Improving the spectral resolution and spectral fitting of 1H MRSI data from human calf muscle by the SPREAD technique

Proton magnetic resonance spectroscopic imaging (¹H MRSI) has been used for the in vivo measurement of intramyocellular lipids (IMCLs) in human calf muscle for almost two decades, but the low spectral resolution between extramyocellular lipids (EMCLs) and IMCLs, partially caused by the magnetic field inhomogeneity, has hindered the accuracy of spectral fitting. The purpose of this paper was to enhance the spectral resolution of ¹H MRSI data from human calf muscle using the SPREAD (spectral resolution amelioration by deconvolution) technique and to assess the influence of improved spectral resolution on the accuracy of spectral fitting and on in vivo measurement of IMCLs. We acquired MRI and ¹H MRSI data from calf muscles of three healthy volunteers. We reconstructed spectral lineshapes of the ¹H MRSI data based on field maps and used the lineshapes to deconvolve the measured MRS spectra, thereby eliminating the line broadening caused by field inhomogeneities and improving the spectral resolution of the ¹H MRSI data. We employed Monte Carlo (MC) simulations with 200 noise realizations to measure the variations of spectral fitting parameters and used an F‐test to evaluate the significance of the differences of the variations between the spectra before SPREAD and after SPREAD. We also used Cramer–Rao lower bounds (CRLBs) to assess the improvements of spectral fitting after SPREAD. The use of SPREAD enhanced the separation between EMCL and IMCL peaks in ¹H MRSI spectra from human calf muscle. MC simulations and F‐tests showed that the use of SPREAD significantly reduced the standard deviations of the estimated IMCL peak areas (p < 10^?8), and the CRLBs were strongly reduced (by ~37%). Copyright © 2014 John Wiley & Sons, Ltd.     

Lipid suppression via double inversion recovery with symmetric frequency sweep for robust 2D‐GRAPPA‐accelerated MRSI of the brain at 7 T

This work presents a new approach for high‐resolution MRSI of the brain at 7 T in clinically feasible measurement times. Two major problems of MRSI are the long scan times for large matrix sizes and the possible spectral contamination by the transcranial lipid signal. We propose a combination of free induction decay (FID)‐MRSI with a short acquisition delay and acceleration via in‐plane two‐dimensional generalised autocalibrating partially parallel acquisition (2D‐GRAPPA) with adiabatic double inversion recovery (IR)‐based lipid suppression to allow robust high‐resolution MRSI. We performed Bloch simulations to evaluate the magnetisation pathways of lipids and metabolites, and compared the results with phantom measurements. Acceleration factors in the range 2–25 were tested in a phantom. Five volunteers were scanned to verify the value of our MRSI method in vivo. GRAPPA artefacts that cause fold‐in of transcranial lipids were suppressed via double IR, with a non‐selective symmetric frequency sweep. The use of long, low‐power inversion pulses (100 ms) reduced specific absorption rate requirements. The symmetric frequency sweep over both pulses provided good lipid suppression (>90%), in addition to a reduced loss in metabolite signal‐to‐noise ratio (SNR), compared with conventional IR suppression (52–70%). The metabolic mapping over the whole brain slice was not limited to a rectangular region of interest. 2D‐GRAPPA provided acceleration up to a factor of nine for in vivo FID‐MRSI without a substantial increase in g‐factors (<1.1). A 64 × 64 matrix can be acquired with a common repetition time of ~1.3 s in only 8 min without lipid artefacts caused by acceleration. Overall, we present a fast and robust MRSI method, using combined double IR fat suppression and 2D‐GRAPPA acceleration, which may be used in (pre)clinical studies of the brain at 7 T. © 2015 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.     

