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Objective The current study examined metabolic alterations associated with a positive response to olanzapine and identified brain regions associated with treatment-related improvement of symptoms in neuroleptic-naive first-episode schizophrenic patients using [18F]fluoro-deoxy-glucose positron emission tomography analysis. Methods Neuroleptic-naive first-episode schizophrenic patients who showed good or poor clinical responses to olanzapine were assessed using the Positive and Negative Syndrome Scale. Data were analyzed using statistical nonparametric mapping. Results Before treatment, responders showed significantly increased metabolism in the superior temporal gyrus and cerebellum compared with healthy controls. Glucose metabolism in responders was significantly increased after treatment in the left precentral gyrus, left postcentral gyrus, and left paracentral lobule, and significantly decreased in the left hypothalamus. An analysis of the Positive and Negative Syndrome Scale symptoms associated with olanzapine treatment revealed that “suspiciousness/persecution” scores were positively correlated with metabolic changes in the right superior frontal gyrus. Conclusions These findings provide evidence of the neural mechanisms underlying the effects of olanzapine on metabolism in the early stages of schizophrenia.

Background: Mutations in the presenilin-1 gene (PSEN1) have been identified in autosomal dominant early-onset cases of Alzheimer’s disease (AD). Aims: To investigate different clinical phenotypes of siblings possessing the same heterozygous P264L mutation in the PSEN1 gene. Methods: We evaluated clinical features, neuroimaging results, and neuropsychological examinations. The PSEN1 gene and other dementia-related gene mutations were screened. Results: We clinically diagnosed the proband as atypical AD with frontotemporal dementia features and diagnosed the elder brother of the proband as typical AD, based on neuropsychological symptoms and a brain imaging examination including amyloid imaging data. A heterozygous P264L mutation in the PSEN1 gene was identified in both siblings. Conclusion: This study is one of few reports of AD siblings possessing the same mutation but exhibiting different clinical phenotypes in a Japanese family possessing a P264L mutation in the PSEN1 gene. The current results suggest that unknown modifiers, including both genetic and epigenetic factors, may alter the pathological and clinical phenotypes of a genetically predetermined disease.

The conventional delayed scan in dual phase of thallium-201 ((201)Tl) single-photon emission computed tomography (SPECT) is useful for estimating the viability of non-small-cell lung cancer (NSCLC). However, the influence of tumor blood flow cannot be ignored by the scan at 4 h after the tracer injection. For the purpose of improving the diagnostic capability and for clarifying the association between (201)Tl uptake and proliferative activity, we investigated the usefulness of super-delayed scan obtained at 24 h in triple-phase (201)Tl SPECT.A total of 122 patients with lung nodule, 106 of NSCLC and 16 of benign nodule, were given (201)Tl SPECT before the tumor resection. Early image (15 min), delayed image (4 h), and super-delayed image (24 h) were obtained after intravenous injection of (201)Tl chloride (111 MBq). On the each SPECT image, regions of interest (ROIs) were placed over the tumor contour (T) and contra-lateral normal lung tissue (N) area on one transverse view clearly defined lesions, and T/N ratio on the early image (ER), the delayed image (DR), and the super-delayed image (sDR), and retention indexes (RI and sRI) were calculated. All patients underwent subsequent surgical excision, and the specimens were immunostained for Ki-67 and CD34. The proliferative capability was measured as a percentage of positive nuclear area for Ki-67 (MIB-1 index). The angiogenesis was measured density of positive micro-vessels for CD34 (micro-vessel density, MVD). Correlation analysis was performed to evaluate the relationship between the MIB-1 index, MVD, and SPECT parameters.The diagnostic accuracy of sDR in the differential of NSCLC was higher than that of DR (83.6% vs. 91.8%). Both DR and sDR were positively correlated with MIB-1 index. The correlation coefficient was higher in sDR (0.53 vs. 0.69). The MIB-1 index of the increasing pattern (RIsRI) group was significantly higher (P0.001) than that of the decreasing pattern (RIsRI) group.The super-delayed scan in the triple-phase (201)Tl SPECT is more useful than conventional delayed scan for both the diagnostic capability and assessing proliferation of NSCLC.

