The usefulness of 3D MR angiography in surgery for ruptured cerebral aneurysms.

BACKGROUND: We have used magnetic resonance angiography (MRA) in screening for unruptured cerebral aneurysms since 1993. The development of high-resolution magnetic resonance (MR) imaging has led to a remarkable improvement in image quality. Three-dimensional (3D) MRA can be used for surgical simulation. Here, we report on the usefulness of and problems associated with 3D MRA for the surgery of ruptured cerebral aneurysms. METHODS: Between June 1998 and June 2000, 106 patients with SAH diagnosed by 3D MRA underwent surgery. We compared 3D MRA images with operative findings and investigated the usefulness of this assessment tool. RESULTS: In 48 of 106 cases (45.3%), we were able to perform surgery based on 3D MRA alone. By using the 3D images, we could easily detect the relative location of the aneurysm, its neck and the surrounding arteries. The remaining cases required further examinations because of uncertainty of diagnosis or insufficient information. CONCLUSION: 3D MRA is a safe and useful procedure for the diagnosis and surgery of ruptured cerebral aneurysms. However, in approximately half of all cases, 3D computed tomographic angiography (CTA) or digital subtraction angiography (DSA) is required in addition for the planning of surgery. It is important to use 3D MRA for surgery only after taking sufficient consideration of certain limitations peculiar to MRA.

Blood flow and metabolism of oligodendrogliomas: a positron emission tomography study with kinetic analysis of 18F-fluorodeoxyglucose.

To accurately characterize the pathophysiology and proliferating activity of oligodendrogliomas, we studied cerebral blood flow and metabolism using positron emission tomography (PET) in five patients with this tumor. Regional cerebral blood flow (rCBF), cerebral blood volume (rCBV), oxygen extraction fraction (rOEF), and cerebral metabolic rates of oxygen (rCMRO2) and of glucose (rCMRGl) were quantitatively measured in tumor lesions and the contralateral gray matter, rCMRGl was analyzed based on both kinetic and autoradiographic methods. Tumor rCBF and rCBV were lower than in the contralateral gray matter in all preoperatively examined patients. Oxygen metabolism, determined by rCMRO2 and rOEF, was consistently reduced in the tumor (rCMRO2, P<0.05 vs. gray matter, determined by the Student's t-test). Tumor rCMRGl was significantly lower than the gray matter rCMRGl in both kinetic (P<0.01) and autoradiographic (P<0.05) analyses. Kinetic tumor rCMRGl varied between 1.22 and 4.13 mg/100 ml/min, but was lower than the gray matter value in all patients. Autoradiographic tumor rCMRGl, which ranged from 1.02 to 5.79 mg/100 ml/min, was also reduced in all tumors but one; the remaining tumor, which had a relatively high value of autoradiographic rCMRGl (comparable to gray matter rCMRGl), infiltrated the contralateral hemisphere through the corpus callosum, and was characterized by high cellular density. In one patient who suffered from tumor recurrence 8 years and 10 months after initial treatment, phosphorylation constant (K3) and kinetic rCMRGl of the recurring tumor were higher than those of the original tumor. No other tumors have regrown or recurred during the postoperative follow-up periods, which ranged from 22 to 130 months (median = 101 months). Circulation and metabolism measured by PET provide in vivo biological characteristics, including proliferating activity, in oligodendrogliomas.

Development of a huge varix following endovascular embolization for cerebellar arteriovenous malformation. A case report.

We report on the case of a huge varix that developed after the endovascular embolization of a cerebellar arteriovenous malformation (AVM) with a single drainer. A 21-year-old male presented with trigeminal neuralgia which was caused by the dilated drainer of the AVM. A varix was found at the basal vein of Rosenthal 2 months after an initial stage of embolization with polyvinyl alcohol particles; it diminished after the surgical extirpation of the AVM. The varix formation might have been facilitated by the stenosis in the vein of Galen and by the dynamic changes that followed the embolization. This rare complication should be kept in mind when embolization is performed for AVMs with impaired venous outlets.

Intracarotid recombinant human tumor necrosis factor-alpha reduces cerebral blood flow and methionine uptake in rat brain tumors.

