 31P metabolite diffusion properties in health and disease on the clinical MR scanner.

Assessing potential correlation between T2 relaxation and diffusion of lactate in the mouse brain.

PURPOSE: While diffusion and T2 relaxation are intertwined, little or no correlation exists between diffusion and T2 relaxation of intracellular metabolites in the rodent brain, as measured by diffusion-weighted MRS at different TEs. However, situation might be different for lactate, since it is present in both extracellular and intracellular spaces, which exhibit different diffusion properties and may also exhibit different T2 . Such a TE dependence would be crucial to account for when interpreting or modeling lactate diffusion. Here we propose to take advantage of a new diffusion sequence, where J-modulation of lactate is canceled even at long TE, thus retaining excellent signal, to assess potential T2 dependence on diffusion of lactate in the mouse brain. METHODS: Using a frequency-selective diffusion-weighted spin-echo sequence that removes J-modulation at 1.3 ppm, thus preserving lactate signal even at long TE, we investigate the effect of TE between 50.9 and 110.9 ms (while keeping diffusion time constant) on apparent diffusivity and kurtosis in the mouse brain. RESULTS: Regardless of the metabolites, no difference appears for the diffusion-weighted signal attenuation with increasing TE. For lactate, apparent diffusivity and kurtosis remain unchanged as TE increases. CONCLUSION: No significant TE dependence of diffusivity and kurtosis is measured for lactate in the 50-110 ms TE range, confirming that potential T2 effects can be ignored when interpreting or modeling lactate diffusion.

Measuring large lipid droplet sizes by probing restricted lipid diffusion effects with diffusion-weighted MRS at 3T.

PURPOSE: The in vivo probing of restricted diffusion effects in large lipid droplets on a clinical MR scanner remains a major challenge due to the need for high b-values and long diffusion times. This work proposes a methodology to probe mean lipid droplet sizes using diffusion-weighted MRS (DW-MRS) at 3T. METHODS: An analytical expression for restricted diffusion was used. Simulations were performed to evaluate the noise performance and the influence of particle size distribution. To validate the method, oil-in-water emulsions were prepared and examined using DW-MRS, laser deflection and light microscopy. The tibia bone marrow was scanned in volunteers to test the method repeatability and characterize microstructural differences at different locations. RESULTS: The simulations showed accurate and precise droplet size estimation when a sufficient SNR is reached with minor dependence on the size distribution. In phantoms, a good correlation between the measured droplet sizes by DW-MRS and by laser deflection (R2 = 0.98; P = 0.01) and microscopy (R2 = 0.99; P < 0.01) measurements was obtained. A mean coefficient of variation of 11.5 % was found for the lipid droplet diameter in vivo. The average diameter was smaller at a proximal (50.1 ± 7.3 µm) compared with a distal tibia location (61.1 ± 6.8 µm) (P < 0.01). CONCLUSION: The presented methods were able to probe restricted diffusion effects in lipid droplets using DW-MRS and to estimate lipid droplet size. The methodology was validated using phantoms and the in vivo feasibility in bone marrow was shown based on a good repeatability and findings in agreement with literature.

Using spectrally-selective radiofrequency pulses to enhance lactate signal for diffusion-weighted MRS measurements in vivo.

Measurement of lactate diffusion properties using diffusion-weighted magnetic resonance spectroscopy in vivo may allow elucidating brain lactate cellular compartmentation, which would be of great importance for neuroscience. However, measuring lactate signal is complicated by low signal-to-noise ratio due to low lactate concentration and J-modulation of its 1.3 ppm peak. In this work, we assess the benefits of using a diffusion-weighting spin echo block and spectrally selective refocusing pulses to suppress the effect of J-coupling on the 1.3 ppm lactate resonance, by not refocusing its coupling partner at 4.1 ppm. Two different kinds of spectrally selective pulses, either polychromatic or single-band, are evaluated in the mouse brain at 11.7 T. Almost complete suppression of J-modulation is shown, resulting in an approximately two-fold signal increase as compared to a reference STE-LASER sequence (for the specific diffusion times used in this work). Repeated measurements confirm that lactate diffusion-weighted signal attenuation is measured with an approximately two-fold precision.

Longitudinal MR spectroscopy of neurodegeneration in multiple sclerosis with diffusion of the intra-axonal constituent N-acetylaspartate.

Multiple sclerosis (MS) is a pathologically complex CNS disease: inflammation, demyelination, and neuroaxonal degeneration occur concurrently and may depend on one another. Current therapies are aimed at the immune-mediated, inflammatory destruction of myelin, whereas axonal degeneration is ongoing and not specifically targeted. Diffusion-weighted magnetic resonance spectroscopy can measure the diffusivity of metabolites in vivo, such as the axonal/neuronal constituent N-acetylaspartate, allowing compartment-specific assessment of disease-related changes. Previously, we found significantly lower N-acetylaspartate diffusivity in people with MS compared to healthy controls (Wood et al., 2012) suggesting that this technique can measure axonal degeneration and could be useful in developing neuroprotective agents. In this longitudinal study, we found that N-acetylaspartate diffusivity decreased by 8.3% (p < 0.05) over 6 months in participants who were experiencing clinical or MRI evidence of inflammatory activity (n = 13), whereas there was no significant change in N-acetylaspartate diffusivity in the context of clinical and radiological stability (n = 6). As N-acetylaspartate diffusivity measurements are thought to more specifically reflect the intra-axonal space, these data suggest that N-acetylaspartate diffusivity can report on axonal health on the background of multiple pathological processes in MS, both cross-sectionally and longitudinally.