Volumetric MR Spectroscopic Imaging Research Articles

Concordance between focal brain temperature elevations and focal edema in temporal lobe epilepsy.

Neuroinflammation (NI) is a pathophysiological factor in many neurological disorders, including epilepsy. Because NI causes microstructural tissue damage that worsens with increasing brain temperature, abnormally elevated brain temperatures may be a surrogate measure of the biochemical consequences of NI. This study investigated whether patients with temporal lobe epilepsy (TLE) have abnormal brain temperature elevations (TCRE ) in seizure-producing regions that show evidence of edema and/or microstructural damage. Twenty adults with TLE and 20 healthy controls (HCs) were scanned at 3-Tesla. TCRE in each voxel was calculated (TCRE =-102.61(ΔH20-CRE) + 206.1°C) by non-invasive volumetric magnetic resonance spectroscopic imaging and thermometry (MRSI-t). Multi-shell diffusion images were processed by neurite orientation and density imaging (NODDI). Voxel wise two-sample t tests computed group differences in imaging data. Multimodal data fusion (joint independent component analysis [ICA]) determined the spatial coupling of TCRE with NODDI. TCRE analyses showed that, compared to HCs, TLEs had higher TCRE (p < .001). NODDI analyses showed increased extracellular free water (pFWE < 0.05) in the medial temporal lobes, with the most pronounced increases ipsilateral to seizure onset. TLEs also had increased angular dispersion of neurites (p < .001) and decreased neurite density (pFWE <0.05) in the ictal-onset medial temporal lobe, as well as more widespread, bilateral patterns of abnormalities. Focal increases in TCRE were spatially concordant with increased free water in the left inferior and middle temporal gyri and the associated cortex. In TLE, ICA loadings extracted from this region of overlap were associated with greater mood disturbance (r=.34, p=.02) and higher depression scores (r=.37, p=.009). The spatial concordance between focal TCRE elevations and edema in TLE supports the notion that brain thermometry visualizes the correlates of focal NI. MRSI-t-based TCRE elevations may, therefore, be a useful biomarker for identifying seizure-producing tissue in patients with focal epilepsy caused by brain damage.

Repeatability and Reproducibility of in-vivo Brain Temperature Measurements.

Background: Magnetic resonance spectroscopic imaging (MRSI) is a neuroimaging technique that may be useful for non-invasive mapping of brain temperature (i.e., thermometry) over a large brain volume. To date, intra-subject reproducibility of MRSI-based brain temperature (MRSI-t) has not been investigated. The objective of this repeated measures MRSI-t study was to establish intra-subject reproducibility and repeatability of brain temperature, as well as typical brain temperature range.Methods: Healthy participants aged 23–46 years (N = 18; 7 females) were scanned at two time points ~12-weeks apart. Volumetric MRSI data were processed by reconstructing metabolite and water images using parametric spectral analysis. Brain temperature was derived using the frequency difference between water and creatine (TCRE) for 47 regions of interest (ROIs) delineated by the modified Automated Anatomical Labeling (AAL) atlas. Reproducibility was measured using the coefficient of variation for repeated measures (COVrep), and repeatability was determined using the standard error of measurement (SEM). For each region, the upper and lower bounds of Minimal Detectable Change (MDC) were established to characterize the typical range of TCRE values.Results: The mean global brain temperature over all subjects was 37.2°C with spatial variations across ROIs. There was a significant main effect for time [F(1, 1,591) = 37.0, p < 0.0001] and for brain region [F(46, 1,591) = 2.66, p < 0.0001]. The time*brain region interaction was not significant [F(46, 1,591) = 0.80, p = 0.83]. Participants' TCRE was stable for each ROI across both time points, with ROIs' COVrep ranging from 0.81 to 3.08% (mean COVrep = 1.92%); majority of ROIs had a COVrep <2.0%.Conclusions: Brain temperature measurements were highly consistent between both time points, indicating high reproducibility and repeatability of MRSI-t. MRSI-t may be a promising diagnostic, prognostic, and therapeutic tool for non-invasively monitoring brain temperature changes in health and disease. However, further studies of healthy participants with larger sample size(s) and numerous repeated acquisitions are imperative for establishing a reference range of typical brain TCRE, as well as the threshold above which TCRE is likely pathological.

High-Resolution 3D Spin-Echo MRSI Using Interleaved Water Navigators, Sparse Sampling and Subspace-Based Processing.

