Optical coherence tomography in otolaryngology: current opportunities and perspectives for use

Recent decade has seen a shift in the causes of childhood blinding diseases from anterior segment to retinal disease in both developed and developing countries. The common retinal disorders are retinopathy of prematurity and vitreoretinal infections in neonates, congenital anomalies in infants, and vascular retinopathies including type 1 diabetes, tumors, and inherited retinal diseases in children (up to 12 years). Retinal imaging helps in diagnosis, management, follow up and prognostication in all these disorders. These imaging modalities include fundus photography, fluorescein angiography, ultrasonography, retinal vascular and structural studies, and electrodiagnosis. Over the decades there has been tremendous advances both in design (compact, multifunctional, tele-consult capable) and technology (wide- and ultra-wide field and noninvasive retinal angiography). These new advances have application in most of the pediatric retinal diseases though at most times the designs of new devices have remained confined to use in adults. Poor patient cooperation and insufficient attention span in children demand careful crafting of the devices. The newer attempts of hand-held retinal diagnostic devices are welcome additions in this direction. While much has been done, there is still much to do in the coming years. One of the compelling and immediate needs is the pediatric version of optical coherence tomography angiography. These needs and demands would increase many folds in future. A sound policy could be the simultaneous development of adult and pediatric version of all ophthalmic diagnostic devices, coupled with capacity building of trained medical personnel.

Optical coherence tomography (OCT) is a novel noninvasive optical imaging technique that enables cross-sectional imaging of highly scattering biological tissues at the axial resolution of 10 micrometers or less. Technological advances in our laboratory and others have been permitted high-contrast and high-resolution OCT imaging of turbid biological tissues at depths of up to 2-3 mm, highly desirable for screening various kinds of superficial lesions and the invasion of these lesions. In this study, we will demonstrate the potential of OCT as a powerful tool of optical biopsy or optical guided biopsy for the purpose of noninvasive imaging diagnosing malignancies in these tissues. We will present ex vivo OCT images of animal urinary bladders and lesions (including cancers) in these tissues in comparison with the corresponding histologic evaluations. Based on the comparative studies between OCT and histology, we will analyze the image contrast of OCT or the patterns in OCT images in relation to the micro morphologies in these tissues and their alternations or lesions at different stages of tumorigenesis. We will also analyze the image contrast of OCT related to the blood vessels as well as other tissue functions such as fluid penetration and buildup in these tissues. Our results demonstrate the utility of OCT in high- resolution imaging to delineate the micro morphology of highly scattering tissues such as urinary bladders and the clinical relevance of OCT in diagnosing alternations or tumor growth in these tissues. Because of limitations to specificity and resolution of current techniques, OCT is presently unable to provide distinctive diagnosis of malignancies that require subcellular imaging or identification of subtle changes in nuclear morphology. However, certain characteristics associated with malignancies in bladders such as heavy vascularization and proliferation within the urothelial tissue can be clearly demonstrated.

Optical Coherence Tomography (OCT) is a non-invasive 3 dimensional optical imaging modality that enables high resolution cross sectional imaging in biological tissues and materials. Unlike other 3 D medical imaging modalities, OCT provides high axial and lateral resolution combined with high sensitivity, imaging depth and wide field of view which makes it suitable for wide variety of medical imaging applications1. Apart from analysing the morphological characteristics of the biological organs with micron scale axial and lateral resolution, OCT also provides functional information from the biological sample. Among the various functional extensions of OCT, angiographic OCT that enables visualization of lumens of blood vessels from the acquired OCT B scan images has been of high research interest in the recent past.

Various optical imaging modalities with different optical contrast mechanisms have been developed over the past years. Although most of these imaging techniques are being used in many biomedical applications and researches, integration of these techniques will allow researchers to reach the full potential of these technologies. Nevertheless, combining different imaging techniques is always challenging due to the difference in optical and hardware requirements for different imaging systems. Here, we developed a multimodal optical imaging system with the capability of providing comprehensive structural, functional and molecular information of living tissue in micrometer scale. This imaging system integrates photoacoustic microscopy (PAM), optical coherence tomography (OCT), optical Doppler tomography (ODT) and fluorescence microscopy in one platform. Optical-resolution PAM (OR-PAM) provides absorption-based imaging of biological tissues. Spectral domain OCT is able to provide structural information based on the scattering property of biological sample with no need for exogenous contrast agents. In addition, ODT is a functional extension of OCT with the capability of measurement and visualization of blood flow based on the Doppler effect. Fluorescence microscopy allows to reveal molecular information of biological tissue using autofluoresce or exogenous fluorophores. In-vivo as well as ex-vivo imaging studies demonstrated the capability of our multimodal imaging system to provide comprehensive microscopic information on biological tissues. Integrating all the aforementioned imaging modalities for simultaneous multimodal imaging has promising potential for preclinical research and clinical practice in the near future.

