Retrospective analysis of Braak stage- and APOE4 allele-dependent associations between MR spectroscopy and markers of tau and neurodegeneration in cognitively unimpaired elderly.

PURPOSE: The pathological hallmarks of Alzheimer's disease (AD), amyloid, tau, and associated neurodegeneration, are present in the cortical gray matter (GM) years before symptom onset, and at significantly greater levels in carriers of the apolipoprotein E4 (APOE4) allele. Their respective biomarkers, A/T/N, have been found to correlate with aspects of brain biochemistry, measured with magnetic resonance spectroscopy (MRS), indicating a potential for MRS to augment the A/T/N framework for staging and prediction of AD. Unfortunately, the relationships between MRS and A/T/N biomarkers are unclear, largely due to a lack of studies examining them in the context of the spatial and temporal model of T/N progression. Advanced MRS acquisition and post-processing approaches have enabled us to address this knowledge gap and test the hypotheses, that glutamate-plus-glutamine (Glx) and N-acetyl-aspartate (NAA), metabolites reflecting synaptic and neuronal health, respectively, measured from regions on the Braak stage continuum, correlate with: (i) cerebrospinal fluid (CSF) p-tau181 level (T), and (ii) hippocampal volume or cortical thickness of parietal lobe GM (N). We hypothesized that these correlations will be moderated by Braak stage and APOE4 genotype. METHODS: We conducted a retrospective imaging study of 34 cognitively unimpaired elderly individuals who received APOE4 genotyping and lumbar puncture from pre-existing prospective studies at the NYU Grossman School of Medicine between October 2014 and January 2019. Subjects returned for their imaging exam between April 2018 and February 2020. Metabolites were measured from the left hippocampus (Braak II) using a single-voxel semi-adiabatic localization by adiabatic selective refocusing sequence; and from the bilateral posterior cingulate cortex (PCC; Braak IV), bilateral precuneus (Braak V), and bilateral precentral gyrus (Braak VI) using multi-voxel echo-planar spectroscopic imaging sequence. Pearson and Spearman correlations were used to examine the relationships between absolute levels of choline, creatine, myo-inositol, Glx, and NAA and CSF p-tau181, and between these metabolites and hippocampal volume or parietal cortical thicknesses. Covariates included age, sex, years of education, Fazekas score, and months between CSF collection and MRI exam. RESULTS: There was a direct correlation between hippocampal Glx and CSF p-tau181 in APOE4 carriers (Pearson's r = 0.76, p = 0.02), but not after adjusting for covariates. In the entire cohort, there was a direct correlation between hippocampal NAA and hippocampal volume (Spearman's r = 0.55, p = 0.001), even after adjusting for age and Fazekas score (Spearman's r = 0.48, p = 0.006). This relationship was observed only in APOE4 carriers (Pearson's r = 0.66, p = 0.017), and was also retained after adjustment (Pearson's r = 0.76, p = 0.008; metabolite-by-carrier interaction p = 0.03). There were no findings in the PCC, nor in the negative control (late Braak stage) regions of the precuneus and precentral gyrus. CONCLUSIONS: Our findings are in line with the spatially- and temporally-resolved Braak staging model of pathological severity in which the hippocampus is affected earlier than the PCC. The correlations, between MRS markers of synaptic and neuronal health and, respectively, T and N pathology, were found exclusively within APOE4 carriers, suggesting a connection with AD pathological change, rather than with normal aging. We therefore conclude that MRS has the potential to augment early A/T/N staging, with the hippocampus serving as a more sensitive MRS target compared to the PCC.

Medial prefrontal cortex neurotransmitter abnormalities in posttraumatic stress disorder with and without comorbidity to major depression.

