Lighting up necrotic neurons from traumatic brain injury with magnetic quantum dots to decode the cellular origin of MRI

The diagnosis of traumatic brain injury (TBI) remains heavily constrained by the limitations of conventional imaging techniques in visualizing the pathological events that determine the disease progression and outcome. To address this clinical challenge, we report a manganese-doped near-infrared quantum dot (QD) to intrinsically integrate the highly sensitive optical imaging with clinical compatible magnetic resonance imaging (MRI). Taking the advantages of optical imaging powered by whole-brain clearing and cellular resolution three-dimensional (3D) panoptic imaging, in combination with the systematic in vitro cell studies on different types of cells involved in TBI, we disclosed the interpretable pathology reflected by TBI imaging through the highly sensitive fluorescence of magnetic QDs, i.e., after systemic administration, the nanoprobes were extravasated through the compromised blood-brain barrier and then selectively phagocytosed by activated microglia, which subsequently migrated into the regions rich in dead neurons and neuronal debris. This microglia-mediated tropism decodes the signal origin of MRI enhanced by the nanometer-sized contrast agent, thereby transforming the MRI from an anatomical tool into a pathological reporter. A biocompatible Fe 3 O 4 nanoparticle of similar size was also compared with the magnetic QD mentioned above for validating the translational merits of nanoparticles in MRI diagnosis of TBI.