Abstract
The object of the study was to demonstrate the abilities of optical coherence tomography (OCT) technique in diagnostics of inflammatory processes in ear, nose, and throat (ENT). When used in diagnostics of the nose and pharynx, OCT facilitates differential diagnostics of rhinitis enabling differentiation between the normal state, two stages of allergic rhinitis, vasomotor and atrophic rhinitis and diagnostics of pharyngitis. This paper also demonstrates the ability of OCT to monitor changes in pharynx induced by cryotherapy. In diagnostics of the tympanic cavity the ability of OCT to differentiate between different stages of chronic otitis and retraction of the tympanic membrane is demonstrated. Finally a correlation is discussed between morphologic alterations induced by inflammatory processes and changes in diagnostic OCT images.
Zusammenfassung
Gegenstand der Studie ist der Nachweis der Einsatzfähigkeit der optischen Kohärenztomographie (optical coherence tomography, OCT) in der Diagnostik von entzündlichen Prozessen im Hals-Nasen-Ohren-Bereich. Im Bereich von Nase und Rachen erlaubt die OCT die Differentialdiagnostik von allergischer (akut/remittierend), vasomotorischer und atropher Rhinitis in Abgrenzung zu gesundem Gewebe sowie die Diagnose von Rachenentzündungen. Außerdem konnten mittels OCT Veränderungen des Rachens nach Kryotherapie dargestellt werden. Im Bereich der Paukenhöhle bietet die OCT die Möglichkeit, zwischen verschiedenen Stadien der chronischen Mittelohrentzündung zu unterscheiden und die Einziehung des Trommelfells darzustellen. Die Korrelation zwischen morphologischen Veränderungen durch entzündliche Prozesse und den damit einhergehenden Veränderungen in den diagnostischen OCT-Bildern wird diskutiert.
1 Introduction
Inflammatory diseases prevail over other ear, nose, and throat (ENT) pathologies and have a higher risk of complication development. Their diagnostics is complicated by a variety of clinical manifestations and morphologic forms, as well as of a prevalence of latent inflammatory processes [1]. The proper selection of treatment should be based on a clear understanding and recognition of the etiological and morphological types of the disease, which if incorrectly assessed, can lead to serious complications [2, 3]. Therefore it is, for example, very important to differentiate between allergic and non-allergic rhinitis, as the treatment strategy for these forms differ dramatically [3, 4]. Currently, simple and inexpensive diagnostic methods are being developed which combine biochemical blood analysis, allergy testing, cytological study of smears from the nasal cavity and even mucosal biopsies. A test for nasal eosinophilia has been shown to be a potential technique for differential diagnostics of which the sensitivity, specificity, positive predictive value, and negative predictive value of this test has been found to be 74, 90, 88, and 77%, respectively [5]. However, further advancement of diagnostic techniques is clearly required.
Optical coherence tomography (OCT) has a high potential for diagnostics and differential diagnostics of inflammatory diseases in ENT. Currently OCT is employed in ENT diagnostics for larynx inspection to reveal possible tumors [6–8].
However, the potential of OCT for the study of the internal structure of mucous membrane of nasal cavity and nasopharynx for diagnosis of non-tumor inflammatory pathologies has already been discussed [9, 10]. This potential lies in the morphological heterogeneity of rhinitis and pharyngitis, which is manifested by a variety of types and subtypes of inflammatory processes in the nose and nasopharynx. Information about morphological features can be a key in the clarification of diagnosis and the decisions to be made about treatment strategies. The possibility of in vivo real-time acquisition of such information using OCT is a very attractive possibility for clinicians.
Inflammatory diseases of the middle ear are the most difficult and dangerous pathological processes in otolaryngology. This is primarily due to the anatomical and physiological connection of the middle ear with the inner ear and topographic proximity to the meninges, which can be instrumental in the development of severe cerebral complications [11]. The most common pathology of the middle ear leading to hearing loss and requiring surgical treatment is chronic suppurative otitis media. The condition of the mucosa of tympanic membrane in patients with chronic otitis media is one of the key factors in selection of treatment strategy. Otomicroscopy is a traditional technique for evaluation of a mucous membrane. However, results of such diagnostics are subjective and strongly depend on the facilities available, qualification of the clinician and his visual perception. In this context, complementary diagnostic techniques that allow procurement of objective results are very important. The most common complementary techniques include histological study, evaluation of blood flow in the mucosa, the study of ciliary activity, etc. All these techniques provide important information about the state of the mucous membrane of the middle ear. However, they are invasive (histological examination), complex, time-consuming and cannot be used in the everyday practice of an otolaryngologist [12]. Thus novel non-invasive and convenient techniques are required for the diagnosis of inflammatory diseases of the middle ear, and OCT has a high potential for this application [13, 14].