Characterization of oligodendrogliomas using short echo time 1H MR spectroscopic imaging

Oligodendroglial tumors may not be distinguished easily from other brain tumors based on clinical presentation and magnetic resonance imaging (MRI) alone. Identification of these tumors however may have therapeutic consequences. The purpose of this study was to characterize and identify oligodendrogliomas by their metabolic profile as measured by (1)H MR spectroscopic imaging (MRSI). Fifteen patients with oligodendroglial tumors (eight high-grade oligodendrogliomas, seven low-grade oligodendrogliomas) underwent MRI and short echo time (1)H MRSI examinations. Five main metabolites found in brain MR spectra were quantified and expressed as ratios of tumor to contralateral white matter tissue. The level of lipids plus lactate was also assessed in the tumor. For comparison six patients with a low grade astrocytoma were also included in the study. The metabolic profile of oligodendrogliomas showed a decreased level of N-acetylaspartate and increased levels of choline-containing compounds and glutamine plus glutamate compared with white matter. The level of glutamine plus glutamate was significantly higher in low-grade oligodendrogliomas than in low-grade astrocytomas and may serve as a metabolic marker in diagnosis and treatment planning. In high-grade oligodendrogliomas large resonances of lipids plus lactate were observed in contrast to low-grade tumors.     

Implications of respiratory motion for the quantification of 2D MR spectroscopic imaging data in the abdomen

Magnetic resonance spectroscopic imaging (MRSI) studies in the abdomen or breast are acquired in the presence of respiratory motion. This modifies the point spread function (PSF) and hence the reconstructed spectra. We evaluated the quantitative effects of both periodic and aperiodic motion on spectra localized by MRSI. Artefactual signal changes, both the modification of native to a voxel and spurious signals arising elsewhere, depend primarily upon the motion amplitude relative to the voxel dimension. A similar dependence on motion amplitude was observed for simple harmonic motion (SHM), quasi-periodic motion and random displacements. No systematic dependence upon the period or initial phase of SHM or on the array size was found. There was also no significant variation with motion direction relative to the internal and external phase-encoding directions. In measured excursion ranges of 20 breast and abdominal tumours, 70% moved < or = 5 mm, while 30% moved 6-23 mm. The diaphragm and fatty tissues in the gut typically moved approximately 15-20 mm. While tumour/organ excursions less than half the voxel dimension do not substantially affect native signals, the bleeding in of strong lipid signals will be problematic in 1H studies. MRSI studies in the abdomen, even of relatively well-anchored tumours, are thus likely to benefit from the addition of respiratory triggering or other motion compensation strategies.     

Spatio‐spectral regularization to improve magnetic resonance spectroscopic imaging quantification

Magnetic resonance spectroscopic imaging (MRSI) is a non‐invasive technique able to provide the spatial distribution of relevant biochemical compounds commonly used as biomarkers of disease. Information provided by MRSI can be used as a valuable insight for the diagnosis, treatment and follow‐up of several diseases such as cancer or neurological disorders. Obtaining accurate metabolite concentrations from in vivo MRSI signals is a crucial requirement for the clinical utility of this technique. Despite the numerous publications on the topic, accurate quantification is still a challenging problem due to the low signal‐to‐noise ratio of the data, overlap of spectral lines and the presence of nuisance components. We propose a novel quantification method, which alleviates these limitations by exploiting a spatio‐spectral regularization scheme. In contrast to previous methods, the regularization terms are not expressed directly on the parameters being sought, but on appropriate transformed domains. In order to quantify all signals simultaneously in the MRSI grid, while introducing prior information, a fast proximal optimization algorithm is proposed. Experiments on synthetic MRSI data demonstrate that the error in the estimated metabolite concentrations is reduced by a mean of 41% with the proposed scheme. Results on in vivo brain MRSI data show the benefit of the proposed approach, which is able to fit overlapping peaks correctly and to capture metabolites that are missed by single‐voxel methods due to their lower concentrations. Copyright © 2016 John Wiley & Sons, Ltd.     

