Radiographic images produced by X-rays have been a staple tool of medical diagnosis for many decades and this technology remains one of the health care system’s workhorses. Nevertheless, important physiological features, such as the emergence or growth of tumours, cannot always be captured in detail, especially in soft tissues such as those in the breast. A variety of agents have therefore been developed to provide the necessary visual contrast around these structures, making it possible to assess changes in an individual’s physical condition.

Investigators continue to refine the application of these contrast agents; among the most recent innovations is changing the droplet size of an agent in order to reveal telling details around areas of interest within the body. A group at Toronto’s Sunnybrook Research Institute has successfully applied this approach to mammographic imaging. 

These photos show how a contrast agent improves radiographic imaging. The photo on the top shows cells found in the lungs of mice, which were X-rayed without such an agent. The red emissions­ in the photo on the bottom are caused by quantum  dots — nanocrystals displaying quantum mechanical properties — inside the perfluoro-octylbromide (PFOB) droplets that are present. Photo credit: Sunnybrook Research Institute

Their work started with perfluoro-octylbromide (PFOB), a medically approved agent that attenuates X-ray signals. Conventional iodinated contrast agents used in radiography are on the order of one nanometre in diameter, much smaller than the pores found on most of the body’s blood vessels, which are up to about four nanometres. When these agents are injected into the bloodstream, they will leak into surrounding tissues. Radiographs will show additional contrast, but key areas could remain indistinguishable. 

The Sunnybrook team, led by nanotechnology specialist Naomi Matsuura, created PFOB droplets with diameters between 100 nanometres and 200 nanometres. These cannot escape normal, healthy blood vessels, but they will make their way into surrounding tissues wherever vessels are compromised in some way. That is exactly the case in angiogenesis, the process by which tumours grow new blood vessels to fuel their growth.

“Angiogenic vasculature tends to be missing a basement membrane and there tend to be gaps between endothelial cells that line the vessel walls,” explains Melissa Hill, a medical biophysics student at University of Toronto who is pursuing the development of breast imaging technology for her PhD. “What you will see on the radiograph are areas where there is greater attenuation in places exhibiting this poorly formed vasculature, compared to the normal tissue where you wouldn’t have any enhancement of the image.”

Hill says that the enhanced attenuation at this key site will make for clearer, more accurate diagnosis of breast cancer with mammography. And while the technique has yet to approach clinical trials, Hill notes that she and Matsuura chose PFOB because it has already been demonstrated as biocompatible. “We foresee that it would be easier to move into humans than starting from scratch with a new molecule,” Hill says.