Discussion
Patient Derived Organoids (PDOs) are multicellular, self-assembled 3D cell structures which mimic the tissue architecture of the organ that they are derived from. These mini organs e.g. mini guts can be used to duplicate normal behaviour or disease pathologies. Studies show that patients and their derived organoids respond similarly to drugs. Therefore, PDOs have the potential to make a marked impact in the field of drug discovery and development as a next generation pre-clinical drug screening tool for application in the pharmaceutical industry. For this to be achieved, it is key to link pathological dynamics and drug impact to quantifiable morphometric features of the organoids. Using colorectal cancer organoid lines expanded using Cellesce Limited’s bio-processor technology, we are developing a pipeline which analyses 3D images of organoids. This will be used to elucidate the mechanism of action of drug compounds and understand their impact on the underlying organoid biology and morphology. To optimise our 3D image analysis pipelines, we embrace advancements in imaging technologies such as Lightsheet microscopy and ever more accessible cloud and cluster computing solutions. A central challenge is to create a reproducible, modular, scalable and data efficient image analysis pipeline for the efficient high content, high throughput, screening of organoids. To do so, we have incorporated computationally efficient modules into a pipeline such as the Segmentation Potts model, LOCO-EFA, and tissue topology analysis. Furthermore, we are developing the image analysis pipeline in a versatile way, such that it will be easily adaptable to incorporate third party modules.