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Several studies and recent models of effects of nicotine, the main addictive and psychoactive component in tobacco, point to action of the drug on the limbic system during maintenance of addiction, either direct or indirect via projections from the ventral tegmental area. The objective of this study was to demonstrate physiological effects of cigarette smoking on the hippocampus and the grey matter of the dorsal anterior cingulate cortex in the human brain with regard to addiction and withdrawal. This aim was achieved by group comparisons of results of magnetic resonance spectroscopy between non-smokers, smokers and smokers during withdrawal. 12 smokers and 12 non-smokers were measured with single voxel proton magnetic resonance spectroscopy for total N-acetyl aspartate, glutamate and glutamine, choline-containing compounds, myo-inositol and total creatine in the right and the left hippocampus and in the right and the left dorsal anterior cingulate cortex. Smokers were examined twice, first during regular cigarette smoking and second on the third day of nicotine withdrawal. The ratios to total creatine were used for better reliability. In our study, Glx/tCr was significantly increased and tCho/tCr was significantly decreased in the left cingulate cortex in smokers compared to non-smokers (p = 0.01, both). Six out of seven smokers showed normalization of the Glx/tCr in the left cingulate cortex during withdrawal. Although these results are preliminary due to the small sample size, our results confirm the assumption that cigarette smoking interferes directly or indirectly with the glutamate circuit in the dorsal anterior cingulate cortex.

BACKGROUND Gliomas propagate diffusely throughout and along white matter structures. Glioma-related changes in structural integrity and metabolism are not detectable by standard magnetic resonance (MR) imaging. OBJECTIVE To investigate differences in the metabolism of fiber tract alterations between gliomas grade II to IV by correlation of fiber density values with metabolite concentrations measured by fiber density mapping and MR spectroscopic imaging. METHODS Fiber density mapping and MR spectroscopic imaging were performed in 48 patients with gliomas WHO grade II to IV. Fiber density mapping data were used to define fiber tracts in tumoral and peritumoral areas. Structural integrity of fiber tracts was assessed as fiber density ipsilateral-to-contralateral ratio (FD ICR). Metabolite concentrations for choline-containing compounds and N-acetyl-aspartate were computed and correlated to FD ICR values after coregistration with anatomic MR imaging. RESULTS In tumoral areas, choline-containing compound concentrations of altered fiber tracts were significantly different between low- and high-grade glioma and showed different courses for the correlations of FD ICR and choline-containing czeompounds. In high-grade glioma, increasing fiber destruction was associated with a massive progression in cell membrane proliferation. Peritumoral fiber structures showed significantly decreased N-acetyl-aspartate concentrations for all patients, but only patients with glioblastoma multiforme had significantly decreased fiber density compared with the contralateral side. Glioma grades II and III had significantly higher peritumoral FD ICR than glioblastoma multiforme. CONCLUSION A multiparametric MR imaging strategy providing information about both structural integrity and metabolism of the tumor is required for detailed assessment of glioma-related fiber tract alterations, which in turn is essential for treatment planning.

Summary To elucidate, in a pilot-study, whether noninvasive transcutaneous vagus nerve stimulation (t-VNS) is a safe and tolerable alternative treatment option in pharmacoresistant epilepsy. t-VNS was applied to 10 patients with pharmacoresistant epilepsies. Stimulation via the auricular branch of the vagus nerve of the left tragus was delivered three times per day for 9 months. Subjective documentation of stimulation effects was obtained from patients’ seizure diaries. For a more reliable assessment of seizure frequency, we carried out prolonged outpatient video–electroencephalography (EEG) monitoring. In addition, computerized testing of cognitive, affective, and emotional functions was performed. Three patients aborted the study. Of the remaining seven patients, an overall reduction of seizure frequency was observed in five patients after 9 months of t-VNS. The noninvasive t-VNS stimulation is a safe and well-tolerated method for relatively long periods, and might be an alternative treatment option for patients with epilepsy.

The aims of this study were to investigate and categorize peritumoral fiber tract alterations while considering changes in metabolism and integrity of fiber structures using multimodal neuroimaging—that is, PET with O-(2-18F-fluoroethyl)-l-tyrosine and diffusion tensor imaging evaluated by fiber density mapping—and to correlate categories of fiber alterations with preoperative neurologic deficits and postoperative course. Methods: We examined 26 patients with cerebral gliomas. Fiber density data were used to segment peritumoral fiber structures and were coregistered to anatomic MR images and PET data. Fiber density and O-(2-18F-fluoroethyl)-l-tyrosine uptake values were evaluated as ipsilateral-to-contralateral ratios. Four metabolic categories were defined on the basis of O-(2-18F-fluoroethyl)-l-tyrosine values: tumor-infiltrated tissue, reactive tissue (astrogliosis and microglial activation), normal brain tissue, and tissue with attenuated amino acid metabolism. Fiber density values were grouped in 3 categories for structural integrity: compressed, normal, and attenuated fibers. Results: We evaluated and classified 103 peritumoral fiber structures with 10 patterns of fiber tract alterations. Fiber structures in tumor-infiltrated, reactive, and normal brain tissue showed compressed fibers, displaced fibers, and (partly) destroyed fibers, respectively. Attenuated amino acid metabolism was associated only with attenuated fiber density. Thirteen patients showed white matter–related neurologic deficits (paresis, hypoesthesia, aphasia, or anopia) as initial symptoms. Three patients showed tumor infiltration in the corresponding fiber tracts; all the others had reactive or normal brain tissue. Fiber structures were compressed or attenuated but not normal. The 3 patients with tumor infiltration in the corresponding fiber tracts and 1 with compressed fibers in normal brain showed no improvements or worsening of the deficits in the postoperative course. Eight patients with the corresponding fiber tracts in reactive or normal brain areas showed improvement of deficits. One patient underwent biopsy only. Conclusion: Our multimodal neuroimaging approach provides complementary information and more detailed understanding of peritumoral fiber tract alterations in gliomas which are more complex as described so far. We presented a classification model for systematic assessment of these alterations that may be helpful for treatment planning and prediction of patients’ prognoses.

