Selective sampling using confocal Raman spectroscopy provides enhanced specificity for urinary bladder cancer diagnosis (original) (raw)
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Urology, 2005
Objectives. To determine whether a fiberoptic Raman system, suitable for in vivo use, is able to differentiate between benign and malignant bladder and prostate pathologic findings in vitro. Raman spectroscopy is an optical technique that provides a measure of the molecular composition of tissue by analyzing the way that tissue scatters laser light. Laboratory studies have shown that the technique can be used to identify and characterize transitional cell carcinoma and prostate adenocarcinoma in vitro. Methods. A total of 220 Raman spectra were recorded from 29 snap-frozen bladder samples collected at cystoscopic procedures, and 197 Raman spectra were recorded from 38 snap-frozen prostate samples collected at transurethral resection of the prostate. The spectra were correlated with the histologic features and used to construct separate diagnostic algorithms for the bladder and prostate. These algorithms were tested as to their ability to determine the pathologic finding of a sample from its Raman spectrum. Results. The bladder algorithm was able to differentiate benign samples (normal and cystitis) from malignant samples (transitional cell carcinoma), with an overall accuracy of 84%. The prostate algorithm was able to differentiate benign samples (benign prostatic hyperplasia and prostatitis) from malignant samples (prostate cancer), with an overall accuracy of 86%. Conclusions. The results of this study have demonstrated that the clinical Raman system can provide an accurate and objective method to diagnose prostate and bladder cancer in vitro. Because the Raman probe is suitable for use during endoscopic, laparoscopic, or open procedures, this work paves the way for in vivo studies.
Bladder cancer diagnosis during cystoscopy using Raman spectroscopy
Proceedings of SPIE - The International Society for Optical Engineering
Raman spectroscopy is an optical technique that can be used to obtain specific molecular information of biological tissues. It has been used successfully to differentiate normal and pre-malignant tissue in many organs. The goal of this study is to determine the possibility to distinguish normal tissue from bladder cancer using this system. The endoscopic Raman system consists of a 6 Fr endoscopic probe connected to a 785nm diode laser and a spectral recording system. A total of 107 tissue samples were obtained from 54 patients with known bladder cancer during transurethral tumor resection. Immediately after surgical removal the samples were placed under the Raman probe and spectra were collected and stored for further analysis. The collected spectra were analyzed using multivariate statistical methods. In total 2949 Raman spectra were recorded ex vivo from cold cup biopsy samples with 2 seconds integration time. A multivariate algorithm allowed differentiation of normal and malignan...
Bladder cancer diagnosis during cystoscopy using Raman spectroscopy
Photonic Therapeutics and Diagnostics V, 2009
Raman spectroscopy is an optical technique that can be used to obtain specific molecular information of biological tissues. It has been used successfully to differentiate normal and pre-malignant tissue in many organs. The goal of this study is to determine the possibility to distinguish normal tissue from bladder cancer using this system. The endoscopic Raman system consists of a 6 Fr endoscopic probe connected to a 785nm diode laser and a spectral recording system. A total of 107 tissue samples were obtained from 54 patients with known bladder cancer during transurethral tumor resection. Immediately after surgical removal the samples were placed under the Raman probe and spectra were collected and stored for further analysis. The collected spectra were analyzed using multivariate statistical methods. In total 2949 Raman spectra were recorded ex vivo from cold cup biopsy samples with 2 seconds integration time. A multivariate algorithm allowed differentiation of normal and malignant tissue with a sensitivity and specificity of 78,5% and 78,9% respectively. The results show the possibility of discerning normal from malignant bladder tissue by means of Raman spectroscopy using a small fiber based system. Despite the low number of samples the results indicate that it might be possible to use this technique to grade identified bladder wall lesions during endoscopy.
