In vivo tracking and quantification of inhaled aerosol using magnetic particle imaging towards inhaled therapeutic monitoring.

Pulmonary delivery of therapeutics is attractive due to rapid absorption and non-invasiveness but it is challenging to monitor and quantify the delivered aerosol or powder. Currently, single-photon emission computed tomography (SPECT) is used but requires inhalation of radioactive labels that typically have to be synthesized and attached by hot chemistry techniques just prior to every scan. Methods: In this work, we demonstrate that superparamagnetic iron oxide nanoparticles (SPIONs) can be used to label and track aerosols in vivo with high sensitivity using an emerging medical imaging technique known as magnetic particle imaging (MPI). We perform proof-of-concept experiments with SPIONs for various lung applications such as evaluation of efficiency and uniformity of aerosol delivery, tracking of the initial aerosolized therapeutic deposition in vivo, and finally, sensitive visualization of the entire mucociliary clearance pathway from the lung up to the epiglottis and down the gastrointestinal tract to be excreted. Results: Imaging of SPIONs in the lung has previously been limited by difficulty of lung imaging with magnetic resonance imaging (MRI). In our results, MPI enabled SPION lung imaging with high sensitivity, and a key implication is the potential combination with magnetic actuation or hyperthermia for MPI-guided therapy in the lung with SPIONs. Conclusion: This work shows how magnetic particle imaging can be enabling for new imaging and therapeutic applications of SPIONs in the lung.

A perspective on a rapid and radiation-free tracer imaging modality, magnetic particle imaging, with promise for clinical translation.

Magnetic particle imaging (MPI), introduced at the beginning of the twenty-first century, is emerging as a promising diagnostic tool in addition to the current repertoire of medical imaging modalities. Using superparamagnetic iron oxide nanoparticles (SPIOs), that are available for clinical use, MPI produces high contrast and highly sensitive tomographic images with absolute quantitation, no tissue attenuation at-depth, and there are no view limitations. The MPI signal is governed by the Brownian and Néel relaxation behavior of the particles. The relaxation time constants of these particles can be utilized to map information relating to the local microenvironment, such as viscosity and temperature. Proof-of-concept pre-clinical studies have shown favourable applications of MPI for better understanding the pathophysiology associated with vascular defects, tracking cell-based therapies and nanotheranostics. Functional imaging techniques using MPI will be useful for studying the pathology related to viscosity changes such as in vascular plaques and in determining cell viability of superparamagnetic iron oxide nanoparticle labeled cells. In this review article, an overview of MPI is provided with discussions mainly focusing on MPI tracers, applications of translational capabilities ranging from diagnostics to theranostics and finally outline a promising path towards clinical translation.