Posttraumatic stress disorder (PTSD) is a chronic psychiatric condition that follows exposure to a traumatic stressor. Though previous in vivo proton (1H) MRS) research conducted at 4 T or lower has identified alterations in glutamate metabolism associated with PTSD predisposition and/or progression, no prior investigations have been conducted at higher field strength. In addition, earlier studies have not extensively addressed the impact of psychiatric comorbidities such as major depressive disorder (MDD) on PTSD-associated 1H-MRS-visible brain metabolite abnormalities. Here we employ 7 T 1H MRS to examine concentrations of glutamate, glutamine, GABA, and glutathione in the medial prefrontal cortex (mPFC) of PTSD patients with MDD (PTSD+MDD+; N = 6) or without MDD (PTSD+MDD-; N = 5), as well as trauma-unmatched controls without PTSD but with MDD (PTSD-MDD+; N = 9) or without MDD (PTSD-MDD-; N = 18). Participants with PTSD demonstrated decreased ratios of GABA to glutamine relative to healthy PTSD-MDD- controls but no single-metabolite abnormalities. When comorbid MDD was considered, however, MDD but not PTSD diagnosis was significantly associated with increased mPFC glutamine concentration and decreased glutamate:glutamine ratio. In addition, all participants with PTSD and/or MDD collectively demonstrated decreased glutathione relative to healthy PTSD-MDD- controls. Despite limited findings in single metabolites, patterns of abnormality in prefrontal metabolite concentrations among individuals with PTSD and/or MDD enabled supervised classification to separate them from healthy controls with 80+% sensitivity and specificity, with glutathione, glutamine, and myoinositol consistently among the most informative metabolites for this classification. Our findings indicate that MDD can be an important factor in mPFC glutamate metabolism abnormalities observed using 1H MRS in cohorts with PTSD.

Uncertainty propagation in absolute metabolite quantification for in vivo MRS of the human brain.

PURPOSE: Absolute spectral quantification is the standard method for deriving estimates of the concentration from metabolite signals measured using in vivo proton MRS (1 H-MRS). This method is often reported with minimum variance estimators, specifically the Cramér-Rao lower bound (CRLB) of the metabolite signal amplitude's scaling factor from linear combination modeling. This value serves as a proxy for SD and is commonly reported in MRS experiments. Characterizing the uncertainty of absolute quantification, however, depends on more than simply the CRLB. The uncertainties of metabolite-specific (T1m , T2m ), reference-specific (T1ref , T2ref ), and sequence-specific (TR , TE ) parameters are generally ignored, potentially leading to an overestimation of precision. In this study, the propagation of uncertainty is used to derive a comprehensive estimate of the overall precision of concentrations from an internal reference. METHODS: The propagated uncertainty is calculated using analytical derivations and Monte Carlo simulations and subsequently analyzed across a set of commonly measured metabolites and macromolecules. The effect of measurement error from experimentally obtained quantification parameters is estimated using published uncertainties and CRLBs from in vivo 1 H-MRS literature. RESULTS: The additive effect of propagated measurement uncertainty from applied quantification correction factors can result in up to a fourfold increase in the concentration estimate's coefficient of variation compared to the CRLB alone. A case study analysis reveals similar multifold increases across both metabolites and macromolecules. CONCLUSION: The precision of absolute metabolite concentrations derived from 1 H-MRS experiments is systematically overestimated if the uncertainties of commonly applied corrections are neglected as sources of error.

In vivo cortical glutathione response to oral fumarate therapy in relapsing-remitting multiple sclerosis: A single-arm open-label phase IV trial using 7-Tesla 1H MRS.

BACKGROUND: This is an open-label, single-arm, single-center pilot study using 7-Tesla in vivo proton magnetic resonance spectroscopy (1H MRS) to measure brain cortical glutathione concentration at baseline before and during the use of oral fumarates as a disease-modifying therapy for multiple sclerosis. The primary endpoint of this research was the change in prefrontal cortex glutathione concentration relative to a therapy-naïve baseline after one year of oral fumarate therapy. METHODS: Brain glutathione concentrations were examined by 1H MRS in single prefrontal and occipital cortex cubic voxels (2.5 × 2.5 × 2.5 cm3) before and during initiation of oral fumarate therapy (120 mg b.i.d. for 7 days and 240 mg b.i.d. thereafter). Additional measurements of related metabolites glutamate, glutamine, myoinositol, total N-acetyl aspartate, and total choline were also acquired in voxels centered on the same regions. Seven relapsing-remitting multiple sclerosis patients (4 f / 3 m, age range 28-50 years, mean age 40 years) naïve to fumarate therapy were scanned at pre-therapy baseline and after 1, 3, 6 and 12 months of therapy. A group of 8 healthy volunteers (4 f / 4 m, age range 33-48 years, mean age 41 years) was also scanned at baseline and Month 6 to characterize 1H-MRS measurement reproducibility over a comparable time frame. RESULTS: In the multiple sclerosis cohort, general linear models demonstrated a significant positive linear relationship between prefrontal glutathione and time either linearly across all time points (+0.05 ± 0.02 mM/month, t(27) = 2.6, p = 0.02) or specifically for factor variable Month 12 (+0.6 ± 0.3 mM/12 months, t(24) = 2.2, p = 0.04) relative to baseline. No such effects of time on glutathione concentration were demonstrated in the occipital cortex or in the healthy volunteer group. Changes in occipital total choline were further observed in the multiple sclerosis cohort as well as prefrontal total choline and occipital glutamine and myoinositol in the control cohort throughout the study duration. CONCLUSIONS: While the open-label single-arm pilot study design and abbreviated control series cannot support firm conclusions about the influence of oral fumarate therapy independent of test-retest factors or normal biological variation in a state of either health or disease, these results do justify further investigation at a larger scale into the potential relationship between prefrontal cortex glutathione increases and oral fumarate therapy in relapsing-remitting multiple sclerosis.

