Quantitative spectroscopic imaging with in situ measurements of tissue water T1, T2, and density

The use of tissue water as a concentration standard in proton magnetic resonance spectroscopy (¹H‐MRS) of the brain requires that the water proton signal be adjusted for relaxation and partial volume effects. While single voxel ¹H‐MRS studies have often included measurements of water proton T₁, T₂, and density based on additional ¹H‐MRS acquisitions (e.g., at multiple echo or repetition times), this approach is not practical for ¹H‐MRS imaging (¹H‐MRSI). In this report we demonstrate a method for using in situ measurements of water T₁, T₂, and density to calculate metabolite concentrations from ¹H‐MRSI data. The relaxation and density data are coregistered with the ¹H‐MRSI data and provide detailed information on the water signal appropriate to the individual subject and tissue region. We present data from both healthy subjects and a subject with brain lesions, underscoring the importance of water parameter measurements on a subject‐by‐subject and voxel‐by‐voxel basis. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

Reproducibility of high spatial resolution proton magnetic resonance spectroscopic imaging in the human brain

The application of proton (¹H) magnetic resonance spectroscopic imaging (MRSI) allows for noninvasive, localized analyses of brain biochemistry; however, minimal work has been devoted to the evaluation of ¹H MRSI reproducibility. This study examined the reproducibility of ¹H MRSI from five normal subjects on two occasions, separated by 10 days. Reproducibility of the MR signal was evaluated in the context of automated shimming, automated processing, and accurate subject repositioning. Reliability measures for physicochemical indices (choline moieties, creatine, N-acetylaspartate, and myo-inositol) were moderately concordant across repeat studies. Gain variation and repositioning results were excellent. It has been concluded that ¹H MRSI reproducibility is adequate for serial studies of brain metabolism.     

Sensitivity encoding for fast 1H MR spectroscopic imaging water reference acquisition

Purpose: Accurate and fast ¹H MR spectroscopic imaging (MRSI) water reference scans are important for absolute quantification of metabolites. However, the additional acquisition time required often precludes the water reference quantitation method for MRSI studies. Sensitivity encoding (SENSE) is a successful MR technique developed to reduce scan time. This study quantitatively assesses the accuracy of SENSE for water reference MRSI data acquisition, compared with the more commonly used reduced resolution technique. Methods: 2D MRSI water reference data were collected from a phantom and three volunteers at 3 Tesla for full acquisition (306 s); 2× reduced resolution (64 s) and SENSE R = 3 (56 s) scans. Water amplitudes were extracted using MRS quantitation software (TARQUIN). Intensity maps and Bland‐Altman statistics were generated to assess the accuracy of the fast‐MRSI techniques. Results: The average mean and standard deviation of differences from the full acquisition were 2.1 ± 3.2% for SENSE and 10.3 ± 10.7% for the reduced resolution technique, demonstrating that SENSE acquisition is approximately three times more accurate than the reduced resolution technique. Conclusion: SENSE was shown to accurately reconstruct water reference data for the purposes of in vivo absolute metabolite quantification, offering significant improvement over the more commonly used reduced resolution technique. Magn Reson Med 73:2081–2086, 2015. © 2014 The Authors. Magnetic Resonance in Medicine Published by Wiley Periodicals, Inc. on behalf of International Society of Medicine in Resonance.     

Multiple-echo proton spectroscopic imaging using time domain parametric spectral analysis

A multiple-echo MR spectroscopic imaging (MRSI) method is presented that enables improved metabolite imaging in the presence of local field inhomogeneities and measurement of transverse relaxation parameters. Short echo spacing is used to maximize signal energy from inhomogeneously line-broadened resonances, and time domain parametric spectral analysis of the entire echo train is used to obtain sufficient spectral resolution from the shortened sampling periods. Optimal sequence parameters for ¹H MRSI are determined by computer simulation, and performance is compared with conventional single-echo acquisition using phantom studies at a field strength of 4.7 T. A preliminary example for use at 1.5 T is also presented using phantom and human brain MRSI studies. This technique is shown to offer improved performance relative to single-echo MRSI for imaging of metabolites with shortened T₂* values due to the presence of local field inhomogeneities. Additional advantages are the intrinsic measurement of metabolite T₂ values and determination of metabolite integrals without T₂ weighting, thereby facilitating quantitative metabolite imaging.     

