| Abstract: |
Purpose MRI has become a powerful tool to distinguish between adjacent tissues by taking into account a variety of chemical, physical and biological properties of living tissue. By use of magnetic contrast agents in MRI one can even gain insight into some metabolic functions of a host. Conclusion on the metabolism, however, can only be drawn if (a) the metabolic function of interest locally affects the concentration of the contrast agent, and (b) the contrast agent leads to a clearly observable change in MRI signal within the region of interest. We present a contrast mechanism which aims to distinguish between magnetic contrast agents which are conjugated to cells or macromolecules and those which are not, independent on their spatial distribution. which is expected to picture the mobility of labeled macromolecules. The mobility might be changed, e.g., by the viscosity of the MNPs surroundings or by the macromolecules reactions to cells or other objects. which instantaneously can be switched on and off and thus provide specific information by immediate comparison between pictures taken with this contrast and those taken without it. The high specificity to chemical reactions of the here proposed contrast mechanism might become basis of a new method for functional imaging. Method The spin-lattice relaxation time T1 of a sample volume decreases if magnetic nanoparticles (MNP) which are connected to mesoscopic objects are subjected to an ultrasonic wave at MRI Larmor frequency. This effect can be interpreted as a change in relaxivity of the MNPs under the influence of resonant ultrasound (US). MNPs subjected to an ultrasonic wave are accelerated periodically with US frequency, which now is assumed to match the Larmor frequency. It is well known that the induced translational movement of the MNPs does not lead to a pronounced change in the MRI relaxation times. If a MNP is connected to a organic macromolecule, however, the compound bends and to tilts periodically in the ultrasonic wave because its center of mass differs from its center of geometry (Fig. to right). Consequently these MNPs act as radio frequency near field antennas, inducing additional relaxation to nuclei in the vicinity of the MNPs. Results We measured the proton spin-lattice relaxation time of a colloidal solution of MNPs (Ø = 50 nm) connected to a macromolecule (chicken IgG) by means of an inversion recovery sequence (TI = 550 ms, TR = 20,000 ms) and analyzed the spectral composition of the 90° FID (cf. Fig. to left). The abscissa denotes the frequency match between Larmor frequencies and US frequency (fUS = 18.32 MHz). When US was applied during the recovery process we could observe a change in signal amplitudes for spectral components matching the US frequency (upper curves). This we interpreted as a gain in relaxivity of the MNP-macromolecule compounds (lower curves). No changes in the FIDs' spectral amplitudes under the influence of resonant US were observed for a comparable solution of standard MNPs. We observed a gain in relaxivity of more than 15 % at US intensities of P = 10-3 W/cm². Conclusion Experiments for observing this contrast in a low field MRI device are underway. Due to the possibility to distinguish between bound an unbound MNPs independent on their spatial distribution and due to the improved contrast reliability by immediate comparison with not-contrast-enhanced pictures we expect this contrast method to fundamentally improve functional MRI. |
, N. Elmiladi