Design and realization of a multi-coil array for B0 field control in a compact 1.5T head-only MRI scanner.

PURPOSE: To design and implement a multi-coil (MC) array for B0 field generation for image encoding and simultaneous advanced shimming in a novel 1.5T head-only MRI scanner. METHODS: A 31-channel MC array was designed following the unique constraints of this scanner design: The vertically oriented magnet is very short, stopping shortly above the shoulders of a sitting subject, and includes a window for the subject to see through. Key characteristics of the MC hardware, the B0 field generation capabilities, and thermal behavior, were optimized in simulations prior to its construction. The unit was characterized via bench testing. B0 field generation capabilities were validated on a human 4T MR scanner by analysis of experimental B0 fields and by comparing images for several MRI sequences acquired with the MC array to those acquired with the system's linear gradients. RESULTS: The MC system was designed to produce a multitude of linear and nonlinear magnetic fields including linear gradients of up to 10 kHz/cm (23.5 mT/m) with MC currents of 5 A per channel. With water cooling it can be driven with a duty cycle of up to 74% and ramp times of 500 µs. MR imaging experiments encoded with the developed multi-coil hardware were largely artifact-free; residual imperfections were predictable, and correctable. CONCLUSION: The presented compact multi-coil array is capable of generating image encoding fields with amplitudes and quality comparable to clinical systems at very high duty cycles, while additionally enabling high-order B0 shimming capabilities and the potential for nonlinear encoding fields.

Proton Magnetic Resonance Spectroscopy in Post-Traumatic Stress Disorder-Updated Systematic Review and Meta-Analysis.

A stressor-related disorder wherein traumatic experience precipitates protracted disruptions to mood and cognition, post-traumatic stress disorder (PTSD) is associated with wide-ranging abnormalities across the body. While various methods have investigated these deviations, only proton magnetic resonance spectroscopy (1H MRS) enables noninvasive measurement of small-molecule metabolites in the living human. 1H MRS has correspondingly been employed to test hypotheses about the composition and function of multiple brain regions putatively involved in PTSD. Here we systematically review methodological considerations and reported findings, both positive and negative, of the current 1H-MRS literature in PTSD (N = 32 studies) to communicate the brain regional metabolite alterations heretofore observed, providing random-effects model meta-analyses for those most extensively studied. Our review suggests significant PTSD-associated decreases in N-acetyl aspartate in bilateral hippocampus and anterior cingulate cortex with less evident effect in other metabolites and regions. Model heterogeneities diverged widely by analysis (I2 < 0.01% to 90.1%) and suggested regional dependence on quantification reference (creatine or otherwise). While observed variabilities in methods and reported findings suggest that 1H-MRS explorations of PTSD could benefit from methodological standardization, informing this standardization by quantitative assessment of the existing literature is currently hampered by its small size and limited scope.

Multiple sclerosis diagnosis and phenotype identification by multivariate classification of in vivo frontal cortex metabolite profiles.

Multiple sclerosis (MS) is a heterogeneous autoimmune disease for which diagnosis continues to rely on subjective clinical judgment over a battery of tests. Proton magnetic resonance spectroscopy (1H MRS) enables the noninvasive in vivo detection of multiple small-molecule metabolites and is therefore in principle a promising means of gathering information sufficient for multiple sclerosis diagnosis and subtype classification. Here we show that supervised classification using 1H-MRS-visible normal-appearing frontal cortex small-molecule metabolites alone can indeed differentiate individuals with progressive MS from control (held-out validation sensitivity 79% and specificity 68%), as well as between relapsing and progressive MS phenotypes (held-out validation sensitivity 84% and specificity 74%). Post hoc assessment demonstrated the disproportionate contributions of glutamate and glutamine to identifying MS status and phenotype, respectively. Our finding establishes 1H MRS as a viable means of characterizing progressive multiple sclerosis disease status and paves the way for continued refinement of this method as an auxiliary or mainstay of multiple sclerosis diagnostics.

