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Optical Coherence Tomography as an Adjunct to Flexible Bronchoscopy in the Diagnosis of Lung Cancer: A Pilot Study FREE TO VIEW

Ross G. Michel, MD; Gary T. Kinasewitz, MD, FCCP; Kar-Ming Fung, MD, PhD; Jean I. Keddissi, MD, FCCP
Author and Funding Information

From the Division of Pulmonary/Critical Care Medicine (Drs Michel, Kinasewitz, and Keddissi), and the Department of Pathology (Dr Fung), Oklahoma City Veterans Affairs Medical Center and the University of Oklahoma Health Sciences Center, Oklahoma City, OK.

Correspondence to: Ross G. Michel, MD, Division of Pulmonary/Critical Care Medicine, University of Oklahoma Health Sciences Center, 920 Stanton L. Young Blvd, WP 1310, Oklahoma City, OK 73104-5020; e-mail: rgmichel2@gmail.com


Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).


© 2010 American College of Chest Physicians


Chest. 2010;138(4):984-988. doi:10.1378/chest.10-0753
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Published online

Lung cancer is the leading cause of cancer-related deaths in the United States and the second most common type of cancer in both men and women. Optical coherence tomography (OCT) scanning can generate high-resolution cross-sectional images of complex, living tissues in real time. The objectives of this study were to determine the feasibility of using OCT imaging during flexible bronchoscopy and to preliminarily assess the ability of OCT imaging to distinguish an endobronchial malignancy from normal endobronchial mucosa. A Niris OCT probe was introduced into the airways of patients with an endobronchial mass during flexible bronchoscopy. An investigational device exemption was approved by the US Food and Drug Administration for the use of the OCT system in this study. Conventional OCT scans of an endobronchial mass and a control area of normal bronchial mucosa were performed to generate real-time images in each patient. Following OCT imaging, the same sites were biopsied for pathologic correlation. We report on the first five patients enrolled. A total of 60 OCT images with corresponding endobronchial biopsy specimens were obtained. The average procedure time was 29 min. The histopathologic diagnoses of the endobronchial masses included two small cell carcinomas, one squamous cell carcinoma, one adenocarcinoma, and one endobronchial schwannoma. Microstructures of normal bronchial mucosa, including epithelium and lamina propria, were identified with OCT imaging. OCT scan features of malignancy included loss of normal, identifiable microstructures and subepithelial “optical fracture” of tissues. All patients tolerated the endobronchial imaging well without complications. Preliminary results suggest that OCT imaging is a technically feasible adjunct to flexible bronchoscopy in the diagnosis of lung cancer. This is the first reported use of OCT to generate images of endobronchial neoplasms during flexible bronchoscopy in the United States. This technology may in the future provide a noninvasive “optical biopsy,” which could potentially guide the bronchoscopist to areas for biopsy or even obviate the need for conventional lung biopsies.

Trial Registration: clinicaltrials.gov; Identifier: NCT01039311

Figures in this Article

Lung cancer is the leading cause of cancer-related deaths in the United States and the second most common type of cancer in both men and women.1 More than 85% of lung tumors originate in the bronchial epithelium with multistage cellular changes advancing over a relatively long period of time before the first presentation of invasive cancer.2 Endobronchial samples are obtained when suspected mucosal abnormalities or visible endobronchial masses are identified, most commonly by chest radiograph, CT scan, and PET scan. Sometimes, it is difficult to identify subtle mucosal changes that may be a precursor or a harbor of a malignant process. Several endobronchial techniques, such as autofluorescence bronchoscopy and endobronchial ultrasound, have been investigated to better identify areas in need of biopsy. Autofluorescence bronchoscopy enhances identification of in situ mucosal abnormalities, but this method is limited by inadequate image resolution and tissue depth penetration.3 High-frequency endobronchial ultrasonography achieves deeper penetration of airway tissue but offers insufficient spatial resolution for clear demarcation of the microstructural profile and morphologic changes.4,5

