Ichiro Sunada

Methionine positron emission tomography for differentiation of recurrent brain tumor and radiation necrosis after stereotactic radiosurgery--in malignant glioma.

ObjectFollowing stereotactic radiosurgery (SRS), we examined how to differentiate radiation necrosis from recurrent malignant glioma using positron emission tomography (PET) with11C-methionine (Met).MethodsMet-PET scans were obtained from 11 adult cases of recurrent malignant glioma or radiation injury, suspected on the basis of magnetic resonance images (MRI). Patients had previously been treated with SRS after primary treatment. PET images were obtained as a static scan of 10 minutes performed 20 minutes after injection of Met. We defined two visual grades (e.g., positive or negative Met accumulation). On Met-PET scans, the portion of the tumor with the highest accumulation was selected as the region of interest (ROI), tumor-versus-normal ratio (TN) was defined as the ratio of average radioisotope counts per pixel in the tumor (T), divided by average counts per pixel in normal gray matter (N). The standardized uptake value (SUV) was calculated over the same tumor ROI. Met-PET scan accuracy was evaluated by correlating findings with subsequent histological analysis (8 cases) or, in cases without surgery or biopsy, by the subsequent clinical course and MR findings (3 cases).ResultsHistological examinations in 8 cases showed viable glioma cells with necrosis in 6 cases, and necrosis without viable tumor cells in 2 cases. Three other cases were considered to have radiation necrosis because they exhibited stable neurological symptoms with no sign of massive enlargement of the lesion on follow-up MR after 5 months. Mean TN was 1.31 in the radiation necrosis group (5 cases) and 1.87 in the tumor recurrence group (6 cases). Mean SUV was 1.81 in the necrosis group and 2.44 in the recurrence group. There were no statistically significant differences between the recurrence and necrosis groups in TN or SUV. Furthermore, we made a 2 x 2 factorial cross table (accumulation or no accumulation, recurrence or necrosis). From this result, the Met-PET sensitivity, specificity, and accuracy in detecting tumor recurrence were determined to be 100%, 60%, and 82% respectively. In a false positive-case, glial fibrillary acidic protein (GFAP) immunostaining showed a positive finding.ConclusionThere were no significant differences between recurrent malignant glioma and radiation necrosis following SRS in Met-PET. However, this study shows Met-PET has a sensitivity and accuracy for differentiating between recurrent glioma and necrosis, and presents important information for developing treatment strategies against post radiation reactions.

Evaluation of treatment effects in brain abscess with positron emission tomography: comparison of fluorine-18-fluorodeoxyglucose and carbon-11-methionine.

Positron emission tomography (PET) imaging is in common use preoperatively to clinically evaluate patients who present with central nervous system mass lesions. The usefulness of PET is also recognized as a method to detect intracranial tumorous lesions. A number of papers report that some inflammatory processes also showed the uptake of Fluorine-18-Fluorodeoxyglucose (FDG) and Carbon-11-Methionine (Met) tracers. We performed two PET studies before and after treatment in 4 patients with brain abscess. PET showed the uptake of both tracers to the brain abscess before treatment. The area showing an increased uptake of Met corresponded closely to the enhanced area on both CT and MR images. FDG-PET visually showed an uptake of FDG in a small area corresponding to an enhanced lesion within the CT and MR images. After treatment the area of lesions became small on enhancement CT or MRI and both PET studies showed reduced lesion and decreased uptake. The mechanism of Met uptake in the inflammatory area may be related to the higher metabolic rate and the active transport of amino acids as well as disruption of the blood brain barrier. Furthermore, it appears that the mechanism of FDG uptake is also related to a higher metabolic rate and, in addition, is related to the increased density of inflammatory cells. PET studies, more directly, reflect the degree of inflammatory response in brain abscess than enhancement CT or MRI. Therefore, PET is useful in detecting the inflammatory lesion and assessing the clinical effects of antibiotics treatment on brain abscesses.