High-resolution simulation of B0 field conditions in the human heart from segmented computed tomography images.

B0 inhomogeneity leads to imaging artifacts in cardiac magnetic resonance imaging (MRI), in particular dark band artifacts with steady-state free precession pulse sequences. The limited spatial resolution of MR-derived in vivo B0 maps and the lack of population data prevent systematic analysis of the problem at hand and the development of optimized B0 shim strategies. We used readily available clinical computed tomography (CT) images to simulate the B0 conditions in the human heart at high spatial resolution. Calculated B0 fields showed consistency with MRI-based B0 measurements. The B0 maps for both the simulations and in vivo measurements showed local field inhomogeneities in the vicinity of lung tips with dominant Z3 spherical harmonic terms in the field distribution. The presented simulation approach allows for the derivation of B0 field conditions at high spatial resolution from CT images and enables the development of subject- and population-specific B0 shim strategies for the human heart.

On the way to routine cardiac MRI at 7 Tesla - a pilot study on consecutive 84 examinations.

INTRODUCTION: Cardiac magnetic resonance (CMR) at ultrahigh field (UHF) offers the potential of high resolution and fast image acquisition. Both technical and physiological challenges associated with CMR at 7T require specific hardware and pulse sequences. This study aimed to assess the current status and existing, publicly available technology regarding the potential of a clinical application of 7T CMR. METHODS: Using a 7T MRI scanner and a commercially available radiofrequency coil, a total of 84 CMR examinations on 72 healthy volunteers (32 males, age 19-70 years, weight 50-103 kg) were obtained. Both electrocardiographic and acoustic triggering were employed. The data were analyzed regarding the diagnostic image quality and the influence of patient and hardware dependent factors. 50 complete short axis stacks and 35 four chamber CINE views were used for left ventricular (LV) and right ventricular (RV), mono-planar LV function, and RV fractional area change (FAC). Twenty-seven data sets included aortic flow measurements that were used to calculate stroke volumes. Subjective acceptance was obtained from all volunteers with a standardized questionnaire. RESULTS: Functional analysis showed good functions of LV (mean EF 56%), RV (mean EF 59%) and RV FAC (mean FAC 52%). Flow measurements showed congruent results with both ECG and ACT triggering. No significant influence of experimental parameters on the image quality of the LV was detected. Small fractions of 5.4% of LV and 2.5% of RV segments showed a non-diagnostic image quality. The nominal flip angle significantly influenced the RV image quality. CONCLUSION: The results demonstrate that already now a commercially available 7T MRI system, without major methods developments, allows for a solid morphological and functional analysis similar to the clinically established CMR routine approach. This opens the door towards combing routine CMR in patients with development of advanced 7T technology.

In vivo evidence of differential frontal cortex metabolic abnormalities in progressive and relapsing-remitting multiple sclerosis.

The pathophysiology of progressive multiple sclerosis remains elusive, significantly limiting available disease-modifying therapies. Proton MRS (1 H-MRS) enables in vivo measurement of small molecules implicated in multiple sclerosis, but its application to key metabolites glutamate, γ-aminobutyric acid (GABA), and glutathione has been sparse. We employed, at 7 T, a previously validated 1 H-MRS protocol to measure glutamate, GABA, and glutathione, as well as glutamine, N-acetyl aspartate, choline, and myoinositol, in the frontal cortex of individuals with relapsing-remitting (N = 26) or progressive (N = 21) multiple sclerosis or healthy control adults (N = 25) in a cross-sectional analysis. Only individuals with progressive multiple sclerosis demonstrated reduced glutamate (F2,65 = 3.424, p = 0.04; 12.40 ± 0.62 mM versus control 13.17 ± 0.95 mM, p = 0.03) but not glutamine (F2,65 = 0.352, p = 0.7; 4.71 ± 0.35 mM versus control 4.84 ± 0.42 mM), reduced GABA (F2,65 = 3.89, p = 0.03; 1.29 ± 0.23 mM versus control 1.47 ± 0.25 mM, p = 0.05), and possibly reduced glutathione (F2,65 = 0.352, p = 0.056; 2.23 ± 0.46 mM versus control 2.51 ± 0.48 mM, p < 0.1). As a group, multiple sclerosis patients demonstrated significant negative correlations between disease duration and glutamate or GABA (ρ = -0.4, p = 0.02) but not glutamine or glutathione. Alone, only relapsing-remitting multiple sclerosis patients exhibited a significant negative correlation between disease duration and GABA (ρ = -0.5, p = 0.03). Taken together, these results indicate that frontal cortex metabolism is differentially disturbed in progressive and relapsing-remitting multiple sclerosis.

