Assessment of Tumour Growth in Murine Cancer Models with Three-Dimensional High-Frequency Ultrasound
Date of Award
2008
Degree Type
Thesis
Degree Name
Doctor of Philosophy
Program
Biomedical Engineering
Supervisor
Dr. Aaron Fenster
Second Advisor
Dr. James C. Lacefield
Third Advisor
Dr. Paula Foster
Abstract
Preclinical cancer research could benefit from quantitative, non-invasive measurements of tumour growth provided by three-dimensional high-frequency ultrasound imaging. High-frequency ultrasound has been shown to be appropriate for tracking experimental liver metastases from a variety of cell fines without exogenous contrast agents. Tumour growth over time can be monitored on an individual tumour basis, allowing a growth curve to be constructed and the tumour to act as its own control in a treatment study. In order to quantify tumour volume and growth, the measurement variability must be known. Inter- and intra-observer variability was determined for tumours in four size ranges with average volume from 0.43 mm3 to 60.42 mm3. Intrarobserver variability was as low as 4% for mid-sized tumours averaging 2.39 mm3, while the inter-observer variability for the smallest and largest tumours measured had the highest variability at 25% and 15%, respectively. Breathing motion did not significantly effect the volume measurements, however, having the region of interest beyond the geometric focus resulted in significantly different measured volumes. Measurement variability is one factor that influences how well growth data can be characterized mathematically through curve fitting. Simulations of tumour growth were performed to relate experimental imaging parameters, such as intervals between acquiring images, minimum and maximum volume recorded and length of time over which data is acquired, to the quality of curve fitting results. Simulations show that improving the ability of the ultrasound system to image small (<1 mm diameter) tumours would improve the ability to draw conclusions from growth parameters. The spatially variant point-spread function influences lesion-size measurement variability and consequently growth curve fitting. The transducer employed is tightly focused, so spatial image resolution is high at the focus but rapidly degrades away from the focus. Synthetic aperture focusing was employed with a variety of weighting techniques to retrospectively focus the images through a range of depths. The iii improvement in focusing was measured using point-like targets and the effect on measurement variability was evaluated using lesion phantom images. Synthetic aperture focusing did not produce a significant reduction in lesion-size measurement variability but did diminish the sensitivity of the measured size to lesion depth.
Recommended Citation
Wirtzfeld, Lauren Ashleigh, "Assessment of Tumour Growth in Murine Cancer Models with Three-Dimensional High-Frequency Ultrasound" (2008). Digitized Theses. 4215.
https://ir.lib.uwo.ca/digitizedtheses/4215