Clinical optical coherence tomography in head and neck oncology

Critical review

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Licensee OA Publishing London 2013. Creative Commons Attribution Licence (CC-BY)

F : Betz CS, Volgger V, Silverman SM, Rubinstein M, Kraft M, Arens C, Wong BJF. Clinical optical coherence tomography in head and neck oncology: overview and outlook. Head Neck Oncol. 2013 Mar 06;5(3):35.

Clinical optical coherence tomography in head and neck oncology: overview and outlook

CS Betz1*, V Volgger1, SM Silverman2, M Rubinstein3, M Kraft4, C Arens5, BJF Wong3

AbstractObjectiveOptical coherence tomography is a high-resolution and minimally inva-sive optical imaging method, which provides in vivo cross-sectional images of living tissue in real-time. Our intention is to present a contem-porary and comprehensive review on the role of optical coherence tomog-raphy in head and neck oncology.

Recent fi ndings Promising results have been published in small, single-centre studies applying optical coherence tomography in clin-ical settings for the diagnostic workup of superficial pathologies of the upper aerodigestive tract, showing that it can be a helpful adjunct to standard white light endoscopy. Using optical coherence tomography, microanatom-ical structures of healthy and diseased mucosa can easily be identified, allowing for a differentiation between benign, premalignant and early malig-nant lesions with high sensitivity and specificity. Also, it may be helpful in the evaluation of neoplastic thyroid disease and in the preclinical diag-nosis of (chemo) radiation therapy-related mucositis.

SummaryOptical coherence tomography enables in vivo, real-time visualisa-tion and diagnosis of healthy and diseased mucosa of the upper aerodi-gestive tract, and might be useful for other indications. Larger, multi-centre trials are needed to validate the current findings and further define the method’s clinical role. With the expected technical advances in acquisition speed and resolution, as well as a wider public acceptance of the method, optical coherence tomography seems to have a bright future in head and neck oncology.

IntroductionEven though white light endoscopy followed by invasive tissue biopsy is still the gold standard for evalu-ating upper aerodigestive tract (UADT) lesions, novel optical imaging methods such as magnification, digital imaging, optical coherence tomography (OCT), confocal micros-copy, narrow band imaging and fluorescence imaging have recently been subjected to thorough evalu-ations with respect to improving the sensitivity and specificity of standard white light endoscopy and to decrease the number of unneces-sary biopsies1,2. Optical imaging tech-niques thus seem to quickly emerge as invaluable tools during cancer diagnosis and treatment because of their ability to non-invasively provide information about the tissue surface and subsurface structures in real-time at the point of care. This article is aimed at reviewing early clinical applications of OCT as one such optical imaging technology.

OCT has found its way into routine clinical use in ophthalmology, and vascular surgery and has been

recently used in clinical studies in the head and neck region. It has a distinc-tive capability to obtain high-resolu-tion images of tissue microstructures that resemble typical histology cross-sections in real time3. At the same time, OCT is non-invasive, easily performed, safe and harmless. These characteristics may help otolaryn-gologists in a whole range of appli-cations, for example for guidance of biopsy and surgery and for post-treatment surveillance.

Technical background of OCT OCT is an optical imaging method using near infrared light to provide high-resolution and cross-sectional images of living tissue. It is often compared with ultrasound as they both rely on reflection (light for OCT, sound for ultrasound) to create an image. Sound waves travel relatively slower (approximately 1500 m/s) compared with light waves (3 × 108

m/s), thus leading to a much higher resolution in OCT imaging compared with that in ultrasound.

Figure 1 illustrates a comparison between OCT and other imaging methods used in the UADT with respect to penetration depth of tissue interrogation versus resolu-tion. As illustrated, OCT has excellent in-depth resolution when compared with conventional imaging methods. Its resolution is about 10 times that of high frequency ultrasound and 100 times that of standard ultrasound, and its penetration depth is conveni-ently higher compared with confocal microscopy.

