Proton Free Induction Decay MRSI at 7T in the Human Brain Using an Egg-Shaped Modified Rosette K-Space Trajectory.

Purpose: 1.1 Proton ( 1 H)-MRSI via spatial-spectral encoding poses high demands on gradient hardware at ultra-high fields and high-resolutions. Rosette trajectories help alleviate these problems, but at reduced SNR-efficiency due to their k-space densities not matching any desired k-space filter. We propose modified rosette trajectories, which more closely match a Hamming filter, and thereby improve SNR performance while still staying within gradient hardware limitations and without prolonging scan time. Methods: 1.2Analytical and synthetic simulations were validated with phantom and in vivo measurements at 7 T. The rosette and modified rosette trajectories were measured in five healthy volunteers in six minutes in a 2D slice in the brain. A 3D sequence was measured in one volunteer within 19 minutes. The SNR, linewidth, CRLBs, lipid contamination and data quality of the proposed modified rosette trajectory were compared to the rosette trajectory. Results: 1.3Using the modified rosette trajectories, an improved k-space weighting function was achieved resulting in an increase of up to 12% in SNR compared to rosette's dependent on the two additional trajectory parameters. Similar results were achieved for the theoretical SNR calculation based on k-space densities, as well as when using the pseudo-replica method for simulated, in-vivo and phantom data. The CRLBs improved slightly, but non-significantly for the modified rosette trajectories, while the linewidths and lipid contamination remained similar. Conclusion: 1.4By improving the rosette trajectory's shape, modified rosette trajectories achieved higher SNR at the same scan time and data quality.

Sodium Hydrosulfide Treatment During Porcine Kidney Ex Vivo Perfusion and Transplantation.

Background: In rodents, hydrogen sulfide (H2S) reduces ischemia-reperfusion injury and improves renal graft function after transplantation. Here, we hypothesized that the benefits of H2S are conserved in pigs, a more clinically relevant model. Methods: Adult porcine kidneys retrieved immediately or after 60 min of warm ischemia (WI) were exposed to 100 µM sodium hydrosulfide (NaHS) (1) during the hypothermic ex vivo perfusion only, (2) during WI only, and (3) during both WI and ex vivo perfusion. Kidney perfusion was evaluated with dynamic contrast-enhanced MRI. MRI spectroscopy was further employed to assess energy metabolites including ATP. Renal biopsies were collected at various time points for histopathological analysis. Results: Perfusion for 4 h pig kidneys with Belzer MPS UW + NaHS resulted in similar renal perfusion and ATP levels than perfusion with UW alone. Similarly, no difference was observed when NaHS was administered in the renal artery before ischemia. After autotransplantation, no improvement in histologic lesions or cortical/medullary kidney perfusion was observed upon H2S administration. In addition, AMP and ATP levels were identical in both groups. Conclusions: In conclusion, treatment of porcine kidney grafts using NaHS did not result in a significant reduction of ischemia-reperfusion injury or improvement of kidney metabolism. Future studies will need to define the benefits of H2S in human, possibly using other molecules as H2S donors.

ECCENTRIC: a fast and unrestrained approach for high-resolution in vivo metabolic imaging at ultra-high field MR.

A novel method for fast and high-resolution metabolic imaging, called ECcentric Circle ENcoding TRajectorIes for Compressed sensing (ECCENTRIC), has been developed and implemented at 7 Tesla MRI. ECCENTRIC is a non-Cartesian spatial-spectral encoding method optimized to accelerate magnetic resonance spectroscopic imaging (MRSI) with high signal-to-noise at ultra-high field. The approach provides flexible and random (k,t) sampling without temporal interleaving to improve spatial response function and spectral quality. ECCENTRIC needs low gradient amplitudes and slew-rates that reduces electrical, mechanical and thermal stress of the scanner hardware, and is robust to timing imperfection and eddy-current delays. Combined with a model-based low-rank reconstruction, this approach enables simultaneous imaging of up to 14 metabolites over the whole-brain at 2-3mm isotropic resolution in 4-10 minutes. In healthy volunteers ECCENTRIC demonstrated unprecedented spatial mapping of fine structural details of human brain neurochemistry. This innovative tool introduces a novel approach to neuroscience, providing new insights into the exploration of brain activity and physiology.