This work presents a new method to achieve accelerated, high-resolution magnetic resonance spectroscopic imaging (MRSI) with spin-echo excitations. A new data acquisition strategy is proposed that integrates adiabatic refocusing, elimination of lipid suppression, rapid spatiospectral encoding with sparse (k,t)-space sampling, and interleaved water navigators. This integration leads to a significantly improved combination of volume coverage, spatial resolution (approximately 3 × 3.4 × 4 mm3) and speed (< 10 minutes), while eliminating additional scans for field mapping and coil sensitivity estimation. A data processing strategy that integrates parallel imaging reconstruction and subspace-based processing is devised to produce high-SNR spatiospectral reconstruction from the sparsely sampled, noisy and highresolution MRSI data. Promising in vivo results have been obtained to demonstrate the potential of the proposed method.Clinical relevance- The proposed method enabled volumetric MRSI with a nominal resolution of 3 × 3.4 × 4 mm3 in less than 10 minutes. With further developments and optimizations, the proposed method is expected to be useful for providing molecular-level information of brain functions and diseases, and has the potential to provide new biomarkers for disease diagnosis and treatment monitoring.

Longitudinal MR Spectroscopy Shows Altered Metabolism in Traumatic Brain Injury.

Brain trauma is known to result in heterogeneous patterns of tissue damage and altered neuronal and glial metabolism that evolve over time following injury; however, little is known on the longitudinal evolution of these changes. In this study, magnetic resonance spectroscopic imaging (MRSI) was used to map the distributions of altered metabolism in a single subject at five time points over a period of 28 months following injury. Magnetic resonance imaging and volumetric MRSI data were acquired in a subject that had experienced a moderate traumatic brain injury (Glasgow Coma Scale 13) at five time points, from 7 weeks to 28 months after injury. Maps of N-acetylaspartate (NAA), total choline (Cho), and total creatine signal were generated and differences from normal control values identified using a z-score image analysis method. The z-score metabolite maps revealed areas of significantly reduced NAA and increased Cho, predominately located in frontal and parietal white matter, which evolved over the complete course of the study. A map of the ratio of Cho/NAA showed the greatest sensitivity to change, which indicated additional metabolic changes throughout white matter. The metabolic changes reduced over time following injury, though with abnormal values remaining in periventricular regions. The use of z-score image analysis for MRSI provides a method for visualizing diffuse changes of tissue metabolism in the brain. This image visualization method is of particularly effective for visualizing widespread and diffuse metabolic changes, such as that due to traumatic injury.

Volumetric MR Spectroscopic Imaging Can Identify Infiltrating Glioblastoma for Targeting Radiation Therapy

Volumetric MR Spectroscopic Imaging Can Identify Infiltrating Glioblastoma for Targeting Radiation Therapy

Distributions of Magnetic Resonance Diffusion and Spectroscopy Measures with Traumatic Brain Injury.

Magnetic resonance spectroscopy (MRS) and diffusion tensor imaging (DTI) studies have demonstrated that measures of altered metabolism and axonal injury can be detected following traumatic brain injury. The aim of this study was to characterize and compare the distributions of altered image parameters obtained by these methods in subjects with a range of injury severity and to examine their relative sensitivity for diagnostic imaging in this group of subjects. DTI and volumetric magnetic resonance spectroscopic imaging data were acquired in 40 subjects that had experienced a closed-head traumatic brain injury, with a median of 36 d post-injury. Voxel-based analyses were performed to examine differences of group mean values relative to normal controls, and to map significant alterations of image parameters in individual subjects. The between-group analysis revealed widespread alteration of tissue metabolites that was most strongly characterized by increased choline throughout the cerebrum and cerebellum, reaching as much as 40% increase from control values for the group with the worse cognitive assessment score. In contrast, the between-group comparison of DTI measures revealed only minor differences; however, the Z-score image analysis of individual subject DTI parameters revealed regions of altered values relative to controls throughout the major white matter tracts, but with considerable heterogeneity between subjects and with a smaller extent than the findings for altered metabolite measures. The findings of this study illustrate the complimentary nature of these neuroimaging methods.

