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Purpose: Retrospective frequency-and-phase correction (FPC) methods attempt to remove frequency-and-phase variations between transients to improve the quality of the averaged MR spectrum. However, traditional FPC methods like spectral registration struggle at low SNR. Here, we propose a method that directly integrates FPC into a 2D linear-combination model (2D-LCM) of individual transients ("model-based FPC"). We investigated how model-based FPC performs compared to the traditional approach, i.e., spectral registration followed by 1D-LCM in estimating frequency-and-phase drifts and, consequentially, metabolite level estimates., Methods: We created synthetic in-vivo-like 64-transient short-TE sLASER datasets with 100 noise realizations at 5 SNR levels and added randomly sampled frequency and phase variations. We then used this synthetic dataset to compare the performance of 2D-LCM with the traditional approach (spectral registration, averaging, then 1D-LCM). Outcome measures were the frequency/phase/amplitude errors, the SD of those ground-truth errors, and amplitude Cramér Rao lower bounds (CRLBs). We further tested the proposed method on publicly available in-vivo short-TE PRESS data., Results: 2D-LCM estimates (and accounts for) frequency-and-phase variations directly from uncorrected data with equivalent or better fidelity than the conventional approach. Furthermore, 2D-LCM metabolite amplitude estimates were at least as accurate, precise, and certain as the conventionally derived estimates. 2D-LCM estimation of FPC and amplitudes performed substantially better at low-to-very-low SNR., Conclusion: Model-based FPC with 2D linear-combination modeling is feasible and has great potential to improve metabolite level estimation for conventional and dynamic MRS data, especially for low-SNR conditions, for example, long TEs or strong diffusion weighting., (© 2024 International Society for Magnetic Resonance in Medicine.)

Purpose: This goal of this study was to optimize spectrally selective 1 H-MRS methods for large-volume acquisition of low-concentration metabolites with downfield resonances at 7 T and 3 T, with particular attention paid to detection of nicotinamide adenine dinucleotide (NAD + ) and tryptophan., Methods: Spectrally selective excitation was used to avoid magnetization-transfer effects with water, and various sinc pulses were compared with a band-selective, uniform response, pure-phase (E-BURP) pulse. Localization using a single-slice selective pulse was compared with voxel-based localization that used three orthogonal refocusing pulses, and low bandwidth refocusing pulses were used to take advantage of the chemical shift displacement of water. A technique for water sideband removal was added, and a method of coil channel combination for large volumes was introduced., Results: Proposed methods were compared qualitatively with previously reported techniques at 7 T. Sinc pulses resulted in reduced water signal excitation and improved spectral quality, with a symmetric, low bandwidth-time product pulse performing best. Single-slice localization allowed shorter TEs with large volumes, enhancing signal, whereas low-bandwidth slice-selective localization greatly reduced the observed water signal. Gradient cycling helped remove water sidebands, and frequency aligning and pruning individual channels narrowed spectral linewidths. High-quality brain spectra of NAD + and tryptophan are shown in 4 subjects at 3 T., Conclusion: Improved spectral quality with higher downfield signal, shorter TE, lower nuisance signal, reduced artifacts, and narrower peaks was realized at 7 T. These methodological improvements allowed for previously unachievable detection of NAD + and tryptophan in human brain at 3 T in under 5 min., (© 2024 The Author(s). Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Purpose: To develop a manifold learning-based method that leverages the intrinsic low-dimensional structure of MR Spectroscopic Imaging (MRSI) signals for joint spectral quantification., Methods: A linear tangent space alignment (LTSA) model was proposed to represent MRSI signals. In the proposed model, the signals of each metabolite were represented using a subspace model and the local coordinates of the subspaces were aligned to the global coordinates of the underlying low-dimensional manifold via linear transform. With the basis functions of the subspaces predetermined via quantum mechanics simulations, the global coordinates and the matrices for the local-to-global coordinate alignment were estimated by fitting the proposed LTSA model to noisy MRSI data with a spatial smoothness constraint on the global coordinates and a sparsity constraint on the matrices., Results: The performance of the proposed method was validated using numerical simulation data and in vivo proton-MRSI experimental data acquired on healthy volunteers at 3T. The results of the proposed method were compared with the QUEST method and the subspace-based method. In all the compared cases, the proposed method achieved superior performance over the QUEST and the subspace-based methods both qualitatively in terms of noise and artifacts in the estimated metabolite concentration maps, and quantitatively in terms of spectral quantification accuracy measured by normalized root mean square errors., Conclusion: Joint spectral quantification using linear tangent space alignment-based manifold learning improves the accuracy of MRSI spectral quantification., (© 2022 International Society for Magnetic Resonance in Medicine.)

Purpose: To develop a robust method for brain metabolite quantification in proton magnetic resonance spectroscopy ( 1 H-MRS) using a convolutional neural network (CNN) that maps in vivo brain spectra that are typically degraded by low SNR, line broadening, and spectral baseline into noise-free, line-narrowed, baseline-removed intact metabolite spectra., Methods: A CNN was trained (n = 40 000) and tested (n = 5000) on simulated brain spectra with wide ranges of SNR (6.90-20.74) and linewidth (10-20 Hz). The CNN was further tested on in vivo spectra (n = 40) from five healthy volunteers with substantially different SNR, and the results were compared with those from the LCModel analysis. A Student t test was performed for the comparison., Results: Using the proposed method the mean-absolute-percent-errors (MAPEs) in the estimated metabolite concentrations were 12.49% ± 4.35% for aspartate, creatine (Cr), γ-aminobutyric acid (GABA), glucose, glutamine, glutamate, glutathione (GSH), myo-Inositol (mI), N-acetylaspartate, phosphocreatine (PCr), phosphorylethanolamine, and taurine over the whole simulated spectra in the test set. The metabolite concentrations estimated from in vivo spectra were close to the reported ranges for the proposed method and the LCModel analysis except mI, GSH, and especially Cr/PCr for the LCModel analysis, and phosphorylcholine to glycerophosphorylcholine ratio (PC/GPC) for both methods. The metabolite concentrations estimated across the in vivo spectra with different SNR were less variable with the proposed method (~10% or less) than with the LCModel analysis., Conclusion: The robust performance of the proposed method against low SNR may allow a subminute 1 H-MRS of human brain, which is an important technical development for clinical studies., (© 2019 International Society for Magnetic Resonance in Medicine.)

Purpose: To simultaneously measure glutamate, glutamine, γ-aminobutyric acid (GABA), and glutathione using spectral editing without subtraction at 7T., Methods: A novel spectral editing approach was proposed to simultaneously measure glutamate, glutamine, GABA, and glutathione using a TE of 56 ms at 7T. By numerical optimization of sequence timing in the presence of an editing pulse, the 4 metabolites all form relatively intense pseudo singlets with maximized peak amplitudes and minimized peak linewidths in 1 of the 3 interleaved spectra. For measuring glutamate, glutamine, and glutathione, the editing pulse targets the H 3 protons of these metabolites near 2.12 parts per million. Both GABA H 2 and H 4 resonances are fully utilized in spectral fitting., Results: Concentration levels (/[total creatine]) of glutamate, glutamine, GABA, and glutathione from an 8 mL voxel in the pregenual anterior cingulate cortex of 5 healthy volunteers were found to be 1.26 ± 0.13, 0.33 ± 0.06, 0.13 ± 0.03, and 0.27 ± 0.03, respectively, with within-subject coefficient of variation at 3.2%, 8.2%, 7.1%, and 10.2%, respectively. The total scan time was less than 4.5 min., Conclusions: The proposed new technique does not require data subtraction. The 3 major metabolites of the glutamatergic and GABAergic systems and the oxidative stress marker glutathione were all measured in 1 short scan with high precision., (© Published 2018. This article is a U.S. Government work and is in the public domain in the USA.)

Purpose: To demonstrate simultaneous editing of the two most commonly edited and overlapping signals, γ-aminobutyric acid (GABA), and glutathione (GSH), with Hadamard encoding and reconstruction of MEGA-edited spectroscopy (HERMES) using sLASER localization at 7T., Methods: Density matrix simulations of HERMES at 7T were carried out and compared with phantom experiments. Additional phantom experiments were performed to characterize the echo time (TE) -dependent modulation of GABA- and GSH-edited HERMES spectra at TE of 80-160 ms. In vivo experiments were performed in 10 healthy volunteers, comparing HERMES (11 min) to sequentially acquired MEGA-sLASER detection of GABA and GSH (2 × 11 min)., Results: Simulations of HERMES show GABA- and GSH-edited spectra with negligible levels of crosstalk, and give modest agreement with phantom spectra. The TE series of GABA- and GSH-edited HERMES spectra modulate as a result of T 2 relaxation and coupling evolution, with GABA showing a stronger TE-dependence. In vivo HERMES experiments show well-edited GABA and GSH signals. Measured concentrations are not statistically different between HERMES and MEGA-sLASER for GABA (1. 051 ± 0.254 i.u. and 1.053 ± 0.248 i.u; P > 0.985) or GSH (0.300 ± 0.091 i.u. and 0.302 ± 0.093 i.u; P > 0.940)., Conclusion: Simulated, phantom and in vivo measurements of HERMES show excellent segregation of GABA- and GSH-edited signals, and excellent agreement with separately acquired MEGA-sLASER data. HERMES allows two-fold acceleration of editing while maintaining spectral quality compared with sequentially acquired MEGA-sLASER measurements. Magn Reson Med 80:474-479, 2018. © 2017 International Society for Magnetic Resonance in Medicine., (© 2017 International Society for Magnetic Resonance in Medicine.)

