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 [less than] 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

Results and interpretation of a fitting challenge for MR spectroscopy set up by the MRS study group of ISMRM.

PURPOSE Fitting of MRS data plays an important role in the quantification of metabolite concentrations. Many different spectral fitting packages are used by the MRS community. A fitting challenge was set up to allow comparison of fitting methods on the basis of performance and robustness. METHODS Synthetic data were generated for 28 datasets. Short-echo time PRESS spectra were simulated using ideal pulses for the common metabolites at mostly near-normal brain concentrations. Macromolecular contributions were also included. Modulations of signal-to-noise ratio (SNR); lineshape type and width; concentrations of γ-aminobutyric acid, glutathione, and macromolecules; and inclusion of artifacts and lipid signals to mimic tumor spectra were included as challenges to be coped with. RESULTS Twenty-six submissions were evaluated. Visually, most fit packages performed well with mostly noise-like residuals. However, striking differences in fit performance were found with bias problems also evident for well-known packages. In addition, often error bounds were not appropriately estimated and deduced confidence limits misleading. Soft constraints as used in LCModel were found to substantially influence the fitting results and their dependence on SNR. CONCLUSIONS Substantial differences were found for accuracy and precision of fit results obtained by the multiple fit packages

In vivo 1H MR spectroscopy with J‐refocusing

Purpose The goal of this study was to propose a novel localized proton MR spectroscopy (MRS) sequence that reduces signal loss due to J‐modulation in the rat brain in vivo. Methods Sprague‐Dawley rats were studied at 9.4 T. A semi‐LASER sequence with evenly distributed echo‐time (TE) was used, and a 90° J‐refocusing pulse was inserted at TE/2. Proton spectra were acquired at two TEs (30 and 68 ms), with and without the J‐refocused pulse. Data were processed in MATLAB and quantified with LCModel. Results The J‐refocused spectrum acquired at TE = 30 ms did not show any signal losses due to J‐modulation and had comparable spectral pattern to the one acquired with semi‐LASER using the minimum achievable TE. Higher signal amplitudes for glutamine, γ‐aminobutyric acid and glutathione led to more reliable quantification precision for these metabolites. The refocused signal intensities at TE = 68 ms were also unaffected by J‐modulation but were smaller than the signals at TE = 30 ms mainly due to transverse T2 relaxation of metabolites. Conclusion The proposed localized MRS sequence will be beneficial in both animal and human MRS studies when using ultra‐short TE is not possible while also providing more reliable quantification precision for J‐coupled metabolites

Rat brain MRI at 16.4T using a capacitively tunable patch antenna in combination with a receive array

For MRI at 16.4T, with a proton Larmor frequency of 698 MHz, one of the principal RF engineering challenges is to generate a spatially homogeneous transmit field over a larger volume of interest for spin excitation. Constructing volume coils large enough to house a receive array along with the subject and to maintain the quadrature symmetry for different loading conditions is difficult at this frequency. This calls for new approaches to RF coil design for ultra-high field MR systems. A remotely placed capacitively tunable patch antenna, which can easily be adjusted to different loading conditions, was used to generate a relatively homogeneous excitation field covering a large imaging volume with a transversal profile similar to that of a birdcage coil. Since it was placed in front of the animal, this created valuable free space in the narrow magnet bore around the subject for additional hardware. To enhance the reception sensitivity, the patch antenna was combined with an actively detunable 3-channel receive coil array. In addition to increased SNR compared to a quadrature transceive surface coil, we were able to get high quality gradient echo and spin-echo images covering the whole rat brain

Voxel placement and data quality.

<p>(A) Images of human brains illustrating the position and size of the VOI. (B) Representative ¹H STEAM spectra (4 T, 27 mL, <i>T</i>_R = 4.5 s, number of averages = 4) measured at seven <i>T</i>_Es from the human occipital lobe in one young (left) and one elderly (right) subject. The vertical scale has been adjusted such that the NAA resonance detected at <i>T</i>_E = 10 ms for both young and elderly subjects has the same intensity. Horizontal dashed lines are visual guides to indicate that the intensity of NAA and tCr signals decrease faster in the elderly than the young subject. The faster signal decay reflects a shorter <i>T</i>₂ value. Spectra are shown without line broadening. NAA, N-acetylaspartate, tCr, total creatine = creatine (Cr) + phosphocreatine (PCr), tCho, total choline = choline containing compounds.</p

<i>T</i>₂ fits for metabolites in young and elderly subjects.