Summary Purpose: Long-term epilepsy associated tumors (LEATs) are a frequent cause of drug-resistant partial epilepsy. A reliable tumor diagnosis has an important impact on therapeutic strategies and prognosis in patients with epilepsy, but often is difficult by magnetic resonance imaging (MRI) only. Herein we analyzed a large LEAT cohort investigated by 18fluoroethyl-l-tyrosine–positron emission tomography (FET-PET). Methods: Thirty-six patients with chronic partial epilepsy and a LEAT-suspect MRI lesion were analyzed by FET-PET using visual inspection and quantitative analysis of standard uptake values (SUV). PET results were correlated with clinical and histopathologic data. Results: FET-PET study was positive in 22 of 36 analyzed lesions and in 14 of 22 histologically verified LEAT lesions. The precise World Health Organization (WHO) tumoral entity was not predicted by FET-PET. Notably, FET uptake correlated strikingly with age at epilepsy onset (p = 0.001). Further correlations were seen for age at surgery (p = 0.007) and gadolinium-contrast enhancement on MRI (p

PurposeThe objective of our study was to gain further insight into the extent of local metabolic alterations in patients with idiopathic generalised epilepsy (IGE), respectively, the subgroup with generalised tonic–clonic seizures (GTCS). The extent of regional metabolic involvement perhaps indicates the key structures in generation of seizures and involvement of specific network of dysfunction.MethodsUsing the multi-voxel technique at a 3T MRI Scanner metabolite levels of 25 age-matched healthy controls and 18 patients with GTCS were obtained from the basal ganglia, insular cortex, cingulum, hippocampus and along both hemispheres in the fronto-parietal white and grey matter.ResultsGroup analysis of GTCS patients versus healthy controls revealed significant (p2 tonic–clonic seizures in the last 12 months a trend towards higher Glx and lower tNAA levels was observed.DiscussionOur results demonstrate the altered metabolic interconnection of cerebral anatomic regions in patients with GTCS, in particular the major role of basal ganglia-central region relay in seizure generation.

Summary Purpose: The objective of this study was to determine if levetiracetam (LEV) modulates brain γ-aminobutyric acid (GABA) in patients with epilepsy. Methods: Occipital GABA was assessed by protein magnetic resonance spectroscopy (1H-MRS) in 16 patients with focal epilepsy at baseline and following the initiation of oral administration of LEV as monotherapy. Responder profiles were calculated as percentage of baseline seizure frequency. Alterations of GABA/Cr (creatine) of baseline measurements compared to GABA/Cr under LEV therapy were analyzed by Student’s t-test for paired samples. Results: After administration of LEV, partial seizure reduction (>50%) was noticed in 5 of 16 patients (31%; 7 of 16 (44%) patients turned out to be free of seizures. Patients with 50–100% seizure reduction under LEV titration were referred to as LEV responders. Of the 32 GABA spectra, only 22 (approximately 70%) yielded a result that met the criteria for spectral quality; therefore, GABA/Cr data from only seven patients were paired. A significant increase of GABA/Cr during titration with LEV was noted in patients responding to LEV (n = 5; p = 0.007). No differences in baseline GABA/Cr levels were detected between patients with and without previous antiepileptic treatment (p = 0.74). Discussion: The increasing GABA/Cr levels under drug titration only in LEV-responding epilepsy patients suggest a more complex and indirect influence of LEV on the GABAergic system.

Rationale and Objectives The objective of this study was to determine how metabolite values (total N-acetyl aspartate [tNAA], glutamate plus glutamine [Glx], total choline [tCho], myoinositol [mI], and total creatine [tCr]) vary across brain regions in healthy subjects. This study was implemented to create an internal reference database for patients with psychiatric disorders and epilepsy. Materials and Methods Using the multivoxel technique with a voxelwise phantom calibration on a 3-T magnetic resonance imaging scanner, metabolite levels of 29 healthy controls (13 men, 16 women; average age, 29 years) were obtained from the hippocampi, basal ganglia, insula cortex, cingulum, and precuneus. Additionally, gray and white matter metabolite values were obtained from the frontal and parietal lobes. Results No significant effect of gender was noticed. The total magnitude of variation was greatest for Glx, followed by tNAA, mI, tCho, and tCr. Glx/tCr, Glx, and tCr were increased in gray matter, while tNAA/tCr, tCho/tCr, respectively tNAA and tCho, were elevated in white matter. These findings indicate (1) anterior-to-posterior increases of tNAA/tCr and Glx/tCr, respectively tNAA and Glx, along the midline in gray matter (cingulum); (2) increased tNAA/tCr, respectively tNAA, in white matter in the fiber tracts of the precentral region; (3) an accentuated anterior-to-posterior increase of tCr in the insula cortex; and (4) an anterior-to-posterior decrease of tCho/tCr and tCho in white matter. Conclusions There are significant metabolic differences within tissue types and within tissue types at different locations; therefore, the spectra and metabolite values presented should provide a useful internal reference for both clinical and research studies.