Analytical and Bioanalytical Chemistry, 2007
Near-infrared Raman spectroscopy, an optical technique that is able to interrogate biological tissues, has been used to study bladder and prostate tissues, with the objective being to provide a first approximation of gross biochemical changes associated with the process of carcinogenesis. Prostate samples for this study were obtained by taking a chip at TURP, and bladder samples from a biopsy taken at TURBT and TURP, following ethical approval. Spectra were taken from purchased biochemical constituents and different pathologies within the bladder and the prostate. We were then able to determine the biochemical basis for these pathologies by utilising an ordinary leastsquares fit. We have shown for the first time that we are able to utilise Raman spectroscopy in determining the biochemical basis for the different pathologies within the bladder and prostate gland. In this way we can achieve a better understanding of disease processes such as carcinogenesis. This could have major implications in the future of the diagnosis of disease within the bladder and the prostate gland.
Modulated Raman spectroscopy for enhanced identification of bladder tumor cells in urine samples
Journal of Biomedical Optics, 2011
Standard Raman spectroscopy (SRS) is a noninvasive technique that is used in the biomedical field to discriminate between normal and cancer cells. However, the presence of a strong fluorescence background detracts from the use of SRS in real-time clinical applications. Recently, we have reported a novel modulated Raman spectroscopy (MRS) technique to extract the Raman spectra from the background. In this paper, we present the first application of MRS to the identification of human urothelial cells (SV-HUC-1) and bladder cancer cells (MGH) in urine samples. These results are compared to those obtained by SRS. Classification using the principal component analysis clearly shows that MRS allows discrimination between Raman spectra of SV-HUC-1 and MGH cells with high sensitivity (98%) and specificity (95%). MRS is also used to distinguish between SV-HUC-1 and MGH cells after exposure to urine for up to 6 h. We observe a marked change in the MRS of SV-HUC-1 and MGH cells with time in urine, indicating that the conditions of sample collection will be important for the application of this methodology to clinical urine samples. C 2011 Society of Photo-Optical Instrumentation Engineers (SPIE).
European Urology, 2011
a v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m j o u r n a l h o m e p a g e : w w w . e u r o p e a n u r o l o g y . c o m Abstract 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 Â100 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 À1 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 lowgrade 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.
Raman chemometric urinalysis (Rametrix) as a screen for bladder cancer
PLOS ONE, 2020
Bladder cancer (BCA) is relatively common and potentially recurrent/progressive disease. It is also costly to detect, treat, and control. Definitive diagnosis is made by examination of urine sediment, imaging, direct visualization (cystoscopy), and invasive biopsy of suspect bladder lesions. There are currently no widely-used BCA-specific biomarker urine screening tests for early BCA or for following patients during/after therapy. Urine metabolomic screening for biomarkers is costly and generally unavailable for clinical use. In response, we developed Raman spectroscopy-based chemometric urinalysis (Rametrix™) as a direct liquid urine screening method for detecting complex molecular signatures in urine associated with BCA and other genitourinary tract pathologies. In particular, the Rametrix TM screen used principal components (PCs) of urine Raman spectra to build discriminant analysis models that indicate the presence/absence of disease. The number of PCs included was varied, and all models were cross-validated by leave-one-out analysis. In Study 1 reported here, we tested the Rametrix™ screen using urine specimens from 56 consented patients from a urology clinic. This proof-of-concept study contained 17 urine specimens with active BCA (BCA-positive), 32 urine specimens from patients with other genitourinary tract pathologies, seven specimens from healthy patients, and the urinalysis control Surine TM. Using a model built with 22 PCs, BCA was detected with 80.4% accuracy, 82.4% sensitivity, 79.5% specificity, 63.6% positive predictive value (PPV), and 91.2% negative predictive value (NPV). Based on the number of PCs included, we found the Rametrix TM screen could be fine-tuned for either high sensitivity or specificity. In other studies reported here, Rametrix TM was also able to differentiate between urine specimens from patients with BCA and other genitourinary pathologies and those obtained from patients with end-stage kidney disease (ESKD). While larger studies are needed to improve Rametrix TM models and demonstrate clinical relevance, this study demonstrates the ability of the Rametrix TM screen to differentiate urine of
Detecting urine metabolites of bladder cancer by surface-enhanced Raman spectroscopy
Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 2021
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