Fiber-optic polarization diversity detection for rotary probe optical coherence tomography.

We report a polarization diversity detection scheme for optical coherence tomography with a new, custom, miniaturized fiber coupler with single mode (SM) fiber inputs and polarization maintaining (PM) fiber outputs. The SM fiber inputs obviate matching the optical lengths of the X and Y OCT polarization channels prior to interference and the PM fiber outputs ensure defined X and Y axes after interference. Advantages for this scheme include easier alignment, lower cost, and easier miniaturization compared to designs with free-space bulk optical components. We demonstrate the utility of the detection system to mitigate the effects of rapidly changing polarization states when imaging with rotating fiber optic probes in Intralipid suspension and during in vivo imaging of human airways.

Has fluorescence spectroscopy come of age? A case series of oral precancers and cancers using white light, fluorescent light at 405 nm, and reflected light at 545 nm using the Trimira Identafi 3000.

BACKGROUND: Optical spectroscopy devices are being developed and tested for the screening and diagnosis of cancer and precancer in multiple organ sites. The studies reported here used a prototype of a device that uses white light, green-amber light at 545 nm, and violet light at 405 nm. Given that oral neoplasia is rare, the need for a device that increases the sensitivity of comprehensive white light oral screening is evident. Such a device, in the hands of dentists, family practitioners, otorhinolaryngologists, general surgeons, obstetrician gynecologists, and internists, could greatly increase the number of patients who have lesions detected in the precancerous phase. OBJECTIVES: The objective of this study was to present a case series of oral precancers and cancers that have been photographed during larger ongoing clinical trials. METHODS: Over 300 patients were measured at 2 clinical sites that are comprehensive cancer centers and a faculty practice associated with a major dental school. Each site is conducting independent research on the sensitivity and specificity of several optical technologies for the diagnosis of oral neoplasia. The cases presented in this case series were taken from the larger database of images from the clinical trials using the aforementioned device. Optical spectroscopy was performed and biopsies obtained from all sites measured, representing abnormal and normal areas on comprehensive white light examination and after use of the fluorescence and reflectance spectroscopy device. The gold standard of test accuracy was the histologic report of biopsies read by the study histopathologists at each of the 3 study sites. RESULTS: Comprehensive white light examination showed some lesions; however, the addition of a fluorescence image and a selected reflectance wavelength was helpful in identifying other characteristics of the lesions. The addition of the violet light-induced fluorescence excited at 405 nm provided an additional view of both the stromal neovasculature of the lesions and the stromal changes associated with lesion growth that were biologically indicative of stromal breakdown. The addition of 545 nm green-amber light reflectance increased the view of the keratinized image and allowed the abnormal surface vasculature to be more prominent. CONCLUSIONS: Optical spectroscopy is a promising technology for the diagnosis of oral neoplasia. The conclusion of several ongoing clinical trials and an eventual randomized Phase III clinical trial will provide definitive findings that sensitivity is or is not increased over comprehensive white light examination.

Accuracy of optical spectroscopy for the detection of cervical intraepithelial neoplasia: Testing a device as an adjunct to colposcopy.

Testing emerging technologies involves the evaluation of biologic plausibility, technical efficacy, clinical effectiveness, patient satisfaction, and cost-effectiveness. The objective of this study was to select an effective classification algorithm for optical spectroscopy as an adjunct to colposcopy and obtain preliminary estimates of its accuracy for the detection of CIN 2 or worse. We recruited 1,000 patients from screening and prevention clinics and 850 patients from colposcopy clinics at two comprehensive cancer centers and a community hospital. Optical spectroscopy was performed, and 4,864 biopsies were obtained from the sites measured, including abnormal and normal colposcopic areas. The gold standard was the histologic report of biopsies, read 2 to 3 times by histopathologists blinded to the cytologic, histopathologic, and spectroscopic results. We calculated sensitivities, specificities, receiver operating characteristic (ROC) curves, and areas under the ROC curves. We identified a cutpoint for an algorithm based on optical spectroscopy that yielded an estimated sensitivity of 1.00 [95% confidence interval (CI) = 0.92-1.00] and an estimated specificity of 0.71 [95% CI = 0.62-0.79] in a combined screening and diagnostic population. The positive and negative predictive values were 0.58 and 1.00, respectively. The area under the ROC curve was 0.85 (95% CI = 0.81-0.89). The per-patient and per-site performance were similar in the diagnostic and poorer in the screening settings. Like colposcopy, the device performs best in a diagnostic population. Alternative statistical approaches demonstrate that the analysis is robust and that spectroscopy works as well as or slightly better than colposcopy for the detection of CIN 2 to cancer.

Confocal fluorescence microendoscopy of bronchial epithelium.

Confocal microendoscopy permits the acquisition of high-resolution real-time confocal images of bronchial mucosa via the instrument channel of an endoscope. We report here on the construction and validation of a confocal fluorescence microendoscope and its use to acquire images of bronchial epithelium in vivo. Our objective is to develop an imaging method that can distinguish preneoplastic lesions from normal epithelium to enable us to study the natural history of these lesions and the efficacy of chemopreventive agents without biopsy removal of the lesion that can introduce a spontaneous regression bias. The instrument employs a laser-scanning engine and bronchoscope-compatible confocal probe consisting of a fiber-optic image guide and a graded-index objective lens. We assessed the potential of topical application of physiological pH cresyl violet (CV) as a fluorescence contrast-enhancing agent for the visualization of tissue morphology. Images acquired ex vivo with the confocal microendoscope were first compared with a bench-top confocal fluorescence microscope and conventional histology. Confocal images from five sites topically stained with CV were then acquired in vivo from high-risk smokers and compared to hematoxylin and eosin stained sections of biopsies taken from the same site. Sufficient contrast in the confocal imagery was obtained to identify cells in the bronchial epithelium. However, further improvements in the miniature objective lens are required to provide sufficient axial resolution for accurate classification of preneoplastic lesions.