Supervised Machine-Learning Enables Segmentation and Evaluation of Heterogeneous Post-treatment Changes in Multi-Parametric MRI of Soft-Tissue Sarcoma

Background: Multi-parametric MRI provides non-invasive methods for response assessment of soft-tissue sarcoma (STS) from non-surgical treatments. However, evaluation of MRI parameters over the whole tumor volume may not reveal the full extent of post-treatment changes as STS tumors are often highly heterogeneous, including cellular tumor, fat, necrosis, and cystic tissue compartments. In this pilot study, we investigate the use of machine-learning approaches to automatically delineate tissue compartments in STS, and use this approach to monitor post-radiotherapy changes. Methods: Eighteen patients with retroperitoneal sarcoma were imaged using multi-parametric MRI; 8/18 received a follow-up imaging study 2-4 weeks after pre-operative radiotherapy. Eight commonly-used supervised machine-learning techniques were optimized for classifying pixels into one of five tissue sub-types using an exhaustive cross-validation approach and expert-defined regions of interest as a gold standard. Final pixel classification was smoothed using a Markov Random Field (MRF) prior distribution on the final machine-learning models. Findings: 5/8 machine-learning techniques demonstrated high median cross-validation accuracies (82.2%, range 80.5-82.5%) with no significant difference between these five methods. One technique was selected (Naive-Bayes) due to its relatively short training and class-prediction times (median 0.73 and 0.69ms, respectively on a 3.5 GHz personal machine). When combined with the MRF-prior, this approach was successfully applied in all eight post-radiotherapy imaging studies and provided visualization and quantification of changes to independent STS sub-regions following radiotherapy for heterogeneous response assessment. Interpretation: Supervised machine-learning approaches to tissue classification in multi-parametric MRI of soft-tissue sarcomas provide quantitative evaluation of heterogeneous tissue changes following radiotherapy.