Hippocampal single-voxel MR spectroscopy with a long echo time at 3 T using semi-LASER sequence.

The hippocampus is one of the most challenging brain regions for proton MR spectroscopy (MRS) applications. Moreover, quantification of J-coupled species such as myo-inositol (m-Ins) and glutamate + glutamine (Glx) is affected by the presence of macromolecular background. While long echo time (TE) MRS eliminates the macromolecules, it also decreases the m-Ins and Glx signal and, as a result, these metabolites are studied mainly with short TE. Here, we investigate the feasibility of reproducibly measuring their concentrations at a long TE of 120 ms, using a semi-adiabatic localization by adiabatic selective refocusing (sLASER) sequence, as this sequence was recently recommended as a standard for clinical MRS. Gradient offset-independent adiabatic refocusing pulses were implemented, and an optimal long TE for the detection of m-Ins and Glx was determined using the T2 relaxation times of macromolecules. Metabolite concentrations and their coefficients of variation (CVs) were obtained for a 3.4-mL voxel centered on the left hippocampus on 3-T MR systems at two different sites with three healthy subjects (aged 32.5 ± 10.2 years [mean ± standard deviation]) per site, with each subject scanned over two sessions, and with each session comprising three scans. Concentrations of m-Ins, choline, creatine, Glx and N-acetyl-aspartate were 5.4 ± 1.5, 1.7 ± 0.2, 5.8 ± 0.3, 11.6 ± 1.2 and 5.9 ± 0.4 mM (mean ± standard deviation), respectively. Their respective mean within-session CVs were 14.5% ± 5.9%, 6.5% ± 5.3%, 6.0% ± 3.4%, 10.6% ± 6.2% and 3.5% ± 1.4%, and their mean within-subject CVs were 17.8% ± 18.2%, 7.5% ± 6.3%, 7.4% ± 6.4%, 12.4% ± 5.3% and 4.8% ± 3.0%. The between-subject CVs were 25.0%, 12.3%, 5.3%, 10.7% and 6.4%, respectively. Hippocampal long-TE sLASER single voxel spectroscopy can provide macromolecule-independent assessment of all major metabolites including Glx and m-Ins.

Are Cramér-Rao lower bounds an accurate estimate for standard deviations in in vivo magnetic resonance spectroscopy?

Due to inherent time constraints for in vivo experiments, it is infeasible to repeat multiple MRS scans to estimate standard deviations on the desired measured parameters. As such, the Cramér-Rao lower bounds (CRLBs) have become the routine method to approximate standard deviations for in vivo experiments. Cramér-Rao lower bounds, however, as the name suggests, are theoretically a lower bound on the standard deviation and it is not clear if and under what circumstances this approximation is valid. Realistic synthetic 3 T spectra were used to investigate the relationship between estimated CRLBs, true CRLBs and standard deviations. Here we demonstrate that, although the CRLBs are theoretically truly a lower bound on the standard deviation (not an equality) for the problem typically encountered in quantification, they are still an adequate approximation to standard deviation as long as the model perfectly characterizes the data. In the case when the macromolecule basis deviates from the measured macromolecules it was shown that the CRLBs can deviate from standard deviations by approximately 50% for N-acetylaspartic acid, creatine and glutamate and of the order of 100% or more for myo-inositol and γ-aminobutyric acid. In the case when the model perfectly reflects the data the CRLBs are within approximately 10% of standard deviations for all metabolites. The result of the CRLB being within 10% of standard deviations means that, for an accurate model, novel quantification methods such as machine learning or deep learning will not be able to obtain substantially more precise estimates for the desired parameters than traditional maximum-likelihood estimation.

FAMASITO: FASTMAP Shim Tool towards user-friendly single-step B0 homogenization.

