OBJECTIVE AND IMPORTANCE:To use intraoperative magnetic resonance imaging, including magnetic resonance angiography and diffusion-weighted imaging, to monitor the surgical treatment of a patient with an intracranial aneurysm.TECHNIQUE:Intraoperative imaging was performed with a ceiling-mounted, mobile, 1.5-T magnet (developed in collaboration with Innovative Magnetic Resonance Imaging Systems, Inc., Winnipeg, MB, Canada) that included high-performance 20-mT/m gradients. Pre- and postclipping, intraoperative, T1-weighted, angiographic and diffusion-weighted magnetic resonance images were obtained from a patient with an incidental, 8-mm, anterior communicating artery aneurysm.RESULTS:T1-weighted images demonstrated brain anatomic features, with visible shifts induced by surgery. Magnetic resonance angiography demonstrated the aneurysm and indicated that, after clipping, the A1 and A2 anterior cerebral artery branches were patent. Diffusion-weighted studies demonstrated no evidence of brain ischemia.CONCLUSION:For the first time, intraoperative magnetic resonance imaging has been used to monitor the surgical treatment of a patient with an intracranial aneurysm.

At the University of Cincinnati, we developed a. shared-resource, intraoperative magnetic resonance imaging (iMRI) center that combines the ability to perform diagnostic scans and intraoperative imaging for tumor resection. The magnet is a Hitachi AIRIS 11, 0.3-T, vertical-field MRI unit similar to open MRI units used for outpatient scanning. The Hitachi unit provides image quality that is comparable with images obtained with a 1.5-T MRI and averages 20 minutes of scanning time. Use of a rotating tabletop allows surgical procedures to be performed outside of the 5-G line where standard neurosurgical instruments and operating microscopes are available. The MRI has demonstrated effectiveness in obtaining optimal resection for pituitary tumors as well as low-grade and high-grade gliomas. We performed 2,832 diagnostic procedures and 213 surgical procedures with the Hitachi AIRIS 11, 0.3-T iMRI and showed its important role in surveillance to prevent complications. The iMRI counteracts the problem of brain shift; skull fiducials are used to update registration for frameless stereotaxy with intraoperative images. This system provides a cost advantage versus other systems, and its ability to perform diagnostic scanning makes this a cost-effective solution for iMRI. In this review, we describe the 0.3-T iMRI center, Our technique of using the iMRI for tumor resection, and our initial results with glioma resection and transsphenoidal procedures.

OBJECTIVE:Brachytherapy with temporary implants may prolong survival in patients with recurrent glioblastoma multiforme (GBM), but it is associated with relatively high costs and morbidity. This study reports the time to progression and survival after permanent implantation of iodine-125 seeds for recurrent GBM and examines factors predictive of outcome.METHODS:Forty patients with recurrent GBM were treated with maximal resection plus permanent placement of iodine-125 seeds into the tumor bed. A total dose of 120 to 160 Gy was administered, and patients were followed up with magnetic resonance imaging scans every 2 to 3 months.RESULTS:Actuarial survival from the time of implantation was 47 weeks, with 7 of 40 patients still alive at a median of 59 weeks after implantation. Survival was significantly better for patients younger than 60 years, and a trend for longer survival was demonstrated with gross total resection and tumors with a low MIB-1 (a nuclear antigen present in all cell cycles of proliferating cells) staining index. Median time to progression was 25 weeks and, on multivariate analysis, was favorably influenced by gross total resection and patient age younger than 60 years. After implantation, 27 of 30 patients with failure had a local component to the failure. No patient developed symptoms attributable to radiation necrosis or injury.CONCLUSION:Permanent iodine-125 implants for recurrent GBM result in survival comparable with that described in previous reports on temporary implants, but with less morbidity. Results are most favorable for patients who are younger than 60 years, and who undergo gross total resection. Despite this aggressive treatment, most patients die as a consequence of locally recurrent disease.

