Follicular tracking is typically conducted using ultrasound technology, but its effectiveness is constrained by limited resolution. High-resolution imaging of deep tissues can be accomplished using luminescence imaging in the near-infrared II window (NIR-II, 1000-1700 nm)
however, the contrast agents that are used lack specificity. Here, it is reported that the FDA-approved indocyanine green (ICG)-conjugated recombinant human chorionic gonadotropin (hCG) protein can target early follicles with long-term effectiveness. A novel high-resolution NIR-II imaging approach is developed for monitoring follicular development as well as ovulation using multi-color imaging of ovarian vessels with a combination of non-overlapping downconversion nanoparticles (DCNPs). The results showed that the ability to monitor early follicles of around 50 µm in diameter exceeded the spatial and temporal resolution of ultrasound or MRI without the reproductive damage associated with computed tomography radiation, and this enabled the clinical identification of the follicular reserve in patients with infertility diseases such as polycystic ovary syndrome (PCOS). In addition, NIR-II imaging clearly targeted ovarian tumors and showed micro-metastatic lesions, thus providing a new tool for monitoring tumors in vivo and guiding surgical resection.