Prediction of Dose Probability Distributions Using Mixture Density Networks

Abstract: In recent years, machine learning has become utilized in external radiation therapy treatment planning. This involves automatic generation of treatment plans based on CT-scans and other spatial information such as the location of tumors and organs. The utility lies in relieving clinical staff from the labor of manually or semi-manually creating such plans. Rather than predicting a deterministic plan, there is great value in modeling it stochastically, i.e. predicting a probability distribution of dose from CT-scans and delineated biological structures. The stochasticity inherent in the RT treatment problem stems from the fact that a range of different plans can be adequate for a patient. The particular distribution can be thought of as the prevalence in preferences among clinicians. Having more information about the range of possible plans represented in one model entails that there is more flexibility in forming a final plan. Additionally, the model will be able to reflect the potentially conflicting clinical trade-offs; these will occur as multimodal distributions of dose in areas where there is a high variance. At RaySearch, the current method for doing this uses probabilistic random forests, an augmentation of the classical random forest algorithm. A current direction of research is learning the probability distribution using deep learning. A novel parametric approach to this is letting a suitable deep neural network approximate the parameters of a Gaussian mixture model in each volume element. Such a neural network is known as a mixture density network. This thesis establishes theoretical results of artificial neural networks, mainly the universal approximation theorem, applied to the activation functions used in the thesis. It will then proceed to investigate the power of deep learning in predicting dose distributions, both deterministically and stochastically. The primary objective is to investigate the feasibility of mixture density networks for stochastic prediction. The research question is the following. U-nets and Mixture Density Networks will be combined to predict stochastic doses. Does there exist such a network, powerful enough to detect and model bimodality? The experiments and investigations performed in this thesis demonstrate that there is indeed such a network.