In vivo magnetic resonance 31 P-Spectral Analysis With Neural Networks: 31P-SPAWNN.

PURPOSE: We have introduced an artificial intelligence framework, 31P-SPAWNN, in order to fully analyze phosphorus-31 ( 31 $$ {}^{31} $$ P) magnetic resonance spectra. The flexibility and speed of the technique rival traditional least-square fitting methods, with the performance of the two approaches, are compared in this work. THEORY AND METHODS: Convolutional neural network architectures have been proposed for the analysis and quantification of 31 $$ {}^{31} $$ P-spectroscopy. The generation of training and test data using a fully parameterized model is presented herein. In vivo unlocalized free induction decay and three-dimensional 31 $$ {}^{31} $$ P-magnetic resonance spectroscopy imaging data were acquired from healthy volunteers before being quantified using either 31P-SPAWNN or traditional least-square fitting techniques. RESULTS: The presented experiment has demonstrated both the reliability and accuracy of 31P-SPAWNN for estimating metabolite concentrations and spectral parameters. Simulated test data showed improved quantification using 31P-SPAWNN compared with LCModel. In vivo data analysis revealed higher accuracy at low signal-to-noise ratio using 31P-SPAWNN, yet with equivalent precision. Processing time using 31P-SPAWNN can be further shortened up to two orders of magnitude. CONCLUSION: The accuracy, reliability, and computational speed of the method open new perspectives for integrating these applications in a clinical setting.

Subnormothermic Ex Vivo Porcine Kidney Perfusion Improves Energy Metabolism: Analysis Using 31P Magnetic Resonance Spectroscopic Imaging.

The ideal preservation temperature for donation after circulatory death kidney grafts is unknown. We investigated whether subnormothermic (22 °C) ex vivo kidney machine perfusion could improve kidney metabolism and reduce ischemia-reperfusion injury. Methods: To mimic donation after circulatory death procurement, kidneys from 45-kg pigs underwent 60 min of warm ischemia. Kidneys were then perfused ex vivo for 4 h with Belzer machine perfusion solution UW at 22 °C or at 4 °C before transplantation. Magnetic resonance spectroscopic imaging coupled with LCModel fitting was used to assess energy metabolites. Kidney perfusion was evaluated with dynamic-contrast enhanced MRI. Renal biopsies were collected at various time points for histopathologic analysis. Results: Total adenosine triphosphate content was 4 times higher during ex vivo perfusion at 22 °C than at 4 °C perfusion. At 22 °C, adenosine triphosphate levels increased during the first hours of perfusion but declined afterward. Similarly, phosphomonoesters, containing adenosine monophosphate, were increased at 22 °C and then slowly consumed over time. Compared with 4 °C, ex vivo perfusion at 22 °C improved cortical and medullary perfusion. Finally, kidney perfusion at 22 °C reduced histological lesions after transplantation (injury score: 22 °C: 10.5 ± 3.5; 4 °C: 18 ± 2.25 over 30). Conclusions: Ex vivo kidney perfusion at 22°C improved graft metabolism and protected from ischemia-reperfusion injuries upon transplantation. Future clinical studies will need to define the benefits of subnormothermic perfusion in improving kidney graft function and patient's survival.

Choreography Controlled (ChoCo) brain MRI artifact generation for labeled motion-corrupted datasets.