Optical coherence tomography (OCT) is a rapidly evolving imaging technology capable of generating real-time, high-resolution, cross-sectional images of complex, living tissues.6 OCT scanning is similar to ultrasound in that it measures phase and intensity differences of reflected or backscattered wave signals from tissues. Unlike ultrasound, which uses sound waves, OCT imaging analyzes interference patterns from low-power, near-infrared light to generate topographic images. Compared with ultrasound, OCT systems used in prior clinical studies demonstrate greater sensitivity and much higher resolution (approximately 10-20 μm with a depth of penetration at 2 mm) of tissues in the lower respiratory tract.7

The objectives of this pilot study were to determine the feasibility of conventional OCT imaging during flexible bronchoscopy and to preliminarily assess its ability to distinguish an endobronchial neoplasm from normal endobronchial mucosa. To our knowledge, this is the first reported use of OCT imaging as an adjunct to diagnostic flexible bronchoscopy in the United States.

Study Population

Subjects were enrolled at the University of Oklahoma Health Sciences Center from June 2009 to December 2009. Study inclusion criteria included subjects 18 to 99 years of age with the presence of an endobronchial mass seen on chest imaging and the need for flexible bronchoscopy with endobronchial biopsies. An arterial blood gas was obtained preprocedurally on all patients. Exclusion criteria included a Paco2 > 47 mm Hg, long-term oxygen therapy, unwillingness to undergo flexible bronchoscopy, coagulopathy (defined as a platelet count < 100,000/μL, an international normalized ratio > 1.4, or a known clinical bleeding disorder), or current therapy with an anticoagulant (including warfarin and clopidogrel). Additional exclusion criteria included renal dysfunction (defined as a creatinine > 2 mg/dL), life-threatening arrhythmias, history of myocardial infarction or cerebrovascular accident within the preceding 6 months, facial abnormalities preventing safe introduction of the bronchoscope, uncontrolled hypertension, active liver disease, pregnancy, breastfeeding, or inability to give informed consent. The study was approved by the institutional review board at the University of Oklahoma Health Sciences Center, and informed consent was obtained for all subjects.

OCT Scanning

Conventional OCT scanning was performed using a commercially available system (Niris Imaging System; Imalux Corp; Cleveland, OH). This system is cleared by the US Food and Drug Administration (FDA) for use as an imaging tool in the evaluation of human tissue microstructure (FDA 510[k] Number K042894). An investigational device exemption for the use of this OCT system during flexible bronchoscopy for lung masses was approved by the FDA (IDE G080136/S002).

The Niris is a compact, time-domain OCT system composed of an imaging console and a flexible, forward-facing, magnetically actuating probe. This system uses near-infrared, backscattered light to generate two-dimensional images with a depth resolution of 10 to 20 μm and a lateral resolution of 20 to 25 μm. Spatial information is determined from the time delay of reflected signals according to the formula z = ΔT × v, where z is the distance the signal travels, T is the time, and v is the light wave propagation velocity (Fig 1). The lateral scanning range is 2.0 mm with an image depth of 2.2 mm (Fig 2). These imaging capabilities allow penetration through the upper layers of exposed tissues on airway surfaces where many airway neoplasms may present and are equivalent to the tissue sampling depth of conventional endobronchial forceps.8

Figure Jump LinkFigure 1. Optical coherence tomography (OCT) principles of operation. Spatial information is determined from the time delay of reflected light signals according to the formula z = ΔT × v, where z is the distance the light signal travels, T is time, and v is the light wave propagation velocity. (Reprinted with permission from Imalux.)Grahic Jump Location
Figure Jump LinkFigure 2. Light signal intensity diminishes at increased tissue depth. Lateral scanning range is 2 mm. For reference, the white horizontal scale bar is 1 mm. (Reprinted with permission from Imalux.)Grahic Jump Location
Procedure

