Detection of lactate in the striatum without contamination of macromolecules by J‐difference editing MRS at 7 T

Lactate levels are measurable by MRS and are related to neural activity. Therefore, it is of interest to accurately measure lactate levels in the basal ganglia networks. If sufficiently stable, lactate measurements may be used to investigate alterations in dopaminergic signalling in the striatum, facilitating the detection and diagnosis of metabolic deficits. The aim of this study is to provide a J‐difference editing MRS technique for the selective editing of lactate only, thus allowing the detection of lactate without contamination of overlapping macromolecules. As a validation procedure, macromolecule nulling was combined with J‐difference editing, and this was compared with J‐difference editing with a new highly selective editing pulse. The use of a high‐field (7T) MR scanner enables the application of editing pulses with very narrow bandwidth, which are selective for lactate. We show that, despite the sensitivity to B₀ offsets, the use of a highly selective editing pulse is more efficient for the detection of lactate than the combination of a broad‐band editing pulse with macromolecule nulling. Although the signal‐to‐noise ratio of uncontaminated lactate detection in healthy subjects is relatively low, this article describes the test–retest performance of lactate detection in the striatum when using highly selective J‐difference editing MRS at 7 T. The coefficient of variation, σ_w and intraclass correlation coefficients for within‐ and between‐subject differences of lactate were determined. Lactate levels in the left and right striatum were determined twice in 10 healthy volunteers. Despite the fact that the test–retest performance of lactate detection is moderate with a coefficient of variation of about 20% for lactate, these values can be used for the design of new studies comparing, for example, patient populations with healthy controls. Copyright © 2015 John Wiley & Sons, Ltd.     

Measurement of brain lactate during visual stimulation using a long TE semi‐LASER sequence at 7 T

Estimation of metabolic changes during neuronal activation represents a challenge for in vivo MRS, especially for metabolites with low concentration and signal overlap, such as lactate. In this work, we aimed to evaluate the feasibility of detecting lactate during brain activation using a long (144 ms) semi‐LASER sequence at 7 T. spectra were acquired on healthy volunteers ( ) during a paradigm with 15 min of visual stimulation. Outer‐volume signals were further attenuated by the use of saturation slabs, and macromolecular signals in the vicinity of the inverted lactate peak were individually fitted with simulated Lorentzian peaks. All spectra were free of artefacts and highly reproducible across subjects. Lactate was accurately quantified with an average Cramér‐Rao lower bound of 8%. Statistically significant ( , one‐tailed ‐test) increases in lactate ( 10%) and glutamate ( 3%) levels during stimulation were detected in the visual cortex. Lactate and glutamate changes were consistent with previous measurements. We demonstrated that quantification of a clear and non‐contaminated lactate peak obtained with a long TE sequence has the potential of improving the accuracy of functional MRS studies targeting non‐oxidative reaction pathways.     

Origin of the 31P MR signal at 5.3 ppm in patients with critical limb ischemia

An unknown intense signal (P_un) with a mean chemical shift of 5.3 ppm was observed in ³¹P MR spectra from the calf muscles of patients with the diabetic foot syndrome. The aim of the study was to identify the origin of this signal and its potential as a biomarker of muscle injury. Calf muscles of 68 diabetic patients (66.3 ± 8.6 years; body mass index = 28.2 ± 4.3 kg/m²) and 12 age‐matched healthy controls were examined by (dynamic) ³¹P MRS (3 T system, ³¹P/¹H coil). Phantoms (glucose‐1‐phosphate, P_i and PCr) were measured at pH values of 7.05 and 7.51. At rest, P_un signals with intensities higher than 50% of the P_i intensity were observed in 10 of the 68 examined diabetic subjects. We tested two hypothetical origins of the P_un signal: (1) phosphorus from phosphoesters and (2) phosphorus from extra‐ and intracellular alkaline phosphate pools. 2,3‐diphosphoglycerate and glucose‐1‐phosphate are the only phosphoesters with signals in the chemical shift region close to 5.3 ppm. Both compounds can be excluded: 2,3‐diphosphoglycerate due to the missing second signal component at 6.31 ppm; glucose‐1‐phosphate because its chemical shifts are about 0.2 ppm downfield from the P_i signal (4.9 ppm). If the P_un signal is from phosphate, it represents a pH value of 7.54 ± 0.05. Therefore, it could correspond to signals of P_i in mitochondria. However, patients with critical limb ischemia have rather few mitochondria and so the P_un signal probably originates from interstitia. Our data suggest that the increased P_un signal observed in patients with the diabetic foot syndrome is a biomarker of severe muscular damage.     

