Masayoshi Kowada

Clinical Value of Pet with 18F-Fluorodeoxyglucose and L-Methyl-11C-Methionine for Diagnosis of Recurrent Brain Tumor and Radiation Injury

We studied 15 patients clinically suspected to have recurrent brain tumor or radiation injury, using positron emission tomography (PET) with 18F-fluorodeoxyglucose (18FDG) and L-methyl-11C-methionine (11C-Met). PET with 11C-Met (Met-PET) clearly delineated the extent of recurrent brain tumor as focal areas of increased accumulation of 11C-Met, and was useful for early detection of recurrent brain tumor. PET with 18FDG (FDG-PET) showed focal 18FDG-hypermetabolism in one patient with malignant transformation of low grade glioma, and demonstrated its usefulness for evaluation of malignant transformation. 18FDG-hypometabolism was observed in all patients with radiation injury, but was also found in one patient with recurrent malignant brain tumor. 11C-Met uptake in 3 patients with radiation injury was similar to that of the normal cortical tissue. FDG-PET can be used to initially exclude recurrent brain tumor which is seen as 18FDG-hypermetabolism. The combined use of Met-PET in addition to FDG-PET can improve the accuracy of differentiation of recurrent brain tumor with 18FDG-hypometabolism from radiation injury.

Fetal spinal cord transplants rescue some axotomized rubrospinal neurons from retrograde cell death in adult rats.

Intraspinal transplants of fetal spinal cord may contribute to recovery after spinal cord injury by keeping axotomized neurons alive. In this study we examined whether transplants rescued axotomized red nucleus (RN) neurons from retrograde cell death in adult rats. RN neurons were labeled by retrograde transport of Fluorogold (FG); 1 week later right-sided RN neurons were axotomized by left-sided hemisection at C3-4 vertebral level, and Embryonic Day 14 spinal cord or gelfoam was introduced into the cavity. Additional rats received hemisection and a transplant of fetal spinal cord or gelfoam without FG injection. At 2 and 4 months, the number of neurons in the magnocellular portion of the RN contralateral to the hemisection decreased 35-40% in rats that received gelfoam; mean soma area of surviving neurons decreased 40%. RN cell loss was reduced to 20% in rats that received fetal spinal cord transplants, but the decrease in mean soma area was unchanged. Transplants therefore rescued about half of the axotomized RN neurons that otherwise would have died but did not prevent perikaryal atrophy. Anterograde transport of WGA-HRP injected into RN 2 months after transplantation showed that rubrospinal axons reached the site of injury but rarely entered transplants; FG injections caudal to transplants showed that axons of transplant neurons extended at least two segments into host spinal cord. Fetal spinal cord transplants may therefore contribute to locomotor recovery in adults with spinal cord injuries both by preventing retrograde cell death and by establishing novel circuits across the site of injury.

Perfusion and metabolism in predicting the survival of patients with cerebral gliomas

Background. Noninvasive measurements of cerebral circulation and metabolism may be useful for diagnosis in patients with brain tumors. The authors tested the prognostic significance of circulatory and metabolic values or ratios determined by positron emission tomography (PET) in patients with gliomas.

Changes of cerebral blood flow, and oxygen and glucose metabolism following radiochemotherapy of gliomas: a PET study.

The effects of radiochemotherapy on blood flow, blood volume, and consumption of oxygen and glucose in tumor tissue and normal brain were studied by positron emission tomography. Thirteen patients with cerebral gliomas were included, and they were examined before, during, and within approximately 1 month after the therapy. The 15O-labeled gas steady state inhalation and the 18F-fluorodeoxyglucose methods were used. After the therapy, glucose consumption and blood volume decreased (p less than 0.03) in the tumoral tissue. In the structurally (CT) normal gray matter, blood flow, blood volume, and oxygen consumption did not show any significant changes; oxygen extraction fraction, glucose consumption, and glucose extraction fraction, however, decreased significantly (p less than 0.05, less than 0.02, and less than 0.03, respectively).

Vascular malformations of the brain in hereditary hemorrhagic telangiectasia (rendu-osler-weber disease)

Six patients with vascular malformation of the brain in hereditary hemorrhagic telangiectasia (HHT) were reviewed to determine clinical and radiographic characteristics of these lesions. There were two patients with arteriovenous fistula (AVF), three with arteriovenous malformation (AVM), and one with multiple AVMs associated with AVF. Seizures were the most common presenting symptom (seen in three patients), and two of them had intracerebral hematomas (ICH). In the remainder, the malformations were incidentally found in the course of evaluation of other diseases. Their locations were variable, but the majority was superficially confined to the cerebral cortex. Arterial supply was from mostly one feeding artery that was a cortical branch of either anterior, middle, or posterior cerebral artery. In six of nine malformations, the venous drainage was through a superficial cerebral vein into either the superior sagittal sinus or transverse sinus. Direct surgery was done on two patients with ICH, artificial embolization on one, and stereotactic radiosurgery on one. The cerebral vascular malformations in HHT are not infrequent, and in particular the importance of computed tomography and cerebral angiography should be recognized in patients with pulmonary AVF associated with HHT.