Elliptical localization with pulsed second‐order fields (ECLIPSE) for robust lipid suppression in proton MRSI

Proton MRSI has great clinical potential for metabolic mapping of the healthy and pathological human brain. Unfortunately, the promise has not yet been fully achieved due to numerous technical challenges related to insufficient spectral quality caused by magnetic field inhomogeneity, insufficient RF transmit power and incomplete lipid suppression. Here a robust, novel method for lipid suppression in ¹H MRSI is presented. The method is based on 2D spatial localization of an elliptical region of interest using pulsed second‐order spherical harmonic (SH) magnetic fields. A dedicated, high‐amplitude second‐order SH gradient setup was designed and constructed, containing coils to generate Z2, X2Y2 and XY magnetic fields. Simulations and phantom MRI results are used to demonstrate the principles of the method and illustrate the manifestation of chemical shift displacement. ¹H MRSI on human brain in vivo demonstrates high quality, robust suppression of extracranial lipids. The method allows a wide range of inner or outer volume selection or suppression and should find application in MRSI, reduced‐field‐of‐view MRI and single‐volume MRS.     

Image-fusion of MR spectroscopic images for treatment planning of gliomas

1H magnetic resonance spectroscopic imaging (MRSI) can improve the accuracy of target delineation for gliomas, but it lacks the anatomic resolution needed for image fusion. This paper presents a simple protocol for fusing simulation computer tomography (CT) and MRSI images for glioma intensity-modulated radiotherapy (IMRT), including a retrospective study of 12 patients. Each patient first underwent whole-brain axial fluid-attenuated-inversion-recovery (FLAIR) MRI (3 mm slice thickness, no spacing), followed by three-dimensional (3D) MRSI measurements (TE/TR: 144/1000 ms) of a user-specified volume encompassing the extent of the tumor. The nominal voxel size of MRSI ranged from 8 x 8 x 10 mm3 to 12 x 12 x 10 mm3. A system was developed to grade the tumor using the choline-to-creatine (Cho/Cr) ratios from each MRSI voxel. The merged MRSI images were then generated by replacing the Cho/Cr value of each MRSI voxel with intensities according to the Cho/Cr grades, and resampling the poorer-resolution Cho/Cr map into the higher-resolution FLAIR image space. The FUNCTOOL processing software was also used to create the screen-dumped MRSI images in which these data were overlaid with each FLAIR MRI image. The screen-dumped MRSI images were manually translated and fused with the FLAIR MRI images. Since the merged MRSI images were intrinsically fused with the FLAIR MRI images, they were also registered with the screen-dumped MRSI images. The position of the MRSI volume on the merged MRSI images was compared with that of the screen-dumped MRSI images and was shifted until agreement was within a predetermined tolerance. Three clinical target volumes (CTVs) were then contoured on the FLAIR MRI images corresponding to the Cho/Cr grades. Finally, the FLAIR MRI images were fused with the simulation CT images using a mutual-information algorithm, yielding an IMRT plan that simultaneously delivers three different dose levels to the three CTVs. The image-fusion protocol was tested on 12 (six high-grade and six low-grade) glioma patients. The average agreement of the MRSI volume position on the screen-dumped MRSI images and the merged MRSI images was 0.29 mm with a standard deviation of 0.07 mm. Of all the voxels with Cho/Cr grade one or above, the distribution of Cho/Cr grade was found to correlate with the glioma grade from pathologic finding and is consistent with literature results indicating Cho/Cr elevation as a marker for malignancy. In conclusion, an image-fusion protocol was developed that successfully incorporates MRSI information into the IMRT treatment plan for glioma.     

