Neurochemical correlations in short echo time proton magnetic resonance spectroscopy.

Neurochemical concentrations determined by magnetic resonance spectroscopy (MRS) have been treated as statistically independent measurements in various clinical MRS studies. However, spectral overlap, independent of any biological effects, could lead to significant correlations between neurochemical concentrations extracted from spectral fitting of MRS data, confounding determination of correlations of biological origin. Short echo time (TE) proton MRS spectra are very crowded because of the comparatively narrow chemical shift dispersion of proton nuclear spins. In this study, the complex neurochemical correlations of spectral origin in short-TE MRS spectra were quantified. The effects of macromolecules and the background spectral baseline on metabolite-metabolite correlations were also analyzed. Our results demonstrate the importance of factoring in spectral correlations when correlating overlapping metabolite signals in short-TE spectra with clinical parameters.

Multiparametric voxel-based analyses of standardized uptake values and apparent diffusion coefficients of soft-tissue tumours with a positron emission tomography/magnetic resonance system: Preliminary results.

OBJECTIVES: To investigate the usefulness of voxel-based analysis of standardized uptake values (SUVs) and apparent diffusion coefficients (ADCs) for evaluating soft-tissue tumour malignancy with a PET/MR system. METHODS: Thirty-five subjects with either ten low/intermediate-grade tumours or 25 high-grade tumours were prospectively enrolled. Zoomed diffusion-weighted and fluorodeoxyglucose (18FDG)-PET images were acquired along with fat-suppressed T2-weighted images (FST2WIs). Regions of interest (ROIs) were drawn on FST2WIs including the tumour in all slices. ROIs were pasted onto PET and ADC-maps to measure SUVs and ADCs within tumour ROIs. Tumour volume, SUVmax, ADCminimum, the heterogeneity and the correlation coefficients of SUV and ADC were recorded. The parameters of high- and low/intermediate-grade groups were compared, and receiver operating characteristic (ROC) analysis was also performed. RESULTS: The mean correlation coefficient for SUV and ADC in high-grade sarcomas was lower than that of low/intermediate-grade tumours (-0.41 ± 0.25 vs. -0.08 ± 0.34, P < 0.01). Other parameters did not differ significantly. ROC analysis demonstrated that correlation coefficient showed the best diagnostic performance for differentiating the two groups (AUC 0.79, sensitivity 96.0%, specificity 60%, accuracy 85.7%). CONCLUSIONS: SUV and ADC determined via PET/MR may be useful for differentiating between high-grade and low/intermediate-grade soft tissue tumours. KEY POINTS: • PET/MR allows voxel-based comparison of SUVs and ADCs in soft-tissue tumours. • A comprehensive assessment of internal heterogeneity was performed with scatter plots. • SUVmax or ADCminimum could not differentiate high-grade sarcoma from low/intermediate-grade tumours. • Only the correlation coefficient between SUV and ADC differentiated the two groups. • The correlation coefficient showed the best diagnostic performance by ROC analysis.

Metabolic coupling between glutamate and N-acetylaspartate in the human brain.

A metabolic coupling between glutamate and N-acetylaspartate measured by in vivo magnetic resonance spectroscopy has been recently reported in the literature with inconsistent findings. In this study, confounders originating from Pearson's spurious correlation of ratios and spectral correlation due to overlapping magnetic resonance spectroscopy signals of glutamate and N-acetylaspartate were practically eliminated to facilitate the determination of any metabolic link between glutamate and N-acetylaspartate in the human brain using in vivo magnetic resonance spectroscopy. In both occipital and medial prefrontal cortices of healthy individuals, correlations between glutamate and N-acetylaspartate were found to be insignificant. Our results do not lend support to a recent hypothesis that N-acetylaspartate serves as a significant reservoir for the rapid replenishment of glutamate during signaling or stress.

Quantification issues of in vivo (1) H NMR spectroscopy of the rat brain investigated at 16.4 T.

