Optimization of 1H MR spectroscopy methods for large volume acquisition of low concentration downfield resonances at 3T and 7T.

Purpose: This goal of this study was to optimize spectrally selective 1H MRS methods for large volume acquisition of low concentration metabolites with downfield resonances at 7T and 3T, with particular attention paid to detection of nicotinamide adenine dinucleotide (NAD+) and tryptophan. Methods: Spectrally selective excitation was used to avoid magnetization transfer effects with water, and various sinc pulses were compared to a pure-phase E-BURP pulse. Localization using a single slice selective pulse was compared to voxel-based localization that used three orthogonal refocusing pulses, and low bandwidth refocusing pulses were used to take advantage of the chemical shift displacement of water. A technique for water sideband removal was added, and a method of coil channel combination for large volumes was introduced. Results: Proposed methods were compared qualitatively to previously-reported techniques at 7T. Sinc pulses resulted in reduced water signal excitation and improved spectral quality, with a symmetric, low bandwidth-time product pulse performing best. Single slice localization allowed shorter TEs with large volumes, enhancing signal, while low bandwidth slice selective localization greatly reduced the observed water signal. Gradient cycling helped remove water sidebands, and frequency aligning and pruning individual channels narrowed spectral linewidths. High quality brain spectra of NAD+ and tryptophan are shown in four subjects at 3T. Conclusion: Improved spectral quality with higher downfield signal, shorter TE, lower nuisance signal, reduced artifacts, and narrower peaks was realized at 7T. These methodological improvements allowed for previously unachievable detection of NAD+ and tryptophan in human brain at 3T in under five minutes.

Quantification of NAD + T 1 and T 2 relaxation times using downfield 1 H MRS at 7 T in human brain in vivo.

Introduction: The purpose of this study was to use a single-slice spectrally-selective sequence to measure T 1 and T 2 relaxation times of NAD + proton resonances in the downfield 1 H MRS spectrum in human brain at 7 T in vivo and assess the propagation of relaxation time uncertainty in NAD + quantification. Methods: Downfield spectra from 7 healthy volunteers were acquired at multiple echo times in all subjects to measure T 2 relaxation, and saturation recovery data were to measure T 1 relaxation. The downfield acquisition used a spectrally-selective 90° sinc pulse for excitation centered at 9.1 ppm with a bandwidth of 2 ppm, followed by a 180° spatially-selective Shinnar-Le Roux refocusing pulse for localization. For the multiple echo experiment, spectra were collected with echo times ranging from 13 to 33 ms. For the saturation recovery experiment, saturation was performed prior to excitation using the same spectrally-selective sinc pulse as was used for excitation. Saturation delay times (TS) ranged from 100 to 600 ms. Uncertainty propagation analysis was performed analytically and with Monte Carlo simulation. Results: The mean ± standard deviation of T 1 relaxation times of the H2, H6, and H4 protons were 152.7 ± 16.6, 163.6 ± 22.3, and 169.9 ± 11.2 ms, respectively. The mean ± standard deviation of T 2 relaxation times of the H2, H6, and H4 protons were 32.5 ± 7.0, 27.4 ± 5.2, and 38.1 ± 11.7 ms, respectively. The mean R 2 of the H2 and H6 T 1 fits were 0.98. The mean R 2 of the H4 proton T 1 fit was 0.96. The mean R 2 of the T 2 fits of the H2 and H4 proton resonances were 0.98, while the mean R 2 of the T 2 fits of the H4 proton was 0.93. The relative uncertainty in NAD + concentration due to relaxation time uncertainty was 8.5%-11%. Conclusion: Using downfield spectrally-selective spectroscopy with single-slice localization, we found NAD + T 1 and T 2 relaxation times to be approximately 162 ms and 32 ms respectively in the human brain in vivo at 7 T.

Identification of new resonances in downfield 1 H MRS of human calf muscle in vivo: Potentially metabolite precursors for skeletal muscle NAD.

