Glioblastoma (GBM) is the most common primary brain tumor and is almost uniformly fatal. The standard of care for GBM patients is neurosurgical resection, followed by radiation therapy and temozolomide chemotherapy. Traditional neurosurgical resection of GBMs has relied on the use of neuronavigation based on pre-operative contrast-enhanced MRI;however, it is known that nonenhancing, infiltrating tumor extends well beyond the margins of enhancement. GBM tumors rarely metastasize outside the central nervous system (CNS). Most tumors will recur within centimeters of the initial tumor, making local control of disease a high priority. Radical resection of GBM tumors, however, is challenging due to their infiltrative nature within the adjacent normal brain. Current technology relies on microsurgery, neuronavigation based on contrast- enhanced MRI, and the use of intraoperative MRI when available to maximize surgical resection. Given the patterns of tumor infiltration and recurrence, more complete resection of these tumors may improve local control and, ultimately, patient survival. We propose to improve the extent of GBM resection beyond the MRI contrast-enhancing tumor margins in patients by combining magnetic resonance spectroscopic imaging (MRSI) and 5-aminolevulinic acid (5-ALA) fluorescent-guided surgery (FGS). With the use of both of these technologies, GBM patients may undergo more complete resections of their tumor. MRSI provides, which can display the distribution of endogenous metabolites within tumor tissue as a molecular image/map, has shown benefit for the differentiation of tumor and non-tumor lesions. Choline/NAA ratio maps derived from these studies can clearly demonstrate infiltrative, high grade tumor beyond MRI contrast-enhancing regions found on preoperative MRI. On the other hand, 5- ALA FGS provides intraoperative real-time guidance to differentiate tumor from normal surrounding brain tissue. By including MRSI registered with MRI neuronavigation in combination with 5-ALA FGS, neurosurgeons will be able to push the margin of tumor resection outside the boundary of contrast-enhancement in patients with noneloquent tumors. Our proposal will take advantage of recent advances in MRSI technology and the image registration and visualization tools, which will permit clinicians to display, review and interpret MRSI data more easily, thereby making routine clinical application possible. Use of MRSI and FGS may facilitate more safe removal of tumor tissue beyond the enhancing tumor margin, potentially improving overall survival clinical outcomes for patients with GBM.

Public Health Relevance

The current standard of care for glioblastoma (GBM) patients is maximal safe resection followed by concurrent radiation therapy and temozolomide chemotherapy;however, the survival benefit conferred by neurosurgery is still under debate. Differences in overall survival depends upon resection status, with the best prognosis occurring when complete resection of enhancing tumor is achieved;otherwise, tumor resection fails to make a meaningful impact on overall survival. In this study, we will combine 5-aminolevulinic acid (5-ALA) fluorescence and high resolution magnetic resonance spectroscopic imaging (MRSI) to maximize resection of all contrast enhancing tumor and nonenhancing tumor from noneloquent brain.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Exploratory/Developmental Grants (R21)
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Special Emphasis Panel (ZRG1-SBIB-W (56))
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Nordstrom, Robert J
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Emory University
Schools of Medicine
United States
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