[Quantitation of glutamate in the brain by using MR proton spectroscopy at 1.5 T and 3 T]. / Quantitative Bestimmung von Glutamat im Hirn mithilfe der MR-Protonenspektroskopie bei 1,5 T und 3 T.

PURPOSE: The influence of different magnetic field strengths on the quantification of glutamate was experimentally investigated by means of IN VITRO and IN VIVO (1)H-MR spectroscopic measurements at 1.5 T and 3 T. MATERIALS AND METHODS: In vitro (1)H-MR measurements of aqueous solutions of NAA, glutamate, glutamine and GABA were performed on two clinical MR scanners at 1.5 T and 3 T using a single voxel PRESS sequence (TR/TE = 10 000 / 30 ms). IN VITRO brain measurements were also performed at both field strengths using a PRESS 2D- (1)H-CSI-sequence (TR/TE = 5000 / 30 ms) in 6 volunteers. Spectra at 1.5 T and 3 T were compared with respect to the overlap of the single compound spectra and the deviations between estimated and nominally adjusted concentrations. In vivo spectra at both field strengths were compared with respect to SNR (Glu), line width and Cramer-Rao values of the estimated glutamate intensities by using the LCModel. For the thalamus, insular and parietal cortex mean Glu/tCr ratios were estimated and compared between 1.5 T and 3 T as well as with corresponding values in the literature. RESULTS: In general, an improved separation of signal maxima was observed in the IN VITRO spectra at 3 T. Except for GABA, all IN VITRO concentrations estimated at 3 T revealed lower deviations from their adjusted nominal concentration compared to 1.5 T: NAA (1.5 T: -5.5 %, 3 T: 0.7 %), glutamate (1.5 T: -18.1 %, 3 T: 12.3 %), glutamine (1.5 T: 44.8 %, 3 T: 9.2 %), GABA (1.5 T: - 24.8 %, 3 T: 33.8 %). The SNR of IN VIVO spectra at 3 T was nearly doubled compared to 1.5 T. The mean number of voxels with %SD (Glu)< 20 was distinctly lower at 1.5 T (53 %) than at 3 T (80 %). Estimated Glu/tCr ratios for thalamus, insular and parietal cortex lay in the upper range of the literature values. CONCLUSION: The results indicate that the advantageous distribution of signal maxima at 3 T allows an improved separation of the individual spectra. Both the higher initial magnetization at 3 T and the improved sensitivity of the phased array matrix coil used in the 3 T study result in an increased SNR, which leads to better reliability of the individual detection as well as a more accurate quantification of glutamate.

31P magnetic resonance spectroscopy in the dorsolateral prefrontal cortex of schizophrenics with a volume selective technique--preliminary findings.

Pettegrew et al (Arch Gen Psychiatry 48:563-568, 1991) were the first to determine abnormalities concerning phospholipids and high energy metabolites in the dorsolateral prefrontal cortex of drug-naive schizophrenics with 31P magnetic resonance spectroscopy (MRS). Other investigations could not replicate these findings. We included in our study 13 schizophrenic inpatients and 14 age-matched controls. Whereas Pettegrew et al found increased levels of phosphodiesters and decreased levels of phosphomonoesters we measured decreased levels of phosphodiesters in the schizophrenics as compared to controls. One possible explanation for the contradictory findings of the both trials might be the different localization techniques used.

Reduced phosphodiesters and high-energy phosphates in the frontal lobe of schizophrenic patients: a (31)P chemical shift spectroscopic-imaging study.

