Imaging is a vitally important tool in the diagnosis and treatment of cancer, but today’s sophisticated scanning techniques are often limited by accessibility and are expensive and cumbersome to use on a day-to-day basis for diagnosis, monitoring of disease progression or treatment efficacy. Clinicians could come to decisions about treatment far more quickly if they could take frequent snapshots of their patients’ tumours—perhaps using a more affordable and portable imaging device that could be brought to a patient’s bedside when required.
Ultrasound imaging should fit the bill perfectly, especially in its new ultrafast incarnation, in which sensitivity and specificity are far higher. Therefore, Imperial bioengineer Mengxing Tang, together with his collaborators Eric Aboagye, Nick Long and Adrian Lim, are using a CRUK/EPSRC multidisciplinary award to develop very high frame rate (up to tens of thousands of frames per second, also known as ultrafast) ultrasound in conjunction with microbubble contrast agents and signal processing algorithms as a technique for imaging cancer. The 42-month award is currently funding three postdoctoral fellows split between the collaborating labs.
Microbubbles resonate in an ultrasound beam, and are several thousand times more reflective than blood cells. As they are about the same size as red blood cells, once injected into the bloodstream they are an excellent way of visualising the circulatory system; this in turn is perfect for spotting oxygen-hungry tumours, which wrap themselves in a network of new blood vessels in a process known as angiogenesis. Microbubbles can also carry molecular hooks that bind specific molecules in the tumour vasculature, meaning that they can be targeted even more precisely to cancer sites. The combination of ultrafast ultrasound imaging and microbubbles, whether targeted or non-targeted, has never been tried in a clinical setting and this is the aim of Mengxing and his colleagues.
Cancer pharmacologist Eric Aboagye’s interest is in finding and validating tumour markers that can be used to arm the microbubbles; work that is also important for both basic and translational cancer research. Making the microbubbles, ensuring they meet clinical standards and working out how to stably equip them with their cancer-targeting ‘hooks’ is inorganic chemist Nick Long’s main challenge, whilst for Mengxing, the problem is to develop an ultrasound imaging tool that can detect the tiny microbubbles right down to the level of just one or a few. All these strands will come together to be tested in a preclinical model, before reaching the stage where breast cancer radiologist Adrian Lim can think about trying the technique out in patients.
Mengxing feels that cancer imaging is a natural fit for his interests in vasculature and flow, and is happy to be involved in a collaboration with such a practical outcome; “sometimes you develop something very cool but you cannot find an immediate use” he says, “but this technique has the potential for widespread use, not just in cancer.” He is also pleased that the project has enabled his lab to make very significant progress in their own field. “The kind of images we can currently generate have superior resolution and contrast compared to the state-of-the-art”, he says. “We are always trying to be ahead of the game, and right now, that’s where we are.”
Mengxing Tang has multiple collaborations set up, and has become something of an expert in how to make them work well. Here, he shares some of his insights.
“Everyone needs to bring something unique to a collaboration—something the other parties can’t do—but the key is to know enough about the other fields to be able to communicate effectively, otherwise you can’t learn from each other. For this project, I try to understand what Eric and Nick are doing so that I can see why they choose one option and not another. Otherwise I would just be passive, which would be very dull. And I think that being someone not in their field, my questions sometimes challenge assumptions that are taken for granted, so it is helpful for them too.
There is invariably a lot of coordination and advance planning needed and people sometimes underestimate how much time that all takes. In this collaboration, the different workflows are quite hard to synchronise. To develop our ultrasound technique, we use very simple test material, as the focus is on getting the algorithms, code, systems and hardware right. The data collection itself is easy. However, the in vivo experiments can take weeks, and sometimes they do not work—that is biology for you! Our research fellows have to make sure that the in vivo experiments only happen when the microbubble contrast agent and the detection systems are ready to go and vice versa.
It helps that we already know each other, it is difficult to find someone whose discipline and expertise are complementary and who can also work with you. It is important to get on with each other! There is a lot of time and effort involved so new collaborations are not easy to get going.
Collaboration obviously works best when you have a good team. We are very lucky in this regard as we have a very good team. It is really the people in your labs who are doing the work, and you really need to have good people who can work together as well as the Principal Investigators do. I sometimes joke that the best way is to recruit the best people then you can just go on holiday and leave them to it!