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Title: Quantitative assessment of tumour response to therapy by diagnostic ultrasound
Author: Chung, Daniel Yiu Fai
ISNI:       0000 0004 6062 5512
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2015
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Chemotherapy forms the mainstay of treatment for patients with liver tumours, which has a number of significant side effects. Treatment response is often assessed some time after commencement of treatment. A quantitative method to detect early liver tumour response to chemotherapy would be beneficial to facilitate termination of ineffective treatment and to minimise unnecessary side effects. This thesis investigated firstly whether fractal analysis of contrast enhanced computed tomography (ceCT) images of colorectal liver metastases could be used to detect early response to chemotherapy. Secondly, a technique based on Nakagami imaging of ultrasound radio-frequency (RF) signals was developed, initially using data from a xenograft mouse tumour model, as a potential early predictor of tumour response. This was subsequently tested using clinical ultrasound data collected from patients undergoing chemotherapy treatment for liver tumours. Mean fractal dimension (FD) obtained from fractal analysis of volumetric ceCT images of colorectal liver metastases was confirmed as a reliable quantitative parameter to detect tumour tissue changes. There was however no significant difference in the interval change of mean FD from baseline between responding and non-responding metastases. Based on the current study, fractal analysis is unable to detect early liver tumour response to chemotherapy. Development of an ultrasound-based tissue assessment technique was then performed, owing to the advantages of ultrasound imaging. A Nakagami imaging-based volumetric tissue assessment technique was developed using backscattered RF ultrasound data from xenograft mice tumour treated in an investigation of high intensity focused ultrasound mediated chemotherapy delivery. The percentage of pre- Rayleigh regions (%PRR) obtained from the new analysis technique demonstrated an indirect correlation with the tumour volume. Interval reduction in %PRR from baseline was also found to be significantly greater in tumours that responded to treatment. These observations confirmed the potential of Nakagami imaging-based techniques to detect early tumour response to treatment. The technique was subsequently used to analyse volumetric ultrasound datasets collected from patients undergoing chemotherapy treatment for liver tumours. The %PRR was found to indirectly correlate with the axial diameter of the liver tumour. Additionally, interval increase in the %PRR between follow-up and baseline study was found to be significantly higher in responding compared to non-responding tumours. These preliminary results demonstrated the potential of the Nakagami imaging-based volumetric tissue assessment technique to detect early response of liver tumour to chemotherapy. Further work is recommended prior to translation into clinical practice.
Supervisor: Coussios, Constantin C. ; Gleeson, Fergus V. Sponsor: Wellcome Trust ; Engineering and Physical Sciences Research Council
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available