Fast, automatic shimming by mapping along projections (FASTMAP) is an elegant analytical method developed to quantify three-dimensional first- and second-order spherical harmonic B0 shapes along six one-dimensional column projections. The straightforward application of this theoretical concept to B0 shimming, however, neglects crucial aspects of sequence implementation and shim hardware, commonly necessitating multistep iterative adjustments. We demonstrate a software package, referred to as FASTMAP Shim Tool (FAMASITO), which is composed of a FASTMAP pulse sequence, automated calibration and analysis routines, and a script for automatically performing experiments. With FAMASITO we demonstrate optimal single-step adjustment of first- and second-order terms (with potential <1% mean refinement of linear terms) in the prefrontal cortex of seven volunteers, one of the most difficult-to-shim areas in the adult human brain.

Minimum Reporting Standards for in vivo Magnetic Resonance Spectroscopy (MRSinMRS): Experts' consensus recommendations.

The translation of MRS to clinical practice has been impeded by the lack of technical standardization. There are multiple methods of acquisition, post-processing, and analysis whose details greatly impact the interpretation of the results. These details are often not fully reported, making it difficult to assess MRS studies on a standardized basis. This hampers the reviewing of manuscripts, limits the reproducibility of study results, and complicates meta-analysis of the literature. In this paper a consensus group of MRS experts provides minimum guidelines for the reporting of MRS methods and results, including the standardized description of MRS hardware, data acquisition, analysis, and quality assessment. This consensus statement describes each of these requirements in detail and includes a checklist to assist authors and journal reviewers and to provide a practical way for journal editors to ensure that MRS studies are reported in full.

INSPECTOR: free software for magnetic resonance spectroscopy data inspection, processing, simulation and analysis.

In vivo magnetic resonance spectroscopy (MRS) is a powerful tool for biomedical research and clinical diagnostics, allowing for non-invasive measurement and analysis of small molecules from living tissues. However, currently available MRS processing and analytical software tools are limited in their potential for in-depth quality management, access to details of the processing stream, and user friendliness. Moreover, available MRS software focuses on selected aspects of MRS such as simulation, signal processing or analysis, necessitating the use of multiple packages and interfacing among them for biomedical applications. The freeware INSPECTOR comprises enhanced MRS data processing, simulation and analytical capabilities in a one-stop-shop solution for a wide range of biomedical research and diagnostic applications. Extensive data handling, quality management and visualization options are built in, enabling the assessment of every step of the processing chain with maximum transparency. The parameters of the processing can be flexibly chosen and tailored for the specific research problem, and extended confidence information is provided with the analysis. The INSPECTOR software stands out in its user-friendly workflow and potential for automation. In addition to convenience, the functionalities of INSPECTOR ensure rigorous and consistent data processing throughout multi-experiment and multi-center studies.

Magnetic resonance Spectrum simulator (MARSS), a novel software package for fast and computationally efficient basis set simulation.

The aim of this study was to develop a novel software platform for the simulation of magnetic resonance spin systems, capable of simulating a large number of spatial points (1283 ) for large in vivo spin systems (up to seven coupled spins) in a time frame of the order of a few minutes. The quantum mechanical density-matrix formalism is applied, a coherence pathway filter is utilized for handling unwanted coherence pathways, and the 1D projection method, which provides a substantial reduction in computation time for a large number of spatial points, is extended to include sequences of an arbitrary number of RF pulses. The novel software package, written in MATLAB, computes a basis set of 23 different metabolites (including the two anomers of glucose, seven coupled spins) with 1283 spatial points in 26 min for a three-pulse experiment on a personal desktop computer. The simulated spectra are experimentally verified with data from both phantom and in vivo MEGA-sLASER experiments. Recommendations are provided regarding the various assumptions made when computing a basis set for in vivo MRS with respect to the number of spatial points simulated and the consideration of relaxation.

Across-vendor standardization of semi-LASER for single-voxel MRS at 3T.