Fundamental, method-specific limi-tations of OCT imaging are the pene-tration depth and the spatial resolu-tion. Human tissue contains many components that naturally reflect near

* Corresponding authorEmail: [email protected] Department of Otorhinolaryngology, Head

and Neck Surgery, Klinikum der Universität München, Munich, Germany

2 University of Michigan, Ann Arbor, Michigan, USA

3 Department of Otolaryngology, Head and Neck Surgery, University of California–Irvine Medical Centre, Irvine, California, USA

4 Department of Otorhinolaryngology, Kanton-sspital Baselland, Liestal, Switzerland

5 Department of Otorhinolaryngology, Uni-versitäts Klinikum Magdeburg, Magdeburg, Germany

Critical review

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infrared light, limiting the ability of light to penetrate tissues and, thus, the maximum depth of imaging to approximately 1.6 mm. Early epithelial cancers of the UADT, however, develop from the most basal epithelial layer at a depth that is usually not greater than 1.0 mm from the surface, so they are well within the limits of near infrared penetration depth. The axial and lateral

resolutions of OCT are independent from one another; the former is deter-mined by the type of OCT system (see below) and the light source used and the latter is dependent on the optical lenses used in the system. The resolu-tion can thereby vary between 3 µm for a microscope-mounted to 15 µm for an endoscope compatible (in vivo) system.

Generally, there are two different types of OCT systems: time-domain OCT (TD-OCT) and frequency-domain OCT (FD-OCT). In 1991, Huang first described a coherence gating technique to enable ‘non-invasive cross-sectional imaging of internal structures in biological tissues’ in real-time4. The first OCT system commercially introduced in 1996 was a TD-OCT system. The system employed a super lumines-cent diode as its ‘low coherence’ light source and produced images one pixel at a time using a Michelson interferometer5. The interference pattern of backscattered light from the sample and the ‘reference’ is calculated using a Michelson inter-ferometer. The strength of the inter-ference signal is measured by a ‘photodetector’. Figure 2 shows the typical setup of a Michelson inter-ferometer-based TD-OCT. In order to produce cross-sectional images, the distance to the ‘reference’ is mechanically adjusted to measure the amount of backscattered light at corresponding depths throughout the sample. Therefore, TD-OCT is somewhat limited by its speed of image creation. By moving the light beam within a confined plane, a two-dimensional image may be displayed (B-scan), composed of a multiplicity of one-dimensional (A-scan) lines5. To date, the only OCT system with international regulatory clearances that is (apart from other fields) specifically marketed for use in the UADT is a TD-OCT (Niris System, Imalux Corporation, Cleveland, Ohio, USA), which works with an imaging probe (2.7 mm diameter) that is placed directly onto the tissue.

During the past decade, the acqui-sition rate of data has been improved by employing FD-OCT systems. They were invented at the beginning of the new century at the University of Vienna. These systems require either a broad-bandwidth or a swept-source laser light source in order to collect all of the various depth data points along one (A-scan) line simultane-

Figure 1: Current medical imaging technologies and their corresponding depth of pen-etration and resolution. CT, computed tomography; MRI, magnetic resonance imaging; OCT, optical coherence tomography; PET, positron emission tomography.

Figure 2: An interferometer measures the interference between two or more light waves, i.e. reflected light from a reference mirror and sample. The interference signal is displayed.

Critical review

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ously. Being independent of mechani-cally moving parts within the system, images are therefore created at a much faster rate, allowing for ‘video-rate’ display of B-scans as well as the generation of three-dimensional and four-dimensional sequences in reasonable time6,7.

Last but not the least, additional information from the acquired signal can be used to derive more informa-tion from the tissue investigated. For example, intravascular speed or vocal cord vibrations can be determined via measurement of Doppler shift (Doppler-OCT)8, or certain tissue structures such as fibrous proteins can be highlighted by detecting the polarisation state of the back-reflected light (polarisation sensitive or PS-OCT)9.

Clinical applications in head and neckOCT has recently been investigated in terms of its applicability in otolaryn-gology. The current review is focused on its clinical application in head and neck cancers, mostly for the differ-entiation of premalignant and early invasive lesions of the UADT. This review also discusses its use in aiding thyroid cancer diagnosis as well as in judging the severity of UADT mucositis as a side-effect of radiation therapy. Other interesting application fields of OCT in otorhinolaryngology

which are not discussed in this paper include its use in otology for visu-alisation of the tympanic membrane, functional assessments of vocal cord mobility and function and neona-tology for three-dimensional recon-struction of the upper airway.

The Medline database was searched for appropriate and rele-vant publications in February 2013 via PubMed using the following search strings: ‘optical coherence tomography’ and ‘optical imaging’ in combination with ‘oral cavity’, ‘larynx’, ‘thyroid’ and ‘mucositis’.

