[Show abstract][Hide abstract] ABSTRACT: Alpha-[11C]methyl-L-tryptophan (alpha-MTrp) positron emission tomography (PET) is a promising tool in the localization of the epileptogenic area in selected group of focal epilepsy patients. Electrophysiological evidence suggests the involvement of the neocortex in periventricular nodular heterotopia (PVNH).
To determine whether alpha-MTrp PET can detect neocortical changes in patients with PVNH.
Four patients (2 male, mean age 28, range 23-35 years) with PVNH and intractable seizures were studied. The functional image in each patient was compared with those from 21 healthy controls (mean age 34.6 +/- 14.2 years) by using statistical parametric mapping (SPM). The location of increased alpha-MTrp uptake was compared with the location of the EEG focus. A significant cluster was defined as a cluster with a height p = 0.005 and an extent threshold 100.
Alpha-MTrp PET revealed increased cortical uptake in two of four patients. The area of increased alpha-MTrp uptake in one patient was widespread. In the other patient, the area of increased uptake did not include the region where most seizures were generated on EEG. alpha-MTrp PET did not show increased uptake in the heterotopic nodules in any of the patients.
Alpha-MTrp PET suggests abnormal metabolism of tryptophan in the neocortex. The increased uptake may be diffuse and may not co-localize with the EEG focus. This preliminary study suggests that alpha-MTrp PET may be useful, in conjunction with other evaluations, in localizing epileptic focus in patients with PVNH and refractory seizures.
[Show abstract][Hide abstract] ABSTRACT: The main objective of this investigation was to test the hypothesis that brain serotonin (5-HT) synthesis, as measured by trapping of alpha-[(11)C]methyl-L-tryptophan (alpha-MTrp) using positron emission tomography (PET), can be modulated by changes in blood oxygen. The study involved six healthy participants (three male and three female), who breathed a 15% or 60% oxygen mixture starting 15 min before the injection of tracer and continuing during the entire acquisition period. Participants were injected with up to 12m Ci of alpha-MTrp. Two sets of PET images were acquired while the participants were breathing each of the oxygen mixtures and, after reconstruction, all images were converted into brain functional images illustrating the brain trapping constant K(*) (microL/g/min). The K(*) values were obtained for 12 regions of interest outlined on the magnetic resonance images. The K(*) values obtained at high and low blood oxygen content were compared by paired statistics using Tukey's post hoc correction. As there were no difference in plasma tryptophan concentrations, these K(*) values are directly related to regional 5-HT synthesis. The results showed highly significant increases (50% on average) in brain serotonin synthesis (K(*) values) at high (mean value of 223+/-41 mmHg) relative to low (mean value 77.1+/-7.7 mmHg) blood oxygen levels. This suggests that tryptophan hydroxylase is not saturated with oxygen in the living human brain and that increases in blood oxygen can elevate brain serotonin synthesis.
Neurochemistry International 01/2006; 47(8):556-64. · 2.66 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Serotonin (5-HT) plays an important role in the pathophysiology of irritable bowel syndrome (IBS). Using alpha-[(11)C]methyl-L-tryptophan-positron emission tomography (PET), it was demonstrated that brain 5-HT synthesis is increased in patients with IBS, in a gender-specific manner. The aims of the study were to evaluate the effects of alosetron on brain 5-HT synthesis in patients with IBS. Six male and five female non-constipation-predominant IBS patients were enrolled. The subjects received alosetron or a placebo for 14 days, separated by a 2-week washout period. On day 14, rectal distensions commenced just prior to the PET scan (which was performed for 80 min), and continued for 20-min periods. The functional images were analysed with SPM99. Alosetron vs placebo treatments, in a randomized, double-blinded, crossover manner, were studied. 5-HT synthesis was greater in several regions in the males than in the females during the alosetron treatment, whereas there was no region in which the females had greater synthesis. There were significant gender-treatment interactions of synthesis in the cingulate gyrus, caudate nucleus, globus pallidus, and cerebellum. The gender differences in the effect of alosetron on brain 5-HT synthesis may be related to the gender differences in the efficacy of alosetron.
