Date of Award
Master of Science
Tumour-associated neovascularization (angiogenesis) is essential for tumour
growth, invasion, and metastases. The trigger for angiogenesis has been termed the 'angiogenic switch'. To non-invasively identify this switch and track angiogenesis, twelve transgenic mouse adenocarcenoma of the prostate (TGMAP) mice with identifiable tumours of a minimum 2 mm diameter and three groups of five nude rats injected with LoVo colorectal cancer cells in the left flank/thigh region underwent CT perfusion (CTP) scans. Mice were scanned every 7-14 days for 63 days and rats in groups 1 and 2 were scanned 3 days post injection and then 7-14 days for 56 days. Blood flow (BF) and blood volume (BV) maps were then generated using the abdominal aorta as the arterial input curve. In TGMAP mice, both BF and BV peaked when prostate plus in situ tumour was 4-6 mm in diameter; and BF and BV were nearly 2 and 1.5 times higher respectively than those at a size of 2 mm in diameter (P < 0.05). The onset of higher BF could account for the rapid tumour growth seen. In LoVo-injected rats however, there was an overall decreasing trend in BF and BV following injection, with both being highest at 3-7 days post injection. BF and BV were significantly higher in the tumour compared to the contra-lateral flank up to 35 days post injection. We have provided preliminary evidence for the detection of the 'angiogenic switch' using dynamic contrast enhanced CT (DCE-CT) in two models of tumour progression.
In a CTP study, an arterial input curve, which is not contaminated by any venous sources, must be selected in order to properly perform the deconvolution and calculate the various perfusion parameters. Arterio-venous anastomoses (AVAs) are a possible
source of such contamination. A second study was done using the same TGMAP mice to identify AVAs and the resulting errors in perfusion measurements. Six TGMAP mice underwent two CT scans: an anatomical scan and a perfusion scan. Anatomical images were rendered in 3-D and two sets of tumour BF and BV maps were generated using the abdominal aorta (AA) and tail artery (TA) as the arterial input curves. AVA was identified in all animals at the level of the bifurcation of the inferior vena cava and TA. Contrast was seen to arrive in the TA 3.3 ± 0.5 seconds (P < 0.05) prior to its arrival in the AA. Mean whole tumour BV and BF calculated with AA compared to that with TA were significantly higher (P < 0.05). Thus, the presence of AVAs in the lower portion of rodents led to significantly underestimation of perfusion parameters when the TA is used as the input artery.
Gabra, Peter, "CT PERFUSION STUDY OF ANGIOGENESIS PROGRESSION AND ARTERIO VENOUS ANASTOMOSES IN RODENT MODELS OF CANCER" (2009). Digitized Theses. 3906.