Investigating the regional effect of the chemical shift displacement artefact on the J-modulated lactate signal at ultra high-field.

The present work aims to show the applicability of an analytical model for the optimisation of the STEAM sequence timing parameters for lactate detection at ultra high-field. The effects of the chemical shift displacement artefact on the J-modulated signal for a weakly-coupled spin system were considered in the three applied directions of field gradients and the product operator formalism was used to obtain expressions for the signal modulation in each compartment of the excited volume. The validity of this model was demonstrated experimentally at 7 T in a phantom and acquisitions with optimised parameters were performed on a healthy volunteer. The spectra acquired with TE = 144 ms with the optimised mixing time and TE = 288 ms showed easily detectable lactate peaks in the normal human brain. Additionally, the acquisition with the longer TE resulted in a spectrum with less lipid/macromolecular contamination. The simulations shown here demonstrated that the proposed analytical model is suitable for correctly predicting the resulting lactate signal. With the optimised parameters, it was possible to use a simple sequence with sufficient signal-to-noise ratio to reliably distinguish lactate from overlapping resonances in a healthy brain.

Measurement of brain lactate during visual stimulation using a long TE semi-LASER sequence at 7 T.

Estimation of metabolic changes during neuronal activation represents a challenge for in vivo MRS, especially for metabolites with low concentration and signal overlap, such as lactate. In this work, we aimed to evaluate the feasibility of detecting lactate during brain activation using a long TE (144 ms) semi-LASER sequence at 7 T. 1H spectra were acquired on healthy volunteers ( N=6 ) during a paradigm with 15 min of visual stimulation. Outer-volume signals were further attenuated by the use of saturation slabs, and macromolecular signals in the vicinity of the inverted lactate peak were individually fitted with simulated Lorentzian peaks. All spectra were free of artefacts and highly reproducible across subjects. Lactate was accurately quantified with an average Cramér-Rao lower bound of 8%. Statistically significant ( P<0.05 , one-tailed t -test) increases in lactate ( ∼ 10%) and glutamate ( ∼ 3%) levels during stimulation were detected in the visual cortex. Lactate and glutamate changes were consistent with previous measurements. We demonstrated that quantification of a clear and non-contaminated lactate peak obtained with a long TE sequence has the potential of improving the accuracy of functional MRS studies targeting non-oxidative reaction pathways.

Glutathione and glutamate in schizophrenia: a 7T MRS study.

In schizophrenia, abnormal neural metabolite concentrations may arise from cortical damage following neuroinflammatory processes implicated in acute episodes. Inflammation is associated with increased glutamate, whereas the antioxidant glutathione may protect against inflammation-induced oxidative stress. We hypothesized that patients with stable schizophrenia would exhibit a reduction in glutathione, glutamate, and/or glutamine in the cerebral cortex, consistent with a post-inflammatory response, and that this reduction would be most marked in patients with "residual schizophrenia", in whom an early stage with positive psychotic symptoms has progressed to a late stage characterized by long-term negative symptoms and impairments. We recruited 28 patients with stable schizophrenia and 45 healthy participants matched for age, gender, and parental socio-economic status. We measured glutathione, glutamate and glutamine concentrations in the anterior cingulate cortex (ACC), left insula, and visual cortex using 7T proton magnetic resonance spectroscopy (MRS). Glutathione and glutamate were significantly correlated in all three voxels. Glutamine concentrations across the three voxels were significantly correlated with each other. Principal components analysis (PCA) produced three clear components: an ACC glutathione-glutamate component; an insula-visual glutathione-glutamate component; and a glutamine component. Patients with stable schizophrenia had significantly lower scores on the ACC glutathione-glutamate component, an effect almost entirely leveraged by the sub-group of patients with residual schizophrenia. All three metabolite concentration values in the ACC were significantly reduced in this group. These findings are consistent with the hypothesis that excitotoxicity during the acute phase of illness leads to reduced glutathione and glutamate in the residual phase of the illness.

Repeatability and reproducibility of multiparametric magnetic resonance imaging of the liver.

As the burden of liver disease reaches epidemic levels, there is a high unmet medical need to develop robust, accurate and reproducible non-invasive methods to quantify liver tissue characteristics for use in clinical development and ultimately in clinical practice. This prospective cross-sectional study systematically examines the repeatability and reproducibility of iron-corrected T1 (cT1), T2*, and hepatic proton density fat fraction (PDFF) quantification with multiparametric MRI across different field strengths, scanner manufacturers and models. 61 adult participants with mixed liver disease aetiology and those without any history of liver disease underwent multiparametric MRI on combinations of 5 scanner models from two manufacturers (Siemens and Philips) at different field strengths (1.5T and 3T). We report high repeatability and reproducibility across different field strengths, manufacturers, and scanner models in standardized cT1 (repeatability CoV: 1.7%, bias -7.5ms, 95% LoA of -53.6 ms to 38.5 ms; reproducibility CoV 3.3%, bias 6.5 ms, 95% LoA of -76.3 to 89.2 ms) and T2* (repeatability CoV: 5.5%, bias -0.18 ms, 95% LoA -5.41 to 5.05 ms; reproducibility CoV 6.6%, bias -1.7 ms, 95% LoA -6.61 to 3.15 ms) in human measurements. PDFF repeatability (0.8%) and reproducibility (0.75%) coefficients showed high precision of this metric. Similar precision was observed in phantom measurements. Inspection of the ICC model indicated that most of the variance in cT1 could be accounted for by study participants (ICC = 0.91), with minimal contribution from technical differences. We demonstrate that multiparametric MRI is a non-invasive, repeatable and reproducible method for quantifying liver tissue characteristics across manufacturers (Philips and Siemens) and field strengths (1.5T and 3T).