Purpose: This study was designed to evaluate a combined modality treatment for malignant gliomas using radiation therapy with a radiosensitizer and an adjuvant chemotherapy regimen designed to modify resistance to BNCU.Methods and Materials: Patients were eligible if they were 15 years of age or older, and had newly diagnosed glioblastoma multiforme (GBM), or anaplastic glioma (AG). Treatment consisted of external beam radiotherapy given to a dose of 60 Gy using a single daily fraction Monday to Friday. Concurrent hydroxyurea at a dose of 300 mg/m2 every 6 h every other day was given during radiation. Following radiotherapy, patients were then treated with BCNU and 6-Thioguanine (6TG). The 6-TG was given by mouth every 6 h for 12 doses prior to BCNU. Patients were initially treated with 60 mg/m2/dose of 6TG, with escalation to a maximum dose of 100 mg/m2/dose. The primary study end points were time to tumor progression and survival.Results: A total of 245 eligible patients were enrolled from 1/18/88 to 12/26/91. The histologic subtypes included 135 GBM, and 110 with AG (103 with anaplastic astrocytoma, 7 with high-grade mixed oligoastrocytoma). For the GBM group, the median time to tumor progression (TTP) and median survival were 33 (95% CI 26, 39) and 56 (95% CI 49, 69) weeks, respectively. For the AG group the median TTP was 282 weeks (95% lower confidence bound = 155 weeks). Median survival for this group has not been reached (95% lower confidence bound = 284 weeks) with a median follow-up for surviving patients of 298 weeks. A proportional hazards model was used to look at potential prognostic factors for survival, including initial Karnofsky Performance Scale (KPS), age, and extent of surgery, as well as dose of 6TG. Higher KPS, and lower age, predicted for longer survival (p < 0.01, < 0.001) in GBM patients; lower age was significant (p = 0.05) for AG cases. A higher (greater than 95 mg/m2) or lower dose of 6TG was not statistically significant in this model.Conclusions: This therapy was no more effective in patients with GBM than other reported series. In patients with malignant gliomas other than GBM, prolonged progression-free and overall survival is noted, without a median survival reached at the time of this report. In this subset of AG patients, survival is comparable to recent studies using halogenated prymidines during radiation and Procarbazine, CCNU, and Vincristine (PCV) as adjuvant chemotherapy.

To reduce the chemical shifts during magnetic resonance (MR) imaging, the authors replaced the petroleum gel in the Brown-Roberts-Well (BRW) MR localizer with chromium chloride. Computed tomography and MR scans were obtained of a phantom skull containing objects with known spatial coordinates. A 2-to 3-mm systematic spatial shift in the frequency-encoded direction was observed with petroleum gel, but not with CrCl3. Results were verified by reconstructing the three-dimensional spatial location of each object using X-Knife computer software. The authors conclude that spatial localization is more accurate with a CrCl3-filled than a petroleum-filled BRW-MR localizer.

Microsatellite length instability, probably resulting from defective DNA mismatch repair mechanisms, has been described in a variety of cancers. Such genetic instability may play a significant role in tumor formation and progression. To investigate the role of microsatellite alterations in meningioma tumorigenesis and progression, we examined 33 microsatellite markers on nine chromosomes for abnormalities in 18 benign, 15 atypical, and 11 malignant meningiomas. In each tumor, at least 15 markers were investigated. Microsatellite instability was not detected in any of the cases examined. However, loss of heterozygosity for markers from various chromosomes was seen frequently among atypical and malignant meningiomas. Although some of these chromosomal losses might represent random events, our data also indicate a role for specific loci on chromosome arms 14q, 1p, 10q, and possibly 9p in the development of malignancy in meningiomas. Our results argue against a significant role for a generalized microsatellite instability phenotype in meningiomas, but they suggest that genomic instability resulting in frequent allelic deletions may contribute to meningioma progression. Genes Chromosom Cancer 16:265–269 (1996). © 1996 Wiley‐Liss, Inc.