Early tumour diagnosis in the UADTAs tissues have different optical back-scattering properties, OCT allows one to visualise and to differentiate the most superficial tissue layers of the UADT. As demonstrated in Figure 3, it thus provides microanatomical infor-mation on the integrity or disrup-tion of the epithelium, basement membrane (BM) and supporting lamina propria.

The earliest studies on clinical applications of OCT in the UADT were reported from Russia. In 1997, Sergeev et al. were the first to report imaging of the larynx as part of the UADT with OCT in vivo10. Normal tissue and cancerous tissue was visualised with OCT and the authors observed ‘a loss of normal tissue

stratification in tumours’ and thought that OCT would be ‘an interesting tool for early diagnosis of tumours and for guidance of biopsies’. In 2001, Shakhov et al. published a descriptive study on TD-OCT exami-nations in 26 patients with small laryngeal squamous cell carcinomas (SCC)11. The authors concluded that a ‘stratification seen in OCT images is a criterion for a healthy larynx’ and that ‘disappearance of such stratifi-cation is a sign of pathologic tissue alterations’. In addition to rather recently published, site-specific ‘normal values’ for epithelial thick-nesses within the larynx12 and the oral cavity13, their findings thus form the basis for our current interpreta-tion of OCT images in the UADT with regard to diagnosis of early invasive SCC versus premalignancy. This can be illustrated by Figures 4 (dysplasia of the tongue) and 5 (early SCC of the floor of the mouth). Other clini-cally challenging diagnoses, such as differentiating hyperplasia versus dysplasia, might also be possible using real-time OCT14,15 as dysplastic lesions seem to show a persistently higher decrease in signal intensity over the axial run of the epithelial layer than hyperplastic lesions.

LarynxThe larynx is the most frequently investigated location with OCT in the UADT, as its sturdy structure as well as its relatively thin epithe-lium in healthy conditions makes it an optimal location for optical imaging1,11,12,14,16. OCT has been studied in >500 patients in single-centre trials as an adjunct diagnostic tool for its value in assessing and diag-nosing early stage laryngeal patholo-gies7,9,11,12,14,16-25, but with consistently and significantly positive results with regard to sensitivity, specificity and correlation with biopsy results. In most cases, OCT imaging probes were placed directly onto the tissue during microlaryngoscopy. However, non-contact OCT image acquisition via 90° rigid laryngoscopy or flexible

Figure 3: A normal human lip. BM, basement membrane; EP, epithelium; GW, glass win-dow of probe tip; LP, lamina propria; MP, muscularis propria. Bar = 1 mm.

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transnasal laryngoscopy in patients who were awake or intraoperatively via surgical microscopes has also been described7,21-24.

In 2005, Wong et al.16 observed laryngeal mucosa in 82 patients with various pathologies during endoscopy. The authors described that OCT enabled them to obtain ‘microanatomical information about the epithelial layer, the integrity of the basement membrane and lamina propria’. The study’s most impor-tant qualitative observation was ‘the clear border between epithelium and lamina propria in all benign and premalignant lesions’. The authors stated that the main benefit from OCT was its ability to illustrate small foci of destruction in the BM, because they define invasive tumour growth.

In a study published by Armstrong et al. in 200619, the authors performed a total of 26 TD-OCT scans during microlaryngoscopy and compared these images to the histopathological diagnosis (n = 24) in patients with suspicious lesions of the larynx. In this series, ‘a loss of the demarca-tion between the epithelium and the submucosal tissue was demonstrated in all (n = 18) cases of invasive cancer’. In the remaining 6 patients with non-malignant and premalignant changes, an intact basal membrane could only be demonstrated in a subgroup of 3 patients. Similar to our own study, the authors attribute this lack in specificity to the fact that the false-positive results were all found in ‘bulky lesions’; they also state that ‘thick, hypercellular tissues increase backscattering at the surface and

limit the propagation of light into deeper layers of the specimen. This results in a limited capability to both identify the basement membrane and image deeper tissue structures’. Apart from this fact, an imprecise correlation of a histopathological section and OCT image might also be (at least in part) responsible for their false-positive findings.

