Early detection of cerebral infarction by31P spectroscopic imaging

Summary Recent advances in magnetic resonance spectroscopy permit noninvasive study of brain metabolism in vivo,³¹P spectroscopic imaging being the method for evaluation of localized phosphorous metabolism. Experimentally, an ischemic-hypoxic brain insult is characterized by depletion of high energy metabolites. These changes are seen immediately after an ischemic insult. We had the opportunity of carrying out³¹P spectroscopic imaging of hyperacute cerebral infarction, while MRI and CT were negative. Cerebral infarction of the middle cerebral artery territory was suggested by³¹P spectroscopic imaging, which was closely consistent with a later-developing region of low density on CT. In cerebral infarction, early detection of the lesion is a useful pointer to the patient's prognosis, making³¹P spectroscopic imaging a potential tool.     

In vivo 31P magnetic resonance spectroscopy using a needle microcoil

Batch fabrication methods have been used to produce low‐cost microcoils for magnetic resonance spectroscopy (MRS) that could be discarded after applications such as insertion into tissue during interventional surgery. Needle‐shaped microcoils were constructed using electroplated conductors buried in shafts formed with different combinations of silicon and plastic and used to acquire in vivo ³¹P spectra of rat thigh muscle at 81 MHz. The designs in this study achieved a maximum signal‐to‐noise ratio (SNR) for phosphocreatine (PCr) of 10.4 in a 10‐min acquisition, with the three adenosine triphosphate (ATP) multiplets also clearly visible. An average 20% reduction in PCr occurred over a 60‐min period, and intracellular pH was estimated to be 6.6, which are both evidence of ischemia. A needle microcoil design could have applications in real‐time MRS of tumors or in evaluating pathology in general during surgical investigations. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

Evaluation of muscle diseases using artificial neural network analysis of 31P MR spectroscopy data

Dermatomyositis is an autoimmune disease characterized by an erythematous rash and severe muscle weakness. ³¹P Magnetic resonance spectroscopy (MRS) provides quantitative data for longitudinal monitoring of disease status and responses to immunosuppressive therapy. A disease variant, amyopathic dermatomyositis, presents with a typical rash but no clinical muscle weakness. However, metabolic abnormalities in the oxidative capacity of muscles of amyopathic patients during exercise were detected with ³¹P MRS. Because MRS provided the best quantitative data for evaluating dermatomyositis, the ³¹P metabolic parameters derived from the MR spectra were further processed using an artificial neural network (XERION). The neural network analyses provided additional clinical information from the weighted correlations of multiple ³¹P parameters, namely, inorganic phosphate, phos-phocreatine, ATP, phosphodiesters, and selected ratios. This investigation analyzes the relative importance of the various metabolic parameters for accurate patient characterization and provides insights into the pathogenesis of the disease.     

Comparisons of ATP turnover in human muscle during ischemic and aerobic exercise using 31P magnetic resonance spectroscopy

To investigate human muscle bioenergetics quantitatively in vivo, we used ³¹P magnetic resonance spectroscopy to study the flexor digitorum superficialis of four adult males during dynamic ischemic and aerobic exercise at 0.50–1.00 W and during recovery from aerobic exercise. During exercise, changes in pH and [PCr] were larger at higher power, but in aerobic exercise neither end-exercise [ADP] nor the initial postexercise PCr resynthesis rate altered with power. In ischemic exercise we estimated total ATP synthesis from the rates of PCr depletion and glycogenolysis (inferred using an analysis of proton buffering); this was linear with power output. In aerobic exercise, again we estimated ATP synthesis rates due to phosphocreatine hydrolysis and glycogenolysis (incorporating a correction for proton efflux) and also estimated oxidative ATP synthesis by difference, using the total ATP turnover rate established during ischemic exercise. We conclude that in early exercise oxidative ATP synthesis was small, increasing by the end of exercise to a value close (as predicted) to the initial postexercise rate of PCr resynthesis. Furthermore, a plausible estimate of proton efflux during aerobic exercise can be inferred from the pH-dependence of proton efflux in recovery.     

Evaluation of radiation injury by 1H and 31P NMR of human urine

¹H and ³¹P NMR techniques were applied to study the changes in metabolite profiles in human urine resulting from radiation exposure following the Chemobyl reactor accident. In cases of acute leukemia and different accumulated doses of external radiation (from 0.20 to 4.00 Sv), the proton spectra were classified on the basis of the peaks due to N-trimethyl groups, creatinine, citrate, glycine, and hippurate. Unidentified resonances were observed between 15.9 and 21.4 ppm in six phosphorus spectra of patients with preleukemia and acute leukemia. Characteristic spectral changes were similar for external radiation and Incorporation-induced internal irradiation. The spectral patterns described may serve as a criterion of radiation injury.     

