1H MRSI Research Articles

Parallel detection of MRI and 1H MRSI for multi-contrast anatomical and metabolic imaging.

MRI and MRSI provide unique and complementary information on anatomy, structure, function, and metabolism. The default strategy for a combined MRI and MRSI study is a sequential acquisition of both modalities, leading to long scan times. As MRI and MRSI primarily detect water and metabolites, respectively, the small frequency difference between resonances can be exploited with frequency-selective RF pulses to achieve interleaved or parallel detection of MRI and MRSI, without an increase in total scan time. Here, we describe the pulse sequence modifications necessary to allow acquisition of T1 and T2-weighted MRI and B0/B1 mapping in parallel with MRSI. In general, the MRSI module, including water suppression, can be used unmodified. MRI methods are executed in 3D using 3- to 4-ms frequency-selective Gaussian RF pulses with acceleration along the third dimension through repetitive small-angle nutation or multi-spin-echo acquisitions. Phantom experiments demonstrated artifact-free 3D MRIs. MRSIs in the absence or presence of MRI elements were identical in sensitivity and spectral resolution (line width) and showed consistent water suppression. Parallel MRI-MRSI was applied to the brains of tumor-bearing rats in vivo. High-contrast, high-sensitivity metabolic MRSI data at 8 μL nominal resolution was acquired in parallel with 3D T1-weighted, T2-weighted, and B0/B1-weighted MRIs for an overall scan duration of 30 min. Multi-contrast MRIs and MRSI can be acquired in parallel by utilizing the small frequency difference between water and metabolites. This opens the possibility for shorter overall scans times, or the acquisition of higher-resolution or additional contrast MRIs.

Reproducibility of 3D MRSI for imaging human brain glucose metabolism using direct (2H) and indirect (1H) detection of deuterium labeled compounds at 7T and clinical 3T

IntroductionDeuterium metabolic imaging (DMI) and quantitative exchange label turnover (QELT) are novel MR spectroscopy techniques for non-invasive imaging of human brain glucose and neurotransmitter metabolism with high clinical potential. Following oral or intravenous administration of non-ionizing [6,6′-2H2]-glucose, its uptake and synthesis of downstream metabolites can be mapped via direct or indirect detection of deuterium resonances using 2H MRSI (DMI) and 1H MRSI (QELT), respectively. The purpose of this study was to compare the dynamics of spatially resolved brain glucose metabolism, i.e., estimated concentration enrichment of deuterium labeled Glx (glutamate+glutamine) and Glc (glucose) acquired repeatedly in the same cohort of subjects using DMI at 7T and QELT at clinical 3T. MethodsFive volunteers (4 m/1f) were scanned in repeated sessions for 60 min after overnight fasting and 0.8 g/kg oral [6,6′-2H2]-glucose administration using time-resolved 3D 2H FID-MRSI with elliptical phase encoding at 7T and 3D 1H FID-MRSI with a non-Cartesian concentric ring trajectory readout at clinical 3T. ResultsOne hour after oral tracer administration regionally averaged deuterium labeled Glx4 concentrations and the dynamics were not significantly different over all participants between 7T 2H DMI and 3T 1H QELT data for GM (1.29±0.15 vs. 1.38±0.26 mM, p=0.65 & 21±3 vs. 26±3 µM/min, p=0.22) and WM (1.10±0.13 vs. 0.91±0.24 mM, p=0.34 & 19±2 vs. 17±3 µM/min, p=0.48). Also, the observed time constants of dynamic Glc6 data in GM (24±14 vs. 19±7 min, p=0.65) and WM (28±19 vs. 18±9 min, p=0.43) dominated regions showed no significant differences. Between individual 2H and 1H data points a weak to moderate negative correlation was observed for Glx4 concentrations in GM (r=-0.52, p<0.001), and WM (r=-0.3, p<0.001) dominated regions, while a strong negative correlation was observed for Glc6 data GM (r=-0.61, p<0.001) and WM (r=-0.70, p<0.001). ConclusionThis study demonstrates that indirect detection of deuterium labeled compounds using 1H QELT MRSI at widely available clinical 3T without additional hardware is able to reproduce absolute concentration estimates of downstream glucose metabolites and the dynamics of glucose uptake compared to 2H DMI data acquired at 7T. This suggests significant potential for widespread application in clinical settings especially in environments with limited access to ultra-high field scanners and dedicated RF hardware.

