Author(s): Wilson, Neil | Advisor(s): Thomas, Michael A | Abstract: Magnetic resonance spectroscopy (MRS) is used to obtain localized biochemical information noninvasively based on the principles of nuclear magnetic resonance. 1H in vivo spectra consist of a large number of metabolites in a relatively small spectral range, making identification difficult. Multidimensional MRS incorporates a variable evolution period to enhance the information content and increase spectral dispersion. Recently, multidimensional MRS has been combined with echo planar gradient readout techniques to produce multidimensional magnetic resonance spectroscopic imaging (MRSI). Despite the fast imaging acquisitions, these scans are long for in vivo studies, so more efficiently sampling strategies were investigated. The first strategy consisted of nonuniform undersampling (NUS) of the volume spanned by the phase-encoded spatial dimensions and the indirect spectral dimension in 5 dimensional (3 spatial + 2 spectral) MRSI. Nonlinear reconstruction was performed according to the theory of compressed sensing (CS) using the split Bregman framework. Formulations that promoted sparsity of the data and its spatial finite differences in 5D J-resolved brain studies were applied, and results were compared favorably to a time-equivalent single slice J-resolved scan. In 5D correlated MRSI calf studies, reconstruction minimized the group sparsity of nearby points, which produced much better results than reconstruction that minimized the overall sparsity of the data.The second strategy used concentrically circular k-space trajectories instead of the conventional rectilinear ones. Concentric circles have the advantages of reduced hardware demands, higher achievable spectral bandwidth, less sensitivity to motion, and faster k-space coverage. Single slice 4D (2 spatial + 2 spectral) correlated MRSI using concentrically circular trajectories was compared to a rectilinear counterpart and showed similar data quality. An improved single slice J-resolved MRSI sequence was presented. The new sequence used adiabatic refocusing pulses that are less sensitive to RF field inhomogeneity and result in reduced chemical shift displacement error compared to conventional pulses. Comparison was made to the nonadiabatic sequence with the same echo time as well as with its minimum echo time.
Deuterium metabolic imaging (DMI) has brought about a renewed interest in the application of 2 H-labeled substrates to map metabolism in vivo, yet deuterium spectroscopy remains challenging. We have shown that metabolism of deuterium-labeled glucose can be observed in the proton spectrum through a reduction in signal of downstream metabolites in a technique called quantitative exchange label turnover MRS (qMRS). Here, we show that prior knowledge fitting that includes unlabeled as well as deuterium-labeled forms of glutamate can be used to map neural metabolism reliably with qMRS.
Four-dimensional (4D) Magnetic Resonance Spectroscopic Imaging (MRSI) data combining 2 spatial and 2 spectral dimensions provides valuable biochemical information in vivo; however, its 20–40 min acquisition time is too long to be used for a clinical protocol. Data acquisition can be accelerated by non-uniformly under-sampling (NUS) the ky− t1 plane, but this causes artifacts in the spatial-spectral domain that must be removed by non-linear, iterative reconstruction. Previous work has demonstrated the feasibility of accelerating 4D MRSI data acquisition through NUS and iterative reconstruction using Compressed Sensing (CS), Total Variation (TV), and Maximum Entropy (MaxEnt) reconstruction. Group Sparse (GS) reconstruction is a variant of CS that exploits the structural sparsity of transform coefficients to achieve higher acceleration factors than traditional CS. In this article, we derive a solution to the GS reconstruction problem within the Split Bregman iterative framework that uses arbitrary transform grouping patterns of overlapping or non-overlapping groups. The 4D Echo-Planar Correlated Spectroscopic Imaging (EP-COSI) gray matter brain phantom and in vivo brain data are retrospectively under-sampled 2×, 4×, 6×, 8×, and 10___ and reconstructed using CS, TV, MaxEnt, and GS with overlapping or non-overlapping groups. Results show that GS reconstruction with overlapping groups outperformed the other reconstruction methods at each NUS rate for both phantom and in vivo data. These results can potentially reduce the scan time of a 4D EP-COSI brain scan from 40 min to under 5 min in vivo.
