Hideki Otsuka

Brain metabolites in the hippocampus-amygdala region and cerebellum in autism : an 1H-MR spectroscopy study

Abstract Histological abnormalities of the brain in autism have been investigated extensively. We studied metabolites in the hippocampus-amygdala (HA) region and cerebellum. We examined the right HA region and left cerebellar hemisphere of 27 autistic patients 2–18 years old, 21 boys and 6 girls and 10 normal children 6–14 years old, 4 boys and 6 girls, using the STEAM sequence. This sequence was used to minimise the influence of relaxation times. The N-acetyl aspartate (NAA) concentration was significantly lower (P = 0.042) in autistic patients than in normal children (9.37 and 10.95 mM, respectively). There was no significant difference in other metabolites. The correlation coefficient (r value) of NAA between the HA region and cerebellum was 0.616. The decreased NAA concentration may be due to neuronal hypofunction or immature neurons. The NAA concentration in the HA region and cerebellum may be related, because of neuronal circuits or networks.

The impact of FDG-PET in the management of patients with salivary gland malignancy

ObjectiveThe aim of this study was to evaluate the impact of FDG-PET in the management of patients with salivary gland malignancy.Patients and MethodsWe performed 45 FDG PET studies in 31 patients with salivary malignant tumors, using PET (33 studies) and PET/CT (12 studies). Patients comprised 21 males and 10 females with a mean age of 69 y (range 38–89). Nineteen patients had a single study, ten patients had 2 and two patients had 3 studies. Twelve studies were performed for initial staging and 33 studies for restaging. Four patients of the initial staging group were restaged with PET after therapy. Histology consisted of 8 adenocarcinomas, 8 squamous cell carcinomas, 4 adenoid cystic carcinomas, 4 carcinoma ex pleomorphic adenomas, 2 mucoepidermoid carcinomas, 2 poorly differentiated carcinomas, 1 salivary duct carcinoma, 1 lymphoepithelial carcinoma and 1 melanoma. PET findings were reviewed with the clinical and radiologic findings and the impact of PET on staging and patient management was determined.ResultsIn the initial staging group, all 12 primary lesions (100%) showed positive FDG uptake (5 squamous cell carcinomas, 2 adenocarcinomas, 2 poorly differentiated carcinomas, 1 carcinoma ex pleomorphic adenoma, 1 salivary duct carcinoma, 1 lymphoepithelial carcinoma). Three patients (25%) had FDG positive distant disease (liver, bone, lymph nodes); surgery was canceled and therapy changed to chemoradiation. One patient (9%) with no FDG uptake in the neck nodes avoided a planned neck dissection. In the restaging group (33 studies in 23 patients), 5 patients (22%) had FDG positive distant disease, which changed the treatment from surgery to chemoradiation or other. A second primary lesion was detected in one patient (4%). One patient (4%) with clinically suspected recurrence was able to avoid other invasive procedures because of the negative PET. Overall, FDG PET resulted in a major change in management in 11 of 31 patients (35%).ConclusionThis study shows that FDG PET has a significant impact on the management of patients with salivary malignant tumors in both the initial staging and restaging.

Multivariate analysis of regional metabolic differences in normal ageing on localised quantitative proton MR spectroscopy

Abstract We performed multivariate analysis of regional differences and normal age-related changes in metabolites in the lentiform nucleus and frontal lobe, as measured by proton MRS. The cerebrospinal fluid (CSF) in the measurement area was estimated and the metabolite concentration adjusted. The concentration of N-acetylaspartate (NAA) in the lentiform nucleus decreased with ageing (F = 4.11, P < 0.01), but that in the frontal lobe did not change (F = 0.93, P = 0.45). This is in marked contrast with pathological dementia, such as Alzheimers disease. In this multivariate analysis, the normal change in metabolism with ageing differed depending on the cerebral region, suggesting that metabolite concentrations, especially that of NAA may be useful metabolic indices for discriminate normal ageing from pathological dementia.

