Sensitive detection of in vivo traumatic brain injury foci using magnetic particle imaging

Diagnosing traumatic brain injury (TBI) remains a major clinical challenge, particularly for mild to moderate cases, due to the limited sensitivity of conventional imaging modalities like magnetic resonance imaging (MRI) and computed tomography (CT) in detecting subtle cerebrovascular damage early after injury occurs. Magnetic particle imaging (MPI) is a novel modality that offers high sensitivity, linear quantification, and unambiguous detection of superparamagnetic tracers such as iron oxide nanoparticles (IONPs). This study evaluates the capacity of MPI to detect and visualize cerebral bleeding resulting from TBI. A controlled cortical impact (CCI) closed-head TBI model was implemented using a calibrated electromagnetic impactor to induce moderate brain injury in C57BL/6 mice. IONPs were administered intravenously after impact, to mimic potential clinical use. CT-registered MPI images revealed strong, localized signals in the impact region of injured animals at early time points, while sham animals showed no residual signal in the brain. This localized signal decayed over time and eventually approached noise levels after 7 days post-injury. A direct comparison between MPI and -weighted MRI demonstrated that only MPI reliably differentiates the early injury foci at 24 hours. These results highlight the sensitivity and specificity of MPI as a potential diagnostic tool for detecting vascular disruption in TBI, offering a promising minimally invasive approach for early injury assessment. Additionally, these results demonstrate nanoparticle accumulation in sites of moderate TBI, highlighting potential theranostic applications of MPI to develop drug carriers suitable for treatment of TBI.