Detection of tumorigenesis in rat bladders with optical coherence tomography.

Optical coherence tomography (OCT) is a novel technique that enables noninvasive cross-sectional imaging of biological tissues. Because of its high resolution (approximately 10 microm), superior dynamic range (140 dB in our case) and up to 2-3 mm penetration depth, OCT is potentially useful for noninvasive screening of superficial lesions. Bladder cancer arises within the transitional epithelium. Despite the ability to visualize the epithelium via cystoscopy, it is often difficult to detect early epithelial cancers and to determine their penetration to the underlying layers. To investigate the potential of OCT to enhance imaging of bladder cancers and other epithelial lesions, we applied OCT to normal and diseased bladder epithelium, and correlated the results with histological findings. OCT images of porcine bladder (a close homolog of human bladder) confirm the ability of this method to image human tissues. To determine whether OCT can track the course of bladder cancer, a standard rat model of bladder cancer in which Fisher rats are exposed to methyl-nitroso-urea (MNU), was followed both with OCT and histological studies. Our results show that the micro morphology of porcine bladder such as the urothelium, submucosa and muscles is identified by OCT and well correlated with the histological evaluations. OCT detected edema, inflammatory infiltrates, and submucosal blood congestion as well as the abnormal growth of urothelium (e.g., papillary hyperplasia and carcinomas). By contrast, surface imaging, which resembles cystoscopy, provided far less sensitivity and resolution than OCT. This is the first OCT study of any tumor documented in a systematic fashion, and the results suggest the potential of OCT for the noninvasive diagnosis of both bladder inflammatory lesions and early urothelial abnormalities, which conventional cystoscopy often misses, by imaging characterization of the increases in urothelial thickening and backscattering. However, because of the depth limitation, OCT may have limited applications in staging the invasion of higher-state urothelial cancers, especially for papillary carcinomas.

[1]  K. Schomacker,et al.  Diagnosis of bladder carcinoma using protoporphyrin IX fluorescence induced by 5‐aminolaevulinic acid , 1999, BJU international.

[2]  Britton Chance,et al.  PHOTON DIFFUSION IN BREAST AND BRAIN: SPECTROSCOPY AND IMAGING , 1993 .

[3]  J. Fujimoto,et al.  In vivo endoscopic optical biopsy with optical coherence tomography. , 1997, Science.

[4]  P. So,et al.  Two-Photon deep tissue ex vivo imaging of mouse dermal and subcutaneous structures. , 1998, Optics express.

[5]  W. Denk,et al.  Two-photon laser scanning fluorescence microscopy. , 1990, Science.

[6]  R. Hicks,et al.  Bladder cancer and N-methyl-N-nitrosourea. II. Sub-cellular changes associated with a single noncarcinogenic dose of MNU. , 1973, Chemico-biological interactions.

[7]  J. Fujimoto,et al.  High resolution imaging of the upper respiratory tract with optical coherence tomography: a feasibility study. , 1998, American journal of respiratory and critical care medicine.

[8]  S A Boppart,et al.  High resolution imaging of transitional cell carcinoma with optical coherence tomography: feasibility for the evaluation of bladder pathology. , 1999, The British journal of radiology.

[9]  Jennifer K. Barton,et al.  OPTICAL COHERENCE TOMOGRAPHY FOR BIODIAGNOSTICS , 1997 .

[10]  J G Fujimoto,et al.  High-resolution optical coherence tomographic imaging using a mode-locked Ti:Al(2)O(3) laser source. , 1995, Optics letters.

[11]  J. Flamm,et al.  The significance of bladder quadrant biopsies in patients with primary superficial bladder carcinoma. , 1989, European urology.

[12]  H Stepp,et al.  Detection of early bladder cancer by 5-aminolevulinic acid induced porphyrin fluorescence. , 1996, The Journal of urology.

[13]  M Rajadhyaksha,et al.  Near-infrared confocal laser scanning microscopy of bladder tissue in vivo. , 1999, Urology.

[14]  J. Bacus,et al.  Cytology, flow cytometry, image analysis, and interphase cytogenetics by fluorescence in situ hybridization in the diagnosis of transitional cell carcinoma in bladder washes: A comparative study , 1995, Diagnostic cytopathology.

[15]  Adolf Friedrich Fercher Optical coherence tomography. , 1996 .

[16]  Reginald Birngruber,et al.  Optical coherence-gated imaging of biological tissues , 1996 .

[17]  R Birngruber,et al.  Contrast limits of coherence-gated imaging in scattering media. , 1997, Applied optics.

[18]  J. Fujimoto,et al.  Optical Coherence Tomography , 1991 .

[19]  D L Farkas,et al.  Noninvasive imaging of living human skin with dual-wavelength optical coherence tomography in two and three dimensions. , 1998, Journal of biomedical optics.

[20]  C. Brendler,et al.  Experimental intravesical therapy for superficial transitional cell carcinoma in a rat bladder tumor model. , 1991, The Journal of urology.

[21]  Reginald Birngruber,et al.  Optical coherence tomography in turbid tissue: theoretical analysis and experimental results , 1996, Other Conferences.

[22]  D. Ducassou,et al.  Initial Evaluation of Cyfra 21-1 Diagnostic Performances as a Urinary Marker in Bladder Transitional Cell Carcinoma , 1998 .

[23]  B. Wilson,et al.  Frequency-domain reflectance for the determination of the scattering and absorption properties of tissue. , 1991, Applied optics.

[24]  Brett E. Bouma,et al.  In vivo cellular optical coherence tomography imaging , 1998, Nature Medicine.

[25]  Joseph M. Schmitt,et al.  MODEL OF OPTICAL COHERENCE TOMOGRAPHY OF HETEROGENEOUS TISSUE , 1997 .

[26]  B. Liu,et al.  Sensitivity and specificity of NMP-22, telomerase, and BTA in the detection of human bladder cancer. , 1999, Urology.

[27]  G. Gelikonov,et al.  Endoscopic applications of optical coherence tomography. , 1998, Optics express.

[28]  D. Pode,et al.  Immunostaining of Lewis X in cells from voided urine, cytopathology and ultrasound for noninvasive detection of bladder tumors. , 1998, The Journal of urology.

[29]  R Birngruber,et al.  Low-coherence optical tomography in turbid tissue: theoretical analysis. , 1995, Applied optics.

[30]  J Mertz,et al.  Combined scanning optical coherence and two-photon-excited fluorescence microscopy. , 1999, Optics letters.

[31]  R. Hicks,et al.  Rapid induction of bladder cancer in rats with N-methyl-N-nitrosourea. I. Histology. , 1972, Chemico-biological interactions.

[32]  R. Webb,et al.  In vivo confocal scanning laser microscopy of human skin: melanin provides strong contrast. , 1995, The Journal of investigative dermatology.

[33]  Steve C. Johnston,et al.  The final science and engineering Internet hunt , 1997 .