Localised in vivo 1H spectroscopy of human bone and soft tissue tumours

Localised ¹H in vivo magnetic resonance spectroscopy was applied to fibrous and bone tumours before and during cytostatic treatment and radiotheraphy. The results of 24 studies in 18 patients with malignant tumours of the leg or pelvis are presented including cases of sarcoma, malignant fibrous histiocytoma, multiple myeloma, malignant lymphoma and metastasis. A double spin echo localisation method with water suppression was implemented on a 1.5 Tesla whole body unit. Voxel size was (13 mm)³ or (20 mm)³. The most common resonances besides lipids (16/18) were those of choline (10/18) and creatine (5/18). Creatine was always decreased in comparison to choline and often absent from tumour spectra. Additional resonances with phase distorsions from J-coupling (chemical shift region 1.8–2.5 and 2.2–4.0 ppm) were recorded. In the presence of lipids, lactate remained undetectable because special editing techniques were not available. Significant spectral differences between different tumour types were not evident. In about 30% of the investigations the spectra contained only water and lipid signals. Follow-up studies in three patients during radio- and chemotheraphy showed a decrease in metabolites (choline, creatine, unassigned signals between 1.0 and 2.5 ppm) after weeks and months. The decrease in choline was most pronounced paralleled by an increase in lipid/choline ratios. Correspondence to: H. BongersPresented at the European Congress of Radiology 1991 in Vienna     

Localized in vivo 1H spectroscopy and chemical shift imaging of the bone marrow in leukemic patients

Six healthy volunteers, ten patients with acute leukemia, one patient with hypersplenia and two with bone marrow carcinoris were studied. Nine patients with leukemia were restudied during chemotheraphy. A double spin echo localization method, implemented on a 1.5 T whole body unit was used for ¹H magnetic resonance spectroscopy (MRS). A cubic (13 mm)³ voxel was chosen in a midlumbar vertebra. For chemical shift imaging (CSI) the SENEX sequence was used. We recorded fat and water images in a representative midsagittal plane. Patients with acute leukemia and hypercellular bone marrow a severe reduction or loss bone marrow fat signal and an increased water signal. Water T1 increaed during therapy in three patients. The bone marrow fat reappeared in the spectra and chemical shift images within 2 or 3 weeks in responders and remained unchanged or reappeared later in non-responders. A normal fat signal could be detected in leukemic patients without hypercellular bone marrow. Specificity was missing for ¹H MRS and CSI; marrow carcinosis and benign stimulation (hypersplenia) could not be seperated from leukemia. In clinical routine, CSI may have advantages over ¹H MRS, because a large anatomic field can be examined. Inhomogenous fat signal distrbutions can be detected and were seen in sveral cases during therapy. ¹H MRS and CSI allow non-invasive therapy monitoring of leukemic patients adn might be of prognostic value. Correspondence to: H. Bongers     

Quantification of the 31P metabolite concentration in human skeletal muscle from RARE image intensity.

A method is described for quantifying the cellular phosphorus-31 (31P) concentration in human skeletal muscle based on RARE (rapid acquisition with relaxation enhancement) image intensities. The 31P concentrations were calculated using relaxation rates, RF coil spatial characteristics, and RARE signal intensities from foot muscle and an external 31P standard. 31P RARE and 1H T2-weighted images of the foot muscles in 11 normal subjects were acquired at 3.0 T using a double-tuned (31P/1H) birdcage coil. 31P PRESS (point-resolved spectroscopy) spectra were acquired to verify the measurable 31P concentrations in a multiecho acquisition. The mean measured concentration was 26.4 +/- 3.1 mM (mean +/- SD) from RARE signal intensities averaged over the entire imaged foot anatomy and 27.6 +/- 4.1 mM for a 3 x 3 pixel region-of-interest measurement. The 31P RARE image acquisition time was 4 min with a 0.55 cm3 voxel size. These results demonstrate that the 31P concentration can be accurately measured noninvasively in human muscle from RARE images acquired in short scan times with relatively high spatial resolution.     