PURPOSE: The purpose of this study was to identify and characterize newly discovered resonances appearing in the downfield proton MR spectrum (DF 1 H MRS) of the human calf muscle in vivo at 7T. METHODS: Downfield 1 H MRS was performed on the calf muscle of five healthy volunteers at 7T. A spectrally selective 90° E-BURP RF pulse with an excitation center frequency at 10.3 ppm and an excitation bandwidth of 2 ppm was used for DF 1 H MRS acquisition. RESULTS: In all participants, we observed new resonances at 9.7, 10.1, 10.3, and 10.9 ppm in the DF 1 H MRS. Phantom experiments at 37°C strongly suggest the new resonance at 9.7 ppm could be from H2-proton of the nicotinamide rings in nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) while the resonance at 10.1 ppm could be attributed to the indole -NH proton of L-tryptophan. We observed that the resonances at 10.1 and 10.9 ppm are significantly suppressed when the water resonance is saturated, indicating that these peaks have either 1 H chemical exchange or cross-relaxation with water. Conversely, the resonances at 9.7 and 10.3 ppm exhibit moderate signal reduction in the presence of water saturation. CONCLUSION: We have identified new proton resonances in vivo in human calf muscle occurring at chemical shifts of 9.7, 10.1, 10.3, and 10.9 ppm. These preliminary results are promising for investigating the role of NR/NMN and L-tryptophan metabolism in understanding the de novo and salvage pathways of NAD+ synthesis in skeletal muscle.

In vivo reproducibility of 3D relayed NOE in the healthy human brain at 7 T.

PURPOSE: Nuclear Overhauser effect (NOE) is based on dipolar cross-relaxation mechanism that enables the indirect detection of aliphatic protons via the water proton signal. This work focuses on determining the reproducibility of NOE magnetization transfer ratio (NOEMTR ) and isolated or relayed NOE (rNOE) contributions to the NOE MRI of the healthy human brain at 7 Tesla (T). METHODS: We optimized the B 1 + $$ {\mathrm{B}}_1^{+} $$ amplitude and length of the saturation pulse by acquiring NOE images with different B 1 + $$ {\mathrm{B}}_1^{+} $$ values with multiple saturation lengths. Repeated NOE MRI measurements were made on five healthy volunteers by using optimized saturation pulse parameters including correction of B0 and B 1 + $$ {\mathrm{B}}_1^{+} $$ inhomogeneities. To isolate the individual contributions from z-spectra, we have fit the NOE z-spectra using multiple Lorentzians and calculated the total contribution from each pool contributing to the overall NOEMTR contrast. RESULTS: We found that a saturation amplitude of 0.72 µT and a length of 3 s provided the highest contrast. We found that the mean NOEMTR value in gray matter (GM) was 26%, and in white matter (WM) was 33.3% across the 3D slab of the brain. The mean rNOE contributions from GM and WM values were 8.9% and 9.6%, which were ∼10% of the corresponding total NOEMTR signal. The intersubject coefficient of variations (CoVs) of NOEMTR from GM and WM were 4.5% and 6.5%, respectively, whereas the CoVs of rNOE were 4.8% and 5.6%, respectively. The intrasubject CoVs of the NOEMTR range was 2.1%-4.2%, and rNOE range was 2.9%-10.5%. CONCLUSION: This work has demonstrated an excellent reproducibility of both inter- and intrasubject NOEMTR and rNOE metrics in healthy human brains at 7 T.

Quantification of cross-relaxation in downfield 1 H MRS at 7 T in human calf muscle.

