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Creatine (Cr) is an amino acid, which upon phosphorylation is utilized as an energy reservoir in cells with high-energy demand. The ongoing catabolism of creatine to creatinine requires a permanent creatine replenishment into the cells. Because neurons themselves cannot synthesize creatine, they have to take it up via the creatine transporter (CrT). Thus, the concentration of intracellular Cr available for the Cr/PCr shuttle system depends on the expression level of CrT protein. The proton magnetic resonance spectroscopy (MRS) creatine peak (total creatine=tCr) constitutes of two metabolites, namely Cr and phosphocreatine (PCr). We have quantified the level of CrT protein expression with western blotting and compared it to tCr content as estimated by in vitro MRS in Sprague-Dawley rats. Under the assumption of hemispheric symmetry, we took identical samples from left and right hemisphere, which were used for in vitro MRS (tCr) and for western blotting (CrT), respectively. Altogether, it was possible to take 90 corresponding brain samples from 31 animals. A Pearson linear regression analysis for CrT and tCr revealed p<0.0001, explaining 14% of the variance. Since MR-detectable alterations of tCr in the human brain are widespread (e.g. in most major psychiatric disorders proton MRS detectable tCr alterations have been described as regionally and usually state dependent) it is stringent to elucidate their meaning. An influence of tCr on the brain's energy regulating system seems plausible.

The anterior cingulate cortex (ACC) plays a major role in modulating executive control of attention. Here, 15 medication-nai ve patients with attention deficit/hyperactivity disorder (ADHD) and 10 carefully matched healthy controls were studied with 2D (1)H-magnetic resonance spectroscopic imaging (MRSI) of the ACC [Brodmann areas 24b'-c' and 32']. Attentional skills were assessed using the identical pairs version of the continuous performance task (CPT-IP). Analysis of regional brain spectra revealed a significantly increased signal of choline-containing compounds (Ch) in the ACC of ADHD patients (p<0.05). Across and within groups, the Ch signal showed high correlations with slowed hit reaction times on the CPT-IP. No group differences in N-acetyl-aspartate (NAA) and creatine (tCr) were detectable. The combination of performance deficits and elevated Ch levels in the ACC supports the hypothesis that subtle structural abnormalities underlie the functional alterations in ACC activation previously observed in ADHD patients.

A fast, full 3D elliptical k-space encoding phosphorous-31 ((31)P) chemical shift imaging sequence, incorporating heteronuclear polarization transfer editing (RINEPT), was established. RINEPT literally requires simultaneous pulses at the frequencies of both the sensitive and the insensitive nuclei, but only a few MR imaging systems feature a second independent transmit channel. In this study, possible signal degradation of a sequential sequence design on systems featuring a single transmit channel was investigated with spin density matrix calculations and phantom measurements. In addition, metabolite signal intensities were determined in vivo as a function of echo and repetition times. The results enable optimization of the signal-to-noise ratio of one or more metabolites of interest. The results convincingly show that the optimized RINEPT sequence is useful in clinical routine (31)PMRS protocols and provides spectra of excellent quality for the study of cell membrane phospholipid turnover in the human brain even at a low field strength of 1.5T. The 3D sequence design allows covering the whole brain in a single measurement, while scan times are compliant with clinical routine protocols., ((c) 2008 Wiley-Liss, Inc.)

The theory of depression is dominated by the monoamine hypothesis but there is increasing evidence that beyond monoamines, glutamate (Glu) and gamma-aminobutyric acid (GABA) play an essential role in the pathogenesis of depression. In this study, the effect of alterations of GABA and Glu were investigated in the congenital learned helplessness paradigm. Proton magnetic resonance spectroscopy is an important monitoring tool to bridge the findings in clinical and preclinical studies. We found increased Glu/GABA ratios in the hippocampus and prefrontal cortex of placebo-treated (saline intraperitoneally) congenital learned helplessness rats versus wild-type rats, and a treatment-induced (desipramine 10 mg/kg intraperitoneally or electroconvulsive shock) decrease of this monoamine ratio in both brain regions. Our results corroborate previous findings of an amino-acid influence on the pathomechanisms of mood disorders.

Background: Cannabinoids present neurotoxic and neuroprotective properties in in vitro studies, inconsistent alterations in human neuroimaging studies, neuropsychological deficits, and an increased risk for psychotic episodes., Methods: Proton magnetic resonance spectroscopy ((1)H-MRS), neuropsychological testing, and hair analysis for cannabinoids was performed in 13 male nontreatment-seeking recreational cannabis users and 13 male control subjects., Results: A significantly diminished N-acetylaspartate/total creatine (NAA/tCr) ratio in the dorsolateral prefrontal cortex (DLPFC) was observed in cannabis users (p = .0003). The NAA/tCr in the putamen/globus pallidum region correlated significantly with cannabidiol (R(2) = .66, p = .004). Results of the Wisconsin Card Sorting test, Trail making Test, and D2 test for attention were influenced by cannabinoids., Conclusions: Chronic recreational cannabis use is associated with an indication of diminished neuronal and axonal integrity in the DLPFC in this study. As chronic cannabis use is a risk factor for psychosis, these results are interesting because diminished NAA/tCr ratios in the DLPFC and neuropsychological deficits were also reported in schizophrenia. The strong positive correlation of NAA/tCr and cannabidiol in the putamen/globus pallidum is in line with neuroprotective properties of cannabidiol, which were also observed in in vitro model studies of Parkinson's disease.