<p>Individual exponential fits (represented by decaying lines) of the experimentally measured data for (A) the NAA singlet at 2.01 ppm, (B) the tCr signal at 3.03 ppm, and (C) the tCho singlet at 3.2 ppm in one representative young and one representative elderly subject. The amplitude of all data sets was normalized by setting the first <i>T</i>_E point to unity for both young and elderly subjects. For all metabolites and all subjects, <i>T</i>₂s were fit with R² ≥ 0.918, with the lowest R² for tCho.</p

Advanced single voxel 1 H magnetic resonance spectroscopy techniques in humans: Experts' consensus recommendations

Conventional proton MRS has been successfully utilized to noninvasively assess tissue biochemistry in conditions that result in large changes in metabolite levels. For more challenging applications, namely, in conditions which result in subtle metabolite changes, the limitations of vendor-provided MRS protocols are increasingly recognized, especially when used at high fields (>/=3 T) where chemical shift displacement errors, B0 and B1 inhomogeneities and limitations in the transmit B1 field become prominent. To overcome the limitations of conventional MRS protocols at 3 and 7 T, the use of advanced MRS methodology, including pulse sequences and adjustment procedures, is recommended. Specifically, the semiadiabatic LASER sequence is recommended when TE values of 25-30 ms are acceptable, and the semiadiabatic SPECIAL sequence is suggested as an alternative when shorter TE values are critical. The magnetic field B0 homogeneity should be optimized and RF pulses should be calibrated for each voxel. Unsuppressed water signal should be acquired for eddy current correction and preferably also for metabolite quantification. Metabolite and water data should be saved in single shots to facilitate phase and frequency alignment and to exclude motion-corrupted shots. Final averaged spectra should be evaluated for SNR, linewidth, water suppression efficiency and the presence of unwanted coherences. Spectra that do not fit predefined quality criteria should be excluded from further analysis. Commercially available tools to acquire all data in consistent anatomical locations are recommended for voxel prescriptions, in particular in longitudinal studies. To enable the larger MRS community to take advantage of these advanced methods, a list of resources for these advanced protocols on the major clinical platforms is provided. Finally, a set of recommendations are provided for vendors to enable development of advanced MRS on standard platforms, including implementation of advanced localization sequences, tools for quality assurance on the scanner, and tools for prospective volume tracking and dynamic linear shim corrections

Aripiprazole Selectively Reduces Motor Tics in a Young Animal Model for Tourette’s Syndrome and Comorbid Attention Deficit and Hyperactivity Disorder

Tourette’s syndrome (TS) is a neurodevelopmental disorder characterized primarily by motor and vocal tics. Comorbidities such as attention deficit and hyperactivity disorder (ADHD) are observed in over 50% of TS patients. We applied aripiprazole in a juvenile rat model that displays motor tics and hyperactivity. We additionally assessed the amount of ultrasonic vocalizations (USVs) as an indicator for the presence of vocal tics and evaluated the changes in the striatal neurometabolism using in vivo proton magnetic resonance spectroscopy (1H-MRS) at 11.7T. Thirty-one juvenile spontaneously hypertensive rats (SHRs) underwent bicuculline striatal microinjection and treatment with either aripiprazole or vehicle. Control groups were sham operated and sham injected. Behavior, USVs, and striatal neurochemical profile were analyzed at early, middle, and late adolescence (postnatal days 35 to 50). Bicuculline microinjections in the dorsolateral striatum induced motor tics in SHR juvenile rats. Acute aripiprazole administration selectively reduced both tic frequency and latency, whereas stereotypies, USVs, and hyperactivity remained unaltered. The striatal neurochemical profile was only moderately altered after tic-induction and was not affected by systemic drug treatment. When applied to a young rat model that provides high degrees of construct, face, and predictive validity for TS and comorbid ADHD, aripiprazole selectively reduces motor tics, revealing that tics and stereotypies are distinct phenomena in line with clinical treatment of patients. Finally, our 1H-MRS results suggest a critical revision of the striatal role in the hypothesized cortico-striatal dysregulation in TS pathophysiology