BACKGROUND: (31)Phosphorous magnetic resonance spectroscopy has been widely used to evaluate schizophrenic patients in comparison to control subjects, because it allows the investigation of both phospholipid and energy metabolism in vivo; however, the results achieved so far are inconsistent. Chemical shift imaging (CSI) has the advantage that instead of only one or a few preselected voxels the tissue of a whole brain slice can be examined. The aim of the present investigation was to determine whether the results of previous studies of our group, showing that phosphodiesters (PDE) are decreased in the frontal lobe of schizophrenic patients as compared to control subjects, might be confirmed in an independent unmedicated patient sample using the CSI technique. METHODS: A carefully selected new cohort including 11 neuroleptic-free schizophrenic patients and 11 age- and gender-matched healthy control subjects was recruited. CSI was applied and an innovative analysis method for CSI data based on a general linear model was used. RESULTS: PDE, phosphocreatine, and adenosine triphosphate (ATP) were found to be significantly decreased in the frontal lobe of patients with schizophrenia. CONCLUSIONS: Because PDE was decreased in schizophrenic patients, the membrane phospholipid hypothesis of schizophrenia could not be corroborated. Further results indicate decreased ATP production in the frontal lobe of patients with schizophrenia.

31Phosphorus magnetic resonance spectroscopy of the dorsolateral prefrontal region in schizophrenics--a study including 50 patients and 36 controls.

BACKGROUND: In a preliminary study we found decreased phosphodiester (PDE)% values and an increased phosphomonoester (PME)/phosphodiester ratio in the dorsolateral prefrontal region (DLPFR) of 13 chronic schizophrenics vs. 14 controls using 31phosphorus magnetic resonance spectroscopy (31P-MRS). Since these results are in contrast to the findings of other groups, we increased our study group to a total of 50 chronic schizophrenics on stable neuroleptic medication and 36 controls to minimize the possibility of a chance result due to small sample size. METHODS: An image-selected in vivo 31P-MRS method on a Philips Gyroscan ACS II scanner working at 1.5 T was used. RESULTS: We could confirm our earlier findings of decreased PDE% levels in schizophrenics. Additionally, we found phosphocreatine (PCr)% and PCr/adenosine triphosphate (ATP) to be increased in the schizophrenics. While no association between PME% and PDE% with neuroleptic medication was found, ATP% correlated positively and PCr/ATP negatively with the chlorpromazine equivalent dose. CONCLUSIONS: The decreased PDE% levels might be characteristic only for chronic, neuroleptic-treated patients. The finding of altered high-energy phosphate levels can be interpreted as an indication of decreased energy-demanding processes in the DLPFR of the investigated patients compared to controls.

Increase of phosphodiesters during neuroleptic treatment of schizophrenics: a longitudinal 31P-magnetic resonance spectroscopic study.

BACKGROUND: Increased levels of phosphodiesters (PDE%) and reduced relative concentrations of phosphomonoesters (PME%) have been reported in unmedicated schizophrenics, whereas findings in brain of medicated patients were not consistent. METHODS: We determined in vivo the metabolism of phospholipids and high-energy phosphates in the left and right frontal lobes of 8 patients with schizophrenia using 31P-magnetic resonance spectroscopy (31P-MRS). Serial investigations were performed first after a neuroleptic-free period (mean 7.5 +/- 1.9 days) and second, after neuroleptic treatment (mean 20.6 +/- 11.1 days). RESULTS: PDE% increased significantly in the left frontal lobe (32.0 +/- 5.9% versus 36.9 +/- 5.6%, p = .009) after medication. All other parameters showed no significant differences. CONCLUSIONS: Our study suggests that neuroleptics do not decrease phospholipase A2 activity in schizophrenia. Individual neuroleptics may have different effects on phospholipase A2 activity as indicated by animal studies. An influence of neuroleptics on high-energy phosphates cannot be confirmed by our data.

Cerebral phosphate metabolism in first-degree relatives of patients with schizophrenia.