SummaryIntroductionThe objective of this study was to quantitate and compare ipsilateral total N-acetyl aspartate (tNAA), creatine (Cr), choline (Cho), myo-inositol (m-Ins) and glutamate plus glutamine (Glx) levels in the hippocampi of patients with temporal lobe epilepsy (TLE) with and without magnetic resonance imaging (MRI) evidence for mesial temporal sclerosis (MRI positive/negative).Patients and methodsTwenty-three age matched healthy controls and 26 consecutive patients with unilateral TLE, based on intensive 24h video-EEG, were investigated with proton magnetic resonance spectroscopy (1H-MRS) (17 with unilateral hippocampal sclerosis (HS) in MRI—MRI positive; 9 MRI negative). For statistical analysis one-way analysis of variance (ANOVA) with post hoc multiple comparisons and Bonferroni correction was applied. The significance level was based on p

The aim of this study was to compare flat-panel volumetric CT (VCT) to conventional CT (cCT) in the visualization of the extent of subarachnoid hemorrhage (SAH) and the width of the ventricles in patients with acute SAH. Included in the study were 22 patients with an acutely ruptured cerebral aneurysm who received VCT during coil embolization. VCT image quality, the extent of SAH (using a modified Fisher score and total slice number with SAH visible) and the width of the ventricles (Evans index) were evaluated by two experienced neuroradiologists (RAD1 and RAD2) and compared to the findings on cCT. Ten patients undergoing VCT for reasons other than SAH served as negative controls. Interobserver agreement in rating image quality was excellent for cCT (Kendall W value 0.94) and good for VCT (0.74). SAH was identified by RAD1 and RAD2 on VCT images in all patients. The modified Fisher scores underestimated the extent of SAH on VCT images in comparison with cCT images. Pearson’s correlation coefficient (r) regarding the number of image slices with SAH visible on cCT images compared with the number on VCT images was 0.85 for RAD1 and 0.84 for RAD2. The r value for the degree of interobserver agreement for the number of slices with SAH visible was 0.99 for cCT, and 0.95 for VCT images (n = 19), respectively. The width of the ventricles measured in terms of the Evans Index showed excellent concordance between the modalities (r = 0.81 vs. 0.82). Our preliminary results indicate that VCT is helpful in evaluating SAH in the angiography suite. Additionally, reliable evaluation of ventricle width is feasible. However, there are limitations with regard to the visibility of SAH on VCT images in comparison to cCT images.

We applied diffusion-weighted MRI (DWI) in the pilocarpine-induced status epilepticus (SE) model to investigate the evolution of acute phase changes in brain diffusion with and without early anticonvulsive therapy correlated to long-term SE-induced neuronal cell loss. Hereby, DWI was performed before (baseline) and serially between 3 and 120 min after onset of SE in untreated and treated animals (n=15 in each group). Anticonvulsive-treated animals received 20 mg/kg diazepam at 15 min after onset of SE. Apparent diffusion coefficients (ADC) were calculated for the parietal, temporal and piriform cortex, thalamus, hippocampus and amygdala and compared to baseline. Neuronal cell loss was quantified at 2 weeks after onset of SE utilizing cresyle-violet-staining. The results of ADC-mapping demonstrated a significant transient increase in ADC (to 116+/-4% of baseline) in the very acute phase starting 3 min after SE onset, lasting for 10 min in both groups. In untreated animals, there was a significant gradual decline in ADC to 75+/-12% of baseline while this decline in diazepam-treated animals was significantly less pronounced (P0.05) and ADC recovered to 93+/-6% of baseline. There was good correlation between neuronal cell loss in specific brain regions at 2 weeks after SE and maximal decrease in ADC (r0.79). In conclusion, serial DWI is a sensitive noninvasive technique for early detection, monitoring and prediction of SE-induced neuronal alterations. Using ADC-mapping, verification of early anticonvulsive therapy in SE seems to be possible as there is good correlation between the maximal decrease in ACD in the acute phase of SE and late neuronal cell loss.

Summary Purpose In this study 30 patients with symptomatic epilepsy caused by cavernomas were investigated in a postoperative follow up study to assess predictors for postoperative outcome with respect to indications, time and approach of surgery. Methods Thirty patients with cavernomas refractory to medical treatment were scheduled for surgery based on the findings of high-resolution MR imaging and intensive EEG-video monitoring. Postoperative outcome of epilepsy was assessed by follow-up examinations based on the basis of classification by Engel and the International League against epilepsy (ILAE). Results The following variables were associated with good postoperative outcome: (1) complete resection of hemosiderin fringe surrounding the cavernoma was correlated to less postoperative seizure frequency versus incomplete resection of the hemosiderin fringe according to the outcome protocol of ILAE. (2) Lower duration of epilepsy at the time of operation was correlated to a better postoperative outcome with a benefit for recovery. (3) Absence of hemorrhage before surgery and unifocal seizure onset was a predictor for a favorable outcome, whereas bilateral or multifocal seizure onset zones showed poorer postoperative outcomes. (4) In patients with dual pathology (hippocampal sclerosis in addition to a cavernoma), lesionectomy plus hippocampectomy as opposed to lesionectomy only, had a better outcome than single lesionectomy. Conclusion Postoperative outcome in patients with cavernomas should be the topic of further prospective multicenter studies involving a large number of patients. In addition to the ideal operation time and handling of dual pathology the role of extended resection including perilesional hemorrhages should be taken into account.