Feasibility of precise and reliable glucose quantification in human whole blood samples by 1 tesla benchtop NMR

The standard procedure for blood glucose measurements is enzymatic testing. This method is cheap, but requires small samples of open blood with direct contact to the test medium. In principle, NMR provides non‐contact analysis of body fluids, but high‐field spectrometers are expensive and cannot be easily utilized under clinical conditions. Low‐field NMR systems with permanent magnets are becoming increasingly smaller and more affordable. The studies presented here aim at exploring the capabilities of low‐field NMR for measuring glucose concentrations in whole blood. For this purpose, a modern 1 T benchtop NMR spectrometer was used. Challenges arise from broad spectral lines, the glucose peak locations close to the water signal, low SNR and the interference with signals from other blood components. Whole blood as a sample comprises even more boundary conditions: crucial for reliable results are avoiding the separation of plasma and cells by gravitation and reliable reference values. First, the accuracy of glucose levels measured by NMR was tested using aqueous glucose solutions and commercially available bovine plasma. Then, 117 blood samples from oral glucose tolerance testing were measured with minimal preparation by simple pulse‐acquire NMR experiments. The analysis itself is the key to achieve high precision, so several approaches were investigated: peak integration, orthogonal projection to latent structure analysis and support vector machine regression. Correlations between results from the NMR spectra and the routine laboratory automated analyzer revealed an RMSE of 7.90 mg/dL for the best model. 91.5% of the model output lies within the limits of the German Medical Association guidelines, which require the glucose measurement to be within 11% of the reference method. It is concluded that spectral quantification of glucose in whole blood samples by high‐quality NMR spectrometers operating at 1 T is feasible with sufficient accuracy.     

Pyruvate‐lactate exchange and glucose uptake in human prostate cancer cell models. A study in xenografts and suspensions by hyperpolarized [1‐13C]pyruvate MRS and [18F]FDG‐PET

Reprogramming of energy metabolism in the development of prostate cancer can be exploited for a better diagnosis and treatment of the disease. The goal of this study was to determine whether differences in glucose and pyruvate metabolism of human prostate cancer cells with dissimilar aggressivenesses can be detected using hyperpolarized [1‐¹³C]pyruvate MRS and [¹⁸F]FDG‐PET imaging, and to evaluate whether these measures correlate. For this purpose, we compared murine xenografts of human prostate cancer LNCaP cells with those of more aggressive PC3 cells. [1‐¹³C]pyruvate was hyperpolarized by dissolution dynamic nuclear polarization (dDNP) and [1‐¹³C]pyruvate to lactate conversion was followed by ¹³C MRS. Subsequently [¹⁸F]FDG uptake was investigated by static and dynamic PET measurements. Standard uptake values (SUVs) for [¹⁸F]FDG were significantly higher for xenografts of PC3 compared with those of LNCaP. However, we did not observe a difference in the average apparent rate constant k_pl of ¹³C label exchange from pyruvate to lactate between the tumor variants. A significant negative correlation was found between SUVs from [¹⁸F]FDG PET measurements and k_pl values for the xenografts of both tumor types. The k_pl rate constant may be influenced by various factors, and studies with a range of prostate cancer cells in suspension suggest that LDH inhibition by pyruvate may be one of these. Our results indicate that glucose and pyruvate metabolism in the prostate cancer cell models differs from that in other tumor models and that [¹⁸F]FDG‐PET can serve as a valuable complementary tool in dDNP studies of aggressive prostate cancer with [1‐¹³C]pyruvate.     

