Abstract

Most transitional cell tumorigenesis involves three stages of subcellular morphological changes: hyperplasia, dysplasia and neoplasia. Previous studies demonstrated that owing to its high spatial resolution and intermediate penetration depth, current OCT technology including endoscopic OCT could delineate the urothelium, submucosa and the upper muscular layers of the bladder wall. In this paper, we will discuss the sensitivity and limitations of OCT in diagnosing and staging bladder cancer. Based on histomorphometric evaluations of nuclear morphology, we modeled the resultant backscattering changes and the characteristic changes in OCT image contrast. In the theoretical modeling, we assumed that nuclei were the primary sources of scattering and were uniformly distributed in the uroepithelium, and compared with the results of the corresponding prior OCT measurements. According to our theoretical modeling, normal bladder shows a thin, uniform and low scattering urothelium, so does an inflammatory lesion except thickening in the submucosa. Compared with a normal bladder, a hyperplastic lesion exhibits a thickened, low scattering urothelium whereas a neoplastic lesion shows a thickened urothelium with increased backscattering. These results support our previous animal study that OCT has the potential to differentiate inflammation, hyperplasia, and neoplasia by quantifying the changes in urothelial thickening and backscattering. The results also suggest that OCT might not have the sensitivity to differentiate the subtle morphological changes between hyperplasia and dysplasia based on minor backscattering differences.

© 2002 Optical Society of America

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References

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Appl. Opt.

BJU International

F. Koenig, F. J. McGovern, R. Larne, H. Enquist, K. T. Schomacker and T. F. Deutsch, "Diagnosis of bladder carcinoma using protoporphyrin IX fluorescence induced by 5-aminolaevulinic acid," BJU International 83, 129-135 (1999).
[CrossRef] [PubMed]

IEEE J. Sel. Top. Quantum Electron.

M. E. Brezinski and J. G. Fujimoto, �??Optical Coherence Tomography: High-Resolution Imaging in Nontransparent Tissue,�?? IEEE J. Sel. Top. Quantum Electron. 5, 1185-1192 (1999).
[CrossRef]

J. M. Schmitt, �??Optical Coherence Tomography (OCT): A Review,�?? IEEE J. Sel. Top. Quantum Electron. 5, 1205-1215 (1999).
[CrossRef]

J. Opt. Soc. Am. A

J. Urology

M. Kriegmair, R. Baumgartner, R. Knuechel, H. Stepp, F. Hofstaedter and A. Hofstetter, "Detection of early bladder cancer by 5-aminolevulinic acid induced porphyrin fluorescence," J. Urology 155, 105-110 (1996).
[CrossRef]

Med. Phys.

Y. Pan, J. P. Lavelle, S. Meyers, G. Pirtskhalaishvili, M. L. Zeidel, and D. L. Frakas, �??Detection of tumorigenesis in rat bladders with optical coherence tomography,�?? Med. Phys. 28, 2432-2440 (2001).
[CrossRef]

Opt. Express

M. Kowalevicz, T. Ko, I. Hartl, J. G. Fujimoto, M. Pollnau, and R. P. Salathe, �??Ultrahigh resolution optical coherence tomography using a superluminescent light source,�?? Opt. Express 10, 349-353, 2002, <a href="http://www.opticsexpress.org/abstract.cfm?URI=OPEX-10-7-349">http://www.opticsexpress.org/abstract.cfm?URI=OPEX-10-7-349</a>.
[CrossRef] [PubMed]

A. M. Sergeev, V. M. Gelikonov, G. V. Gelikonov, F. I. Feldchtein, R. V. Kuranov, N. D. Gladkova, N. M. Shakhova, L. B. Snopova, A. V. Shakhov, I. A. Kuznetzova, A. N. Denisenko, V. V. Pochinko, Yu. P. Chumakov, and O. S. Streltzova, "In vivo endoscopic OCT imaging of precancer and cancer states of human mucosa," Opt. Express 1, 432-440 (1997), <a href="http://epubs.osa.org/oearchive/source/2788.htm">http://epubs.osa.org/oearchive/source/2788.htm</a>.
[CrossRef] [PubMed]

Johannes F. de Boer, Shyam M. Srinivas, Arash Malekafzali, Zhongping Chen, and J. Stuart Nelson, �??Imaging thermally damaged tissue by polarization sensitive optical coherence tomography,�?? Opt. Express 3, 212-218 (1998), <a href="http://www.opticsexpress.org/abstract.cfm?URI=OPEX-3-6-212">http://www.opticsexpress.org/abstract.cfm?URI=OPEX-3-6-212</a>.
[CrossRef] [PubMed]

Andrew Rollins, Joseph Izatt, Manish Kulkarni, Siavash Yazdanfar, Rujchai Ung-arunyawee, �??In vivo video rate optical coherence tomography,�?? Opt. Express 3, 219-229 (1998), <a href="http://www.opticsexpress.org/abstract.cfm?URI=OPEX-3-6-219">http://www.opticsexpress.org/abstract.cfm?URI=OPEX-3-6-219</a>.
[CrossRef] [PubMed]

B. W. Colston, U. S. Sathyam, L. B. DaSilva, M. J. Everett, P. Stroeve, and L. L. Otis, �??Dental OCT,�?? Opt. Express 3, 230-238 (1998), <a href="http://www.opticsexpress.org/abstract.cfm?URI=OPEX-3-6-230">http://www.opticsexpress.org/abstract.cfm?URI=OPEX-3-6-230</a>.
[CrossRef] [PubMed]