FDG-PET/CT findings of sarcomatous transformation in neurofibromatosis: a case report

We herein report FDG-PET/CT findings of sarcomatous transformation in a patient with neurofibromatosis type 1 (NF-1). About 5% of patients with NF-1 develop sarcomatous transformation of a malignant peripheral nerve sheath tumor which arises from plexiform neurofibromas and is often associated with a poor prognosis. Morphologic imaging techniques such as Magnetic Resonance Imaging (MRI) and Computed Tomography (CT) are the standard methods to define the anatomic extent of the tumor, although tumor heterogeneity prevents reliable differentiation between benign and malignant lesions. The degree of fluoro-deoxyglucose (FDG) uptake correlates with histologic grade in neurogenic tumors in NF-1 patients. Our patient had a huge mass in the left gluteus area with a large nearly circular focus of increased FDG uptake in the tumor. The mass had a photopenic center. The maximum Standard Uptake Value (SUVmax) of this mass was 6.6. There was CT evidence of invasion of the left iliac wing, left acetabulum, and left superior pubic ramus; however there was no increased FDG uptake in these areas on the PET study. We surmised that the high FDG uptake indicated a high grade sarcoma, which was confirmed histologically. There was also a focal region of increased uptake in the L5 vertebral body, correlating with the CT hypodense lesion, with 2.9 SUVmax. FDG-PET/CT can identify sarcomatous change from benign neurogenic tumor with minimal misregistration, and can also detect metastatic disease. This case illustrates the importance of evaluating both metabolic and morphologic abnormalities to be able to formulate a proper treatment plan. This information can be obtained in a single session, using PET/CT.

18F-fluorodeoxyglucose positron emission tomography/computed tomography is useful in postoperative follow-up of asymptomatic non-small-cell lung cancer patients

OBJECTIVES Postoperative follow-up and surveillance after curative resection for non-small-cell lung cancer (NSCLC) patients are generally performed. However, there is no consensus on the best programme at this time. The aim of this study was to evaluate the diagnostic capability of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) in postoperative NSCLC patients without clinical and radiological evidence of recurrence, as a follow-up and surveillance programme. METHODS Between January 2005 and April 2010, a total of 101 NSCLC patients underwent potentially curative operations and follow-up FDG-PET/CT was performed in patients without clinical and radiological evidence of recurrence at least once a year in principle. A total of 233 FDG-PET/CT studies were entered and retrospectively reviewed. RESULTS Eighteen (18%) asymptomatic patients had recurrent diseases and 22 recurrent sites were confirmed. Of 22 recurrent sites, recurrence was diagnosed by histological examination in 9 (41%) sites and by imaging examination in 13 (59%) sites. FDG-PET/CT correctly diagnosed recurrence in 17 of the 18 (94%) patients and 21 of the 22 (95%) recurrent sites. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 94.4, 97.6, 89.5, 98.8 and 97.0%, respectively. On the other hand, in 3 patients, other diseases were detected and treated appropriately. Post-recurrence therapies were performed in all patients with recurrence, but 4 (22%) patients died of the original diseases. The median post-recurrence survival was 25.2 months, and the 1- and 2-year post-recurrence survival rates were 83.3 and 69.6%, respectively. CONCLUSIONS FDG-PET/CT is a useful tool that has high capability to detect recurrences in asymptomatic NSCLC patients after a potentially curative operation. However, a large-scale multi-institutional randomized control trial may be needed to ascertain the benefit of surveillance with FDG-PET/CT.

The effect of oral contrast on large bowel activity in FDG-PET/CT.

PurposeThe purpose of this study was to determine the effect of oral contrast on FDG uptake in the colon and to determine the normal distribution of FDG in the colon.MethodsSixty patients (30 patients in no contrast group and 30 patients in the received contrast group) underwent FDG-PET/ CT scans. The pattern of FDG uptake was classified into 5 patterns (diffuse, segmental, single-nodular, multi-nodular, and other) in 5 segments (ascending, transverse, descending, and rectosig-moid colon). SUVs of the no oral contrast group were examined. The ratios of FDG uptake patterns were compared in the received contrast group and no contrast group to evaluate the effect of oral contast. The effect of attenuation correction on the uptake pattern was evaluated by comparison of the attenuation-corrected and non-attenuation-corrected PET images.ResultsIn the no contrast group, there was no significant uptake in 72 segments (59%) and a diffuse pattern was seen in 29 segments (24%), most frequently in the ascending colon and descending colon. A segmental pattern was seen in 15 segments (13%), most frequently in the rectosigmoid colon. A single-nodular pattern was seen in 3 segments (3%) and multi-nodular pattern in 1 segment (1%). A nodular pattern was seen only in the ascending colon. SUVmax of the ascending colon and that of the rectosigmoid colon were significantly higher than those of the transverse and descending colon. The frequencies of diffuse, multi-nodular and ‘other’ patterns were significantly higher in the received contrast group than in no contrast group. There was no significant difference between the frequency of the segmental pattern or the single nodular pattern in the two groups. There was no significant difference between the uptake patterns with attenuation correction and those without attenuation correction in either the received contrast group or no contrast group.ConclusionNormal FDG uptake in the large bowel may show various degrees and patterns of uptake among the colonic segments. Oral contrast agent can cause focal or diffuse increased FDG uptake, which may be induced not only by the high CT density of oral contrast but also by an accelerated physiologic reaction of the large bowel.