Purpose: UTE sequences with a minimal nominal TE of 8 µs have shown promise for direct imaging of myelin protons (T 2 , < 1 ms). However, there is still debate about the efficiency of 2D slice-selective UTE sequences in exciting myelin protons because the half excitation pulses used in these sequences have a relatively long duration (e.g., 0.3-0.6 ms). Here, we compared UTE and inversion-recovery (IR) UTE sequences used with either hard or half excitation pulses (durations 32 µs or 472 µs, respectively) for imaging myelin in native and deuterated ovine brain at 3T., Methods: Freshly frozen ovine brains were dissected into ∼2 mm-thick pure white matter and ∼3 to 8 mm-thick cerebral hemisphere specimens, which were imaged before and/or after different immersion time in deuterium oxide., Results: Bicomponent T2* analysis of UTE signals obtained with hard excitation pulses detected an ultrashort T 2 component (STC) fraction (f S ) of 0% to 10% in native specimens, and up to ∼86% in heavily deuterated specimens. f S values were significantly affected by the TIs used in IR-UTE sequences with either hard or half excitation pulses in native specimens but not in heavily deuterated specimens. The STC T2* was in the range of 150 to 400 µs in all UTE and IR-UTE measurements obtained with either hard or half excitation pulses., Conclusion: Our results further support myelin protons as the major source of the ultrashort T2* signals seen on IR-UTE images and demonstrate the potential of IR-UTE sequences with half excitation pulses for directly imaging myelin using clinical scanners. Magn Reson Med 80:538-547, 2017. © 2017 International Society for Magnetic Resonance in Medicine., (© 2017 International Society for Magnetic Resonance in Medicine.)

Purpose: To investigate the utility of an advanced magnetic resonance spectroscopy (MRS) protocol in the clinical setting, and to compare the localization accuracy, spectral quality, and quantification repeatability between this advanced and the conventional vendor-provided MRS protocol on a clinical 3T platform., Methods: Proton spectra were measured from the posterior cingulate cortices in 30 healthy elderly subjects by clinical MR technologists using a vendor-provided (point resolved spectroscopy with advanced 3D gradient-echo B 0 shimming) and an advanced (semi-LASER with FAST(EST)MAP shimming) protocol, in random order. Spectra were quantified with LCModel using standard pipelines for the clinical and research settings, respectively., Results: The advanced protocol outperformed the vendor-provided protocol in localization accuracy (chemical-shift-displacement error: 2.0%/ppm, semi-LASER versus 11.6%/ppm, point resolved spectroscopy), spectral quality (water linewidth: 6.1 ± 1.8 Hz, FAST(EST)MAP versus 10.5 ± 3.7 Hz, 3D gradient echo; P < 7e-6; residual water: 0.08 ± 0.12%, VAPOR versus 0.45 ± 0.50%, WET; P < 2e-5) and within-session repeatability of metabolite concentrations, particularly of low signal-to-noise ratio data with two to eight averages (test-retest coefficients of variance of metabolite concentrations, P < 0.01). Concentrations of J-coupled metabolites such as γ-aminobutyric acid and glutamate were biased when using the default pipeline with simulated macromolecules., Conclusions: The quality of MRS data can be improved using advanced acquisition and analysis protocols on standard 3T hardware in the clinical setting, which can facilitate robust applications in central nervous system diseases. Magn Reson Med 79:1241-1250, 2018. © 2017 International Society for Magnetic Resonance in Medicine., (© 2017 International Society for Magnetic Resonance in Medicine.)

Purpose: Accumulation of triglycerides in nonadipose tissue (e.g. ectopic lipids) is characteristic of metabolic derangements and is linked to insulin resistance and cardiovascular disease. Although the detrimental effects of the total amount of ectopic fat has been established, the role of composition of the ectopic lipid stores is unknown. In this study we used proton magnetic resonance spectroscopy ( 1 H-MRS) homonuclear spectral editing to characterize lipid stores in adipose tissue and skeletal muscle at 4 T., Methods: A MEGA-sLASER sequence was used to selectively detect lipid resonances that are scalar coupled to the methine resonance at 5.31 ppm and that can be used to estimate saturated fatty acid and mono- and polyunsaturated fatty acids. Phantom experiments were performed to empirically determine correction factors for editing efficiency of the different lipid groups., Results: The spectral editing approach enabled the estimation of saturated, mono-unsaturated, and polyunsaturated fatty acid contributions in phantoms and in vivo. These estimations are in the same order as reported in studies using invasive biopsies., Conclusions: In this study, we have shown the feasibility of spectral editing techniques for ectopic lipid store characterization with 1 H-MRS, regardless of spectral resolution (e.g., B 0- field strength). This new approach offers the opportunity to study ectopic lipid composition in relation to metabolic diseases. Magn Reson Med 79:619-627, 2018. © 2017 International Society for Magnetic Resonance in Medicine., (© 2017 International Society for Magnetic Resonance in Medicine.)

Purpose: In vivo carbon-13 ( 13 C) MR spectroscopy (MRS) is capable of measuring energy metabolism and neuroenergetics, noninvasively in the brain. Indirect ( 1 H-[ 13 C]) MRS provides sensitivity benefits compared with direct 13 C methods, and normally includes a 1 H surface coil for both localization and signal reception. The aim was to develop a coil platform with homogenous B1+ and use short conventional pulses for short echo time proton observed carbon edited (POCE) MRS., Methods: A 1 H-[ 13 C] MRS coil platform was designed with a volumetric resonator for 1 H transmit, and surface coils for 1 H reception and 13 C transmission. The Rx-only 1 H surface coil nullifies the requirement for a T/R switch before the 1 H preamplifier; the highpass filter and preamplifier can be placed proximal to the coil, thus minimizing sensitivity losses inherent with POCE-MRS systems described in the literature. The coil platform was evaluated with a PRESS-POCE sequence (TE = 12.6 ms) on a rat model., Results: The coil provided excellent localization, uniform spin nutation, and sensitivity. 13 C labeling of Glu-H4 and Glx-H3 peaks, and the Glx-H2 peaks were observed approximately 13 and 21 min following the infusion of 1- 13 C glucose, respectively., Conclusion: A convenient and sensitive platform to study energy metabolism and neurotransmitter cycling is presented. Magn Reson Med 79:628-635, 2018. © 2017 International Society for Magnetic Resonance in Medicine., (© 2017 International Society for Magnetic Resonance in Medicine.)

Purpose: We present a new Bloch-Siegert four Angle Saturation Transfer (BOAST) method for measuring the creatine kinase (CK) first-order effective rate constant k f in human myocardium at 7 tesla (T). BOAST combines a variant of the four-angle saturation transfer (FAST) method using amplitude-modulated radiofrequency pulses, phosphorus Bloch-Siegert B1+-mapping to determine the per-voxel flip angles, and nonlinear fitting to Bloch simulations for postprocessing., Methods: Optimal flip angles and repetition time parameters were determined from Monte Carlo simulations. BOAST was validated in the calf muscle of two volunteers at 3T and 7T. The myocardial CK forward rate constant was then measured in 10 volunteers at 7T in 82 min (after 1 H localization)., Results: BOAST kfCK values were 0.281 ± 0.002 s -1 in the calf and 0.35 ± 0.05 s -1 in myocardium. These are consistent with literature values from lower fields. Using a literature values for adenosine triphosphate concentration, we computed CK flux values of 4.55 ± 1.52 mmol kg -1 s -1 . The sensitive volume for BOAST depends on the B 1 inhomogeneity of the transmit coil., Conclusion: BOAST enables measurement of the CK rate constant in the human heart at 7T, with spatial localization in three dimensions to 5.6 mL voxels, using a 10-cm loop coil. Magn Reson Med 78:20-32, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited., (© 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.)