Reproducibility of 3D 1H MR spectroscopic imaging of the prostate at 1.5T

Purpose:

To determine the reproducibility of 3D proton magnetic resonance spectroscopic imaging (¹H‐MRSI) of the human prostate in a multicenter setting at 1.5T.

Materials and Methods:

Fourteen subjects were measured twice with 3D point‐resolved spectroscopy (PRESS) ¹H‐MRSI using an endorectal coil. MRSI voxels were selected in the peripheral zone and combined central gland at the same location in the prostate in both measurements. Voxels with approved spectral quality were included to calculate Bland–Altman parameters for reproducibility from the choline plus creatine to citrate ratio (CC/C). The repeated spectroscopic data were also evaluated with a standardized clinical scoring system.

Results:

A total of 74 voxels were included for reproducibility analysis. The complete range of biologically interesting CC/C ratios was covered. The overall within‐voxel standard deviation (SD) of the CC/C ratio of the repeated measurements was 0.13. This value is equal to the between‐subject SD of noncancer prostate tissue. In >90% of the voxels the standardized clinical score did not differ relevantly between the measurements.

Conclusion:

Repeated measurements of in vivo 3D ¹H‐MRSI of the complete prostate at 1.5T produce equal and quantitative results. The reproducibility of the technique is high enough to provide it as a reliable tool in assessing tumor presence in the prostate. J. Magn. Reson. Imaging 2012;35:166‐173. © 2011 Wiley Periodicals, Inc.     

Spectral resolution amelioration by deconvolution (SPREAD) in MR spectroscopic imaging

Purpose

To develop, implement, and evaluate a novel postprocessing method for enhancing the spectral resolution of in vivo MR spectroscopic imaging (MRSI) data.

Materials and Methods

Magnetic field inhomogeneity across the imaging volume was determined by acquiring MRI datasets with two differing echo times. The lineshapes of the MRSI spectra were derived from these field maps by simulating an MRSI scan of a virtual sample whose resonance frequencies varied according to the observed variations in the magnetic field. By deconvolving the lineshapes from the measured MRSI spectra, the linebroadening effects of the field inhomogeneities were reduced significantly.

Results

Both phantom and in vivo proton MRSI spectra exhibited significantly enhanced spectral resolutions and improved spectral lineshapes following application of our method. Quantitative studies on a phantom show that, on average, the full width at half maximum of water peaks was reduced 42%, the full width at tenth maximum was reduced 38%, and the asymmetries of the peaks were reduced 86%.

Conclusion

Our method reduces the linebroadening and lineshape distortions caused by magnetic field inhomogeneities. It substantially improves the spectral resolution and lineshape of MRSI data. J. Magn. Reson. Imaging 2009;29:1395–1405. © 2009 Wiley‐Liss, Inc.     

Short echo time 1H MRSI of the human brain at 3T with adiabatic slice‐selective refocusing pulses; reproducibility and variance in a dual center setting

Purpose:

To assess the reproducibility of ¹H‐MR spectroscopic imaging (MRSI) of the human brain at 3T with volume selection by a double spin echo sequence for localization with adiabatic refocusing pulses (semi‐LASER).

Materials and Methods:

Twenty volunteers in two different institutions were measured twice with the same pulse sequence at an echo time of 30 msec. Magnetic resonance (MR) spectra were analyzed with LCModel with a simulated basis set including an experimentally acquired macromolecular signal profile. For specific regions in the brain mean metabolite levels, within and between subject variance, and the coefficient of variation (CoV) were calculated (for taurine, glutamate, total N‐acetylaspartate, total creatine, total choline, myo‐inositol + glycine, and glutamate + glutamine).