MRI is a non-invasive medical imaging modality that is sensitive to patient motion, which constitutes a major limitation in most clinical applications. Solutions may arise from the reduction of acquisition times or from motion-correction techniques, either prospective or retrospective. Benchmarking the latter methods requires labeled motion-corrupted datasets, which are uncommon. Up to our best knowledge, no protocol for generating labeled datasets of MRI images corrupted by controlled motion has yet been proposed. Hence, we present a methodology allowing the acquisition of reproducible motion-corrupted MRI images as well as validation of the system's performance by motion estimation through rigid-body volume registration of fast 3D echo-planar imaging (EPI) time series. A proof-of-concept is presented, to show how the protocol can be implemented to provide qualitative and quantitative results. An MRI-compatible video system displays a moving target that volunteers equipped with customized plastic glasses must follow to perform predefined head choreographies. Motion estimation using rigid-body EPI time series registration demonstrated that head position can be accurately determined (with an average standard deviation of about 0.39 degrees). A spatio-temporal upsampling and interpolation method to cope with fast motion is also proposed in order to improve motion estimation. The proposed protocol is versatile and straightforward. It is compatible with all MRI systems and may provide insights on the origins of specific motion artifacts. The MRI and artificial intelligence research communities could benefit from this work to build in-vivo labeled datasets of motion-corrupted MRI images suitable for training/testing any retrospective motion correction or machine learning algorithm.

New Insight in Hyperinsulinism/Hyperammonemia Syndrome by Magnetic Resonance Imaging and Spectroscopy.

Hyperinsulinism/hyperammonemia syndrome (HI/HA) is an autosomal dominant disorder caused by monoallelic activating mutations in the glutamate dehydrogenase 1 (GLUD1) gene. While hyperinsulinism may be explained by a reduction in the allosteric inhibition of GLUD1, the pathogenesis of HA in HI/HA remains uncertain; interestingly, HA in the HI/HA syndrome is not associated with acute hyperammonemic intoxication events. We obtained a brain magnetic resonance (MR) in a woman with HI/HA syndrome with chronic asymptomatic HA. On MR spectroscopy, choline and myoinositol were decreased as in other HA disorders. In contrast, distinct from other HA disorders, combined glutamate and glutamine levels were normal (not increased). This observation suggests that brain biochemistry in HI/HA may differ from that of other HA disorders. In HI/HA, ammonia overproduction may come to the expense of glutamate levels, and this seems to prevent the condensation of ammonia with glutamate to produce glutamine that is typical of the other HA disorders. The absence of combined glutamate and glutamine elevation might be correlated to the absence of acute cerebral ammonia toxicity.

Whole-brain high-resolution metabolite mapping with 3D compressed-sensing SENSE low-rank 1 H FID-MRSI.

There is a growing interest in the neuroscience community to map the distribution of brain metabolites in vivo. Magnetic resonance spectroscopic imaging (MRSI) is often limited by either a poor spatial resolution and/or a long acquisition time, which severely restricts its applications for clinical and research purposes. Building on a recently developed technique of acquisition-reconstruction for 2D MRSI, we combined a fast Cartesian 1 H-FID-MRSI acquisition sequence, compressed-sensing acceleration, and low-rank total-generalized-variation constrained reconstruction to produce 3D high-resolution whole-brain MRSI with a significant acquisition time reduction. We first evaluated the acceleration performance using retrospective undersampling of a fully sampled dataset. Second, a 20 min accelerated MRSI acquisition was performed on three healthy volunteers, resulting in metabolite maps with 5 mm isotropic resolution. The metabolite maps exhibited the detailed neurochemical composition of all brain regions and revealed parts of the underlying brain anatomy. The latter assessment used previous reported knowledge and a atlas-based analysis to show consistency of the concentration contrasts and ratio across all brain regions. These results acquired on a clinical 3 T MRI scanner successfully combined 3D 1 H-FID-MRSI with a constrained reconstruction to produce detailed mapping of metabolite concentrations at high resolution over the whole brain, with an acquisition time suitable for clinical or research settings.

Super-resolution reconstruction of T2-weighted thick-slice neonatal brain MRI scans.