All procedures were conducted in a bronchoscopy suite at the University of Oklahoma Health Sciences Center. After informed consent was obtained, patients were sedated using midazolam and meperidine. The upper airways were anesthetized with topical lidocaine. Using transnasal flexible bronchoscopy, a complete airway examination was performed. Upon identification of an endobronchial mass, a saline wash of the mass was obtained for cytology. The bronchoscope was then removed, and a second flexible bronchoscope preloaded with the OCT probe (Fig 3 was introduced transnasally into the lower airways. Because the reusable OCT probe (outer diameter of 2.7 mm) does not fit through the working channel of a conventional flexible bronchoscope, the probe tip was attached to the exterior of the scope using a size 28F Rusch (Teleflex Inc; Limerick, PA) polyvinyl chloride nasal airway. The flexible bronchoscope was then used to guide the OCT probe tip to the endobronchial mass under direct visualization.

Figure Jump LinkFigure 3. Flexible bronchoscope with the OCT imaging probe attached to the scope exterior using a size 28F Rusch polyvinyl chloride nasal airway. See Figure 1 legend for expansion of the abbreviation.Grahic Jump Location

Once mucosal contact was made with the OCT probe tip, an imaging console was used to generate and save six real-time OCT images of the mass. The bronchoscope and attached OCT probe were then moved to an area of normal-appearing bronchial mucosa, and six additional OCT images of the normal-appearing mucosa were generated. Upon completion of the imaging, six corresponding biopsies of the endobronchial mass and six control biopsies of the imaged normal-appearing area were performed. Brushings of the endobronchial masses were then done and sent for analysis.

Patients were monitored for any immediate postprocedure complications. A Steris sterilization system was used to sterilize both the OCT probe and the bronchoscopes. All OCT images from this study were reviewed by the investigators. Collected data included subject’s demographics, smoking history, comorbid pulmonary conditions, tumor size, biopsy site locations, and total procedure time.

Histologic Analysis

Biopsy specimens were processed by the Department of Pathology of the University of Oklahoma Health Sciences Center. Formalin-fixed, paraffin-embedded sections were cut at a thickness of 5 μm for both normal control and tumor biopsy samples. The tumor biopsy specimens were examined and reported on in routine fashion. These samples were further examined with their corresponding normal control samples by an experienced pulmonary pathologist (K. M. F.). Immunohistochemistry for S100 was performed with a rabbit polyclonal antibody using an automated immunohistochemistry system (Ventana BenchMark ULTRA; Ventana Medical Systems, Inc; Tuscon, AZ) with diaminobenzidine as chromogen and lightly counterstained by hematoxylin. Immunohistochemistry was performed with adequate positive and negative controls.

Eight patients with endobronchial masses on chest imaging were screened during the study period. Five patients were found to be eligible and participated in the study. A single endobronchial mass was identified in each subject during flexible bronchoscopy. A total of 60 endobronchial OCT images and corresponding biopsy specimens were obtained from the five subjects: 30 from an endobronchial mass and 30 from areas of normal-appearing bronchial mucosa. A library of OCT images with their corresponding histology was constructed (e-Figs 1-3).

Clinical characteristics of all five patients are summarized in Table 1. The histopathologic diagnoses of the endobronchial masses included two small cell carcinomas, one squamous cell carcinoma, one adenocarcinoma, and one endobronchial schwannoma. These tumors all displayed classic histopathologic features of their respective types. There was no histopathologic evidence of neoplastic or other abnormal changes in the control biopsies from areas of normal-appearing bronchial mucosa. All four patients with carcinomas were smokers with a history of COPD. The single benign tumor was an endobronchial schwannoma that was found in the left lower lobe bronchus of the youngest, and only nonsmoking, subject. The average procedure length was 29 min. All subjects tolerated the procedure well without any immediate complications.

