Reproducibility of human cardiac 31P-NMR spectroscopy.

The reproducibility of the phosphocreatine to adenosine triphosphate ratio (PCr/ATP) was assessed from cardiac phosphorus-31 (31P) NMR spectra of the human left ventricle acquired with three different localization techniques. Cardiac 31P-NMR spectra (n = 68) were obtained at rest from 16 healthy subjects with three-dimensional (3D) image selected in vivo spectroscopy (ISIS), 1D spectroscopic imaging (SI), or with a combination of 2D ISIS and the 1D SI technique (ISIS + SI). The average PCr/ATP ratios were 1.41 +/- 0.20 for ISIS + SI and 1.31 +/- 0.19 for ISIS and were in the lower range of values obtained in previous studies, mainly because of a lower saturation correction factor for the cardiac PCr/ATP ratio. The SI experiment yielded an average PCr/ATP value of 0.98 +/- 0.20, significantly lower as compared to the correct values obtained with ISIS + SI and ISIS (p < 0.001), underscoring the need for 3D localization to avoid contamination of the NMR signal by liver tissue. Intersubject standard deviations of the PCr/ATP ratio were comparable to values reported previously. For all three localization techniques the absolute intra-examination differences in PCr/ATP (0.06 for ISIS to 0.15 for ISIS + SI) were significantly smaller (p approximately 0.03) than inter-examination differences (0.24 for ISIS to 0.29 for ISIS + SI). Therefore, consecutive acquisition of cardiac 31P-NMR spectra from the same patient during a single examination, e.g. under various cardiac loading conditions, appears to be a reliable approach for metabolic evaluation of heart disease.

Inflow versus deoxyhemoglobin effects in BOLD functional MRI using gradient echoes at 1.5 T.

Modified gradient-echo MR techniques were applied to study the effects of inflow on functional brain imaging studies using visual and motor cortex stimulation. The results demonstrate that the large signal changes, seen in previously reported gradient-echo studies at 1.5-2.0 T, are dominated by direct inflow effects, in particular when using a large flip angle and a thin slice. The findings suggest that inflow-based functional imaging, along with Blood Oxygenation Level Dependent (BOLD) functional MRI, may play an important role in future research towards the functional organization of the human brain.

P-31 MR spectroscopy of skeletal and cardiac muscle metabolism in patients with systemic sclerosis: a multiple case study.

Three-dimensionally localized proton-decoupled phosphorus-31 magnetic resonance (MR) spectroscopy of skeletal and cardiac muscle was performed in six patients with systemic sclerosis. Cardiac (n = 9) and skeletal (n = 6) spectra were also obtained in healthy volunteers. Metabolite ratios and intracellular pH were determined from the spectra of skeletal and cardiac muscle. The phosphocreatine-to-adenosine triphosphate ratio was normal for both skeletal and cardiac muscle in patients with systemic sclerosis. The pH values of skeletal muscle were similar in patients and control subjects (7.13 +/- 0.02 vs 7.12 +/- 0.01, respectively). In skeletal muscle, the inorganic phosphate-to-phosphocreatine ratio in patients was increased relative to that of control subjects (0.106 +/- 0.014 vs 0.086 +/- 0.006, respectively; P = .02). P-31 MR spectroscopy showed no abnormalities in the myocardium of patients with systemic sclerosis. Assessment of the inorganic phosphate-to-phosphocreatine ratio in peripheral skeletal muscle may be helpful for assessing disease activity.

Lactate imaging of the human brain at 1.5 T using a double-quantum filter.

The use of a double-quantum filtered 1H NMR spectroscopic imaging technique is described to detect the spatial distribution of lactate in the human brain. In two patients the feasibility of this technique is shown and compared with existing single-quantum spectroscopic imaging and single voxel techniques. Single-slice double-quantum filtered lactate images were obtained showing the lactate distribution over the entire slice in the brain. The lipid signal suppression was sufficient for the unambiguous detection of lactate. The signal loss of the lactate signal due to the incorporation of the double-quantum filter was 50-70% relative to the single-quantum signal.

Reduced lipid contamination in in vivo 1H MRSI using time-domain fitting and neural network classification.