Post-acquisition water-signal removal in 3D water-unsuppressed 1 H-MR spectroscopic imaging of the prostate.

To develop a robust processing procedure of raw signals from water-unsuppressed MRSI of the prostate for the mapping of absolute tissue concentrations of metabolites. Water-unsuppressed 3D MRSI data were acquired from a phantom, from healthy volunteers, and a patient with prostate cancer. Signal processing included sequential computation of the modulus of the FID to remove water sidebands, a Hilbert transformation, and k-space Hamming filtering. For the removal of the water signal, we compared Löwner tensor-based blind source separation (BSS) and Hankel Lanczos singular value decomposition techniques. Absolute metabolite levels were quantified with LCModel and the results were statistically analyzed to compare the water removal methods and conventional water-suppressed MRSI. The post-processing algorithms successfully removed the water signal and its sidebands without affecting metabolite signals. The best water removal performance was achieved by Löwner tensor-based BSS. Absolute tissue concentrations of citrate in the peripheral zone derived from water-suppressed and unsuppressed 1 H MRSI were the same and as expected from the known physiology of the healthy prostate. Maps for citrate and choline from water-unsuppressed 3D 1 H-MRSI of the prostate showed expected spatial variations in metabolite levels. We developed a robust relatively simple post-processing method of water-unsuppressed MRSI of the prostate to remove the water signal. Absolute quantification using the water signal, originating from the same location as the metabolite signals, avoids the acquisition of additional reference data.

Baseline Correction of the Human 1H MRS(I) Spectrum Using T2* Selective Differential Operators in the Frequency Domain.

The baseline distortion caused by water and fat signals is a crucial issue in the 1H MRS(I) study of the human brain. This paper suggests an effective and reliable preprocessing technique to calibrate the baseline distortion caused by the water and fat signals exhibited in the MRS spectral signal. For the preprocessing, we designed a T2* (or linewidth within the spectral signal) selective filter for the MRS(I) data based on differential filtering within the frequency domain. The number and types for the differential filtering were determined by comparing the T2* selectivity profile of each differential operator with the T2* profile of the metabolites to be suppressed within the MRS(I) data. In the performance evaluation of the proposed differential filtering, the simulation data for MRS spectral signals were used. Furthermore, the spectral signal of the human 1H MRSI data obtained by 2D free induction decay chemical shift imaging with a typical water suppression technique was also used in the performance evaluation. The absolute values of the average of the filtered dataset were quantitatively analyzed using the LCModel software. With the suggested T2* selective (not frequency selective) filtering technique, in the simulated MRS data, we removed the metabolites from the simulated MRS(I) spectral signal baseline distorted by the water and fat signal observed in the most frequency band. Moreover, in the obtained MRSI data, the quantitative analysis results for the metabolites of interest showed notable improvement in the uncertainty estimation accuracy, the CRLB (Cramer-Rao Lower Bound) levels.

Quality control of 3D MRSI data in glioblastoma: Can we do without the experts?

Proton magnetic resonance spectroscopic imaging (1H MRSI) is a noninvasive technique for assessing tumor metabolism. Manual inspection is still the gold standard for quality control (QC) of spectra, but it is both time-consuming and subjective. The aim of the present study was to assess automatic QC of glioblastoma MRSI data using random forest analysis. Data for 25 patients, acquired prospectively in a preradiotherapy examination, were submitted to postprocessing with syngo.MR Spectro (VB40A; Siemens) or Java-based magnetic resonance user interface (jMRUI) software. A total of 28 features were extracted from each spectrum for the automatic QC. Three spectroscopists also performed manual inspections, labeling each spectrum as good or poor quality. All statistical analyses, with addressing unbalanced data, were conducted with R 3.6.1 (R Foundation for Statistical Computing; https://www.r-project.org). The random forest method classified the spectra with an area under the curve of 95.5%, sensitivity of 95.8%, and specificity of 81.7%. The most important feature for the classification was Residuum_Lipids_Versus_Fit, obtained with syngo.MR Spectro. The automatic QC method was able to distinguish between good- and poor-quality spectra, and can be used by radiation oncologists who are not spectroscopy experts. This study revealed a novel set of MRSI signal features that are closely correlated with spectral quality.