Combination of feature-reduced MR spectroscopic and MR imaging data for improved brain tumor classification

The purpose of this paper is to evaluate the effect of the combination of magnetic resonance spectroscopic imaging (MRSI) data and magnetic resonance imaging (MRI) data on the classification result of four brain tumor classes. Suppressed and unsuppressed short echo time MRSI and MRI were performed on 24 patients with a brain tumor and four volunteers. Four different feature reduction procedures were applied to the MRSI data: simple quantitation, principal component analysis, independent component analysis and LCModel. Water intensities were calculated from the unsuppressed MRSI data. Features were extracted from the MR images which were acquired with four different contrasts to comply with the spatial resolution of the MRSI. Evaluation was performed by investigating different combinations of the MRSI features, the MRI features and the water intensities. For each data set, the isolation in feature space of the tumor classes, healthy brain tissue and cerebrospinal fluid was calculated and visualized. A test set was used to calculate classification results for each data set. Finally, the effect of the selected feature reduction procedures on the MRSI data was investigated to ascertain whether it was more important than the addition of MRI information. Conclusions are that the combination of features from MRSI data and MRI data improves the classification result considerably when compared with features obtained from MRSI data alone. This effect is larger than the effect of specific feature reduction procedures on the MRSI data. The addition of water intensities to the data set also increases the classification result, although not significantly. We show that the combination of data from different MR investigations can be very important for brain tumor classification, particularly if a large number of tumors are to be classified simultaneously.     

Evaluation of short‐TE 1H MRSI for quantification of metabolites in the prostate

Back‐to‐back ¹H MRSI scans, using an endorectal and phased‐array coil combination, were performed on 18 low‐risk patients with prostate cancer at 3 T, employing TEs of 32 and 100 ms in order to compare metabolite visualization at each TE. Outer‐volume suppression of lipid signals was performed using regional saturation (REST) slabs and the quantification of spectra at both TEs was achieved with the quantitation using quantum estimation (QUEST) routine. Metabolite nulling experiments in an additional five patients found that there were negligible macromolecule background signals in prostate spectra at TE = 32 ms. Metabolite visibility was judged using the criterion Cramér–Rao lower bound (CRLB)/amplitude < 20%, and metabolite concentrations were corrected for relaxation effects and referenced to the data acquired in corresponding water‐unsuppressed MRSI scans. For the first time, the prostate metabolites spermine and myo‐inositol were quantified individually in vivo, together with citrate, choline and creatine. All five metabolite visibilities were higher in TE = 32 ms MRSI than in TE = 100 ms MRSI. At TE = 32 ms, citrate was visible in 99.0% of lipid‐free spectra, whereas, at TE = 100 ms, no metabolite simulation of citrate matched the in vivo peaks. Spermine, choline and creatine were visualised separately in 30.4% more spectra at TE = 32 ms than at TE = 100 ms, and myo‐inositol in 72.5% more spectra. T₂ values were calculated for spermine (53 ± 16 ms), choline (62 ± 17 ms) and myo‐inositol (90 ± 48 ms). Data from the TE = 32 ms spectra showed that the concentrations of citrate and spermine secretions were positively correlated in both the peripheral zone and central gland (R² = 0.73 and R² = 0.43, respectively), and that the citrate content was significantly higher in the former at 64 ± 22 mm than in the latter at 32 ± 16 mm (p = 0.01). However, lipid contamination at TE = 32 ms was substantial; therefore, to make clinical use of the greater visualisation of prostate metabolites at TE = 32 ms rather than at TE = 100 ms, three‐dimensional MRSI at TE = 32 ms with effective lipid suppression must be implemented. ©2014 The Authors. NMR in Biomedicine published by John Wiley & Sons, Ltd.     

Transrectal ultrasound-guided biopsy of prostate voxels identified as suspicious of malignancy on three-dimensional (1)H MR spectroscopic imaging in patients with abnormal digital rectal examination or raised prostate specific antigen level of 4-10 ng/ml