Table Graphic Jump Location
Table 1 —Clinical Characteristics of the Five Patients

B = black; F = female; LUL = left upper lobe; M = male; RUL = right upper lobe; W = white.

OCT images showed differences between neoplasms and normal bronchial mucosa. Images from normal areas displayed defined layers of epithelium, basement membrane, and lamina propria (Fig 4A). Subepithelial areas in normal tissues had a variety of polymorphic light and dark areas, which were likely produced by microscopic structures, including seromucinous glands, fibroconnective tissues, and cartilage. Malignant tumors in the first four patients had loss of normal, identifiable microstructures (Fig 4B). The thickness of surface epithelium in OCT images ranged from 20 to 50 μm and corresponded to the thickness of the lining epithelium in the histologic sections. OCT images from neoplastic lesions displayed irregular, ragged, dark lines between two light areas that had the appearance of a fracture in the subepithelium. We termed these dark lines “optical fractures” (Fig 5) and postulate that they represent an OCT scan feature of neoplasm.

Figure Jump LinkFigure 4. OCT images from normal bronchial mucosa in patient 1, showing normal layers of epithelium (white arrow) and lamina propria (black arrow) (A). OCT image from the tumor area in the same patient, showing loss of identifiable microstructures (B). The scale bars are 1 mm. See Figure 1 legend for expansion of the abbreviation.Grahic Jump Location
Figure Jump LinkFigure 5. “Optical fracture” in an OCT image of small cell carcinoma from patient 2. This ragged, irregular, dark line between two light areas in the subepithelium was seen in OCT images of neoplastic lesions. The scale bar is 1 mm. See Figure 1 legend for expansion of the abbreviation.Grahic Jump Location

The objective of this pilot study was to determine if it is feasible to use conventional OCT imaging as an adjunct to flexible bronchoscopy in the evaluation of patients with suspected lung cancer. Although the use of OCT imaging during rigid bronchoscopy for tracheal lesions has been reported,8,9 this is the first reported use of OCT imaging in the United States during flexible bronchoscopy for bronchial lesions. Our data show that OCT imaging can be used during flexible bronchoscopy to provide images of endobronchial tumors in large airways with a relatively short total procedure time. Because none of our patients experienced any complications during or following the procedure, we believe that the use of OCT imaging likely adds minimal risk to conventional flexible bronchoscopy in selected patients.

The earliest and most extensive clinical use of OCT scanning has been in ophthalmology for retinal imaging in patients with macular degeneration.10,11 This technology has been used by otolaryngologists and has been shown to be a feasible adjunct to awake transnasal laryngoscopy.12 OCT imaging can clearly identify basement membrane violation and transition zones at cancer margins in patients with laryngeal cancer.13 Gastroenterologists have found that in vivo OCT scanning correctly detected disease features of ulcerative colitis in endoscopically affected colon segments with high sensitivity.14 OCT imaging has been studied for use by dermatologists for monitoring cutaneous inflammation and hyperkeratotic conditions.15 In the field of cardiology, OCT imaging is being compared with intravascular ultrasound for characterization of coronary artery disease.16 Anatomic OCT imaging, a variant of conventional OCT imaging, has been shown to be helpful for real-time large-diameter airway measurements.17,18

Although using OCT imaging during flexible bronchoscopy appears to be feasible, it remains technically difficult. The Niris is the only OCT imaging system with a flexible probe that is approved by the FDA for use in the United Sates. Currently, no commercially available flexible bronchoscope can accommodate the Niris probe, because the rigid probe tip will not pass through the working channel. Using the OCT probe on the exterior of the bronchoscope resulted in limited scope flexion, causing a somewhat difficult passage of the bronchoscope through the upper and lower airways. FDA clearance of an OCT probe that fits down the working channel of a standard flexible bronchoscope is needed for practical use of this technology in the United States.

