Evaluating uptake of multiple fluorescent contrast agents in brain tumors simultaneously using whole animal multi-spectral cryo-imaging.

Abstract

MRI images of gadolinium-based contrast agents (GBCA's) acquired before surgery are often registered to patients and used to guide surgical resection of intracranial tumors. Yet, the accuracy of these MR images in describing the surgical field degrades as surgery progresses; a well-recognized problem which has prompted efforts to develop new techniques that provide updated guidance information on residual tumor location. These efforts span a wide array of technologies, including image updating with deformation models, intraoperative MRI, and fluorescence guided surgery, among others. However, introduction of a straightforward technique that provides surgeons with a current view of GBCA distribution in real time remains an important goal. In this context, development of a fluorescent agent that recapitulates the kinetic behavior of GBCA's could provide familiar information directly in the surgical field in real time. To advance this strategy, we have begun identifying fluorescent contrast agents that show similar kinetic behavior to GBCA's. Using a novel hyperspectral whole body cryo-imaging system, we acquired high-resolution 3-D volumes of the distribution of multiple candidate fluorophores in whole heads bearing orthotopic brain tumors. Preliminary results reveal significant differences in the distribution of candidate optical agents, some of which show strong similarity to the GBCA uptake. Identification and eventual translation of a reliable GBCA-optical analog could improve and simplify surgical resection of brain tumors.