Aspects of perfusion quantification using contrast-enhanced ultrasound within the clinical context of colorectal liver metastases

Abstract

There is a need for non-invasive, reproducible, and undemanding methods to assess response at an earlier stage for novel cancer therapies targeting vascularity due to the large number of drugs in clinical development and the associated cost implications. RECIST assessments are limited, as effective biological agents are often initially cytostatic rather than cytotoxic. Imaging biomarkers as predictors of response to vascular targeting agents have not been translated into routine clinical practice yet, due to difficulties relating to reproducibility, resource-intensity, and standardization. Measuring changes in hepatic arterial and portal venous contributions to total liver blood flow may present an opportunity to devise novel such imaging biomarkers. While their clinical utility has been demonstrated to detect occult colorectal liver metastases, it remains to be investigated that surrogates of total liver blood flow may be used to assess response at an earlier stage for novel cancer therapies targeting vascularity. In light of the above, I devised a method to assess macrocirculation flow with dynamic contrast-enhanced ultrasound following the injection of contrast agent as a bolus. The impact of using linearized log-compressed data (commonly available on commercial scanners) vs. linear data (reference) to form time-intensity curves from DCE-US image loops was investigated. The impact of adjusting ultrasound scanner settings and contrast bolus volume was also considered. Under operating conditions recommended based on the aforementioned analysis, the relationship between parameters derived from quantitative analysis of DCE-US image loops and flow characteristics was empirically established and the potential and reproducibility of quantitative analysis of contrast bolus kinetics to reflect total liver blood flow and to differentiate healthy volunteers from patients with focal liver lesions were studied. Lastly I conducted a preliminary evaluation of the method in vivo in subjects with colorectal liver metastases treated with combined systemic cytotoxic and anti-angiogenic therapy.