Interpretation of the OCT images in the lung is an evolving field of study. OCT scanning is capable of generating images of epithelium, mucosa, cartilage, and subepithelial structures in animal and human trachea6,19,20 and has been shown to identify morphologic changes associated with inflammatory infiltrates, squamous metaplasia, and tumor presence in resected lung specimens.21,22 In a recent study by Lam et al23 using radial scanning endobronchial OCT imaging, bronchial epithelial thickness of invasive lung carcinoma was significantly greater than that of carcinoma in situ. Investigators from that study used a radially scanning OCT probe, which generates different views of bronchial mucosa than the forward-scanning probe used in our study. In our study, no areas of carcinoma in situ were identified and there was no significant difference in epithelial thickness from benign mucosa and the malignant tumors that had an identifiable epithelial layer. Although increased epithelial thickness can be an important feature of lung malignancies, we believe that other OCT architectural features may be equally important in distinguishing lung malignancies from normal bronchial mucosa.

A goal of our pilot study was to generate a library of OCT images with corresponding pathology findings to preliminarily determine if OCT scanning can distinguish malignancies from normal bronchial mucosa. We believe that we may have identified some OCT characteristics of malignancy, including the loss of normal, identifiable epithelial and subepithelial microstructures and possibly subepithelial optical fracture. The mechanism of optical fracture is uncertain. Because infiltrative carcinomatous tissue tends to be more fibrotic than the surrounding normal tissue, we postulate that optical fracture is due to the interference pattern of backscattered light from an interface between two distinct tissue densities that are found in tumors. To further characterize OCT features of malignancy, we intend to continue our current recruitment. Once we identify these features, we plan to validate our findings prospectively in a separate, larger group of patients.

Limitations of this pilot study include a small sample size and an inherent inability to precisely biopsy the exact sites from which the OCT images were obtained. In addition to our ongoing trial, further studies are needed to determine the sensitivity and specificity of this evolving technology in identifying lung cancer during routine diagnostic flexible bronchoscopy.

OCT imaging could become a powerful tool in diagnostic pulmonary medicine, not only in the early recognition of lung cancer but also in the evaluation and monitoring of microstructures in the lower respiratory tract that are affected by other inflammatory or invasive disease processes. It could potentially be used in conjunction with endobronchial ultrasound, autofluorescence bronchoscopy, or narrow band imaging to guide the location of biopsies. Using a combination of multiple imaging modalities can provide increased diagnostic yield during bronchoscopy. This technology may provide a noninvasive optical biopsy, which could potentially obviate the need for conventional biopsies, particularly in patients with high risks for biopsy-related complications, such as bleeding.

Conventional OCT imaging during flexible bronchoscopy appears to be feasible in patients with endobronchial tumors. This is the first reported use of this technology during flexible bronchoscopy in the United States. OCT scan features of malignancy may include loss of normal landmarks in the bronchial epithelium and lamina propria. Further studies are needed to determine the diagnostic yield of OCT imaging in the evaluation of endobronchial lesions.

Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Other contributors: We thank Randall G. Michel, MD; Julie A. Stoner, PhD; and Paul V. Carlile, MD for their intellectual contributions to this study.

Additional Information: The e-Figures can be found in the Online Supplement at http://chestjournal.chestpubs.org/content/138/4/984/suppl/DC1.

FDA

US Food and Drug Administration

OCT

optical coherence tomography

Spira A, Ettinger DS. Multidisciplinary management of lung cancer. N Engl J Med. 2004;3504:379-392. [CrossRef] [PubMed]
 
Rom WN, Hay JG, Lee TC, Jiang Y, Tchou-Wong KM. Molecular and genetic aspects of lung cancer. Am J Respir Crit Care Med. 2000;1614 pt 1:1355-1367. [PubMed]
 
Hirsch FR, Prindiville SA, Miller YE, et al. Fluorescence versus white-light bronchoscopy for detection of preneoplastic lesions: a randomized study. J Natl Cancer Inst. 2001;9318:1385-1391. [CrossRef] [PubMed]
 
