Development of Magnetomotive Ultrasound Imaging

Sammanfattning: The earlier abnormalities coupled with disease can be discovered in the body, the larger is the chance to survive the disease. Molecular imaging is a growing research field which aims to detect these abnormalities at a molecular level, when the chance of survival is still high. The main idea of molecular imaging is to use target specific contrast agents that accumulate at the diseased region at a detectable concentration. Nanoparticles have shown to be very suitable as molecular imaging contrast agents due to their small size, which enable them to cross biological barriers and to bind to the biological entity of interest.

In this thesis has the potential of magnetomotive ultrasound (MMUS), a new ultrasound imaging technique which enables detection of superparamagnetic iron oxide nanoparticles (SPIONs), been examined. Nanoparticles are too small to be detected with conventional ultrasound since their small size make them unable to backscatter ultrasound at a detectable level. Instead, MMUS imaging makes profits of the induced movement, created when a time-varying magnetic field is applied to a sample containing SPIONs. As the particles start to move, their surrounding will move and ultrasound is used to detect this motion.

In the first study (paper I), was a frequency and phase tracking MMUS algorithm developed. The algorithm is able to filter out the nanoparticle movement from other artifactual movements and the location of the nanoparticles may then be revealed. To evaluate the potential of the developed algorithm, phantom studies (paper I, II and IV) were performed. Different parameters such as the nanoparticle concentration and the magnetic field frequency were altered in order to examine their impact on the magnetomotive displacement. Simulations were performed, where models of experimental setups were created. The results from the simulations were verified with the experimental findings (paper II and IV) and a good agreement was found.

Moreover, to evaluate the potential of MMUS to be used in health care, animal studies have been performed (paper III, V and VI). In this thesis, the MMUS technique was evaluated in a clinical relevant model, where SPION-laden sentinel lymph nodes (SLNs) in rats were imaged. In this model MMUS was thought to serve as a complementary imaging modality to standard methods, providing high-resolution bedside surgical guidance during SLN surgery in breast cancer or malignant melanoma. In order to test the model in a clinical scenario, prestaging of the SPION-laden SLNs was done with MRI or PET (paper III and VI, respectively), thereafter MMUS imaging was performed.

The results, both from the phantom and the animal studies, have shown to be very promising. Displacement in the sub-micrometer range has been detected in all studies. Although displacement artifacts have been more than two orders of magnitudes larger than the MMUS signal, the algorithm has been able to provide a clear representation of the location of the SPION-laden regions (e.g. paper III and V). This indicates that the MMUS technique has potential for future clinical use.