Blood flow to tumours – new drugs and detection

Joanna Brunker, a PhD student at University College London and biological sciences & biomedical sciences gold medal winner at last night’s SET for Britain awards, describes her research into a new method for measuring blood flow which has the potential to improve our understanding and treatment of tumours.

Tumours develop a chaotic system of blood vessels to raid the body’s normal blood supply. Some of the latest anti-cancer drugs (Vascular Disrupting Agents) work by damaging these vessels: the tumour is then denied access to nutrients essential for its growth. However, to reveal the extent to which such therapies actually conquer the tumour we need to measure blood flow in the tumour vessels.

There are currently very few imaging methods able to measure blood flow non-invasively. Many methods rely on injecting dyes (contrast agents), so that the flow can be seen more clearly. Doppler ultrasound is a method that is used without contrast agents, but it is only really suitable for measuring flow in large vessels, such as major arteries. These vessels have diameters of several mm and the blood flows at speeds greater than 100 mm/s. Tumour blood vessels are much smaller: they have diameters 0.005 to 0.1 mm (similar to the diameter of human hair) and the blood flow is variable, although usually less than 50 mm/s.

Our new technique, called “acoustic-resolution photoacoustic Doppler flowmetry”, has the potential to non-invasively measure blood flow in tumour vessels. Photoacoustic imaging involves detecting ultrasound waves generated by pulses of light (the Photoacoustic Effect, discovered by Alexander Graham Bell in 1880). It has resulted in remarkable, but static, images of blood vessels.

We hope to gain additional insight by including movement or flow information; we could do this by monitoring changes (time shifts) in the photoacoustic signals. This is a novel idea, and so has required initial testing using laboratory equipment and computer programming. Our experiments have involved various blood-like materials, for example carbon spheres flowing through plastic tubes.

Now, for the first time, we have obtained preliminary velocity measurements using blood itself. We have identified technical challenges, but our current research is overcoming these in order to achieve our ultimate goal: to measure flow in living tissue.

Brunker J, & Beard P (2012). Pulsed photoacoustic Doppler flowmetry using time-domain cross-correlation: accuracy, resolution and scalability. The Journal of the Acoustical Society of America, 132 (3), 1780-91 PMID: 22978905