Deep learning for dose assessment in radiotherapy by the super-localization of vaporized nanodroplets in high frame rate ultrasound imaging

Objective. External beam radiotherapy is aimed to precisely deliver a high radiation dose to malignancies, while optimally sparing surrounding healthy tissues. With the advent of increasingly complex treatment plans, the delivery should preferably be verified by quality assurance methods. Recently, online ultrasound imaging of vaporized radiosensitive nanodroplets was proposed as a promising tool for in vivo dosimetry in radiotherapy. Previously, the detection of sparse vaporization events was achieved by applying differential ultrasound (US) imaging followed by intensity thresholding using subjective parameter tuning, which is sensitive to image artifacts. Approach. A generalized deep learning solution (i.e. BubbleNet) is proposed to localize vaporized nanodroplets on differential US frames, while overcoming the aforementioned limitation. A 5-fold cross-validation was performed on a diversely composed 5747-frame training/validation dataset by manual segmentation. BubbleNet was then applied on a test dataset of 1536 differential US frames to evaluate dosimetric features. The intra-observer variability was determined by scoring the Dice similarity coefficient (DSC) on 150 frames segmented twice. Additionally, the BubbleNet generalization capability was tested on an external test dataset of 432 frames acquired by a phased array transducer at a much lower ultrasound frequency and reconstructed with unconventional pixel dimensions with respect to the training dataset. Main results. The median DSC in the 5-fold cross validation was equal to similar to 0.88, which was in line with the intra-observer variability (=0.86). Next, BubbleNet was employed to detect vaporizations in differential US frames obtained during the irradiation of phantoms with a 154 MeV proton beam or a 6 MV photon beam. BubbleNet improved the bubble-count statistics by similar to 30% compared to the earlier established intensity-weighted thresholding. The proton range was verified with a -0.8 mm accuracy. Significance. BubbleNet is a flexible tool to localize individual vaporized nanodroplets on experimentally acquired US images, which improves the sensitivity compared to former thresholding-weighted methods.