|Year : 2017 | Volume
| Issue : 6 | Page : 883-888
Optical coherence tomography in oral cancer: A transpiring domain
Reddy Sudhakara Reddy, Kotu Nagavenkata Sai Praveen
Department of Oral Medicine and Radiology, Vishnu Dental College, Bhimavaram, West Godavari, Andhra Pradesh, India
|Date of Web Publication||13-Dec-2017|
Dr. Kotu Nagavenkata Sai Praveen
Department of Oral Medicine and Radiology, Vishnu Dental College, Vishnupur, Kovvada, Bhimavaram - 534 202, West Godavari, Andhra Pradesh
Source of Support: None, Conflict of Interest: None
Identification of oral cancer at an early curable stage not only aids in controlling the mortality and morbidity rate but also improves the quality of life of the patient. Indeed, regular monitoring of such life-threatening disease has held an imperative role in cancer diagnostics. Various light-based diagnostics are currently available to the clinician for early diagnosis of oral cancer. Optical coherence tomography (OCT) is one such emerging light-based diagnostic modality that provides noninvasive, real-time images at a depth of 1.5–2 mm and can also be compared to corresponding histopathological sections, hence this procedure can also be referred as optical biopsy. This technique can also be used as an adjunct to histopathology in circumstances where large areas are needed to be examined, screening apprehensive patients, larger populations, and for regular monitoring of patients. The current article is a brief review that highlights basic principle, various versions, and applications of OCT in the diagnosis of oral cancer.
Keywords: Diagnosis, optical coherence tomography, oral cancer, radiation mucositis
|How to cite this article:|
Reddy RS, Sai Praveen KN. Optical coherence tomography in oral cancer: A transpiring domain. J Can Res Ther 2017;13:883-8
| > Introduction|| |
The oral cavity is a transition zone between the skin and gastrointestinal system, usually lined by epithelium formerly known as oral mucosa. Based on its adaptive functions, oral mucosa can be broadly categorized into three types. They are masticatory mucosa lining the hard palate and gingiva to resist masticatory forces, specialized mucosa lining dorsal surface of the tongue for taste sensation, and lining mucosa that covers rest of the regions which are comparatively less subjected to the masticatory forces.
Oral cancer, one of the dreadful diseases affecting the humankind, is the sixth most common cancer in the world. Squamous cell carcinoma is established to be the most common, accounting for about 90% of oral cancers. Diagnosis of oral cancer at a very early stage helps to provide prompt treatment which in turn enhances the provision to cure the disease and improvise the survival rate. But it is rather being a difficult task. It has been documented that only 20% of reported oral squamous cell carcinomas were preceded by a potentially malignant lesion, and also most of the potentially malignant lesions are usually asymptomatic, due to which early diagnosis is being difficult.
The standard method followed for diagnosing these potentially malignant and malignant lesions is by conventional oral examination and confirming the suspected lesion by biopsy and histological examination. Other methods of diagnosis include vital staining, serum and salivary biomarkers, DNA ploidy, brush biopsy, and imaging methods such as plain radiographs, computed tomography, cone beam computed tomography, magnetic resonance imaging, nuclear imaging, and optical techniques.
In the latest era, optical techniques have been illuminated in cancer diagnostics which uses light for diagnosis. It mainly depends on light and tissue interactions. The light that has been reflected is displayed and assessed to know the histological and biological changes of oral tissues. Various optical diagnostic techniques include elastic scattering spectroscopy, fluorescence spectroscopy, chemiluminescence, contact endoscopy, Raman spectroscopy, and optical coherence tomography (OCT).
OCT is one of the light-based diagnostic aids which uses backscattered reflections to create images up to a depth of 1.5–2 mm and conceptually similar to that of ultrasound. It was first introduced in the field of ophthalmology and at present it is being used in clinical studies related to oral cancer. The present review emphasizes on the application of OCT for diagnosis of premalignant and malignant lesions of the oral cavity.
| > History|| |
Duguay in the year 1971 was the first person to use light and optics for imaging of biological tissues and had created new avenues for usage of light in diagnosis. Later, in 1991, Fujimoto has first demonstrated cross-sectional imaging of retina by using OCT, from then it had been widely used in the field of ophthalmology. With the developing technology, OCT also has advanced and at present, it has been widely used in many fields of medicine for clinical and research applications. OCT was first introduced by Otis et al. in the year 2000. The usage of OCT in a clinical setup was approved by the Federal Drug Administration in the year 2002.
| > Basic Principle|| |
When a beam of light is incident over a tissue surface, it can be transmitted, reflected, or absorbed. Light that is absorbed by the tissues is considered to be omitted from the incident light. Chromophores like hemoglobin and melanin present in the tissues are responsible for absorption and produces photochemical changes, which further depends on the wavelength of incident beam. Light that is transmitted through tissues is free to interact with underlying tissues and is used for the assessment of internal aspects up to a particular depth.