Extraction of artefactual MRS patterns from a large database using non-negative matrix factorization

Despite the success of automated pattern recognition methods in problems of human brain tumor diagnostic classification, limited attention has been paid to the issue of automated data quality assessment in the field of MRS for neuro-oncology. Beyond some early attempts to address this issue, the current standard in practice is MRS quality control through human (expert-based) assessment. One aspect of automatic quality control is the problem of detecting artefacts in MRS data. Artefacts, whose variety has already been reviewed in some detail and some of which may even escape human quality control, have a negative influence in pattern recognition methods attempting to assist tumor characterization. The automatic detection of MRS artefacts should be beneficial for radiology as it guarantees more reliable tumor characterizations, as well as the development of more robust pattern recognition-based tumor classifiers and more trustable MRS data processing and analysis pipelines. Feature extraction methods have previously been used to help distinguishing between good and bad quality spectra to apply subsequent supervised pattern recognition techniques. In this study, we apply feature extraction differently and use a variant of a method for blind source separation, namely Convex Non-Negative Matrix Factorization, to unveil MRS signal sources in a completely unsupervised way. We hypothesize that, while most sources will correspond to the different tumor patterns, some of them will reflect signal artefacts. The experimental work reported in this paper, analyzing a combined short and long echo time ¹H-MRS database of more than 2000 spectra acquired at 1.5T and corresponding to different tumor types and other anomalous masses, provides a first proof of concept that points to the possible validity of this approach.     

Comparative evaluation of MRS and SPECT in prognostication of patients with mild to moderate head injury

Magnetic resonance spectroscopy (MRS) and single-photon emission computed tomography (SPECT) have only been individually studied in patients with head injury. This study aimed to comparatively assess both in patients with mild to moderate head injury. Patients with a Glasgow Coma Scale (GCS) score of 9–14 who underwent MRS and/or SPECT were evaluated in relation to various clinical factors and neurological outcome at 3 months. There were 56 SPECT (Tc99m-ethylcysteinate dimer [ECD]) studies and 41 single voxel proton MRS performed in 53 patients, with 41 patients having both. Of the 41 who underwent MRS, 13 had a lower N-acetyl-aspartate/creatine (NAA/Cr) ratio, 14 had a higher choline (Cho)/Cr ratio, 19 were normal, and nine had bilateral MRS abnormalities. Of the 56 who underwent SPECT, 22 and 19 had severe and moderate hypoperfusion, respectively. Among those in Traumatic Coma Data Bank CT scan category 1 and 2, 50% had MRS abnormalities, whereas 64% had SPECT hypoperfusion, suggesting greater incremental validity of SPECT over MRS. In univariate analyses, GCS, moderate/severe hypoperfusion and bilateral SPECT changes were found to have significant association with unfavorable outcome (odds ratio 13.2, 15.9, and 4.4, and p values <0.01, 0.01, and 0.05, respectively). Patients with lower NAA/Cr ratio in MRS had more unfavorable outcomes, however this was not significant. In multivariate analysis employing binary logistic regression, GCS and severe hypoperfusion on SPECT were noted to have significant association with unfavorable outcome, independent of age, CT scan category, and MRS abnormalities (p values = 0.02 and 0.04, respectively). To conclude, ECD-SPECT seems to have greater sensitivity, incremental validity and prognostic value than single voxel proton MRS in select patients with head injury, with only severe hypoperfusion in SPECT significantly associated with unfavorable outcome independent of other confounding factors.     

Eliminating side excitations in PROPELLER‐based 2D‐selective RF excitations

Recently, spatially two‐dimensional selective radiofrequency excitations based on the PROPELLER trajectory have been presented and were applied to minimize partial volume effects in single‐voxel MR spectroscopy. Thereby, residual side excitations appeared due to limitations of the Voronoi diagram that was used to consider the nonconstant sampling density, and trajectory distortions caused by eddy currents varying between the differently rotated blades. In this extension, one of the refocusing radiofrequency pulses of a PRESS‐based pulse sequence is applied in the blip direction of each segment to eliminate the side excitations. This corresponds to an infinitely dense sampling of the blade and the required sampling density correction can easily be calculated. Thus, signal contributions from outside the desired region‐of‐interest are completely avoided. The feasibility of this approach to acquire single‐voxel MR spectra of anatomically defined regions‐of‐interest is demonstrated in the human brain in vivo on a 3T whole‐body MR system. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.