BACKGROUND AND PURPOSE: Super-resolutionreconstruction (SRR) can be used to reconstruct 3-dimensional (3D) high-resolution (HR) volume from several 2-dimensional (2D) low-resolution (LR) stacks of MRI slices. The purpose is to compare lengthy 2D T2-weighted HR image acquisition of neonatal subjects with 3D SRR from several LR stacks in terms of image quality for clinical and morphometric assessments. METHODS: LR brain images were acquired from neonatal subjects to reconstruct isotropic 3D HR volumes by using SRR algorithm. Quality assessments were done by an experienced pediatric radiologist using scoring criteria adapted to newborn anatomical landmarks. The Wilcoxon signed-rank test was used to compare scoring results between HR and SRR images. For quantitative assessments, morphology-based segmentation was performed on both HR and SRR images and Dice coefficients between the results were computed. Additionally, simple linear regression was performed to compare the tissue volumes. RESULTS: No statistical difference was found between HR and SRR structural scores using Wilcoxon signed-rank test (p = .63, Z = .48). Regarding segmentation results, R2 values for the volumes of gray matter, white matter, cerebrospinal fluid, basal ganglia, cerebellum, and total brain volume including brain stem ranged between .95 and .99. Dice coefficients between the segmented regions from HR and SRR ranged between .83 ± .04 and .96 ± .01. CONCLUSION: Qualitative and quantitative assessments showed that 3D SRR of several LR images produces images that are of comparable quality to standard 2D HR image acquisition for healthy neonatal imaging without loss of anatomical details with similar edge definition allowing the detection of fine anatomical structures and permitting comparable morphometric measurement.

Metabolic changes in the cingulate gyrus, precuneus, and white matter in anorexia nervosa using multivoxel MR spectroscopy.

BACKGROUND AND PURPOSE: This study aimed to highlight anorexia nervosa-related metabolic changes in different brain regions with different gray and white matter contents. METHODS: In a prospective study, 25 anorexic patients with mean body mass index (BMI) of 14.79 kg/m2 (range 10.04-20.58) were compared with 15 healthy controls with mean BMI of 21.08 kg/m2 (range 18.36-27.34). Two-dimensional magnetic resonance spectroscopic imaging was acquired in the axial plane above the corpus callosum, including frontal, precentral, postcentral, cingular, and parietal regions, as well as the precuneus, each voxel containing gray and white matter. RESULTS: In the anorexic group, a significant increase of choline/creatine was observed in all brain regions except the precuneus: frontal (p = 0.009), cingulate (p = 0.001), precentral (p = 0.001), postcentral (p = 0.001), and parietal (p = 0.002); and in white and gray matter (p< 0.001). Macromolecules09/creatine was decreased in the following regions: frontal (p = 0.003), cingulate (p< 0.001), precentral (p = 0.004), and precuneus (p = 0.007), and in white and gray matter (p< 0.05). We observed significantly lower values of N-acetyl aspartate/creatine in the frontal (p < 0.001) and precentral (p< 0.001) regions and in voxels containing more than 50% white matter (p = 0.001); and significantly lower values of myo-inositol/creatine in the precentral (p = 0.006), postcentral (p< 0.001), and precuneus (p = 0.006) regions. CONCLUSIONS: We observed an increase in choline/creatine in anorexics, possibly reflecting increased cell turnover; a decrease in macromolecules, which was particularly low in the cingulate and precuneus the former being known to be altered in eating disorders; and a decrease in N-acetyl aspartate/creatine considered as a marker of neuronal density and function.

Achieving high-resolution 1H-MRSI of the human brain with compressed-sensing and low-rank reconstruction at 7 Tesla.