The aim of the present study is to understand the therapeutic effects of recombinant human tumor necrosis factor-alpha (rH-TNF) on hemocirculation and metabolism of brain tumors. Using double-label autoradiographic technique, we have monitored changes in regional cerebral blood flow (rCBF) and protein-bound fraction of (3H-methyl)-L-methionine, expressed as acid-insoluble fraction (AIF), in rat brain tumors following treatment with intracarotid rH-TNF. The central portion of tumors showed a significant decrease in rCBF and AIF at 4 hours after the injection (p < 0.01, p < 0.05, respectively, as compared with non-treated control rats), turned microscopically necrotic at 24 hours, and became more extensively necrotic at 72 hours. Tumor cells remained viable only in the peripheral portion of the tumors after the treatment. The peripheral portion also showed a moderate decrease in rCBF, but less change in AIF to 4 to 72 hours after the treatment. Neither ipsilateral nor contralateral non-involved cortex demonstrated appreciable changes in rCBF and AIF during the observed period. Intracarotid rH-TNF selectively reduces tumor rCBF and AIF, resulting in histological modification.

[Laparoscopic retrieval of a dislocated ventriculoperitoneal shunt catheter: report of three cases and a review of the literature].

Described are 3 cases of a disconnected ventriculoperitoneal shunting system that was successfully retrieved by using a laparoscopic procedure, with a review of the literature. All patients had symptoms of increased intracranial pressure. Roentgenograms showed disconnection of a ventriculoperitoneal shunt catheter at the connecting device and its migration into the peritoneal cavity. A laparoscope was introduced into the peritoneal cavity using the double puncture procedure and the catheter was extracted in less than 15 minutes. The use of a laparoscope enabled exploration of the entire space of the cavity without any large laparotomy incision. Furthermore, the laparoscopic procedure also easily enabled introduction of a replaceable ventriculoperitoneal shunt catheter into the appropriate portion in the cavity and confirmed the CSF flow into the cavity. Because catheters which have migrated into the cavity might cause an acute abdomen, it is important that they should be removed as soon as possible. It should be kept in mind, during the procedures of extracting catheters, that the inner absorptive surface of the peritoneal cavity must be preserved as much as possible. In this regard, laparoscopic retrieval of disconnected shunt catheters is a promising method.

Tumor extent of slowly progressive oligodendroglioma determined by 18F-fluorophenylalanine positron emission tomography.

We report the use of positron emission tomography (PET) and 18F-fluorophenylalanine (18F-Phe) to determine the extent of a slowly progressive oligodendroglioma, which gradually grew over 10 years after the onset of convulsions. The tumor exhibited intense accumulation of 18F-Phe and was easily distinguished from the surrounding brain tissue. The tumor lesion indicated by 18F-phe PET was more extensive than the lesion detected by computerized tomography (CT) and was comparable to the hypointense lesion detected by T2-weighted magnetic resonance imaging (MRI). The tumor, a histologically verified oligodendroglioma, was extensively resected, and its extent corresponded to the high uptake region of 18F-Phe. The accuracy of the 18F-Phe PET technique for determining the extent of a tumor is valuable and will aid in the selection of an appropriate therapy modality for the management of oligodendrogliomas.

Central neurocytoma with clinically malignant behavior.

We describe two cases of central neurocytoma that did not show histopathologic features of anaplasia but did show tumor dissemination after surgery and radiation therapy. CT and MR imaging before surgery depicted extraventricular extension of the tumors. The importance of radiologic findings is stressed.

[Study on potentiation of nitrosourea-cytotoxicity by DNA repair enzyme inhibitors in human brain tumor cells].