The aim of this study was to demonstrate the principal ability of OCT to distinguish morphological changes of mucosa of the nasal cavity, pharynx and middle ear caused by inflammatory diseases. This study was performed for the first time in a clinical environment, both for differential diagnostics of various forms of inflammatory diseases and for dynamic examination of patients, allowing typical OCT images of mucosa to be obtained at different stages of inflammatory processes throughout the course of the study.
2 Materials and methods
2.1 General data and OCT device parameters
The study was performed at the ENT department of the Volga District Medical Centre, Nizhny Novgorod, Russia. In total, 76 patients with inflammatory diseases of the nose, pharynx and middle ear were registered for the study (Table 1).
Composition of the cohort of patients and volunteers enrolled into the study.
| Site of OCT inspection | Diagnosis | Number of volunteers/patients | Sex (M/F) | Mean age±SD (years) |
|---|---|---|---|---|
| Nose | Normal (control) | 35 | 18/17 | 41±5 |
| Allergic rhinitis in the acute stage/in remission stagea | 15 | 7/8 | 34±7 | |
| Vasomotor rhinitis | 25 | 12/13 | 48±8 | |
| Atrophic rhinitis | 10 | 6/4 | 61±6 | |
| Pharynx | Normal (control) | 5 | 2/3 | 40±11 |
| Chronic pharyngitis | 10 | 6/4 | 41±10 | |
| Tympanic cavity | Normal (control) | 8 | 4/4 | 41±10 |
| Chronic otitis media in remission stage/in the period of exacerbationa | 16 | 4/12 | 45±7 |
M, males; F, females.
aNote: the numbers of patients for allergic rhinitis and chronic otitis media subgroups are the same for acute and remission stages because the same patients were monitored during both stages of the disease.
All patients underwent a standard clinical examination in combination with OCT. The OCT-1300U set-up (BioMedTech Ltd, Russia) featured the following characteristics: central probing wavelength of 1300 nm, axial resolution in air of 20 μm, lateral resolution of 25 μm, and an image acquisition rate of 10 frames per second. The set-up was equipped with a forward-looking contact miniprobe.
All subjects involved signed the informed written consent in conforming with the World Medical Association’s Declaration of Helsinki. The study was authorized by the Human Research Ethics Committee (Protocol No. 8 of 03.11.2009).
2.2 OCT inspection of the nose
The group of patients with chronic inflammatory diseases of the nose was made up of 50 patients (25 females, 25 males, average age: 41.5 years). The group of chronic rhinitis was made up of four subgroups:
allergic rhinitis in the acute stage with complaints about nasal congestion, nasal breathing difficulty, sneezing, itchy nose, copious mucus;
allergic rhinitis in remission stage in the course of treatment (intranasal corticosteroids, antihistamines) with no complaints at the time of examination;
vasomotor rhinitis with complaints of nasal congestion, mucous or watery nasal discharge;
atrophic rhinitis with complaints of nasal dryness, recurrent epistaxis, crusting in the nose, reduced sense of smell.
The control group for unaltered nasal cavity mucosa included 35 volunteers with a history of lack of chronic rhinitis, as well as the absence of complaints and evident changes of the mucosa.
OCT examination was performed within the course of a standard rhinoscopy procedure. The miniprobe was brought into contact with the mucosal surface of the lower turbinate under visual control. This study was conducted in an outpatient setting, without anesthesia and additional training of the patients.
2.3 OCT inspection of the pharynx
In 10 patients with chronic pharyngitis (4 females, 6 males, average age: 41 years) the OCT examination was performed within the course of the cryotherapy procedure. Before cryotherapy, pharyngeal mucosa was treated with a solution of local anesthetic (lidocaine 10% spray) to remove the gag reflex, which is important for ensuring OCT contact. The control group for unaltered pharyngeal mucosa included 5 volunteers with a history of lack of chronic pharyngitis, as well as the absence of complaints and evident changes in the mucosa.
2.4 OCT inspection of tympanic cavity
The group of patients with chronic otitis media included 16 patients (12 females, 4 males, average age: 45 years). All patients suffered from chronic otitis media with a defect of the stretched eardrum without cholesteatoma. The group of chronic otitis media contained two subgroups:
chronic otitis media in remission stage; all patients demonstrated a similar picture in otomicroscopy: the absence of external signs of inflammation, a dry perforation, the tympanic cavity mucosa is translucent with color varying from grey to pink;
chronic otitis media in the period of exacerbation with complaints of persistent hearing loss and suppuration of the ear; otomicroscopy demonstrates purulent discharge in the ear canal and tympanic cavity, manifested hyperemia and edema of the mucosa.