Results:

Repeated measurements showed no significant differences with a paired t‐test and a high reproducibility (CoV ranging from 3%–30% throughout the selected volume). Mean metabolite levels and CoV obtained in similar regions in the brain did not differ significantly between two contributing institutions. The major source of differences between different measurements was identified to be the between‐subject variations in the volunteers.

Conclusion:

We conclude that semi‐LASER ¹H‐MRSI at 3T is an adequate method to obtain quantitative and reproducible measures of metabolite levels over large parts of the brain, applicable across multiple centers. J. Magn. Reson. Imaging 2010;31:61–70. © 2009 Wiley‐Liss, Inc.     

MR spectroscopic imaging: Principles and recent advances

MR spectroscopic imaging (MRSI) has become a valuable tool for quantifying metabolic abnormalities in human brain, prostate, breast and other organs. It is used in routine clinical imaging, particularly for cancer assessment, and in clinical research applications. This article describes basic principles of commonly used MRSI data acquisition and analysis methods and their impact on clinical applications. It also highlights technical advances, such as parallel imaging and newer high‐speed MRSI approaches that are becoming viable alternatives to conventional MRSI methods. Although the main focus is on ¹H‐MRSI, the principles described are applicable to other MR‐compatible nuclei. This review of the state‐of‐the‐art in MRSI methodology provides a framework for critically assessing the clinical utility of MRSI and for defining future technical development that is expected to lead to increased clinical use of MRSI. Future technical development will likely focus on ultra‐high field MRI scanners, novel hyperpolarized contrast agents using metabolically active compounds, and ultra‐fast MRSI techniques because these technologies offer unprecedented sensitivity and specificity for probing tissue metabolic status and dynamics. J. Magn. Reson. Imaging 2013;37:1301–1325. © 2012 Wiley Periodicals, Inc.     

Reduced phase encoding in spectroscopic imaging

The effect of different spatial-encoding (k-space) sampling distributions are evaluated for magnetic resonance spectroscopic imaging (MRSI) using Fourier reconstruction. Previously, most MRSI studies have used square or cubic k-space functions, symmetrically distributed. These studies examine the conventional k-space distribution with spherical distribution, and 1/2 k-space acquisition, using computer simulation studies of the MRSI acquisition for three spatial dimensions and experimental results. Results compare the spatial response function, Gibbs ringing effects, and signal contamination for different spatial-encoding distribution functions. Results indicate that spherical encoding, in comparison with cubic encoding, results in a modest improvement of the re sponse function with approximately equivalent spatial resolution for the same acquisition time. For spin-echo acquired data, reduced acquisition times can readily be obtained using 1/2 k-space methods, with a concomitant reduction in signal to noise ratio.     

Comparison of methods for reduction of lipid contamination for in vivo proton MR spectroscopic imaging of the brain.

In vivo proton MR spectroscopic imaging (MRSI) of human brain is complicated by the presence of a strong signal from subcutaneous lipids, which may result in signal contamination in metabolite images obtained following Fourier-transform reconstruction. In this study, two approaches for reduction of lipid contamination--using postprocessing and additional data acquisition--are compared. The first uses extrapolation of k-space information for subcutaneous lipid, which has been applied to data obtained using conventional fully phase-encoded MRSI with circularly sampled k-space or echo-planar spectroscopic imaging (EPSI). The second uses a dual EPSI technique that combines multiple-averaged central k-space data with a single EPSI acquisition of additional information that is used for improved lipid reconstruction. Comparisons are carried out with data obtained from human brain in vivo at 1.5 T with short and medium TEs. Results demonstrate that the performance of both methods for reducing the effects of lipid contamination is similar, and that both are limited by the effects of instrumental instabilities and subject motion, which also depend on the acquisition method used.     