Low sensitivity MR techniques such as magnetic resonance spectroscopic imaging (MRSI) greatly benefit from the gain in signal-to-noise provided by ultra-high field MR. High-resolution and whole-slab brain MRSI remains however very challenging due to lengthy acquisition, low signal, lipid contamination and field inhomogeneity. In this study, we propose an acquisition-reconstruction scheme that combines 1H free-induction-decay (FID)-MRSI sequence, short TR acquisition, compressed sensing acceleration and low-rank modeling with total-generalized-variation constraint to achieve metabolite imaging in two and three dimensions at 7 Tesla. The resulting images and volumes reveal highly detailed distributions that are specific to each metabolite and follow the underlying brain anatomy. The MRSI method was validated in a high-resolution phantom containing fine metabolite structures, and in five healthy volunteers. This new application of compressed sensing acceleration paves the way for high-resolution MRSI in clinical setting with acquisition times of 5 min for 2D MRSI at 2.5 mm and of 20 min for 3D MRSI at 3.3 mm isotropic.

Ex Vivo Analysis of Kidney Graft Viability Using 31P Magnetic Resonance Imaging Spectroscopy.

BACKGROUND: The lack of organs for kidney transplantation is a growing concern. Expansion in organ supply has been proposed through the use of organs after circulatory death (donation after circulatory death [DCD]). However, many DCD grafts are discarded because of long warm ischemia times, and the absence of reliable measure of kidney viability. P magnetic resonance imaging (pMRI) spectroscopy is a noninvasive method to detect high-energy phosphate metabolites, such as ATP. Thus, pMRI could predict kidney energy state, and its viability before transplantation. METHODS: To mimic DCD, pig kidneys underwent 0, 30, or 60 min of warm ischemia, before hypothermic machine perfusion. During the ex vivo perfusion, we assessed energy metabolites using pMRI. In addition, we performed Gadolinium perfusion sequences. Each sample underwent histopathological analyzing and scoring. Energy status and kidney perfusion were correlated with kidney injury. RESULTS: Using pMRI, we found that in pig kidney, ATP was rapidly generated in presence of oxygen (100 kPa), which remained stable up to 22 h. Warm ischemia (30 and 60 min) induced significant histological damages, delayed cortical and medullary Gadolinium elimination (perfusion), and reduced ATP levels, but not its precursors (AMP). Finally, ATP levels and kidney perfusion both inversely correlated with the severity of kidney histological injury. CONCLUSIONS: ATP levels, and kidney perfusion measurements using pMRI, are biomarkers of kidney injury after warm ischemia. Future work will define the role of pMRI in predicting kidney graft and patient's survival.

Impact of an intra-abdominal cooling device during open kidney transplantation in pigs.

BACKGROUND: Transplantation of kidneys from deceased donors is still associated with a high rate of postoperative renal dysfunction. During implantation into the recipient, the kidney rewarms. This second warm ischaemia time, which is not monitored, is harmful especially if prolonged. We recently developed an intra-abdominal cooling device that efficiently prevents kidney rewarming during robotic transplantation, and prevents ischaemia-reperfusion injuries. We tested the benefits of this cooling device during open kidney transplantation in pigs. METHODS: Kidneys were procured from large pigs by open bilateral nephrectomy. Following procurement, kidneys were flushed with 4°C Institut Georges Lopez-1 preservation solution, and placed on ice. Animals then underwent double sequential autologous open renal transplantation with (n = 7) and without (n = 6) intra-abdominal cooling. RESULTS: Mean anastomosis time was similar between groups (43.9 ± 13 minutes). At reperfusion, the renal cortex temperature was lower in the group with cooling (4.3 ± 1.1°C vs 26.5 ± 5.5°C, p <0.001). The cooled kidneys tended to be protected from injury, including some histopathological ischaemia-reperfusion lesions. With the device, kidneys had a better immediate postoperative urine output (p = 0.05). CONCLUSION: Our results indicate that the intra-abdominal cooling device significantly reduced second warm ischaemic time during transplantation, is technically safe and does not prolong anastomotic time.