The control group for unaltered tympanic membrane included 8 volunteers with a history of lack of chronic otitis, as well as the absence of complaints and evident changes of the tympanic cavity.
OCT examination was performed within the course of a standard otoscopy procedure; the miniprobe was brought into contact with the mucosal surface of the tympanic cavity under microscope control. This study was conducted in an outpatient setting, without anesthesia and additional training of the patients.
3 Results
3.1 OCT diagnostics of the nose
The OCT images of nasal mucosa are consistent with the known morphologic features in both normal and various forms of rhinitis. Figure 1A shows the OCT image of normal nasal mucosa which corresponds to typical morphology i.e., top layer with moderate signal level corresponding to the epithelium, a lower layer with higher signal level corresponding to the sub-epithelial lamina propria, the fuzzy boundary between the layers indicating minor differences in optical properties of the epithelium of lower nasal concha and lastly, the sub-epithelial layer. Vasomotor rhinitis is manifested by alterations in the epithelial layer: disorders in ciliary and transport activity of ciliated epithelium and hypersecretion of goblet cells, which promotes the formation of multilayer ciliated epithelium. This leads to a thickening of the upper layer with a moderate signal level in the OCT image (Figure 1B). Allergic rhinitis is usually manifested by alterations in the characteristics that relate to discharge from the nasal cavity accompanied by development of eosinophilia of the discharge. These alterations are accompanied by severe tissue edema, which is manifested by the appearance of areas of irregular shape with low signals in the OCT image (Figure 1C). Atrophic rhinitis is manifested by thinning of the mucous membrane mainly due to the epithelial layer and sclerosis of the sub-epithelial tissues. This leads to the absence of the top layer in the OCT image resulting in an increase in the signal level for all areas in the OCT image (Figure 1D).
OCT images of mucosa of inferior nasal concha: norm (A), chronic vasomotor rhinitis (B), allergic rhinitis (C) and atrophic rhinitis (D).
3.2 OCT diagnostics of the pharynx
Chronic pharyngitis also reveals morphological heterogeneity. The prevalence of certain morphological alterations determines the form of the disease i.e., catarrhal, hypertrophic or atrophic. Figure 2A–C shows the OCT images of healthy mucosa of the pharynx, and hypertrophic pharyngitis before and after cryotherapy.
OCT images of mucosa of pharynx: norm (A), chronic pharyngitis before (B) and after cryotherapy (C).
The OCT image of the normal pharynx (Figure 2A) fully corresponds to the morphological structure of the pharynx. The upper layer is characterized by a moderate signal level corresponding to stratified squamous epithelium, while the lower layer with a high signal level corresponds to lamina propria with a high content of elastin fibers. In submucous layer glands and lymphoid, elements are manifested in OCT images by irregular shaped areas of different size and signal level. In the case of the catarrhal form of chronic pharyngitis, a persistent diffuse congestion of the veins accompanied by pronounced edema of tissues is observed leading to disintegration of morphological structures and an increase in the volume of lymphoid tissue (Figure 2B). Quite often, chronic pharyngitis has a mixed form, in this case the morphological features of hypertrophic pharyngitis can be observed in the background of changes typical for catarrhal form of the disease, for example, formation of cysts in the sub-epithelial cystic expansions, bulbs and “bights”.
Since OCT examination of the pharynx was conducted during the course of cryotherapy procedure, OCT images of the same site after cryotherapy were also obtained (Figure 2C), which again demonstrates the high sensitivity of OCT to changes in the morphological characteristics of tissues. OCT images obtained from the same site of the same patient before and after cryotherapy differ significantly (Figure 2B and C). Cryotherapy is accompanied by water crystallization manifested in OCT images by disappearance of low-signal areas and a balance of the signal level in the upper layers.
3.3 OCT diagnostics of tympanic cavity
No OCT images of the tympanic cavity mucosa are possible in the normal state because the cavity cannot be reached due to access being blocked by an intact tympanic membrane. Different pathologies may induce holes in the tympanic membrane or decrease the inner pressure causing the tympanic membrane to be brought into contact with tympanic cavity mucosa. In such situations the tympanic cavity mucosa can be reached by an OCT probe and OCT imaging allows morphological changes typical for different stages of an inflammatory process to be obtained (Figure 3A–D).
Otomicroscopy and OCT images of tympanic cavity in case of chronic otitis without exacerbation (A, C) and in the period of exacerbation (B, D). 1 – mucosa, 2 – bone layer, 3 – epithelial layer. The black circles indicate the site of OCT inspection.