Purpose: Multislice maps of extracellular pH (pHe) are needed to interrogate the heterogeneities of tumors and normal organs. To address this need, we have developed a multislice chemical exchange saturation transfer (CEST) MRI acquisition method with a CEST spectrum-fitting method that measures in vivo pHe over a range of 6.3 to 7.4., Methods: The phase offset multiplanar (POMP) method was adapted for CEST fast imaging with steady-state free precession (FISP) MRI to acquire multiple image slices with a single CEST saturation pulse. The Bloch-McConnell equations were modified to include pH based on a calibration of pH and chemical exchange rate for the contrast agent iopamidol. These equations were used to estimate the pixel-wise pHe values throughout the multislice acidoCEST MR images of the tumor, kidney, bladder, and other tissues of a MDA-MB-231 tumor model., Results: Multislice acidoCEST MRI successfully mapped a gradient of pHe from 6.73 to 6.81 units from the tumor core to rim, and also mapped a gradient of pHe 6.56 to 6.97 across the mouse kidney. The bladder was found to be pHe 6.3., Conclusion: AcidoCEST MRI with POMP acquisition and Bloch-McConnel analysis can map pHe in multiple imaging slices through the tumor, kidney, and bladder. This multislice evaluation facilitates assessments of spatial heterogeneity of tissue pHe. Magn Reson Med 78:97-106, 2017. © 2016 International Society for Magnetic Resonance in Medicine., (© 2016 International Society for Magnetic Resonance in Medicine.)

Purpose: Classification of pediatric brain tumors from 1 H-magnetic resonance spectroscopy (MRS) can aid diagnosis and management of brain tumors. However, varied incidence of the different tumor types leads to imbalanced class sizes and introduces difficulties in classifying rare tumor groups. This study assessed different imbalanced multiclass learning techniques and compared the use of complete spectra and quantified metabolite profiles for classification of three main childhood brain tumor types., Methods: Single-voxel, Short echo time MRS data were collected from 90 patients with pilocytic astrocytoma (n = 42), medulloblastoma (n = 38), or ependymoma (n = 10). Both spectra and metabolite profiles were used to develop the learning algorithms. The borderline synthetic minority oversampling technique and AdaboostM1 were used to correct for the skewed distribution. Classifiers were trained using five different pattern recognition algorithms., Results: Use of imbalanced learning techniques improved the balanced accuracy rate (BAR) of all classification methods (average BAR over all classification methods for spectra: oversampled data = 0.81, original = 0.63, P < 0.001; metabolite concentration: oversampled-data = 0.91, original = 0.75, P < 0.0001). Performance of all classifiers in discriminating ependymomas increased when oversampled data were used compared with original data for both complete spectra (F-measure P < 0.01) and metabolite profile (F-measure P < 0.001)., Conclusion: Imbalanced learning techniques improve the classification accuracy of childhood brain tumors from MRS where group sizes differ and facilitate the inclusion of rarer tumor types into clinical decision support systems. Magn Reson Med 77:2114-2124, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited., (© 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.)

Purpose: To develop an efficient MRI approach to estimate the nonwater proton fraction (f) in human brain., Methods: We implement a brief, efficient magnetization transfer (MT) pulse that selectively saturates the magnetization of the (semi-) solid protons, and monitor the transfer of this saturation to the water protons as a function of delay after saturation., Results: Analysis of the transient MT effect with two-pool model allowed robust extraction of f at both 3 and 7 T. This required estimating the longitudinal relaxation rate constant (R 1,MP and R 1,WP ) for both proton pools, which was achieved with the assumption of uniform R 1,MP and R 1,WP across brain tissues. Resulting values of f were approximately 50% higher than reported previously, which is partly attributed to MT-pulse efficiency and R 1,MP being higher than assumed previously., Conclusion: Experiments performed on human brain in vivo at 3 and 7 T demonstrate the ability of the method to robustly determine f in a scan time of approximately 5 min. Magn Reson Med 77:2174-2185, 2017. © 2016 International Society for Magnetic Resonance in Medicine., (© 2016 International Society for Magnetic Resonance in Medicine.)

Purpose: 1 H MRI is an established diagnostic method that generally relies on detection of water. Imaging specific macromolecules is normally accomplished only indirectly through the use of paramagnetic tags, which alter the water signal in their vicinity. We demonstrate a new approach in which macromolecular constituents, such as proteins and drug delivery systems, are observed directly and quantitatively in vivo using 1 H MRI of 13 C-labeled poly(ethylene glycol) ( 13 C-PEG) tags., Methods: Molecular imaging of 13 C-PEG-labeled species was accomplished by incorporating a modified heteronuclear multiple quantum coherence filter into a gradient echo imaging sequence. We demonstrate the approach by monitoring the real-time distribution of 13 C-PEG and 13 C-PEGylated albumin injected into the hind leg of a mouse., Results: Filtering the 1 H PEG signal through the directly coupled 13 C nuclei largely eliminates background water and fat signals, thus enabling the imaging of molecules using 1 H MRI., Conclusion: PEGylation is widely employed to enhance the performance of a multitude of macromolecular therapeutics and drug delivery systems, and 13 C-filtered 1 H MRI of 13 C-PEG thus offers the possibility of imaging and quantitating their distribution in living systems in real time. Magn Reson Med 77:1553-1561, 2017. © 2016 International Society for Magnetic Resonance in Medicine., (© 2016 International Society for Magnetic Resonance in Medicine.)

The Proton magnetic resonance ( 1 H-MRS) spectrum contains information about the concentration of tissue metabolites within a predefined region of interest (a voxel). The conventional spectrum in some cases obscures information about less abundant metabolites due to limited separation and complex splitting of the metabolite peaks. One method to detect these metabolites is to reduce the complexity of the spectrum using editing. This review provides an overview of the one-dimensional editing methods available to interrogate these obscured metabolite peaks. These methods include sequence optimizations, echo-time averaging, J-difference editing methods (single BASING, dual BASING, and MEGA-PRESS), constant-time PRESS, and multiple quantum filtering. It then provides an overview of the brain metabolites whose detection can benefit from one or more of these editing approaches, including ascorbic acid, γ-aminobutyric acid, lactate, aspartate, N-acetyl aspartyl glutamate, 2-hydroxyglutarate, glutathione, glutamate, glycine, and serine. Magn Reson Med 77:1377-1389, 2017. © 2017 International Society for Magnetic Resonance in Medicine., (© 2017 International Society for Magnetic Resonance in Medicine.)

Purpose: Cartesian k-space sampling in three-dimensional magnetic resonance spectroscopic imaging (MRSI) of the prostate limits the selection of voxel size and acquisition time. Therefore, large prostates are often scanned at reduced spatial resolutions to stay within clinically acceptable measurement times. Here we present a semilocalized adiabatic selective refocusing (sLASER) sequence with gradient-modulated offset-independent adiabatic (GOIA) refocusing pulses and spiral k-space acquisition (GOIA-sLASER-Spiral) for fast prostate MRSI with enhanced resolution and extended matrix sizes., Methods: MR was performed at 3 tesla with an endorectal receive coil. GOIA-sLASER-Spiral at an echo time (TE) of 90 ms was compared to a point-resolved spectroscopy sequence (PRESS) with weighted, elliptical phase encoding at an TE of 145 ms using simulations and measurements of phantoms and patients (n = 9)., Results: GOIA-sLASER-Spiral acquisition allows prostate MR spectra to be obtained in ∼5 min with a quality comparable to those acquired with a common Cartesian PRESS protocol in ∼9 min, or at an enhanced spatial resolution showing more precise tissue allocation of metabolites. Extended field of views (FOVs) and matrix sizes for large prostates are possible without compromising spatial resolution or measurement time., Conclusion: The flexibility of spiral sampling enables prostate MRSI with a wide range of resolutions and FOVs without undesirable increases in acquisition times, as in Cartesian encoding. This approach is suitable for routine clinical exams of prostate metabolites. Magn Reson Med 77:928-935, 2017. © 2016 International Society for Magnetic Resonance in Medicine., (© 2016 International Society for Magnetic Resonance in Medicine.)

Purpose: Acetylcarnitine formation is suggested to be crucial in sustaining metabolic flexibility and glucose homeostasis. Recently, we introduced a method to detect acetylcarnitine in vivo with long TE 1 H-MRS. Differences in T 1 relaxation time between lipids and acetylcarnitine can be exploited for additional lipid suppression in subjects with high myocellular lipid levels., Methods: Acquisition of spectra with an inversion recovery sequence was alternated with standard signal acquisition to suppress short T 1 metabolite signals. A proof of principle experiment was conducted in a lean subject and the new approach was subsequently tested in four overweight/obese subjects., Results: Using the new T 1 editing approach, lipid signals in spectra of skeletal muscle can be (additionally) suppressed by a factor of 10 using a TI of 900 ms. Combination of the long TE protocol with the T 1 editing resulted in a well-resolved acetylcarnitine peak in the obese subjects., Conclusion: The T 1 editing approach suppresses short T 1 metabolites and offers a new contrast in 1 H-MRS. The approach should be used in combination with a long TE in subjects with high lipid contamination for accurate quantification of the acetylcarnitine concentration. Magn Reson Med 77:505-510, 2017. © 2016 International Society for Magnetic Resonance in Medicine., (© 2016 International Society for Magnetic Resonance in Medicine.)

