ABSTRACT
Currently there is a gap between pre-operative imaging techniques, such as magnetic resonance imaging (MRI), that provide a rough location and diagnosis of the disease (e.g. tumor, seizure focus), and the histopathology that provides an accurate diagnosis, but up to 24 hours after the surgery. Occasionally, intra-operative analysis using hematoxylin-and-eosin (H&E) stained sections of snap-frozen material or smear preparations is performed by the pathologist to help establish brain tumor boundaries, but this procedure only allows analysis of small, selected regions, can only be performed on tissue fragments that are already resected, and is rather time-consuming (frozen section diagnosis) or does not allow analysis of tumors in the histological context (smear preparations). Fluorescence imaging techniques are increasingly used during surgery [1,2] but are associated with several drawbacks, such as heterogeneous delivery and nonspecific staining [3,4]. In particular, low-grade gliomas and normal brain tissue have an intact blood–brain barrier and take up little circulating dye [5–7]. Alternative techniques are therefore required, that can diagnose tissue without fluorescent labels and with a speed that enables “live” feedback to the surgeon while he/she operates.