The accuracy and precision of the quantification of metabolite concentrations in in vivo (1) H NMR spectroscopy are affected by linewidth and signal-to-noise ratio (SNR). To study the effect of both factors in in vivo (1) H NMR spectra acquired at ultrahigh field, a reference spectrum was generated by summing nine in vivo (1) H NMR spectra obtained in rat brain with a STEAM sequence at 16.4 T. By progressive deterioration of linewidth and SNR, 6400 single spectra were generated. In an accuracy study, the variation in the mean concentrations of five metabolites was mainly dependent on SNR, whereas 11 metabolites were predominantly susceptible to the linewidth. However, the standard deviations of the concentrations obtained were dependent almost exclusively on the SNR. An insignificant correlation was found between most of the heavily overlapping metabolite peaks, indicating independent and reliable quantification. Two different approaches for the consideration of macromolecular signals were evaluated. The use of prior knowledge derived by parameterization of a metabolite-nulled spectrum demonstrated improved fitting quality, with reduced Cramér-Rao lower bounds, compared to the calculation of a regularized spline baseline.

Magnetic Field Dependence of Spectral Correlations between 31P-Containing Metabolites in Brain.

Spectral correlations between metabolites in 31P magnetic resonance spectroscopy (MRS) spectra of human brain were compared at 3 and 7 Tesla, the two commonly used magnetic field strengths for clinical research. It was found that at both field strengths, there are significant correlations between 31P-containing metabolites arising from spectral overlap, and their downfield correlations are markedly altered by the background spectral baseline. Overall, the spectral correlations between 31P-containing metabolites are markedly reduced at 7 Tesla with the increased chemical shift dispersion and the decreased membrane phospholipid signal. The findings provide the quantitative landscape of pre-existing correlations in 31P MRS spectra due to overlapping signals. Detailed procedures for quantifying the pre-existing correlations between 31P-containing metabolites are presented to facilitate incorporation of spectral correlations into statistical modeling in clinical correlation studies.

Monte Carlo study of metabolite correlations originating from spectral overlap.

Monte Carlo simulations and a mathematical model of spectral fitting were used to study the correlations between metabolites with overlapping resonances. The dependence of the polarity and the magnitude of cross-correlation coefficients between overlapping metabolites on the spectral patterns of MRS signals was investigated. The results demonstrate the importance of quantifying metabolite correlations originating from spectral overlap as they may confound determination of correlations of biological origin. The findings also indicate that it is possible to minimize unwanted metabolite correlations by altering spectral patterns in the presence of significant spectral overlap.

Determination of regional variations and reproducibility in in vivo 1H NMR spectroscopy of the rat brain at 16.4 T.

In vivo (1)H NMR spectroscopy was used to obtain the neurochemical profile in the posterior parts of the brain, the cerebellum and the medulla oblongata in comparison to the hippocampus and the thalamus. Using small voxel sizes between 16 and 32 µl to avoid partial volume effects, most metabolites demonstrated significant regional differences except acetate, γ-aminobutyric acid, and phosphorylcholine. Noticeable regional differences in metabolite concentrations were the significant increase of total creatine in the cerebellum and the substantial decrease of taurine in thalamus and medulla oblongata. In particular, the glycine concentration in the medulla oblongata was determined to be 4.37 ± 0.68 µmol/g (Cramér-Rao lower bounds 7%) and thus significantly higher than in the other regions, consistent with findings reported in both in vivo (1)H NMR spectroscopy and in vitro biochemical assays. Intraindividual reproducibility and interindividual variability were investigated by acquiring spectra from the thalamus of the same rats in two sessions. No prominent influence on measurement session was observed in metabolite concentrations with coefficients of variations being below 20% in 16 metabolites.

Enhanced neurochemical profile of the rat brain using in vivo (1)H NMR spectroscopy at 16.4 T.

Single voxel magnetic resonance spectroscopy with ultrashort echo time was implemented at 16.4 T to enhance the neurochemical profile of the rat brain in vivo. A TE of 1.7 msec was achieved by sequence optimization and by using short-duration asymmetric pulses. Macromolecular signal components were parameterized individually and included in the quantitative analysis, replacing the use of a metabolite-nulled spectrum. Because of the high spectral dispersion, several signals close to the water line could be detected, and adjacent peaks could be resolved. All 20 metabolites detected in this study were quantified with Cramér-Rao lower bounds below 20%, implying reliable quantification accuracy. The signal of acetate was detected for the first time in rat brain in vivo with Cramér-Rao lower bounds of 16% and a concentration of 0.52 µmol/g. The absolute concentrations of most metabolites showed close agreement with values previously measured using in vivo (1)H NMR spectroscopy and in vitro biochemical assay.

