Categorizing Extent of Tumor Cell Death Response to Cancer Therapy Using Quantitative Ultrasound Spectroscopy and Maximum Mean Discrepancy

Quantitative ultrasound (QUS) spectroscopic techniques in conjunction with maximum mean discrepancy (MMD) have been proposed to detect, and to classify noninvasively the levels of cell death in response to cancer therapy administration in tumor models. Evaluation of xenograft tumor responses to cancer treatments were carried out using conventional-frequency ultrasound at different times after chemotherapy exposure. Ultrasound data were analyzed using spectroscopic techniques and multi-parametric QUS spectral maps were generated. MMD was applied as a distance criterion, measuring alterations in each tumor in response to chemotherapy, and the extent of cell death was classified into less/more than 20% and 40% categories. Statistically significant differences were observed between pre- and post-treatment groups at different times after chemotherapy exposure, suggesting a high capability of proposed framework for detecting tumor response noninvasively. Promising results were also obtained for categorizing the extent of cell death response in each tumor using the proposed framework, with gold standard histological quantification of cell death as ground truth. The best classification results were obtained using MMD when applied on histograms of QUS parametric maps. In this case, classification accuracies of 84.7% and 88.2% were achieved for categorizing extent of tumor cell death into less/more than 20% and 40%, respectively.