Prediction of Lung Nodule Progression with an Uncertainty-Aware Hierarchical Probabilistic Network

Predicting whether a lung nodule will grow, remain stable or regress over time, especially early in its follow-up, would help doctors prescribe personalized treatments and better surgical planning. However, the multifactorial nature of lung tumour progression hampers the identification of growth patterns. In this work, we propose a deep hierarchical generative and probabilistic network that, given an initial image of the nodule, predicts whether it will grow, quantifies its future size and provides its expected semantic appearance at a future time. Unlike previous solutions, our approach also estimates the uncertainty in the predictions from the intrinsic noise in medical images and the inter-observer variability in the annotations. The evaluation of this method on an independent test set reported a future tumour growth size mean absolute error of 1.74 mm, a nodule segmentation Dice's coefficient of 78% and a tumour growth accuracy of 84% on predictions made up to 24 months ahead. Due to the lack of similar methods for providing future lung tumour growth predictions, along with their associated uncertainty, we adapted equivalent deterministic and alternative generative networks (i.e., probabilistic U-Net, Bayesian test dropout and Pix2Pix). Our method outperformed all these methods, corroborating the adequacy of our approach.