Shirakawa T, Imamura F, Hamamoto J, et al. Usefulness of endobronchial ultrasonography for transbronchial lung biopsies of peripheral lung lesions. Respiration. 2004;713:260-268. [CrossRef] [PubMed]
 
Kurimoto N, Murayama M, Yoshioka S, Nishisaka T. Analysis of the internal structure of peripheral pulmonary lesions using endobronchial ultrasonography. Chest. 2002;1226:1887-1894. [CrossRef] [PubMed]
 
Han S, El-Abbadi NH, Hanna N, et al. Evaluation of tracheal imaging by optical coherence tomography. Respiration. 2005;725:537-541. [CrossRef] [PubMed]
 
Hanna N, Saltzman D, Mukai D, et al. Two-dimensional and 3-dimensional optical coherence tomographic imaging of the airway, lung, and pleura. J Thorac Cardiovasc Surg. 2005;1293:615-622. [CrossRef] [PubMed]
 
Colt H, Murgu SD, Ahn YC, Brenner M. Multimodality bronchoscopic [corrected] imaging of tracheopathica osteochondroplastica. J Biomed Opt. 2009;143:034035. [CrossRef] [PubMed]
 
Colt HG, Murgu SD, Jung B, Ahn YC, Brenner M. Multimodality bronchoscopic imaging of recurrent respiratory papillomatosis. Laryngoscope. 2010;1203:468-472. [CrossRef] [PubMed]
 
Voo I, Mavrofrides EC, Puliafito CA. Clinical applications of optical coherence tomography for the diagnosis and management of macular diseases. Ophthalmol Clin North Am. 2004;171:21-31. [CrossRef] [PubMed]
 
Puliafito CA, Hee MR, Lin CP, et al. Imaging of macular diseases with optical coherence tomography. Ophthalmology. 1995;1022:217-229. [PubMed]
 
Sepehr A, Armstrong WB, Guo S, et al. Optical coherence tomography of the larynx in the awake patient. Otolaryngol Head Neck Surg. 2008;1384:425-429. [CrossRef] [PubMed]
 
Armstrong WB, Ridgway JM, Vokes DE, et al. Optical coherence tomography of laryngeal cancer. Laryngoscope. 2006;1167:1107-1113. [CrossRef] [PubMed]
 
Familiari L, Strangio G, Consolo P, et al. Optical coherence tomography evaluation of ulcerative colitis: the patterns and the comparison with histology. Am J Gastroenterol. 2006;10112:2833-2840. [CrossRef] [PubMed]
 
Gambichler T, Moussa G, Sand M, Sand D, Altmeyer P, Hoffmann K. Applications of optical coherence tomography in dermatology. J Dermatol Sci. 2005;402:85-94. [CrossRef] [PubMed]
 
Pinto TL, Waksman R. Clinical applications of optical coherence tomography. J Interv Cardiol. 2006;196:566-573. [CrossRef] [PubMed]
 
Armstrong JJ, Leigh MS, Sampson DD, Walsh JH, Hillman DR, Eastwood PR. Quantitative upper airway imaging with anatomic optical coherence tomography. Am J Respir Crit Care Med. 2006;1732:226-233. [CrossRef] [PubMed]
 
Williamson JP, McLaughlin RA, Phillips MJ, et al. Using optical coherence tomography to improve diagnostic and therapeutic bronchoscopy. Chest. 2009;1361:272-276. [CrossRef] [PubMed]
 
Mahmood U, Hanna NM, Han S, et al. Evaluation of rabbit tracheal inflammation using optical coherence tomography. Chest. 2006;1303:863-868. [CrossRef] [PubMed]
 
Jung W, Zhang J, Mina-Araghi R, et al. Feasibility study of normal and septic tracheal imaging using optical coherence tomography. Lasers Surg Med. 2004;352:121-127. [CrossRef] [PubMed]
 