31P MR spectroscopic imaging detects regenerative changes in human liver stimulated by portal vein embolization

Purpose:

First, to evaluate hepatocyte phospholipid metabolism and energetics during liver regeneration stimulated by portal vein embolization (PVE) using proton‐decoupled ³¹P MR spectroscopic imaging (³¹P‐MRSI). Second, to compare the biophysiologic differences between hepatic regeneration stimulated by PVE and by partial hepatectomy (PH).

Materials and Methods:

Subjects included six patients with hepatic metastases from colorectal cancer who were scheduled to undergo right PVE before definitive resection of right‐sided tumor.³¹P‐MRSI was performed on the left liver lobe before PVE and 48 h following PVE. Normalized quantities of phosphorus‐containing hepatic metabolites were analyzed from both visits. In addition, MRSI data at 48 h following partial hepatectomy were compared with the data from the PVE patients.

Results:

At 48 h after PVE, the ratio of phosphomonoesters to phosphodiesters in the nonembolized lobe was significantly elevated. No significant changes were found in nucleoside triphosphates (NTP) and Pi values. The phosphomonoester (PME) to phosphodiester (PDE) ratio in regenerating liver 48 h after partial hepatectomy was significantly greater than PME/PDE 48 h after PVE.

Conclusion:

³¹P‐MRSI is a valid technique to noninvasively evaluate cell membrane metabolism following PVE. The different degree of biochemical change between partial hepatectomy and PVE indicates that hepatic growth following these two procedures does not follow the same course. J. Magn. Reson. Imaging 2011;. © 2011 Wiley‐Liss, Inc.     

Removal of lipid artifacts in 1H spectroscopic imaging by data extrapolation

Proton MR spectroscopic imaging (MRSI) of human cerebral cortex is complicated by the presence of an intense signal from subcutaneous lipids, which, if not suppressed before Fourier reconstruction, causes ringing and signal contamination throughout the metabolite images as a result of limited k-space sampling. In this article, an improved reconstruction of the lipid region is obtained using the Papoulis-Gerchberg algorithm. This procedure makes use of the narrow-band-limited nature of the subcutaneous lipid signal to extrapolate to higher k-space values without alteration of the metabolite signal region. Using computer simulations and in vivo experimental studies, the implementation and performance of this algorithm were examined. This method was found to permit MRSI brain spectra to be obtained without applying any lipid suppression during data acquisition, at echo times of 50 ms and longer. When applied together with optimized acquisition methods, this provides an effective procedure for imaging metabolite distributions in cerebral cortical surface regions.     

1H spectroscopic imaging of human brain at 3 Tesla: Comparison of fast three‐dimensional magnetic resonance spectroscopic imaging techniques

Purpose

To investigate the signal‐to‐noise‐ratio (SNR) and data quality of time‐reduced three‐dimensional (3D) proton magnetic resonance spectroscopic imaging (¹H MRSI) techniques in the human brain at 3 Tesla.

Materials and Methods

Techniques that were investigated included ellipsoidal k‐space sampling, parallel imaging, and echo‐planar spectroscopic imaging (EPSI). The SNR values for N‐acetyl aspartate, choline, creatine, and lactate or lipid peaks were compared after correcting for effective spatial resolution and acquisition time in a phantom and in the brains of human volunteers. Other factors considered were linewidths, metabolite ratios, partial volume effects, and subcutaneous lipid contamination.

Results

In volunteers, the median normalized SNR for parallel imaging data decreased by 34–42%, but could be significantly improved using regularization. The normalized signal to noise loss in flyback EPSI data was 11–18%. The effective spatial resolutions of the traditional, ellipsoidal, sensitivity encoding (SENSE) sampling scheme, and EPSI data were 1.02, 2.43, 1.03, and 1.01 cm³, respectively. As expected, lipid contamination was variable between subjects but was highest for the SENSE data. Patient data obtained using the flyback EPSI method were of excellent quality.