In vivo 31P MR spectroscopic imaging of the human prostate at 7 T: Safety and feasibility

³¹P MR spectroscopic imaging of the human prostate provides information about phosphorylated metabolites that could be used for prostate cancer characterization. The sensitivity of a magnetic field strength of 7 T might enable 3D ³¹P MR spectroscopic imaging with relevant spatial resolution in a clinically acceptable measurement time. To this end, a ³¹P endorectal coil was developed and combined with an eight‐channel ¹H body‐array coil to relate metabolic information to anatomical location. An extensive safety validation was performed to evaluate the specific absorption rate, the radiofrequency field distribution, and the temperature distribution of both coils. This validation consisted of detailed Finite Integration Technique simulations, confirmed by MR thermometry and B measurements in a phantom and in vivo temperature measurements. The safety studies demonstrated that the presence of the ³¹P endorectal coil had no influence on the specific absorption rate levels and temperature distribution of the external eight‐channel ¹H array coil. To stay within a 10 g averaged local specific absorption rate of 10 W/kg, a maximum time‐averaged input power of 33 W for the ¹H array coil was allowed. For transmitting with the ³¹P endorectal coil, our safety limit of less than 1°C temperature increase in vivo during a 15‐min MR spectroscopic imaging experiment was reached at a time‐averaged input power of 1.9 W. With this power setting, a second in vivo measurement was performed on a healthy volunteer. Using adiabatic excitation, 3D ³¹P MR spectroscopic imaging produced spectra from the entire prostate in 18 min with a spatial resolution of 4 cm³. The spectral resolution enabled the separate detection of phosphocholine, phosphoethanolamine, inorganic phosphate, and other metabolites that could play an important role in the characterization of prostate cancer. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.     

31P-MR spectroscopic imaging in hypertensive heart disease

Hypertensive heart disease (HHD) causes structural changes (e.g., fibrosis) that result in diastolic and systolic myocardial dysfunction. Alterations of ³¹P metabolism and cardiac energy impairments were assessed in patients with HHD by MR spectroscopy (MRS) and correlated with left ventricular systolic function. Thirty-six patients with HHD and 20 healthy controls (mean age 35.2±10.7 years) were examined with ³¹P-MRS at 1.5 T by using an ECG-gated CSI sequence. Twenty-five patients (mean age 64.3±9.3 years) had diastolic dysfunction, but preserved systolic function (HHD-D), whereas 11 patients (62.3±11.4 years) suffered from additional impaired systolic function (HHD-S). In both patient groups, the PCr/γ-ATP ratio was lower than in the controls (controls: 2.07±0.17; P<0.001), and in HHD-S was lower than in HHD-D (1.43±0.21 vs. 1.65±0.25; P=0.012). PCr/γ-ATP ratios were linearly correlated with LVEF (Pearson's r: 0.39; P=0.025). In the HHD-S group, the PDE/γ-ATP ratio was significantly lower (0.56±0.36) than in the controls (1.14±0.42; P=0.001). In contrast to the group of HHD-D patients, whose slightly decreased PCr/γ-ATP ratios compared to controls may be explained by age differences, the more distinct changes observed in HHD-S patients indicate an altered energy metabolism. The observed metabolic changes were related to functional impairments, as indicated by a reduced LVEF. Reduced PDE/ATP ratios indicate changes in the phospholipid metabolism.     

Comparison of pig cornea preservation solutions using quantitative 31P NMR spectroscopy

We compared the abilities of three solutions (bicarbonate-free glucose-phosphate Ringer's solution (EP II), lactated Ringer's solution, and physiologic saline solution) to preserve pig cornea by measuring phosphate metabolites with ³¹P NMR spectroscopy. EP II preserves corneal viability better than others, and preserving extracted cornea also is better than preserving the whole eye.     

Quantitative (31)P spectroscopic imaging of human brain at 4 Tesla: assessment of gray and white matter differences of phosphocreatine and ATP.

This report describes the implementation and application of a multicompartment analysis of (31)P spectroscopic imaging data to determine the tissue-specific heterogeneities in metabolite content in the human brain and surrounding tissue. Using this information and a multicompartment regression analysis the phosphocreatine and ATP content of "pure" cerebral gray and white matter, the cerebellum, and skeletal muscle was determined in a group of 10 healthy volunteers. The data were converted to mM units using previously reported values for the T(1)s of phosphocreatine and ATP at 4 T, the water content of human brain, and an external reference for absolute quantification. The phosphocreatine concentration in cerebral gray and white matter, the cerebellum, and skeletal muscle was 3.53 +/- 0.33, 3.33 +/- 0.37, 3.75 +/- 0.66, and 25.8 +/- 2.3 mM, respectively. The ATP concentration in cerebral gray and white matter, the cerebellum, and skeletal muscle was 2.19 +/- 0.33, 3.41 +/- 0.33, 1.75 +/- 0.58, and 8.5 +/- 1.9 mM, respectively. Magn Reson Med 45:46-52, 2001.     

