Presentation Abstract

Session: Top Abstracts 1
Abstract Number: ST-22
Title: Combined fluorescence and reflectance spectroscopy for in vivo quantification of cancer biomarkers in low- and high-grade glioma surgery
Presentation Start: 11/18/2011 9:30:00 AM
Presentation End: 11/18/2011 9:45:00 AM
Authors: Pablo A. Valdes1, Anthony Kim2, Frederic Leblond1, Olga M. Conde3, Brent T. Harris4, Keith D. Paulsen1, Brian C. Wilson2, David W. Roberts5, 1Dartmouth College, Hanover, NH, 2Ontario Cancer Institute/University of Toronto, Toronto, ON, Canada, 3University of Cantabria, Santander, Spain, 4Georgetown University, Washington, DC, 5Dartmouth Hitchcock Medical Center, Lebanon, NH
Category: Surgical Therapies
Educational Objective 1: 6. Apply advances in imaging and neuropathology to diagnose, prognose, and measure response to therapy for patients with CNS tumors
Educational Objective 2: 3. Discuss new research on cell biology, signal transduction inhibition strategies, and factors associated with angiogenesis and invasion in brain tumors
Educational Objective 3: 4. Apply therapeutic strategies related to new research on genes that are associated with brain tumors
Abstract: Gliomas represent a heterogeneous group of brain tumors, with extent of resection shown as a significant factor influencing post-surgical recurrence and prognosis. Recently, use of 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) fluorescence-guided resection has shown promise for improving the degree of resection in high-grade gliomas. We have shown that absolute quantification of PpIX biomarker in tissue significantly improves tumor detection across a range of tumor histologies. Nevertheless, despite improved detection for tumor tissue with this biomarker, and as a result of the inter- and intra-tumor heterogeneity of gliomas and multifaceted nature of neoplastic processes, individual biomarkers are not sufficient for achieving optimal tumor tissue diagnosis. Here, we hypothesized that use of multiple factors (i.e., biomarkers) is necessary to maximize the diagnostic and predictive power of optical technologies for tumor tissue delineation. We used fluorescence and reflectance spectral signatures for in vivo quantification of multiple biomarkers during glioma surgery, with fluorescence contrast provided by exogenously-induced PpIX following administration of ALA. We performed light-transport modeling to quantify multiple biomarkers indicative of tumor biological processes intraoperatively, including the local concentration of PpIX and associated photoproducts, total hemoglobin concentration, oxygen saturation and optical scattering parameters. We developed a diagnostic algorithm for intraoperative tissue delineation that accounts for the combined tumor-specific predictive capabilities of these quantitative biomarkers. Tumor tissue delineation achieved accuracies of up to 94% (specificity = 94%, sensitivity = 94%) across a range of glioma histologies beyond current state-of-the-art optical approaches, including state-of-the-art fluorescence image guidance. These results suggest the ability of a quantitative multiple biomarker approach to detect both tumor bulk and infiltrating glioma tissues, especially in low-grade gliomas where the impact on patient prognosis and survival could be substantial. This multiple biomarker strategy opens the door to optical methods for surgical guidance that use in vivo quantification of well-established neoplastic processes.

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