Although cognitive side effects may occur after electroconvulsive therapy (ECT), no structural brain abnormalities have been detected after ECT with conventional magnetic resonance imaging (MRI). Transient disturbances of memory function are common findings after ECT indicating functional compromise. Diffusion weighted imaging (DWI) has been shown to be sensitive to focal tissue changes associated with compromise of energy metabolism in cerebral ischemia and after prolonged ictal activity. We used conventional MRI and DWI in an exploratory study examining ten patients after treatment with ECT, eight of whom experienced short-lasting memory disturbances. MRI and DWI showed no definite signal abnormalities on qualitative and quantitative analysis. In three patients, equivocal marginal DWI hyperintensity was noted in the hippocampal formation. These findings are in line with previous negative studies using conventional MRI. Higher resolution DWI and serial imaging may be necessary to visualize possible minimal signal changes after ECT.

Purpose: We evaluated sildenafil for erectile dysfunction and lower urinary tract symptoms in men with the 2 conditions., Materials and Methods: This was a 12-week, double-blind, placebo controlled study of sildenafil in men 45 years or older who scored 25 or less on the erectile function domain of the International Index of Erectile Function and 12 or greater on the International Prostate Symptom Score. Men with confirmed or suspected prostate malignancy, or prostate specific antigen 10 ng/ml or more were excluded. End points were changes in International Index of Erectile Function domain scores, International Prostate Symptom Score (irritative, obstructive and quality of life), the Benign Prostatic Hyperplasia Impact Index, the Self-Esteem And Relationship questionnaire and Erectile Dysfunction Inventory of Treatment Satisfaction Index Score., Results: The 189 men receiving sildenafil had significant improvements in erectile function domain score vs the 180 on placebo (9.17 vs 1.86, p<0.0001) and on all other International Index of Erectile Function domains. In men on sildenafil vs placebo significant improvements were observed in International Prostate Symptom Score (-6.32 vs -1.93, p<0.0001), Benign Prostatic Hyperplasia Impact Index (-2.0 vs -0.9, p<0.0001), mean International Prostate Symptom Score quality of life score (-0.97 vs -0.29, p<0.0001) and total Self-Esteem And Relationship questionnaire scores (24.6 vs 4.3, p<0.0001). There was no difference in urinary flow between the groups (p=0.08). Significantly more sildenafil vs placebo treated patients were satisfied with treatment (71.2 vs 41.7, p<0.0001). Sildenafil was well tolerated., Conclusions: Improved erectile dysfunction and lower urinary tract symptoms with sildenafil in men with the 2 conditions were associated with improved quality of life and treatment satisfaction. Daily dosing with sildenafil may improve lower urinary tract symptoms. However, the lack of effect on urinary flow rates may mean that a new basic pathophysiology paradigm is needed to explain the etiology of lower urinary tract symptoms.

The purpose of the present study was to determine whether MR-detectable alterations of choline-containing compounds in two key neural systems involved in major depression disorder namely the hippocampus and the basal ganglia can be detected. Multislice proton magnetic resonance spectroscopic imaging was applied in 11 patients with major depressive disorder (MDD) and ten matched healthy subjects. Voxels were selected from the left and right side of the hippocampus and the putamen. Significantly lower choline-containing compounds in the hippocampus and significantly higher choline-containing compounds in the putamen of patients with MDD compared to healthy subjects were found. No significant differences were found for the other metabolites in the two regions evaluated. Abnormal levels of choline-containing compounds most likely reflect altered membrane phospholipid metabolism. A reduced level in the hippocampus and an increased level in the putamen suggest regionally opponent membrane abnormalities.

Background: Although the major principles of dopamine (DA) signaling have been well described previously, its precise modulatory impact on the prefrontal cortex (PFC) in humans is poorly understood. Two major neurophysiological models propose segregated functional circuits on the systems level as well as D(1) and D(2) receptor-dependent processing states on the cellular level (two-state model)., Methods: We examined the predictive validity of these models in 10 healthy male volunteers with a haloperidol challenge (HLP). Cortico-striatal-thalamo-cortical (CSTC) motor loop functions were examined during functional magnetic resonance imaging (fMRI) with a sequential finger opposition task. Neuropsychological implications of the two-state model were evaluated with a test battery of D(1)- or D(2)-sensitive prefrontal measures., Results: Analysis of fMRI data revealed a significant HLP-induced blood oxygen level dependent-signal decrease in the sensorimotor striatum and a lateralized activation loss of ipsilateral higher order motor cortices and contralateral cerebellum. Neuropsychological evaluation demonstrated a preferential impairment of D(2)-sensitive functions, whereas D(1) or non-dopaminergic domains were unaffected., Conclusions: Our data support the hypothesis that mesocortical D(1) and D(2) receptors exert differential influences in the PFC for cognitive function, but the nigrostriatal CSTC network model for the motor domain could not be confirmed.

