Nonlinear susceptibility magnitude imaging of magnetic nanoparticles

• Development of a nonlinear susceptibility magnitude imaging model
• Demonstration of nonlinear SMI with primary and harmonic frequencies
• Demonstration of nonlinear SMI with primary and intermodulation frequencies
• Demonstration of a six-fold improvement in imaging resolution using nonlinear SMI
• Demonstration of time-multiplexing imaging resolution improvements

This study demonstrates a method for improving the resolution of susceptibility magnitude imaging (SMI) using spatial information that arises from the nonlinear magnetization characteristics of magnetic nanoparticles (mNPs). In this proof-of-concept study of nonlinear SMI, a pair of drive coils and several permanent magnets generate applied magnetic fields and a coil is used as a magnetic field sensor. Sinusoidal alternating current (AC) in the drive coils results in linear mNP magnetization responses at primary frequencies, and nonlinear responses at harmonic frequencies and intermodulation frequencies. The spatial information content of the nonlinear responses is evaluated by reconstructing tomographic images with sequentially increasing voxel counts using the combined linear and nonlinear data. Using the linear data alone it is not possible to accurately reconstruct more than 2 voxels with a pair of drive coils and a single sensor. However, nonlinear SMI is found to accurately reconstruct 12 voxels (R2=0.99, CNR=84.9) using the same physical configuration. Several time-multiplexing methods are then explored to determine if additional spatial information can be obtained by varying the amplitude, phase and frequency of the applied magnetic fields from the two drive coils. Asynchronous phase modulation, amplitude modulation, intermodulation phase modulation, and frequency modulation all resulted in accurate reconstruction of 6 voxels (R2>0.9) indicating that time multiplexing is a valid approach to further increase the resolution of nonlinear SMI. The spatial information content of nonlinear mNP responses and the potential for resolution enhancement with time multiplexing demonstrate the concept and advantages of nonlinear SMI.