OCT mainly works on the principle of white light Michelson interferometry in which produced white light is split into two equal beams, namely reference path beam and sample path beam that are at right angles to each other. Reference path beam is directed toward a reference mirror and sample path beam is directed toward the tissues. The reflected light from both the directions is combined at beam splitter to obtain interference. Reflected light from sample path will lose some of its intensity because of light-tissue interactions and when this light is combined with reference path beam where reflection is because of a reference mirror the difference in reflected light intensities leads to production of a signal known as interference signal which is further recorded by the spectrophotometer [Figure 1].
| > Different Versions of Optical Coherence Tomography|| |
The first or the original version is time domain (TD)-OCT in which the position of reference mirror is changeable and this property helps to detect the backscattered tissue intensity levels from different depths in a tissue sample. This prototype allows for obtaining images in both axial or A-scan (depth of penetration) and lateral or angular axis. TD-OCT works at a speed of 400 axial scans per se cond. Advancements in the basic version are mainly aimed at increasing the scanning speed with better axial resolution.
Fourier domain optical coherence tomography
It is so named because it makes use of intensity profiles (A-scans) obtained by using a Fourier transform of the detected frequencies. This type further includes spectral domain (SD)-OCT and swept source (SS)-OCT.
- SD-OCT makes use of broadband light source with a stationary reference mirror and intensity of backscattered light is split by grating into frequency components which is detected by a charge-coupled device (CCD) that helps in improvising the resolution of axial scans. SD-OCT works at a speed of 312,500 axial scans per se cond [Figure 2],
- SS-OCT is a combination of both TD-OCT and SD-OCT in which the light source is a single tunable laser but not broadband light as in SD-OCT, also the CCD are replaced by a single photodetector. This modification resulted in improved transverse resolution and is mainly useful for visualizing finer transverse details like imaging of axons and blood vessels. SS-OCT works at a speed of 249,000 axial scans per se cond.,
|Figure 2: Modification of basic principle for spectral domain - optical coherence tomography|
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Advances in OCT not only confined to structural imaging of biological tissues but also for providing functional changes of living tissues, which laid down the concept of functional OCT that includes the following versions:
Doppler optical coherence tomography
Doppler OCT is mainly used for measuring the flow of fluids within blood vessels and microvessel morphology. It works similar to Doppler acoustic imaging where the speed of moving particles alters the frequencies of backscattered light and this helps in obtaining functional images. The main alteration in this type is within the detector which is locked for a certain frequency that indicates the depth at which light is reflected. Any alteration to this value adds to the Doppler effect.
Polarization-sensitive optical coherence tomography
Polarization-sensitive OCT is another functional variant that uses polarization properties of light for imaging. Usually, light travels in the form of an electromagnetic wave in which the electric and magnetic fields are orthogonal to its propagation direction. Lightwave is said to be linear polarized when all its electric field vectors are in a straight line during its propagation. Light tissue interactions alter this polarization of light and recording this alteration will help in knowing both structural and functional abnormalities for a given tissue specimen. In order to achieve this, light emitted from the source is first polarized by a polarizer before it passes through the beam splitter. A quarter-wave plate is added near the reference mirror that aid in confirming the polarized nature of reference beam, and an additional polarized beam splitter near detectors that directs the resultant light toward the horizontal and vertical detectors. It is mainly used for imaging neoplasms, teeth defects, and collagen alterations in tissues [Figure 3].
|Figure 3: Modification of basic principle for polarization-sensitive optical coherence tomography|
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Differential absorption optical coherence tomography
Differential absorption OCT makes use of two different wavelength light sources in the process of imaging. One will be more than the absorption peak of selected tissue, and the other will be lesser. This helps in the validation of structural and functional abnormalities for a selected tissue specimen.
Molecular optical coherence tomography
Molecular OCT makes use of the differential light absorption properties of various biomarkers in a tissue sample. It is mainly useful for detecting neoplasms and tissue oxygenation properties where there will be alterations in the biomarkers., Optical coherence elastography mainly uses elastic modulus property of tissues for imaging which gets altered in cases of edema, neoplasms, calcifications, and fibrosis.