The aim of this work was to evaluate the relationship between the amount of alcohol consumption of a group of social drinkers and the magnetic resonance spectroscopy signal of choline-containing compounds (Cho) in the frontal lobe. Two independent long echo (TE = 135 ms) (1)H MRSI studies, the first comprising 24 subjects with very low alcohol consumption, the second 18 subjects with a more widespread alcohol consumption were conducted. Significant correlations of Cho measures from frontal white matter and from the anterior cingulate gyrus with alcohol consumption in the last 90 days prior to the MR examination were found. Age, gender, and smoking did not show significant effects on the metabolite measures. Partialling out the effect of the voxel white matter content did not change the correlation of choline measures with alcohol consumption. The main conclusion from the repeated finding of a positive correlation of alcohol consumption and frontal Cho signals is that monitoring for alcohol consumption is mandatory in MRS studies where pathology depended Cho changes are hypothesized.

Proton magnetic resonance spectroscopy ((1)H-MRS) has provided evidence for a reduction of N-acetyl-aspartate (NAA) in the medial temporal lobe (MTL) in cerebral disorders such as Alzheimer's Disease. Within the (1)H-MRS study of the German Research Network on Dementia, we determined the multicenter reproducibility of single-voxel (1)H-MRS of the MTL. At five sites with 1.5T MR systems, single-voxel (1)H spectra from the MTL of an identical healthy subject were measured. The same subject was also examined at one of the sites five times to assess intracenter stability. The protocol included water-suppressed spectra with TE 272 ms and TE 30 ms and unsuppressed spectra for absolute quantification of metabolite concentrations. The intracenter reproducibility of absolute NAA concentration, expressed as coefficient of variation (CV), was 1.8%. CV for the concentrations of creatine (Cr), choline (Cho), and myoinositol (MI) and for the ratios NAA/Cr, NAA/Cho, and MI/NAA varied by 11-16%. Intercenter CV was 3.9% for NAA and were below 10% for all other metabolites and metabolic ratios. Our study demonstrates that quantitative assessment of NAA with single-voxel MRS can be performed with high intercenter reproducibility. This is the basis for applying (1)H-MRS in large-scale early recognition and treatment studies in MTL affecting disorders.

Key neural systems involved in the processing and communication of emotions are impaired in patients with major depressive disorder (MDD). Emotional and behavioral symptoms are thought to be caused by damage or dysfunction in specific areas of the brain that are responsible for directing attention, motivating behavior, and learning the significance of environmental stimuli. Functional brain studies with positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) give support for functional abnormalities in MDD that are predominantly located in areas known to play an important role in the communication and processing of emotions. Disturbances in emotional processing as they are observed in MDD, if any, have very subtle morphometrical brain correlates. With proton magnetic resonance spectroscopy (1H MRS), brain metabolites can be measured noninvasively in vivo, thus furthering the understanding of the effects of changes in neurotransmitters within the brain. The current literature on 1H MRS studies in MDD is small with a large diversity of MRS methods applied, brain regions studied, and metabolite changes found. Nevertheless, there is strong evidence that changes in neurometabolite concentrations in MDD occur within brain regions, which are involved in the processing and communication of emotions that can be monitored by 1H MRS. This review summarizes the literature about biochemical changes quantified via 1H MRS in MDD patients in brain regions that play an important role for the communication and processing of emotions.

Hippocampal choline-containing compounds (Cho) determined with 1H MR spectroscopy (MRS) are decreased in major depression episodes and return to baseline levels after antidepressive electroconvulsive therapy (ECT). A rise in hippocampal Cho has been observed in rats upon electroconvulsive shocks (ECS), an analogue of human ECT. Choline production involves the activity of various phospholipases. In order to investigate whether the increase of Cho correlates with an enhanced expression of phosphoslipase A2 (PLA2) we took rectangular tissue samples from the region of the MRS voxel for immunoblotting. Our data show a significant inverse correlation (p = 0.018) between PLA2 protein levels and MRS Cho/NAA levels suggesting a possible downregulation of PLA2 in compensation for an upregulation of other phospholipases.

Background: This study focused on metabolic brain alterations in recently detoxified alcohol-dependent patients (S1) and their possible reversibility after 3 (S2) and 6 months (S3) of abstinence., Methods: Thirty-three alcohol-dependent patients and 30 healthy control subjects were studied with multislice proton magnetic resonance spectroscopic imaging (echo time = 135 msec at 1.5 T at three time points)., Results: In the patient group, we found that choline-containing compounds (Ch) in three frontal and cerebellar subregions at S1 were significantly below normal, whereas N-acetyl aspartate (NAA) differences did not reach significance but showed a trend toward below-normal values in frontal white matter. Abstinent patients showed a significant increase of Ch in all subregions at S2. At S3, no further significant metabolite changes in abstinent patients compared with S2 could be detected. No significant increase of NAA could be detected at follow-up., Conclusions: The increase of the Ch signal in the follow-up measurement after 3 months in abstinent alcohol-dependent patients supports the hypotheses of an alcohol- or alcohol detoxification-induced altered cerebral metabolism of lipids in membranes or myelin, which seems to be reversible with duration of alcohol abstinence.