Purpose: We sought to retrospectively investigate differences in correlation of absolute metabolites concentrations and metabolite ratios with histopathologic parameters of stereotactic biopsies from the border zone of gliomas. Materials and Methods: Proton magnetic resonance spectroscopic imaging (1H-MRSI) with high spatial resolution was performed in 10 glioma patients at 1.5 T. Magnetic resonance spectroscopic imaging (MRSI) data were coregistered to a 3D MR data set used for stereotactic procedures. Metabolite concentrations of choline-containing compounds (Cho), creatine (Cr), and total N-acetyl-aspartate (tNAA) in addition to metabolite ratios of Cho/Cr, tNAA/Cr, and Cho/tNAA were calculated for voxel positions at biopsy loci with low tumor cell infiltration. Metabolite values were correlated with histopathologic findings expressed as a relative (% tumor infiltration, %TI) and an absolute parameter (tumor cell number, TCN). Results: We found a strong negative linear correlation for tNAA with %TI (R = −0.773, P 0.05). On the other hand, the metabolite ratio of Cho/Cr showed a moderate positive linear correlation with %TI (R = 0.523, P = 0.012) and TCN (R = 0.486, P = 0.019), but no correlation was obtained for tNAA/Cr (P > 0.05). Differences in correlation between tNAA and Cho as well as tNAA/Cr and Cho/Cr were significant for both %TI (P = 0.012 and P = 0.024) and TCN (P = 0.016 and P = 0.040) using a t test. Conclusions: We conclude that absolute values of tNAA are more significant than Cho in the detection of low tumor cell infiltration. On the basis of absolute metabolite values, neuronal damage seems to be more distinct than cell membrane proliferation in the border zone of gliomas. Furthermore, the calculation of metabolite ratios versus Cr for the border zone may yield to misleading results because Cr is not constant in this area.

Summary: Purpose: In this study, hippocampal metabolite alterations in 1 H-MR spectroscopy ( 1 H-MRS) were correlated to the findings of intensive video-EEG monitoring and duration of seizure symptoms in patients with temporal lobe epilepsy (TLE). Methods: The 14 patients with mesial TLE and no pathological findings in imaging were investigated by 1 H-MRS. Seizures were analyzed by: number of clinical seizures in 24 h, exact duration of clinical symptoms in 24 h, frequency of interictal epileptiform discharges (IEDs) and ictal activity, duration of ictal activity, and IEDs occurring within 24 h in intensive EEG monitoring. Pearson Correlation Coefficient (PCC) was calculated between spectral metabolite alterations and the parameters mentioned above. Results: In the analysis, a negative correlation was found between total (t) NAA values and degree of IEDs in EEG (p = 0.04); a positive correlation was found between Cr levels and duration of seizure symptoms registered by video monitoring (p = 0.01). Conclusions: Our study shows that, in some patients, 1 HMRS is able to refer the severity of TLE. The degree of tNAA reduction in 1 H-MRS, probably indicating neuronal dysfunction, is associated with interictal spiking in intensive EEG monitoring. Duration of seizure symptoms associated with increased Cr peaks probably reflects increased gliosis.

Fiber tracking is increasingly used to plan and guide neurosurgical procedures of intracranial tumors in the vicinity of functionally important areas of the brain. However, valid data concerning the reliability of tracking with respect to the actual pathoanatomical situation are lacking. We retrospectively correlated fiber tracking based on magnetic resonance (MR) DT imaging with the histopathological data of 25 patients with WHO grade II and III gliomas. Fiber tracking using the Fiber Assignment by Continuous Tracking (FACT) method was performed to investigate the integrity of white matter tracts in the surrounding border zone of the lesions. The tracking procedure was stopped when fractional anisotropy (FA) thresholds = 0.1, 0.15, 0.2, 0.25, and 0.3, or a tract turning angle > 60° were encountered. In 9 patients we were able to reconstruct brain fiber tracts at biopsy loci (2–32% tumor infiltration) using an FA threshold of 0.15 and 0.2, but not for a threshold of 0.25 or 0.3. The neurological outcome demonstrated potential tumor cell infiltration of functionally intact brain fiber tracts in the range of 2–8%. These findings may be useful in planning therapeutic approaches to gliomas in the vicinity of eloquent brain regions.

To retrospectively correlate changes in fractional anisotropy (FA) and mean diffusivity in gliomas at diffusion-tensor magnetic resonance (MR) imaging with the degree of tumor cell infiltration determined histologically.The institutional review board required neither ethics committee approval nor patient informed consent for this study. Twenty patients (eight women, 12 men; age range, 18-53 years) with glioma (seven World Health Organization grade II and 13 grade III tumors) underwent diffusion-tensor MR imaging at 1.5 T. Diffusion-tensor data were obtained with an echo-planar imaging sequence with six diffusion directions (b = 1000 sec/mm(2)), isotropic 1.9-mm voxels, and five averages. FA and mean diffusivity values were calculated from diffusion-tensor data. Coregistration with a three-dimensional MR imaging data set (used for stereotactic brain biopsies) enabled correlation of FA and mean diffusivity values with the histopathologic findings total cell number (CN), tumor CN, and percentage tumor infiltration (TI) by using linear, exponential, and logarithmic models. Student t and Mann-Whitney U tests were performed.Histopathologic findings of 77 MR image-guided stereotactic biopsies in all 20 patients were correlated with FA and mean diffusivity values at the biopsy locus. For FA and mean diffusivity, a logarithmic model showed strongest correlation with tumor CN and total CN; a linear model showed strongest correlation with percentage TI. For FA there were negative logarithmic (R = -0.802, P.001) and linear (R = -0.796, P.001) correlations with tumor CN and percentage TI, respectively. For mean diffusivity there were positive logarithmic (R = 0.557, P.001) and linear correlations (R = 0.521, P.001) with tumor CN and percentage TI, respectively. Differences between correlations for FA and mean diffusivity versus tumor CN (P.001) and percentage TI (P.001) were significant.FA is better than mean diffusivity for assessment and delineation of different degrees of pathologic changes (ie, TI) in glioma.