In the normal state, the epithelial layer of the tympanic cavity mucosa is located on the basal membrane, behind which lamina propria is situated. In this case the mucosa is tight against the bone wall. The OCT image of chronic otitis without exacerbation demonstrates a typical structure allowing not only the epithelial layer be distinguished but also a clear boundary between the mucosa and promontorium bone (Figure 3C). Exacerbation induces a distinguished edema accompanied by cellular infiltration of all layers of the mucosa which causes blurring of the boundaries between layers and structural elements in the OCT image (Figure 3D).
OCT imaging of the tympanic membrane also allows it to be distinguished in its various pathologies. Figure 4A–D demonstrates OCT images of tympanic membrane in its normal and in three pathologic states. In normal state the tympanic membrane appears in an OCT image as a separate object with a high signal level. Layered structures can be distinguished, revealing the epithelial, fibrous and mucosal layers (Figure 4A). Analysis of diagnostic OCT images obtained in patients with chronic otitis without exacerbation allowed us to conclude that OCT enables retractions of tympanic membrane to be seen. In the case of retraction the tympanic membrane is sucked into the middle ear space due to lower inner pressure and may come in contact with tympanic cavity mucosa which can be clearly detected by OCT (Figure 4B). Acute exudative otitis is usually manifested by inflammation resulting in bulging of tympanic membrane resulting in a loss of the OCT signal level and a thickening of the layer that corresponds to the tympanic membrane in the OCT image (Figure 4C). Behind the layer, a weakly scattering media can be observed which is associated with exudate. Chronic mesotympanitis is manifested by significant thickening of the epithelial layer of tympanic membrane which can be clearly seen in the OCT image (Figure 4D), and its perforation appears as low signal areas (right part of the image).
OCT images of tympanic membrane in norm (A), in case of retraction with the background of chronic otitis media without exacerbation (B), acute exudative otitis (C) and chronic mesotympanitis during exacerbation stage (D).
4 Discussion and conclusion
This study demonstrates the potential use of the OCT technique in ENT diagnostics. For diagnostics of the nose and pharynx, OCT images manifested changes that correlate with morphologic alterations. This would allow differential diagnostics of rhinitis enabling differentiation between the normal state, two stages of allergic rhinitis, vasomotor and chronic rhinitis and diagnostics of pharyngitis. Also the ability of OCT to monitor changes in the pharynx induced by cryotherapy was demonstrated. The usefulness of OCT for diagnostics of the tympanic cavity was illustrated in its ability to differentiate between different stages of chronic otitis media and reveal tympanic membrane retraction. Unfortunately comparative analysis and interpretation of OCT in comparison with histologic date was not possibly as biopsy was contraindicated. Information was taken therefore from the literature about the features of nose, pharynx and tympanic cavity morphology and its alterations in cases of various forms of inflammation, and was used instead for the interpretation of the obtained images.
Both normal and pathological OCT images in ENT vary significantly from patient to patient. This complicates the interpretation of diagnostic OCT images and requires the development of algorithms for the numerical processing of OCT images to increase diagnostic accuracy of the technique. Such algorithms are usually based on the extraction of numerical parameters of the OCT images, such as individual optical properties of tissue layers [15], parameters of the histograms of entire OCT image [16] or preselected region of interest [17]. Extracted values can be sensitive to morphological alterations in cases when a clinician’s visual perception is not able to distinguish changes.
Numerous studies have consistently proved that the pathological processes in biological tissues significantly change their optical properties, which can be sensed by OCT (see, for example, [15–17]). In this study it was possible to show that OCT could be used for diagnosis of inflammatory processes in ENT. In the case of rhinitis and rhinopharyngitis, OCT provides information about the morphological features of the nose and pharynx tissues which can be further employed for diagnosis of various forms of inflammation and can contribute to a better choice of treatment. In diagnosis of otitis media, OCT is a promising method for accurate determination of inflammation stages, to reveal indications for surgery (tympanoplasty), and in selecting the optimal timing for surgery. Moreover the principal possibility of employing OCT for monitoring of treatment of ENT diseases was shown. Non-invasive and real-time imaging increases the attractiveness of OCT for clinicians, especially in diagnosing inflammatory diseases of ENT organs when biopsies are contraindicated.
In our opinion, OCT has a high potential for noninvasive differential diagnostics of different forms of ENT chronic inflammatory diseases and real-time monitoring during the course of treatment. However, further studies with an increased number of patients with a variety of ENT pathologies are required to qualitatively evaluate diagnostic efficacy of OCT in diagnosing ENT pathologies for translation of the technique into clinical practice.
This work was financially supported by the basic financing of the Institute of Applied Physics within the framework of the Theme 12.16 “Acoustics and optical methods for investigation of structure and dynamics of physiological processes in biological tissues”.
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