Lead Research Organisation: University College London
Department Name: Medical Physics and Biomedical Eng


The purpose of this research is to develop a promising new biomedical imaging technique called photoacoustic (PA) imaging. This involves firing very short (nanosecond) pulses of laser light into tissue. The light is absorbed by structures such as blood vessels producing a small heating effect. This leads to rapid thermoelastic expansion which generates high frequency (~tens of MHz) acoustic waves which travel though the tissue back to the surface. By measuring the time of arrival of these acoustic waves at a number of detectors positioned over the tissue surface, and with knowledge of the speed of sound, the acoustic signals can be backprojected to produce a 3D image of the internal absorbing structures within the tissue. The key advantage of the technique is that it combines the strong contrast of optical methods with the high spatial resolution available to ultrasound. This may make the technique a powerful diagnostic tool for identifying abnormalities such as certain types of cancer tumours that would be difficult to see using conventional medical imaging techniques such as X-ray or ultrasound imaging. This technique has many potential clinical applications, including detecting tumours in the breast, assessing skin abnormalities such as malignant melanomas or soft tissue damage such as burns or wounds. It can also be used to image small animals such as mice which are used extensively to model a wide range of human diseases. One of the most exciting features of photoacoustic imaging is its potential to characterise specific molecular processes, so called molecular imaging. This is achieved using probe molecules that strongly absorb certain wavelengths of light and have a high affinity for a specific cellular or molecular receptor that is characteristic of a particular disease such as cancer. In order to advance the technique to practical application, a substantial research program will be undertaken. A novel high resolution instrument, designed for non invasive imaging to depths of several mm, will be developed both for clinical use, for example to study skin pathologies and for the pre-clinical study of disease processes in small animal models. Endoscopic probes that are capable of being inserted into the body and guided deep within to image, for example, the inside of coronary arteries to assess the plaques that can build up and cause heart attacks will be developed. In addition, a dedicated instrument will be designed for the early detection and diagnosis of breast cancers and monitoring their treatment. Novel methods for recovering physiological information such as blood oxygenation and flow will also be explored and clinically tested. A programme of in vivo imaging both in humans and small animals to apply and validate these methods is planned, with specific emphasis on demonstrating the utility of the technique for the diagnosis and treatment of cancer, cardiovascular disease and neurological conditions. Overall this research offers the prospect of developing a powerful new diagnostic imaging tool that can be used to advance our understanding of disease mechanisms at an anatomical, physiological and molecular level and improving the clinical diagnosis and treatment of cancer and other major diseases.
Description A key outcome of this Fellowship project has been the demonstration of a new type of medical photoacoustic scanner based on a novel Fabry Perot (FP) polymer film ultrasound sensor. The exquisite 3D images of tissue structures that the system can provide have excited significant interest as evidenced by the award of several international prizes and awards. As well as developing the technology, its application to studying the temporal evolution of the blood supply of a tumour and its response to anti-vascular therapy has been demonstrated. The technology has also been used to obtain the first in vivo images of mouse embryos, the renal vasculature in a mouse model of polycystic kidney disease and the re-vascularisation of artificial tissues. This work underpinned the recent development of a clinical scanner which is currently being evaluated for the assessment of head and neck cancer, inflammatory arthritis and diabetes.

Specific instrumentation related developments include the first in vivo demonstration of a combined multimodal OCT-photoacoustic tomography mode scanner for dermatological applications and a range of miniature photoacoustic imaging probes for the guiding surgical interventions. Significant progress in molecular imaging techniques has been made by genetically engineering (in collaboration with researchers at UCL Cancer Institute) a tyrosinase expressing reporter gene which yields photoacoustic image contrast via eumelanin production. This offers the prospect of directly tracking cancer cells which can be used to study the mechanisms of tumour development and aid the development of new treatments. Other developments in functional and molecular imaging include the development of a new photoacoustic Doppler blood flowmetry technique based on time correlation and quantitative spectroscopic methods of measuring blood oxygen saturation.
Exploitation Route .
Sectors Healthcare,Pharmaceuticals and Medical Biotechnology

Description The technology developed under the project is currently being used to assess the utility of photoacoustic imaging for assessing rheumatoid arthritis and peripheral vascular disease. A total of 25 patients have been scanned to date. Patients with inflammatory arthritis form the largest cohort to date and initial indications appear promising. By quantifying the photoacoustic image contrast in the synovial membrane where inflammation and increased vascularisation are hallmarks of arthritis, it has been shown that it may be possible to not only distinguish between joints with and without inflammation but also to grade their severity. The next step is to increase the sample size and diversity, correlate images with additional clinical indicators and assess therapeutic response for treatment planning. Patients with diabetes have also been scanned revealing previously unseen irregular vascular patterns characterised by tortuous vessels, venous insufficiency and other microcirculatory abnormalities. Clinical relevance at this early stage remains to be established but, at the very least, these early results suggest the technology could be useful for studying the microcirculation in diabetes research.
First Year Of Impact 2019
Sector Healthcare
Impact Types Societal