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.