Fluorescence-Based Microendoscopic Sensing System for Minimally Invasive In Vivo Bladder Cancer Diagnosis

Abstract

Bladder cancer is commonly diagnosed by evaluating the tissue morphology through cystoscopy, and tumor resection is used as the primary treatment approach. However, these methods are limited by lesion site specificity and resection margin, and can thereby fail to detect cancer lesions at early stages. Nevertheless, rapid diagnosis without biopsy may be possible through fluorescence sensing. Herein, we describe a minimally invasive imaging system capable of sensing even small tumors through a 1.2 mm diameter flexible fiber bundle microprobe. We demonstrate that this new device can be used for the early diagnosis of bladder cancer in rats. Bladder cancer was induced in rats using the carcinogen N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN), and a togglable filter capable of PpIX fluorescence sensing was installed in the microendoscopic system. Following 5-aminolevulinic acid administration, tissue in the early stages of bladder cancer was successfully identified with fluorescence detection and confirmed with hematoxylin/eosin and ferrochelatase staining. Although the time required for BBN to induce bladder cancer varied between 3 and 4 weeks among the rats, the microendoscopic system allowed the minimally invasive follow-up on cancer development.