Two-dimensional (2D) imaging is always not sufficient to visualize the morphological features and also to determine margins of cancerous tissue, three-dimensional (3D) images helps in better visualization and better treatment plan. OCT also has been expanded for 3D imaging by adding silicon-based microelectromechanical system (MEMS) mirror to the normal 2D scanner. 3D images were obtained by combining both transverse and longitudinal scans of MEMS scanner with the axial scanning of rapid scanning optical delay.
| > Optical Coherence Tomography Instrumentation|| |
An OCT system comprises a light source, beam splitter, reference arm, and an imaging catheter or a microscope (sample arm) that helps in both delivering and collecting light from tissue surface [Figure 4]. Three types of OCT probes are currently available. They are bulk OCT system setup which is mainly used in immediate and delayed ex vivo imaging in laboratory which is not useful in clinical application.In vivo OCT with the flexible probe (Imulax system) works with a spatial depth resolution of about 10–20 μm, scanning range of about 2 mm depth, and lateral scanning range of 1.5–2.5 mm. This system setup is most commonly used for imaging human and animal oral cavities.In vivo OCT probe (Michelson VivoSight) system setup provides 7.5 μm lateral and 10 μm vertical resolution and is most frequently used for skin imaging in dermatology clinics. From the imaging catheter, the received backscattered light is transferred to interferometry device where reflected sample beam is mixed with reflected reference beam so as to obtain coherence and eventually ends up in the detector where analog data are converted into digital data and final image is displayed over the computer screen.
|Figure 4: Schematic representation of optical coherence tomography instrumentation|
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| > Optical Coherence Tomography in Oral Cancer|| |
Histopathology stands next to clinical examination in confirming the diagnosis of oral potentially malignant and malignant lesions. But, this requires removal of tissue which is again an invasive process. A surgical biopsy may result in patient anxiety, discomfort, and sampling errors that may further require re-biopsy and also may land up with some undesirable side effects.
OCT is a noninvasive real-time imaging modality that helps in obtaining images that can be compared to histopathological sections and hence this procedure is also termed as optical biopsy. It is important to note that contrast in OCT images is mainly because of difference in light-absorbing capacity of tissues, whereas in histopathology specific stains are used to study cellular and subcellular features. Hence, OCT can be used as an adjunct but not analogous to histopathology.
Wilder-Smith et al. had first checked the reliability of OCT imaging for oral malignancies in golden Syrian hamster cheek pouches by inducing carcinogen into their oral tissues, its progression and further compared with histopathological sections, in which they noticed 80% agreement between the two. Fomina et al. in the year 2004 investigated 43 patients with 56 intraoral lesions, and they were able to differentiate oral squamous cell carcinoma from all other oral pathologies with a sensitivity of 83% and specificity of 98%.
Ridgway et al. during operative endoscopy examined both normal and abnormal oral- and oro-pharyngeal mucosa in 41 patients using OCT and correlated it with histologic images and based on the observations they had given a composite series of helpful in vivo normal and pathologic OCT images of oral- and oro-pharyngeal mucosa.
Davoudi et al. used SD-OCT to visualize oral tissues and its layers in both healthy volunteers and patients with ulcers. They also used Doppler technique for visualizing the alterations in underlying vasculature of normal and ulcerative oral mucosa and a speckle variance OCT for obtaining 3D images of scar tissue over labial mucosa of a healthy volunteer and noticed increased subsurface microvasculature compared to healthy volunteers. Based on acquired images, authors proposed that developed SD-OCT provides a quantifiable subsurface tool to monitor oral diseases which cause oral mucosal alterations.
Hamdoon et al. had conducted a study using SS-OCT in a total of 73 patients with 78 suspicious oral lesions and correlated OCT images with corresponding histopathology sections and had noticed a good agreement between alterations in tissue layers such as keratin layer, epithelial layer, basement membrane, and rete pegs. Authors also reported that obtained OCT images cannot provide cellular and subcellular information necessary for grading potentially malignant disorders. Lee et al. had studied normal oral mucosa of 54 volunteers, 39 patients with mild dysplasia, and 44 patients with moderate dysplasia using SS-OCT with aided computer analysis of the final images and was able to differentiate all lesions with a sensitivity of 82% and specificity of 90%.
Jerjes et al. had conducted a study using SS-OCT over 19 patients with 24 oral lesions of leukoplakia and erythroplakia. Authors had noticed that architectural changes up to a depth of 1.5 mm can be correlated to the corresponding histopathological images. Tsai et al. had also used SS-OCT for differentiating normal oral mucosa from those with potentially malignant and malignant lesions and obtained same results as that of Lee et al. and also stated that SS-OCT is more advantageous than SD-OCT in differentiating potentially malignant and malignant lesions.
