Nanobubbles for earlier pancreatic cancer detection

Pancreatic cancer is the tenth most common cancer in the UK, with an incidence that has increased by 30% increase over the last 40 years but persistently low 5-year survival of approximately 8% that has not improved over the same time period. Currently only around 10% of patients are suited to surgery. Earlier detection of disease could play a significant role in patient outcomes by increasing the number of patients whose cancer remains suited to surgical resection. Those patients whose tumour is not accessible or too advanced for surgery are reliant on chemotherapy or immune-therapy treatments. However, pancreatic ductal carcinoma is characterised by the evolution of a dense fibrotic stroma and collagen-rich extra-cellular matrix that can severely limit the penetration of drugs available to treat it. This has led to considerable interest in the development of therapeutics that can target this dense stroma to enable treatment. Improved methods of imaging stroma density and susceptibility to drug penetration are urgently required to better optimise and monitor treatments to improve patient outcomes.
We previously demonstrated how contrast enhanced ultrasound (CEUS), where microbubbles can improve image quality and provide physiological information, are effective in the identification of metastasis [1]. However, the contrast agent microbubbles commonly used are confined to the circulation, limiting their ability to highlight disease until the blood vessels supplying the tumour begin to be affected and unable to image tumour tissue itself. In this project we will investigate nanobubbles as a more suitable contrast agent for early stage cancer detection. They are small enough to escape the blood vessels and are naturally retained in tumour tissues. They have the potential to provide information on the penetration of different sized particles into the tumour stroma, but to realise the potential of this new area of ultrasound imaging novel imaging approaches are needed.
Although quantitative ultrasound imaging, particularly in the context of breast imaging, has been investigated since the 1970s, it is only in the last decade that developments in solid state electronics and array technology have facilitated sufficient sensitivity and specificity to compete with alternative medical imaging modalities [2]. Contrary to MRI scans, ultrasound imaging can provide quantitative information (such as the spatial distribution of wave speed) and thus facilitate material characterisation of the heterogeneous structures under inspection. Furthermore, in the field of non-destructive evaluation (NDE), there has been a recent surge in using ultrasonic travel time tomography to map the anisotropic grain structures and orientations of polycrystalline metals [3]. However, in both medical and NDE applications, the success of these methods is highly dependent on the extent of the inspection aperture and the availability of prior knowledge about the global structure and properties of the inspected object. To circumvent these challenges in the context of tumour characterisation, this project will examine the potential of using CEUS to construct quantitative images of cancerous tissues.