Cancer therapy prognosis using quantitative ultrasound spectroscopy and a kernel-based metric

In this study, a kernel-based metric based on the Hilbert-Schmidt independence criterion (HSIC) is proposed in a computer-aided-prognosis system to monitor cancer therapy effects. In order to induce tumour cell death, sarcoma xenograft tumour-bearing mice were injected with microbubbles followed by ultrasound and X-ray radiation therapy successively as a new anti-vascular treatment. High frequency (central frequency 30 MHz) ultrasound imaging was performed before and at different times after treatment and using spectroscopy, quantitative ultrasound (QUS) parametric maps were derived from the radiofrequency (RF) signals. The intensity histogram of midband fit parametric maps was computed to represent the pre- and post-treatment images. Subsequently, the HSIC-based metric between preand post-treatment samples were computed for each animal as a measure of distance between the two distributions. The HSIC-based metrics computes the distance between two distributions in a reproducing kernel Hilbert space (RKHS), meaning that by using a kernel, the input vectors are non-linearly mapped into a different, possibly high dimensional feature space. Computing the population means in this new space, enhanced group separability (compared to, e.g., Euclidean distance in the original feature space) is ideally obtained. The pre- and post-treatment parametric maps for each animal were thus represented by a dissimilarity measure, in which a high value of this metric indicated more treatment effect on the animal. It was shown in this research that this metric has a high correlation with cell death and if it was used in supervised learning, a high accuracy classification was obtained using a k-nearest-neighbor (k-NN) classifier.

[1]  E. Madsen,et al.  Nonlinearity parameter for tissue-mimicking materials. , 1999, Ultrasound in medicine & biology.

[2]  D. Vaux,et al.  Apoptosis in the development and treatment of cancer. , 2004, Carcinogenesis.

[3]  F. S. Foster,et al.  Ultrasound backscatter microscopy images the internal structure of living tumour spheroids , 1987, Nature.

[4]  Michael C. Kolios,et al.  Quantitative Ultrasound Characterization of Responses to Radiotherapy in Cancer Mouse Models , 2009, Clinical Cancer Research.

[5]  Omar Falou,et al.  Quantitative ultrasound spectral parametric maps: Early surrogates of cancer treatment response , 2012, 2012 Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[6]  Mohamed S. Kamel,et al.  Assessment of cancer therapy effects using texton-based characterization of quantitative ultrasound parametric images , 2013, 2013 IEEE 10th International Symposium on Biomedical Imaging.

[7]  Gregory J. Czarnota,et al.  Ultrasound detection of cell death , 2010 .

[8]  Bernhard Schölkopf,et al.  A Kernel Two-Sample Test , 2012, J. Mach. Learn. Res..

[9]  Robert P. W. Duin,et al.  The Dissimilarity Representation for Pattern Recognition - Foundations and Applications , 2005, Series in Machine Perception and Artificial Intelligence.

[10]  Kevin M Brindle,et al.  Imaging tumour cell metabolism using hyperpolarized 13C magnetic resonance spectroscopy. , 2010, Biochemical Society transactions.

[11]  Robert P. W. Duin,et al.  A Generalized Kernel Approach to Dissimilarity-based Classification , 2002, J. Mach. Learn. Res..

[12]  Ronald H. Silverman,et al.  Ultrasonic spectrum analysis for tissue assays and therapy evaluation , 1997, Int. J. Imaging Syst. Technol..

[13]  Michael C. Kolios,et al.  Low-frequency quantitative ultrasound imaging of cell death in vivo. , 2013, Medical Physics (Lancaster).

[14]  Le Song,et al.  A Hilbert Space Embedding for Distributions , 2007, Discovery Science.

[15]  Michael C. Kolios,et al.  Potential use of ultrasound for the detection of cell changes in cancer treatment. , 2009, Future oncology.

[16]  Michael C. Kolios,et al.  Ultrasonic biomicroscopy of viable, dead and apoptotic cells. , 1997, Ultrasound in medicine & biology.

[17]  Michael C. Kolios,et al.  Conventional frequency ultrasonic biomarkers of cancer treatment response in vivo. , 2013, Translational oncology.

[18]  Michael C. Kolios,et al.  Quantitative ultrasound characterization of cancer radiotherapy effects in vitro. , 2008, International journal of radiation oncology, biology, physics.

[19]  Chun Li,et al.  The Imaging of Apoptosis with the Radiolabeled annexin V: Optimal Timing for Clinical Feasibility , 2004, Technology in cancer research & treatment.

[20]  J W Hunt,et al.  © 1999 Cancer Research Campaign Article no. bjoc.1999.0724 Ultrasound imaging of apoptosis: high-resolution noninvasive , 2022 .

[21]  Michael C. Kolios,et al.  Ultrasound imaging of apoptosis in tumor response: novel preclinical monitoring of photodynamic therapy effects. , 2008, Cancer research.

[22]  Bernhard Schölkopf,et al.  Kernel Methods for Measuring Independence , 2005, J. Mach. Learn. Res..

[23]  Lale Kostakoglu,et al.  PET in the assessment of therapy response in patients with carcinoma of the head and neck and of the esophagus. , 2004, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[24]  Martin J. Yaffe,et al.  Imaging innovations for cancer therapy response monitoring , 2012 .

[25]  Robert P. W. Duin,et al.  Dissimilarity representations allow for building good classifiers , 2002, Pattern Recognit. Lett..

[26]  Le Song,et al.  A dependence maximization view of clustering , 2007, ICML '07.

[27]  Bernhard Schölkopf,et al.  Measuring Statistical Dependence with Hilbert-Schmidt Norms , 2005, ALT.