Nonlinear optical imaging: toward chemical imaging during neurosurgery

Tumor recognition and precise tumor margin detection presents a central challenge during neurosurgery. In this contribution we present our recent all-optical approach to tackle this problem. We introduce various nonlinear optical techniques, such as coherent anti-Stokes Raman scattering (CARS), second-harmonic generation (SHG) and two-photon fluorescence (TPEF), to study the morphology and chemical composition of (ex vivo) brain tissue. As the experimental techniques presented are contact-free all-optical techniques, which do not rely on the administration of external (fluorescence) labels, we anticipate that their implementation into surgical microscopes will provide significant advantages of intraoperative tumor diagnosis. In this contribution an introduction to the different optical spectroscopic methods will be presented and their implementation into a multimodal microscopic setup will be discussed. Furthermore, we will exemplify their application to brain tissue, i.e. both pig brain as a model for healthy brain tissue and human brain samples taken from surgical procedures. The data to be discussed show the capability of a joint CARS/SHG/TPEF multimodal imaging approach in highlighting various aspects of tissue morphochemistry. The consequences of this microspectroscopic potential, when combined with the existing technology of surgical microscopes, will be discussed.