PURPOSE: The purpose of this study was to characterize the 1 H downfield MR spectrum from 8.0 to 10.0 ppm of human skeletal muscle at 7 T and determine the T1 and cross-relaxation rates of observed resonances. METHODS: We performed downfield MRS in the calf muscle of 7 healthy volunteers. Single-voxel downfield MRS was collected using alternately selective or broadband inversion-recovery sequences and spectrally selective 90° E-BURP RF pulse excitation centered at 9.0 ppm with bandwidth = 600 Hz (2.0 ppm). MRS was collected using TIs of 50-2500 ms. We modeled recovery of the longitudinal magnetization of three observable resonances using two models: (1) a three-parameter model accounting for the apparent T1 recovery and (2) a Solomon model explicitly including cross-relaxation effects. RESULTS: Three resonances were observed in human calf muscle at 7 T at 8.0, 8.2, and 8.5 ppm. We found broadband (broad) and selective (sel) inversion recovery T1 = mean ± SD (ms): T1-broad,8.0ppm = 2108.2 ± 664.5, T1-sel,8.0ppm = 753.6 ± 141.0 (p = 0.003); T1-broad,8.2ppm = 2033.5 ± 338.4, T1-sel,8.2ppm = 135.3 ± 35.3 (p < 0.0001); and T1-broad,8.5ppm = 1395.4 ± 75.4, T1-sel,8.5ppm = 107.1 ± 40.0 (p < 0.0001). Using the Solomon model, we found T1 = mean ± SD (ms): T1-8.0ppm = 1595.6 ± 491.1, T1-8.2ppm = 1737.2 ± 963.7, and T1-8.5ppm = 849.8 ± 282.0 (p = 0.04). Post hoc tests corrected for multiple comparisons showed no significant difference in T1 between peaks. The cross-relaxation rate σAB = mean ± SD (Hz) of each peak was σAB,8.0ppm = 0.76 ± 0.20, σAB,8.2ppm = 5.31 ± 2.27, and σAB,8.5ppm = 7.90 ± 2.74 (p < 0.0001); post hoc t-tests revealed the cross-relaxation rate of the 8.0 ppm peak was significantly slower than the peaks at 8.2 ppm (p = 0.0018) and 8.5 ppm (p = 0.0005). CONCLUSION: We found significant differences in effective T1 and cross-relaxation rates of 1 H resonances between 8.0 and 8.5 ppm in the healthy human calf muscle at 7 T.

Integrating 1H MRS and deuterium labeled glucose for mapping the dynamics of neural metabolism in humans.

In the technique presented here, dubbed 'qMRS', we quantify the change in 1H MRS signal following administration of 2H-labeled glucose. As in recent human DMRS studies, we administer [6,6'-2H2]-glucose orally to healthy subjects. Since 2H is not detectable by 1H MRS, the transfer of the 2H label from glucose to a downstream metabolite leads to a reduction in the corresponding 1H MRS resonance of the metabolite, even if the total concentration of both isoforms remains constant. Moreover, introduction of the deuterium label alters the splitting pattern of the proton resonances, making indirect detection of the deuterated forms- as well as the direct detection of the decrease in unlabeled form- possible even without a 2H coil. Because qMRS requires only standard 1H MRS acquisition methods, it can be performed using commonly implemented single voxel spectroscopy (SVS) and chemical shift imaging (CSI) sequences. In this work, we implement qMRS in semi-LASER based CSI, generating dynamic maps arising from the fitted spectra, and demonstrating the feasibility of using qMRS and qCSI to monitor dynamic metabolism in the human brain using a 7T scanner with no auxiliary hardware.

Single-Cell Analyses Identify Brain Mural Cells Expressing CD19 as Potential Off-Tumor Targets for CAR-T Immunotherapies.

CD19-directed immunotherapies are clinically effective for treating B cell malignancies but also cause a high incidence of neurotoxicity. A subset of patients treated with chimeric antigen receptor (CAR) T cells or bispecific T cell engager (BiTE) antibodies display severe neurotoxicity, including fatal cerebral edema associated with T cell infiltration into the brain. Here, we report that mural cells, which surround the endothelium and are critical for blood-brain-barrier integrity, express CD19. We identify CD19 expression in brain mural cells using single-cell RNA sequencing data and confirm perivascular staining at the protein level. CD19 expression in the brain begins early in development alongside the emergence of mural cell lineages and persists throughout adulthood across brain regions. Mouse mural cells demonstrate lower levels of Cd19 expression, suggesting limitations in preclinical animal models of neurotoxicity. These data suggest an on-target mechanism for neurotoxicity in CD19-directed therapies and highlight the utility of human single-cell atlases for designing immunotherapies.

1H magnetic resonance spectroscopy of 2H-to-1H exchange quantifies the dynamics of cellular metabolism in vivo.

Quantitative mapping of the in vivo dynamics of cellular metabolism via non-invasive imaging contributes to our understanding of the initiation and progression of diseases associated with dysregulated metabolic processes. Current methods for imaging cellular metabolism are limited by low sensitivities, costs or the use of specialized hardware. Here, we introduce a method that captures the turnover of cellular metabolites by quantifying signal reductions in proton magnetic resonance spectroscopy (MRS) resulting from the replacement of 1H with 2H. The method, which we termed quantitative exchanged-label turnover MRS, only requires deuterium-labelled glucose and standard magnetic resonance imaging scanners, and with a single acquisition provides steady-state information and metabolic rates for several metabolites. We used the method to monitor glutamate, glutamine, γ-aminobutyric acid and lactate in the brains of unaffected and glioma-bearing rats following the administration of 2H2-labelled glucose and 2H3-labelled acetate. Quantitative exchanged-label turnover MRS should broaden the applications of routine 1H MRS.