Nitrosoureas are antitumor alkylating agents widely used in the chemotherapy of malignant brain tumors. However, the effectiveness of adjuvant nitrosourea chemotherapy has proved inadequate, failing to provide any significant prolongation of survival time. One of the reasons for the poor results is a drug resistance system in the form of the DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT). O6-alkylguanine derivatives are well known to be inhibitors of MGMT, and inactivation of MGMT by these derivatives leads to increased tumor cell sensitivity to nitrosoureas. In this study, the authors tested the ability of O6-benzylguanine, O6-(4-, 3- and 2-fluorobenzyl) guanines, O6-(4-, 3- and 2-trifluoromethylbenzyl) guanines, O6-(4-, 3- and 2-pyridylmethyl) guanines and O6-(2- and 1-naphthylmethyl) guanines to reduce MGMT activity in SF-188 cell-free extract by using [3H] methylated substrate DNA and analyzed their enhancing effect on the cytotoxicity of 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl) -3-nitrosourea hydrochloride (ACNU) by using a calorimetric cytotoxicity assay. The MGMT activity in the SF-188 cell-free extract was 944 +/- 43 fmol/mg protein (Mean +/- SD, n = 5). O6-(4- and 3-fluorobenzyl) guanines were found to be more effective in inactivating MGMT than O6-benzylguanine. O6-(4-trifluoromethylbenzyl) guanine considerably reduced MGMT activity as did O6-benzylguanine. O6-(3-trifluoromethylbenzyl) guanine, O6-(4- and 3-pyridylmethyl) guanines, and O6-(2-naphthylmethyl) guanine were intermediately effective, but O6-(2-fluorobenzyl) guanine, O6-(2-trifluoromethylbenzyl) guanine and O6-(1-naphthylmethyl) guanine were less effective. ACNU cytotoxicity in SF-188 cells was strongly enhanced by pretreatment with O6-(4- and 3-fluorobenzyl) guanines and O6-(4-trifluoromethylbenzyl) guanine and moderately enhanced by O6-(3- trifluoromethylbenzyl) guanine and O6-(4- and 3-pyridylmethyl) guanines, but not enhanced by O6-(2-fluorobenzyl) guanine, O6-(2-trifluoromethylbenzyl) guanine and O6-(1-naphthylmethyl) guanine. The test compounds were not cytotoxic at concentrations between 0.5 and 5.0 microM. The enhancing effects on ACNU cytotoxicity were consistent with the inhibition of MGMT activity after two-hour pretreatment with O6-arylmethylguanine derivatives. These results indicate that the 2-position of the O6-benzyl group plays an important role in the inactivation of the MGMT activity and the potentiation of ACNU cytotoxicity.

Subependymoma of the septum pellucidum: characterization by PET.

We report the evaluation of a subependymoma of the septum pellucidum by positron emission tomography (PET) with analysis of 18F-fluorodeoxyglucose (FDG) kinetics. The tumor showed exceedingly low rates of glucose metabolism (rCMRG1) and kinetic constants (K1, K2, and K3). This hypometabolism indicates low cellular density and slow growth.

Indications for differential diagnosis of nontumor central nervous system diseases from tumors. A positron emission tomography study.

To accurately differentiate nontumor central nervous system (CNS) diseases from brain tumors, we retrospectively evaluated the cerebral circulation and metabolism in patients with nontumor CNS diseases using positron emission tomography (PET). Regional cerebral blood flow (rCBF), cerebral blood volume (rCBV), oxygen extraction fraction (rOEF), the metabolic rates of oxygen (rCMRO2), and of glucose (rCMRGI), and the uptake of 11C-methyl-L-methionine (11C-Met) were visually evaluated in lesions and compared with values for the contralateral white matter regions. PET findings were correlated with those of x-ray computed tomography (CT) and magnetic resonance imaging (MRI), and were analyzed for nontumor CNS diseases and cerebral gliomas. rCBF and rCBV were changeable from disease to disease or from stage to stage of disease progression. rOEF and rCMRO2 remained low in 5 and 6, respectively, of 9 nontumor CNS diseases examined, whereas these parameters were increased in CNS infections such as brain abscess. Overall, noteworthy was the locally increased rOEF and rCMRO2 in the patients with a brain abscess in contrast to the values for patients with gliomas. rCMRGI reflected biological characteristics of each disease, and correlated with cell density, whether reactive glial cells or inflammatory cells. 11C-Met was accumulated at a certain stage of nontumor CNS diseases, which implied uptake of the tracer as a result of disruption of the blood-brain barrier as well as metabolic incorporation.

Early delineation of cerebral glioma using amino acid positron tracers.

A 56-yr-old housewife with cerebral astrocytoma was reported with positron emission tomography findigns using 11C-methyl-L-methionine (11C-Met) and 18F-fluorophenylalanine (18F-Phe) tracers. 11C-Met and 18F-Phe accumulated intensely in tumor lesions, although CT scans showed only a foggy low-density area. Five years and one month after, an enhancing mass appeared on CT scans. Thus, amino acid tracers may play a important role in the early diagnosis of gliomas.

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.

Human brain tumor O(6)-methylguanine-DNA methyltransferase mRNA and its significance as an indicator of selective chloroethylnitrosourea chemotherapy.

O(6)-methylguanine-DNA methyltransferase (MGMT) removes and repairs chloroethylnitrosourea (CENU)-induced O(6)-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 U138MG 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 covariance). 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 Gehan's 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.

