Application of magnetic particle imaging to pulmonary imaging using nebulized magnetic nanoparticles: Phantom and small animal experiments

Abstract

INTRODUCTION:Recently, a magnetic targeting method has been proposed for localizing drug carriers such as liposomes containing both magnetic nanoparticles (MNPs) and drugs in the objective organ or tissue by applying an external magnetic field, and it attracts attention as a next-generation therapeutic strategy for cancer. The application of this approach with use of nebulized MNPs to lung cancer has also been considered. The development of a method to specifically image MNPs is desired to realize this therapeutic strategy. This study was undertaken to investigate the feasibility of applying magnetic particle imaging (MPI) to pulmonary imaging using nebulized MNPs and to evaluate the usefulness and reliability of this approach using phantom and small animal experiments. METHODS:In phantom experiments, we prepared a Y-shaped bifurcated tube made of Teflon which simulated tracheal bifurcation, and connected an inhaler to the outlets of the tube. We then nebulized MNPs using a nebulizer and they were sucked from the inlet of the bifurcated tube to the outlets. Furthermore, we placed the urethane sponges simulating pulmonary tissues at the left and right outlets of the bifurcated tube. We also placed two flowmeters between the inhaler and Y-shaped bifurcated tube to control the flow of nebulized MNPs. In addition, we put a neodymium magnet (0.5 Tesla) on the bifurcation of the Y-shaped tube. After the experiment, we imaged the urethane sponges using our MPI scanner [1, 2] and calculated an asymmetry index (AI) from (L-R)/(L+R), where L and R represent the MPI values of the urethane sponge at the left and right outlets of the Y-shaped bifurcated tube, respectively. In this study, the MPI value was defined as the pixel value of the transverse image reconstructed from the third-harmonic signals extracted using a gradiometer coil and a lock-in amplifier [1, 2]. We then investigated the relationships between the AI value and the distance between the Y-shaped bifurcated tube and neodymium magnet and between the AI value and flow rate.In animal experiments, seven-week-old male ICR mice were used. Intrapulmonary administration of MNPs was performed using a nebulizing microsprayer connected to a high-pressure syringe containing 50 L of MNPs (Resovist ). We imaged the lungs using our MPI scanner [1, 2] two and a half hours after the intrapulmonary administration of MNPs. After the MPI studies, X-ray CT images were obtained using a 4-row multi-slice CT scanner. The MPI image was co-registered with the X-ray CT image using parameters for magnification and rotation that were previously obtained using a phantom with 3 point sources. RESULTS:In phantom experiments, there was an excellent negative correlation between the AI value and the distance between the bifurcated tube and neodymium magnet (r=-0.995). The AI value decreased significantly with increasing flow rate, and there was also a significant negative correction between the AI value and flow rate (r=-0.958). These results suggest that MPI is useful for monitoring the effect...

Magnetic Particle Imaging in Vascular Imaging, Immunotherapy, Cell Tracking, and Noninvasive Diagnosis

“…These images consist solely of tracer particles, making them similar to images produced in nuclear medicine. MPI is particularly useful for vascular imaging [28][29][30][31] and for tracking cytotherapies, such as red blood cells (RBCs) [32], stem cells [33][34][35], and white blood cells (WBCs) [23,36,37], all without any radiation.…”