Absolute choline tissue concentration mapping for prostate cancer localization and characterization using 3D 1 H MRSI without water-signal suppression.

PurposeUntil now, 1H MRSI of the prostate has been performed with suppression of the large water signal to avoid distortions of metabolite signals. However, this signal can be used for absolute quantification and spectral corrections. We investigated the feasibility of water‐unsuppressed MRSI in patients with prostate cancer for water signal–mediated spectral quality improvement and determination of absolute tissue levels of choline.MethodsEight prostate cancer patients scheduled for radical prostatectomy underwent multi‐parametric MRI at 3 T, including 3D water‐unsuppressed semi‐LASER MRSI. A postprocessing algorithm was developed to remove the water signal and its artifacts and use the extracted water signal as intravoxel reference for phase and frequency correction of metabolite signals and for absolute metabolite quantification.ResultsWater‐unsuppressed MRSI with dedicated postprocessing produced water signal and artifact‐free MR spectra throughout the prostate. In all patients, the absolute choline tissue concentration was significantly higher in tumorous than in benign tissue areas (mean ± SD: 7.2 ± 1.4 vs 3.8 ± 0.7 mM), facilitating tumor localization by choline mapping. Tumor tissue levels of choline correlated better with the commonly used (choline + spermine + creatine)/citrate ratio (r = 0.78 ± 0.1) than that of citrate (r = 0.21 ± 0.06). The highest maximum choline concentrations occurred in high‐risk cancer foci.ConclusionThis report presents the first successful water‐unsuppressed MRSI of the whole prostate. The water signal enabled amelioration of spectral quality and absolute metabolite quantification. In this way, choline tissue levels were identified as tumor biomarker. Choline mapping may serve as a tool in prostate cancer localization and risk scoring in multi‐parametric MRI for diagnosis and biopsy procedures.

Overdiscrete echo-planar spectroscopic imaging with correlated higher-order phase correction.

To introduce a robust methodology for fast 1 H MRSI of the brain at 3T with improved SNR and reduced phase-related artifacts. An accelerated acquisition scheme using echo-planar spectroscopic imaging (EPSI) was combined with the overdiscrete reconstruction framework. This approach enables the interleaved acquisition of a water reference scan at each phase encoding step, maximizing its correlation with the water-suppressed measurement. Moreover, a generalized high-order phase correction was incorporated into the reconstruction pipeline. The spatial-temporal phase correction term was estimated from the reference scan and interpolated to high resolution using a polynomial basis. The method was implemented at 3T and validated with phantom and in vivo experiments. The methodology showed the elimination of spectral artifacts generated by phase disturbances and achieved mean SNR gains in vivo of 3.18 and 1.19 compared to standard reconstructions with corrections performed at nominal and high resolution, respectively. EPSI scans with interleaved water acquisition showed to be robust to system instabilities and potentially to patient motion. Moreover, phase distortions were effectively corrected in a single step, avoiding additional reference measurements and post-processing steps. The overdiscrete reconstruction framework with high-order phase correction allowed to effectively correct for distortions, related to B0 inhomogeneities, B0 drift, eddy currents, and system vibrations. Furthermore, the presented reconstruction method, combined with EPSI acquisitions, demonstrated improved measurement stability, substantial SNR enhancement, better spectral linewidth, and effective artifact removal.