Single-Voxel 1 H MR spectroscopy of cerebral nicotinamide adenine dinucleotide (NAD+ ) in humans at 7T using a 32-channel volume coil.

PURPOSE: Reliable monitoring of tissue nicotinamide adenine dinucleotide (NAD+ ) concentration may provide insights on its roles in normal and pathological aging. In the present study, we report a 1 H MRS pulse sequence for the in vivo, localized 1 H MRS detection of NAD+ from the human brain. METHODS: Studies were carried out on a 7T Siemens MRI scanner using a 32-channel product volume coil. The pulse sequence consisted of a spectrally selective low bandwidth E-BURP-1 90° pulse. PRESS localization was achieved using optimized Shinnar-Le Roux 180° pulses and overlapping gradients were used to minimize the TE. The reproducibility of NAD+ quantification was measured in 11 healthy volunteers. The association of cerebral NAD+ with age was assessed in 16 healthy subjects 26-78 years old. RESULTS: Spectra acquired from a voxel placed in subjects' occipital lobe consisted of downfield peaks from the H2 , H4 , and H6 protons of the nicotinamide moiety of NAD+ between 8.9-9.35 ppm. The mean ± SD within-session and between-session coefficients of variation were found to be 6.14 ± 2.03% and 6.09 ± 3.20%, respectively. In healthy volunteers, an age-dependent decline of the NAD+ levels in the brain was also observed (ß = -1.24 µM/y, SE = 0.21, P < 0.001). CONCLUSION: We demonstrated the feasibility and robustness of a newly developed 1 H MRS technique to measure localized cerebral NAD+ at 7T MRI using a commercially available RF head coil. This technique may be further applied to detect and quantify NAD+ from different regions of the brain as well as from other tissues.

Prior-knowledge Fitting of Accelerated Five-dimensional Echo Planar J-resolved Spectroscopic Imaging: Effect of Nonlinear Reconstruction on Quantitation.

1H Magnetic Resonance Spectroscopic imaging (SI) is a powerful tool capable of investigating metabolism in vivo from mul- tiple regions. However, SI techniques are time consuming, and are therefore difficult to implement clinically. By applying non-uniform sampling (NUS) and compressed sensing (CS) reconstruction, it is possible to accelerate these scans while re- taining key spectral information. One recently developed method that utilizes this type of acceleration is the five-dimensional echo planar J-resolved spectroscopic imaging (5D EP-JRESI) sequence, which is capable of obtaining two-dimensional (2D) spectra from three spatial dimensions. The prior-knowledge fitting (ProFit) algorithm is typically used to quantify 2D spectra in vivo, however the effects of NUS and CS reconstruction on the quantitation results are unknown. This study utilized a simulated brain phantom to investigate the errors introduced through the acceleration methods. Errors (normalized root mean square error >15%) were found between metabolite concentrations after twelve-fold acceleration for several low concentra- tion (<2 mM) metabolites. The Cramér Rao lower bound% (CRLB%) values, which are typically used for quality control, were not reflective of the increased quantitation error arising from acceleration. Finally, occipital white (OWM) and gray (OGM) human brain matter were quantified in vivo using the 5D EP-JRESI sequence with eight-fold acceleration.

Non-caloric sweetener provides magnetic resonance imaging contrast for cancer detection.