In another important study, Kraft et al. prospectively investigated 193 patients (217 laryngeal lesions) undergoing microlaryngoscopy alone and in conjunction with OCT14. Microlaryngoscopy with OCT led to the correct diagnosis in 89% of cases, while microlaryngoscopy alone was only able to correctly diagnose 80% of the cases (p = 0.006). The exact grade of dysplasia was correctly predicted in 71% of patients with precancerous disease when OCT was utilised. Sensitivity for identifying dysplasia increased when OCT was added to microlaryngoscopy (66% vs. 78%), as did sensitivity for predicting inva-sion (87% to 93%). Apart from their encouraging results, the authors mentioned three commonly encoun-tered problems with OCT-based diag-nosis: 1) due to strong light absorp-tion, hyperkeratosis may prevent deeper layers from being adequately evaluated; 2) ulcers may be confused with invasive carcinomas due to the absence of a BM and 3) microinvasive cancer often cannot be safely delin-eated from high grade dysplasia or

Figure 4: A) ‘Normal’ tongue OCT with high contrast between EP and LP. B) White tongue plaque OCT with irregular surface, decreased contrast and intact BM. C) Photograph of the tongue. EP, epithelium; LP, lamina propria; MP, muscularis propria. Black arrows indicate the BM. Bar = 1 mm.

Figure 5: A) An OCT image of the ‘normal’ floor of the mouth shows contrast between EP and LP. B) An OCT image of the adjacent muscle invasive tumour shows total loss of microstructure, without visible EP or LP. EP, epithelium; LP, lamina propria.

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carcinoma in situ due to the current spatial resolution of OCT. The authors concluded that OCT is a simple, rapid and reliable aid in the early diagnosis of laryngeal disease.

In 2011, Burns et al. used PS-OCT and conventional OCT to image laryngeal disease. The authors found PS-OCT to be useful especially when differentiating between normal vocal cord tissue and scar tissue, because the increased collagen content in the scar tissue led to different birefrin-gence patterns9. Also, PS-OCT was found to be useful for determining the exact extent of malignant invasion and submucosal spread into adjacent normal structures. However, larger studies are needed to determine the true value of PS-OCT9,26.

In conclusion, OCT appears to be an ideal imaging tool for evaluating discrete and superficial laryngeal abnormalities. To date, its applica-tion helps in locating the best site for decisive biopsy in widespread lesions and to determine the lateral extensions of those mucosal patholo-gies. The results from the studies performed so far suggest that OCT might serve as an ‘optical biopsy’ for live tissue, which would help to decrease costs, time to treat (‘one stop shop’), patient anxiety and the risk of permanent harm to the vocal cord function from unnecessary biopsies. On the downside and apart from the aforementioned general

limitations of OCT, some anatomical sites within the larynx (such as the anterior commissure) can be difficult to image15, and certain conditions such as hyperkeratosis and ulcera-tions can be hard to interpret. With upcoming technical advances and following more thorough investiga-tions, however, the method has the potential to gain a much more wide-spread acceptance in laryngology.

Oral cavityFewer but not less interesting single-centre studies have been published on the clinical use of OCT in the oral cavity. As early as 2004, Fomina et al.27,28 investigated 43 patients with 56 intraoral lesions. The authors were able to detect SCC versus all other pathologies with a sensitivity of 83% and a specificity of 98%. A composite and helpful series of OCT images of a variety of normal and pathologic states from oral and oropharyngeal mucosa were published by Ridgway et al. in 200629. In 2009, Wilder-Smith studied 50 patients with dysplastic and malig-nant oral lesions and found OCT to have 93.1% sensitivity and 97.3% specificity for detecting SCC versus all other pathologies with an excellent intra- and inter-observer agreement (λ = 0.844–0.896)30. Similarly, prom-ising results were reported by Volgger et al. who studied 100 UADT lesions (66% oral cavity and oropharynx, 34% larynx) and were able to distin-

guish non-invasive lesions from inva-sive lesions with a sensitivity of 88.9% and a specificity of 89.0%15.

Similar to the larynx, OCT has been found to be useful in the differentia-tion between benign, premalignant and malignant mucosal changes. In addition, OCT can be used in the oral cavity for screening, monitoring existing lesions, guiding biopsies (and thereby reducing the number of biopsies necessary), surgical guid-ance and post-treatment surveil-lance. The oral cavity is thereby easily accessed, and the OCT investi-gations (usually performed by direct placement of an imaging probe onto the tissue) can be performed in an outpatient setting. Compared to the larynx, the oral cavity’s normal epithelium is thicker in average and shows a greater intra- and inter-indi-vidual variability12,13, so a definitive identification of the BM (especially in cases of benign hyperplasia) is often difficult. Also, oral (pre)malignancies are often associated with hyperkera-tosis, which has a negative influence on the image quality. Therefore, this site might be slightly less suitable for OCT-based diagnosis than the larynx.