NIMG-57. SERIAL HYPERPOLARIZED 13C PYRUVATE AND 1H METABOLIC IMAGING IN RECURRENT HIGH-GRADE GLIOMA

Abstract INTRODUCTION Hyperpolarized (HP) 13C MRI is a novel metabolic imaging that allows for real time in vivo probing of pathway-specific metabolic processes relevant to gliomas. The first human brain application reports were published recently. In this study, we characterized longitudinal dynamic and static brain metabolism changes from serial HP 13C and 1H metabolic imaging in a patient with multiply recurrent glioma. METHODS Eight dynamic HP 13C imaging, 1H MRI and MRSI examinations were acquired over a period of 15 months in a patient with multiply recurrent glioma that underwent malignant transformation. The patient was imaged after initial tumor debulking, after chemoradiotherapy, at first recurrence, after re-irradiation and anti-angiogentic therapy, and at second recurrence. Ratios of pyruvate-to-lactate and pyruvate-to-bicarbonate were calculated from HP 13C imaging and choline-to-NAA index (CNI) was derived from 1H MRSI. RESULTS/ DISCUSSION Successful therapies are usually associated with a drop in pyruvate-to-lactate conversion, mediated by different mechanisms from various treatments. We identified three key findings over repeat HP 13C MRIs: 1) a marked response to therapy with a reduction in pyruvate-to-lactate conversion corresponding to associated imaging response to therapy at the primary site of disease. Following chemoradiotherapy, the volume of T2 hyperintensity decreased from 28.21cc to 15.29 cc, and the volume of metabolic abnormality (CNI &gt;3) decreased from 27.84 cc to 10.36 cc. 2) increasing pyruvate-to-lactate conversion in a region of recurrence before morphologic signal abnormality, and 3) a reduction in pyruvate-to-lactate conversion in a recurrent lesion following anti-angiogenic therapy. CONCLUSION Here we show that one can reliably image glioma patients using HP 13C MRI alongside standard of care morphologic and physiologic MRI including diffusion, perfusion, and 1H MRSI. Serial HP 13C MRI can be performed in the neuro-oncologic clinical setting and pyruvate-to-lactate metabolism may be useful to monitor treatment response.

The principle, present and prospect of IMCL measurement based on&amp;lt;sup&amp;gt;1&amp;lt;/sup&amp;gt;H MRSI technology

It has been found that, as a main mechanism for diabetes, insulin resistance may have appeared more than a decade before the onset of diabetes. Therefore, early detection of insulin resistance has vital significance for the early prevention, diagnosis, and treatment of diabetes. The content of intramyocellular lipid (IMCL) in human calf muscle has close and complex relationship with insulin resistance and metabolic disorders and, therefore, is associated with type 2 diabetes mellitus and even a variety of mental diseases. However, the current “gold standard” for IMCL measurement is the invasive biopsy technology, which is not suitable for large-scale basic research and long-term clinical applications. IMCL measurement technology based on proton magnetic resonance spectroscopy and spectroscopic imaging (1H MRSI) provides a radiation-free, non-invasive, and high-precision detection method. More than this, 1H MRSI has been expected to clarify the relationship between IMCL content and insulin resistance, as well as the relationship between insulin resistance and type 2 diabetes mellitus, and has the potential to be applied in clinical practice. This paper describes and summarizes the technical development of 1H MRSI-based IMCL content measurement. It also points out the challenges and the latest solutions of this technique from the aspects of physiological and structural characteristics of calves, muscle fiber direction, the bulk fat distribution, and the demand for precise quantification of IMCL content. In addition to reviewing the latest technical solutions to these problems, we particularly discuss the combination of 1H MRSI with some new technologies such as multi-mode magnetic resonance imaging (MRI) and magnetic resonance fingerprinting spectroscopy (MRFS), which will synergically provide more diversified, multi-dimensional and multi-scale measurement method for high-precision measurement of IMCL.

Lost in translation: lessons learned from the "demise" of MRSI of the prostate.

At times, technologies fail for reasons other than an inability to deliver on their promises. The iconic Blackberry, for example, was once coined "Research in Motion", sold tens of millions of units, and then "disappeared" from the market because it did not accompany the new trends in design. Promising technologies may also "disappear" in the medical field. What follows is the tale of the rise and fall of proton magnetic resonance spectroscopic imaging (1H MRSI) of the prostate.

An 8-channel receive array for improved 31 P MRSI of the whole brain at 3T.