Purpose: To improve signal-to-noise ratio (SNR) for high-resolution spectroscopic imaging using a subspace-based technique known as SPectroscopic Imaging by exploiting spatiospectral CorrElation (SPICE)., Methods: The proposed method is based on a union-of-subspaces model of MRSI signals, which exploits the partial separability properties of water, lipid, baseline and metabolite signals. Enabled by this model, a special scheme is used for accelerated data acquisition, which includes a double-echo CSI component used to collect a "training" dataset (for determination of the basis functions) and a short-TE EPSI component used to collect a sparse "imaging" dataset (for determination of the overall spatiospectral distributions). A set of signal processing algorithms are developed to remove the water and lipid signals and jointly reconstruct the metabolite and baseline signals., Results: In vivo 1 H-MRSI results show that the proposed method can effectively remove the remaining water and lipid signals from sparse MRSI data acquired at 20 ms TE. Spatiospectral distributions of metabolite signals at 2 mm in-plane resolution with good SNR were obtained in a 15.5 min scan., Conclusions: The proposed method can effectively remove nuisance signals and reconstruct high-resolution spatiospectral functions from sparse data to make short-TE SPICE possible. The method should prove useful for high-resolution 1 H-MRSI of the brain. Magn Reson Med 77:467-479, 2017. © 2016 International Society for Magnetic Resonance in Medicine., (© 2016 International Society for Magnetic Resonance in Medicine.)

Purpose: This study suggests a noninvasive and repetitive measurement method using 1 H magnetic resonance spectroscopy to monitor changes in cellular metabolites within a single sample., Methods: Longitudinal acquisition of cellular metabolites from three-dimensional cultured human osteosarcoma (MG-63) cells was conducted using 3.0 Tesla 1 H MRS for 2 weeks at three time points: days 1, 7, and 14. During the MR spectroscopy (MRS) scan, cell specimen temperatures were kept constant at 37°C by a lab-developed magnetic resonance compatible thermostatic device. A DNA assay and live/dead staining of the cell specimens were carried out at each time point to verify the MRS measurements., Results: Cell viability in the proposed device did not significantly differ from that of cells in a conventional incubator (P = 0.946). Cell proliferation and choline concentration increased during the first week, but remained constant during the second week. Lactate did not change during the first week, but increased during the second week. Likewise, cell viability remained constant until day 7, then decreased., Conclusion: The proposed MRS technique results in a survivable environment for longitudinal studies of cells and provides a new way to measure metabolomic changes over time in single specimens of cells. Magn Reson Med 76:1912-1918, 2016. © 2016 International Society for Magnetic Resonance in Medicine., (© 2016 International Society for Magnetic Resonance in Medicine.)

Purpose: A new method is proposed for noninvasive detection of glucose in vivo using proton MR spectroscopy at 7 Tesla., Theory and Methods: The proposed method utilizes J-difference editing to uncover the resonance of beta-glucose (β-glc) at 3.23 ppm, which is strongly overlapped with choline. Calculations using the density matrix formalism are used to maximize the signal-to-noise ratio of the β-glc resonance at 3.23 ppm. The calculations are verified using phantom and in vivo data collected at 7 Tesla., Results: The proposed method allows observation of the glucose signal at 3.23 ppm in the human brain spectrum. Additional co-edited resonances of N-acetylaspartylglutamatate and glutathione are also detected in the same experiment., Conclusion: The proposed method does not require carbon ( 13 C)- labeled glucose injections and 13 C hardware; as such, it has a potential to provide valuable information on intrinsic glucose concentration in the human brain in vivo. Magn Reson Med 76:1653-1660, 2016. © 2016 International Society for Magnetic Resonance in Medicine., (© 2016 International Society for Magnetic Resonance in Medicine.)

Purpose: To develop data acquisition and image reconstruction methods to enable high-resolution (1) H MR spectroscopic imaging (MRSI) of the brain, using the recently proposed subspace-based spectroscopic imaging framework called SPICE (SPectroscopic Imaging by exploiting spatiospectral CorrElation)., Theory and Methods: SPICE is characterized by the use of a subspace model for both data acquisition and image reconstruction. For data acquisition, we propose a novel spatiospectral encoding scheme that provides hybrid data sets for determining the subspace structure and for image reconstruction using the subspace model. More specifically, we use a hybrid chemical shift imaging /echo-planar spectroscopic imaging sequence for two-dimensional (2D) MRSI and a dual-density, dual-speed echo-planar spectroscopic imaging sequence for three-dimensional (3D) MRSI. For image reconstruction, we propose a method that can determine the subspace structure and the high-resolution spatiospectral reconstruction from the hybrid data sets generated by the proposed sequences, incorporating field inhomogeneity correction and edge-preserving regularization., Results: Phantom and in vivo brain experiments were performed to evaluate the performance of the proposed method. For 2D MRSI experiments, SPICE is able to produce high-SNR spatiospectral distributions with an approximately 3 mm nominal in-plane resolution from a 10-min acquisition. For 3D MRSI experiments, SPICE is able to achieve an approximately 3 mm in-plane and 4 mm through-plane resolution in about 25 min., Conclusion: Special data acquisition and reconstruction methods have been developed for high-resolution (1) H-MRSI of the brain using SPICE. Using these methods, SPICE is able to produce spatiospectral distributions of (1) H metabolites in the brain with high spatial resolution, while maintaining a good SNR. These capabilities should prove useful for practical applications of SPICE. Magn Reson Med 76:1059-1070, 2016. © 2015 Wiley Periodicals, Inc., (© 2015 Wiley Periodicals, Inc.)

Purpose: To estimate the exchange rates of labile (1) H in citrate and spermine, metabolites present in prostatic secretions, to predict the size of the citrate and spermine CEST effects in vivo., Methods: CEST z-spectra were acquired at high-field [11.7 Tesla (T)] from citrate and spermine solutions at physiological pH (6.5) using saturation power 6 μT. CEST was performed at different temperatures to determine exchange regimes (slow, intermediate or fast). For low pH solutions of spermine, exchange rates were estimated from resonance line width, fitting z-spectra using the Bloch equations incorporating exchange, and using quantifying exchange using saturation time experiments (QUEST). These rates were extrapolated to physiological pH., Results: Citrate showed little CEST effect at pH 6.5 and temperature (T) = 310 K (maximum 0.001% mM(-1) ), indicating fast exchange, whereas spermine showed greater CEST effects (maximum 0.2% mM(-1) ) indicating intermediate-to-fast exchange. Extrapolating data acquired from low pH spermine solutions predicts exchange rates at pH 6.5 and T of 310 K of at least 2 × 10(4) s(-1) ., Conclusion: Citrate and spermine show minimal CEST effects at 11.7T even using high saturation power. These effects would be much less than 2% at clinical field-strengths due to relatively faster exchange and would be masked by CEST from proteins. Magn Reson Med 76:742-746, 2016. © 2015 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited., (© 2015 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.)

Purpose: Proton resonance frequency thermometry is well established for monitoring small temperature changes in tissue. Application of the technique to the measurement of complex temperature distributions within fluid flow is of great interest to the engineering community and could also have medical applications. This work presents an experimental approach to reliably measure three-dimensional (3D) temperature fields in fluid flow using proton resonance frequency thermometry., Methods: A velocity-compensated three-dimensional gradient echo sequence was used. A flexible pumping system was attached to an MR compatible double pipe heat exchanger. The temperature of two separate flow circuits could be adjusted to produce various three-dimensional spatial temperature distributions within the fluid flow. Validation was performed using MR compatible temperature probes in a uniformly heated flow. A comparative study was conducted with thermocouples in the presence of a spatially varying temperature distribution., Results: In uniformly heated flow, temperature changes were accurately measured to within 0.5 K using proton resonance frequency thermometry, while spatially varying temperature changes measured with MR showed good qualitative agreement with pointwise measurements using thermocouples., Conclusion: Proton resonance frequency thermometry can be used in a variety of complex flow situations to address medical as well as engineering questions. This work makes it possible to gain new insights into fundamental heat transfer phenomena. Magn Reson Med 76:145-155, 2016. © 2015 Wiley Periodicals, Inc., (© 2015 Wiley Periodicals, Inc.)