Quantitative lactate-specific MR imaging and 1H spectroscopy of skeletal muscle at macroscopic and microscopic resolutions using a zero-quantum/double-quantum coherence filter and SLIM/GSLIM localization

Quantitative lactate imaging and spectroscopy were performed on phantoms and on electrically stimulated, excised frog skeletal muscle at macroscopic and microscopic resolutions. Lactate selectivity was achieved by use of a zero-quantum/double-quantum coherence (ZQC/DQC) lactate filter, which suppressed all signals besides lactate, including water and lipid, to below noise level. Three-dimensional lactate data sets were acquired in 1–3 h; one of these spatial dimensions was frequency-encoded and the other two were phase-encoded. High-resolution images were reconstructed using the spectral localization by imaging (SLIM) and generalized SLIM (GSLIM) techniques. Lactate quantitation was achieved by employing an external lactate concentration standard and was verified by comparison to quantitative STEAM-localized and nonlocalized spectra that used total creatine as an internal concentration reference. Additionally, quantitatively accurate behavior of the SLIM and GSLIM techniques as applied to data sets of low signal-to-noise ratio and to macroscopically heterogeneous objects was verified using simulations and real muscle lactate data sets with known heterogeneity.     

Optimized detection of changes in glucose-6-phosphate levels in human skeletal muscle by 31P MR spectroscopy.

As glucose-6-phosphate (G6P) plays a central role in muscle energy metabolism, the possibility to observe changes in the tissue level of this compound in vivo is very relevant. G6P can be detected noninvasively by (31)P MR spectroscopy, but its visibility in vivo is severely hampered due to low tissue levels and spectral overlap with other, stronger phosphomonoester signals. To optimize the observation of changes in G6P levels in human calf muscle by (31)P MR spectroscopy at 1.5 T, we implemented an approach involving a new RF probe and a postacquisition correction method. An anatomically shaped circularly polarized (31)P coil was designed for high intrinsic sensitivity. Together with an additional (1)H coil and (1)H blocking circuits this allowed the application of NOE and (1)H decoupling to further enhance sensitivity. A hyperglycemic hyperinsulinemic clamp was used to increase G6P levels. The spectra were corrected for frequency and phase drift due to scanner instability and leg movements using an automated phase and frequency correction method. Difference (31)P spectroscopy was applied to detect changes of the G6P signal. The result, in five healthy subjects, demonstrated that the combination of sensitivity optimization with automated drift correction enabled a robust detection of G6P changes in time series experiments down to a resolution of 10 min.     

1H NMR spectroscopic imaging of the mouse brain at 9.4 T

Purpose

To assess the feasibility of ¹H spectroscopic imaging (SI) in the mouse brain at 9.4 T, and investigate regional variations in brain metabolites.

Materials and Methods

A total of 21 SI studies were performed in CD‐1 mice to evaluate the basal ganglia (N = 5), hippocampus and thalamus (N = 11), and cerebellum (N = 5). We adjusted the B₀ homogeneity for each slice using a fully automated shim calculation method based on the B₀ map, which we measured using a multislice gradient‐echo sequence with multiple phase evolution delays. The SI employed a modified localization by adiabatic selective refocusing (LASER) sequence with TE/TR of 50/2000 msec, 24 × 24 encodes over a field of view (FOV) of 24 mm × 24 mm, 1 μL voxel resolution, and two averages, for a total acquisition time of 38 minutes.

Results

Sufficient shimming was achieved and high‐quality spectra were consistently obtained in each slice. N‐acetyl aspartate (NAA)/creatine (Cr) ratios in the basal ganglia and thalamus (0.86 ± 0.07, and 0.87 ± 0.07, respectively) were significantly higher than those in the hippocampus and cerebellum (0.76 ± 0.03 and 0.67 ± 0.07), which were also significantly different from each other.

Conclusion

¹H SI of the mouse brain is highly reproducible and allows differences in regional metabolite ratios to be easily visualized. J. Magn. Reson. Imaging 2006. © 2006 Wiley‐Liss, Inc.

     

(1)H MR spectroscopy of human brain tumours: a practical approach

Magnetic resonance spectroscopy (MRS) is proposed in addition to magnetic resonance imaging (MRI) to help in the characterization of brain tumours by detecting metabolic alterations that may be indicative of the tumour class. MRS can be routinely performed on clinical magnets, within a reasonable acquisition time and if performed under adequate conditions, MRS is reproducible and thus can be used for longitudinal follow-up of treatment. MRS can also be performed in clinical practice to guide the neurosurgeon into the most aggressive part of the lesions or to avoid unnecessary surgery, which may furthermore decrease the risk of surgical morbidity.     