Multivendor implementation and comparison of volumetric whole‐brain echo‐planar MR spectroscopic imaging

To assess volumetric proton MR spectroscopic imaging (MRSI) of the human brain on multivendor MRI instruments. Echo-planar spectroscopic imaging was developed on instruments from three manufacturers, with matched specifications and acquisition protocols that accounted for differences in sampling performance, radiofrequency (RF) power, and data formats. Intersite reproducibility was evaluated for signal-normalized maps of N-acetylaspartate (NAA), creatine (Cre), and choline using phantom and human subject measurements. Comparative analyses included metrics for spectral quality, spatial coverage, and mean values in atlas-registered brain regions. Intersite differences for phantom measurements were less than 1.7% for individual metabolites and less than 0.2% for ratio measurements. Spatial uniformity ranged from 79% to 91%. The human studies found differences of mean values in the temporal lobe, but good agreement in other white matter regions, with maximum differences relative to their mean of under 3.2%. For NAA/Cre, the maximum difference was 1.8%. In gray matter, a significant difference was observed for frontal lobe NAA. Primary causes of intersite differences were attributed to shim quality, B0 drift, and accuracy of RF excitation. Correlation coefficients for measurements at each site were over 0.60, indicating good reliability. A volumetric intensity-normalized MRSI acquisition can be implemented in a comparable manner across multivendor MR instruments.

Use of high-resolution volumetric MR spectroscopic imaging in assessing treatment response of glioblastoma to an HDAC inhibitor.

Improved predictive imaging would enable personalization and adjustment of treatment, which are critical for patients with glioblastomain whom therapy is likely to fail. This article describes the use of MR spectroscopic imaging (MRSI) to predict early clinical and behavioral response to a therapy and an effort to develop high-resolution, volumetric MRSI to improve its clinical application. MRSI may enable quantitative analysis of brain tumor response, offering a precise tool for monitoring of patients in clinical trials.

Volumetric Spectroscopic Imaging of Glioblastoma Multiforme Radiation Treatment Volumes

Magnetic resonance (MR) imaging and computed tomography (CT) are used almost exclusively in radiation therapy planning of glioblastoma multiforme (GBM), despite their well-recognized limitations. MR spectroscopic imaging (MRSI) can identify biochemical patterns associated with normal brain and tumor, predominantly by observation of choline (Cho) and N-acetylaspartate (NAA) distributions. In this study, volumetric 3-dimensional MRSI was used to map these compounds over a wide region of the brain and to evaluate metabolite-defined treatment targets (metabolic tumor volumes [MTV]). Volumetric MRSI with effective voxel size of ∼1.0 mL and standard clinical MR images were obtained from 19 GBM patients. Gross tumor volumes and edema were manually outlined, and clinical target volumes (CTVs) receiving 46 and 60 Gy were defined (CTV46 and CTV60, respectively). MTVCho and MTVNAA were constructed based on volumes with high Cho and low NAA relative to values estimated from normal-appearing tissue. The MRSI coverage of the brain was between 70% and 76%. The MTVNAA were almost entirely contained within the edema, and the correlation between the 2 volumes was significant (r=0.68, P=.001). In contrast, a considerable fraction of MTVCho was outside of the edema (median, 33%) and for some patients it was also outside of the CTV46 and CTV60. These untreated volumes were greater than 10% for 7 patients (37%) in the study, and on average more than one-third (34.3%) of the MTVCho for these patients were outside of CTV60. This study demonstrates the potential usefulness of whole-brain MRSI for radiation therapy planning of GBM and revealed that areas of metabolically active tumor are not covered by standard RT volumes. The described integration of MTV into the RT system will pave the way to future clinical trials investigating outcomes in patients treated based on metabolic information.

Impact of reduced k‐space acquisition on pathologic detectability for volumetric MR spectroscopic imaging

PurposeTo assess the impact of accelerated acquisitions on the spectral quality of volumetric magnetic resonance spectroscopic imaging (MRSI) and to evaluate their ability in detecting metabolic changes with mild injury.Materials and MethodsThe implementation of a generalized autocalibrating partially parallel acquisition (GRAPPA) method for a high‐resolution whole‐brain echo planar SI (3D‐EPSI) sequence is first described and the spectral accuracy of the GRAPPA‐EPSI method is investigated using lobar and voxel‐based analyses for normal subjects and patients with mild traumatic brain injuries (mTBI). The performance of GRAPPA was compared with that of fully encoded EPSI for five datasets collected from normal subjects at the same scanning session, as well as on 45 scans (20 normal subjects and 25 mTBI patients) for which the reduced k‐space sampling was simulated. For comparison, a central k‐space lower‐resolution 3D‐EPSI acquisition was also simulated. Differences in individual metabolites and metabolite ratio distributions of the mTBI group relative to those of age‐matched control subjects were statistically evaluated using analyses divided into hemispheric brain lobes and tissue types.ResultsGRAPPA‐EPSI with 16‐minute scan time yielded robust and similar results in terms of MRSI quantitation, spectral fitting, and accuracy with that of fully sampled 3D‐EPSI acquisitions and was more accurate than central k‐space acquisition. Primary findings included high correlations (accuracy of 92.6%) between the GRAPPA and fully sampled results.ConclusionAlthough the reduced encoding method is associated with lower signal‐to‐noise ratio (SNR) that impacts the quality of spectral analysis, the use of the parallel imaging method can lead to the same diagnostic outcomes as the fully sampled data when using the sensitivity‐limited volumetric MRSI. J. Magn. Reson. Imaging 2014;39:224–234. © 2013 Wiley Periodicals, Inc.