Purpose: To investigate a novel Hadamard-encoded spectral editing scheme and evaluate its performance in simultaneously quantifying N-acetyl aspartate (NAA) and N-acetyl aspartyl glutamate (NAAG) at 3 Tesla., Methods: Editing pulses applied according to a Hadamard encoding scheme allow the simultaneous acquisition of multiple metabolites. The method, called HERMES (Hadamard Encoding and Reconstruction of MEGA-Edited Spectroscopy), was optimized to detect NAA and NAAG simultaneously using density-matrix simulations and validated in phantoms at 3T. In vivo data were acquired in the centrum semiovale of 12 normal subjects. The NAA:NAAG concentration ratio was determined by modeling in vivo data using simulated basis functions. Simulations were also performed for potentially coedited molecules with signals within the detected NAA/NAAG region., Results: Simulations and phantom experiments show excellent segregation of NAA and NAAG signals into the intended spectra, with minimal crosstalk. Multiplet patterns show good agreement between simulations and phantom and in vivo data. In vivo measurements show that the relative peak intensities of the NAA and NAAG spectra are consistent with a NAA:NAAG concentration ratio of 4.22:1 in good agreement with literature. Simulations indicate some coediting of aspartate and glutathione near the detected region (editing efficiency: 4.5% and 78.2%, respectively, for the NAAG reconstruction and 5.1% and 19.5%, respectively, for the NAA reconstruction)., Conclusion: The simultaneous and separable detection of two otherwise overlapping metabolites using HERMES is possible at 3T. Magn Reson Med 76:11-19, 2016. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Purpose: To develop reliable three-dimensional (3D) segmented echo planar imaging (seg-EPI) proton resonance frequency (PRF) temperature monitoring in the presence of respiration-induced B0 variation., Methods: A free induction decay (FID) phase navigator was inserted into a 3D seg-EPI sequence before and after EPI readout to monitor B0 field variations. Using the field change estimates, the phase of each k-space line was adjusted to remove the additional phase from the respiratory induced off-resonance. This correction technique was evaluated while heating with MR-guided focused ultrasound (MRgFUS) in phantoms with simulated breathing and during nonheating conditions in healthy in vivo breasts., Results: With k-space phase correction, the standard deviation of magnitude images and PRF temperature measurements in breast from five volunteers improved by an average factor of 1.5 and 2.1, respectively. Improved accuracy of temperature estimates was observed after correction while heating with MRgFUS in phantoms., Conclusion: Phase correction based on two FID navigators placed before and after the echo train provides promising results for implementing 3D monitoring of thermal therapy treatments in the presence of field variations due to respiration. Magn Reson Med 76:206-213, 2016. © 2015 Wiley Periodicals, Inc., (© 2015 Wiley Periodicals, Inc.)

Purpose: To propose an accurate methodological framework for automatically segmenting pulmonary proton MRI based on an optimal consensus of a spatially normalized library of annotated lung atlases., Methods: A library of 62 manually annotated lung atlases comprising 48 mixed healthy, chronic obstructive pulmonary disease, and asthmatic subjects of a large age range with multiple ventilation levels is used to produce an optimal segmentation in proton MRI, based on a consensus of the spatially normalized library. An extension of this methodology is used to provide best-guess estimates of lobar subdivisions in proton MRI from annotated computed tomography data., Results: A leave-one-out evaluation strategy was used for evaluation. Jaccard overlap measures for the left and right lungs were used for performance comparisons relative to the current state-of-the-art (0.966 ± 0.018 and 0.970 ± 0.016, respectively). Best-guess estimates for the lobes exhibited comparable performance levels (left upper: 0.882 ± 0.059, left lower: 0.868 ± 0.06, right upper: 0.852 ± 0.067, right middle: 0.657 ± 0.130, right lower: 0.873 ± 0.063)., Conclusion: An annotated atlas library approach can be used to provide good lung and lobe estimation in proton MRI. The proposed framework is useful for subsequent anatomically based analysis of structural and/or functional pulmonary image data. Magn Reson Med 76:315-320, 2016. © 2015 Wiley Periodicals, Inc., (© 2015 Wiley Periodicals, Inc.)

Purpose: To propose and optimize diffusion-weighted stimulated echo acquisition mode (DW-STEAM) for measuring fat unsaturation in the presence of a strong water signal by suppressing the water signal based on a shorter T2 and higher diffusivity of water relative to fat., Methods: A parameter study for point-resolved spectroscopy (PRESS) and STEAM using oil phantoms was performed and correlated with gas chromatography (GC). Simulations of muscle tissue signal behavior using DW-STEAM and long-echo time (TE) PRESS and a parameter optimization for DW-STEAM were conducted. DW-STEAM and long-TE PRESS were applied in the gastrocnemius muscles of nine healthy subjects., Results: STEAM with TE and mixing time (TM) up to 45 ms exhibited R(2) correlations above 0.98 with GC and little T2 -weighting and J-modulation for the quantified olefinic/methylene peak ratio. The optimal parameters for muscle tissue using DW-STEAM were b-value = 1800 s/mm(2), TE = 33 ms, TM = 30 ms, and repetition time = 2300 ms. In vivo measured mean olefinic signal-to-noise ratios were 72 and 40, mean apparent olefinic water fractions were 0.19 and 0.11 for DW-STEAM and long-TE PRESS, respectively., Conclusion: Optimized DW-STEAM MR spectroscopy is superior to long-TE PRESS for measuring fat unsaturation, if a strong water peak prevents the olefinic fat signal's quantification at shorter TEs and water's tissue specific ADC is substantially higher than fat., (© 2015 Wiley Periodicals, Inc.)

Purpose: MR spectroscopic imaging (SI) of glycine (Gly) in the human brain is challenging due to the interference of the abundant neighboring J-coupled resonances. Our aim is to accomplish reliable imaging of Gly in healthy brain and brain tumors using an optimized MR sequence scheme at 3 tesla., Methods: Two-dimensional (1)H SI was performed with a point-resolved spectroscopy scheme. An echo time of 160 ms was used for separation between Gly and myo-inositol signals. Data were collected from eight healthy volunteers and 14 subjects with gliomas. Spectra were analyzed with the linear combination model using numerically calculated basis spectra. Metabolite concentrations were estimated with reference to creatine in white matter (WM) regions at 6.4 molar concentrations (mM)., Results: From a linear regression analysis with respect to the fractional gray matter (GM) content, the Gly concentrations in pure GM and WM in healthy brains were estimated to be 1.1 and 0.3 mM, respectively. Gly was significantly elevated in tumors. The tumor-to-contralateral Gly concentration ratio was more extensive with higher grades, showing ∼ 10-fold elevation of Gly in glioblastomas., Conclusion: The Gly level is significantly different between GM and WM in healthy brains. Our data indicate that SI of Gly may provide a biomarker of brain tumor malignancy., (© 2015 Wiley Periodicals, Inc.)

Purpose: This study evaluated the longitudinal metabolic alterations after neonatal hypoxia-ischemia (HI) in rats and tested the neuroprotective effect of acetyl-L-carnitine (ALCAR) using in vivo proton short-TE Point-RESolved Spectroscopy method., Methods: Rice-Vannucci model was used on 7-day-old Sprague-Dawley rats. Data were acquired from contralateral and ipsilateral cortex and hippocampus, respectively at 4 time points (24-h, 72-h, 7-days, 28-days) post-HI. The effect of subcutaneous administration of ALCAR (100 mg/kg) immediately after HI, at 4-h, 24-h, and 48-h post-HI was determined., Results: Significant reductions in glutathione (P < 0.005), myo-inositol (P < 0.002), taurine (P < 0.001), and total creatine (P < 0.005) were observed at 24-h postinjury compared with the control group in the ipsilateral hippocampus of the HI rat pups. ALCAR-treated-HI rats had lower levels of lactate and maintained total creatine at 24-h and had smaller lesion size compared with the HI only rats., Conclusion: Severe oxidative, osmotic stress, impaired phosphorylation, and a preference for anaerobic glycolysis were found in the ipsilateral hippocampus in the HI pups at 24-h postinjury. ALCAR appeared to have a neuroprotective effect if administered early after HI by serving as an energy substrate and promote oxidative cerebral energy producing and minimize anaerobic glycolysis., (© 2014 Wiley Periodicals, Inc.)