Results of the evaluation of transrectal ultrasound (TRUS) guided needle biopsy of voxels identified as suspicious of malignancy on magnetic resonance spectroscopic imaging (MRSI) in a large cohort of men (n = 83) with abnormal digital rectal examination (DRE) [prostate specific antigen (PSA) 0-4 ng/ml] or PSA less than 10 ng/ml, are reported. Three-dimensional (1)H MRSI was carried out at 1.5 T using a pelvic-phased array coil in combination with an endorectal surface coil. Voxels were classified as suspicious of malignancy based on Cit/(Cho + Cr) metabolite ratio. TRUS-guided biopsy of suspicious voxels was performed using the z- and x-coordinates obtained from MR images and two to three cores were taken from the suspected site. A systematic sextant biopsy was also carried out. MRSI showed voxels suspicious of malignancy in 44 patients while biopsy revealed cancer in 11 patients (25%). Patients who were negative for malignancy on MRSI were also negative on biopsy. An overall sensitivity of 100%, specificity of 54%, negative predictive value of 100% and accuracy of 60% were obtained. The site of biopsy was confirmed (n = 20) as a hypo-intense area on repeat MRI while repeat MRSI revealed high choline and low citrate. The overall success rate of MRI-directed TRUS-guided biopsy of 25% was higher compared with a 9% success rate achieved without MR guidance in another group of 120 patients. Our results indicate that TRUS-guided biopsy of suspicious area identified as malignant from MRSI can be performed using the coordinates of the voxel derived from MR images. This increases the detection rate of prostate cancer in men with PSA level <10 ng/ml or abnormal DRE and also demonstrates the potential of MR in routine clinical practice.     

Proton spectroscopic imaging of the human prostate at 7 T

The sensitivity of proton MR Spectroscopic Imaging (¹H‐MRSI) of the prostate can be optimized by using the high magnetic field strength of 7 T in combination with an endorectal coil. In the work described in this paper we introduce an endorectal transceiver at 7 T, validate its safety for in vivo use and apply a pulse sequence, optimized for three‐dimensional (3D) ¹H‐MRSI of the human prostate at 7 T. A transmit/receive endorectal RF coil was adapted from a commercially available 3 T endorectal receive‐only coil and validated to remain within safety guidelines for radiofrequency (RF) power deposition using numerical models, MR thermometry of phantoms, and in vivo temperature measurements. The ¹H‐MRSI pulse sequence used adiabatic slice selective refocusing pulses and frequency‐selective water and lipid suppression to selectively obtain the relevant metabolite signals from the prostate. Quantum mechanical simulations were used to adjust the inter‐pulse timing for optimal detection of the strongly coupled spin system of citrate resulting in an echo time of 56 ms. Using this endorectal transceiver and pulse sequence with slice selective adiabatic refocusing pulses, 3D ¹H‐MRSI of the human prostate is feasible at 7 T with a repetition time of 2 s. The optimized inter‐pulse timing enables the absorptive detection of resonances of spins from spermine and citrate in phase with creatine and choline. These potential tumor markers may improve the in vivo detection, localization, and assessment of prostate cancer. Copyright © 2009 John Wiley & Sons, Ltd.     

MRSI‐based molecular imaging of therapy response to temozolomide in preclinical glioblastoma using source analysis

Characterization of glioblastoma (GB) response to treatment is a key factor for improving patients' survival and prognosis. MRI and magnetic resonance spectroscopic imaging (MRSI) provide morphologic and metabolic profiles of GB but usually fail to produce unequivocal biomarkers of response. The purpose of this work is to provide proof of concept of the ability of a semi‐supervised signal source extraction methodology to produce images with robust recognition of response to temozolomide (TMZ) in a preclinical GB model. A total of 38 female C57BL/6 mice were used in this study. The semi‐supervised methodology extracted the required sources from a training set consisting of MRSI grids from eight GL261 GBs treated with TMZ, and six control untreated GBs. Three different sources (normal brain parenchyma, actively proliferating GB and GB responding to treatment) were extracted and used for calculating nosologic maps representing the spatial response to treatment. These results were validated with an independent test set (7 control and 17 treated cases) and correlated with histopathology. Major differences between the responder and non‐responder sources were mainly related to the resonances of mobile lipids (MLs) and polyunsaturated fatty acids in MLs (0.9, 1.3 and 2.8 ppm). Responding tumors showed significantly lower mitotic (3.3 ± 2.9 versus 14.1 ± 4.2 mitoses/field) and proliferation rates (29.8 ± 10.3 versus 57.8 ± 5.4%) than control untreated cases. The methodology described in this work is able to produce nosological images of response to TMZ in GL261 preclinical GBs and suitably correlates with the histopathological analysis of tumors. A similar strategy could be devised for monitoring response to treatment in patients. Copyright © 2016 John Wiley & Sons, Ltd.     

