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Anal Chem. 2017 Jun 20;89(12):6893-6899. doi: 10.1021/acs.analchem.7b01403. Epub 2017 Jun 5.

Noninvasive Diagnosis of High-Grade Urothelial Carcinoma in Urine by Raman Spectral Imaging.

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Department of Biophysics, Ruhr-University Bochum , 44780 Bochum, Germany.
Bergmannsheil Hospital, Ruhr-University Bochum , 44789 Bochum, Germany.
Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr-University Bochum (IPA) , 44789 Bochum, Germany.
Department of Urology, Marien Hospital Herne, Ruhr-University Bochum , 44625 Herne, Germany.


The current gold standard for the diagnosis of bladder cancer is cystoscopy, which is invasive and painful for patients. Therefore, noninvasive urine cytology is usually used in the clinic as an adjunct to cystoscopy; however, it suffers from low sensitivity. Here, a novel noninvasive, label-free approach with high sensitivity for use with urine is presented. Coherent anti-Stokes Raman scattering imaging of urine sediments was used in the first step for fast preselection of urothelial cells, where high-grade urothelial cancer cells are characterized by a large nucleus-to-cytoplasm ratio. In the second step, Raman spectral imaging of urothelial cells was performed. A supervised classifier was implemented to automatically differentiate normal and cancerous urothelial cells with 100% accuracy. In addition, the Raman spectra not only indicated the morphological changes that are identified by cytology with hematoxylin and eosin staining but also provided molecular resolution through the use of specific marker bands. The respective Raman marker bands directly show a decrease in the level of glycogen and an increase in the levels of fatty acids in cancer cells as compared to controls. These results pave the way for "spectral" cytology of urine using Raman microspectroscopy.

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