A Polynomial Fitting Improved Bayesian Reconstruction Method for Whole Brain Volumetric MRSI Metabolite Images

In this paper, a polynomial fitting improved Bayesian approach is proposed for the reconstruction of volumetric metabolite images from long echo time (TE) whole brain proton magnetic resonance spectroscopic imaging (MRSI) data. The proposed algorithm uses a modified EM (expectation maximization) algorithm that takes into account the partial volume effects contained inside a thick slice MRSI. It incorporates high resolution volumetric magnetic resonance imaging (MRI) as a priori information. It further integrates the polynomial fitting method to smooth out artificial edges before the high resolution metabolite images are reconstructed. Our proposed reconstruction method has successfully extended our existing reconstruction of two dimensional (2D) metabolite images to 3D cases. The experimental results show that resolution enhanced volumetric metabolite images are reconstructed.

Whole‐Brain Proton MR Spectroscopic Imaging in Parkinson's Disease

To examine the distributions of proton magnetic resonance spectroscopy (MRS) observed metabolites in Parkinson's disease (PD) throughout the whole brain. Twelve PD patients and 18 age-matched controls were studied using neuropsychological testing, MRI and volumetric MR spectroscopic imaging. Average values of signal normalized metabolite values for N-acetyl-aspartate, total-creatine, and total-choline (NAA, total-Cre, total-Cho, respectively) and their ratios were calculated for gray matter (GM) and white matter (WM) in each lobar brain region. Analyses revealed altered metabolite values in PD subjects relative to controls within the GM of the temporal lobe (right: elevated Cre, P = .027; decreased NAA/Cre, P = .019; decreased Cho/Cre, P = .001 and left: decreased NAA/Cre; P = .001, decreased Cho/Cre, P = .007); the right occipital lobe (decreased NAA, P = .032 and NAA/Cre, P = .016); and the total cerebrum GM (decreased NAA/Cre, P = .029). No meaningful correlations were obtained between abnormal metabolite values and the neuropsychological measures. PD is associated with widespread alterations of brain metabolite concentrations, with a primary finding of increased creatine. Higher creatine values in our PD sample may reflect greater neuronal energy expenditure early in the disease process that is compensatory. This is the first whole brain MRS study of PD that has examined metabolite changes across a large fraction of the brain volume, including the cortical mantle.

Atlas‐based automated positioning of outer volume suppression slices in short‐echo time 3D MR spectroscopic imaging of the human brain

Spatial suppression of peripheral lipid-containing regions in volumetric MR spectroscopic imaging of the human brain requires placing large numbers of outer volume suppression (OVS) slices, which is time-consuming, prone to operator error and may introduce subject-dependent variability in volume coverage. We developed a novel, computationally efficient atlas-based approach for automated positioning of up to 16 OVS slices and the MR spectroscopic imaging slab. Standardized positions in Montreal Neurological Institute atlas space were established offline using a recently developed iterative optimization procedure. During the scanning session, positions in subject space were computed using affine transformation of standardized positions in Montreal Neurological Institute space. Offline analysis using magnetization prepared rapid gradient echo scans from 11 subjects demonstrated reliable OVS placement, comparable with but faster than iterative placement in subject space. This atlas-based method was further validated in 14 subjects using 3D short-echo time proton-echo-planar-spectroscopic-imaging at 3 T. Comparison of manual and automatic placement using 8 OVS slices demonstrated consistent MR spectroscopic imaging volume selection and comparable spectral quality with similar degree of lipid suppression and number of usable voxels. Automated positioning of 16 OVS slices enabled larger volume coverage, while maintaining similar spectral quality and lipid suppression. Atlas-based automatic prescription of short echo time MR spectroscopic imaging is expected to be advantageous for longitudinal and cross-sectional studies.