Does partial volume corrected maximum SUV based on count recovery coefficient in 3D-PET/CT correlate with clinical aggressiveness of non-Hodgkin’s lymphoma?

ObjectiveThere is much controversy about the correlation between the degree of 2-[18F]fluoro-2-deoxy-d-glucose (FDG) uptake and clinical aggressiveness of non-Hodgkin’s lymphoma (NHL). In this study, we investigated whether partial volume corrected FDG uptake based on count recovery coefficient in 3D-positron emission tomography (PET)/computed tomography (CT) correlates with the clinical aggressiveness of NHL and improves diagnostic accuracy.MethodsForty-two patients with NHL underwent FDG-PET/CT scans (26 aggressive NHLs and 16 indolent ones). Count recovery curve was obtained using NEMA 2001 body phantom. Scan protocol and reconstructive parameters in the phantom study were the same as those in a clinical scan except for emission time. Relative recovery coefficient (RC) was calculated as RC = A/B (A, maximum pixel count of each hot sphere; B, maximum pixel count of greatest sphere). Partial volume corrected maximum count of standardized uptake value (PVC-SUV) was calculated as PVC-SUV = NC-SUV/RC (NC-SUV: non-corrected maximum count of SUV). Three parameters (NC-SUV, PVC-SUV, and size) between aggressive and indolent NHLs were compared.ResultsSignificant differences were shown in all parameters between aggressive and indolent NHLs. Means ± SD of NC-SUV, PVC-SUV, and size was as following: NC-SUV (15.3 ± 6.9, 8.7 ± 7.0; P < 0.01), PVC-SUV (18.2 ± 8.1, 12.7 ± 7.8; P < 0.05), and size (mm, 32.4 ± 18.3, 21.9 ± 10.3; P < 0.05). When an NC-SUV of 9.5 was the cutoff for aggressive NHL, the receiver-operating-characteristic (ROC) analysis correctly identified 21 of 26 aggressive ones. Sensitivity and specificity were 81% each, and the positive and negative predictive values were 88% and 72%, respectively. When a PVCSUV of 11.2 was the cutoff, the ROC analysis revealed 81% sensitivity, 63% specificity, and positive and negative predictive values of 78% and 67%, respectively. At a cutoff for aggressive NHL of a size of 27 mm, the ROC analysis revealed 50% sensitivity, 81% specificity, and positive and negative predictive values of 81% and 50%, respectively. The comparison of area under the curve in ROC analyses indicated that NC-SUV showed the greatest diagnostic accuracy (NC-SUV 0.84, PVC-SUV 0.72, and size 0.69).ConclusionsDiagnostic accuracy of PVC-SUV was inferior to that of NC-SUV. These results suggest that NC-SUV, which contains information on both size and FDG density, provides better differentiation between aggressive and indolent NHLs than PVC-SUV.

18F-fluorodeoxyglucose positron emission tomography/computed tomography and the relationship between fluorodeoxyglucose uptake and the expression of hypoxia-inducible factor-1α, glucose transporter-1 and vascular endothelial growth factor in thymic epithelial tumours.