OBJECTIVE: Most phosphorus-31 magnetic resonance spectroscopy ((31)P-MRS) studies have described measures of lower membrane anabolism or greater catabolism in the frontal lobes of patients with schizophrenia. The purpose of the present study was to evaluate whether these findings can also be detected in young subjects at genetic risk for schizophrenia. METHOD: Fourteen children and siblings of patients with schizophrenia (mean age=16.7 years) and 14 comparison subjects (mean age=16.9 years) were included in a (31)P-MRS study of the frontal lobe. RESULTS: The high-risk subjects had significantly lower mean ratios of phosphomonoesters to phosphodiesters (0.25 versus 0.31) and higher mean phosphodiester values (37.59% versus 34.87%) than comparison subjects. CONCLUSIONS: These findings suggest greater phospholipid breakdown even in young first-degree relatives of patients with schizophrenia. This suggestion is discussed with respect to the membrane phospholipid hypothesis of schizophrenia.

High-energy phosphates in the frontal lobe correlate with Wisconsin Card Sort Test performance in controls, not in schizophrenics: a 31phosphorus magnetic resonance spectroscopic and neuropsychological investigation.

In recent years, a number of 31phosphorus magnetic resonance spectroscopy (P-MRS) studies on the frontal lobe of schizophrenics have been performed, reporting alterations of phospholipids and high-energy phosphates. Deicken et al. (1994b) recently found positive correlations between left frontal phosphomonoester% (PME%) levels and the performance of a specific frontal lobe task, the Wisconsin Card Sorting Test (WCST), in schizophrenics. In the present paper, the correlations between phospholipids and high-energy phosphates in the frontal lobe of 26 schizophrenics and 23 controls measured with a volume-selective P-MRS method were investigated. Overall, we could not find any correlations between WCST results and phospholipid levels, but in controls phosphocreatine% (PCr%) and PCr/adenenosine triphosphate (ATP) ratios were negatively correlated with test performance. Since PCr behaves as a buffer of ATP, in the sense that when ATP is consumed by neuronal activity PCr is catalysed rapidly to ATP, increased PCr% values and, moreover, increased PCr/ATP ratios point to a decreased ATP consumption. Thus, the correlations found between PCr% and PCr/ATP and test performance in controls point to an association between reduced performance in a specific frontal lobe task and decreased energy demanding processes at rest. This association was not found in schizophrenics, possibly due to the influence of neuroleptic medication or the disease process per se.

fMRI during word processing in dyslexic and normal reading children.

The present study addresses phonological processing in children with developmental dyslexia. Following the hypothesis of a core deficit of assembled phonology in dyslexia a set of hierarchically structured tasks was applied that specifically control for different kinds of phonological coding (assembled versus addressed phonological strategies). Seventeen developmental dyslexics and 17 normal reading children were scanned during four different tasks: (1) passive viewing of letter strings (control condition), (2) passive reading of non-words, (3) passive reading of legal words, and (4) a task requiring phonological transformation. Statistical analysis of the data was performed using statistical parametric mapping (SPM96). Comparison of patterns of activation in dyslexic and normal reading children revealed significant differences in Broca's area and the left inferior temporal region for both, non-word reading and the phonological transformation task. The present data provide new evidence for alteration of the phonological system in dyslexic children, and in particular, the system that mediates assembled phonological coding.

Simultaneous surface electromyography (SEMG) and 31P-MR spectroscopy measurements of the lumbar back muscle during isometric exercise.

The aim of this study was to demonstrate the feasibility of simultaneous surface electromyography (SEMG) and 31P-MR spectroscopy (31P-MRS) measurements on the back muscle of volunteers during the performance of an isometric exercise. Six volunteers (three male, three female) performed a modified Biering-Sörensen test inside a 1.5 T MR scanner while simultaneously recording SEMG signals. A surface coil was used for 31P-MRS with a CSI sequence. Spectra were collected with a voxel resolution of 40 mm x 40 mm x 100 mm and a temporal resolution of 30 s during periods of rest, sustained muscle contraction and recovery. The duration of muscle contraction was 150 s. SEMG analysis yielded a decrease of the mean SEMG frequency of approximately 20%. The SEMG amplitudes were constant or increased up to approximately 150% during exercise. 31P-MRS showed a maximum decrease of the phosphocreatine (PCr) amplitude down to approximately 32% of its initial value. Simultaneously, a doubling of the inorganic phosphate (Pi) signal was observed. The present study demonstrates that simultaneous SEMG and 31P-MRS measurements of the back muscle are feasible during isometric exercises.