F. I. Feldchtein, V. M. Gelikonov, G. V. Gelikonov, A. M. Sergeev, N. D. Gladkova, A. V. Shakhov, N. M. Shakhova, L. B. Snopova, A. B. Terent�??eva, E. V. Zagainova, Y. P. Chumakov, and I. A. Kuznetzova, �??Endoscopic applications of optical coherence tomography,�?? Opt. Express 3, 257- 270 (1998), <a href="http://www.opticsexpress.org/abstract.cfm?URI=OPEX-3-6-257">http://www.opticsexpress.org/abstract.cfm?URI=OPEX-3-6-257</a>.
[CrossRef] [PubMed]

Gang Yao, Lihong Wang, �??Propagation of polarized light in turbid media: simulated animation sequences,�?? Opt. Express 7, 198-203 (2000), <a href="http://www.opticsexpress.org/abstract.cfm?URI=OPEX-7-5-198">http://www.opticsexpress.org/abstract.cfm?URI=OPEX-7-5-198</a>.
[CrossRef] [PubMed]

Opt. Lett.

Phys. Med. Biol.

J M Schmitt, A Knuttel, M Yadlowsky and M A Bckhause, �??Optical-coherence tomography of a dense tissue: statistics of attention of backscattering,�?? Phys. Med. Biol. 39, 1705-1720 (1993).
[CrossRef]

Gang Yao and Lihong V Wang, �??Monte Carlo simulation of an optical coherence tomography signal in homogeneous turbid media,�?? Phys. Med. Biol. 44, 2307-2320 (1999).
[CrossRef] [PubMed]

Proc. SPIE

Tuqiang Xie, Zhigang Li, Mark L. Zeidel, Yingtian Pan, �??Optical imaging diagnostics of bladder tissue with optical coherence tomography,�?? Proc. SPIE 4609, in print.

A. M. Sergeev, V. M. Gelikonov, G. V. Gelikonov, F. I. Feldchtein, K. I. Pravdenko, D. V. Shabanov, N. D. Gladkova, V. V. Pochinko, V. A. Zhegalov, G. I. Dmitriev, I. R. Vazina, G. A. Petrova, and N. K. Nikulin, �??In vivo optical coherence tomography of human skin microstructure,�?? Proc. SPIE 2328, 144-150 (1994).
[CrossRef]

Science

G. J. Tearney, M. E. Brezinski, B. E. Bouma, S. A. Boppart, C. Pitris, J. F. Southern, and J. G. Fujimoto, �??In Vivo Endoscopic Optical Biopsy with Optical Coherence Tomography,�?? Science 276, 2037-2039 (1997).
[CrossRef] [PubMed]

D. Huang, E. A. Swanson, C. P. Lin, et al., �??Optical coherence tomography,�?? Science 254, 1178-1181 (1991).
[CrossRef] [PubMed]

Skin Research and Technology

J. Welzel, �??Optical coherence tomography in dermatology: a review,�?? Skin Research and Technology 7, 1-9 (2001).
[CrossRef] [PubMed]

Other

<a href="http://www.cancernews.com/category.asp?cat=28&aid=235">http://www.cancernews.com/category.asp?cat=28&aid=235</a>, �??Diagnosis and Treatment of Bladder Cancer.�??

C. A. Puliafito, M. R. Hee, J. S. Schuman, and J. G. Fujimoto, Optical Coherence Tomography of Ocular Diseases (SLACK, Thorofare, NJ, 1996).

T. Xie, H. Xie, G. K. Fedder, M. Zeidel, and Y. Pan, �??Endoscopic Optical Coherence Tomography with a Micromachined Mirror,�?? 2nd Annual International IEEE-EMBS, Madison, Wisconsin, USA, May 2-4, 208-211 (2002).

William M. Murphy, Bruce Beckwith, George M. Farrow, Tumors of the kidney, bladder and related urinary structures, Chapter 2 (Armed Forces Institute of Pathology, Washington, 1994).

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Figures (6)

Fig. 1.
Fig. 1.

Schematic diagram of the fiber optic OCT system. BBS: broadband light source; LD: aiming laser diode; PD: photo diode; CM: fiber-optic collimator. High-speed reference mirror scanning is grating-lens delay line.

Fig. 2.
Fig. 2.

OCT images of a normal rabbit bladder (A) and rabbit bladder samples injected with saline (B), blood (C) and intralipid (D). U: urothelium, SM: submucosa, M: muscular layers.

Fig. 3.
Fig. 3.

Histologic pictures of normal, hyperplastic, dysplastic, and neoplastic urothelial cells.

Fig. 4.
Fig. 4.

Calculated results of backscattering changes as a function of nuclear morphology (e.g., size, density depicted in Fig. 3).

Fig. 5.
Fig. 5.

Comparisons of hyperplastic and neoplastic rat bladders imaged by OCT with histology. U: normal urothelium, SM: submucosa, M: muscular layer, U’: diseased urothelium.

Fig. 6.
Fig. 6.

A-scans on the normal, hyperplastic and neoplastic regions acquired from the OCT images in Fig. 5. Consecutive A-scans were averaged to reduce speckle noises.

Tables (1)

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Table 1: Histological evaluations of nuclear morphology

Equations (5)

Equations on this page are rendered with MathJax. Learn more.

Δ z = L C = ( 2 ln 2 π ) · ( λ ¯ 2 Δ λ )
Δ r = 2 λ 0 πNA = 4 λ 0 f πϕ
ρ v = 1.33 ρ s 3 2
I ˜ d ( L r ) = 2 I s I r · [ R ( L s ) C ( L s ) ]
I ˜ d ( z ) = k I 0 μ b e μ S z Δ L L C e 4 ( Δ L L c ) 2 cos k ¯ Δ L

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