Inhibition of methionine uptake by cis-diamminedichloroplatinum (II) in experimental brain tumors.

cis-diamminedichloroplatinum (II) (CDDP) has been used both alone and in combination with other chemotherapeutics for cancer chemotherapy. Although CDDP acts primarily on DNA, it can also act at the tumor-cell membrane to inhibit methionine transport. The latter mechanism of CDDP is reported to have an important role as a chemical modulator in enhancing chemotherapeutic effects of 5-fluorouracil in tumor cells. We report here the effects of CDDP on methionine uptake in an in vivo brain-tumor model. C6 brain-tumor cells were stereotactically inoculated in the right basal ganglia of 6-week-old male Sprague-Dawley rats. Ten days after the inoculation, autoradiographic images were obtained using (14C-methyl)-L-methionine. The tracer uptake, represented as differential absorption ratio (DAR) and an acid-insoluble fraction (AIF), was measured in both brain tumors and normal brain with or without an intravenous injection of CDDP. The tumor/non-tumor DAR and AIF decreased significantly (P < 0.01, as determined by the Mann-Whitney U-test) after CDDP treatment, whereas the non-tumor DAR and AIF remained almost unchanged. These findings indicate that CDDP inhibits methionine uptake selectively in brain-tumor tissue and may therefore be a potent chemical modulator in the chemotherapy of brain tumors.

[Recanalization of dural sinus occlusion following the disappearance of dural arteriovenous fistula: report of a case].

A 73-year-old female was admitted to our hospital because of disturbed consciousness and left-sided motor weakness. Computed tomographic scans demonstrated a hemorrhagic infarction in the right parietal region. Right carotid angiograms showed both the posterior portion of the superior sagittal sinus (SSS) and the entire left transverse sinus simultaneously occluded. Left carotid angiograms revealed an enlarged occipital artery, which had direct communications to the left sigmoid sinus and the superior petrosal sinus. These findings were consistent with dural arteriovenous fistula (D-AVF). The laboratory examinations yieled normal results. The patient was managed conservatively with glyceol and anticonvulsants for four weeks and eventually recovered with complete resolution of hemiparesis. Follow-up angiography carried out 6 weeks later showed the SSS, partially stenotic, but recanalized with no evidence of venous congestion. The D-AVF still remained opacified, but there was a marked reduction in retrograde flow to the sigmoid sinus. Further repeated angiograms obtained at 10 months after the onset confirmed complete recanalization of the SSS and disappearance of the D-AVF. From the timing of the angiographies, we considered that the sinus occlusion was caused by the high arterial flow to the fistula and its disappearance made recanalization of SSS possible.

[Usefulness and problems of high dose chemotherapy using CBDCA, VP-16, and MCNU with peripheral blood stem cell transplantation in pediatric malignant brain tumors].

The aim of this study was to evaluate efficacy of high dose chemotherapy and restoration of hamatopoiesis following peripheral blood stem cell transplantation (PBSCT). Three patients with pediatric malignant brain tumors (two medulloblastomas and one medullomyoblastoma) underwent high dose chemotherapy including CBDCA, VP-16, and MCNU with PBSCT. Postcontrast-MR images revealed no abnormal enhancing lesions after high dose chemotherapy in all patients. One patient with medulloblastoma has remained complete remission one year and seven months after the termination of treatment. Another patient with medullomyoblastoma died of respiratory distress syndrome one month after the second course of high dose chemotherapy. The other patient with medulloblastoma, which received PBSCT and high dose chemotherapy at the time of tumor recurrence after failure of initial treatment, suffered from multiple disseminated lesions five months after the treatment. PBSCT contributed prompt recovery from hematopoietic dysfunction in all patients. These results indicate that PBSCT may play an important adjuvant to chemotherapy and further offer a safer and more effective high dose chemotherapy in pediatric malignant brain tumor patients.

Superselective angio-CT of brain tumors.

PURPOSE: To determine the efficacy of superselective angio-CT in the diagnosis of astrocytoma. METHODS: Nineteen patients with astrocytoma had superselective angio-CT before chemotherapeutic agents were administered via superselective intraarterial infusion. CT was performed after contrast material was delivered through a microcatheter, which had been advanced into the feeding arteries of the tumor. Superselective angio-CT scans were compared with digital subtraction angiograms, conventional contrast-enhanced CT scans, and contrast-enhanced T1-weighted MR images. RESULTS: Superselective angio-CT scans depicted contrast enhancement of the tumor in all of the patients and the medullary veins of the tumors in 32% of the patients. Digital subtraction angiograms showed tumor stains in 68% of the patients and the medullary veins in only 5%. Conventional CT scans and MR images showed contrast enhancement of the tumor in 89% of the patients. Superselective angio-CT scans confirmed the proper position of the catheter tip for the infusion of a chemotherapeutic agent. CONCLUSIONS: Superselective angio-CT can be used to depict contrast enhancement of tumors and the vascular structures that are characteristic of astrocytomas.

