Dynamic contrast-enhanced and T2-weighted magnetic resonance imaging study of the correlation between tumour angiogenesis and growth kinetics

Abstract

Accumulating evidence indicates that tumour growth is angiogenesis-dependent. Non-invasive assessment of the relationship between tumour growth and associated angiogenesis is essential for diagnosis and for therapeutic interventions. We utilized a combination of high-resolution T2-weighted and dynamic contrast-enhanced magnetic resonance imaging to investigate the dynamics of angiogenesis during tumour growth in a mouse tumour model expressing Epstein-Barr virus-encoded latent membrane protein 1 isolated from a nasopharyngeal carcinoma in Taiwan. Serial imaging acquisitions were performed starting on the third day after subcutaneous implantation of tumours, through day 28. We observed a progressive increase in tumour volume until day 14, followed by rapid and exponential growth. The volume transfer constant, K(trans), also increased significantly on day 14, and then gradually decreased, suggesting that the angiogenic switching occurs prior to significant tumour growth. At the initial stage, the K(trans) values were significantly higher in the tumour peripheral region than in the tumour core, but, during tumour growth, the K(trans) values in the region between the tumour periphery and core gradually increased, becoming larger than those of the periphery. These results demonstrate that the ability to perform repeated measurements assessing the correlation between tumour growth kinetics and tumour angiogenesis makes it possible to determine the critical time of angiogenic switching prior to rapid tumour growth, as well as suggesting the timing of therapy.