Up to 30% of patients with temporal lobe epilepsy (TLE) remain without remarkable changes in MRI. In this study we investigated the role of (1)H-MR spectroscopy ((1)H-MRS) in lateralizing the affected hemisphere in the mentioned patient group. Twenty-two consecutive patients diagnosed with TLE were investigated by high resolution MRI and (1)H-MRS. We examined the incidence and diagnostic accuracy of temporal metabolite alterations determined by Linear Combination of Model Spectra (L C Model) via water reference. Metabolite values of each hemisphere of TLE patients were compared with healthy controls. Results of metabolite alterations were related to intensive video EEG focus localization. Reduction of N-acetylaspartate + N-acetylaspartyl-glutamate (tNAA) in the affected hemisphere revealed identification in six of nine patients (66%) with unilateral TLE. Group comparison revealed a significant reduction of tNAA (6.1+/-0.8*) in the involved temporal lobe compared with controls (6.67+/-0.4*, P=0.026). Choline levels were significantly increased in the affected hemisphere (1.42+/-0.17*) compared with healthy controls (1.22+/-0.17*, P=0.035). The results of our study show that (1)H-MRS is able to identify the affected hemisphere of MRI negative TLE patients and can be used as an additive tool in multimodal focus localization.

To evaluate proton magnetic resonance (MR) spectroscopic imaging with high spatial resolution for preoperative grading of suspected World Health Organization grades II and III gliomas.Institutional ethics committee approval and informed consent were obtained for control subjects but were not required for the retrospective component involving patients. Twenty-six patients (10 women, 16 men; mean age, 37.5 years) suspected of having gliomas and 26 age- and sex-matched control subjects underwent proton MR spectroscopy. Absolute metabolite concentrations for choline-containing compounds (Cho), creatine (Cr), and N-acetylaspartate (NAA)-N-acetylaspartylglutamate (total NAA [tNAA]) were calculated by using a user-independent spectral fit program. Metabolic maps of Cho/tNAA ratios were calculated, segmented, and used for MR spectroszpcopy-guided stereotactic brain biopsy. Two-sided paired Student t tests were used to test for statistical significance.Significantly lower Cho levels (P = .002) and higher tNAA levels (P = .010) were found in grade II tumors (n = 9) compared with grade III tumors (n = 17). The average Cho/tNAA ratio over the voxels in the tumor center showed a distinct difference (P.001) between grade II and III gliomas at a threshold of 0.8 (with ratios0.8 for grade II). The maximum Cr concentration in the tumor showed a clear-cut threshold between grade III oligodendrogliomas and oligoastrocytomas (Cr level,7 mmol/L) and grade III astrocytomas (Cr level,7 mmol/L; P = .020). Comparison between the histopathologic findings from the MR spectroscopy-guided biopsy samples (76 biopsies from 26 patients) and molar metabolite values in corresponding voxels located at the biopsy sampling points showed a negative linear correlation for tNAA (r = -0.905) and a positive exponential correlation for Cho (r = 0.769) and Cho/tNAA (r = 0.885).Proton MR spectroscopic imaging with high spatial resolution allows preoperative grading of gliomas.

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.

The purpose of our study was to evaluate inter- and intra-subject variability and scan-rescan reproducibility of single-voxel 1H-MR spectroscopy (1H-MRS) in hippocampal structures at 1.5 T field strength. Thirty healthy adults were studied bilaterally by optimized, standardized short echo time single-voxel 1H-MRS (PRESS, TE=30 ms, TR=3000 ms, oblique voxel orientation, voxel size 2 cm3). Spectral analysis and absolute metabolite quantitation of N-acetylaspartate+N-acetylaspartyl-glutamate (tNAA), choline (Cho), creatine (Cr), total glutamate plus glutamine (Glu+Gln) and myo-inositol (Ins) were carried out by LCModel. Inter- and intra-individual reproducibility of these metabolite values were investigated by calculation of mean, standard deviation, coefficient of variation (CV), and by analysis of variance for repeated measurements. The smallest CV in intersubject variability was obtained for tNAA, followed by Cr, Cho, Ins and Glu+Gln. The results of the analysis of variance for repeated measures in inter-subject variability showed a marginal effect of scan repetition for Cr (p=0.063) and Glu+Gln (p=0.082); the rescan of both metabolites showed slightly higher concentrations. No statistical significant effect of scan repetition was seen for tNAA (p=0.913), Cho (p=0.857), and Ins (p=0.826). Rescan led to the same results and gave proof of good reproducibility. Scan-rescan testing in one subject showed comparable results: tNAA (CV=4.8%), followed by Cr, Ins, Glu+Gln and Cho (all CV above 10%).

Nuclear magnetic resonance spectroscopy (1H-MRS) is a non-invasive method in detecting abnormal spectra of various brain metabolites containing N-acetylaspartate (NAA), Choline (Cho), Creatine (Cr), gamma-Aminobutyric acid (GABA) and Glutamate. Technical processing of the MR-systems, improved automated shimming methods and further development of special shim coils increase the magnetic field homogeneity and lead to a better spectral quality and spectral resolution. The handling of the systems becomes more user-friendly and is more likely to be used in routine diagnostics. The 1H-MRS has become a diagnostic tool for assessing a number of diseases of the central nervous system mainly including epilepsies and brain tumours. The role of 1H-MRS in the assessment of epilepsies will probably increase in future. In the following article, the principles of 1H-MRS and an overview of it in the evaluation and treatment of epilepsies with special regard to temporal lobe epilepsies (TLE) has been illustrated.