Positron emission tomography (PET) with fluorodeoxyglucose-F18 was used to examine glucose metabolism in patients with late-onset major depression, all hospitalized non-responders to antidepressant medication. The three-dimensional stereotactic surface projection (3D-SSP) method provided 3D-SSP images and relative metabolic values with minimal partial volume effects. The 3D-SSP score map showed decreased relative metabolism in the prefontal, cingulate and parietal regions in both hemispheres, and in the temporal region on the right, and increased relative metabolism in the occipital pole, vermis, cerebellum, dorsal-frontal, central convexity areas and basal ganglia in both hemispheres in patients compared with controls. The ratio of the parietal to occipital values in right plus left hemispheres was significantly decreased. Correlation coefficients of the anterior cingulate-primary sensorimotor, posterior cingulate-primary sensorimotor and occipital-media frontal in both hemispheres, of the frontal-primary sensorimotor, occipital-parahippocampal, primary visual-medial frontal and parahippocampal-amygdala in the right, and the frontal-vermis, parietal-thalamus, temporal-vermis, occipital-putamen, primary visual-putamen, thalamus-vermis and thalamus-cerebellum in the left were significantly different in patients compared with controls. Patients with late-onset depression who were treatment non-responders showed alterations not only in limbic-cortical circuits, but also in a wider network of thalamo-cortical circuits.

Purpose Firstly, to assess the effect of percutaneous endoscopic gastrostomy (PEG) tube placement on gastric emptying, gastrointestinal (GI) tract motility and the rate of gastroesophageal reflux (GER). Secondly, to confirm whether correlations exist between drug absorption behaviour and GI tract motility using the combination method of absorption function analysis with the motility study. Methods Subjects comprised 11 patients with neurological dysphagia. Gastric-emptying scintigraphy was performed both before PEG via nasogastric tube feeding and after PEG placement. After fasting for more than 8 h, each patient was administered 111 MBq of 99mTc-labelled diethylenetriaminepentaacetic acid (DTPA) with a 100 ml liquid meal via a nutrition tube. Dynamic imaging was performed immediately after administration of a radiolabelled liquid meal for a 1 h period and static imaging was performed after 1, 2, 3 and 6 h. Gastric emptying half-time (T50) was calculated in each patient, and GER ratio and GI transit rate were also evaluated. Simultaneously, we administered 10 mg of famotidine in six of the 11 patients and measured serum concentrations of famotidine at 0, 1, 2, 3 and 6 h. Using the time-concentration curve of famotidine, the maximum concentration of famotidine (Cmax) and area under the curve of famotidine (AUCf) were calculated for each patient. Results In seven of 11 patients, T50 changed after PEG placement, but not significantly. The GER ratio was significantly decreased and complicated pneumonia improved after PEG placement. GI transit rate for each GI segment was unchanged after PEG placement. Significant linear correlations were identified between T50 and both Cmax and AUCf. Conclusion Gastric-emptying scintigraphy with Tc-DTPA was effective in the evaluation of GI transit before and after PEG, as well as in assessing GER. Motility and famotidine absorption were maintained after PEG placement. Significant linear correlations were found between T50 and both Cmax and AUCf. These findings suggest that drug absorption may have some relationship between T50. The result may be more reliable with a larger population.

PURPOSE To investigate whether 201Tl uptake is associated with cell proliferation and angiogenesis in non-small-cell lung carcinoma (NSCLC). METHODS Eighty-four patients with scheduled NSCLC underwent 201Tl single photon emission computed tomography (SPECT) imaging: 15 min (early scan) and 240 min (delayed scan) after intravenous injection of 111 MBq of 201Tl chloride. 201Tl indices were calculated on early images (early ratio: ER) and delayed images (delayed ratio: DR). The retention index (RI) was also calculated from these two parameters. Using surgically resected cancer specimens (54 adenocarcinoma, 24 squamous cell carcinoma (SCC), six large-cell carcinoma), immunohistochemical stains for both Ki-67 (MIB-1 index) and CD34 were performed to examine the proliferative activity and the micro-vessel density (MVD), respectively. RESULTS The mean value of 201Tl index was 1.69+/-0.77 (ER) and 2.31+/-1.08 (DR). The average RI was 42.6+/-42.9%, respectively. Both DR and RI positively correlated with MIB-1 index (r = 0.68, P < 0.05 and r = 0.52, P < 0.05). When we analyse adenocarcinoma and SCC separately, there was a significant positive correlation (r = 0.62, P < 0.05) between RI and MIB-1 index in adenocarcinoma but not in SCC (r = 0.20, P = NS). The value of ER positively correlated with MVD (r = 0.75, P < 0.05). It demonstrated strong positive correlation with both histological types (adenocarcinoma: r = 0.80, P < 0.05, SCC: r = 0.66, P < 0.05). CONCLUSION 201Tl SPECT imaging is effective non-invasive method for assessing both the proliferation and the angiogenesis in NSCLC. Both DR and RI are useful indicators for assessing cancer cell proliferation in lung adenocarcinoma. ER is a useful marker for assessing the tumour angiogenesis in NSCLC.