Fast high-resolution brain metabolite mapping on a clinical 3T MRI by accelerated 1 H-FID-MRSI and low-rank constrained reconstruction.

PURPOSE: Epitomizing the advantages of ultra short echo time and no chemical shift displacement error, high-resolution-free induction decay magnetic resonance spectroscopic imaging (FID-MRSI) sequences have proven to be highly effective in providing unbiased characterizations of metabolite distributions. However, its merits are often overshadowed in high-resolution settings by reduced signal-to-noise ratios resulting from the smaller voxel volumes procured by extensive phase encoding and the related acquisition times. METHODS: To address these limitations, we here propose an acquisition and reconstruction scheme that offers both implicit dataset denoising and acquisition acceleration. Specifically, a slice selective high-resolution FID-MRSI sequence was implemented. Spectroscopic datasets were processed to remove fat contamination, and then reconstructed using a total generalized variation (TGV) regularized low-rank model. We further measured reconstruction performance for random undersampled data to assess feasibility of a compressed-sensing SENSE acceleration scheme. Performance of the lipid suppression was assessed using an ad hoc phantom, while that of the low-rank TGV reconstruction model was benchmarked using simulated MRSI data. To assess real-world performance, 2D FID-MRSI acquisitions of the brain in healthy volunteers were reconstructed using the proposed framework. RESULTS: Results from the phantom and simulated data demonstrate that skull lipid contamination is effectively removed and that data reconstruction quality is improved with the low-rank TGV model. Also, we demonstrated that the presented acquisition and reconstruction methods are compatible with a compressed-sensing SENSE acceleration scheme. CONCLUSIONS: An original reconstruction pipeline for 2D 1 H-FID-MRSI datasets was presented that places high-resolution metabolite mapping on 3T MR scanners within clinically feasible limits.

Molecular oxygen loading in candidate theranostic droplets stabilized with biocompatible fluorinated surfactants: Particle size effect and application to in situ19F MRI mapping of oxygen partial pressure.

OBJECTIVE: Perfluorocarbon nano- and micron-sized emulsions are a new field of investigation in cancer treatment due to their ability to be used as imaging contrast agents, or as delivery vectors for pharmaceuticals. They also demonstrated capability to enhance the efficiency of high intensity focused ultrasound thermo-therapy. In the context of new biomedical applications we investigated perfluorooctyl bromide (PFOB) theranostic droplets using 19F NMR. Each droplet contains biocompatible fluorinated surfactants composed of a polar Tris(hydroxymethyl)aminomethane head unit and hydrophobic perfluorinated tail (abbreviated as F-TAC). The influence of the droplet size on the oxygen loading capacity was determined from longitudinal relaxation (T1) data of 19F NMR signal. MATERIAL AND METHODS: Liquid PFOB and five samples of PFOB droplets of average diameter 0.177, 0.259, 1.43, 3.12 and 4.53 µm were tested with different oxygen levels. A dedicated gas exchange system was validated to maintain steady state oxygen concentrations, including a spatial gradient of oxygen concentration. A prototyped transmit-receive switchable 19F/1H quadrature coil was integrated on a 3 T clinical scanner. The coil is compatible with focused ultrasound sonication for future application. A spectroscopy FID inversion-recovery (IR) sequence was used to measure the T1 value per sample and per value of equilibrium oxygen pressure. Pixel wise, spatial T1 mapping was performed with magnetization prepared 2D gradient echo sequences in tissue mimicking gels doped with theranostic droplets. RESULTS: Experimental data indicated that the longitudinal relaxation rate of 19F signal of the investigated theranostic droplets depended approximately linearly on the oxygen level and its slope decreased with the particle size according to a second order polynomial over the investigated range. This semi-empirical model was derived from general thermodynamics and weak electrostatic forces theory and fitted the experimental data within 0.75% precision. The capacity of oxygen transportation for the described theranostic droplets tended to that of pure PFOB, while micron-sized droplets lost up to 50% of this capacity. In a specific setup producing a steady state gradient of oxygen concentration, we demonstrated spatial mapping of oxygen pressure gradient of 6 kPa/mm with 1 mm in-plane resolution. CONCLUSION: The size-tunable PFOB theranostic droplets stabilized with F-TAC surfactants could be characterized by 19F MRI in a clinical setup readily compatible with interventional in vivo studies under MR guidance. Current precision and spatial resolution of T1 mapping are promising. A potential challenge for further in vivo studies is the reduction of the imaging time.