It is a well-known problem that metabolite maps, reconstructed from in vivo 1H MRSI data sets, may suffer from contamination caused by the presence of strong lipid signals. In the present investigation, the lipid problem was addressed by applying specific signal processing and data-analysis techniques, combined with pattern recognition based on the concept of the artificial neural network. In order to arrive at images, cleaned from lipid artifacts, we have applied our previously introduced iterative and noniterative time-domain fitting procedures. Furthermore, reduction in computational time of the image reconstructions could be realized by using information provided by a neural network classification of the spectra, calculated from the MRSI data sets.

Cardiac metabolism in patients with dilated and hypertrophic cardiomyopathy: assessment with proton-decoupled P-31 MR spectroscopy.

Proton-decoupled phosphorus-31 heart spectroscopy was performed in healthy subjects (n = 9) and patients with dilated cardiomyopathy (DCM, n = 9) or hypertrophic cardiomyopathy (HCM, n = 8). The phosphocreatine (PCr)-to-adenosine triphosphate ratio (+/- one standard deviation) after correction for blood contribution and partial saturation was significantly lower in HCM patients relative to the control subjects (1.32 +/- 0.29 vs 1.65 +/- 0.26, P < .05) but not in DCM patients (1.52 +/- 0.58 vs 1.65 +/- 0.26). The inorganic phosphate (Pi) peak was resolved only in patients with the highest spectral quality. Myocardial pH was lower in HCM patients (n = 6) relative to control subjects (n = 4) (7.07 +/- 0.07 vs 7.15 +/- 0.03, P < .05). The Pi/PCr ratio was higher in DCM (n = 3) and HCM (n = 6) patients relative to control subjects (n = 4) (0.29 +/- 0.06 and 0.20 +/- 0.04, respectively, vs 0.14 +/- 0.06; P < .05). Elevated phosphodiester signal in DCM patients correlated with 2,3-diphosphoglycerate signal (r = .94), reflecting blood pool contamination. P-31 spectroscopy enabled detection of abnormalities in cardiac metabolism and determination of pH in patients with HCM and DCM.

Application of time-domain fitting in the quantification of in vivo 1H spectroscopic imaging data sets.

Time-domain model function fitting techniques were applied to improve the reconstruction of metabolite maps from the data sets obtained from in vivo 1H spectroscopic imaging (SI) experiments. First, residual water-related signals were removed from the SI data sets by using SVD-based linear time-domain fitting based upon the HSVD (State Space) approach. Second, peak integrals of the metabolites of interest were obtained by quantifying the proton spin-echoes of the voxels by means of non-linear time-domain fitting based upon the maximum likelihood principle. Third, in order to save computational time, interpolation of the metabolite images (from size 32 x 32 to 128 x 128) was performed in the image-domain by applying one-dimensional cubic splines. It was found that the residual water signals can be almost completely removed from the SI data sets by applying the linear HSVD fitting method. Furthermore, it was found that voxel dependency of certain NMR parameters (e.g., variations of the spin-echo offset frequencies and/or phase factors) can be accounted for automatically by applying the nonlinear time-domain fitting technique. For that purpose it appeared to be essential to employ prior knowledge of the NMR spectral parameters.

In vivo imaging of glucose consumption and lactate concentration in human gliomas.

Twenty patients with histologically confirmed gliomas were studied with positron emission tomography (PET) and proton magnetic resonance spectroscopy (1H-MRS). PET with 18F-2-fluoro-2-deoxy-D-glucose (FDG) provided tomograms of the metabolic rate of glucose. MRS images were obtained by combining volume-selective excitation with phase-encoded acquisition. With 32 x 32 gradient phase-encoding steps, an in-plane resolution of 7 x 7 mm was achieved. From this set of spectra, lactate maps were created and compared with PET maps of glucose metabolism. Maximum glucose metabolic rates within tumors (relative to metabolic rates of glucose in contralateral regions of the brain) were correlated significantly with maximum lactate concentrations (relative to N-acetyl aspartate peaks in the contralateral part of the brain). In 8 tumors, no lactate was detected, and in 7 of these the maximum glucose metabolic rate was below the median value. The tumor with the highest lactate concentration also had the highest glucose metabolic rate. The topographic relation between glucose metabolic rate and lactate concentration could be analyzed in 9 patients by three-dimensional alignment of the PET and MRS images. In that analysis, maximum lactate concentrations were often not found in the same location as maximum glucose metabolism, but lactate tended to accumulate in tumor cysts, necrotic areas, and the vicinity of the lateral ventricles. The combination of FDG PET and 1H-MRS imaging demonstrates details of the spatial relation between the two poles of nonoxidative glycolysis, glucose uptake and lactate deposition.(ABSTRACT TRUNCATED AT 250 WORDS)