BACKGROUND: Image contrast enhanced by exogenous contrast agents plays a crucial role in the early detection, characterization, and determination of the precise location of cancers. Here, we investigate the feasibility of using a non-nutritive sweetener, sucralose (commercial name, Splenda), as magnetic resonance imaging (MRI) contrast agent for cancer studies. METHODS: High-resolution nuclear-magnetic-resonance spectroscopy and MR studies on sucralose solution phantom were performed to detect the chemical exchange saturation transfer (CEST) property of sucralose hydroxyl protons with bulk water (sucCEST). For the animal experiments, female Fisher rats (F344/NCR) were used to generate 9L-gliosarcoma model. MRI with CEST experiments were performed on anesthetized rats at 9.4 T MR scanner. Following the baseline CEST scans, sucralose solution was intravenously administered in control and tumor bearing rats. CEST acquisitions were continued during and following the administration of sucralose. Following the sucCEST, Gadolinium-diethylenetriamine pentaacetic acid was injected to perform Gd-enhanced imaging for visualizing the tumor. RESULTS: The sucCEST contrast in vitro was found to correlate positively with the sucralose concentration and negatively with the pH, indicating the potential of this technique in cancer imaging. In a control animal, the CEST contrast from the brain was found to be unaffected following the administration of sucralose, demonstrating its blood-brain barrier impermeability. In a 9L glioma model, enhanced localized sucCEST contrast in the tumor region was detected while the unaffected brain region showed unaltered CEST effect implying the specificity of sucralose toward the tumorous tissue. The CEST asymmetry plots acquired from the tumor region before and after the sucralose infusion showed elevation of asymmetry at 1 ppm, pointing towards the role of sucralose in increased contrast. CONCLUSIONS: We show the feasibility of using sucralose and sucCEST in study of preclinical models of cancer. This study paves the way for the potential development of sucralose and other sucrose derivatives as contrast agents for clinical MRI applications.

Pilot Assessment of Brain Metabolism in Perinatally HIV-Infected Youths Using Accelerated 5D Echo Planar J-Resolved Spectroscopic Imaging.

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.

Localized, gradient-reversed ultrafast z-spectroscopy in vivo at 7T.

PURPOSE: To collect ultrafast z-spectra in vivo in situations where voxel homogeneity cannot be assured. THEORY: Saturating in the presence of a gradient encodes the frequency offset spatially across a voxel. This encoding can be resolved by applying a similar gradient during readout. Acquiring additional scans with the gradient polarity reversed effectively mirrors the spatial locations of the frequency offsets so that the same physical location of a positive offset in the original scan will contribute a negative offset in the gradient-reversed scan. METHODS: Gradient-reversed ultrafast z-spectroscopy (GRUFZS) was implemented and tested in a modified, localized PRESS sequence at 7T. Lysine phantoms were scanned at various concentrations and compared with coventionally-acquired z-spectra. Scans were acquired in vivo in human brain from homogeneous and inhomogeneous voxels with the ultrafast direction cycled between read, phase, and slice. Results were compared to those from a similar conventional z-spectroscopy PRESS-based sequence. RESULTS: Asymmetry spectra from GRUFZS are more consistent and reliable than those without gradient reversal and are comparable to those from conventional z-spectroscopy. GRUFZS offers significant acceleration in data acquisition compared to traditional chemical exchange saturation transfer methods with high spectral resolution and showed higher relative SNR effficiency. CONCLUSION: GRUFZS offers a method of collecting ultrafast z-spectra in voxels with the inhomogeneity often found in vivo. Magn Reson Med 76:1039-1046, 2016. © 2016 Wiley Periodicals, Inc.

3D spatially encoded and accelerated TE-averaged echo planar spectroscopic imaging in healthy human brain.

Several different pathologies, including many neurodegenerative disorders, affect the energy metabolism of the brain. Glutamate, a neurotransmitter in the brain, can be used as a biomarker to monitor these metabolic processes. One method that is capable of quantifying glutamate concentration reliably in several regions of the brain is TE-averaged (1) H spectroscopic imaging. However, this type of method requires the acquisition of multiple TE lines, resulting in long scan durations. The goal of this experiment was to use non-uniform sampling, compressed sensing reconstruction and an echo planar readout gradient to reduce the scan time by a factor of eight to acquire TE-averaged spectra in three spatial dimensions. Simulation of glutamate and glutamine showed that the 2.2-2.4 ppm spectral region contained 95% glutamate signal using the TE-averaged method. Peak integration of this spectral range and home-developed, prior-knowledge-based fitting were used for quantitation. Gray matter brain phantom measurements were acquired on a Siemens 3 T Trio scanner. Non-uniform sampling was applied retrospectively to these phantom measurements and quantitative results of glutamate with respect to creatine 3.0 (Glu/Cr) ratios showed a coefficient of variance of 16% for peak integration and 9% for peak fitting using eight-fold acceleration. In vivo scans of the human brain were acquired as well and five different brain regions were quantified using the prior-knowledge-based algorithm. Glu/Cr ratios from these regions agreed with previously reported results in the literature. The method described here, called accelerated TE-averaged echo planar spectroscopic imaging (TEA-EPSI), is a significant methodological advancement and may be a useful tool for categorizing glutamate changes in pathologies where affected brain regions are not known a priori. Copyright © 2016 John Wiley & Sons, Ltd.