Conclusion

Data from all ¹H 3D‐MRSI techniques were qualitatively acceptable, based upon SNR, linewidths, and metabolite ratios. The larger field of view obtained with the EPSI methods showed negligible lipid aliasing with acceptable SNR values in less than 9.5 min without compromising the point‐spread function. J. Magn. Reson. Imaging 2009;30:473–480. © 2009 Wiley‐Liss, Inc.     

Automated spectral analysis III: Application to in Vivo proton MR Spectroscopy and spectroscopic imaging

An automated method for analysis of in vivo proton magnetic resonance (MR) spectra and reconstruction of metabolite distributions from MR spectroscopic imaging (MRSI) data is described. A parametric spectral model using acquisition specific, a priori information is combined with a wavelet-based, nonparametric characterization of baseline signals. For image reconstruction, the initial fit estimates were additionally modified according to a priori spatial constraints. The automated fitting procedure was applied to four different examples of MRS data obtained at 1.5 T and 4.1 T. For analysis of major metabolites at medium TE values, the method was shown to perform reliably even in the presence of large baseline signals and relatively poor signal-to-noise ratios typical of in vivo proton MRSI. identification of additional metabolites was also demonstrated for short TE data. Automated formation of metabolite images will greatly facilitate and expand the clinical applications of MR spectroscopic imaging.     

Fast 3D 1H MRSI of the corticospinal tract in pediatric brain

Purpose

To develop a ¹H magnetic resonance spectroscopic imaging (MRSI) sequence that can be used to image infants/children at 3T and by combining it with diffusion tensor imaging (DTI) tractography, extract relevant metabolic information corresponding to the corticospinal tract (CST).

Materials and Methods

A fast 3D MRSI sequence was developed for pediatric neuroimaging at 3T using spiral k‐space readout and dual band RF pulses (32 × 32 × 8 cm field of view [FOV], 1 cc iso‐resolution, TR/TE = 1500/130, 6:24 minute scan). Using DTI tractography to identify the motor tracts, spectra were extracted from the CSTs and quantified. Initial data from infants/children with suspected motor delay (n = 5) and age‐matched controls (n = 3) were collected and N‐acetylaspartate (NAA) ratios were quantified.

Results

The average signal‐to‐noise ratio of the NAA peak from the studies was ≈22. Metabolite profiles were successfully acquired from the CST by using DTI tractography. Decreased NAA ratios in those with motor delay compared to controls of ≈10% at the CST were observed.

Conclusion

A fast and robust 3D MRSI technique targeted for pediatric neuroimaging has been developed. By combining with DTI tractography, metabolic information from the CSTs can be retrieved and estimated. By combining DTI and 3D MRSI, spectral information from various tracts can be obtained and processed. J. Magn. Reson. Imaging 2009;29:1–6. © 2008 Wiley‐Liss, Inc.     

Reproducibility study of whole‐brain 1H spectroscopic imaging with automated quantification

A reproducibility study of proton MR spectroscopic imaging (¹H‐MRSI) of the human brain was conducted to evaluate the reliability of an automated 3D in vivo spectroscopic imaging acquisition and associated quantification algorithm. A PRESS‐based pulse sequence was implemented using dualband spectral‐spatial RF pulses designed to fully excite the singlet resonances of choline (Cho), creatine (Cre), and N‐acetyl aspartate (NAA) while simultaneously suppressing water and lipids; 1% of the water signal was left to be used as a reference signal for robust data processing, and additional lipid suppression was obtained using adiabatic inversion recovery. Spiral k‐space trajectories were used for fast spectral and spatial encoding yielding high‐quality spectra from 1 cc voxels throughout the brain with a 13‐min acquisition time. Data were acquired with an 8‐channel phased‐array coil and optimal signal‐to‐noise ratio (SNR) for the combined signals was achieved using a weighting based on the residual water signal. Automated quantification of the spectrum of each voxel was performed using LCModel. The complete study consisted of eight healthy adult subjects to assess intersubject variations and two subjects scanned six times each to assess intrasubject variations. The results demonstrate that reproducible whole‐brain ¹H‐MRSI data can be robustly obtained with the proposed methods. Magn Reson Med 60:542–547, 2008. © 2008 Wiley‐Liss, Inc.     