1H and 31P magnetic resonance spectroscopy of the brain in degenerative cerebral disorders.

Proton and phosphorus magnetic resonance spectroscopy of the brain was performed in 35 patients with degenerative cerebral disorders: 24 patients had demyelinating (white matter) disorders and 11 patients had neuronal (gray matter) disorders. Four grades of demyelination and three grades of cerebral atrophy were distinguished by magnetic resonance imaging criteria. The spectroscopic data were compared with normal values previously obtained. With increasing degrees of demyelination, lower ratios of phosphodiesters to beta-ATP were found. This trend was statistically significant. Decreased phosphodiester-beta-ATP ratios occurred simultaneously with imaging abnormalities. The decrease in phosphodiester-beta-ATP ratio in demyelinated areas is attributed to white matter rarefaction. Increasing cerebral atrophy was accompanied by lower ratios of N-acetyl aspartate to creatine. This trend was statistically significant. The decrease in the N-acetyl aspartate-creatine ratio was demonstrated before the magnetic resonance images showed signs of cerebral atrophy in patients with neuronal disorders. As N-acetyl aspartate is located exclusively in neurons and their branches, a decrease of the N-acetyl aspartate-creatine ratio can be attributed to neuronal and axonal damage and loss.

Acquisition and quantitation in proton spectroscopy.

Localized proton NMR spectroscopy in the human brain is one of the more technically advanced applications of human in vivo NMR spectroscopy. Spin/echo techniques introduced reliable localization procedures, whereas the introduction of phase encoding techniques improved the spatial information content considerably. Using the sensitivity of the 1H NMR signal, a spatial resolution of 7 X 7 X 15 mm can be obtained. Chemical shift images can be reconstructed to represent the choline, creatine, N-acetyl aspartate and lactate distribution in the human brain. These low resolution images may be used as a new functional imaging modality to visualize and derive quantitative biochemical information from focal brain lesions under normal and pathological conditions.

What the clinician can learn from MR glutamine/glutamate assays.

At present in vivo NMR spectroscopic studies of brain glutamate and glutamine concentrations relative to encephalopathy have mainly been performed in hepatic encephalopathy (HE). In vivo proton NMR studies were performed in rats with hyperammonemia and acute HE due to acute liver ischemia as well as in rats with hyperammonemia due to either repeated urease i.p. injection or i.p. administration of methionine sulfoximine, a well known inhibitor of glutamine synthetase. In man, in vivo proton NMR is described in patients with chronic liver disease: cirrhosis of different etiology and associated with different degrees of HE. In the experimental models proton NMR spectroscopy of the cerebral cortex revealed an increase in glutamine concentration, a decrease in glutamate concentration and a decrease in phosphocholine compounds. In humans no clear distinction between cerebral cortex glutamate and glutamine concentration could be made by in vivo 1H NMR spectroscopy. However, the combined glutamate/glutamine peak increased in a way compatible with an increased cerebral cortex glutamine concentration during chronic HE. In the cirrhotic patients too a decrease in cerebral cortex phosphocholine compounds was observed, the explanation of which is unclear. Both the experimental work and the clinical observations support the hypothesis that impairment of the glutamate/glutamine cycle between astrocytes and neurons plays a role in the pathogenesis of hepatic encephalopathy.

In vivo monitoring of fructose metabolism in the human liver by means of 31P magnetic resonance spectroscopy.

It has been shown that fructose metabolism in the human liver can be monitored quantitatively by means of 1H image-guided 31P MRS, implemented on a clinical MR imaging system equipped with surface coils and with appropriate data processing software. Temporal resolution of the 31P MRS measurements is of the order of 2 min.