Objective: The authors' goal was to investigate the distribution of metabolites and voxel composition in the pons and three cerebellar subregions and compare metabolite integral values and differences in voxel composition between patients with schizophrenia and healthy subjects., Method: Proton magnetic resonance spectroscopic imaging was used to study the cerebellum and pons of 14 patients with schizophrenia and 14 healthy comparison subjects., Results: The voxel composition was not significantly different between the groups, but the patients with schizophrenia had significantly lower N-acetylaspartate levels in the cerebellar cortex and vermis., Conclusions: The lower integral value of N-acetylaspartate in the cerebellar cortex and the vermis of patients with schizophrenia supports the theory of a dysfunctional corticocerebellar-thalamic-cortical circuit in schizophrenia.

Modern neuroimaging techniques such as magnetic resonance imaging (MRI) and positron emission tomography (PET) have contributed tremendously to our current understanding of psychiatric disorders in the context of functional, biochemical and microstructural alterations of the brain. Since the mid-nineties, functional MRI has provided major insights into the neurobiological correlates of signs and symptoms in schizophrenia. The current paper reviews important fMRI studies of the past decade in the domains of motor, visual, auditory, attentional and working memory function. Special emphasis is given to new methodological approaches, such as the visualisation of medication effects and the functional characterisation of risk genes.

Metabolic changes in the hippocampus formation can be investigated with in vivo magnetic resonance spectroscopy (MRS). Learned helplessness (LH) is a well validated animal model of depression which we established in Sprague-Dawley rats defining some as "learned helpless" (LH) or not "learned helpless" (NLH). Helpless and non-helpless rats received a course of daily administered electroconvulsive shocks (ECS) for 6 days. MRS measurements were performed on a 4.7 T animal scanner with an average voxel size within the rat hippocampus of 10 microl. In LH rats hippocampal creatine/NAA rose significantly (14%) whereas creatine/NAA of NLH rats showed no increase at all. A possible connection between hippocampal creatine levels and major depressive disorders as a reflection of changes in energy metabolism is discussed.

Degenerative alterations of cortical and subcortical regions in Alzheimer disease (AD) can be estimated by the extent of brain metabolite changes as measured by magnetic resonance spectroscopic imaging (MRSI). A neuropsychological assessment may correlate with metabolite levels and could evaluate underlying degenerative processes. Probabilistic-related classification learning, which represents one form of procedural learning, is associated with the neostriatum. The present study was aimed at examining the correlation of spectroscopic imaging in subcortical regions with the evaluation of specific neuropsychological findings. Twenty-two patients with Alzheimer's disease were compared to 15 healthy elderly control subjects. Proton MRSI of the basal ganglia (BG) and thalamus region was performed for detection of N-acetylaspartate (NAA), trimethylamine (TMA) and creatine ((P)Cr). In addition, a probabilistic-related classification learning task (Weather Prediction Task (WT)) was applied. We observed that in patients a high TMA signal in the basal ganglia region was correlated with a poorer performance in the probabilistic learning task (Spearman rank order correlation (SROC)=-0.6, P<0.009). Although Alzheimer's patients, as a group, did not differ from controls with regard to probabilistic learning capacity (PLC), male AD patients, as compared to male controls, displayed an impairment in the task performance by 28% (P<0.03) and showed a 16% elevation in TMA signaling (P<0.04). The altered metabolite signals and ratios in combination with the cognitive performance might suggest gender-related neuronal degeneration and dysfunction within subcortical regions in AD.

Background: In a previous proton magnetic resonance spectroscopic imaging ((1)H MRSI) study of the hippocampus in patients receiving electroconvulsive therapy (ECT), the metabolite signals for N-acetylaspartate (NAA), creatine and phosphocreatine, and choline-containing compounds (Ch) were evaluated before and directly after a course of ECT. Stable metabolite signals for NAA and creatine and phosphocreatine but increasing signals from choline-containing compounds post-ECT compared with pre-ECT were found. The purpose of this investigation was to monitor the long-term course of the hippocampal metabolite signals post-ECT treatment., Method: Twelve of 17 depressed patients (DSM-IV and ICD-10 criteria), examined while receiving ECT, were reevaluated after a minimum interval of 12 months. Data were gathered between 1997 and 2000. In all patients, (1)H MRSI studies of the hippocampus were performed and relative contributions of cerebrospinal fluid, gray matter, and white matter to each MRSI voxel were determined. Patients' cognitive as well as psychopathologic status was obtained., Results: Two of the examined patients suffered a relapse. All other patients were in stable remission. No changes in hippocampal NAA signals were detected after a mean interval of 20 months (SD = 8.6) after the last ECT. The initially significant increase in the Ch signal was found to be reversed to nearly pre-ECT values., Conclusion: The results of our long-term follow-up corroborate our original finding that ECT has no influence on NAA signals. The observed reversal of the Ch signal might reflect alterations in membrane turnover. Increased Ch signals are thought to reflect an increased membrane turnover and should reverse accordingly. This increase in membrane turnover could potentially play a role in the therapeutic effect of ECT.