31P NMR of phospholipid metabolites in prostate cancer and benign prostatic hyperplasia

¹H MRSI in vivo is increasingly being used to diagnose prostate cancer noninvasively by measurement of the resonance from choline‐containing phospholipid metabolites. Although ³¹P NMR in vivo or in vitro is potentially an excellent method for probing the phospholipid metabolites prominent in prostate cancer, it has been little used recently. Here, we report an in vitro ³¹P NMR comparison of prostate cancer and benign prostatic hyperplasia, focusing on the levels of the major phospholipid metabolites. Unlike phosphocholine and glycerophosphocholine, phosphoethanolamine and glycerophosphoethanolamine (and their ratio) were significantly different between cancer and benign prostatic hyperplasia. The high level of phosphoethanolamine+glycerophosphoethanolamine relative to phosphocholine+glycerophosphocholine suggests that the former may be significant contributors to the “total choline” resonance observed by ¹H MRSI in vivo. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

Post‐processing correction of the endorectal coil reception effects in MR spectroscopic imaging of the prostate

Purpose:

To develop and validate a post‐processing correction algorithm to remove the effect of the inhomogeneous reception profile of the endorectal coil on MR spectroscopic imaging (MRSI) data.

Materials and Methods:

A post‐processing algorithm to correct for the endorectal coil reception effects on MRSI data was developed based upon theoretical modeling of the endorectal coil reception profile and of the spatial saturation pulse profiles. This algorithm was evaluated on three‐dimensional (3D) MRSI data acquired at 3T from a uniform phantom and from 18 patients with known or suspected prostate cancer.

Results:

For the phantom data, the coefficient of variation of metabolite peak areas decreased 16% to 46% and the peak area distributions became more Gaussian with correction, as demonstrated by higher Q‐Q plot linear correlations (R² = 0.98 ± 0.007 vs. R² = 0.89 ± 0.066). Across the 18 patients, the mean coefficient of variation for suppressed water decreased significantly, from 0.95 ± 0.18, to 0.66 ± 0.11, (P < 10^?6, paired t‐test) and the linear correlations of the Q‐Q plots for the suppressed water increased from R² = 0.91 to R² = 0.95 (P = 0.0083, paired t‐test) with correction.

Conclusion:

An algorithm for reducing the effect of the inhomogeneous reception profile in endorectal coil acquired 3D MRSI prostate data was demonstrated, illustrating increased homogeneity and more Gaussian peak area distributions. J. Magn. Reson. Imaging 2010;32:654–662. © 2010 Wiley‐Liss, Inc.

     

Design of cosine modulated very selective suppression pulses for MR spectroscopic imaging at 3T

The advantages of using a 3 Tesla (T) scanner for MR spectroscopic imaging (MRSI) of brain tissue include improved spectral resolution and increased sensitivity. Very selective saturation (VSS) pulses are important for maximizing selectivity for PRESS MRSI and minimizing chemical shift misregistration by saturating signals from outside the selected region. Although three‐dimensional (3D) PRESS MRSI is able to provide excellent quality metabolic data for patients with brain tumors and has been shown to be important for defining tumor burden, the method is currently limited by how much of the anatomic lesion can be covered within a single examination. In this study we designed and implemented cosine modulated VSS pulses that were optimized for 3T MRSI acquisitions. This provided improved coverage and suppression of unwanted lipid signals with a smaller number of pulses. The use of the improved pulse sequence was validated in volunteer studies, and in clinical 3D MRSI exams of brain tumors. Magn Reson Med, 2009. © 2008 Wiley‐Liss, Inc.