Reproducibility of serial whole‐brain MR Spectroscopic Imaging

The reproducibility of serial measurements using a volumetric proton MR Spectroscopic Imaging (MRSI) acquisition implemented at 3 Tesla and with lipid suppression by inversion-recovery has been evaluated. Data were acquired from two subjects at five time points, and processed using fully-automated procedures that included rigid registration between studies. These data were analyzed to determine coefficients of variance (COV) for each metabolite and for metabolite ratio images based on an individual voxel analysis, as well as for average and grey-matter and white-matter values from atlas-defined brain regions. The volumetric MRSI acquisition was found to obtain data of sufficient quality for analysis over 70 +/- 6% of the total brain volume, and spatial distributions of the resultant COV values were found to reflect the known distributions of susceptibility-induced magnetic field inhomogeneity. Median values of the resultant voxel-based COVs were 6.2%, 7.2%, and 9.7% for N-acetylaspartate, creatine, and choline respectively. The corresponding mean values obtained following averaging over lobar-scale brain regions within the cerebrum were 3.5%, 3.7%, and 5.2%. These results indicate that longitudinal volumetric MRSI studies with post-acquisition registration can provide an intra-subject reproducibility for voxel-based analyses that is comparable to previously-reported single-voxel MRS measurements, while additionally enabling increased sensitivity by averaging over larger tissue volumes.

Automatic placement of outer volume suppression slices in MR spectroscopic imaging of the human brain

Spatial suppression of peripheral regions (outer volume suppression) is used in MR spectroscopic imaging to reduce contamination from strong lipid and water signals. The manual placement of outer volume suppression slices requires significant operator interaction, which is time consuming and introduces variability in volume coverage. Placing a large number of outer volume saturation bands for volumetric MR spectroscopic imaging studies is particularly challenging and time consuming and becomes unmanageable as the number of suppression bands increases. In this study, a method is presented that automatically segments a high-resolution MR image in order to identify the peripheral lipid-containing regions. This method computes an optimized placement of suppression bands in three dimensions and is based on the maximization of a criterion function. This criterion function maximizes coverage of peripheral lipid-containing areas and minimizes suppression of cortical brain regions and regions outside of the head. Computer simulation demonstrates automatic placement of 16 suppression slices to form a convex hull that covers peripheral lipid-containing regions above the base of the brain. In vivo metabolite mapping obtained with short echo time proton-echo-planar spectroscopic imaging shows that the automatic method yields a placement of suppression slices that is very similar to that of a skilled human operator in terms of lipid suppression and usable brain voxels.

Application of volumetric MR spectroscopic imaging for localization of neocortical epilepsy

The aim of this study was to evaluate volumetric proton magnetic resonance spectroscopic imaging (MRSI) for localization of epileptogenic foci in neocortical epilepsy. Twenty-five subjects reporting seizures considered to be of neocortical origin were recruited to take part in a 3-T MR study that included high-resolution structural MRI and a whole-brain MRSI acquisition. Using a fully automated MRSI processing protocol, maps for signal intensity normalized N-acetylaspartate (NAA), creatine, and choline were created, together with the relative volume fraction of grey-matter, white-matter, and CSF within each MRSI voxel. Analyses were performed using visual observation of the metabolite and metabolite ratio maps; voxel-based calculation of differences in these metabolite maps relative to normal controls; comparison of average grey-matter and white-matter metabolite values over each lobar volume; and examination of relative left-right asymmetry factors by brain region. Data from 14 subjects were suitable for inclusion in the analysis. Eight subjects had MRI-visible pathologies that were associated with decreases in NAA/creatine, which extended beyond the volume indicated by the MRI. Five subjects demonstrated no significant metabolic alterations using any of the analysis methods, and one subject had no findings on MRI or MRSI. This proof of principle study supports previous evidence that alterations of MR-detected brain metabolites can be detected in tissue areas affected by neocortical seizure activity, while additionally demonstrating advantages of the volumetric MRSI approach.