Quantitative MR spectroscopic imaging in metachromatic leukodystrophy: value for prognosis and treatment.

OBJECTIVE: To determine whether proton magnetic resonance spectroscopic imaging is useful in predicting clinical course of patients with metachromatic leukodystrophy (MLD), an inherited white matter disorder treatable with haematopoietic cell transplantation (HCT). METHODS: 21 patients with juvenile or adult MLD (12 HCT-treated) were compared with 16 controls in the same age range. Clinical outcome was determined as good, moderate or poor. Metabolites were quantified in white matter, and significance of metabolite concentrations at baseline for outcome prediction was assessed using logistic regression analysis. Evolution of metabolic changes was assessed for patients with follow-up examinations. RESULTS: In this retrospective study, 16 patients with baseline scans were included, 5 with good, 3 with moderate and 8 with poor outcome, and 16 controls. We observed significant group differences for all metabolite concentrations in white matter (p<0.001). Compared with controls, patients had decreased N-acetylaspartate and glutamate, and increased myo-inositol and lactate, most pronounced in patients with poor outcome (post hoc, all p<0.05). Logistic regression showed complete separation of data. Creatine could distinguish poor from moderate and good outcome, the sum of glutamate and glutamine could distinguish good from moderate and poor outcome, and N-acetylaspartate could distinguish all outcome groups. For 13 patients (8 with baseline scans), one or more follow-up examinations were evaluated, revealing stabilisation or even partial normalisation of metabolites in patients with moderate and good outcome, clearly visible in the ratio of choline/N-acetylaspartate. CONCLUSION: In MLD, quantitative spectroscopic imaging at baseline is predictive for outcome and aids in determining eligibility for HCT.

Metabolites predict lesion formation and severity in relapsing-remitting multiple sclerosis.

BACKGROUND: Multiple sclerosis is characterized by white matter lesions, which are visualized with conventional T2-weighted magnetic resonance imaging (MRI). Little is known about local metabolic processes preceding the appearance and during the pathological development of new lesions. OBJECTIVE: To identify metabolite changes preceding white matter (WM) lesions and pathological severity of lesions over time. METHODS: A total of 59 relapsing-remitting multiple sclerosis (MS) patients were scanned four times, with 6-month intervals. Imaging included short-TE magnetic resonance spectroscopic imaging (MRSI) and diffusion tensor imaging (DTI). RESULTS: A total of 16 new lesions appeared within the MRSI slab in 12 patients. Glutamate increased (+1.0 mM (+19%), p = 0.039) 12 and 6 months before new lesions appeared. In these areas, the increase in creatine and choline 6 months before until lesion appearance was negatively correlated with radial diffusivity (ρ = -0.73, p = 0.002 and ρ = -0.72, p = 0.002). Increase in creatine also correlated with the increase of axial diffusivity in the same period (ρ = -0.53, p = 0.034). When splitting the lesions into "mild" and "severe" based on radial diffusivity, only mild lesions showed an increase in creatine and choline during lesion formation ( p = 0.039 and p = 0.008, respectively). CONCLUSION: Increased glutamate heralded the appearance of new T2-visible WM lesions. In pathologically "mild" lesions, an increase in creatine and choline was found during lesion formation.

Multi-scale MRI spectrum detects differences in myelin integrity between MS lesion types.

