An Unsupervised Approach for Treatment Effectiveness Monitoring Using Curvature Learning

Contrast-enhanced ultrasound could assess whether cancer chemotherapeutic agents work in days, rather than waiting 2–3 months, as is typical using the Response Evaluation Criteria in Solid Tumors (RECIST), therefore avoiding toxic side effects and expensive, ineffective therapy. A total of 40 mice were implanted with human colon cancer cells: treatment-sensitive mice in control (n = 10, receiving saline) and treated (n = 10, receiving bevacizumab) groups and treatment-resistant mice in control (n = 10) and treated (n = 10) groups. Each mouse was imaged using 3D dynamic contrast-enhanced ultrasound with Definity microbubbles. Curvature learning, an unsupervised learning approach, quantized pixels into three classes—blue, yellow, and red—representing normal, intermediate, and high cancer probability, both at baseline and after treatment. Next, a curvature learning score was calculated for each mouse using statistical measures representing variations in these three color classes across each frame from cine ultrasound images obtained during contrast administration on a given day (intra-day variability) and between pre- and post-treatment days (inter-day variability). A Wilcoxon rank-sum test compared score distributions between treated, treatment-sensitive mice and all others. There was a statistically significant difference in tumor score between the treated, treatment-sensitive group (n = 10) and all others (n = 30) (p = 0.0051). Curvature learning successfully identified treatment response, detecting changes in tumor perfusion before changes in tumor size. A similar technique could be developed for humans.