Increased excitability in the primary motor cortex and supplementary motor area in patients with phantom limb pain after upper limb amputation.

Using functional magnetic resonance imaging and single slice FLASH technique, we investigated reorganization of the hand representation of the primary sensorimotor cortex (SMC) in 16 patients with upper extremity amputation. Patients were asked to perform finger tapping with the intact hand, repetitive eye closing and anteflexion of the amputation stump or intact shoulder. Six normal volunteers served as control. In the normal volunteers activations during shoulder anteflexion, finger tapping and eye closure were located within the central sulcus in a medio-lateral fashion. Patients demonstrated invasion of the face or shoulder representation into the hand representation of the amputated limb. Eight phantom limb pain patients showed significantly greater activation in SMC and supplementary motor area (SMA) in contrast to eight patients without phantom limb pain. We conclude, that different parts of the motor system are affected in patients with phantom limb pain--possibly in the sense of an up-regulation of excitability.

Abnormal motor cortex organization contralateral to early upper limb amputation in humans.

We performed both a functional magnetic resonance imaging (fMRI) study using single slice FLASH technique and an investigation with transcranial magnetic stimulation (TMS) in a 21-year-old patient. He had suffered a left upper extremity amputation at age 7. Anteflexion of the amputation stump produced an unusual, broad activation contralateral to the movement. TMS revealed an enlarged cortical motor output area of the deltoid muscle at the amputation stump. Application of paired magnetic stimulation demonstrated decreased intracortical inhibition (ICI). A T1-weighted image indicated a lack of the characteristic shape of the central sulcus contralateral to the amputation. In addition to previous functional studies, these new structural data suggest that maturation of the central sulcus develops in response to daily practice of the contralateral hand, possibly until adolescence.

Brain activation during cognitive stimulation with the Wisconsin Card Sorting Test--a functional MRI study on healthy volunteers and schizophrenics.

It has been demonstrated by single photon emission computed tomography (SPECT) and positron emission tomography (PET) that frontal brain regions are stimulated during performance of the Wisconsin Card Sorting Test (WCST). The WCST is also regarded as one of the standard tests for the assessment of frontal activity in brain imaging studies of schizophrenia. In this study cerebral activation was assessed by means of functional magnetic resonance imaging (fMRI). In healthy volunteers WCST stimulation resulted in a right lateralized frontal activation. In 13 chronic schizophrenics on stable neuroleptic medication, a lack of activation in the right prefrontal cortex and--as a trend--an increased left temporal activity during execution of the WCST was noted compared to controls. Since a one-slice technique was used, no information about the activation pattern in adjacent brain regions was obtained. However, as fMRI possesses a superior spatial resolution compared to SPECT and PET, the anatomical localization of the activation effect in the measured slice can be defined more precisely. Beside these methodological considerations, the results are discussed in relation to prior findings of a reduced ability of schizophrenics to coordinate cerebral function.

Decreased energy demanding processes in the frontal lobes of schizophrenics due to neuroleptics? A 31P-magneto-resonance spectroscopic study.

In the present investigation on 31P-magneto-resonance spectroscopic parameters in the frontal lobe, we found phosphocreatine levels and the ratio phosphocreatine/adenosine triphosphate to be increased (12.62 +/- 1.98% resp. 0.31 +/- 0.06) in 50 neuroleptic-treated schizophrenics, whereas no differences were detected in 10 neuroleptic-free patients (11.66 +/- 2.57% resp. 0.29 +/- 0.08) compared to 36 controls (11.37 +/- 1.45 resp. 0.29 +/- 0.04). This result points to a major role of neuroleptics in the metabolism of high-energy phosphates.