BACKGROUND: Lesions with different extents of myelin pathology are found at autopsy in multiple sclerosis (MS), but the differences are not discernible in magnetic resonance imaging (MRI). OBJECTIVE: To determine whether analysis of the local spectrum in MRI is sensitive to lesion differences in myelin integrity. METHODS: We imaged fresh brain slices from 21 MS patients using 1.5T scanners. White matter lesions were identified in T2-weighted MRI, matched to corresponding specimens, and then classified into five categories in histology: pre-active (intact myelin); active, chronic active, chronic inactive (complete demyelination); and remyelinated lesions. Voxel-based frequency spectrum was calculated using T2-weighted MRI to characterize lesion structure (image texture). RESULTS: MRI texture heterogeneity resulting from all spectral scales was greater in completely demyelinated lesions than in myelin-preserved lesions (p = 0.02) and normal-appearing white matter (p < 0.01). Moreover, the spectral distribution pattern over low-frequency scales differentiated demyelinated lesions from remyelinated and pre-active lesions (p < 0.01), where different lesion types also showed distinct texture scales. CONCLUSION: Using multi-scale spectral analysis, it may be possible for standard MRI to evaluate myelin integrity in MS lesions. This can be critical for monitoring disease activity and assessing remyelination therapies for MS patients.

Magnetic resonance spectroscopic imaging at superresolution: Overview and perspectives.

The notion of non-invasive, high-resolution spatial mapping of metabolite concentrations has long enticed the medical community. While magnetic resonance spectroscopic imaging (MRSI) is capable of achieving the requisite spatio-spectral localization, it has traditionally been encumbered by significant resolution constraints that have thus far undermined its clinical utility. To surpass these obstacles, research efforts have primarily focused on hardware enhancements or the development of accelerated acquisition strategies to improve the experimental sensitivity per unit time. Concomitantly, a number of innovative reconstruction techniques have emerged as alternatives to the standard inverse discrete Fourier transform (DFT). While perhaps lesser known, these latter methods strive to effect commensurate resolution gains by exploiting known properties of the underlying MRSI signal in concert with advanced image and signal processing techniques. This review article aims to aggregate and provide an overview of the past few decades of so-called "superresolution" MRSI reconstruction methodologies, and to introduce readers to current state-of-the-art approaches. A number of perspectives are then offered as to the future of high-resolution MRSI, with a particular focus on translation into clinical settings.

Longitudinal absolute metabolite quantification of white and gray matter regions in healthy controls using proton MR spectroscopic imaging.

The purpose of this study was to evaluate quality parameters, metabolite concentrations and concentration ratios, and to investigate the reproducibility of quantitative proton magnetic resonance spectroscopic imaging ((1)H-MRSI) of selected white and gray matter regions of healthy adults. 2D-quantitative short-TE (1)H-MRSI spectra were obtained at 1.5T from the healthy human brain. Subjects (n = 12) were scanned twice with an interval of six months. Absolute metabolite concentrations were obtained based on coil loading, taking into account differences in sensitivity of the phased-array head coil. Spectral quality parameters, absolute metabolite concentrations, concentration ratios, and their reproducibility were determined and compared between time-points using a repeated measures general linear model. The quality of the spectra of selected brain areas was good, as determined by a mean spectral linewidth between 4.8 and 7.3 Hz (depending on the region). No significant differences between the two time-points were observed for spectral quality, concentrations, or concentration ratios. The mean intrasubject coefficient of variation (CoV) varied between 4.0 and 8.5% for total N-acetylaspartate, 7.2 and 10.8% for total creatine, 5.9 and 9.8% for myo-inositol, and 8.0 and 13.3% for choline, and remained below 20% for glutamate. CoV was generally lower when concentration ratios were considered. The study shows that longitudinal quantitative short-TE (1)H-MRSI generates reproducible absolute metabolite concentrations in healthy human white and gray matter. This may serve as a background for longitudinal clinical studies in adult patients.