An investigation into the in vivo performance of Changsha and rhodamine fluorophores

Iatrogenic nerve injury remains one of the most common surgical complications, often resulting in permanent disabilities that severely impact patient quality of life following surgery. Current means of intraoperative nerve identification are limited beyond white light visualization and neuroanatomical knowledge but include ultrasound and the gold standard electromyography (EMG). However, nerve identification in the surgical field of view often remains inadequate. Though fluorophores like rhodamine, cyanine, and others have found extensive and diverse uses in the life sciences, in the realm of fluorescence-guided surgery (FGS), fluorophores that absorb and emit in the NIR region (650-900 nm) have the highest potential for clinical translation. Combining the structural characteristics of a long wavelength emitting fluorophore cyanine like indocyanine green (ICG) with those of a topically nerve-specific fluorophore, like rhodamine B, could offer a strategy for generating NIR-emissive and nerve-specific fluorophores. This study investigated whether the topical nerve-affinity observed in rhodamines extends to systemic administration and whether the structural hybridization strategy used in the previously published Changsha dyes could prove useful in generating long-wavelength nerve-specific contrast agents for use in FGS.