PurposeTo demonstrate a 1H/31P whole human brain volume coil configuration for 3 Tesla with separate 31P transmit and receive components that maintains 1H MRS performance and delivers optimal 31P MRSI with 1H decoupling.MethodsWe developed an 8‐channel 31P receive array coil covering the head to be used as an insert for a commercial double‐tuned 1H/31P birdcage transmit‐receive coil. This retains the possibility of using low‐power rectangular pulses for 1H‐decoupled 3D 31P MRSI (nominal resolution 17.6 cm3; acquisition duration 13 min) but increases the SNR with the receive sensitivity of 31P surface coils. The performance of the combined coil setup was evaluated by measuring 1H and 31P SNR with and without the 31P receive array and by assessing the effect of the receive array on the transmit efficiencies of the birdcage coil.ResultsCompared to the birdcage coil alone, the 31P insert in combination with the birdcage achieved an average 31P SNR gain of 1.4 ± 0.4 in a center partition of the brain. The insert did not cause losses in 1H MRS performance and transmit efficiency, whereas for 31P approximately 20% more power was needed to achieve the same γB1.ConclusionThe new coil configuration allows 1H MRSI and optimal 1H‐decoupled 3D 31P MRSI, with increased SNR of the human brain without patient repositioning, for clinical and research purposes at 3 Tesla.

Metabolic consequences of HIF silencing in a triple negative human breast cancer xenograft.

Hypoxia is frequently encountered in tumors and results in the stabilization of hypoxia inducible factors (HIFs). These factors transcriptionally activate genes that allow cells to adapt to hypoxia. In cancers, hypoxia and HIFs have been associated with increased invasion, metastasis, and resistance to chemo and radiation therapy. Here we have characterized the metabolic consequences of silencing HIF-1α and HIF-2α singly or combined in MDA-MB-231 triple negative human breast cancer xenografts, using non-invasive proton magnetic resonance spectroscopic imaging (1H MRSI) of in vivo tumors, and high-resolution 1H MRS of tumor extracts. Tumors from all three sublines showed a significant reduction of growth rate. We identified new metabolic targets of HIF, and demonstrated the divergent consequences of silencing HIF-1α and HIF-2α individually on some of these targets. These data expand our understanding of the metabolic pathways regulated by HIFs that may provide new insights into the adaptive metabolic response of cancer cells to hypoxia. Such insights may lead to novel metabolism based therapeutic targets for triple negative breast cancer.

In vivo MR spectroscopic imaging of the prostate, from application to interpretation

In vivo MR spectroscopic imaging of the prostate, from application to interpretation

Elevations of ventricular lactate levels occur in both chronic fatigue syndrome and fibromyalgia

ABSTRACT Background: Chronic fatigue syndrome (CFS) and fibromyalgia (FM) frequently have overlapping symptoms, leading to the suggestion that the same disease processes may underpin the two disorders – the unitary hypothesis. However, studies investigating the two disorders have reported substantial clinical and/or biological differences between them, suggesting distinct pathophysiological underpinnings. Purpose: The purpose of this study was to further add to the body of evidence favoring different disease processes in CFS and FM by comparing ventricular cerebrospinal fluid lactate levels among patients with CFS alone, FM alone, overlapping CFS and FM symptoms, and healthy control subjects. Methods: Ventricular lactate was assessed in vivo with proton magnetic resonance spectroscopic imaging (1H MRSI) with the results normed across the two studies in which the data were collected. Results: Mean CSF lactate levels in CFS, FM and CFS + FM did not differ among the three groups, but were all significantly higher than the mean values for control subjects. Conclusion: While patients with CFS, FM and comorbid CFS and FM can be differentiated from healthy subjects based on measures of CFS lactate, this neuroimaging outcome measure is not a viable biomarker for differentiating CFS from FM or from patients in whom symptoms of the two disorders overlap.

Multimodality imaging using proton magnetic resonance spectroscopic imaging and 18F-fluorodeoxyglucose-positron emission tomography in local prostate cancer.