To elucidate, in a pilot-study, whether noninvasive transcutaneous vagus nerve stimulation (t-VNS) is a safe and tolerable alternative treatment option in pharmacoresistant epilepsy. t-VNS was applied to 10 patients with pharmacoresistant epilepsies. Stimulation via the auricular branch of the vagus nerve of the left tragus was delivered three times per day for 9 months. Subjective documentation of stimulation effects was obtained from patients' seizure diaries. For a more reliable assessment of seizure frequency, we carried out prolonged outpatient video-electroencephalography (EEG) monitoring. In addition, computerized testing of cognitive, affective, and emotional functions was performed. Three patients aborted the study. Of the remaining seven patients, an overall reduction of seizure frequency was observed in five patients after 9 months of t-VNS. The noninvasive t-VNS stimulation is a safe and well-tolerated method for relatively long periods, and might be an alternative treatment option for patients with epilepsy.

Proton magnetic resonance spectroscopy ( 1 H-MRS) is a noninvasive method for detecting brain metabolites. This chapter focuses on techniques and applications of 1 H-MRS and phosphorus ( 31 P) magnetic resonance spectroscopy ( 31 P-MRS) in the diagnosis of the epilepsies. First, basics of 1 H-MRS and 31 P-MRS are provided, and the metabolites of clinical spectroscopy and their clinical significance are listed. Using 1 H-MRS, compounds such as N -acetylaspartate, choline, creatine, myoinositol, γ-aminobutyric acid (GABA), and glutamate can be detected. The second technique ( 31 P-MRS) provides information about the energetics of human tissue, and the chapter describes the alterations in the energetic state of the brain in patients with epilepsy, especially those with temporal lobe epilepsy (TLE). The following clinical topics of 1 H-MRS in the diagnosis of epilepsies are mentioned: (1) applications of 1 H-MRS in the evaluation of extratemporal focal epilepsies in which mainly the frontal lobe is involved; (2) applications of 1 H-MRS in patients with TLE, which includes the majority of studies because TLE is the most common focal epilepsy; and (3) the role of 1 H-MRS in predicting outcomes of epilepsy therapy. In this last section it is shown that the preoperative distribution of metabolite alterations detected by 1 H-MRS is correlated with postoperative outcome. In addition, the technique of intracerebral GABA spectroscopy as a tool for assessment of antiepileptic treatment schedules is described. Intracerebral alterations of GABA under antiepileptic treatment correlate with clinical responder profiles under therapy.

Summary Purpose This study aimed to investigate the potential contribution of morphometric MRI analysis in comparison to other modalities, such as MEG, SPECT and PET, in identifying the epileptogenic focus in patients with cryptogenic epilepsy. Patients and methods Study inclusion was limited to epilepsy patients with a monolobar focus hypothesis, as concluded from EEG/seizure semiology and the best individual concordance rate. Feature maps, generated by the MATLAB ® “morphometric analysis program” (MAP), were evaluated by a neuroradiologist blinded to conventional MRI and the focus hypothesis (MAP 1 ). In addition, the feature maps were also interpreted by simultaneous matching conventional MRI but, again, with the reader having no knowledge of the focus hypothesis (MAP 2 ). Results In 12 out of 51 patients, true-positive findings were achieved (MAP 1 : sensitivity 24%; specificity 96%). The sensitivity of the MAP 1 results was superior extratemporally. After matching conventional MRI, FCD was traced in six of the 12 patients (MAP 2 : sensitivity 12%; specificity 100%). MEG sensitivity was 62%. Sensitivity of interictal and ictal SPECT was 20% and 50%, respectively. PET was not as sensitive extratemporally (19%) as temporally (82%). The greatest correspondence with the best individual concordance rate was noted with PET (14/16; 88%) and MEG (8/10; 80%), followed by interictal (5/8; 63%) and ictal (9/15; 60%) SPECT. Results for MAP 1 were 53% (10/19), and 100% for MAP 2 (6/6). Conclusion Although MAP sensitivity and specificity results are lower in comparison to other modalities, implementation of the technique should be considered first, before arranging any further investigations. The present study results offer guidelines for the implementation, interpretation and concordance of diagnostic procedures.

The interplay of amyloid and mitochondrial function is considered crucial in the pathophysiology of Alzheimer's disease (AD). We tested the association of the putative marker of mitochondrial function N-acetylaspartate (NAA) as measured by proton magnetic resonance spectroscopy within the medial temporal lobe and cerebrospinal fluid amyoid-β42 (A{beta}42), total Tau and pTau181. 109 patients were recruited in a multicenter study (40 mild AD patients, 14 non-AD dementia patients, 29 mild cognitive impairment (MCI) AD-type patients, 26 MCI of non-AD type patients). NAA correlated with A{beta}42 within the AD group. Since the NAA concentration is coupled to neuronal mitochondrial function, the correlation between NAA and Aβ42 may reflect the interaction between disrupted mitochondrial pathways and amyloid production.

Long-term epilepsy associated tumors (LEATs) are a frequent cause of drug-resistant partial epilepsy. A reliable tumor diagnosis has an important impact on therapeutic strategies and prognosis in patients with epilepsy, but often is difficult by magnetic resonance imaging (MRI) only. Herein we analyzed a large LEAT cohort investigated by 18fluoroethyl-L-tyrosine-positron emission tomography (FET-PET).Thirty-six patients with chronic partial epilepsy and a LEAT-suspect MRI lesion were analyzed by FET-PET using visual inspection and quantitative analysis of standard uptake values (SUV). PET results were correlated with clinical and histopathologic data.FET-PET study was positive in 22 of 36 analyzed lesions and in 14 of 22 histologically verified LEAT lesions. The precise World Health Organization (WHO) tumoral entity was not predicted by FET-PET. Notably, FET uptake correlated strikingly with age at epilepsy onset (p = 0.001). Further correlations were seen for age at surgery (p = 0.007) and gadolinium-contrast enhancement on MRI (p0.05).FET-PET is a helpful tool for LEAT diagnosis, particularly when MRI readings are ambiguous. FET uptake, which is likely mediated by the l-amino acid transporter (LAT) family, might indicate a principally important biologic property of certain LEATs, since LAT molecules also are involved in cell growth regulation.

