Introduction: Fluorescence guided surgery has been shown to help guide the resection of brain tumors. State of the art modified fluorescence microscopes perform visual assessments of the raw fluorescence(1). Studies have demonstrated that current state of the art clinical systems perform assessments that are subjective and qualitative in nature. We have shown that these assessments are limited in their diagnostic potential and do not fully exploit the full potential of intraoperative fluorescent agents, leaving tumor tissue behind(2). Here we present a novel technique that performs quantitative estimates in real time and across the full surgical field of view to extract both absolute fluorophore levels and intrinsic biomarkers such as hemoglobin concentration and oxygen saturation.
Methods: We developed a system that performs simultaneous fluorescence estimates and single snapshot optical properties (SSOP) imaging, which we call qF-SSOP. SSOP imaging estimates tissue optical properties and applies them in a light transport model to correct the raw fluorescence. Studies in tissue simulating phantoms and glioma rodent models were used to demonstrate the quantitative capabilities of the technique.
Results: Analysis of tissue simulating phantoms demonstrated a clear improvement in estimating the actual, true fluorophore levels using qF-SSOP compared to standard raw fluorescence estimates. Results in glioma rodent models confirmed that qF-SSOP assessments of fluorescence enable proper delineation of tumor compared to the raw fluorescence. Further, estimates of tissue optical properties have the potential for estimation of multiple biomarkers to further enhance optical multiplexing of tumor.
Conclusions: We present a novel intraoperative technique, qF-SSOP, that performs quantitative estimates of the tissue fluorescence. This technique is a significant allowing for the first time to perform quantitative fluorescence imaging in real-time during surgery. qF-SSOP provides a technique for real time multiplexing of fluorophore and intrinsic biomarker levels which has the to potential to significantly advance optical imaging in neurosurgical applications
Patient Care: Provides a practical, feasible technology to significantly improve neurosurgical fluorescence guidance
Learning Objectives: 1) Learn about tissue light interaction in the context of fluorescence attenuation
2) Learn about the difference between relative and quantitative fluorescence
3) Learn about qF-SSOP as a novel optical imaging technique for neurosurgical guidance
References: 1. Stummer W et al. Lancet Oncol 7:392-401, 2006
2. Valdes PA et al. J Neurosurg 115:11-17, 2011
3. Vervandier J & Gioux SBiomed Opt Express 4:2938-2944, 2013