[31P-MR spectroscopy of the brain in patients with anorexia nervosa: characteristic differences in the spectra between patients and healthy control subjects]. / 31P-MRS des Hirns bei Anorexia nervosa: Charakteristische Unterschiede in den Spektren von Patienten und gesunden Vergleichspersonen.

PURPOSE: To investigate whether 31 P-MR spectroscopy can detect reduced concentrations of high-energy phosphates, like PCr and NTP, caused by decreased metabolic activity in the brain of patients with anorexia nervosa (AN) and, furthermore, whether any impairment of the cerebral membrane metabolism can be derived from the spectra. MATERIAL AND METHODS: 10 female patients, age range 12 - 20 years and mean BMI (body mass index) of 14.8 +/- 1.6 kg/m 2, with clinically diagnosed AN (ICD-10, F50.0) and 10 healthy control subjects, age range 12 - 21 years and mean BMI 19.0 +/- 2.1 kg/m 2, without nutritional disturbances: were investigated. 31P-MR spectroscopy was performed with a 1.5 T MRI unit using single volume selection in the frontal/prefrontal region of brain. Relative metabolic concentrations were quantified by normalizing the peak areas of the metabolites with the total area of the complete phosphorous spectrum, P tot, as well as with the peak area of beta-NTP. RESULTS: Significant differences between the two groups were observed for the metabolic ratios PDE/P tot, PDE/beta-NTP and alpha-NTP/P tot which were lower in the patient group except for alpha-NTP/P tot. These ratios also revealed a statistically significant correlation with the BMI (r PDE/Ptot = 0.747, r PDE/beta-NTP = 0.57, r alpha-NTP/Ptot = -0.56; p

Decreased frontal activation in schizophrenics during stimulation with the continuous performance test--a functional magnetic resonance imaging study.

The Continuous Performance Test (CPT) has become an essential constituent of the neuropsychological investigation of schizophrenia. Also, a vast number of brain imaging studies, mostly PET investigations, have employed the CPT as a cognitive challenge and established a relative hypofrontality in schizophrenics compared to controls. The aim of the present investigation was to clarify whether this predescribed hypofrontality could also be verified using functional magnetic resonance imaging (fMRI). 20 healthy volunteers and 14 schizophrenics on stable neuroleptic medication were included. Imaging was performed using the CPT-double-T-version and a clinical 1.5 T MRI-scanner with a single slice technique and a T(2)*-weighted gradient-echo-sequence. The schizophrenics exhibited a decreased activation in the right mesial prefrontal cortex, the right cingulate and the left thalamus compared to controls. These results obtained by fMRI are discussed in relation to published findings using PET.

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 (31)P 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 (31)P-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/gamma-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/gamma-ATP ratios were linearly correlated with LVEF (Pearson's r: 0.39; P=0.025). In the HHD-S group, the PDE/gamma-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/gamma-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.

Noninvasive measurements of cardiac high-energy phosphate metabolites in dilated cardiomyopathy by using 31P spectroscopic chemical shift imaging.

Dilated cardiomyopathy (DCM) is accompanied by an impaired cardiac energy metabolism. The aim of this study was to investigate metabolic ratios in patients with DCM compared to controls by using spectroscopic two-dimensional chemical shift imaging (2D-CSI). Twenty volunteers and 15 patients with severe symptoms (left ventricular ejection fraction, LVEF<30%) and ten patients with moderate symptoms (LVEF>30%) of DCM were investigated. Cardiac 31P MR 2D-CSI measurements (voxel size: 40x40x100 mm3) were performed with a 1.5 T whole-body scanner. Measurement time ranged from 15 min to 30 min. Peak areas and ratios of different metabolites were evaluated, including high-energy phosphates (PCr, ATP), 2,3-diphosphoglycerate (2,3-DPG) and phosphodiesters (PDE). In addition, we evaluated how PCr/ATP ratios correlate with LVEF as an established prognostic factor of heart failure. The PCr/gamma-ATP ratio was significantly decreased in patients with moderate and severe DCM and showed a linear correlation with reduced LVEFs. PDE/ATP ratios were significantly increased only in patients with severe DCM as compared to volunteers. Applying 31P MRS with commonly-available 2D-CSI sequences is a valuable technique to evaluate DCM by determining PCr/ATP ratios noninvasively. In addition to reduced PCr/ATP ratios observed in patients suffering from DCM, significantly-increased PDE/ATP ratios were found in patients with severe DCM.