Correlation of amino-acid uptake using methionine PET and histological classifications in various gliomas

ObjectiveThe uptake of L-methyl-11C-methionine (MET) by gliomas is greater than that by intact tissue, making methionine very useful for evaluation of tumor extent. If the degree of malignancy of brain tumors can be evaluated by MET-PET, the usefulness of MET-PET as a means of diagnosing brain tumors will increase.MethodsWe performed this study on 67 glioma patients between 3 and 69 years of age (36 males and 31 females). Tumors included diffuse astrocytoma, anaplastic astrocytoma, glioblastoma, ependymoma, oligodendroglioma, medulloblastoma, dysembryoplastic neuroepithelial tumor, choroid plexus papilloma, central neurocytoma, optic glioma, gliomatosis cerebri, pleomorphic xanthoastrocytoma, and ganglioglioma. Tumor activity and degree of malignancy were evaluated using Ki-67LI (LI: labeling index) and Kaplan-Meier survival curves. The correlations between methionine uptake and tumor proliferation (tumor versus contralateral gray matter ratio (T/N) and Ki-67LI) were determined for the group of all subjects. The existence of significant correlations between T/N and KJ-67LI and between SUV and Ki-67LI was determined for astrocytic tumors. Receiver operating characteristics (ROC) analysis of T/N and standardized uptake value (SUV) was performed for the group of astrocytic tumors. We also determined the ROC cut-off levels to ensure high accuracy of the analysis.ResultsFor the 67 cases of glioma, the degree of accumulation was variable. Ki-67LI differed significantly between the high-grade group and low-grade group at T/N levels between 1.5 and 1.8 on analysis using tumor proliferative potential (p - 0.019–0.031). The prognosis differed significantly between the highgrade and low-grade groups when T/N was in the range of 1.6–1.8 (p = 0.028–0.032). The accuracy thus calculated was highest (85.7%) when T/N was 1.5 as determined by ROC analysis.ConclusionsWhen analysis was confined to cases of astrocytic tumor, a correlation was noted between methionine accumulation and Ki-67LI. For the astrocytic tumors, T/N ratio seemed to be more useful as a diagnostic indicator than SUV. The cut-off level of T/N ratio for distinction between high-grade and low-grade astrocytoma appears to lie between 1.5 and 1.6.

Immunohistochemical Analyses of Cell Cycle-related Proteins, Apoptosis, and Proliferation in Pituitary Adenomas

To analyze the cell cycle regulatory mechanisms in the growth of pituitary adenomas, we investigated immunohistochemically the expression of the cell cycle-related proteins cyclin A and p27 in 48 pituitary adenomas. The frequency of apoptosis and the proliferative potential were also examined. The percentage of apoptotic cells was evaluated by immunohistochemical analysis using the anti-single-strand DNA antibody. The proliferative potential was assessed using the anti-Ki-67 antibody. The mean cyclin A labeling index (LI) for the non-recurrent group was 1.03% and for the recurrent group 2.31%. A positive linear correlation between cyclin A LI and Ki-67 LI was found. The mean p27 LI for the non-recurrent group was 67.4% and for the recurrent group 47.0%. There were significant differences in cyclin A LI and p27 LI between the non-recurrent group and the recurrent group. The mean apoptotic rate for the non-recurrent group was 0.87% and for the recurrent group 1.05%. There was no significant difference. Multivariate regression analysis revealed that high cyclin A LI and high Ki-67 LI were significant factors for shorter progression-free survival. The results suggest that the cyclin A LI is a useful prognostic factor in pituitary adenomas. (J Histochem Cytochem 49:1193–1194, 2001)

Interictal Patterns of Cerebral Glucose Metabolism, Perfusion, and Magnetic Field in Mesial Temporal Lobe Epilepsy

Summary:  Purpose: To characterize the epileptogenic condition of patients with mesial temporal lobe epilepsy, the interictal patterns of glucose metabolism, perfusion, and magnetic field in the temporal lobe were evaluated by using [18F]fluorodeoxyglucose–positron emission tomography, [99mTc]‐ethylcysteinate dimer–single photon emission computed tomography, and magnetoencephalography (MEG).

