A statistical, voxelised model of prostate cancer for biologically optimised radiotherapy.

Background and purpose: Radiation therapy (RT) is commonly indicated for treatment of prostate cancer (PC). Biologicallyoptimised RT for PC may improve disease-free survival. This requires accurate spatial localisation and characterisation of tumour lesions. We aimed to generate a statistical, voxelised biological model to complement Material and methods: Ex vivo prostate MRI and histopathological imaging were acquired for 63 PC patients. These data were co-registered to derive three-dimensional distributions of graded tumour lesions and cell density. Novel registration processes were used to map these data to a common reference geometry. Voxelised statistical models of tumour probability and cell density were generated to create the PC biological atlas. Cell density models were analysed using the Kullback-Leibler divergence to compare normal vs. lognormal approximations to empirical data. Results: A reference geometry was constructed using ex vivo MRI space, patient data were deformably registered using a novel anatomy-guided process. Substructure correspondence was maintained using peripheral zone definitions to address spatial variability in prostate anatomy between patients. Three distinct approaches to interpolation were designed to map contours, tumour annotations and cell density maps from histology into ex vivo MRI space. Analysis suggests a log-normal model provides a more consistent representation of cell density when compared to a linear-normal model. Conclusion: A biological model has been created that combines spatial distributions of tumour characteristics from a population into three-dimensional, voxelised, statistical models. This tool will be used to aid the development of biologically-optimised RT for PC patients.