Background: The hippocampus, thalamus and basal ganglia are among the brain regions of major interest in schizophrenia., Aims: The purpose of this study was to corroborate previous findings of reduced N-acetylaspartate in the hippocampal and thalamic regions and to investigate possible metabolite changes in the putamen in schizophrenia., Method: MRSI study of the thalamus, basal ganglia, and hippocampus in 13 schizophrenic patients under stable medication and age-matched healthy controls., Results: A decrease of the N-acetylaspartate signal was found in the hippocampal region and the thalamus but not in the putamen of patients compared to controls. No significant group differences in the signals from creatine and phosphocreatine, and choline-containing compounds were found in the hippocampal region and the putamen but the signal from choline-containing compounds was decreased in the thalamus of patients., Conclusion: Metabolic processes in the basal ganglia of schizophrenic patients seem to be opposite the hippocampal and thalamus findings.

Magnetic resonance spectroscopic imaging provides a non-invasive approach for testing the hypothesis that neuronal function can improve under atypical antipsychotic medication leading to improvement in cognitive function. We studied two groups of schizophrenic patients, one treated exclusively with typical neuroleptics, the other with atypical medications. 1H MR-spectroscopic imaging of the anterior cingulate gyrus was performed in all patients. Perseveration errors in the Wisconsin Card Sorting Test (WCST) served as an additional marker for cingulate gyrus function. Our results showed that N-acetylaspartate (NAA), a measure of neuronal function, was closely correlated with perseveration errors seen on the WCST. Patients treated with atypical medications had fewer errors on the WCST and higher NAA levels than those on typical medications, and there was a correlation between the time treated with atypical medication, higher NAA levels and better test performance. These results suggest that atypical antipsychotics modify the function of anterior cingulate neurons in a specific manner.

Objective: Using proton magnetic resonance spectroscopic imaging, the authors measured thalamic N-acetylaspartate (NAA) concentrations in patients with schizophrenia., Method: The study included 15 schizophrenic patients on a stable medication regimen and 15 age-matched healthy comparison subjects. Concentrations of NAA, creatine plus phosphocreatine, and choline-containing compounds in bilateral thalamic regions were determined., Results: Previous findings of lower NAA concentration in the left and right mediodorsal region of the thalamus and significant correlations between left and right thalamic NAA measures in patients with schizophrenia were corroborated. Furthermore, the concentrations of choline-containing compounds were significantly lower in the schizophrenic patients. No group differences in creatine plus phosphocreatine were found., Conclusions: There is strong evidence for neuronal dysfunction or loss in the mediodorsal region of the thalamus in patients with schizophrenia.

In recent years the illicit drug ecstasy (MDMA, 3,4-methylenedioxymethamphetamine) has come into widespread use among young people. Despite clear evidence for the neurotoxic potential of MDMA in animals, corresponding evidence in humans is limited to indirect findings. In an exploratory study we compared the hippocampal 1H-MRSI (magnetic resonance spectroscopic imaging) spectra of five MDMA users with those of controls with no history of substance abuse. Although 1H

Purpose: To study the feasibility and clinical potential of visual inspection of hydrogen 1 magnetic resonance (MR) spectroscopic metabolite images for the lateralization of unilateral nonlesional temporal lobe epilepsy (TLE)., Materials and Methods: MR imaging and 1H MR spectroscopic imaging were performed of the temporal lobes in 50 patients with TLE and 23 age-matched healthy volunteers. N-acetylaspartate (NAA) and creatine plus choline metabolite images were read by two neuroradiologists who determined lateralization according to the side of lower NAA signal intensity. Quantitative estimates of NAA were calculated by using an automated fitting program., Results: Agreement in lateralization between readers was significant with a kappa score of 0.53 for all patients with TLE and 0.63 for patients displaying mild or marked NAA asymmetry. Among the 50 patients with TLE, lateralization was determined correctly by reader 1 in 38 (76%) patients and by reader 2 in 31 (62%) patients. If limited to patients with mild or marked NAA asymmetry, correct lateralization improved to 30 (77%) of 39 and 16 (80%) of 20 patients, respectively. Combined qualitative reading and quantitative spectral fitting enabled lateralization in 34 (85%) of 40 patients with TLE for reader 1 and 30 (77%) of 39 for reader 2, including nine of 14 patients with TLE with negative MR images., Conclusion: Reading of metabolite images is a feasible and fast means for noninvasive evaluation of patients with TLE who are candidates for surgery and enables lateralization in some patients with negative MR images.

Background: We monitored the effect of electroconvulsive therapy (ECT) on the nuclear magnetic resonance-detectable metabolites N-acetylaspartate, creatine and phosphocreatine, and choline-containing compounds in the hippocampus by means of hydrogen 1 magnetic resonance spectroscopic imaging. We hypothesized that if ECT-induced memory deterioration was associated with neuronal loss in the hippocampus, the N-acetylaspartate signal would decrease after ECT and any increased membrane turnover would result in an increase in the signal from choline-containing compounds., Methods: Seventeen patients received complete courses of ECT, during which repeated proton magnetic resonance spectroscopic imaging studies of the hippocampal region were performed. Individual changes during the course of ECT were compared with values obtained in 24 healthy control subjects and 6 patients remitted from major depression without ECT., Results: No changes in the hippocampal N-acetylaspartate signals were detected after ECT. A significant mean increase of 16% of the signal from choline-containing compounds after 5 or more ECT treatments was observed. Despite the mostly unilateral ECT application (14 of 17 patients), the increase in the choline-containing compound signal was observed bilaterally. Lactate or elevated lipid signals were not detected. All patients showed clinical amelioration of depression after ECT., Conclusions: Electroconvulsive therapy is not likely to induce hippocampal atrophy or cell death, which would be reflected by a decrease in the N-acetylaspartate signal. Compared with an age-matched control group, the choline-containing compounds signal in patients with a major depressive episode was significantly lower than normal, before ECT and normalized during ECT.