MO‐EE‐A4‐02: Metabolic Changes in Malignant Brain Tumors During Mid‐Course Radiation Therapy: Initial Findings of 3Tesla Volumetric Magnetic Resonance Spectroscopic Imaging

Purpose: Metabolic activity of tumors obtained non‐invasively by magnetic resonance spectroscopic imaging (MRSI) during mid‐course of radiation therapy (RT) can be useful in the evaluating tumor response as well as to design effective boost RT plans. The purpose of this work is to assess the changes in metabolic status of malignant brain tumors using 3Tesla volumetric proton MRSI at three weeks of radiation therapy. Method and Materials: The MRSI data from 11 patients with malignant brain tumors acquired during pre‐ and at 3rd week of RT were analyzed retrospectively. The 3D MRSI was performed on a Siemens 3T TRIO TIM scanner using PRESS (point resolved spectroscopy) sequence with TE/TR: 135/1510 ms, 16×16×8 matrix, FOV: 16×16×8 resulting in MRSI voxel size of 10×10×10 mm3. Linear combination (LC) model was used to analyze the acquired spectra. Tumor activity was determined from the values of metabolites ratio “Choline to N‐Acetyl‐Aspartate” (Cho/NAA). MRSI voxels segmented from metabolically active tumor regions were compared for further analysis. Results: The mean Cho/NAA values at 3rd week of RT compared to their pre‐RT values were found to decrease 26% to 79% in 7 out of 11 patients and increase73% in one case. Three patients had minimal changes (−6% to +17%). Voxels with higher tumor activity (i.e., larger Cho/NAA value) at pre‐RT were observed to show large decrease at 3 weeks of RT. The spatial patterns of metabolic abnormality considerably altered during 3 weeks of RT compared to that of pre‐RT. Conclusion: MRSI derived metabolic status of malignant brain tumors in patients undergoing RT obtained during mid‐course of treatment provides valuable functional tumor information that is not available from other conventional anatomical imaging methods and it could help to devise patient‐specific effective treatment interventions.

Mapping of brain metabolite distributions by volumetric proton MR spectroscopic imaging (MRSI)

Distributions of proton MR-detected metabolites have been mapped throughout the brain in a group of normal subjects using a volumetric MR spectroscopic imaging (MRSI) acquisition with an interleaved water reference. Data were processed with intensity and spatial normalization to enable voxel-based analysis methods to be applied across a group of subjects. Results demonstrate significant regional, tissue, and gender-dependent variations of brain metabolite concentrations, and variations of these distributions with normal aging. The greatest alteration of metabolites with age was observed for white-matter choline and creatine. An example of the utility of the normative metabolic reference information is then demonstrated for analysis of data acquired from a subject who suffered a traumatic brain injury. This study demonstrates the ability to obtain proton spectra from a wide region of the brain and to apply fully automated processing methods. The resultant data provide a normative reference for subsequent utilization for studies of brain injury and disease.

Detection and correction of frequency instabilities for volumetric 1H echo‐planar spectroscopic imaging

Spectral quality in 1H magnetic resonance spectroscopic imaging (MRSI) critically depends on the stability of the main magnetic field. For echo-planar MRSI implemented at 3 T, temperature variation in the passive steel shims of the magnet system can lead to a significant drift in the resonance frequency. A method is presented that incorporates interleaved measurement of the instantaneous resonance frequency of a reference water signal into a volumetric MRSI sequence and allows correction for the drift during postprocessing. Results from normal human brain at 3 T indicate that the correction largely removes lineshape distortions, recovers metabolite signal loss, and improves spectral quality by reducing the width of spectral lines; however, particularly in inferior regions, other sources of distortion may be present that cause broadening of spectral lines.

Volumetric multishot echo-planar spectroscopic imaging.

Rapid volumetric magnetic resonance spectroscopic imaging (MRSI) is potentially of great relevance to the diagnosis and treatment of focal cerebral diseases such as cancer and epilepsy. A strategy for volumetric multishot echo-planar spectroscopic imaging (MEPSI) is described which allows whole-brain metabolite mapping in approximately 20 min. A multishot trajectory is used in both the spatial and temporal domains which reduces the accumulated phase during each echo train and tolerates conventional Fourier reconstruction without regridding. Also described is a generalized correction for phase discontinuities arising from the multishot acquisition of the time domain, which is independent of the spatial k-space trajectory and is therefore also applicable to multishot spiral MRSI. Whole-brain, lipid-suppressed MEPSI data were acquired from five normal subjects. The mean signal-to-noise ratios (SNRs) (+/-SE) for the n-acetylaspartate (NAA), choline (Cho), and creatine (Cr) maps across all subjects were 21.3 +/- 1.8, 11.7 +/- 0.6, and 9.2 +/- 0.6, respectively, with a computed voxel size of 2.33 ml.