Whiteman SC, Yang Y, Gey van Pittius D, Stephens M, Parmer J, Spiteri MA. Optical coherence tomography: real-time imaging of bronchial airways microstructure and detection of inflammatory/neoplastic morphologic changes. Clin Cancer Res. 2006;123 pt 1:813-818. [CrossRef] [PubMed]
 
Tsuboi M, Hayashi A, Ikeda N, et al. Optical coherence tomography in the diagnosis of bronchial lesions. Lung Cancer. 2005;493:387-394. [CrossRef] [PubMed]
 
Lam S, Standish B, Baldwin C, et al. In vivooptical coherence tomography imaging of preinvasive bronchial lesions. Clin Cancer Res. 2008;147:2006-2011. [CrossRef] [PubMed]
 

Figures

Figure Jump LinkFigure 1. Optical coherence tomography (OCT) principles of operation. Spatial information is determined from the time delay of reflected light signals according to the formula z = ΔT × v, where z is the distance the light signal travels, T is time, and v is the light wave propagation velocity. (Reprinted with permission from Imalux.)Grahic Jump Location
Figure Jump LinkFigure 2. Light signal intensity diminishes at increased tissue depth. Lateral scanning range is 2 mm. For reference, the white horizontal scale bar is 1 mm. (Reprinted with permission from Imalux.)Grahic Jump Location
Figure Jump LinkFigure 3. Flexible bronchoscope with the OCT imaging probe attached to the scope exterior using a size 28F Rusch polyvinyl chloride nasal airway. See Figure 1 legend for expansion of the abbreviation.Grahic Jump Location
Figure Jump LinkFigure 4. OCT images from normal bronchial mucosa in patient 1, showing normal layers of epithelium (white arrow) and lamina propria (black arrow) (A). OCT image from the tumor area in the same patient, showing loss of identifiable microstructures (B). The scale bars are 1 mm. See Figure 1 legend for expansion of the abbreviation.Grahic Jump Location
Figure Jump LinkFigure 5. “Optical fracture” in an OCT image of small cell carcinoma from patient 2. This ragged, irregular, dark line between two light areas in the subepithelium was seen in OCT images of neoplastic lesions. The scale bar is 1 mm. See Figure 1 legend for expansion of the abbreviation.Grahic Jump Location

Tables

Table Graphic Jump Location
Table 1 —Clinical Characteristics of the Five Patients

B = black; F = female; LUL = left upper lobe; M = male; RUL = right upper lobe; W = white.

References

Spira A, Ettinger DS. Multidisciplinary management of lung cancer. N Engl J Med. 2004;3504:379-392. [CrossRef] [PubMed]
 
Rom WN, Hay JG, Lee TC, Jiang Y, Tchou-Wong KM. Molecular and genetic aspects of lung cancer. Am J Respir Crit Care Med. 2000;1614 pt 1:1355-1367. [PubMed]
 
Hirsch FR, Prindiville SA, Miller YE, et al. Fluorescence versus white-light bronchoscopy for detection of preneoplastic lesions: a randomized study. J Natl Cancer Inst. 2001;9318:1385-1391. [CrossRef] [PubMed]
 
Shirakawa T, Imamura F, Hamamoto J, et al. Usefulness of endobronchial ultrasonography for transbronchial lung biopsies of peripheral lung lesions. Respiration. 2004;713:260-268. [CrossRef] [PubMed]
 
Kurimoto N, Murayama M, Yoshioka S, Nishisaka T. Analysis of the internal structure of peripheral pulmonary lesions using endobronchial ultrasonography. Chest. 2002;1226:1887-1894. [CrossRef] [PubMed]
 
Han S, El-Abbadi NH, Hanna N, et al. Evaluation of tracheal imaging by optical coherence tomography. Respiration. 2005;725:537-541. [CrossRef] [PubMed]
 