The semi-adiabatic localization by adiabatic selective refocusing (sLASER) sequence provides single-shot full intensity signal with clean localization and minimal chemical shift displacement error and was recommended by the international MRS Consensus Group as the preferred localization sequence at high- and ultra-high fields. Across-vendor standardization of the sLASER sequence at 3 tesla has been challenging due to the B1 requirements of the adiabatic inversion pulses and maximum B1 limitations on some platforms. The aims of this study were to design a short-echo sLASER sequence that can be executed within a B1 limit of 15 µT by taking advantage of gradient-modulated RF pulses, to implement it on three major platforms and to evaluate the between-vendor reproducibility of its perfomance with phantoms and in vivo. In addition, voxel-based first and second order B0 shimming and voxel-based B1 adjustments of RF pulses were implemented on all platforms. Amongst the gradient-modulated pulses considered (GOIA, FOCI and BASSI), GOIA-WURST was identified as the optimal refocusing pulse that provides good voxel selection within a maximum B1 of 15 µT based on localization efficiency, contamination error and ripple artifacts of the inversion profile. An sLASER sequence (30 ms echo time) that incorporates VAPOR water suppression and 3D outer volume suppression was implemented with identical parameters (RF pulse type and duration, spoiler gradients and inter-pulse delays) on GE, Philips and Siemens and generated identical spectra on the GE 'Braino' phantom between vendors. High-quality spectra were consistently obtained in multiple regions (cerebellar white matter, hippocampus, pons, posterior cingulate cortex and putamen) in the human brain across vendors (5 subjects scanned per vendor per region; mean signal-to-noise ratio > 33; mean water linewidth between 6.5 Hz to 11.4 Hz). The harmonized sLASER protocol is expected to produce high reproducibility of MRS across sites thereby allowing large multi-site studies with clinical cohorts.

Preprocessing, analysis and quantification in single-voxel magnetic resonance spectroscopy: experts' consensus recommendations.

Once an MRS dataset has been acquired, several important steps must be taken to obtain the desired metabolite concentration measures. First, the data must be preprocessed to prepare them for analysis. Next, the intensity of the metabolite signal(s) of interest must be estimated. Finally, the measured metabolite signal intensities must be converted into scaled concentration units employing a quantitative reference signal to allow meaningful interpretation. In this paper, we review these three main steps in the post-acquisition workflow of a single-voxel MRS experiment (preprocessing, analysis and quantification) and provide recommendations for best practices at each step.

Development and validation of 3D MP-SSFP to enable MRI in inhomogeneous magnetic fields.

PURPOSE: We demonstrate the feasibility of MRI with missing-pulse steady-state free precession (MP-SSFP) in a 4T magnet with artificially degraded homogeneity. METHODS: T1 , T2 , and diffusion contrast of MP-SSFP was simulated with constant and alternate radiofrequency (RF) phase using an extended phase graph. To validate MP-SSFP performance in human brain imaging, MP-SSFP was tested with two types of artificially introduced inhomogeneous magnetic fields: (1) a pure linear gradient field, and (2) a pseudo-linear gradient field introduced by mounting a head-gradient set at 36 cm from the magnet isocenter. Image distortion induced by the nonlinear inhomogeneous field was corrected using B0 mapping measured with MP-SSFP. RESULTS: The maximum flip angle in MP-SSFP was limited to ≤10° because of the large range of resonance frequencies in the inhomogeneous magnetic fields tested in this study. Under this flip-angle limitation, MP-SSFP with constant RF phase provided advantages of higher signal-to-noise ratio and insensitivity to B1+ field inhomogeneity as compared with an alternate RF phase. In diffusion simulation, the steady-state magnetization in constant RF phase MP-SSFP increased with an increase of static field gradient up to 8 to 21 mT/m depending on simulation parameters. Experimental results at 4T validated these findings. In human brain imaging, MP-SSFP preserved sufficient signal intensities, but images showed severe image distortion from the pseudo-linear inhomogeneous field. However, following distortion correction, good-quality brain images were achieved. CONCLUSION: MP-SSFP appears to be a feasible MRI technique for brain imaging in an inhomogeneous magnetic field.

Contribution of macromolecules to brain 1 H MR spectra: Experts' consensus recommendations.

Proton MR spectra of the brain, especially those measured at short and intermediate echo times, contain signals from mobile macromolecules (MM). A description of the main MM is provided in this consensus paper. These broad peaks of MM underlie the narrower peaks of metabolites and often complicate their quantification but they also may have potential importance as biomarkers in specific diseases. Thus, separation of broad MM signals from low molecular weight metabolites enables accurate determination of metabolite concentrations and is of primary interest in many studies. Other studies attempt to understand the origin of the MM spectrum, to decompose it into individual spectral regions or peaks and to use the components of the MM spectrum as markers of various physiological or pathological conditions in biomedical research or clinical practice. The aim of this consensus paper is to provide an overview and some recommendations on how to handle the MM signals in different types of studies together with a list of open issues in the field, which are all summarized at the end of the paper.