Purpose To measure cerebral metabolite levels in perinatally HIV-infected youths and healthy controls using the accelerated five dimensional (5D) echo planar J-resolved spectroscopic imaging (EP-JRESI) sequence, which is capable of obtaining two dimensional (2D) J-resolved spectra from three spatial dimensions (3D). Materials and Methods After acquisition and reconstruction of the 5D EP-JRESI data, T1-weighted MRIs were used to classify brain regions of interest for HIV patients and healthy controls: right frontal white (FW), medial frontal gray (FG), right basal ganglia (BG), right occipital white (OW), and medial occipital gray (OG). From these locations, respective J-resolved and TE-averaged spectra were extracted and fit using two different quantitation methods. The J-resolved spectra were fit using prior knowledge fitting (ProFit) while the TE-averaged spectra were fit using the advanced method for accurate robust and efficient spectral fitting (AMARES). Results Quantitation of the 5D EP-JRESI data using the ProFit algorithm yielded significant metabolic differences in two spatial locations of the perinatally HIV-infected youths compared to controls: elevated NAA/(Cr+Ch) in the FW and elevated Asp/(Cr+Ch) in the BG. Using the TE-averaged data quantified by AMARES, an increase of Glu/(Cr+Ch) was shown in the FW region. A strong negative correlation (r < -0.6) was shown between tCh/(Cr+Ch) quantified using ProFit in the FW and CD4 counts. Also, strong positive correlations (r > 0.6) were shown between Asp/(Cr+Ch) and CD4 counts in the FG and BG. Conclusion The complimentary results using ProFit fitting of J-resolved spectra and AMARES fitting of TE-averaged spectra, which are a subset of the 5D EP-JRESI acquisition, demonstrate an abnormal energy metabolism in the brains of perinatally HIV-infected youths. This may be a result of the HIV pathology and long-term combinational anti-retroviral therapy (cART). Further studies of larger perinatally HIV-infected cohorts are necessary to confirm these findings.
Motivation: NAD+ and tryptophan are important in energy metabolism, DNA repair, mitochondrial function, and aging. Both have recently been observed in brain at 7T, but observation at 3T is more challenging and has not been shown previously. Goal(s): To detect NAD+ and tryptophan at 3T in brain in a clinically feasible scan time less than 5 minutes. Approach: A single slice spectroscopy sequence with spectrally selective excitation was developed and optimized, allowing high sensitivity acquisition. Results: The H2 (9.3 ppm) and H6 (9.1 ppm) peaks of NAD+ and the indole (10.1 ppm) peak of tryptophan are both unambiguously observed in four healthy subjects. Impact: The ability to identify NAD+ and tryptophan at 3T in less than 5 minutes has the potential to significantly enhance the adoption of this method as part of existing neuroimaging protocols.
Purpose Two‐dimensional creatine CEST (2D‐CrCEST), with a slice thickness of 10‐20 mm and temporal resolution (τ Res ) of about 30 seconds, has previously been shown to capture the creatine‐recovery kinetics in healthy controls and in patients with abnormal creatine‐kinase kinetics following the mild plantar flexion exercise. Since the distribution of disease burden may vary across the muscle length for many musculoskeletal disorders, there is a need to increase coverage in the slice‐encoding direction. Here, we demonstrate the feasibility of 3D‐CrCEST with τ Res of about 30 seconds, and propose an improved voxel‐wise ‐calibration approach for CrCEST. Methods The current 7T study with enrollment of 5 volunteers involved collecting the baseline CrCEST imaging for the first 2 minutes, followed by 2 minutes of plantar flexion exercise and then 8 minutes of postexercise CrCEST imaging, to detect the temporal evolution of creatine concentration following exercise. Results Very good repeatability of 3D‐CrCEST findings for activated muscle groups on an intraday and interday basis was established, with coefficient of variance of creatine recovery constants (τ Cr ) being 7%‐15.7%, 7.5%, and 5.8% for lateral gastrocnemius, medial gastrocnemius, and peroneus longus, respectively. We also established a good intraday and interday scan repeatability for 3D‐CrCEST and also showed good correspondence between τ Cr measurements using 2D‐CrCEST and 3D‐CrCEST acquisitions. Conclusion In this study, we demonstrated for the first time the feasibility and the repeatability of the 3D‐CrCEST method in calf muscle with improved correction to measure creatine‐recovery kinetics within a large 3D volume of calf muscle.