Reproducibility of single- and multi-voxel 1H MRS measurements of intramyocellular lipid in overweight and lean subjects under conditions of controlled dietary calorie and fat intake

The reproducibility of repeated single-voxel 1H MRS (SV-MRS) and spectroscopic imaging (MRSI) measurements of intramyocellular lipid (IMCL) in the tibialis anterior muscle of five lean and five overweight female Caucasians, during 7 days of controlled dietary fat and calorie intake, was assessed at 1.5 T. Duplicate measures of IMCL relative to total muscle creatine (IMCL/tCr) obtained 3 days apart by both SV-MRS and MRSI correlated well (r = 0.65 and r = 0.95, respectively, P < 0.05). The coefficients of variation for repeated measures of IMCL/tCr by SV-MRS and MRSI were 24.4% and 10.7%, respectively. IMCL/tCr measured by MRSI was higher in overweight subjects than in lean subjects (8.3 +/- 3.8 vs 4.3 +/- 2.4, P < 0.05). Although both methods achieved good reproducibility in measuring IMCL in vivo, MRSI was found to offer greater flexibility and reliability, and higher sensitivity to IMCL differences, whereas SV-MRS was advantageous with respect to shorter scan time and ease of implementation.     

Analysis of metabolic abnormalities in high‐grade glioma using MRSI and convex NMF

Clinical use of MRSI is limited by the level of experience required to properly translate MRSI examinations into relevant clinical information. To solve this, several methods have been proposed to automatically recognize a predefined set of reference metabolic patterns. Given the variety of metabolic patterns seen in glioma patients, the decision on the optimal number of patterns that need to be used to describe the data is not trivial. In this paper, we propose a novel framework to (1) separate healthy from abnormal metabolic patterns and (2) retrieve an optimal number of reference patterns describing the most important types of abnormality. Using 41 MRSI examinations (1.5 T, PRESS, T_E 135 ms) from 22 glioma patients, four different patterns describing different types of abnormality were detected: edema, healthy without Glx, active tumor and necrosis. The identified patterns were then evaluated on 17 MRSI examinations from nine different glioma patients. The results were compared against BraTumIA, an automatic segmentation method trained to identify different tumor compartments on structural MRI data. Finally, the ability to predict future contrast enhancement using the proposed approach was also evaluated.     

MR spectroscopy in Alzheimer's disease: gender differences in probabilistic learning capacity

Degenerative alterations of cortical and subcortical regions in Alzheimer disease (AD) can be estimated by the extent of brain metabolite changes as measured by magnetic resonance spectroscopic imaging (MRSI). A neuropsychological assessment may correlate with metabolite levels and could evaluate underlying degenerative processes. Probabilistic-related classification learning, which represents one form of procedural learning, is associated with the neostriatum. The present study was aimed at examining the correlation of spectroscopic imaging in subcortical regions with the evaluation of specific neuropsychological findings. Twenty-two patients with Alzheimer's disease were compared to 15 healthy elderly control subjects. Proton MRSI of the basal ganglia (BG) and thalamus region was performed for detection of N-acetylaspartate (NAA), trimethylamine (TMA) and creatine ((P)Cr). In addition, a probabilistic-related classification learning task (Weather Prediction Task (WT)) was applied. We observed that in patients a high TMA signal in the basal ganglia region was correlated with a poorer performance in the probabilistic learning task (Spearman rank order correlation (SROC)=-0.6, P<0.009). Although Alzheimer's patients, as a group, did not differ from controls with regard to probabilistic learning capacity (PLC), male AD patients, as compared to male controls, displayed an impairment in the task performance by 28% (P<0.03) and showed a 16% elevation in TMA signaling (P<0.04). The altered metabolite signals and ratios in combination with the cognitive performance might suggest gender-related neuronal degeneration and dysfunction within subcortical regions in AD.     