Accelerated five-dimensional echo planar J-resolved spectroscopic imaging: Implementation and pilot validation in human brain.

PURPOSE: To implement an accelerated five-dimensional (5D) echo-planar J-resolved spectroscopic imaging sequence combining 3 spatial and 2 spectral encoding dimensions and to apply the sequence in human brain. METHODS: An echo planar readout was used to acquire a single spatial and a single spectral dimension during one readout. Nonuniform sampling was applied to the two phase-encoded spatial directions and the indirect spectral dimension. Nonlinear reconstruction was used to minimize the ℓ1-norm or the total variation and included a spectral mask to enhance sparsity. Retrospective reconstructions at multiple undersamplings were performed in phantom. Ten healthy volunteers were scanned with 8× undersampling and compared to a fully sampled single slice scan. RESULTS: Retrospective reconstruction of fully sampled phantom data showed excellent quality at 4×, 8×, 12×, and 16× undersampling using either reconstruction method. Reconstruction of prospectively acquired in vivo scans with 8× undersampling showed excellent quality in the occipito-parietal lobes and good quality in the frontal lobe, consistent with the fully sampled single slice scan. CONCLUSION: By utilizing nonuniform sampling with nonlinear reconstruction, 2D J-resolved spectra can be acquired over a 3D spatial volume with a total scan time of 20 min, which is reasonable for in vivo studies.

Correlated spectroscopic imaging of calf muscle in three spatial dimensions using group sparse reconstruction of undersampled single and multichannel data.

PURPOSE: To implement a 5D (three spatial + two spectral) correlated spectroscopic imaging sequence for application to human calf. THEORY AND METHODS: Nonuniform sampling was applied across the two phase encoded dimensions and the indirect spectral dimension of an echo planar-correlated spectroscopic imaging sequence. Reconstruction was applied that minimized the group sparse mixed ℓ2,1-norm of the data. Multichannel data were compressed using a sensitivity map-based approach with a spatially dependent transform matrix and utilized the self-sparsity of the individual coil images to simplify the reconstruction. RESULTS: Single channel data with 8× and 16× undersampling are shown in the calf of a diabetic patient. A 15-channel scan with 12× undersampling of a healthy volunteer was reconstructed using 5 virtual channels and compared to a fully sampled single slice scan. Group sparse reconstruction faithfully reconstructs the lipid cross peaks much better than ℓ1 minimization. CONCLUSION: COSY spectra can be acquired over a 3D spatial volume with scan time under 15 min using echo planar readout with highly undersampled data and group sparse reconstruction.

Accelerated echo planar J-resolved spectroscopic imaging in prostate cancer: a pilot validation of non-linear reconstruction using total variation and maximum entropy.

The overlap of metabolites is a major limitation in one-dimensional (1D) spectral-based single-voxel MRS and multivoxel-based MRSI. By combining echo planar spectroscopic imaging (EPSI) with a two-dimensional (2D) J-resolved spectroscopic (JPRESS) sequence, 2D spectra can be recorded in multiple locations in a single slice of prostate using four-dimensional (4D) echo planar J-resolved spectroscopic imaging (EP-JRESI). The goal of the present work was to validate two different non-linear reconstruction methods independently using compressed sensing-based 4D EP-JRESI in prostate cancer (PCa): maximum entropy (MaxEnt) and total variation (TV). Twenty-two patients with PCa with a mean age of 63.8 years (range, 46-79 years) were investigated in this study. A 4D non-uniformly undersampled (NUS) EP-JRESI sequence was implemented on a Siemens 3-T MRI scanner. The NUS data were reconstructed using two non-linear reconstruction methods, namely MaxEnt and TV. Using both TV and MaxEnt reconstruction methods, the following observations were made in cancerous compared with non-cancerous locations: (i) higher mean (choline + creatine)/citrate metabolite ratios; (ii) increased levels of (choline + creatine)/spermine and (choline + creatine)/myo-inositol; and (iii) decreased levels of (choline + creatine)/(glutamine + glutamate). We have shown that it is possible to accelerate the 4D EP-JRESI sequence by four times and that the data can be reliably reconstructed using the TV and MaxEnt methods. The total acquisition duration was less than 13 min and we were able to detect and quantify several metabolites.

