Researchers in the EU-funded TAMIRUT (targeted microbubbles and remote ultrasound transduction) project have developed a way to attach antibodies onto the surface of microbubbles. Selecting the appropriate antibody ensures that the bubbles only adhere to targeted cells - for example, endothelial cells of vessels lining the tumours. However, detecting the resulting hotspots on an ultrasound scan is not necessarily straightforward.
"We are looking at the very earliest stages of tumour growth, so there are not many cells present expressing the marker of interest," explained project coordinator Alessandro Nencioni, from Italian medical imaging equipment vendor Esaote. "There may be only three or four microbubbles adhered to a site and current ultrasound equipment is not able to pick these up."
Esaote is now working with partners - including French imaging probe maker Vermon and Cypriot signal-processing specialist SignalGeneriX - to develop the required hardware and signal-processing capabilities. The goal is to produce a scanner and dedicated probe that can transmit and receive ultrasound signals across a wide range of frequencies and waveforms, in order to exploit the harmonic components caused by nonlinear scattering from the microbubbles.
The researchers are also developing dedicated signal-processing methods that can detect a limited number of microbubbles (down to a single bubble), estimate their concentration and track their behaviour. Differentiation between bound and unbound microbubbles is achieved by extended imaging: after 10 minutes, microbubbles attached to the target cells remain in place while free ones diffuse away.
The TAMIRUT team has already demonstrated in simulations that the targeted microbubble contrast agent, the improved ultrasound hardware and the signal processing show potential for early detection of prostate cancer. The new probe will enable visualization of any areas of high microbubble density within an entire organ. Repeating the imaging process over time could help medical staff assess the evolution of a tumour, especially its vascularization.
"Our approach goes a long way to eliminating or strongly reducing the problem of false-negative diagnosis, offering a second degree of evaluation after blood test screening," said Nencioni. "It is sensitive, specific and you are able to examine the whole organ, which is not possible by biopsy."
Esaote is now working with its commercial partners to incorporate the new signal-processing features into its medical imaging equipment by the end of 2009. While the microbubble agent is unlikely to be available for at least three years, due to requirements for clinical trials prior to use in humans, the improved signal-processing algorithms can help increase the sensitivity of ultrasound equipment.
• The TAMIRUT project received funding from the ICT strand of the Sixth Framework Programme for research. Project partners are: Esaote, Italy; The University of Twente, the Netherlands; Bracco Research, Switzerland; Università di Genova, Italy; Vermon, France; Medizinische Universität Innsbruck, Austria; SignalGeneriX, Cyprus; Erasmus Medical Center, the Netherlands; Fraunhofer Institut für Biomedizinische Technik, Germany. Information compiled from ICT Results.