Thyroid cancer workupAccording to two ex vivo studies performed on thyroid tissue31,32, OCT might be helpful for biopsy guid-ance during open, minimally inva-sive, endoscopic or robot-assisted thyroid surgery or could be used as an adjunct to fine needle aspira-tion under ultrasound imaging for the screening of thyroid nodules. With a fundamental knowledge of histopathology, OCT might enable the surgeon properly to distinguish between lymph nodes, parathyroid glands and the thyroid gland and to identify normal, degenerative, hyper-plastic, adenomatous and malignant thyroid tissue by revealing charac-teristic image features that relate to comparable histopathological find-ings (Figure 6). Obviously, these results need to be confirmed in larger investigations.

Figure 6: A) An OCT image of the ‘normal’ thyroid tissue with uniform thyroid follicles (arrows). B) An OCT image of the thyroid nodule with a thickened thyroid capsule and C) thyroid follicle enlargement (arrows).

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Diagnosis of (chemo) radiation-induced mucositisMucositis is a common complication of head and neck cancer treatment that often cannot be diagnosed until changes are visible on clinical evalu-ation or the patient reports pain. Mucositis results from the deleterious effects of radiation and chemotherapy on the basal epithelial cells of the oral mucosa. Physicians are in need of a method to identify the earliest stages of mucositis, allowing for early inter-vention with the goal of increasing the patients’ quality of life and decreasing the total cost of patient care. Muanza et al. found that OCT revealed thinning of the epithelium of the oral mucosa in mice before any clinical signs or symptoms were apparent33. Others have confirmed these findings in vivo in humans34,35. In 2013, Calantog et al. reported that specific imaging-based changes were a consistent predictor of clinical mucositis36. Mucositis progression thus shows a decrease of epithelial thickness, followed by loss of the BM and layer distinction. OCT might thus be used in an office setting for early detection and monitoring of mucositis in the future.

ConclusionOCT is a young, non-invasive imaging method that provides high-resolu-tion, cross-sectional images of the most superficial tissue layers and that seamlessly integrates into other diagnostic procedures. It has shown highly promising results in smaller clinical studies which have applied OCT for the diagnostic workup of superficial pathologies of the UADT, mainly dysplastic, precancerous and micro-invasive early cancerous lesions. For this indication, certain conditions such as pronounced hyperkeratosis and/or epithelial hyperplasia, as well as mucosal ulcer-ations, have a negative impact on the interpretability of the acquired images. Apart from its application for the diagnosis of superficial UADT lesions, OCT may also be helpful in the evaluation of neoplastic thyroid

disease and in the preclinical diag-nosis of (chemo) radiation therapy-related mucositis.

In conclusion, OCT is a very attrac-tive technology that has the capa-bility to satisfy several vital needs in head and neck oncology: high-risk population screening, guiding biopsy and surgical procedures and enhancing post-treatment surveil-lance. Larger, multi-centre trials are needed to validate the current find-ings and further define the method’s clinical role. With the expected tech-nical advances in acquisition of speed and resolution, as well as a wider public acceptance of the method, OCT seems to have a bright future in head and neck oncology.

Abbreviations listBM, basement membrane; FD-OCT, frequency-domain optical coherence tomography; OCT, optical coherence tomography; PS-OCT, polarisation sensitive optical coherence tomog-raphy; SCC, squamous cell carci-noma; TD-OCT, time-domain optical coherence topography; UADT, upper aerodigestive tract.