Metabolic imaging of patients with intracranial tumors: H-1 MR spectroscopic imaging and PET.

Hydrogen-1 magnetic resonance (MR) spectroscopic images of patients with intracranial tumors were obtained. Metabolite maps of N-acetyl aspartate, choline, lactate, and creatine concentrations were reconstructed with a nominal spatial resolution of 7 mm and a section thickness of 25 mm. The metabolite maps showed variations in metabolite concentrations across the tumor. In one patient, it was observed that choline concentration was increased in one part of the tumor but decreased in another part. In another patient, the concentration of N-acetyl aspartate was extremely low in one part of the tumor but only slightly increased in another part of the tumor. Lactate was observed in all patients. In one patient, a combined measurement made with positron emission tomography (PET) and MR spectroscopic imaging was performed. This demonstrated that increased lactate concentration measured with H-1 MR spectroscopic imaging corresponded topographically with increased glucose uptake measured with fluorine-18 fluoro-2-deoxyglucose PET. Combined MR spectroscopic and PET measurements provide an opportunity to investigate, in greater detail than before, glucose uptake and catabolism by intracranial tumors.

Detection of metabolic heterogeneity of human intracranial tumors in vivo by 1H NMR spectroscopic imaging.

Patients with intracranial tumors (gliomas) were examined by means of localized water-suppressed 1H NMR single volume spectroscopy and spectroscopic imaging. The 1H NMR spectra of the tumors exhibit signal intensities of the N-acetyl aspartate, choline compounds, and creatine plus phosphocreatine resonance lines that are different from the corresponding intensities observed on normal brain tissue. Also, for 6 out of the 10 patients examined so far, lactate resonance lines were detected in the tumor spectra. For one patient, abnormal 1H NMR spectra were obtained of a hemisphere which appeared normal with 1H NMR imaging. Metabolic heterogeneity of the tumorous regions could be demonstrated with 1H NMR spectroscopic imaging, using a spatial resolution in the order of 1 cm. These results suggest a spectrum of metabolic observations that may ultimately provide an important means for characterizing brain tumors.

Broadband proton decoupled natural abundance 13C NMR spectroscopy of humans at 1.5 T.

The feasibility of broadband proton decoupled in vivo 13C NMR spectroscopy of humans at 1.5 T was explored. A dual surface coil set-up was used, comprising a circular 13C coil and a butterfly 1H decoupling coil placed at one third of its width away from the body. A calibration procedure was introduced to evaluate the specific absorption rate (SAR) in any gram of tissue for the inhomogeneous decoupling field generated by a surface coil. For the WALTZ-4 sequence it was demonstrated that broadband decoupled spectra of both subcutaneous adipose and underlying muscle or liver tissue could be obtained at 1.5 T without exceeding recommended maximum SAR values. Broadband decoupling caused an additional resolution enhancement ascribed to the removal of (1H-13C) long range couplings. Broadband proton decoupled spectra of subcutaneous adipose tissue were obtained in less than 10 min showing highly resolved and intense signals of fully relaxed carbon spin systems of triacylglycerols. Broadband proton decoupled 13C NMR spectra of calf muscle showed several resonances for metabolites resolved from triacylglycerol signals (e.g. C1-C5 of glycogen, C4 of histidine, aromatic and carbonyl carbons of aminoacids and N linked carbons of ethanolamine, choline and creatine). With an acquisition time of 20-30 min, the C1 glycogen signal was observed with a root mean square signal-to-noise ratio of about 15. Not only the glycogen C1 signal but also its C2-C6 signals could be monitored in dynamic studies. Finally broadband proton decoupled 13C spectra were obtained with signals from liver tissue (notably the carbons of glycogen).(ABSTRACT TRUNCATED AT 250 WORDS)

1H image-guided localized 31P MR spectroscopy of human brain: quantitative analysis of 31P MR spectra measured on volunteers and on intracranial tumor patients.

