Purpose: Magnetic spectroscopy of Brownian motion (MSB) has been used previously to measure temperature, viscosity, and cellular binding in vitro. The MSB signal - a ratio of the 5th to 3rd harmonic of the response from magnetic nanoparticles to an oscillating field - provides insight into particle microenvironment. These biosensing capabilities would be productive in vivo but until now were prevented by sensitivity limits. Our goal was to design and create a similar apparatus for work in vivo. In vivo spectroscopy is a viable precursor to imaging, and is essential for drug delivery or therapeutic methods like hyperthermia.

Methods: Coil geometries were modeled to optimize a uniform Helmholtz drive coil and imaging coil with maximal spatial resolution. The completed apparatus includes balancing and trim coils to zero out unwanted background fields. The coils were characterized and experiments were performed to verify consistency with previous in vitro experiments. Finally, as an in vivo experiment, we took MSB spectra on living mice with five week old melanomas injected with 200ug of 100nm starch coated nanoparticles.

Results: The drive coil is capable of sustaining 12.5mT fields up to 1.5kHz with a field variation of 3% throughout the sample volume. The pickup coil is frequency independent and has a vertical and horizontal range of 5mm and 10mm respectively before the MSB signal drops below 50%. The minimum sensitivity is 50-70μg of iron. MSB signal response to viscosity changes shows the same signatures as the in vitro apparatus. The in vivo data showed successful sensing of nanoparticles. We also saw the MSB signal decay with time showing the apparatus can detect changes in particle behavior due to interactions with biology.

Conclusions: We achieved in vivo MSB and due to sufficient sensitivity we are motivated to further work in monitoring in vivo cellular uptake and viscosity.

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http://dx.doi.org/10.1118/1.4734798DOI Listing

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