The expression of connexin43, the primary gap-junction constituent of glial cells, was evaluated at the messenger RNA and protein levels in different grades of astrocytoma to investigate the relevance of gap junctions in herpes simplex virus-thymidine kinase (HSV-tk)-mediated gene therapy of brain tumors. Transduction of the retroviral-mediated HSV-tk gene into tumor cells with subsequent administration of ganciclovir has recently been used as an experimental therapeutic strategy for treatment of brain tumors. One aspect of this approach is the bystander effect, which augments the efficacy of this therapeutic approach. Glioblastoma cells with minimum levels of connexin43 protein were transfected with a connexin43 complementary DNA. These cells manifested a marked increase in the in vitro bystander effect, supporting the contention that the in vitro bystander effect is a consequence of metabolic cooperation between cells mediated by gap junctions. To assess relative levels of gap-junction protein expression in the relevant tumor type, we examined primary astrocytomas, primary astrocytoma cell cultures, and glioblastoma cell lines. Although most astrocytoma tumor samples expressed connexin43, they differed in the level of expression, with the greatest variation exhibited in high-grade astrocytomas. Primary glioblastoma cell cultures and established glioblastoma cell lines also displayed some variability in connexin43 levels. In aggregate, our results anticipate that glioblastomas will have a varied bystander effect during HSV-tk gene therapy depending on the level of connexin43 expression.

Vascular permeability can be visualized by Evans Blue (EB) extravasation and quantified by spectrophotometry after formamide extraction of the tissue. However, formamide extracts show significant turbidity, which may contribute to the total optical density at the wavelength of measurement (e.g., 620 lambda). We developed a simple method for estimating the component of the total optical density of a dyed specimen contributed by turbidity. Our method, which uses a determination of turbidity made at another point of the light spectrum (740 lambda), was more precise than two other EB quantification techniques. We therefore recommend it for individual correction of formamide extracts of spinal cord specimens. The application of this technique to the brain remains to be determined.

To investigate chromosomal events that underlie formation and progression of meningiomas, we have examined a set of 18 benign (WHO grade I), 15 atypical (grade II), and 13 anaplastic/malignant (grade III) meningiomas for loss of heterozygosity (LOH) on chromosomes 1p, 6p, 9q, 10q, and 14q. Frequent loss of loci on these chromosomes was seen in grade II and grade III tumors, specifically, 14q (II and III, 47 and 55%), 1p (40 and 70%), and 10q (27 and 40%). In contrast, LOH for these loci was infrequent in benign meningiomas, specifically, 14q (0%), 1p (11%), and 10q (12%). The smallest common regions of deletion that could be defined were 14q24-q32, 1p32-pter, and 10q24-qter. These observations indicate the likely presence of tumor suppressor genes in these regions that are involved in the development of WHO grade II and grade III meningiomas. Because LOH for loci on chromosomes 1p and 10q was found in tumors of all grades and because the frequency of LOH in all three regions increased with tumor grade, these results would support a model for the formation of aggressive meningiomas through tumor progression.

We examined levels of mRNA and protein for N-cadherin, the predominant cadherin in neural tissues, and mRNA levels for the cadherin-associated protein, alpha-catenin, in a series of gliomas and in glioblastoma cell lines. mRNA levels for N-cadherin and alpha-catenin were significantly higher in glioblastomas than in low-grade astrocytomas or normal brain, while the levels of intact N-cadherin protein were similar in glioblastomas, low-grade astrocytomas and brain. In addition, there was no consistent relationship between invasiveness and expression of N-cadherin and alpha-catenin in highly invasive vs minimally invasive tumours within the same histopathological grade. To assess further the relationship between cadherin expression and neural tumour invasion, we measured N-cadherin expression, calcium-dependent cell adhesion and motility of several glioblastoma cell lines. While all N-cadherin-expressing lines were adhesive, no correlation was seen between the level of N-cadherin expression and cell motility. Together, these findings imply that, in contrast to the role played by E-cadherin in carcinomas, N-cadherin does not restrict the invasion of glioblastomas.

The expression of complement regulatory proteins (CRP) on the surface of neoplastic cells has been proposed as a mechanism by which these cells evade immune surveillance. We have examined the RNA expression of the genes that encode 5 kinds of CRP in various human brain tumors to determine whether CRP expression might play a role in the malignant progression of these tumors. The benign and atypical meningiomas, and the astrocytomas showed high expression of SP-40,40, low expression of CD59, and barely detectable expression of CD46, CD55 and S-protein. The benign and atypical menigiomas showed significantly greater expression of SP-40,40 at the RNA level when compared to malignant meningiomas. This study describes the mRNA expression of meningiomas, astrocytomas, tumor cell lines and normal human tissues.