Quantitative Susceptibility Mapping to Measure Focused Ultrasound-Mediated Delivery of Size-Variable Model Drugs to the Brain

Motivation: We lack a quantitative MRI method to investigate the effect of molecular size on the delivery profile of a model drug in focused ultrasound (FUS)-mediated blood-brain barrier disruption (BBBD). Goal(s): Demonstrate that quantitative susceptibility mapping (QSM) is capable of measuring the delivery of size-varied paramagnetic contrast agents in FUS-mediated BBBD. Approach: Utilize FUS to deliver paramagnetic contrast agents to the striatum of healthy mice, employing QSM to quantify and convert susceptibility changes to agent concentration. Results: Our work demonstrates that QSM is capable of measuring the 3D, in-vivo distribution of large-scale contrast agents after FUS-mediated BBB disruption with high spatial resolution. Impact: This study offers a new tool to measure the FUS-mediated delivery of molecules within the size range of common neurotherapeutics, enabling both clearer interpretation of therapeutic outcomes and size-specific dosage and treatment planning in both pre-clinical and clinical settings.