Purpose

The human cerebellum plays an important role in the functional activity of the cerebrum, ranging from motor to cognitive systems given its relaying role between the spinal cord and cerebrum. The cerebellum poses many challenges to Magnetic Resonance Spectroscopic Imaging (MRSI) due to its caudal location, susceptibility to physiological artifacts, and partial volume artifacts resulting from its complex anatomical structure. Thus, in the present study, we propose a high-resolution MRSI acquisition scheme for the cerebellum.

Methods

A zoom or reduced field of view (rFOV) metabolite-cycled MRSI acquisition at 3 Tesla, with a grid of 48 × 48, was developed to achieve a nominal resolution of 62.5 μL. Single-slice rFOV MRSI data were acquired from the cerebellum of 5 healthy subjects with a nominal resolution of 2.5 × 2.5 × 10 mm³ in 9.6 min. Spectra were quantified using the LCModel package. A spatially unbiased atlas template of the cerebellum was used to analyze metabolite distributions in the cerebellum.

Results

The superior quality of the achieved spectra-enabled generation of high-resolution metabolic maps of total N-acetylaspartate, total Creatine (tCr), total Choline (tCho), glutamate+glutamine, and myo-inositol, with Cramér-Rao lower bounds below 50%. A template-based regions of interest (ROI) analysis resulted in spatially dependent metabolite distributions in 9 ROIs. The group-averaged high-resolution metabolite maps across subjects increased the contrast-to-noise ratio between cerebellum regions.

Conclusion

These findings indicate that very high-resolution metabolite probing of the cerebellum is feasible using rFOV or zoomed MRSI at 3 Tesla.

Water-suppressed MRS acquisition techniques have been the standard MRS approach used in research and for clinical scanning to date. The acquisition of a non-water-suppressed MRS spectrum is used for artefact correction, reconstruction of phased-array coil data and metabolite quantification. Here, a two-scan metabolite-cycling magnetic resonance spectroscopic imaging (MRSI) scheme that does not use water suppression is demonstrated and evaluated. Specifically, the feasibility of acquiring and quantifying short-echo (TE  = 14 ms), two-dimensional stimulated echo acquisition mode (STEAM) MRSI spectra in the motor cortex is demonstrated on a 3 T MRI system. The increase in measurement time from the metabolite-cycling is counterbalanced by a time-efficient concentric ring k-space trajectory. To validate the technique, water-suppressed MRSI acquisitions were also performed for comparison. The proposed non-water-suppressed metabolite-cycling MRSI technique was tested for detection and correction of resonance frequency drifts due to subject motion and/or hardware instability, and the feasibility of high-resolution metabolic mapping over a whole brain slice was assessed. Our results show that the metabolite spectra and estimated concentrations are in agreement between non-water-suppressed and water-suppressed techniques. The achieved spectral quality, signal-to-noise ratio (SNR) > 20 and linewidth <7 Hz allowed reliable metabolic mapping of five major brain metabolites in the motor cortex with an in-plane resolution of 10 × 10 mm2 in 8 min and with a Cramér-Rao lower bound of less than 20% using LCModel analysis. In addition, the high SNR of the water peak of the non-water-suppressed technique enabled voxel-wise single-scan frequency, phase and eddy current correction. These findings demonstrate that our non-water-suppressed metabolite-cycling MRSI technique can perform robustly on 3 T MRI systems and within a clinically feasible acquisition time.

Magnetic resonance spectroscopic imaging (MRSI) is a promising technique in both experimental and clinical settings. However, to date, MRSI has been hampered by prohibitively long acquisition times and artifacts caused by subject motion and hardware-related frequency drift. In the present study, we demonstrate that density weighted concentric ring trajectory (DW-CRT) k-space sampling in combination with semi-LASER excitation and metabolite-cycling enables high-resolution MRSI data to be rapidly acquired at 3 Tesla. Single-slice full-intensity MRSI data (short echo time (TE) semi-LASER TE = 32 ms) were acquired from 6 healthy volunteers with an in-plane resolution of 5 × 5 mm in 13 min 30 sec using this approach. Using LCModel analysis, we found that the acquired spectra allowed for the mapping of total N-acetylaspartate (median Cramer-Rao Lower Bound [CRLB] = 3%), glutamate+glutamine (8%), and glutathione (13%). In addition, we demonstrate potential clinical utility of this technique by optimizing the TE to detect 2-hydroxyglutarate (long TE semi-LASER, TE = 110 ms), to produce relevant high-resolution metabolite maps of grade III IDH-mutant oligodendroglioma in a single patient. This study demonstrates the potential utility of MRSI in the clinical setting at 3 Tesla.

It has been shown that density-weighted (DW) k-space sampling with spiral and conventional phase encoding trajectories reduces spatial side lobes in magnetic resonance spectroscopic imaging (MRSI). In this study, we propose a new concentric ring trajectory (CRT) for DW-MRSI that samples k-space with a density that is proportional to a spatial, isotropic Hanning window. The properties of two different DW-CRTs were compared against a radially equidistant (RE) CRT and an echo-planar spectroscopic imaging (EPSI) trajectory in simulations, phantoms and in vivo experiments. These experiments, conducted at 7 T with a fixed nominal voxel size and matched acquisition times, revealed that the two DW-CRT designs improved the shape of the spatial response function by suppressing side lobes, also resulting in improved signal-to-noise ratio (SNR). High-quality spectra were acquired for all trajectories from a specific region of interest in the motor cortex with an in-plane resolution of 7.5 × 7.5 mm2 in 8 min 3 s. Due to hardware limitations, high-spatial-resolution spectra with an in-plane resolution of 5 × 5 mm2 and an acquisition time of 12 min 48 s were acquired only for the RE and one of the DW-CRT trajectories and not for EPSI. For all phantom and in vivo experiments, DW-CRTs resulted in the highest SNR. The achieved in vivo spectral quality of the DW-CRT method allowed for reliable metabolic mapping of eight metabolites including N-acetylaspartylglutamate, γ-aminobutyric acid and glutathione with Cramér-Rao lower bounds below 50%, using an LCModel analysis. Finally, high-quality metabolic mapping of a whole brain slice using DW-CRT was achieved with a high in-plane resolution of 5 × 5 mm2 in a healthy subject. These findings demonstrate that our DW-CRT MRSI technique can perform robustly on MRI systems and within a clinically feasible acquisition time.