Long-term positron emission tomography evaluation of slowly progressive gliomas.

Non-invasive positron emission tomography (PET) was performed to identify changes in blood flow and metabolism, specific to early stages of tumour occurrence or recurrence. 2 patients with slowly progressive gliomas from early to late stages of tumour development were analysed by serial PET measurements of circulation and metabolism using 15O-gas and 18F-fluorodeoxyglucose. PET revealed a persistent depression of oxygen metabolism, as indicated by the regional oxygen extraction fraction or metabolic rate of oxygen, in the regions where tumours were later found. Abnormal blood flow and metabolism may precede the morphological changes detected by computed tomography (CT) in patients with gliomas.

[Sequential analysis of the integrated images of PET, CT and MR in malignant brain tumors before and after radiotherapy].

11C-methyl-L-methionine (C-11 Met)PET, CT and MR imaging were performed in eleven patients with malignant brain tumors before and after RT to evaluate the usefulness of positron emission tomography (PET) in monitoring tumor response to radiotherapy (RT). The subjects included five cases of intracranial malignant lymphoma (ICML) and six cases of glioma. C-11 Met uptake by the tumor (T) and the contralateral gray matter (NT) was calculated on the PET images. The mean T/NT ratio of the ICMLs and gliomas changed from 2.33 and 1.87, respectively, before RT to 1.31 and 1.58, respectively, after RT.No significant difference was found between the T/NT ratios before and after RT in either the ICMLs or the gliomas (t-test). We tentatively defined the minimum T/NT ratio, 1.2, as the threshold between tumor and nontumor regions. Tumors with a ratio of 1.2 or more were imaged as "hot" (MET) and coincided with CT or MR image lesions which were visualized as contrast-enhancing (CE) and low-density (LD) or high-intensity (HI). The relationships between PET, CT and MRI lesions were classified as follows: Type I (MET < or = CE), Type II [CE < MET < LD (HI)], Type III [LD(HI) < or = MET]. MET lesions extending regionally ( > 1 cm) beyond the respective CT or MR image lesions were designated "MET-extension" and LD (HI) lesions protruding ( > 1 cm) beyond the MET lesions were recorded as "LD (HI)-extension" on the integrated images. The type II pattern of the MET areas in all five cases of ICML before RT had changed to Type I in one case, Type III in one case and Type II in three cases, after RT, while the two Type II patterns and four Type III patterns of the gliomas had converted to four Type II and two Type III patterns. These findings indicate that gliomas tend to invade into areas of peritumoral edema more than ICMLs. There were two ICML MET-extension sites in the cortex before RT, as opposed to two in the cortex, one in the basal ganglia, one in the thalamus, and one in the corpus callosum among the gliomas. On follow-up CT or MR images MET-extension (75%) had converted to a CE or LD (HI) region. Four ICML LD (HI)-extension sites before RT were found in periventricular white matter, versus one in the cortex and three in the white matter among the gliomas. LD (HI)-extension appeared to represent vascular edema because it decreased or diminished after completion of therapy. Sequential analysis of integrated C-11 Met PET, CT and MR images is useful in detecting the extent of tumor infiltration by ICMLs and gliomas, particularly at an early stage, and for evaluating the effect of RT in the treatment of both.

Enhancement of 5-fluorouracil cytotoxicity by cisplatin in brain tumour cell lines.

Cisplatin reportedly plays an important role as a chemical modulator in enhancing the chemotherapeutic effects of 5-fluorouracil on tumour cells. The aim of the present study was to test the synergistic cytotoxicity of cisplatin and 5-fluorouracil in 5-fluorouracil-resistant (C6) and -sensitive (9L) rat brain tumour cell lines. Survival fractions, determined using colony-formation assays, were compared following 5-fluorouracil treatment, with and without cisplatin. The presence of cisplatin (1-10 microM) enhanced cytotoxicity by more than three times compared with 5-fluorouracil alone in 5-fluorouracil-resistant C6 cells, whereas no enhancement effects were noted in 9L cells. These results suggest that a cisplatin-fluorouracil-based regimen may be promising in the treatment of 5-fluorouracil-resistant brain tumours.