Fenestration of the Vertebral Artery with a Review of 23 Cases in Japan

Abstract Seven cases of angiographically demonstrated vertebral artery fenestration are presented, and 23 cases are reviewed. In the 7 cases described, fenestration occurred at the level of the atlantoaxial junction, on the left side in 5 cases, and on the right in 2. Fenestration or partial duplication of the vertebral artery is considered to be an anastomosis anomaly occurring during embrologic development. This anomaly is frequently associated with other congenital intracranial and extracranial vascular abnormalities including aneurysms and arteriovenous malformations.

Positron emission tomographic evaluation of histological malignancy in gliomas using oxygen-15 and fluorine-18-fluorodeoxyglucose.

HEADTOME III, a high resolution PET, has been employed using 15O and 18F labelled pharmaceuticals to evaluate histological malignancy of gliomas preoperatively. PET study was applied on eighteen preoperative gliomas including two recurrent cases. Haemocirculatory and metabolic indices of regional cerebral blood flow (rCBF), cerebral blood volume (rCBV), oxygen extraction fraction (rOEF), cerebral metabolic rates for oxygen (rCMRO2) and glucose (rCMRGI) were measured in the viable portion of the tumour, and the contralateral grey and white matter. In the tumour region, rCBF and rCBV were variable and unrelated to grades of tumour malignancy. rCMRO2 and rOEF values reduced significantly (p less than 0.01) relative to the contralateral brain tissue. The average rCMRGI values was 3.00 +/- 1.06 mg 100 ml-1 min-1 (mean +/- SD) for 7 low grade gliomas (grade II), and 5.91 +/- 3.61 mg 100 ml-1 min-1 for 11 high grade gliomas (grade III and IV). These results would support that anaerobic glycolysis increased in the metabolism of gliomas with malignancy. In comparison with normal volunteers, rCBF, rCMRO2, and rCMRGI values in the contralateral grey matter of gliomas were markedly reduced (p less than 0.01, p less than 0.05, p less than 0.01, respectively) possibly due in part to raised intracranial pressure and depressed cerebral functional activity, so that rOEF was increased to a level of approximately 0.5.(ABSTRACT TRUNCATED AT 250 WORDS)

Intramedullary spinal cord germinoma: case report and review of the literature.

We discuss the case of a patient with a recurring intramedullary spinal cord germinoma of the lower thoracic spinal cord, which was successfully excised. A primary intramedullary spinal cord germinoma is very rare, and only four other cases have been reported in the literature. All five cases are reviewed regarding the appearance of the germinomas, their neuroradiological features, and their histopathological findings. We also discuss treatment choices for germinomas of the spinal cord.

Human brain tumor O6-methylguanine-DNA methyltransferase mRNA and its significance as an indicator of selective chloroethylnitrosourea chemotherapy

O6‐methylguanine‐DNA methyltransferase (MGMT) removes and repairs chloroethylnitrosourea (CENU)‐induced O6‐methylguanine‐DNA by accepting the alkyl group at a cysteine moiety. MGMT activity is, therefore, predictive of resistance or sensitivity to CENU chemotherapy. We measured the levels of MGMT mRNA expression in human brain tumors using a reverse transcription‐polymerase chain reaction (RT‐PCR) method, and studied the significance of MGMT mRNA levels in CENU chemotherapy. The level of MGMT mRNA was represented as a percentage relative to the MGMT mRNA in UI38MG brain tumor cells. Forty‐three patients with brain tumors were entered into the study. High‐grade gliomas had significantly lower levels of MGMT mRNA than did low‐grade gliomas and non‐glial tumors (p < 0.05 determined by analysis of co‐variance). Out of 14 high‐grade gliomas, 4 had a level of MGMT mRNA below 10%, indicating chemosensitivity to CENU. Out of 11 patients who received CENU chemotherapy, 3 had a partial response. All 3 responders had a low level of MGMT mRNA. The time to tumor progression (TTP) for 6 patients with a level lower than the median was short, but significantly longer than the TTP for 5 patients with a higher level (p < 0.05 determined by Gehans Wilcoxon test). These results indicate that a fraction of brain tumors have a low expression of MGMT mRNA, and that the level of MGMT mRNA is a useful indicator of effectiveness in selective CENU chemotherapy.

Blood flow and metabolism of central neurocytoma. A positron emission tomography study

Background. New World Health Organization classifications have categorized central neurocytomas as neuronal tumors. The differential diagnosis between central neurocytomas and other tumors is important for selection of the optimal therapy modality for the management of intraventricular tumors. To characterize the pathophysiology and proliferating activity of central neurocytoma accurately, cerebral blood flow and metabolism in five patients with central neurocytoma were studied using positron emission tomography (PET).