European researchers have developed highly sensitive ultrasound equipment that can detect tiny quantities of reflective microbubbles engineered to stick to specific tumour cells. The technique should pick up tumours early and improve patients' chances of survival.
Most of the current diagnostic methods - biopsy analysis, biochemical tests and medical imaging - are not sufficiently sensitive. They frequently return a false negative; the tumour is only discovered when it is much bigger, and too late.
European researchers are developing a new technique that will help medical professionals visualise tiny quantities of pathological tissue in patients. The technology could localise tumours in their very earliest stages of development and help doctors begin treatments much earlier, giving patients a much better chance of survival.
The new approach uses medical ultrasound, a safe technology most commonly used for pre-natal visualisation of the foetus and the imaging of other soft tissues. A probe sends high-frequency acoustic waves into the body and detects how they bounce off the interfaces between different tissues.
To improve the sensitivity of this imaging technique, a sonographer may sometimes inject a so-called contrast agent into patients, which greatly increases the scattering of the acoustic waves back to the probe. For ultrasound imaging, contrast agents are based on 'microbubbles', micron-sized gas-filled balls that show up brightly on the ultrasound image.
Researchers in the EU-funded TAMIRUT project have developed a microbubble medium that can specifically target and bind to certain pathogenic cells in the body (such as endothelial cells of vessels lining the tumours). Combined with enhanced ultrasound equipment and signal processing capabilities, the system can detect where microbubbles adhere to target cells, and reveal the presence of early-stage tumours.
Working with the pharmaceutical company Bracco Research S.A. in Switzerland, TAMIRUT researchers have developed a way to attach antibodies onto the surface of microbubbles. By selecting an antibody with an affinity for marker molecules found only on target vascular cells, the microbubbles 'stick' only to the target cells.
But it is not easy to pick up these hotspots on a scan. "We are looking at the very earliest stages of tumour growth, so there are not many cells present expressing the marker of interest," explains Alessandro Nencioni who coordinated the project.
"There may be only three or four microbubbles adhered to a site and current ultrasound equipment is not able to pick these up. Work on the hardware and signal processing is an essential aspect of this project as we seek to develop next-generation ultrasound imaging capabilities."
Strong signals
Esaote, an Italian manufacturer of medical imaging equipment, is working with several research partners and two SMEs: Vermon, a French manufacturer of medical imaging probes, and SignalGeneriX, a small firm based in Cyprus with expertise in signal processing. Their aim is to produce a scanner and a dedicated probe that can transmit and receive ultrasound waves across a wide range of frequencies and wave forms in order to exploit (without any modification) the harmonic components caused by nonlinear scattering of the acoustic wave of the microbubbles.
The scanning equipment must have sufficient processing power to interpret the waves picked up by the probe, update the live image and adjust the transmitted waveforms in real time. Their detecting function is ensured by a specifically developed signal processing methods, able to detect a very limited number of microbubbles (down to a single bubble), to estimate their concentration, and to track their behaviour to get the diagnostic answer searched.