Purpose: Low spatial resolution in conventional 1H brain chemical shifting imaging (CSI) studies causes partial volume error (PVE) or signal "bleed" that is especially deleterious to voxels near the scalp. The standard spatial apodization approach adversely affects spatial resolution. Here, a novel automated post-processing strategy of partial volume correction employing grid shifting ("PANGS") is presented, which minimizes residual PVE without compromising spatial resolution., Methods: PANGS shifts the locations of the reconstruction coordinates in a designated region of image space-the scalp, to match the tissue "centers-of-mass" instead of the geometric centers of each voxel, by iteratively minimizing the PVE from the scalp into outside voxels. PANGS' performance was evaluated by numerical simulation, and in 3 Tesla 1H CSI human studies employing outer volume suppression and long echo times., Results: PANGS reduced lipid contamination of cortical spectra by up to 86% (54% on average). Metabolite maps exhibited significantly less lipid artifact than conventional and spatially-filtered CSI. All methods generated quantitatively identical spectral peak areas from central brain locations, but spatial filtering increased spectral linewidths and reduced spatial resolution., Conclusion: PANGS significantly reduces lipid artifacts in 1H brain CSI spectra and metabolite maps, and improves metabolite detection in cortical regions without compromising resolution., (© 2014 Wiley Periodicals, Inc.)

Purpose: Because pH plays a crucial role in several diseases, it is desirable to measure pH in vivo noninvasively and in a spatially localized manner. Spatial maps of pH were quantified in vitro, with a focus on method-based errors, and applied in vivo., Methods: In vitro and in vivo (13) C mapping were performed for various flip angles for bicarbonate (BiC) and CO2 with spectral-spatial excitation and spiral readout in healthy Lewis rats in five slices. Acute subcutaneous sterile inflammation was induced with Concanavalin A in the right leg of Buffalo rats. pH and proton images were measured 2 h after induction., Results: After optimizing the signal to noise ratio of the hyperpolarized (13) C-bicarbonate, error estimation of the spectral-spatial excited spectrum reveals that the method covers the biologically relevant pH range of 6 to 8 with low pH error (< 0.2). Quantification of pH maps shows negligible impact of the residual bicarbonate signal. pH maps reflect the induction of acute metabolic alkalosis. Inflamed, infected regions exhibit lower pH., Conclusion: Hyperpolarized (13) C-bicarbonate pH mapping was shown to be sensitive in the biologically relevant pH range. The mapping of pH was applied to healthy in vivo organs and interpreted within inflammation and acute metabolic alkalosis models., (© 2014 Wiley Periodicals, Inc.)

Purpose: To evaluate the T2 relaxation time of lactate (Lac) in brain tumors and the correlation of the T2 and concentration with tumor grades., Methods: Eight pairs of the subecho time sets of point-resolved spectroscopy were selected between 58 and 268 ms, with numerical and phantom analyses, for Lac T2 measurement. In vivo spectra were acquired from 24 subjects with gliomas (13 low grade and 11 high grade) and analyzed with LCModel using numerically-calculated basis spectra. The metabolite T2 relaxation time was obtained from monoexponential fitting of the multi-echo time (TE) signal estimates versus TE. The metabolite concentration was estimated from the zero-TE extrapolation of the T2 fits., Results: The Lac T2 was estimated to be approximately 240 ms, without a significant difference between low and high grade tumors. The Lac concentration was estimated to be 4.1 ± 3.4 and 7.0 ± 4.7 mM for low and high grades respectively, but the difference was not significant., Conclusion: The Lac T2 was similar among gliomas regardless of their tumor grades. This suggests that the T2 value from this study may be applicable to obtain the T2 relaxation-free estimates of Lac in a subset of brain tumors., (© 2014 Wiley Periodicals, Inc.)

Purpose: Proton magnetic resonance spectroscopy ((1) H-MRS) for quantitative in vivo assessment of mouse myocardial metabolism requires accurate acquisition timing to minimize motion artifacts and corrections for T1 -dependent partial saturation effects. In this study, mouse myocardial water and metabolite T1 relaxation time constants were quantified., Methods: Cardiac-triggered and respiratory-gated PRESS-localized (1) H-MRS was employed at 9.4 T to acquire signal from a 4-µL voxel in the septum of healthy mice (n = 10) while maintaining a steady state of magnetization using dummy scans during respiratory gates. Signal stability was assessed via standard deviations (SD) of zero-order phases and amplitudes of water spectra. Saturation-recovery experiments were performed to determine T1 values., Results: Phase SD did not vary for different repetition times (TR), and was 13.1° ± 4.5°. Maximal amplitude SD was 14.2% ± 5.1% at TR = 500 ms. Myocardial T1 values (mean ± SD) were quantified for water (1.71 ± 0.25 s), taurine (2.18 ± 0.62 s), trimethylamine from choline-containing compounds and carnitine (1.67 ± 0.25 s), creatine-methyl (1.34 ± 0.19 s), triglyceride-methylene (0.60 ± 0.15 s), and triglyceride-methyl (0.90 ± 0.17 s) protons., Conclusion: This work provides in vivo quantifications of proton T1 values for mouse myocardial water and metabolites at 9.4 T., (© 2014 Wiley Periodicals, Inc.)

Purpose: Cross-relaxation of protons with (14) N nuclei in proteins enhances relaxivity in the quadrupolar dip range of typically 2-3 MHz Larmor frequency. The magnitude of these dips was suggested as a means of assessing the degeneracy of articular cartilage during osteoarthritis (OA). However, so far only proteoglycans have been considered whereas collagen nitrogen was neglected. This study addresses the relative importance of glycosaminoglycans (GAG), collagen, and water content for the cross-relaxation effect., Methods: Relaxation dispersion data were acquired for protons in samples of bovine articular cartilage, collagen, and GAG before and after the addition of trypsin or collagenase, and were compared with spatially resolved dGEMRIC experiments at 0.27 Tesla., Results: Both collagen as well as GAG show quadrupolar dips that strongly depend on hydration. For typical water concentrations in cartilage, the effect of enzymatic activity onto GAG is minor but a strong dependence on water concentration is found., Conclusion: Quadrupolar dips in the (1) H relaxation dispersion of cartilage possess similar contributions from both GAG and collagen. The reduction of the cross-relaxation contribution observed in OA tissue is thus not directly proportional to GAG concentration, but maintains a collagen contribution and reflects predominantly the increase in water concentration during OA., (© 2014 Wiley Periodicals, Inc.)

Purpose: To determine whether neurochemical concentrations obtained at two MRI sites using clinical 3T scanners can be pooled when a highly optimized, nonvendor short-echo, single-voxel proton MRS pulse sequence is used in conjunction with identical calibration and quantification procedures., Methods: A modified semi-LASER sequence (TE = 28 ms) was used to acquire spectra from two brain regions (cerebellar vermis and pons) on two Siemens 3T scanners using the same B0 and B1 calibration protocols from two different cohorts of healthy volunteers (N = 24-33 per site) matched for age and body mass index. Spectra were quantified with LCModel using water scaling., Results: The spectral quality was very consistent between the two sites and allowed reliable quantification of at least 13 metabolites in the vermis and pons compared with 3-5 metabolites in prior multisite magnetic resonance spectroscopy trials using vendor-provided sequences. The neurochemical profiles were nearly identical at the two sites and showed the feasibility to detect interindividual differences in the healthy brain., Conclusion: Highly reproducible neurochemical profiles can be obtained on different clinical 3T scanners at different sites, provided that the same, optimized acquisition and analysis techniques are used. This will allow pooling of multisite data in clinical studies, which is particularly critical for rare neurological diseases., (© 2014 Wiley Periodicals, Inc.)

Purpose: To decompose 1H MR spectra of glioma patients into normal and abnormal tissue proportions for tumor classification and delineation., Methods: Anatomical imaging and 1H magnetic resonance spectroscopic imaging data have been acquired from 11 grade II and 13 grade IV glioma patients. LCModel was used to decompose the magnetic resonance spectroscopic imaging data into normal brain, grade II, and grade IV tissue proportions using a tissue type basis set. Simulations were conducted to evaluate the accuracy of the methodology. Results were visualized using colormaps and abnormality contours showing tumor grade and extent., Results: Simulations suggest that infiltrative tumor proportions as low as 20% can be identified at the typical 1H magnetic resonance spectroscopy signal-to-noise found in vivo. Tumor grading according to the highest estimated tumor grade within a lesion gave a classification accuracy of 86% discriminating between grade II and grade IV glioma. Voxels with significant proportions of tumor type spectra were found beyond the margins of contrast enhancement for most grade IV cases consistent with infiltration whereas the abnormality contours show that some tumors are confined within the hyperintensities shown by both post contrast T1 weighted and T2 weighted imaging., Conclusion: LCModel can be used to decompose 1H MR spectra into proportions of normal and abnormal tissue to identify tumor extent, infiltration, and overall grade., (© 2014 Wiley Periodicals, Inc.)