Differentiation of intracranial tuberculomas and high grade gliomas using proton MR spectroscopy and diffusion MR imaging

Objective

The purpose of this study was to determine whether proton MR spectroscopy (¹H MRS) and diffusion-weighted (DW) imaging can be used to differentiate intracranial tuberculomas from high grade gliomas (HGGs).

Materials and methods

A total of 41 patients (19 with intracranial tuberculomas and 22 with HGGs) were examined in our study. ¹H MRS and DW imaging were performed at a 1.5T MR scanner before operation or treatment. Concentrations of N-acetylaspartate (NAA), creatine (Cr), choline (Cho), and lipid and lactate (LL) in the contrast-enhancing rim of each lesion were expressed as metabolite ratios and were normalized to the contralateral hemisphere. The apparent diffusion coefficient (ADC) was also calculated. The metabolite ratios and ADC values in the enhancing rim of intracranial tuberculomas and HGGs were compared using the Wilcoxon rank sum test. Diagnostic accuracy was compared using receiver operating characteristic (ROC) analysis.

Results

Significant differences were found in the maximum Cho/Cr (P = 0.015), Cho/NAA (P = 0.001) and Cho/Cho-n ratios (P = 0.002), and minimum ADC value (P < 0.001) between the intracranial tuberculomas and HGGs. Diagnostic accuracy was higher by minimum ADC value than maximum Cho/Cr, Cho/NAA and Cho/Cho-n ratios (93.8% versus 75.7%, 80.8% and 78.1%).

Conclusion

These results suggest a promising role for ¹H MRS and DW imaging in the differentiation between the intracranial tuberculomas and HGGs.     

Metabolic assessment of a neuron-enriched fraction of rat cerebrum using high-resolution 1H and 13C NMR spectroscopy

This study explored the utility of ¹H and ¹³C magnetic resonance spectroscopy to study a neuron-enriched preparation made from rat cerebrum. The preparation contained high concentrations of N-acetylaspartate and γ-aminobutyric acid and low concentrations of glutamine, indicating that it was in fact rich in neuronal cytosol. This was confirmed by immunohistochemical studies with antibodies to neuronal and glial markers. A method of metabolite quantification based on the creatine signal yielded metabolite concentrations similar to those of rat cerebrum, whereas concentrations based on the metabolite/protein ratio were five times lower, suggesting that much protein in the preparation was not associated with functioning cytoplasm. The metabolic competence of the preparation was assessed by quantitative measurements of its ability to convert 1?¹³C-glucose into lactate, glutamate, aspartate, and other metabolites under well oxygenated conditions for 30 min. Calculated from the creatine standard, the mean glycolytic rate was the same as in a synaptosomal preparation studied under similar conditions and the same as rat cerebrum in vivo. Tricarboxylic acid cycle flux occurred at half the rate observed in the synaptosomal preparation and 16% of the basal cerebral metabolic rate in vivo.     

Comparison of the clinical state and its changes in patients with Duchenne and Becker muscular dystrophy with results of in vivo 31P magnetic resonance spectroscopy

A total of 14 boys with the Duchenne and Becker forms of muscular dystrophy (DMD, BMD) were examined using ³¹P magnetic resonance (MR) spectroscopy; 12 boys were examined repeatedly. The results were correlated with clinical findings (including those of genetic tests) and with data obtained from examinations of an age-matched control group. Evaluation of results using principal component analysis revealed maximum variability in the following ratios: phosphocreatine/inorganic phosphate (PCr/Pi), phosphocreatine/phosphodiesters (PCr/PDe) and phosphocreatine/phosphomonoesters (PCr/PMe). A decrease in PCr/Pi correlates with weakness of the hip girdle and of the lower part of the shoulder girdle in DMD/BMD patients. The values of all ratios in the group of patients with the DMD phenotype differ significantly from results obtained in the group with the BMD phenotype. Continoous follow-up of patients using ³¹P MR spectroscopy revealed a marked decrease in PCr/Pi in DMD/BMD patients at an age that could be expected in subjects with a typical clinical course of DMD/BMD. An attempt to manage a concomitant disease with prednisone and carnitene was followed by an increase in PCr/Pi in 3 cases. A rise in the PCr/Pi ratio signalled clinical improvement in the patients. A decrease in PCr/Pi was found after controlled physical training, a finding consistent with data obtained from clinical observations describing an adverse effect of physical stress on the dystrophic process. Correspondence to: M. Hájek