Comparison of reproducibility of single voxel spectroscopy and whole‐brain magnetic resonance spectroscopy imaging at 3T

To date, single voxel spectroscopy (SVS) is the most commonly used MRS technique. SVS is relatively easy to use and provides automated and immediate access to the resulting spectra. However, it is also limited in spatial coverage. A new and very promising MRS technique allows for whole‐brain MR spectroscopic imaging (WB‐MRSI) with much improved spatial resolution. Establishing the reproducibility of data obtained using SVS and WB‐MRSI is an important first step for using these techniques to evaluate longitudinal changes in metabolite concentration. The purpose of this study was to assess and directly compare the reproducibility of metabolite quantification at 3T using SVS and WB‐MRSI in ‘hand‐knob’ areas of motor cortices and hippocampi in healthy volunteers. Ten healthy adults were scanned using both SVS and WB‐MRSI on three occasions one week apart. N‐acetyl aspartate (NAA), creatine (Cr), choline (Cho) and myo‐inositol (mI) were quantified using SVS and WB‐MRSI with reference to both Cr and H₂O. The reproducibility of each technique was evaluated using the coefficient of variation (CV), and the correspondence between the two techniques was assessed using Pearson correlation analysis. The measured mean (range) intra‐subject CVs for SVS were 5.90 (2.65‐10.66)% for metabolites (i.e. NAA, Cho, mI) relative to Cr, and 8.46 (4.21‐21.07)% for metabolites (NAA, Cr, Cho, mI) relative to H₂O. The mean (range) CVs for WB‐MRSI were 7.56 (2.78‐11.41)% for metabolites relative to Cr, and 7.79 (4.57‐14.11)% for metabolites relative to H₂O. Significant positive correlations were observed between metabolites quantified using SVS and WB‐MRSI techniques when the Cr but not H₂O reference was used. The results demonstrate that reproducibilities of SVS and WB‐MRSI are similar for quantifying the four major metabolites (NAA, Cr, Cho, mI); both SVS and WB‐MRSI exhibited good reproducibility. Our findings add reference information for choosing the appropriate ¹H‐MRS technique in future studies.     

Multiparametric human hepatocellular carcinoma characterization and therapy response evaluation by hyperpolarized 13C MRSI

Individual tumor characterization and treatment response monitoring based on current medical imaging methods remain challenging. This work investigates hyperpolarized ¹³ C compounds in an orthotopic rat hepatocellular carcinoma (HCC) model system before and after transcatheter arterial embolization (TAE). HCC ranks amongst the top six most common cancer types in humans and accounts for one‐third of cancer‐related deaths worldwide. Early therapy response monitoring could aid in the development of personalized therapy approaches and novel therapeutic concepts. Measurements with selectively ¹³ C ‐labeled and hyperpolarized urea, pyruvate and fumarate were performed in tumor‐bearing rats before and after TAE. Two‐dimensional, slice‐selective MRSI was used to obtain spatially resolved maps of tumor perfusion, cell energy metabolic conversion rates and necrosis, which were additionally correlated with immunohistochemistry. All three injected compounds, taken together with their respective metabolites, exhibited similar signal distributions. TAE induced a decrease in blood flow into the tumor and thus a decrease in tumor to muscle and tumor to liver ratios of urea, pyruvate and its metabolites, alanine and lactate, whereas conversion rates remained stable or increased on TAE in tumor, muscle and liver tissue. Conversion from fumarate to malate successfully indicated individual levels of necrosis, and global malate signals after TAE suggested the washout of fumarase or malate itself on necrosis. This study presents a combination of three ¹³ C compounds as novel candidate biomarkers for a comprehensive characterization of genetically and molecularly diverse HCC using hyperpolarized MRSI, enabling the simultaneous detection of differences in tumor perfusion, metabolism and necrosis. If, as in this study, bolus dynamics are not required and qualitative perfusion information is sufficient, the desired information could be extracted from hyperpolarized fumarate and pyruvate alone, acquired at higher fields with better spectral separation. Copyright © 2016 John Wiley & Sons, Ltd.     