OBJECTIVES The objective of this study was to evaluate the usefulness of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) and the relationships among the expressions of hypoxia-inducible factor-1α (HIF-1α), glucose transporter-1 (Glut-1) and vascular endothelial growth factor (VEGF), histological type, other clinical factors and FDG uptake in thymic epithelial tumours. METHODS Thirty-three patients who underwent FDG-PET/CT before treatment were reviewed. All types of tumours were reclassified into three subgroups: low-risk thymomas (types A, AB and B1), high-risk thymomas (types B2 and B3) and thymic carcinomas. Tumour contour, pattern of FDG uptake, tumour size and maximum standardized uptake value (SUVmax) were obtained. Expressions of HIF-1α, Glut-1 and VEGF were analysed immunohistochemically, and these expressions were evaluated using grading scales. RESULTS FDG uptake was visually recognized in all (100%) tumours. A homogeneous pattern of FDG uptake was increasingly observed in the order of low-risk thymomas to high-risk thymomas to thymic carcinomas (P = 0.016). SUVmax for thymic carcinomas was significantly higher than that for thymomas (P = 0.008). With the optimal cut-off value of SUVmax of 5.6, the sensitivity, specificity and accuracy for diagnosing thymic carcinoma were 0.75, 0.80 and 0.79, respectively. Regarding the mean scoring of HIF-1α, Glut-1 and VEGF, increasing trends were observed in the order of low-risk thymomas to high-risk thymomas to thymic carcinomas. Tumour size revealed a significant correlation with SUVmax (r = 0.60, P < 0.001), and the expression of HIF-1α showed a moderate association, but the expression of Glut-1 showed no correlation with SUVmax. Regarding correlations between the expression of the three markers, there were moderate associations between HIF-1α and Glut-1, and HIF-1α and VEGF, and a significant correlation between Glut-1 and VEGF (r = 0.60, P < 0.001). In type B1 thymoma, HIF-1α and Glut-1 were partly expressed in non-neoplastic immature lymphocytes. CONCLUSIONS FDG-PET/CT should be performed in patients with tumours in the anterior mediastinum because the pattern of FDG uptake and SUVmax are useful in the differential diagnosis of thymic epithelial tumours. Furthermore, the expressions of HIF-1α, Glut-1 and VEGF might be associated with malignancy of thymic epithelial tumours. In contrast, FDG uptake might be dependent on tumour size rather than Glut-1 overexpression.

Selection of endogenous 13C substrates for observation of intracellular metabolism using the dynamic nuclear polarization technique

PurposeThe aim of this study was to select a suitable substrate candidate for dynamic nuclear polarization (DNP) studies and demonstrate its utility for evaluating intracellular metabolism.Materials and methodsHyperpolarized substances included 1-13C-pyruvate (Pyr), 1-13C-glucose (Glc), and 1-13C-acetate. A DNP polarizer and a 600-MHz vertical small-bore scanner were used for 13C-MR spectroscopic measurements. After polarization for 1 h, the dissolved solution was injected via a capillary line into the nuclear magnetic resonance tube in the scanner. The sequential spectra of the hyperpolarized 13C-labeled substrates were acquired in durations of more than 120 s, and a thermal spectrum was obtained more than 1 h thereafter. FM3A cancer cells of mammary tumors were cultured for intracellular detection of the hyperpolarized 13C-substances.ResultsThe greatest sensitivity was found using Pyr with the longest T1 decay (51.5 s); and remarkably, the least sensitivity was observed using Glc with a signal decay of less than 2 s. An effective increase in sensitivity was shown using the other substances. The hyperpolarized intracellular study using 13C-Pyr showed distinct elevation of lactate levels.ConclusionThe DNP technique is useful for evaluating intracellular metabolism. However, Glc is not suitable for use with the DNP technique.

The retention indices of201Tl-SPECT in brain tumors

Objective: The aim of this study was to assess the utility of201Tl SPECT in the differential diagnosis of intracranial tumors and to determine the relationship between201Tl uptake and histological types.Methods: Thirty-eight patients (19 males and 19 females) with thirty-eight brain tumors were evaluated with201Tl-SPECT. The early and delayed201Tl uptake ratio was calculated, and the retention index (RI) was applied as follows; RI=delayed uptake ratio/early uptake ratio.Results: The RI of malignant tumors was higher (0.72±0.18) than that of benign tumors (0.50±0.16) and the difference was statistically significant (p=0.00045). The difference between high-grade glioma (0.80±0.15) and metastatic tumors (0.64±0.19) was statistically significant (p=0.039).Conclusion:201Tl-SPECT may add useful biochemical information and could differentiate malignant brain tumors from benign lesions, but the RI of metastatic tumors varied depending on the organs with the primary lesion and histological types.