The purpose of the present study was to evaluate the cortical response to motor stimulation in neuroleptic-naive first episode schizophrenics in comparison to matched controls using a high speed functional magnetic resonance imaging technique (fMRI). Twelve patients satisfying ICD 10 criteria (F20.0) for schizophrenia (paranoid subtype) as well as sex- and age-matched healthy volunteers participated in this study. All subjects underwent fMRI examination on a conventional 1.5 T MR unit equipped with an echo-planar imaging booster. The blood oxygen level dependent (BOLD) response of the sensorimotor cortex and the higher order SMA region was evaluated during performance of a left hand sequential finger opposition task. Special care was taken to minimize performance and motion artifacts. Patients and controls showed no notable difference with respect to laterality, changes of signal intensity or spatial extent of activation within the primary and higher order motor regions. Using high speed fMRI no fundamental motor cortical dysfunction was evident in a group of paranoid neuroleptic-naive first episode schizophrenic patients. In contrast to data previously reported for chronic disorganized medicated patients, these results suggest that motor dysfunction is not part of the phenomenology of acute paranoid first episode patients.

Brain function and laterality in schizophrenia were investigated by means of a simple motor task with a self-generated left-hand sequential finger opposition (SFO) using a whole-brain high-speed (100 ms per slice) functional imaging technique. Neuroleptic-naïve, acutely ill schizophrenic patients were compared to schizophrenic patients under stable neuroleptic medication and matched controls. The goal was to evaluate both the motor function in first-episode patients and possible effects of different neuroleptic treatments on functional MRI results. Forty patients satisfying ICD 10 criteria (F20.x) for schizophrenia and sex- and age-matched healthy volunteers participated in this study. All subjects underwent fMRI examinations on a conventional 1.5 T MR unit. The primary sensorimotor cortex and the high-order supplementary motor area (SMA) were evaluated. There was a close similarity in the activation of the primary and high-order (SMA) sensorimotor areas between first-episode schizophrenic patients and controls. In contrast, a significant reduction in the overall blood oxygen level dependent (BOLD) response was seen in sensorimotor cortices (contra- and ipsilateral) in schizophrenic patients under stable medication with typical neuroleptics. This effect was not present in patients treated with atypical antipsychotics. Both antipsychotic treatments, however, led to a significant reduction in activation of the SMA region compared to controls and neuroleptic-naïve subjects. Thus, the present study provides no evidence for the localized involvement of the primary motor cortex or the SMA as a relatively stable vulnerability marker in schizophrenia. There is, however, strong evidence that neuroleptics themselves influence fMRI activation patterns and that there are major differences between typical neuroleptics and atypical antipsychotics.

Purpose: 31P MR spectroscopic imaging (31P SI) was evaluated in a clinical study as a method for monitoring presurgical devascularization of meningiomas. The aim was to assess noninvasively metabolic alterations in tumor and in healthy brain tissue before and after embolization., Methods: Localized 31P MR spectra of the brain were obtained by means of 2D-SI (voxel size: 36 cm3) using a 1,5-T whole-body MR tomograph., Results: Eleven of 19 patients with intracranial meningiomas examined in this study underwent preoperative embolization therapy; eight patients were examined before and after treatment. After embolization, alterations of pH and of the concentrations of high-energy phosphates (nucleoside-5' triphosphate = NTP, phosphocreatine = PCr), inorganic phosphate (Pi), and membrane constituents were observed in the tumors. A tendency of [Pi] increase and decrease of [NTP], [PCr], and pH predominated, which is explained by ischemic processes after tumor devascularization., Conclusion: 31P SI is applicable in clinical studies and detects alterations of phosphate metabolism in a meningioma after embolization.

The purpose of this study was to compare 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET), hippocampal volumetry (HV), T2 relaxometry, and proton magnetic resonance spectroscopic imaging (1H-MRSI) in the presurgical neuroimaging lateralization of patients with nonlesional, electroencephalogram (EEG)-defined unilateral temporal lobe epilepsy (TLE). Twenty-five patients were prospectively studied, along with age-matched controls. T2 relaxometry examinations were performed in 13 patients. Comparison of FDG-PET, HV, and 1H-MRSI was possible in 23 patients. FDG-PET lateralized 87% of patients, HV 65%, N-acetyl aspartate (NAA)/(choline [Cho] + creatine [Cr]) 61%, and [NAA] 57%. Combined HV and NAA/(Cho + Cr) results lateralized 83% of the patients, a value similar to PET. Of 10 patients with normal magnetic resonance imaging (MRI) scans, 2 were lateralized with HV, 6 with FDG-PET, 4 with NAA/(Cho + Cr), and 3 with [NAA]. T2 relaxometry lateralized no patients without hippocampal atrophy. Bilateral abnormality was present in 29 to 33% of patients with 1H-MRSI measures and 17% with HV. Only hippocampal atrophy correlated with postoperative seizure-free outcome. FDG-PET remains the most sensitive imaging method to correlate with EEG-lateralized TLE. Both FDG-PET and 1H-MRSI can lateralize patients with normal MRI, but only the presence of relative unilateral hippocampal atrophy is predictive of seizure-free outcome. Bilaterally abnormal MRI and 1H-MRSI measures do not preclude good surgical outcome.