Purpose: A feasibility study of an echo-planar spectroscopic imaging (EPSI) using a short echo time (TE) that trades off sensitivity, compared with other short-TE methods, to achieve whole brain coverage using inversion recovery and spatial oversampling to control lipid bleeding., Methods: Twenty subjects were scanned to examine intersubject variance. One subject was scanned five times to examine intrasubject reproducibility. Data were analyzed to determine coefficients of variance (COV) and intraclass correlation coefficient (ICC) for N-acetylaspartate (NAA), total creatine (tCr), total choline (tCho), glutamine/glutamate (Glx), and myo-inositol (mI). Regional metabolite concentrations were derived by using multi-voxel analysis based on lobar-level anatomic regions., Results: For whole-brain mean values, the intrasubject COVs were 14%, 15%, and 20% for NAA, tCr, and tCho, respectively, and 31% for Glx and mI. The intersubject COVs were up to 6% higher. For regional distributions, the intrasubject COVs were ≤ 5% for NAA, tCr, and tCho; ≤ 9% for Glx; and ≤15% for mI, with about 6% higher intersubject COVs. The ICCs of 5 metabolites were ≥ 0.7, indicating the reliability of the measurements., Conclusion: The present EPSI method enables estimation of the whole-brain metabolite distributions, including Glx and mI with small voxel size, and a reasonable scan time and reproducibility., (© 2014 Wiley Periodicals, Inc.)

Purpose: To study the apparent diffusivity and its directionality for metabolites of skeletal muscle in humans in vivo by (1) H magnetic resonance spectroscopy., Methods: The diffusion tensors were determined on a 3 Tesla MR system using optimized acquisition and processing methods including an adapted STEAM sequence with orientation-dependent diffusion weighting, pulse-triggering with individually adapted delays, eddy-current correction schemes, median filtering, and simultaneous prior-knowledge fitting of all related spectra., Results: The average apparent diffusivities, as well as the fractional anisotropies of taurine (ADCav=0.74 × 10(-3) s/mm(2) , FA=0.46), creatine (ADCav =0.41 × 10(-3) s/mm(2) , FA=0.33), trimethylammonium compounds (ADCav =0.48 × 10(-3) s/mm(2) , FA=0.34), carnosine (ADCav =0.46 × 10(-3) s/mm(2) , FA=0.47), and water (ADCav=1.5 × 10(-3) s/mm(2) , FA=0.36) were estimated. The diffusivities of most metabolites and water were significantly different from each other. Diffusion was found to be anisotropic and the diffusion tensors showed tensor correlation coefficients close to 1 and were hence found to be essentially coaligned. The magnitudes of apparent metabolite diffusivities were largely ordered according to molecular weight, with taurine as the smallest molecule diffusing fastest, both along and across the fiber direction., Conclusion: Diffusivities, directional dependence of diffusion and fractional anisotropies of (1) H MRS-visible muscle metabolites were presented. It was shown that metabolites share diffusion directionality with water and have similar fractional anisotropies, hinting at similar diffusion barriers., (© 2014 Wiley Periodicals, Inc.)

Purpose: To substantially improve spatial localization in magnetic resonance spectroscopic imaging (MRSI) accelerated by parallel imaging. This is important in order to make MRSI more reliable as a tool for clinical applications., Methods: The sensitivity encoding acceleration technique with spatial overdiscretization is applied for the reconstruction of parallel MRSI. In addition, the spatial response function is optimized by minimizing its deviation from a previously chosen target function. This modified minimum-norm sensitivity encoding-MRSI reconstruction approach is applied in this article for in vivo pulse-acquire MRSI of human brain at 7T with simulated acceleration factors of 2, 4, and 9 as well as actual 4-fold accelerated MRSI., Results: The sidelobes of the spatial response function are significantly suppressed, which reduces far-reaching voxel bleeding. At the same time, the major enlargement of the effective voxel size, which would be introduced by conventional k-space apodization methods, is largely avoided. Regularization allows for a practical trade-off between noise minimization, effective voxel size, and unaliasing. Although not aiming at increasing the nominal spatial resolution, a better spatial specificity is achieved., Conclusion: Simultaneous suppression of short- and far-reaching voxel bleeding in MRSI is analyzed and reconstruction of highly accelerated parallel in vivo MRSI is demonstrated., (© 2014 Wiley Periodicals, Inc.)

Purpose: To characterize a new approach to magnetization transfer (MT) imaging with improved specificity for myelinated tissues relative to conventional MT., Methods: Magnetization transfer preparation sequences were implemented with all radiofrequency power centered on a single frequency and also with power evenly divided between positive and negative frequencies. Dual frequency saturation was achieved both with short, alternating frequency pulses and with sinusoidal modulation of continuous irradiation. Images following preparation were acquired with a single shot fast spin echo sequence. Single and dual frequency preparation should achieve similar saturation of molecules except for those with inhomogenously broadened lines. Inhomogenous MT (IHMT) images were generated by subtraction of dual from single frequency prepared images. IHMT imaging was performed with different power and frequency in the brains of normal volunteers., Results: The IHMT method demonstrated a greater white/gray matter ratio than conventional MT and virtual elimination of signal in scalp and other unmyelinated tissues. IHMT exceeded 5% of the fully relaxed magnetization in white matter. A broad frequency spectrum and signs of axonal angular dependence at high frequency were observed that are consistent with dipolar broadening., Conclusion: IHMT shows promise for myelin-specific imaging. Further study of physical mechanisms and diagnostic sensitivity are merited., (© 2014 Wiley Periodicals, Inc.)

In (1)H MR spectroscopic imaging ((1)H-MRSI) of the prostate the spatial distribution of the signal levels of the metabolites choline, creatine, polyamines, and citrate are assessed. The ratio of choline (plus spermine as the main polyamine) plus creatine over citrate [(Cho+(Spm+)Cr)/Cit] is derived from these metabolites and is used as a marker for the presence of prostate cancer. In this review, the factors that are of importance for the metabolite ratio are discussed. This is relevant, because the appearance of the metabolites in the spectrum depends not only on the underlying anatomy, metabolism, and physiology of the tissue, but also on acquisition parameters. These parameters influence especially the spectral shapes of citrate and spermine resonances, and consequently, the (Cho+(Spm+)Cr)/Cit ratio. Both qualitative and quantitative approaches can be used for the evaluation of (1)H-MRSI spectra of the prostate. For the quantitative approach, the (Cho+(Spm+)Cr)/Cit ratio can be determined by integration or by a fit based on model signals. Using the latter, the influence of the acquisition parameters on citrate can be taken into account. The strong overlap between the choline, creatine, and spermine resonances complicates fitting of the individual metabolites. This overlap and (unknown, possibly tissue-related) variations in T1, T2, and J-modulation hamper the application of corrections needed for a "normalized" (Cho+(Spm+)Cr)/Cit ratio that would enable comparison of spectra measured with different prostate MR spectroscopy protocols. Quantitative (Cho+(Spm+)Cr)/Cit thresholds for the evaluation of prostate cancer are therefore commonly established per institution or per protocol. However, if the same acquisition and postprocessing protocol were used, the ratio and the thresholds would be institution-independent, promoting the clinical usability of prostate (1)H-MRSI., (© 2014 Wiley Periodicals, Inc.)

Purpose: To design a proton MR spectroscopy ((1) H-MRS) localization sequence that combines the signal-to-noise-ratio (SNR) benefits of point resolved spectroscopy (PRESS) with the high pulse bandwidths, low chemical shift displacements (CSD), low specific absorption rates (SAR), short echo times (TE), and superior radiofrequency transmit field (B1+) immunity of stimulated echo acquisition mode (STEAM), by simultaneously refocusing and acquiring both the double-spin and stimulated echo coherence pathways from the volume of interest., Theory and Methods: We propose a family of (1)H-MRS sequences comprising three orthogonal spatially selective pulses with flip angles 90° < α, β, γ < 128°. The stimulated and double-spin echo are refocused in-phase simultaneously by altering the pulses' phases, flip angles and timing, as well as the interpulse gradient spoiling moments. The ≈ 90° nutations of α, β, γ provide STEAM-like advantages (lower SAR, in-plane CSD and TE; greater B1+ immunity), but with SNRs comparable with PRESS., Results: Phantom and in vivo brain experiments show that 83-100% of the PRESS SNR (metabolite-dependent) is achieved at under 75% of the SAR and 66% lower in-plane CSD., Conclusion: The advantages of STEAM can be augmented with the higher SNR of PRESS by combining the spin and stimulated echoes. Quantification, especially of J-coupled resonances and intermediate and long TEs, must be carefully considered., (© 2014 Wiley Periodicals, Inc.)