Estimation of postmortem metabolic changes in porcine brain tissue using 1H-MR spectroscopy--preliminary results.

To investigate the potential for estimating the time since death by monitoring the evolution of different metabolites in brain tissue by (1)H-MRS, an animal model using pig heads was established. The maximum examination interval was 3 weeks. Within this time interval spectra revealed different compositions of metabolites, including metabolites observed in the normal brain and as products of bacterial decomposition processes (N-acetyl-aspartate 0-130 h, creatine 0-170 h, bound trimethylammonium, e. g. choline compounds, during the whole time course with fluctuating intensities, lactate 0-200 h, alanine and acetate during the whole time course, succinate and free trimethylammonium after approx. 100 h postmortem). The proposed approach may offer a new method to estimate later postmortem intervals although these observations have to be confirmed by further studies.

31P magnetic resonance spectroscopy in fibromyalgic muscle.

OBJECTIVE: To measure inorganic phosphate (Pi), phosphocreatine (PCr), ATP and phosphodiesters (PDE) in fibromyalgic muscle tissue by (31)P magnetic resonance spectroscopy. METHODS: A 1.5 Tesla scanner with a P 100 surface coil was used to examine 15 patients (mean age 49.9+/-14.3 yr) with fibromyalgia, according to the American College of Rheumatology criteria, and 17 healthy controls (mean age 30.2+/-5.8 yr). RESULTS: Compared with the controls, there were increases in the levels of PDE (+22%, P = 0.032) and Pi (+19%, P = 0.019) in the spectra of fibromyalgia patients, but there was no difference in pH. CONCLUSION: The metabolic differences we found may have been related to weakness and fatigue in the fibromyalgia patients, but they do not fully explain the fibromyalgia symptoms.

Imaging in ureteral complications of renal transplantation: value of static fluid MR urography.

Ureteral obstruction is an infrequent complication after renal transplantation that may cause rapid loss of transplant function. We tested static fluid MR urography for determining the cause of graft hydronephrosis. Magnetic resonance urography was performed in nine transplants with dilated collecting systems on ultrasound. A heavily T2-weighted 3D turbo spin-echo sequence on a 1.5-T scanner was used and maximum intensity projections were obtained. The patients also underwent excretory urography (n = 1), renal scintigraphy (n = 1), antegrade pyelography (n = 3), voiding cystourethrography (n = 4), and non-enhanced CT (n = 2). Six patients had pathologic conditions including ureteral stricture, compression by lymphoceles, implantation stenosis, vesicoureteral reflux, and late-occurring transitional cell carcinoma at the implantation site. Static MRU was able to diagnose or exclude a dilation of the graft collecting system. It visualized the course of the ureters and localized the obstruction site in four of five obstructed transplants. In one case the ureter was obscured by lymphoceles, which were demonstrated by hydrographic MRU as well. The definite cause for obstruction was provided in only 2 of 5 cases. Dilation due to vesicoureteral reflux could not be differentiated. The current multimodality approach to renal transplant imaging already provides comprehensive assessment of graft hydronephrosis. Static MRU may be useful in some cases since complications associated with intravenous iodinated contrast or antegrade pyelography can be avoided. Its main drawback, the lack of functional information, may be overcome by combining it with contrast-enhanced MRU.