References1. Hughes OR, Stone N, Kraft M, Arens C, Birchall MA. Optical and molecular techniques to identify tumor margins within the larynx. Head Neck. 2010 Nov;32(11):1544–53.2. Steele TO, Meyers A. Early detec-tion of premalignant lesions and oral cancer. Otolaryngol Clin North Am. 2011 Feb;44(1):221–9.3. Fujimoto JG, Brezinski ME, Tearney GJ, Boppart SA, Bouma B, Hee MR, et al. Optical biopsy and imaging using optical coherence tomography. Nat Med. 1995 Sep;1(9):970–2.4. Huang D, Swanson EA, Lin CP, Schuman JS, Stinson WG, Chang W, et al. Optical Coherence Tomography. Science. 1991 Nov;254(5035):1178–81.5. Drexler W, Fujimoto JG, editors. Optical Coherence Tomography Technology and Applications. Berlin/Heidelberg: Springer; 2008.p9–22.6. Kobler JB, Chang EW, Zeitels SM, Yun SH. Dynamic imaging of vocal fold oscilla-tion with four-dimensional optical coher-

ence tomography. Laryngoscope. 2010 Jul;120(7):1354–62.7. Yu L, Liu G, Rubinstein M, Saidi A, Wong BJ, Chen Z. Office-based dynamic imaging of vocal cords in awake patients with swept-source optical coherence tomography. J Biomed Opt. 2009 Nov–Dec;14(6):064020.8. Liu G, Rubinstein M, Saidi A, Qi W, Foulad A, Wong B, et al. Imaging vibrating vocal folds with a high speed 1050 nm swept source OCT and ODT. Opt Express. 2011 Jun;19(12):11880–9.9. Burns JA, Kim KH, de Boer JF, Anderson RR, Zeitels SM. Polarization-sensitive optical coherence tomography imaging of benign and malignant laryngeal lesions: an in vivo study. Otolaryngol Head Neck Surg. 2011 Jul;145(1):91–9.10. Sergeev AM, Gelikonov VM, Gelikonov GV, Feldchtein FI, Kuranov RV, Glad-kova ND, et al. In vivo endoscopic OCT imaging of precancer and cancer states of human mucosa. Optics Express. 1997 Dec;1(13):432–40.11. Shakhov AV, Terentjeva AB, Kamensky VA, Snopova LB, Gelikonov VM, Feld-chtein FI, et al. Optical coherence tomog-raphy monitoring for laser surgery of laryngeal carcinoma. J Surg Oncol. 2001 Aug;77(4):253–8.12. Kaiser ML, Rubinstein M, Vokes DE, Ridgway JM, Guo S, Gu M, et al. Laryn-geal epithelial thickness: a comparison between optical coherence tomography and histology. Clin Otolaryngol. 2009 Oct;34(5):460–6.13. Prestin S, Rothschild SI, Betz CS, Kraft M. Measurement of epithelial thick-ness within the oral cavity using optical coherence tomography. Head Neck. 2012 Dec;34(12):1777–81.14. Kraft M, Glanz H, von Gerlach S, Wisweh H, Lubatschowski H, Arens C. Clinical value of optical coherence tomog-raphy in laryngology. Head Neck. 2008 Dec;30(12):1628–35.15. Volgger V, Stepp H, Ihrler S, Kraft M, Leunig A, Patel PM, et al. Evalua-tion of optical coherence tomography to discriminate lesions of the upper aerodi-gestive tract. Head Neck. 2012 (in press).16. Wong BJ, Jackson RP, Guo S, Ridgway JM, Mahmood U, Su J, et al. In vivo optical coherence tomography of the human larynx: normative and benign pathology in 82 patients. Laryngoscope. 2005 Nov;115(11):1904–11.17. Klein AM, Pierce MC, Zeitels SM, Anderson RR, Kobler JB, Shishkov M, et

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osur

e.



al. Imaging the human vocal folds in vivo with optical coherence tomography: a preliminary experience. Ann Otol Rhinol Laryngol. 2006 Apr;115(4):277–84.18. Lüerssen K, Lubatschowski H, Ursinus K, Gasse H, Koch R, Ptok M. Charakterisierung von Stimmlippen mittels optischer Koharenztomographie. Head Neck Oncol. 2006;54(8):611–5. German.19. Armstrong WB, Ridgway JM, Vokes DE, Guo S, Perez J, Jackson RP, et al. Optical coherence tomography of laryngeal cancer. Laryngoscope. 2006 Jul;116(7):1107–13.20. Kraft M, Luerssen K, Lubatschowski H, Glanz H, Arens C. Technique of optical coherence tomography of the larynx during microlaryngoscopy. Laryngo-scope. 2007 May;117(5):950–2.21. Vokes DE, Jackson R, Guo S, Perez JA, Su J, Ridgway JM, et al. Optical coherence tomography-enhanced microlaryngos-copy: preliminary report of a noncon-tact optical coherence tomography system integrated with a surgical micro-scope. Ann Otol Rhinol Laryngol. 2008 Jul;117(7):538–47.22. Sepehr A, Armstrong WB, Guo S, Su J, Perez J, Chen Z, et al. Optical coherence tomography of the larynx in the awake patient. Otolaryngol Head Neck Surg. 2008 Apr;138(4):425–9.23. Just T, Lankenau E, Hüttmann G, Pau HW. Intra-operative application of optical coherence tomography with an oper-ating microscope. J Laryngol Otol. 2009 Sep;123(9):1027–30.24. Guo S, Yu L, Sepehr A, Perez J, Su J, Ridgway JM, et al. Gradient-index

