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A new sequence for single-voxel diffusion-weighted 1H MRS (DWS), named DW-SPECIAL, is proposed to improve the detection and subsequent estimation of the diffusion properties of strongly J-coupled metabolites. It combines the semi-adiabatic SPECIAL sequence with a stimulated echo (STE) diffusion block. Acquisitions with DW-SPECIAL and STE-LASER, the current gold-standard for rodent DWS experiments at high fields, were performed at 14.1T on phantoms and in vivo on the rat brain. The apparent diffusion coefficient and intra-stick diffusivity (Callaghan's model) were fitted and compared between the sequences for glutamate, glutamine (Gln), myo-inositol, taurine, total N-acetylaspartate, total choline, total creatine and the macromolecules. The shorter echo time achieved with DW-SPECIAL (18 ms against 33 ms with STE-LASER) substantially limited the metabolites' signal loss caused by J-evolution. In addition, DW-SPECIAL preserved the main advantages of STE-LASER: absence of cross-terms, diffusion time during a STE and limited sensitivity to B1 inhomogeneities. In vivo, compared to STE-LASER, DW-SPECIAL yielded the same spectral quality and reduced the Cramer Rao Lower Bounds (CRLB) for J-coupled metabolites, irrespective of the b-value. DW-SPECIAL also reduced the standard deviation of the metabolites' diffusion estimates based on individual animal fitting without loss of accuracy compared to the fit on the averaged decay. We conclude that due to its reduced echo time, DW-SPECIAL can serve as an alternative to STE-LASER when strongly J-coupled metabolites like Gln are investigated, thereby extending the range of accessible metabolites in the context of DWS acquisitions., Comment: Submitted to Magnetic Resonance in Medecine

It was demonstrated that nonpersistent radicals can be generated in frozen solutions of metabolites such as pyruvate by irradiation with ultraviolet (UV) light, enabling radical-free dissolution DNP. Although pyruvate is endogenous, an excess of additional pyruvate may perturb metabolic processes, making it potentially unsuitable as a polarizing agent when studying fatty acids or carbohydrate metabolism. Therefore, the aim of the study was to characterize solutions containing endogenously-occurring alternatives to pyruvate as UV-induced nonpersistent radical precursors for in vivo hyperpolarized MRI. The metabolites alpha-ketovalerate (AKV) and alpha-ketobutyrate (AKB) are analogues of pyruvate and were chosen as potential radical precursors. Sample formulations containing AKV and AKB were studied with UV-visible spectroscopy, irradiated with UV light, and their nonpersistent radical yields were quantified with ESR and compared to pyruvate. The addition of 13C labeled substrates to the sample matrix altered the radical yield of the precursors. Using AKB increased the 13C-labeled glucose liquid state polarization to 16.3 +/- 1.3% compared with 13.3 +/- 1.5% obtained with pyruvate, and 8.9 +/- 2.1% with AKV. For [1-13C]butyric acid, polarization levels of 12.1 +/- 1.1% for AKV and 12.9 +/- 1.7% for AKB were achieved. Hyperpolarized [1-13C]butyrate metabolism in the heart revealed label incorporation into [1-13C]acetylcarnitine, [1-13C]acetoacetate, [1-13C]butyrylcarnitine, [5-13C]glutamate and [5-13C]citrate. This study demonstrates the potential of AKV and AKB as endogenous polarizing agents for in vivo radical-free hyperpolarized MRI. UV-induced, nonpersistent radicals generated in endogenous metabolites enable high polarization without requiring radical filtration, thus simplifying the quality-control tests in clinical applications., Comment: 38 pages, 5 Tables, 8 Figures, Submitted to NMR in Biomedicine

Resting state functional MRI (rs-fMRI) is a widespread and powerful tool for investigating functional connectivity and brain disorders. However, functional connectivity analysis can be seriously affected by random and structured noise from non-neural sources such as physiology. Thus, it is essential to first reduce thermal noise and then correctly identify and remove non-neural artefacts from rs-fMRI signals through optimized data processing methods. However, existing tools that correct for these effects have been developed for human brain and are not readily transposable to rat data. Therefore, the aim of the present study was to establish a data processing pipeline that can robustly remove random and structured noise from rat rs-fMRI data. It includes a novel denoising approach based on the Marchenko-Pastur Principle Component Analysis (MP-PCA) method, FMRIB's ICA-based Xnoiseifier (FIX) for automatic artefact classification and cleaning, and global signal regression. Our results show that: I) MP-PCA denoising substantially improves the temporal signal-to-noise ratio; II) the pre-trained FIX classifier achieves a high accuracy in artefact classification; III) both artefact cleaning and global signal regression are essential steps in minimizing the within-group variability in control animals and identifying functional connectivity changes in a rat model of sporadic Alzheimer's disease, as compared to controls., Comment: 25 pages, 11 figures

Balanced steady-state free precession (bSSFP) can be used as an alternative to gradient-echo (GE) EPI for BOLD functional MRI when image distortions and signal drop-outs are severe such as at ultra-high field. However, 3D-bSSFP acquisitions have distinct drawbacks on either human or animal MR systems. On clinical scanners, 3D imaging is suboptimal for localized fMRI applications, and also results in distortions, blurring, and increased sensitivity to motion or physiological noise. On pre-clinical systems, 3D acquisitions have low temporal resolution due to limited acceleration options, while single slice offers insufficient coverage. The aim of the present study was to implement a multi-slice bSSFP acquisition with Cartesian read-out to obtain non-distorted BOLD fMRI activation maps in the human and rat brain at ultra-high field. We show that the bSSFP signal characteristics are preserved in a new pseudo-steady-state. In the human brain at 7 Tesla, we demonstrate that both task- and resting-state fMRI can be performed with 2D-bSSFP, with a temporal SNR that matches that of 3D-bSSFP, resulting in - at least - equal performance. In the rat brain at 14 Tesla, we show that the multi-slice bSSFP protocol has similar sensitivity to gradient-echo EPI for task fMRI, while benefitting from much reduced distortions and drop-outs. The advantages of passband bSSFP at 14 Tesla in comparison with GE-EPI are expected to be even more marked for mouse fMRI.

We propose a novel compressed sensing technique to accelerate the magnetic resonance imaging (MRI) acquisition process. The method, coined spread spectrum MRI or simply s2MRI, consists of pre-modulating the signal of interest by a linear chirp before random k-space under-sampling, and then reconstructing the signal with non-linear algorithms that promote sparsity. The effectiveness of the procedure is theoretically underpinned by the optimization of the coherence between the sparsity and sensing bases. The proposed technique is thoroughly studied by means of numerical simulations, as well as phantom and in vivo experiments on a 7T scanner. Our results suggest that s2MRI performs better than state-of-the-art variable density k-space under-sampling approaches