title: Direct Administration of Nerve-Specific Contrast to Improve Nerve Sparing Radical Prostatectomy.
abstract: Nerve damage remains a major morbidity following nerve sparing radical prostatectomy, significantly affecting quality of life post-surgery. Nerve-specific fluorescence guided surgery offers a potential solution by enhancing nerve visualization intraoperatively. However, the prostate is highly innervated and only the cavernous nerve structures require preservation to maintain continence and potency. Systemic administration of a nerve-specific fluorophore would lower nerve signal to background ratio (SBR) in vital nerve structures, making them difficult to distinguish from all nervous tissue in the pelvic region. A direct administration methodology to enable selective nerve highlighting for enhanced nerve SBR in a specific nerve structure has been developed herein. The direct administration methodology demonstrated equivalent nerve-specific contrast to systemic administration at optimal exposure times. However, the direct administration methodology provided a brighter fluorescent nerve signal, facilitating nerve-specific fluorescence imaging at video rate, which was not possible following systemic administration. Additionally, the direct administration methodology required a significantly lower fluorophore dose than systemic administration, that when scaled to a human dose falls within the microdosing range. Furthermore, a dual fluorophore tissue staining method was developed that alleviates fluorescence background signal from adipose tissue accumulation using a spectrally distinct adipose tissue specific fluorophore. These results validate the use of the direct administration methodology for specific nerve visualization with fluorescence image-guided surgery, which would improve vital nerve structure identification and visualization during nerve sparing radical prostatectomy.
authors.affiliation: Biomedical Engineering Department, Oregon Health & Science University, Portland, OR 97201.
authors.forename: Connor W
authors.initials: CW
authors.lastname: Barth
authors.affiliation: Biomedical Engineering Department, Oregon Health & Science University, Portland, OR 97201.; Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97201.; OHSU Center for Spatial Systems Biomedicine, Oregon Health & Science University, Portland, OR 97201.
authors.forename: Summer L
authors.initials: SL
authors.lastname: Gibbs
mesh_terms: D000287:Administration, Topical; D000818:Animals; D003287:Contrast Media / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D009420:Nervous System / Q000000981:diagnostic imaging*; D011468:Prostatectomy / Q000009:adverse effects / Q000379:methods*; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging / Q000601:surgery
chemical_list: D003287:Contrast Media
keywords: direct administration.; fluorescence image-guided surgery; nerve sparing radical prostatectomy; nerve-specific fluorophore; prostate cancer