1H image-guided 31P MR spectra of normal human brain and of intracranial tumors have been analyzed quantitatively. Tumor types examined include prolactinoma, lymphoma, and various grade gliomas. The experimental signals were processed by means of a time-domain least-square fitting procedure, which yields the spectral parameters, as well as a prediction of the standard deviations. Significant spectral variations are observed within both populations of normal brain and of intracranial tumor 31P MR spectra. The metabolic ratios derived from the glioma 31P MR spectra and from corresponding uninfiltrated brain tissue do not differ significantly. Significant differences are, however, observed between the metabolic ratios of prolactinoma and uninfiltrated tissue 31P MR spectra. Alkaline pH values are found for the prolactinoma and the high-grade gliomas. Furthermore, spectral differences are observed between the patient's uninfiltrated tissue 31P MR spectra and those of an unmatched population of volunteers. This underscores the necessity for control measurements on the uninfiltrated tissue of the patient and for controls from a matched population of healthy individuals.

Experimental approaches to image localized human 31P NMR spectroscopy.

Experimental procedures for obtaining localized 31P NMR spectra of humans by means of the ISIS sequence are discussed in detail. The technique is optimized for use with volume coils and with surface coils in order to measure localized 31P NMR spectra of different tissues and organs. Selective frequency-modulated (FM) inversion and excitation pulses are applied for optimal inversion or excitation despite B1 inhomogeneity. Pulse imperfection may lead to spurious signal contributions from outside the selected volume; this contamination is reduced by using long pulse intervals, by properly ordering the ISIS acquisitions, and by using FM excitation pulses. Simultaneous measurement of multiple volumes was implemented by including an additional selective inversion pulse, and an extension of the ISIS addition/subtraction scheme. Localized T1 measurements with surface coils are implemented by using a B1-insensitive inversion pulse in the inversion recovery sequence. The quantitative reproducibility of localized 31P NMR spectra was verified. Absolute metabolite concentration can be determined after a suitable calibration of the 31P NMR spectrum. Localized shimming is required to obtain localized 31P NMR spectra of excellent spectral resolution. This is done by monitoring the 1H NMR signal from water by a single-shot localization technique. The techniques discussed can be applied to obtain spectra of brain, liver, heart, and other organs. 31P NMR spectra of intracranial tumors demonstrate its applicability in the examination of patients.

1H and 31P NMR measurement of cerebral lactate, high-energy phosphate levels, and pH in humans during voluntary hyperventilation: associated EEG, capnographic, and Doppler findings.

In order to explore the sensitivity of spatially resolved 1H and 31P NMR spectroscopy on a whole-body NMR instrument, cerebral metabolic changes in human volunteers were measured during hyperventilation provocation. During hyperventilation the flow velocity in the middle cerebral artery decreased significantly and the EEG showed a marked increase in slow activity. 1H NMR spectra revealed an increase in cerebral lactate concentration. 31P NMR spectra showed no changes in ATP or PCr peak heights, but a shift toward tissue alkalosis was derived from changes in Pi chemical shift. During subsequent recovery, lactate concentration decreased and a slight intracellular acidosis was detected. In three experiments broadening of the lactate resonance peak resulted in separation into two components at 1.32 and 1.48 ppm, in which the latter signal possibly arose from alanine.

Broadband proton decoupling in human 31P NMR spectroscopy.

The limited chemical shift dispersion of in vivo 31P NMR spectra obtained at the relatively low field strengths used for human applications is the cause of poor spectral resolution. This makes it difficult to obtain accurate quantitative information from overlapping resonances, and interesting resonances may be obscured. At 1.5 T unresolved 1H-31P couplings contribute significantly to the linewidth of in vivo 31P NMR resonances. Therefore, proton decoupling can improve spectral resolution substantially, resulting in better resolved resonances and more reliable quantitative information. In this work it is shown that well resolved resonances of glycerophosphocholine, glycerophosphoethanolamine and phosphoethanolamine are obtained in 1H decoupled 31P NMR spectra of human muscle, brain, and liver. In spectra of the human heart it has been possible to resolve the myocardial Pi signal from the signals of 2,3-diphosphoglycerate from blood. With surface coils it is difficult to achieve broadband decoupling over the entire sensitive region of the coil by using conventional decoupling sequences. This problem has been overcome by applying a train of frequency modulated inversion pulses to achieve proper decoupling despite B2 inhomogeneity. Broadband 1H decoupling of 31P NMR spectra was possible without exceeding specific absorption rate guidelines.