Jung et al. had conducted a study to validate the 3D OCT images by inducing carcinogen into oral mucosa of 34 hamsters. Cancer progression at various stages was checked and confirmed by histopathology. Based on the findings, author had reported that 3D images provide detailed structural information at any location, which can be viewed at any desired angle by clinician; also their appearance corresponds to histopathological images.
| > Nanotechnology in Optical Coherence Tomography|| |
Incorporation of contrast agents to OCT system helps in enhancing the final image contrast that in turn facilitates better differentiation of normal and neoplastic tissues. Inorganic nanoparticles such as nanorods, nanospheres, nanoshells, and nanocages are used as contrast agents. Gold nanoparticles are most commonly and widely used contrast agents, owing to their biocompatibility, ease to synthesize, and can be delivered both systemically or topically.
Local delivery of gold nanoparticles over keratinized oral mucosal surface is greatly hampered by stratum corneum. Kim et al. had suggested that microneedles had produced micropassages through stratum corneum which has enhanced the passage of topically applied gold nanoparticles. SD-OCT was used for imaging and author had noticed better penetration of gold nanoparticles with 150% increased OCT contrast levels in the standard model for oral carcinogenesis. In the case of systemic administration, intravenously injected nanoparticles get accumulated at the site of tumor due to leakiness of tumor vasculature.
These nanoparticles apart from providing contrast also can aid in the treatment of tumors. Nanoshells absorb the light at near-infrared wavelength and cause photothermal ablation, which is useful for treating tumors and improving the survival rate of the patient. Gobin et al. had demonstrated the therapeutic effect of gold nanoshells in tumor-induced mice. They had divided the tumor-induced mice into two groups in which one group received nanoshells + OCT light therapy and the other received phosphate-buffered saline + OCT light therapy. The first group had showed decreased tumor size with increased survival rate within 7-week follow-up period.
| > Optical Coherence Tomography in Late Radiation Toxicity|| |
The mainstay of oral cancer treatment is surgery followed by radiotherapy and chemotherapy. Radiotherapy which involves delivery of higher doses of radiation to tumor site causes various undesirable effects to the normal adjacent mucosa. This is mainly because delineation of tumor margin is perhaps impossible. Despite advances in radiation delivery like intensity-modulated radiation therapy and image-guided radiation therapy, various adverse effects are still common which can manifest during the course of treatment or following several months to years after treatment.
This radiation-dependent oral mucosal change can be monitored by using OCT at an early stage. Davoudi et al. have conducted a clinical study in 14 patients with late radiation toxicities with five age-matched healthy controls. OCT images are obtained from sites that received radiation dose >50 Gy and those sites that received <50 Gy in 14 patients. Oral sites that received a dose of <50 Gy had showed normal oral mucosal features except in one patient, whereas rest of the sites that received higher doses had showed total layer disruption along with thinning of epithelium. Thus, OCT can be used periodically to monitor oral subsurface changes after radiotherapy.
| > Limitations of Optical Coherence Tomography|| |
Imaging in OCT is mainly based on light absorption and scattering properties of targeted tissue sites.
- Contrast in OCT is mainly because of light scattering, whereas with respect to histopathology it is mainly because of specific stains that are being used. Hence, it can be stated that OCT is not analogous to histopathological examination 
- When there is any strong absorption or scattering of light due to hemorrhage, there will be strong attenuation of light and shadowing of deeper structures leading to decreased diagnostic value of final image 
- The depth of penetration is limited to 1.5–2 mm. Thus, definitive identification of basement membrane is difficult 
- Most of the oral premalignancies are often associated with hyperkeratosis which in turn has a negative influence on image quality.
| > Conclusion|| |
OCT is an evolving, noninvasive imaging technique that provides images with resolutions comparable to that of histopathological sections; hence, this can be perhaps used for the diagnosis of oral potentially malignant and malignant lesions. Researchers and clinicians can obtain not only the structural images but also the functional alterations at desired tissue sites with the emerging recent advances. With the advent of 3D imaging, detailed structural information of the pathological site can be viewed from any desired angle and thus assists to overcome and alleviate corresponding challenges. OCT has been driven into research for diagnosis as well as treatment of cancerous tissue by incorporation of resonant nanoshells. Although this emerging technology has perhaps balanced its merits and demerits, yet it lacks sensitivity and specificity. Thus, future studies are required so that this latest field of science can reach the horizon of early diagnosis and probably as a therapeutic modality for oral cancer.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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