AIMTo assess the relationship using multimodality imaging between intermediary citrate/choline metabolism as seen on proton magnetic resonance spectroscopic imaging (1H-MRSI) and glycolysis as observed on 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) in prostate cancer (PCa) patients.METHODSThe study included 22 patients with local PCa who were referred for endorectal magnetic resonance imaging/1H-MRSI (April 2002 to July 2007) and 18F-FDG-PET/CT and then underwent prostatectomy as primary or salvage treatment. Whole-mount step-section pathology was used as the standard of reference. We assessed the relationships between PET parameters [standardized uptake value (SUVmax and SUVmean)] and MRSI parameters [choline + creatine/citrate (CC/Cmax and CC/Cmean) and total number of suspicious voxels] using spearman’s rank correlation, and the relationships of PET and 1H-MRSI index lesion parameters to surgical Gleason score.RESULTSAbnormal intermediary metabolism on 1H-MRSI was present in 21/22 patients, while abnormal glycolysis on 18F-FDG-PET/CT was detected in only 3/22 patients. Specifically, index tumor localization rates were 0.95 (95%CI: 0.77-1.00) for 1H-MRSI and 0.14 (95%CI: 0.03-0.35) for 18F-FDG-PET/CT. Spearman rank correlations indicated little relationship (ρ = -0.36-0.28) between 1H-MRSI parameters and 18F-FDG-PET/CT parameters. Both the total number of suspicious voxels (ρ = 0.55, P = 0.0099) and the SUVmax (ρ = 0.46, P = 0.0366) correlated weakly with the Gleason score. No significant relationship was found between the CC/Cmax, CC/Cmean or SUVmean and the Gleason score (P = 0.15-0.79).CONCLUSIONThe concentration of intermediary metabolites detected by 1H MRSI and glycolytic flux measured 18F-FDG PET show little correlation. Furthermore, only few tumors were FDG avid on PET, possibly because increased glycolysis represents a late and rather ominous event in the progression of PCa.

Effect of Bilingualism in the Anterior Cingulate Cortex: A Proton Magnetic Resonance Spectroscopy Study in Two Centres

Effect of Bilingualism in the Anterior Cingulate Cortex: A Proton Magnetic Resonance Spectroscopy Study in Two Centres

Proton MR spectroscopic imaging of human glioblastomas at 1.5 Tesla.

In this study we evaluated clinical feasibility of proton magnetic resonance spectroscopy metabolite mapping (1H MRSI) by using 1.5 Tesla MR-scanner in 10 patients with high-grade glioblastoma. In vivo 1H MRSI performed with a relatively short scan time of 20 minutes enabled to obtain comprehensive information about metabolic changes in glioblastoma and adjacent tissues namely in the peritumoral edema, in the middle and solid part of the tumor, and in the normal-appearing brain tissue. Spectroscopically it was possible to identify initiation of neuronal cell death in the solid tumorous tissue via decreased N-acetyl-aspartate to creatine ratio (↓ tNAA/tCr) and expanding carcinogenesis reflected in elevated choline ratios (↑ tCho/tCr and tCho/tNAA). We showed also the central necrosis of glioblastoma accompanied by the tissue hypoxia, which were apparent as increased lactate and lipids ratios (↑ Lac/tCr and lip/Lac). Metabolic changes were noticeable also in the peritumoral area, showing the glioblastoma infiltration into the surrounding tissues. In intracranial tumors, 1H MRSI performed on 1.5 Tesla field strength was sufficient to provide information about the stage of carcinogenesis, tumor expansion or necrotization and thus it could be considered as a useful diagnostic tool in oncology.

An advanced MRI and MRSI data fusion scheme for enhancing unsupervised brain tumor differentiation

An advanced MRI and MRSI data fusion scheme for enhancing unsupervised brain tumor differentiation

Low episodic memory performance in cognitively normal elderly subjects is associated with increased posterior cingulate gray matter N-acetylaspartate: a 1H MRSI study at 7 Tesla

Low episodic memory performance in cognitively normal elderly subjects is associated with increased posterior cingulate gray matter N-acetylaspartate: a 1H MRSI study at 7 Tesla

MP79-10 PROTON MAGNETIC RESONANCE IMAGING SPECTROSCOPY IMPROVES PREDICTION OF HIGH GRADE PROSTATE CANCER WHEN INTEGRATED IN PI-RADS 2

MP79-10 PROTON MAGNETIC RESONANCE IMAGING SPECTROSCOPY IMPROVES PREDICTION OF HIGH GRADE PROSTATE CANCER WHEN INTEGRATED IN PI-RADS 2