Background and Purpose: In conventional MR imaging, it is often diffi cult to delineate the heterogeneous structure of gliomas. Proton magnetic resonance spectroscopic imaging ( 1 H- MRSI) is a noninvasive tool for investigating the spatial distribution of metabolic changes in brain lesions. The aim of this study was to assess the improvements in delineation of gliomas based on segmentation of metabolic changes measured with 1 H-MRSI. Material and Methods: Twenty patients with gliomas (WHO grade II and III) were examined using a standard 1 H-MRSI sequence. Metabolic maps for choline (Cho), N-acetyl-aspartate (NAA) and Cho / NAA ratios were calculated and seg- mented based on the assumption of a Gaussian distribution of the Cho / NAA values for normal brain. Areas of hyperintensity on T2-weighted (T2w) MR images were compared with the areas of the segmented tumor on Cho / NAA maps. Ste- reotactic biopsies were obtained from the MRSI / T2w diff erence areas. Results: In all patients, the segmented MRSI tumor areas were greater than the T2w hyper- intense areas, on average, by 20 % (range 6 - 34 % ). In nine patients, biopsy sampling from the MRSI / T2w diff erence areas showed tumor infi ltration ranging from 4 - 17 % (mean 9 % ) tumor cells, in the areas detected only by MRSI. Discussion and Conclusion: Our method for automated segmentation of the lesion-related metabolic changes achieved signifi cantly improved delineation for gliomas compared to routine clinical methods. We demonstrate that this method can improve delineation of tumor borders compared to routine imaging strategies in clinics. Metabolic images of the segmented tumor may thus be helpful for therapeutic planning.

The objective of this study was to determine if levetiracetam (LEV) modulates brain γ-aminobutyric acid (GABA) in patients with epilepsy.Occipital GABA was assessed by protein magnetic resonance spectroscopy (¹H-MRS) in 16 patients with focal epilepsy at baseline and following the initiation of oral administration of LEV as monotherapy. Responder profiles were calculated as percentage of baseline seizure frequency. Alterations of GABA/Cr (creatine) of baseline measurements compared to GABA/Cr under LEV therapy were analyzed by Student's t-test for paired samples.After administration of LEV, partial seizure reduction (50%) was noticed in 5 of 16 patients (31%; 7 of 16 (44%) patients turned out to be free of seizures. Patients with 50-100% seizure reduction under LEV titration were referred to as LEV responders. Of the 32 GABA spectra, only 22 (approximately 70%) yielded a result that met the criteria for spectral quality; therefore, GABA/Cr data from only seven patients were paired. A significant increase of GABA/Cr during titration with LEV was noted in patients responding to LEV (n = 5; p = 0.007). No differences in baseline GABA/Cr levels were detected between patients with and without previous antiepileptic treatment (p = 0.74).The increasing GABA/Cr levels under drug titration only in LEV-responding epilepsy patients suggest a more complex and indirect influence of LEV on the GABAergic system.

Mesial temporal lobe epilepsy (MTLE) constitutes a heterogenic entity with different clinical histories, pathomorphological hippocampal findings and varying postoperative outcome.64 patients with MTLE, scheduled for hippocampal resection, were included. Initial precipitating injuries (IPI), structural and functional findings and neuropathological classification of hippocampal specimens were related to prediction of surgical outcome.Patients with severe hippocampal sclerosis (mesial temporal sclerosis (MTS) type 1b) became completely seizure free (80% Engel Ia) significantly more often compared with approximately 40% of seizure freedom in other types of MTS or in patients without hippocampal cell loss (non-MTS), irrespective of the extent of hippocampal resection. Age at IPI was found to be related to MTS variants (p0.01) and significantly correlated with cell loss in the CA1 sector and the dentate gyrus (p0.05). Presurgical MRI discriminated between MTS and non-MTS, but did not discriminate between different MTS subtypes. The most reliable predictors of MTS type 1b were the Wada memory scores combined with interictal and ictal EEG.A particular cohort of MTLE patients benefit most from surgical treatment. These patients are clinically best recognised as presenting with (1) very early IPI; (2) a silent period of about 5 years; (3) unequivocal unilateral EEG localisation; (4) MRI signs of MTS; and (5) Wada Test indicates contralateral memory compensation and ipsilateral reduced memory capacity. MTS type 1b, characterised by severe cell loss in all hippocampal subfields including the dentate gyrus, and associated with optimal postoperative seizure control, was preoperatively clinically best differentiated from other MTS types by the Wada Memory Test.

Gamma aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the human brain. It plays a decisive role in a variety of nervous system disorders, such as anxiety disorders, epilepsy, schizophrenia, insomnia, and many others. The reproducibility of GABA quantification results obtained with a single-voxel spectroscopy J-difference editing sequence with Point Resolved Spectroscopy localization (MEGA-PRESS) was determined on a 3.0 Tesla MR scanner in healthy adults. Eleven volunteers were measured in long- and short-term intervals. Intra- and inter-subject reproducibility were evaluated. Internal referencing of GABA+ to total creatine (tCr) and water (H(2)O), as well as two different post-processing methods for the evaluation (signal integration and time-domain fitting) were compared. In all subjects lower coefficient of variation and therefore higher reproducibility can be observed for fitting compared to integration. The GABA+/tCr ratio performs better than the GABA+/H(2)O ratio or GABA+ without internal referencing for both fitting and integration (GABA+/tCr: 13.3% and 17.0%; GABA+/H(2)O: 15.0% and 17.8%; GABA+: 19.2% and 21.7%). Four-day measurements on three subjects showed higher intra- than inter-subject reproducibility (GABA+/tCr approximately 10-12%). With a coefficient of variation of about 13% for inter-subject and 10-12% for intra-subject variability of GABA+/tCr, this technique seems to be a precise tool that can detect GABA confidently. The results of this study show the reproducibility limitations of GABA quantification in vivo, which are necessary for further clinical studies.