Neurogastroenterology and Motility 05/2005; 17(2):212-21. · 2.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Usefulness of 11C-Methionine PET in the Diagnosis of Benign Tumors Presenting with Temporal Lobe Epilepsy. * TaketoshiMaehara, * TadashiNariai, † NobutakaArai, ‡ KensukeKawai, ‡ HiroyukiShimizu, § KenjiIshii, § KiichIshiwata, and * KikuoOhno ( Neurosurgery, Department of Brain Medical Science, Tokyo Medical and Dental University; Bunkyo-ku ; Department of Clinical Neuropathology, Tokyo Metropolitan Institute for Neuroscience, Fuchu ; Department of Neurosurgery, Tokyo Metropolitan Neurological Hospital; Fuchu ; Tokyo Metropolitan Institute of Gerontology; Itabashi, Tokyo, Japan ). Purpose: We assessed the diagnostic value of 11C-methionine (MET)-PET in the differential diagnosis of benign tumors presenting with temporal lobe epilepsy. Methods: This series consisted of seven patients who had a type of complex partial seizure (CPS) associated with temporal lobe epilepsy, and were found to have benign tumors in the temporal lobe. They included three males and four females, ranging in age from 13 to 48 years. The age at seizure onset ranged from 6 to 26 years old, and the time to operation ranged from 2 to 28 years. High-resolution magnetic resonance imaging (MRI) with a 1.5 T magnet revealed organic lesions in the temporal lobes. MET-PET was performed in all seven patients, and 18F-fluoro-2-deoxy-glucose (FDG)-PET was performed in four patients. After presurgical examinations including repeated EEGs, video-EEG monitoring, and neuropsychological testing, three patients underwent invasive monitoring for focus detection and functional mapping. All seven patients underwent tumor resection together with focus excision under intraoperative ECoG guidance. Using the image analysis software Dr. View (Asahi Kasei Joho, Tokyo, Japan) on a personal computer, the region of interests (ROIs) were placed on the tumor and contralateral brain over the MRI, and then transferred to the PET images co-registered with MRI. The uptake of tracers was evaluated by the lesion-to-contralateral ratio (L/C ratio) and the standardized uptake value (SUV), a value calculated by dividing the brain activity of tracer per volume of brain by the injected activity of tracer per body weight. Surgical specimens were examined to investigate the tumor histology and Ki-67 labeling index. Microdygenesis of the resected foci was also examined. Statistical significance of differences in MET uptake between patients with dysembryoplastic neuroepithelial tumor (DNT) and those with ganglioglioma and gliomas was analyzed using the SUV and L/C ratio by the Student's t test. Results: After surgery, six patients remained seizure-free and one achieved a rare-seizure outcome for at least 6 months. The tumor was identified as high MET uptake lesion in three cases and was not depicted on MET-PET in four patients. Among the four patients who underwent FDG-PET, two patients showed high MET uptake in the tumor. However, all four patients showed low glucose uptake in the tumor and surrounding cerebral cortex. Pathological examination demonstrated DNTs in four cases, ganglioglioma in one case, low grade astrocytoma in one case, and pleomorphic xanthoastrocytoma (PXA) in one case. One patient with DNT showed a number of ectopic neurons in the white matter, a finding compatible with microdysgenesis. Ki-67 labeling index was 4% in one patient with DNT and 5% in one patient with PXA. The labeling index of the remaining five patients was 1% or lower. While four patients with DNT did not show visually high MET uptake, ganglioglioma and gliomas of the remaining three patients were identified as high-MET-uptake-lesions. MET uptake was significantly higher in patients with gliomas than in patients with DNT (SUV: P = 0.045, L/C ratio: P = 0.0079). The Ki-67 labeling index was not related to MET uptake expressed in SVU (P = 0.91) and L/C ratio (P = 0.38). Conclusion: In the seven patients with temporal lobe epilepsy and benign tumors in this study, we observed a high MET uptake in brain gliomas but not in DNTs. This high MET uptake was not related to the proliferation capacity measured by Ki-67 labeling index. MET-PET was useful for the differential diagnosis of DNT.
[Show abstract][Hide abstract] ABSTRACT: To determine whether metabolism in the brain serotonergic system, including the kynurenine pathway, is involved in temporal lobe epilepsy (TLE).
The authors studied 14 patients with intractable TLE by PET using alpha-[11C] methyl-L-tryptophan (alpha-MTrp) and 2-[18F]-fluoro-deoxy-glucose (FDG) and compared results with 21 healthy control subjects who had alpha-MTrp PET studies. Seven patients had unilateral hippocampal atrophy (HA), and seven had normal hippocampal volumes (NV). The regional uptake constant (K*) for alpha-MTrp and regional FDG uptake were calculated in regions with high serotonergic innervation, including the hippocampus, amygdala, lateral temporal lobe, frontal lobe, thalamus, lenticular nucleus, and cingulate cortex.
A significant increase of alpha-MTrp uptake was observed in the hippocampus ipsilateral to the seizure focus in seven TLE patients with NV compared to seven patients with HA as well as to healthy controls. In patients with TLE, glucose utilization in the lateral temporal lobe ipsilateral to the seizure focus was correlated negatively with K* for alpha-MTrp in the ipsilateral hippocampus and positively with K* in the ipsilateral lenticular nucleus and cingulate cortex. Glucose utilization in the frontal lobe ipsilateral to the seizure shows a reduction in the glucose utilization which relates to the increase in the alpha-MTrp uptake in the ipsilateral lateral temporal lobe.
This study demonstrates dysfunction of the serotonergic system, which could include metabolism through the kynurenine pathway in TLE patients with normal hippocampal volumes. alpha-MTrp PET studies might be useful for lateralizing the epileptic focus in TLE patients with normal hippocampal volumes.
[Show abstract][Hide abstract] ABSTRACT: The main objective of described work was a generation of the functional images of the brain trapping constant (K*; μL/g/min) of -methyl-L-tryptophan, an index of 5-HT synthesis, which under some assumptions is related to the se-rotonin synthesis. Comparisons of the regional K* calculated by the Patlak approximation, non-linear fitting and the line-arized form of the non-linear operational equation were made and discussed. In addition a contrast between the white and gray matter K* values was evaluated by different methods. Results presented suggest that the linearized form of the opera-tional equation yields the best gray to white matter contrast. It was also shown that with this calculation approach, as was shown before for the Patlak approximation, the use of the venous sinus-venous blood normalized input function instead of the arterial input function is satisfactory. Also results show that the error of the K* estimates is smaller than those in the Patlak estimates, when the linearized solution of the model equation is used. Simulation results indicate that the coeffi-cient of variation for K* is smaller than some errors for the equation parameters.