Unveiling Dipolar Interaction-Driven Magnetic Field Inhomogeneities in T2 MRI Contrast Agents.

Modulating local magnetic field inhomogeneities, combined with ultra-high-field MRI (UHF-MRI) is a promising strategy to enhance the performance of next-generation T2 contrast agents (CAs). Although dipolar interactions likely contribute to contrast enhancement, their role in magnetic inhomogeneities and proton dephasing remains poorly understood, limiting further optimization. In this study, the fundamental role of dipolar interactions on the modulation of the transverse relaxivity (r2) of iron oxide-based CAs is demonstrated by shaping local magnetic field inhomogeneities. A nanoscale-distance-tuned model system is developed by coating superparamagnetic iron oxide nanoprobes with silica shells of increasing thickness, thereby modulating the intensity of the dipolar interactions. An exponential dependence of r2 on dipolar interaction strength is observed, with a sharp initial increase followed by a plateau as interactions reached their effective range, resulting in up to a sevenfold enhancement compared to interaction-free CAs. Furthermore, the dependence of r2 on B0 is evaluated across conventional field-MRI (1.4 and 3.0 T) to UHF-MRI (7.0 and 11.7 T), in both interacting and non-interacting CA systems, revealing a nonlinear behavior. These findings establish dipolar interaction control as a key parameter for optimizing T2-CAs performance, advancing the design of next-generation MRI nanoprobes for diagnostic applications.