In Vivo Photoacoustic Imaging of Brain Injury and Rehabilitation by High‐Efficient Near‐Infrared Dye Labeled Mesenchymal Stem Cells with Enhanced Brain Barrier Permeability

Stem cell migration and interaction with pathology are critical to understand the complexity and status of disease recovery progress. However, the dynamic visualization still remains a great challenge due to imaging technical limitation, cell labeling difficulty, or blood-brain barrier (BBB). Herein, fast photoacoustic tomography (PAT) with optical molecular probes is applied to noninvasively monitor traumatic brain injury (TBI) and its rehabilitation. The vascular distribution and TBI hemorrhage are clearly imaged, longitudinally monitored, and quantified. Bone mesenchymal stem cells (BMSCs) labeled with modified Prussian blue particles (PBPs), excellent near-infrared dyes and photoacoustic contrasts, are intravenously injected to the mice for improved observation and efficient therapy. BMSCs are demonstrated to be capable of overcoming BBB with enhanced delivery of PBPs to the brain parenchyma. Notably, the versatile BMSCs are observed by PAT to home to the damage region and repair the ruptured vasculature. Moreover, the wound treated by BMSCs exhibits much faster recovery speed than that without treatment. These findings can potentially provide a new noninvasive and high-resolution approach to image TBI, monitor recovery process, and especially trace BMSCs. This study will stimulate extensive researches on brain diseases and provide promising strategies of dye labeled BMSCs in regenerative medicine.