PET for diagnosis of malignant lymphoma of the scalp : Comparison of [11C]methyl-L-methionine and [18F]fluoro-2-deoxyglucose

A 43-year-old woman was admitted with a tumor mass in her forehead. Two months previously, a lump in her breast had been diagnosed as mastopathy. Palpation revealed an elastically hard immobile tumor mass in her forehead. MRI detected a tumoral lesion of generally uniform contrast involving frontal subcutaneous, cranial, and intracranial regions. PET demonstrated more intensive and wider accumulation of [11C]methyl-L-methionine (Met) than of [18F]fluoro-2-deoxyglucose (FDG). Biopsy of the forehead mass was performed, which was diagnosed as B-cell-type malignant lymphoma. The tumor mass in the forehead then shrank spontaneously, as confirmed by palpation and MRI. The tumor mass in the left breast was totally extirpated and histologically diagnosed as B-cell-type malignant lymphoma, like the tumor mass in the forehead. Postoperatively, chemotherapy (VEPA) was performed. Although FDG accumulation had not been detected, postchemotherapy PET demonstrated slight Met accumulation, suggesting the presence of a residual tumor. PET served well to detect the lesion and evaluate therapeutic efficacy in malignant lymphoma. Met-PET was more sensitive to malignant lymphoma than FDG-PET.

A discrepancy between Tc-99m HMPAO SPECT and Tc-99m ECD SPECT in Creutzfeldt–Jacob disease

We observed a discrepancy between the perfusion patterns seen in single photon emission computed tomography (SPECT) images obtained using technetium-99m hexamethyl propylene amine oxime (HMPAO) and SPECT images obtained using technetium-99m ethyl cysteinate dimer (ECD) in an 84-year-old man with Creutzfeldt-Jacob disease (CJD). HMPAO-SPECT demonstrated a reduction in perfusion in the parieto-temporal regions, especially the left temporal area. However, ECD-SPECT revealed a significant reduction in the bifrontal regions. At autopsy, the characteristic pathological findings of CJD, spongiform vacuolation, were most prominent in the bifrontal regions. Thus, the clinical features and the pathological findings were more closely correlated with the ECD-SPECT images than the HMPAO-SPECT images.

Clinical Usefulness of (15O)H2O in Positron Emission Computed Tomography.

The clinical usefulness of [15O] H2O was evaluated in 59 patients (16 patients with brain disease, 19 with neck disease, 4 with chest disease, and 20 with abdominal disease) . [15O] H2O was produced in a medical cyclotron (AMWR01, NKK Co., Tokyo, Japan) . The images by positron emission computed tomography with [15O] H2O were judged clinically useful (“fairly useful” or better) in 14 (88%) of the 16 patients with brain disease, all 19 patients with neck disease, all 4 patients with chest disease, and 19 (95%) of the 20 patients with abdominal disease (19 with chronic liver disease) . In 14 of the patients with liver disease, hepatic arterial blood flow and portal blood flow were measured in the same session. The mean portal blood flow in cirrhotic patients with varices was significantly lower than that in cirrhotic patients without varices. There were no side effects during or after the computed tomography. Positron emission computed tomography with [15O] H2O was clinically useful.

Cerebral Blood Flow Measurement in Head Trauma Patients

Cerebral blood flow (CBF) measurements were obtained in 40 patients with head trauma by single photon emission CT using 99m-Tc-exametazime (HMPAO) and N-isopropyl-p-(1231)iodo-amphetamine (IMP). Measurement of CBF by using HMPAO in the acute phase enabled immediate detection of brain lesions which could not be detected by CT scan performed immediately after the trauma had occurred. It, however, did not correlate the outcome of patients. In the subacute and chronic phase, it demonstrated insufficiency of cerebral blood flow which could not be detected by CT scan or MRI, but it also did not correlate the outcome. As for measurement of CBF by using IMP, early images indicated perfusion abnormalities similar to those suggested by HMPAO. The patients whose delayed images showed reduced areas of ligand accumulation defect took more favorable courses than the patients who showed no reductions in the area of ligand accumulation defect. When measured by using 99m-DTPA-human serum albumin (HSA-D), blood volume in the injured area showed increases in subacute phase, and decreases in chronic phase.