Future Prospects for Contrast Ultrasound

Abstract

E-mail: [email protected] New technical approaches in ultrasound are already having an impact on contrast imaging; the most striking among these is planewave imaging. By abandoning focused beams in favour of a broad insonation encompassing the field of view, an image is acquired each pulse, increasing the famerate to the PRF (typically around 5,000 per second). Both linear and nonlinear Doppler processing can be performed with coherent ensemble lengths of around 100, producing simultaneous contrast, colour and spectral Doppler imaging at framerates of 50-100Hz. This allows a new imaging mode, showing real-time anatomy, perfusion and velocity resolved spectral and colour Doppler, greatly increasing the versatility of the clinical contrast exam, particularly in fast moving structures. Efforts are already underway to implement such schemes in 3D using matrix a array probes. A consequence of very high speed acquisition is that ensembles of bubbles, or even individual bubbles, can be tracked from frame to frame. For the former case, combining such ‘short track MIP’ imaging with curvature operators already used in CT and MR angiography produces real time images of vessel morphology of unprecedented quality. In the latter case, if the agent is sufficiently sparse in tissue yet samples all of the microvessels over time, the path of individual bubbles can be tracked to create ‘super-resolution’ images of the perfusion bed, whose dimensions are below the wavelength of the ultrasound, which for conventional imaging, defines a lower limit of spatial resolution. The current generation of microbubbles were developed before the nonlinear imaging methods used to detect them were invented. To a great extent, the resonant properties of these bubbles which are the basis of their use in diagnosis an therapy have come about by serendipity. Slowly, a new generation of agents that are designed for specific applications or functionalised for biological interactions is emerging. Bubbles which are targeted with ligands specific for inflammation, angiogenesis or thrombosis have already been demonstrated. Bubbles can be loaded with drugs or plasmid DNA for theranosis. Yet to date, all of these targets are the endothelial cells that line blood vessels. While microbubbles stay within the vasculature offer a number of advantages to contrast ultrasound imaging, there are situations where the pattern of extravasation of a diffusible tracer has important clinical relevance. Liquid nano-droplets of perfluorocarbon (PFC) of a 200-400nm diameter range can selectively diffusible through angiogenic vascular endothelium and, due to the so-called ‘enhanced permeability and retention’ (EPR) effect, accumulate in solid tumours. An externally applied ultrasound field then ‘activates’ the droplets into bubbles while they remain in the interstitium. Such bubbles can not only report on tumours for diagnosis, they can in principle be targeted to extravascular molecules (such as those expressed on malignantly transformed hepatocytes), and may further be capable of degrading the extracellular matrix, so driving drugs into hitherto hard to treat solid tumours. While the development of instruments results in rapid translation of technological ideas to the clinic, the cycle for new drug development is inevitably slowed by the complexity and cost and of the regulatory process. Nonetheless, developments already apparent in the research field assure a bright and diverse future for ultrasound contrast.