Imaging tortuosity: the potential utility of acoustic angiography in cancer detection and tumor assessment

The morphology and structure of the vasculature associated with malignant tumors has long been observed to be chaotic and unusual compared with that of healthy tissues. In tumors, vessel diameters and branching patterns appear random, and the actual trajectories charted through the 3D tumor volume are often tortuous [1,2]. These morphological abnormalities are hypothesized to be a result of a number of complicated physiological effects occurring in parallel, such as tumor cells’ high metabolic demand and their unusual microenvironment (hypoxic, acidic and so on). These factors contribute to a heightened level of angiogenic activity in and around the tumor, which becomes a self-amplifying cycle when the newly formed vessels fail to supply the tumor cells’ insatiable appetite for nutrients [3]. The heightened angiogenic activity also causes the basement membrane and support structure of the vessels to break down. Additionally, the poor organization of the vessel network results in an increase in pressure within the vessels, which is further exacerbated by the absence of lymphatic drainage from the tumor stroma. Of interest from a cancer screening perspective, tumor-associated vascular irregularities can extend beyond the margins of a lesion, as angiogenic growth factors promoted by tumor cells can influence the morphologies of even major vessels in the vicinity of tumors [4]. Additionally, cancer-associated tortuous vessel morphologies have been observed in animal models much sooner than the arrival of a palpable mass. For example, vascular remodeling has been observed via microscopy and window chamber models when only tens to hundreds of tumor cells are present within an otherwise healthy tissue volume [5].