Previous magnetic resonance spectroscopy (MRS) studies have shown that N-acetylaspartate (NAA) is reduced not only in the ipsilateral but also in the contralateral hippocampus of many patients with mesial temporal lobe epilepsy (mTLE). The reason for the contralateral damage is not clear. To test whether the hippocampus is also damaged if the focus is outside the hippocampus, we have measured patients with neocortical epilepsy (NE). Therefore, the goals of this study were to determine if hippocampal NAA is reduced in NE and if hippocampal NAA discriminates NE from mTLE. MRS imaging (MRSI) studies were performed on 10 NE patients and compared with MRSI results in 23 unilateral mTLE patients and 16 controls. The results show that, in contrast to mTLE, NAA was not reduced in the hippocampus of NE patients, neither ipsilateral nor contralateral to the seizure focus. These results suggest that repeated seizures do not cause secondary damage to the hippocampus. The absence of spectroscopic differences in NE may help to distinguish NE from mTLE.

Direct volume rendering is a visualization method that allows display of all information hidden in three-dimensional data sets of, for example, computed tomography or magnetic resonance imaging (MRI). In contrast to commonly used surface rendering methods, these algorithms need no preprocessing but suffer from a high computational complexity. A real-time rendering system, VIRIM (Vitec: Visualization Technology GmbH, Mannheim, Germany), cuts down rendering times of minutes on normal workstations to an interactive rate of 1 second or less. The immediate visual feedback allows interactive steering of the visualization process to achieve insight into the internal three-dimensional structure of objects. Additional information is obtained by using an interactive gray-value segmentation tool that both allows segmentation of the data set according to bone, tissue, and liquor and display of multifunctional data sets (e.g., functional MRI [fMRI] data sets). Thus, real-time direct volume rendering allows segmentation and volume data processing of functional and anatomical MR data sets simultaneously. As this method can be integrated in the clinical routine, it is of great importance for real-time motion artifact detection and the interpretation of fMRI data acquired during cognitive experiments with normal subjects and psychiatric patients. Because of the free programmability of VIRIM, more complex matching procedures are currently being investigated for future implementation.

Purpose: To determine which proton magnetic resonance (MR) spectroscopic imaging measures are best for lateralizing the seizure focus in patients who have temporal lobe epilepsy with and in those without hippocampal atrophy on MR images, the extent of contralateral abnormalities, and whether there is a correlation between MR spectroscopic imaging findings and surgical outcome., Materials and Methods: MR spectroscopic imaging was performed in 16 adult patients with temporal lobe epilepsy and unilateral electroencephalographic findings and in 16 adult control subjects. Eleven patients underwent surgery; all patients underwent MR imaging., Results: Nine patients had hippocampal atrophy on MR images. An ipsilateral decrease in the N-acetylaspartate concentration or the ratio of N-acetylaspartate to the sum of creatine and choline (N-acetylaspartate/ [creatine + choline]) was found in all patients. Decreased contralateral N-acetylaspartate concentration, N-acetylaspartate/(creatine + choline), or N-acetylaspartate concentration and N-acetylaspartate/(creatine + choline) were detected in eight patients (50%), which suggests bilateral abnormalities not detected with MR imaging. In the five patients who underwent surgery and did not show hippocampal atrophy on MR images, successful and unsuccessful outcomes were correctly predicted with N-acetylaspartate concentration., Conclusion: Decreased N-acetylaspartate concentration is not due solely to hippocampal atrophy. Contralateral abnormalities are much more frequent than expected. MR spectroscopic imaging is valuable in the presurgical evaluation of epilepsy.

Leber's hereditary optic neuropathy (LHON) is a maternally inherited disease associated with mitochondrial DNA (mtDNA) mutations. We describe the distribution of seven different mtDNA mutations and the clinical findings in 334 LHON patients belonging to 29 families. Mutations described only in LHON at nucleotide positions 11778, 3460, and 14484 were found in 15, two, and nine families respectively. In three families none of these mutations was found. Mutations described in LHON but also in controls at nucleotide positions 15257, 13708, 4917, and 4216 were found in one, 10, three and 12 families respectively. Combinations of mtDNA mutations were found in most families. The patient population mainly consisted of 79.2% to 89.5% males except for one family with only 10 of 17 patients being males (58.9%, p approximately 0.036). In 11 families only the 11778 mutation was found; in this group (WX) the affected males had a mean age of onset of 29.2 years and a mean visual outcome of 0.113. In seven families the 14484, 13708, and 4216 mutations were found; in this group (MA) the affected males had a mean age of onset of 22.0 years and a mean visual outcome of 0.442. In two families no mutation was found at all; in this group (YX) the affected males had a mean age of onset of 18.9 years and a mean visual outcome of 0.167. The mean age of onset in the WX group is significantly higher than in the MA group (p < or = 0.001) and in the YX group (p approximately 0.01). The mean visual outcome in the MA group is significantly better than in the WX group (p