Non-uniformly under-sampled multi-dimensional spectroscopic imaging in vivo: maximum entropy versus compressed sensing reconstruction.

The four-dimensional (4D) echo-planar correlated spectroscopic imaging (EP-COSI) sequence allows for the simultaneous acquisition of two spatial (ky, kx) and two spectral (t2, t1) dimensions in vivo in a single recording. However, its scan time is directly proportional to the number of increments in the ky and t1 dimensions, and a single scan can take 20­40 min using typical parameters, which is too long to be used for a routine clinical protocol. The present work describes efforts to accelerate EP-COSI data acquisition by application of non-uniform under-sampling (NUS) to the ky­t1 plane of simulated and in vivo EP-COSI datasets then reconstructing missing samples using maximum entropy (MaxEnt) and compressed sensing (CS). Both reconstruction problems were solved using the Cambridge algorithm, which offers many workflow improvements over other l1-norm solvers. Reconstructions of retrospectively under-sampled simulated data demonstrate that the MaxEnt and CS reconstructions successfully restore data fidelity at signal-to-noise ratios (SNRs) from 4 to 20 and 5× to 1.25× NUS. Retrospectively and prospectively 4× under-sampled 4D EP-COSI in vivo datasets show that both reconstruction methods successfully remove NUS artifacts; however, MaxEnt provides reconstructions equal to or better than CS. Our results show that NUS combined with iterative reconstruction can reduce 4D EP-COSI scan times by 75% to a clinically viable 5 min in vivo, with MaxEnt being the preferred method.

Application of compressed sensing to multidimensional spectroscopic imaging in human prostate.

The application of compressed sensing is demonstrated in a recently implemented four-dimensional echo-planar based J-resolved spectroscopic imaging sequence combining two spatial and two spectral dimensions. The echo-planar readout simultaneously acquires one spectral and one spatial dimension. Therefore, the compressed sensing undersampling is performed along the indirectly acquired spatial and spectral dimensions, and the reconstruction is performed using the split Bregman algorithm, an efficient TV-minimization solver. The four-dimensional echo-planar-based J-resolved spectroscopic imaging data acquired in a prostate phantom containing metabolites at physiological concentrations are accurately reconstructed with as little as 20% of the original data. Experimental data acquired in six healthy prostates using the external body matrix "receive" coil on a 3T magnetic resonance imaging scanner are reconstructed with acquisitions using only 25% of the Nyquist-Shannon required amount of data, indicating the potential for a 4-fold acceleration factor in vivo, bringing the required scan time for multidimensional magnetic resonance spectroscopic imaging within clinical feasibility.

Spectroscopic imaging using concentrically circular echo-planar trajectories in vivo.

An alternative to the standard echo-planar spectroscopic imaging technique is presented, spectroscopic imaging using concentrically circular echo-planar trajectories (SI-CONCEPT). In contrast to the conventional chemical shift imaging data, the sampled data from each set of concentric rings were regridded into Cartesian space. Usage of concentric k-space trajectories has the advantage of requiring significantly reduced slew rates than echo-planar spectroscopic imaging, allowing for the collection of higher spectral bandwidths and opening the door for high-bandwidth echo-planar styled spectroscopic imaging at higher magnetic fields. Before two-dimensional spatial and one-dimensional spectral encoding, the volume of interest was localized using the standard point-resolved spectroscopy sequence. The feasibility of using concentric k-space trajectories is demonstrated, and the spatial profiles and representative spectra are compared with the standard echo-planar spectroscopic imaging technique in a gray matter phantom containing metabolites at physiological concentrations and healthy human brain in vivo. The symmetric nature of the concentric circles also reduces the number of required excitations for a given resolution by a factor of two. Possible artifacts and limitations are discussed.