Ultrasound Molecular Imaging Techniques in Small and Large Vessels

Ultrasound molecular imaging (USMI) is a diagnostic technique that combines the anatomic information of ultrasound imaging with the molecular-scale information of a targeted molecular assay. In USMI protocols, highly echogenic blood pool ultrasound contrast agents known as microbubbles (MBs) are conjugated to antibodies or peptides to target specific molecular markers presented on the vascular endothelium. Ultrasound is then used to detect and quantify molecular disease markers based on MB signal intensity. In all USMI protocols, separation of contrast agent signals from surrounding tissue signals and reliable detection of MB binding events is essential to acquiring a meaningful diagnostic result. In this dissertation, several imaging and image processing techniques are used to facilitate automated detection and classification of molecularly adherent MB signals in both small and large vessels.

The first part of this dissertation focuses on separating adherent MB signals from other source signals in the complex microvasculature of a mouse hindlimb tumor. Custom-programmed ultrasound sequences are used to simultaneously perform contrast-mode imaging and mechanical perturbation of molecularly bound VEGFR-2-targeted MBs. Offline processing is then used to separate adherent MB signals from static tissue signals based on localized measurements of interframe signal decorrelation. In another technique, normalized singular spectrum area (NSSA), a singular value decomposition (SVD)-based statistical metric, is validated against differential targeted enhancement (dTE) for the detection and classification of adherent and non-adherent MB signals. NSSA is later integrated into a complete non-destructive image filtering technique designed to automatically segment MB signals and identify MB binding events.

In the second part of this dissertation, a new dual-probe imaging system is used to deliver modulated acoustic radiation force (ARF) to translate molecularly targeted MBs to the mouse suprarenal aorta for the detection of abdominal aortic aneurysm (AAA). The efficacy of this system in translating MBs to the vessel wall is validated at physiologically relevant flow velocities using an in vitro flow phantom.