Dynamic nuclear polarization of the coupled 13C-1H spin system was studied for optimizing the signal-to-noise ratio of in vivo 13C MR spectra. In particular, the truncated driven and transient nuclear Overhauser effect (NOE) of the proton-decoupled 13C resonances from methylene carbons in vegetable oil and in human calf tissue was observed. Maximum in vivo NOE enhancements eta = 1.5 and 0.9 were found, respectively. Theoretical fits to the data yield 13C-1H cross-relaxation times in the order of 0.6 s. Significant signal enhancement over the whole in vivo 13C chemical shift range is obtained with minimum expense utilizing the NOE of the dipolar coupled 13C-1H spin system in addition to proton-decoupling. NOE-enhanced proton-decoupled in vivo 13C MR spectra were acquired within 17 min in volunteer examinations from the human breast and the calf. These spectra show well-resolved resonances of carbons in lipids and several other cellular compounds.

Conservative therapeutic concepts with initial chemotherapy for patients with breast cancer represent a challenge to non-invasive techniques for monitoring response to therapy. Experimental magnetic resonance spectroscopy studies have been able to show exemplary applications for therapy monitoring of breast cancer patients. The characteristic phosphomonoester resonances and their changes during therapy are possible clinical parameters. The additional information which can be obtained from proton and carbon spectroscopy increases the amount of detectable metabolites. On-going studies are investigating clinical applications of multinuclear spectroscopic studies in patients with breast cancer.

Vast numbers of spores of the thermophilic actinomycetes Excellospora flexuosa, Thermomonospora alba, T. curvata and T. fusca were collected from the air in fermentation tunnels during the spawning of mushroom compost, i.e. over 10(9) CFU m-3 of air. Five different genera of fungi, namely, Aspergillus, Aureobasidium, Cladosporium, Penicillium and Scytalidium, were found at only 10(3) CFU m-3 of air. Agaricus bisporus, used for spawning, was absent. Sera of 10 mushroom growers affected by Mushroom Worker's Lung (MWL) were tested by a qualitative dot-ELISA for antibodies against the spores of these micro-organisms. All 10 were positive for one or more of the actinomycetes E. flexuosa, T. alba, T. curvata and T. fusca. No antibodies were found against Streptomyces thermovulgaris, Thermoactinomyces vulgaris and T. sacchari nor against the fungi Aspergillus fumigatus, Penicillium brevicompactum, P. chrysogenum, Scytalidium thermophilum and Trichoderma viride. Sera of 11 of 14 workers engaged in routine spawning of compost in tunnels reacted positively with 1 or more of the actinomycetes. Their 10log serum titres increased with the duration of employment to an upper limit of 2.5. The sera of 19 non-exposed individuals were negative. Because high numbers of spores of E. flexuosa, T. alba, T. curvata and T. fusca were present in the air that was used for successful inhalation provocation of mushroom workers with MWL and because of the elevated serum titres of these workers, we presume these organisms to contribute in the occurrence of MWL.

Image correlation methods enable the complementary use of information from different medical images of a patient. These images can be obtained from different imaging devices (CT, MR, PET), or, from one imaging device taken at different times. Unfortunately, there are few cases in which the requirements for later image correlation are taken into account at the time of image acquisition. There is therefore a need for correlation techniques requiring no preparation in advance. We have developed two correlation methods, both based on three or more anatomical or artificial landmarks, to be defined in corresponding image data sets. These methods have been evaluated with phantom data as well as with patient data. We have improved these correlation methods by using more landmarks and special selection criteria. They are applicable to all medical tomograms and to x-ray pictures taken under stereotactical conditions. The results obtained have error ranges in the order of the three-dimensional image resolution.

Over a period of 3 months during the summer, 362 African children admitted to King Edward VIII Hospital, Durban, were screened for the faecal excretion of Cryptosporidium oocysts. Of 259 children with diarrhoea, oocysts were detected in 31 (11.9%), while none was found in the faeces of 103 children without diarrhoea (controls). All those children excreting Cryptosporidium were under 2 years of age, giving a prevalence of 15% for this group. Other potential enteric pathogens were detected in the faeces of 12 (38.7%) of these children. The case fatality rate for patients with Cryptosporidium was 22.6%, which may reflect the selection of patients in a study concentrating on hospital inpatients. Cryptosporidium was the second most common organism detected in diarrhoeal faeces, and the only one detected in 9.2% of diarrhoeal children aged less than two years. These findings indicate that Cryptosporidium should be regarded as a potential pathogen in children admitted to this hospital with severe diarrhoea. Such association of Cryptosporidium with diarrhoea in children accords with recent studies in other parts of the world.