Engineering 3D living brain tumour equivalents as macroscopic test-systems for the development of optical imaging and sensing applications (Conference Presentation)

Successful clinical translation of optical techniques and therapies that advance the detection and treatment of high-grade brain cancer, glioblastoma multiforme (GBM), needs controlled, ethical and practical GBM models that accurately represent the biological reality. However, the available test-beds are not biologically accurate (artificial phantoms); are hindered by complex physiology and ethical concerns (animal models); or involve practical complexity due to rapid biological degradation of the samples ex vivo (surgical biopsies). Here, we present the development and validation of an in vitro, biologically accurate, 3-dimensional living GBM tumour model produced by tissue engineering techniques. Our 3D living equivalents of GBM tumour tissue are in the millimeter size range, consist of brain-specific extracellular matrix and living cells, and exhibit the relevant (often unfavorable) tissue optical properties such as scattering and tissue auto-fluorescence. The model also reproduces essential challenges in translational neurophotonics that are due to uneven tissue surface topography, variation in structural, optical and biochemical properties of matrix, heterogeneous cellular phenotypes and uneven distribution of exogenous contrast and therapeutic agents. We will show results of depth-resolved and wide-field imaging of the living GBM-equivalents in laboratory microscopic and theatre-based imaging systems under normal and fluorescence-guided surgery conditions using the typical 5-ALA to fluorescent PpIX conversion by GBM cells, in addition to 3D mapping of exogenous contrast agents such as fluorescent cell viability markers. These results illustrate the versatility of our 3D-engineered GBM model as macroscopic test-bed for the development of optical tools to improve the detection and treatment of brain cancer.