Purpose: Improved diagnostic sensitivity could be obtained in cancer detection and staging when individual compounds of the choline pool can be detected. Therefore, a novel coil design is proposed, providing the ability to acquire both (1) H and (31) P magnetic resonance spectroscopic imaging (MRSI) in patients with prostate cancer., Methods: A two-element (1) H/(31) P endorectal coil was designed by adjusting a commercially available 3T endorectal coil. The two-element coil setup was interfaced as a transceiver to a whole body 7T MR scanner. Simulations and phantom measurements were performed to compare the efficiency of the coil. (1) H MRSI and (31) P MRSI were acquired in vivo in prostate cancer patients., Results: The efficiency of the (1) H/(31) P coil is comparable to the dual channel (1) H coil previously published. Individually distinguishable phospholipid metabolites in the in vivo (31) P spectra were: phosphoethanolamine, phosphocholine, phosphate, glycerophosphoethanolamine, glycerophosphocholine, phosphocreatine, and adenosine triposphate. (1) H MRSI was performed within the same scan session, visualizing choline, polyamines, creatine, and citrate., Conclusion: (1) H MRSI and (31) P MRSI can be acquired in the human prostate at 7T within the same scan session using an endorectal coil matched and tuned for (1) H (quadrature) and (31) P (linear) without the need of cable traps and with negligible efficiency losses in the (1) H and (31) P channel., (© 2013 Wiley Periodicals, Inc.)

Purpose: To reduce the specific-absorption-rate (SAR) and chemical shift displacement (CSD) of three-dimensional (3D) Hadamard spectroscopic imaging (HSI) and maintain its point spread function (PSF) benefits., Methods: A 3D hybrid of 2D longitudinal, 1D transverse HSI (L-HSI, T-HSI) sequence is introduced and demonstrated in a phantom and the human brain at 3 Tesla (T). Instead of superimposing each of the selective Hadamard radiofrequency (RF) pulses with its N single-slice components, they are cascaded in time, allowing N-fold stronger gradients, reducing the CSD. A spatially refocusing 180° RF pulse following the T-HSI encoding block provides variable, arbitrary echo time (TE) to eliminate undesirable short T2 species' signals, e.g., lipids., Results: The sequence yields 10-15% better signal-to-noise ratio (SNR) and 8-16% less signal bleed than 3D chemical shift imaging of equal repetition time, spatial resolution and grid size. The 13 ± 6, 22 ± 7, 24 ± 8, and 31 ± 14 in vivo SNRs for myo-inositol, choline, creatine, and N-acetylaspartate were obtained in 21 min from 1 cm(3) voxels at TE ≈ 20 ms. Maximum CSD was 0.3 mm/ppm in each direction., Conclusion: The new hybrid HSI sequence offers a better localized PSF at reduced CSD and SAR at 3T. The short and variable TE permits acquisition of short T2 and J-coupled metabolites with higher SNR., (Copyright © 2013 Wiley Periodicals, Inc.)

Purpose: The macromolecule signal plays a key role in the precision and the accuracy of the metabolite quantification in short-TE (1) H MR spectroscopy. Macromolecules have been reported at 1.5 Tesla (T) to depend on the cerebral studied region and to be age specific. As metabolite concentrations vary locally, information about the profile of the macromolecule signal in different tissues may be of crucial importance., Methods: The aim of this study was to investigate, at 7T for healthy subjects, the neurochemical profile differences provided by macromolecule signal measured in two different tissues in the occipital lobe, predominantly composed of white matter tissue or of grey matter tissue., Results: White matter-rich macromolecule signal was relatively lower than the gray matter-rich macromolecule signal from 1.5 to 1.8 ppm and from 2.3 to 2.5 ppm with mean difference over these regions of 7% and 12% (relative to the reference peak at 0.9 ppm), respectively. The neurochemical profiles, when using either of the two macromolecule signals, were similar for 11 reliably quantified metabolites (CRLB < 20%) with relatively small concentration differences (< 0.3 μmol/g), except Glu (± 0.8 μmol/g)., Conclusion: Given the small quantification differences, we conclude that a general macromolecule baseline provides a sufficiently accurate neurochemical profile in occipital lobe at 7T in healthy human brain., (Copyright © 2013 Wiley Periodicals, Inc.)

Purpose: To test whether citrate is elevated in adult patients with gliomas using (1)H magnetic resonance spectroscopy (MRS) at 3T in vivo., Methods: Thirty-four adult patients were enrolled in the study, including six subjects with glioblastomas, eight subjects with astrocytomas (World Health Organization grade 3, n = 5; grade 2, n = 3), and 20 subjects with oligodendrogliomas (grade 3, n = 5; grade 2, n = 15). Five healthy volunteers were studied for baseline citrate data. Single-voxel localized spectra were collected with point-resolved spectroscopy (PRESS) echo times of 35 and 97 ms and were analyzed with LCModel software using numerically calculated basis spectra that included the effects of the PRESS radiofrequency and gradient pulses., Results: Citrate was not measurable by MRS in healthy brain but was detected in tumor patients at both echo times. The citrate concentration was estimated to be as high as 1.8 mM with reference to water at 42 M, with Cramér-Rao lower bounds (CRLB) as low as 5%. The mean citrate level was 0.7 ± 0.4 mM (mean ± SD, n = 32) with a median CRLB of ∼12%. No correlation was identified between citrate concentration and tumor grade or histological type., Conclusion: Citrate was increased in the majority of gliomas in adult patients. The elevated citrate in our data indicates an altered metabolic state of tumor relative to healthy brain., (Copyright © 2013 Wiley Periodicals, Inc.)

Purpose: To increase the signal-to-noise ratio (SNR) and to reduce artifacts in non-proton magnetic resonance imaging (MRI) by incorporation of a priori information from (1) H MR data in an iterative reconstruction., Methods: An iterative reconstruction algorithm for 3D projection reconstruction (3DPR) is presented that combines prior anatomical knowledge and image sparsity under a total variation (TV) constraint. A binary mask (BM) is used as an anatomical constraint to penalize non-zero signal intensities outside the object. The BM&TV method is evaluated in simulations and in MR measurements in volunteers., Results: In simulated BM&TV brain data, the artifact level was reduced by 20% while structures were well preserved compared to gridding. SNR maps showed a spatially dependent SNR gain over gridding reconstruction, which was up to 100% for simulated data. Undersampled 3DPR (23) Na MRI of the human brain revealed an SNR increase of 29 ± 7%. Small anatomical structures were reproduced with a mean contrast loss of 14%, whereas in TV-regularized iterative reconstructions a loss of 66% was found., Conclusion: The BM&TV algorithm allows reconstructing images with increased SNR and reduced artifact level compared to gridding and performs superior to an iterative reconstruction using an unspecific TV constraint only., (Copyright © 2013 Wiley Periodicals, Inc.)

Purpose: The aims of this study were (i) to establish a robust and fast method to quantify hepatocellular phosphorus compounds in molar concentration on a 3T clinical scanner, (ii) to evaluate its reproducibility, and (iii) to test its feasibility for a use in large cohort studies., Method: Proton-decoupled (31) P magnetic resonance spectroscopy of liver (31) P compounds were acquired on 85 healthy subjects employing image selected in-vivo spectroscopy localization in 13 min of acquisition at 3T. Absolute quantification was achieved using an external reference and double-matching phantoms (inorganic phosphates and adenosine triphosphate (ATP) solutions). Reproducibility of the method was also examined., Results: This method showed a high intra- and interday as well as inter- and intraobserver reproducibility (r > 0.98; P < 0.001), with a high signal to noise ratio (SNR) (i.e., mean SNR of γ-ATP: 16). The mean liver concentrations of 85 healthy subjects were assessed to be 1.99 ± 0.51 and 2.74 ± 0.55 mmol/l of wet tissue volume for Pi and γ-ATP, respectively., Conclusion: This method reliably quantified molar concentrations of liver (31) P compounds on 85 subjects with a short total examination time (∼25 min) on a 3T clinical scanner. Thus, the current method can be readily utilized for a clinical study, such as a large cohort study., (Copyright© 2013 Wiley Periodicals, Inc.)

Purpose: Magnetic resonance spectroscopy (MRS) experiments rely on a homogeneous and stable magnetic field within the sample. Field homogeneity is typically optimized by static B0 shimming while reproducible effects from dynamic field variation are commonly diminished by means of gradient system calibration as well as calibration based on non-water suppressed reference data. However, residual encoding deficiencies from incomplete calibration and nonreproducible field perturbations deteriorate the quality of the obtained data. To overcome this problem, we propose to adapt higher-order feedback field control based on NMR field probes for its application in MRS., Methods: To allow for field measurements simultaneously with the spectroscopy readout, radiofrequency-shielded field probes were employed. The setup was evaluated in vitro and tested in vivo for single-voxel MRS at 7T to correct for field perturbations that occur due to subject breathing and limb motion., Results: The in vitro experiments showed an effective field control during the MRS sequence. The resulting spectroscopy data were free of spurious signal and the achieved field stabilization improved the spectral resolution in vitro and in vivo., Conclusion: High-field MRS is limited by nonreproducible field perturbations for which spatiotemporal field feedback provides a solution without compromising sequence timing and efficiency., (Copyright © 2013 Wiley Periodicals, Inc.)