Multi-color magnetic nanoparticle imaging using magnetorelaxometry.

Magnetorelaxometry (MRX) is a well-known measurement technique which allows the retrieval of magnetic nanoparticle (MNP) characteristics such as size distribution and clustering behavior. This technique also enables the non-invasive reconstruction of the spatial MNP distribution by solving an inverse problem, referred to as MRX imaging. Although MRX allows the imaging of a broad range of MNP types, little research has been done on imaging different MNP types simultaneously. Biomedical applications can benefit significantly from a measurement technique that allows the separation of the resulting measurement signal into its components originating from different MNP types. In this paper, we present a theoretical procedure and experimental validation to show the feasibility of MRX imaging in reconstructing multiple MNP types simultaneously. Because each particle type has its own characteristic MRX signal, it is possible to take this a priori information into account while solving the inverse problem. This way each particle type's signal can be separated and its spatial distribution reconstructed. By assigning a unique color code and intensity to each particle type's signal, an image can be obtained in which each spatial distribution is depicted in the resulting color and with the intensity measuring the amount of particles of that type, hence the name multi-color MNP imaging. The theoretical procedure is validated by reconstructing six phantoms, with different spatial arrangements of multiple MNP types, using MRX imaging. It is observed that MRX imaging easily allows up to four particle types to be separated simultaneously, meaning their quantitative spatial distributions can be obtained.

Toward 2D and 3D imaging of magnetic nanoparticles using EPR measurements.

PURPOSE: Magnetic nanoparticles (MNPs) are an important asset in many biomedical applications. An effective working of these applications requires an accurate knowledge of the spatial MNP distribution. A promising, noninvasive, and sensitive technique to visualize MNP distributions in vivo is electron paramagnetic resonance (EPR). Currently only 1D MNP distributions can be reconstructed. In this paper, the authors propose extending 1D EPR toward 2D and 3D using computer simulations to allow accurate imaging of MNP distributions. METHODS: To find the MNP distribution belonging to EPR measurements, an inverse problem needs to be solved. The solution of this inverse problem highly depends on the stability of the inverse problem. The authors adapt 1D EPR imaging to realize the imaging of multidimensional MNP distributions. Furthermore, the authors introduce partial volume excitation in which only parts of the volume are imaged to increase stability of the inverse solution and to speed up the measurements. The authors simulate EPR measurements of different 2D and 3D MNP distributions and solve the inverse problem. The stability is evaluated by calculating the condition measure and by comparing the actual MNP distribution to the reconstructed MNP distribution. Based on these simulations, the authors define requirements for the EPR system to cope with the added dimensions. Moreover, the authors investigate how EPR measurements should be conducted to improve the stability of the associated inverse problem and to increase reconstruction quality. RESULTS: The approach used in 1D EPR can only be employed for the reconstruction of small volumes in 2D and 3D EPRs due to numerical instability of the inverse solution. The authors performed EPR measurements of increasing cylindrical volumes and evaluated the condition measure. This showed that a reduction of the inherent symmetry in the EPR methodology is necessary. By reducing the symmetry of the EPR setup, quantitative images of larger volumes can be obtained. The authors found that, by selectively exciting parts of the volume, the authors could increase the reconstruction quality even further while reducing the amount of measurements. Additionally, the inverse solution of this activation method degrades slower for increasing volumes. Finally, the methodology was applied to noisy EPR measurements: using the reduced EPR setup's symmetry and the partial activation method, an increase in reconstruction quality of ≈ 80% can be seen with a speedup of the measurements with 10%. CONCLUSIONS: Applying the aforementioned requirements to the EPR setup and stabilizing the EPR measurements showed a tremendous increase in noise robustness, thereby making EPR a valuable method for quantitative imaging of multidimensional MNP distributions.