Bone Disease Imaging through the Near-Infrared-II Window

Abstract

Bone health related skeletal disorders are commonly diagnosed by X-ray imaging, but the radiation limits its use. Light excitation and optical imaging through the near-infrared-II window (NIR-II, 1000–1700 nm) can penetrate deep tissues without radiation risk, but the targeting of contrast agent is non-specific. Here, we report that lanthanide-doped nanocrystals can be passively transported by endothelial cells and macrophages from the blood vessels into bone marrow microenvironment. We found that this bone targeting scheme can be effective for longer than two months. We therefore developed an intravital 3D and high-resolution planar imaging instrumentation for bone disease diagnosis. We demonstrated the regular monitoring of 1 mm bone defects for 11 days in NIR-II window, with spatial resolution similar to X-ray imaging result, but more flexible use in prognosis. Moreover, the passive targeting can be used to reveal the early onset inflammation at the joints as the synovitis in the early stage of rheumatoid arthritis. Furthermore, the proposed method is comparable to micro computed tomography (µCT) in recognizing symptoms of osteoarthritis, including the mild hyperostosis in femur which is ~ 100 µm thicker than normal, and the growth of millimeter-scale osteophyte in the knee joint, which further proves the power and universality of our approach.