Evaluation of the Potential of Dipole Field Navigation for the Targeted Delivery of Therapeutic Agents in a Human Vascular Network

Magnetically guided agents in the vascular network are expected to enable the targeted delivery of therapeutics to localized regions while avoiding their systemic circulation. Due to the small size of the medically applicable superparamagnetic microscale agents required to reach the smaller arteries, high magnetic fields and gradients are required to reach saturation magnetization and generate sufficient directional forces, respectively, for their effective navigation in the vascular environment. Currently, the only method that provides both a high field and high magnetic gradient strengths in deep tissues at the human scale is known as dipole field navigation (DFN). This method relies on the controlled distortion of the field inside a magnetic resonance imaging scanner by precisely positioning ferromagnetic cores around the patient. This paper builds on previous works that have experimentally demonstrated the feasibility of the method and proposed optimization algorithms for placing the cores. The maximum gradient strengths that can be generated for single and multibifurcation vascular routes are investigated while considering the major constraints on core positions (limited space in the scanner, magnetic interactions). Using disc cores, which were previously shown particularly effective for the DFN, results show that gradient strengths exceeding 400 mT/m (a tenfold increase with respect to typical gradients generated by clinical MRI scanners) can be achieved at 10 cm inside the patient, but decrease as the complexity of the vascular route increases. The potential of the method is evaluated for targeting regions of a vascular model of a human liver, segmented from clinical data, with encouraging results showing strengths up to 150 mT/m for generating gradients at three consecutive bifurcations within 20 degrees of average gradient direction error.