Raman Molecular Imaging: a Novel Spectroscopic Technique for Diagnosis of Bladder Cancer in Urine Specimens

Background: Raman molecular imaging (RMI) is an optical technology that combines the molecular chemical analysis of Raman spectroscopy with high-definition digital microscopic visualization. This approach permits visualization of the physical architecture and molecular environment of cells in the urine. The Raman spectrum of a cell is a complex product of its chemical bonds.

Objective: In this work, we studied the possibility of using the Raman spectrum of epithelial cells in voided urine for diagnosing urothelial carcinoma (UC).

Design, Setting, And Participants: Raman signals were obtained from UC tissue, then from UC touch preps obtained from surgical specimens and studied using the FALCON microscope (ChemImage, Pittsburgh, PA, USA), with a×100 collection objective and green laser illumination (532 nm). Then, urine samples were obtained from 340 patients, including 116 patients without UC, 92 patients with low-grade tumors, and 132 patients with high-grade tumors. Spectra were obtained from an average of five cells per slide.

Measurements: Raman spectroscopy of cells from bladder cancer (BCa) tissues and patients.

Results And Limitations: The Raman spectra from UC tissue demonstrate a distinct peak at a 1584 cm(-1) wave shift not present in benign tissues. The height of this peak correlated with the tumor's grade. The signal obtained from epithelial cells correctly diagnosed BCa with sensitivity of 92% (100% of the high-grade tumors), specificity of 91%, and a positive predictive value of 94% and a negative predictive value of 88%. The signal correctly assigned a tumor's grade in 73.9% of the low-grade tumors and 98.5% of the high-grade tumors. RMI for diagnosis of BCa is limited by the need for specialized equipment and training of laboratory personnel.

Conclusions: RMI has the potential to become a powerful diagnostic tool that allows noninvasive, accurate diagnosis of UC.