Identification of MRI and 1H MRSI parameters that may predict survival for patients with malignant gliomas

Although MR imaging (MRI) and MR spectroscopic imaging (MRSI) have been applied in the diagnosis and treatment planning for brain tumors, their prognostic significance has not yet been determined. The goal of this study was to identify pre-treatment MRI and MRSI parameters for patients with malignant glioma that may be useful in predicting survival. Two populations of patients with newly-diagnosed malignant glioma were examined with MRI and three-dimensional proton ((1)H) MRSI. Thirty-nine patients (22 grade 3 and 17 glioblastoma multiforme, GBM) were studied prior to surgery, and 33 GBM patients were studied after surgery but prior to treatment with radiation and chemotherapy. Signal intensities of choline (Cho), creatine (Cr), N-acetyl aspartate (NAA), and lactate/lipid (LL) were estimated from the spectra. Recursive partitioning methods were applied to parameters that included age, histological grade, MRI and MRSI variables to generate survival trees. Patients were grouped into high and low risk categories and the corresponding Kaplan-Meier curves were plotted for comparison between groups. The parameters that were selected by recursive partitioning as being predictive of poor outcome were older age, larger contrast enhancement, higher Cho-to-Cr, higher Cho-to-NAA, higher LL and lower Cr-to-NAA abnormalities. The survival functions were significantly different between the sub-groups of patients obtained from the survival tree for both pre-surgery and post-surgery data. The results of this study suggest that pre-treatment MRI and three-dimensional (1)H-MRSI provide information that predicts outcome for patients with malignant gliomas and have drawn attention to variables that should be examined prospectively in future studies using these techniques.     

Fast data acquisition techniques in magnetic resonance spectroscopic imaging

Magnetic resonance spectroscopic imaging (MRSI) is an important technique for assessing the spatial variation of metabolites in vivo. The long scan times in MRSI limit clinical applicability due to patient discomfort, increased costs, motion artifacts, and limited protocol flexibility. Faster acquisition strategies can address these limitations and could potentially facilitate increased adoption of MRSI into routine clinical protocols with minimal addition to the current anatomical and functional acquisition protocols in terms of imaging time. Not surprisingly, a lot of effort has been devoted to the development of faster MRSI techniques that aim to capture the same underlying metabolic information (relative metabolite peak areas and spatial distribution) as obtained by conventional MRSI, in greatly reduced time. The gain in imaging time results, in some cases, in a loss of signal‐to‐noise ratio and/or in spatial and spectral blurring. This review examines the current techniques and advances in fast MRSI in two and three spatial dimensions and their applications. This review categorizes the acceleration techniques according to their strategy for acquisition of the k‐space. Techniques such as fast/turbo‐spin echo MRSI, echo‐planar spectroscopic imaging, and non‐Cartesian MRSI effectively cover the full k‐space in a more efficient manner per T_R. On the other hand, techniques such as parallel imaging and compressed sensing acquire fewer k‐space points and employ advanced reconstruction algorithms to recreate the spatial‐spectral information, which maintains statistical fidelity in test conditions (ie no statistically significant differences on voxel‐wise comparisions) with the fully sampled data. The advantages and limitations of each state‐of‐the‐art technique are reviewed in detail, concluding with a note on future directions and challenges in the field of fast spectroscopic imaging.