Integration of 5-ALA Fluorescence Lifetime Imaging with Stereotactic Surgical Navigation for Quantitative Real-Time Spatial Localization of Tumor During Neurosurgical Procedures

PROJECT SUMMARY/ABSTRACT
Maximal surgical resection of the most common primary brain cancer, glioblastoma (GBM), has been shown to
improve overall survival in a highly morbid disease. However, delineation of residual tumor at the margins of
surgical resections can be challenging using conventional techniques, and therefore the use of fluorescence
guided surgery (FGS) has emerged as an adjuvant tool for tumor detection. At present, only one agent, 5-
aminoleveulinic acid (5-ALA), is approved for detection of GBM during surgery. Metabolism of 5-ALA into
protoporphyrin IX (PpIX) is detected qualitatively by wide-field fluorescence imaging through the surgical
microscope. This intensity-based detection is non-quantitative and background light-sensitive, requiring the
surgeon to work in a dark field. We have developed a fiber-based pulse-excitation time-resolved method for
Fluorescence Lifetime Imaging (FLIm) to detect quantitative PpIX fluorescence in real-time under full
illumination conditions. Our goal in this study is to integrate the point-scanning FLIm technology with an
existing intraoperative stereotactic neuronavigation system produced by BrainLab to spatially co-register FLIm
data across the surgical field for applicable surgical guidance. We aim to develop new software and tissue
classifiers based on primary patient data, and to apply the integrated technology in a prospective clinical study
to demonstrate the benefits for surgical navigation.
To achieve the overall goal of developing a new integrated technology which is immediately applicable for
routine use in brain tumor resections, we will undertake the following aims: Aim 1) To develop new software for
integration of the FLIm device with the BrainLab neuronavigation system for real-time acquisition of spatial
positioning of FLIm data and display of the data overlaid on the patient’s imaging in the navigation space. Aim
2) To develop classifiers for surgically resectable tumor based on PpIX fluorescence lifetime thresholds
determined through a prospective study correlating FLIm data to tissue biopsies. Aim 3) To validate the
accuracy of integrated FLIm-based navigation in identifying residual tumor tissue to facilitate a greater extent of
resection in a prospective clinical study.

Grant Number: 5R01CA277380-03
NIH Institute/Center: NIH
Principal Investigator: Orin Bloch