A Near-Infrared Fluorogenic Spray Probe for Rapid and Wash-Free Intraoperative Nerve Imaging

Intraoperative nerve injury remains a major surgical challenge. Rapid, wash-free nerve visualization is highly desirable for fluorescence image-guided surgery (FIGS), yet existing probes lack spray compatibility and sufficient fluorogenicity. Here we introduce N4, a near-infrared fluorogenic spray probe that enables ∼10 s, wash-free visualization of peripheral nerves. N4 is engineered to remain nonfluorescent in its spirocyclic form under physiological conditions but undergoes MBP-triggered spiro-opening to a bright zwitterionic state, yielding a 6.3-fold turn-on. Topical spraying of N4 produces clear sciatic and vagus nerve imaging with nerve-to-muscle contrast up to 6.4 and allows visualization of branches as small as 0.12 mm, even under blood-contaminated fields. N4 provides a robust platform for real-time FIGS nerve mapping and advances the development of next-generation fluorogenic surgical probes.