To prospectively quantify differences in age-related changes in the diffusivity parameters and fiber characteristics between association, callosal, and projection fibers.This study was approved by the institutional review board, and informed consent was obtained. Diffusion-tensor imaging data with an isotropic voxel size of 1.9 mm(3) were acquired at 3 T in 38 healthy volunteers (age range, 18-88 years; 18 women). Quantitative fiber tracking was used to calculate fractional anisotropy (FA) and mean diffusivity values, eigenvalues (lambda(1), lambda(2), and lambda(3)), the number of fiber projections, and the number of fiber projections per voxel for three-dimensional reconstructed association, callosal, projection, and total brain fibers. Bivariate linear regression models were used to analyze correlations. Significant differences between correlations were assessed with the Hotelling-Williams test.For FA, the strongest degradation in association fibers and no significant changes in projection fibers were observed. The difference in correlation was significant (P = .002). The number of fiber projections and the number of fiber projections per voxel showed strong to moderate negative correlations that were dependent on age (P.001) in the three fiber structures and total brain fibers, with the exception of the number of fiber projections per voxel in projection fibers, which showed no significant correlation. The decrease in the number of fiber projections was significantly greater (P = .043) in projection fibers than in total brain fibers, whereas the decrease in the number of fiber projections per voxel was significantly weaker (P = .005). Association fibers showed the largest changes per decade of age for FA (-1.13%) and for the number of fiber projections per voxel (-4.7%), whereas callosal fibers showed the largest changes per decade of age for the number of fiber projections (-10.4%).Quantitative fiber tracking enables identification of differences in diffusivity and fiber characteristics due to normal aging.

We assessed (1)H-MRS as a screening tool for detection of hippocampal sclerosis in patients with temporal lobe epilepsy (TLE). (1)H-MRS was carried out in the hippocampus of 23 patients with unilateral TLE. Metabolite alterations detected by (1)H-MRS correlated with degree of segmental neuronal cell loss and amount of astrogliosis. Positive correlation was found between total N-Acetylaspartate (tNAA) reduction and neuronal density in hippocampal CA1 (P < 0.001), CA3 (P = 0.015), and CA4 subfields (P = 0.031) and the dentate gyrus (P = 0.006). Neuronal cell loss in CA1 turned out to be the most predictive and only significant variable for tNAA reduction (P = 0.027). The association between myo-inositol (m-Ins) and astroglial glial fibrillary acidic protein (GFAP) expression revealed significantly increased m-Ins concentrations associated with diffuse astrogliosis (m-Ins = 6.4 +/- 1.1 institutional units) compared with gliosis restricted to isolated sectors of the hippocampus (i.e. hilus) (m-Ins = 5.2 +/- 1.2 institutional units) (P = 0.039). A negative correlation was found between m-Ins and neuronal loss in the CA4 subfield of the hippocampus (P = 0.028). Our results support (1)H-MRS as a suitable non-invasive method for preoperative identification of hippocampal sclerosis in patients with TLE. The extent of tNAA reduction correlates with hippocampal neuronal cell density. Furthermore, m-Ins is associated with the extent of hippocampal astrogliosis.

Volumetric approaches for the analysis of hippocampal structures (HS) are required for the diagnosis of different diseases. In order to diagnose, evaluate and compare patient datasets, standardized and reproducible analysis supports physicians in clinical routine and research. In this paper, we present a practical application for volumetry in MR volume datasets. The approach combines the semiautomatic linear registration of an atlas based polygonal model with T1-weighted (based on inversion recovery protocol) and T2-weighted MR images and the automatic volumetric assessment of diseased structures. The approach was evaluated and compared with manually segmented MR datasets.

Pharmacoresistant focal epilepsies due to periventricular nodular heterotopia are a diagnostic and therapeutic challenge because of the need of invasive presurgical diagnostics and the selection of an optimal surgical approach. Invasive investigations in previous studies showed that focal epileptic activity can be correlated predominantly either with one of the nodular heterotopia or with neocortical epileptogenic zones distant to the periventricular nodules. Up to now, invasive recordings were required for localization of epileptic activity and its correlation to heterotopia. The following case presentation reports on a non-invasive approach using magnetic source imaging (MSI) combined with intraoperative ECoG. MSI combines preoperative data from magnetic resonance imaging (MRI) with magnetoencephalography (MEG). The MSI data for definition of the localization of the epileptic activity and functional important areas were coregistered with the intraoperative high-field-MRI and diffusion tensor imaging-based fiber tracking (DTI) of the visual pathway using a neuronavigational system. A neuronavigation-guided surgical resection of the epileptogenic area was performed leaving the heterotopia and the visual tract fibers intact. Postoperatively preservation of the visual fields was documented and the frequency of seizures was markedly reduced.

Streamline representation of major fiber tract systems along with high-resolution anatomical data provides a reliable orientation for the neurosurgeon. For intraoperative visualization of these data either on navigation screens near the surgical field or directly in the surgical field applying heads-up displays of operating microscopes, wrapping of all streamlines of interest to render an individual object representing the whole fiber bundle is the most suitable representation. Integration of fiber tract data into a neuronavigation setup allows removal of tumors adjacent to eloquent brain areas with low morbidity.