Rat strain-dependent variations in brain metabolites detected by in vivo (1) H NMR spectroscopy at 16.4T.

Localized in vivo (1) H NMR spectroscopy is playing an increasing role in preclinical studies, because of its ability to quantify the concentrations of up to 20 metabolites in rat brain. To assess the differences between often-used rat strains, the neurochemical profiles of Sprague-Dawley, Wistar and Fischer rats were determined at ultrashort TE at 16.4 T. To ascertain high-qualitative quantification, a first experiment examined the dependence of the measuring time on the quantification results and precision by precisely the number of averages between 16 and 320. It was shown that most metabolites can be quantified accurately within a short scan time, yielding Cramér-Rao lower bounds below 20% and stable concentrations for 16 metabolites with as few as 32 or 64 averages in the thalamus and hippocampus, respectively. Interstrain differences in metabolite concentrations were shown to be moderate, with taurine varying significantly between Sprague-Dawley and Wistar rats, and slightly more distinct differences from Fischer rats, including variations in glutamate and myo-inositol. The high spectral quality and quantification precision of all data again demonstrated the potential of in vivo (1)H NMR spectroscopy at ultrahigh field.

Highly Accelerated Real-Time Free-Breathing Cine CMR for Patients With a Cardiac Implantable Electronic Device.

RATIONALE AND OBJECTIVES: To develop a 16-fold accelerated real-time, free-breathing cine cardiovascular magnetic resonance (CMR) pulse sequence with compressed sensing reconstruction and test whether it is capable of producing clinically acceptable summed visual scores (SVS) and accurate left ventricular ejection fraction (LVEF) in patients with a cardiac implantable electronic device (CIED). MATERIALS AND METHODS: A 16-fold accelerated real-time cine CMR pulse sequence was developed using gradient echo readout, Cartesian k-space sampling, and compressed sensing. We scanned 13 CIED patients (mean age = 59 years; 9/4 males/females) using clinical standard, breath-hold cine and real-time, free-breathing cine. Two clinical readers performed a visual assessment of image quality in four categories (conspicuity of endocardial wall at end diastole, temporal fidelity of wall motion, any artifact level on the heart, noise) using a five-point Likert scale (1: worst; 3: clinically acceptable; 5: best). SVS was calculated as the sum of 4 individual scores, where 12 was defined as clinical acceptable. The Wilcoxon signed-rank test was performed to compare SVS, and the Bland-Altman analysis was conducted to evaluate the agreement of LVEF. RESULTS: Median scan time was 3.7 times shorter for real-time (3.5 heartbeats per slice) than clinical standard (13 heartbeats per slice, excluding nonscanning time between successive breath-hold acquisitions). Median SVS was not significantly different between clinical standard (15.0) and real-time (14.5). The mean difference in LVEF was -2% (4.7% of mean), and the limits of agreement was 5.8% (13.5% of mean). CONCLUSION: This study demonstrates that the proposed real-time cine method produces clinically acceptable SVS and relatively accurate LVEF in CIED patients.

Variation of the choline signal intensity in the dorsolateral prefrontal cortex of rats exposed to the forced swimming test as detected by in vivo 1H MR spectroscopy.

BACKGROUND: (1)H magnetic resonance spectroscopy (MRS) has documented an increased Cho/Cr ratio in the dorsolateral prefrontal cortex (DLPFC) in major depressive disorder (MDD). The aim of this study was to investigate neurochemical alterations in the left DLPFC, considered a main area of pathogenesis in depression, using rats exposed to the forced swimming test (FST). MATERIALS AND METHODS: Twenty-four male rats were used for the MRI and in vivo(1)H MRS studies. Rats exposed to the FST to induce a depressed mental status. Using in vivo(1)H MRS, the metabolite ratios of the rats with a depressed mental status and the controls, were measured and the values of the two groups were compared. RESULTS: The Cho/Cr and Cho/NAA ratios in the DLPFC of the rats with a depressed mental status were significantly higher than that in the controls. CONCLUSIONS: The present study demonstrates a significantly increased Cho/Cr ratio in the DLPFC of rats with depression compared with controls. This result may suggest an accelerated turnover of membrane without neuronal loss is occurring in the DLPFC of the rats with depression.