Hanna N, Saltzman D, Mukai D, et al. Two-dimensional and 3-dimensional optical coherence tomographic imaging of the airway, lung, and pleura. J Thorac Cardiovasc Surg. 2005;1293:615-622. [CrossRef] [PubMed]
 
Colt H, Murgu SD, Ahn YC, Brenner M. Multimodality bronchoscopic [corrected] imaging of tracheopathica osteochondroplastica. J Biomed Opt. 2009;143:034035. [CrossRef] [PubMed]
 
Colt HG, Murgu SD, Jung B, Ahn YC, Brenner M. Multimodality bronchoscopic imaging of recurrent respiratory papillomatosis. Laryngoscope. 2010;1203:468-472. [CrossRef] [PubMed]
 
Voo I, Mavrofrides EC, Puliafito CA. Clinical applications of optical coherence tomography for the diagnosis and management of macular diseases. Ophthalmol Clin North Am. 2004;171:21-31. [CrossRef] [PubMed]
 
Puliafito CA, Hee MR, Lin CP, et al. Imaging of macular diseases with optical coherence tomography. Ophthalmology. 1995;1022:217-229. [PubMed]
 
Sepehr A, Armstrong WB, Guo S, et al. Optical coherence tomography of the larynx in the awake patient. Otolaryngol Head Neck Surg. 2008;1384:425-429. [CrossRef] [PubMed]
 
Armstrong WB, Ridgway JM, Vokes DE, et al. Optical coherence tomography of laryngeal cancer. Laryngoscope. 2006;1167:1107-1113. [CrossRef] [PubMed]
 
Familiari L, Strangio G, Consolo P, et al. Optical coherence tomography evaluation of ulcerative colitis: the patterns and the comparison with histology. Am J Gastroenterol. 2006;10112:2833-2840. [CrossRef] [PubMed]
 
Gambichler T, Moussa G, Sand M, Sand D, Altmeyer P, Hoffmann K. Applications of optical coherence tomography in dermatology. J Dermatol Sci. 2005;402:85-94. [CrossRef] [PubMed]
 
Pinto TL, Waksman R. Clinical applications of optical coherence tomography. J Interv Cardiol. 2006;196:566-573. [CrossRef] [PubMed]
 
Armstrong JJ, Leigh MS, Sampson DD, Walsh JH, Hillman DR, Eastwood PR. Quantitative upper airway imaging with anatomic optical coherence tomography. Am J Respir Crit Care Med. 2006;1732:226-233. [CrossRef] [PubMed]
 
Williamson JP, McLaughlin RA, Phillips MJ, et al. Using optical coherence tomography to improve diagnostic and therapeutic bronchoscopy. Chest. 2009;1361:272-276. [CrossRef] [PubMed]
 
Mahmood U, Hanna NM, Han S, et al. Evaluation of rabbit tracheal inflammation using optical coherence tomography. Chest. 2006;1303:863-868. [CrossRef] [PubMed]
 
Jung W, Zhang J, Mina-Araghi R, et al. Feasibility study of normal and septic tracheal imaging using optical coherence tomography. Lasers Surg Med. 2004;352:121-127. [CrossRef] [PubMed]
 
Whiteman SC, Yang Y, Gey van Pittius D, Stephens M, Parmer J, Spiteri MA. Optical coherence tomography: real-time imaging of bronchial airways microstructure and detection of inflammatory/neoplastic morphologic changes. Clin Cancer Res. 2006;123 pt 1:813-818. [CrossRef] [PubMed]
 
Tsuboi M, Hayashi A, Ikeda N, et al. Optical coherence tomography in the diagnosis of bronchial lesions. Lung Cancer. 2005;493:387-394. [CrossRef] [PubMed]
 
Lam S, Standish B, Baldwin C, et al. In vivooptical coherence tomography imaging of preinvasive bronchial lesions. Clin Cancer Res. 2008;147:2006-2011. [CrossRef] [PubMed]
 
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