John E. Wanebo

In vivo imaging in a murine model of glioblastoma

OBJECTIVETo use in vivo imaging methods in mice to quantify intracranial glioma growth, to correlate images and histopathological findings, to explore tumor marker specificity, to assess effects on cortical function, and to monitor effects of chemotherapy. METHODSMice with DBT glioma cell tumors implanted intracranially were imaged serially with a 4.7-T small-animal magnetic resonance imaging (MRI) scanner. MRI tumor volumes were measured and correlated with postmortem histological findings. Different nonspecific and specific positron emission tomography radiopharmaceuticals, [18F]2-fluoro-2-deoxy-d-glucose, [18F]3′-deoxy-3′-fluorothymidine, or [11C]RHM-I, a σ2-receptor ligand, were visualized with microPET (CTI-Concorde MicroSystems LLC, Knoxville, TN). Intrinsic optical signals were imaged serially during contralateral whisker stimulation to study the impact of tumor growth on cortical function. Other groups of mice were imaged serially with MRI after one or two doses of the antimitotic N,N′-bis(2-chloroethyl)-N-nitrosourea (BCNU). RESULTSMRI and histological tumor volumes were highly correlated (r2 = 0.85). Significant binding of [11C]RHM-I was observed in growing tumors. Over time, tumors reduced and displaced (P # 0.001) whisker-activated intrinsic optical signals but did not change intrinsic optical signals in the contralateral hemisphere. Tumor growth was delayed 7 days after a single dose of BCNU and 18 days after two doses of BCNU. Mean tumor volume 15 days after DBT implantation was significantly smaller for treated mice (1- and 2-dose BCNU) compared with controls (P = 0.0026). CONCLUSIONMouse MRI, positron emission tomography, and optical imaging provide quantitative and qualitative in vivo assessments of intracranial tumors that correlate directly with tumor histological findings. The combined imaging approach provides powerful multimodality assessments of tumor progression, effects on brain function, and responses to therapy.

Hyperbaric oxygen therapy for treatment of adverse radiation effects after stereotactic radiosurgery of arteriovenous malformations: case report and review of literature

BACKGROUND Adverse radiation effects are a known complication after the use of SRS for AVMs, although it is difficult to predict which patients will manifest with these side effects. Treatment of swelling due to ARE is usually medical, but refractory cases may require surgical decompression. CASE DESCRIPTION This report presents a case of a patient who experienced AREs after SRS (edema, headaches, and nausea) that failed to respond to steroid treatment but was successfully treated with HBO. The treatment characteristics of this and of 5 other cases of radiation injury after SRS for AVM managed with HBO therapy are reviewed, and the pathophysiology is discussed. CONCLUSION Hyperbaric oxygen therapy provides a therapeutic option to treat AREs following SRS of cerebral AVMs.

Gliomas in rodent whisker barrel cortex: a new tumor model

OBJECT Surgical treatment of gliomas is difficult because they are invasive. Invasion of essential cortex often limits or precludes surgical resection. A tumor model was developed in which the rodent whisker barrel cortex was used to examine how gliomas affect cortical function and structure. METHODS Both DBT (mouse) and C6 (rat) glioma cell lines were grown in culture and labeled with the fluorescent marker Dil in vitro. Labeled tumor cells were then injected into the whisker barrel cortex of adult mice and rats. Neurological assessments were made daily and magnetic resonance (MR) images were obtained. Animals were killed by perfusion 6 to 14 days after injection, and histological sections were prepared and studied. Tumors were found in all 20 rats and 10 mice that had been injected with the C6 and DBT cell lines, respectively. The animal cells had been labeled with Dil in vitro, and all in vivo tumors proved to be Dil positive. The MR images revealed the tumor locations and serial MR images demonstrated tumor growth. Histological evaluation confirmed the location of the tumor and the disruption of barrel cortex architecture. CONCLUSIONS Both DBT and C6 glioma cell lines can be used to generate malignant glial tumors reproducibly in the whisker barrel cortex. Fluorescent labeling and cytochrome oxidase staining permit visualization of tumor growth patterns, which disrupt the barrel cortex by microscopic invasion and by gross tissue deformation. Magnetic resonance imaging demonstrates the anatomical extension of these tumors in live rodents. Using this model for further studies on the effects of malignant glioma growth on functional cerebral cortex should advance our understanding of the neurological issues and management of patients with these tumors.