lens rod based probe for office-based optical coherence tomography of the human larynx. J Biomed Opt. 2009 Jan–Feb;14(1):014017.25. Rubinstein M, Fine EL, Sepehr A, Armstrong WB, Crumley RL, Kim JH, et al. Optical coherence tomography of the larynx using the Niris system. J Otolaryngol Head Neck Surg. 2010 Apr;39(2):150–6.26. Burns JA. Optical coherence tomog-raphy: imaging the larynx. Curr Opin Otolaryngol Head Neck Surg. 2012 Dec;20(6):477–81.27. Fomina I, Urutina MN, Leont’ev VK, Gladkova ND, Gazhva SI, Snopova LB, et al. Opticheskaiakogerentnaiato-mografiia v otsenkesostoianiiaslizis-toiobolochkipolostirta. Soobshchenie 1. Normal’naiaslizistaiaobolochka. Stoma-tologiia (Mosk). 2004;83(3):15–21. Russian.28. Fomina I, Gladkova ND, Leont’ev VK, Urutina MN, Gazhva SI, Snopova LB, et al. Opticheskaiakogerentnaiatomografiia v otsenkesostoianiiaslizistoiobolochkipo-lostirta. Soobshchenie II. Dobrokachest-vennyeizlokachestvennyezabolevaniia. Stomatologiia (Mosk). 2004;83(4):25–32. Russian.29. Ridgway JM, Armstrong WB, Guo S, Mahmood U, Su J, Jackson RP, et al. In vivo optical coherence tomography of the human oral cavity and oropharynx. Arch Otolaryngol Head Neck Surg. 2006 Oct;132(10):1074–81.30. Wilder-Smith P, Lee K, Guo S, Zhang J, Osann K, Chen Z, et al. In vivo diag-nosis of oral dysplasia and malignancy using optical coherence tomography:

preliminary studies in 50 patients. Lasers Surg Med. 2009 Jul;41(5):353–7.31. Zhou C, Wang Y, Aguirre AD, Tsai TH, Cohen DW, Connolly JL, et al. Ex vivo imaging of human thyroid pathology using integrated optical coherence tomography and optical coherence microscopy. J Biomed Opt. 2010 Jan–Feb;15(1):016001.32. Pantanowitz L, Hsiung PL, Ko TH, Schneider K, Herz PR, Fujimoto JG, et al. High-resolution imaging of the thyroid gland using optical coherence tomography. Head Neck. 2004 May;26(5):425–34.33. Muanza TM, Cotrim AP, McAuliffe M, Sowers AL, Baum BJ, Cook JA, et al. Evalu-ation of radiation-induced oral mucositis by optical coherence tomography. Clin-ical cancer research: an official journal of the American Association for Cancer Research. 2005 Jul;11(14):5121–7.34. Kawakami-Wong H, Gu S, Hammer-Wilson MJ, Epstein JB, Chen Z, Wilder-Smith P. In vivo optical coherence tomog-raphy-based scoring of oral mucositis in human subjects: a pilot study. J Biomed Opt. 2007 Sep–Oct;12(5):051702.35. Maslennikova AV, Balalaeva IV, Glad-kova ND, Karabut MM, Kiseleva EB, Iksanov RR, et al. Use of optical coher-ence tomography for prognosis of the severity of oral mucositis. Vopr Onkol. 2009;55(5):572–9. Russian.36. Calantog A, Hallajian L, Nabelsi T, Mansour S, Le A, Epstein J, et al. A prospective study to assess in vivo optical coherence tomography imaging for early detection of chemotherapy-induced oral mucositis. Lasers Surg Med. 2013 Jan;45(1):22–7.

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