Optical Coherence Tomography (OCT; LightLab) is a catheter-based technology producing images from backscattered “echoes” similar to intravascular ultrasound (IVUS), but using high-bandwidth light sources (infrared light). This new technology provides ultra-high resolution for endovascular visualization. In comparison to common IVUS imaging, OCT enables optimal plaque identification, detection of thin tissue structures (eg, re-endotheli- alization, dissections) and …

Superluminescent diodes (SLDs) are of great interest as optical sources for various field applications like fibre-optic gyroscopes (Culter et al, 1980), optical time-domain reflectometry (Takada et al, 1987), sensing systems (Burns et al, 1983) (such as Faraday-effect electric current sensors and distributed Bragg-grating sensor systems) and short and medium distance optical communication systems (Friebele & Kersey, 1994). One of the most attractive applications of SLDs has emerged after the successful demonstration of the optical coherence tomography (OCT) technique, and identification of its advantages compared to other imaging techniques in medical research and clinical practices. OCT is a real time and non-invasive imaging technique that uses low-coherence light to generate resolution down to the sub-micron-level, twoor three-dimensional cross-sectional images of materials and biological tissues. The earliest version of the OCT imaging technique was demonstrated in 1991 by Huang and co-workers (Huang et al, 1991), by probing the human retina ex vivo. Imaging was performed with 15μm axial resolution in tissue using a light source with a central wavelength of 830nm. Two years later, in vivo retinal images were reported independently by Fercher et al. (Fercher et al, 1993) and Swanson et al (Swanson et al, 1993). Although 800nm OCT systems can resolve all major microstructural layers of tissues, image quality can be severally degraded by light scattering phenomena. In low-coherence interferometry, the axial resolution is given by the width of the field autocorrelation function, which is inversely proportional to the bandwidth of the light source. In other words, light sources with broadband spectra are required to achieve high axial resolution. Although at longer wavelengths the bandwidth requirement increases, there is a significant advantage in using light sources of longer central wavelengths for which the light scattering is significantly reduced. In recent few years, broadband light sources around 1m have received considerable attention for their use in medical imaging technologies. It is due to the optimal compromise between water absorption and human tissue scattering that the 1000-1100 nm wavelength range has been proposed, and demonstrated, to be more suitable for OCT applications as compared to those that use a light source with a central wavelength of 800nm (Pavazay et al,

Optical coherence tomography (OCT) is a recently developed optical imaging technique that performs high resolution, cross-sectional tomographic imaging of microstructure in biological systems. OCT is analogous to ultrasound B mode imaging except that it uses light instead of sound. OCT performs imaging by using low coherence interferometry to measure the optical backscattering of tissue as a function of echo delay and transverse position [1]. The resulting two-dimensional data set can be displayed as a gray scale or false color image. OCT functions as a type of "optical biopsy" to provide cross sectional images of tissue structure on the micron scale. OCT is a powerful imaging technology because, unlike conventional histopathology, which requires removal of a tissue specimen and processing for microscopic examination, OCT can provide images of tissue in situ and in real time, without the need for excision. OCT has originally been developed and applied by our group for tomographic diagnostics in ophthalmology [2,3]. OCT can provide images of the retina with resolutions of 10 p,m, one order of magnitude higher than conventional ultrasound. Working in collaboration with the New England Eye Center and MIT Lincoln Laboratory, we have developed a clinical prototype OCT instrument and examined over 5000 patients. The technology has been transferred to industry, and a commercial product was introduced into the ophthalmic market in 1996. Studies in ophthalmology show that OCT is especially promising for the diagnosis and monitoring of diseases such as glaucoma or macular edema associated with diabetic retinopathy where it provides quantitative information on disease progression. In many cases OCT has the ability to detect and diagnose early stages of disease before physical symptoms and loss of vision occur. Recent research on OCT has focused on developing technology to perform optical biopsy in internal medicine [4-6]. OCT at optical wavelengths in the near infrared where tissue scattering is minimized allows imaging to be performed to depths of 2-3 mm. Using solid state modelocked laser sources which can provide both short coherence lengths and high powers, high resolution and high speed imaging may be achieved. Image resolutions of 5-10 im and high speed acquisition of 250 x 250 pixel images at rates of 8 frames per second have been achieved. OCT imaging has been integrated with microscopy to perform imaging of specimens in vitro. A prototype single mode fiber optic catheter/endoscope with a diameter of 1 mm has been developed which can transluminally image internal tissue structures such as the respiratory tract, gastrointestinal tract, or arteries. In recent studies, catheter/endoscope based OCT imaging of internal organs in an animal model has been demonstrated [7]. Endoscopic OCT imaging in patients has also been demonstrated [8]. Ultrahigh resolution OCT has recently been developed and demonstrated. Kerr lens modelocked Ti:sapphire lasers have achieved sub-two cycle duration optical pulses with a corresponding bandwidth from 650 nm to 1000 nm [9]. Since the axial resolution of OCT is inversely proportional to the bandwidth of the light source, axial resolutions of 1 -2 im can be achieved. A novel C-scan focus tracking and image fusion technique has also been demonstrated to overcome depth of field limitations and permit 3 im transverse resolutions. This system can achieve subcellular level resolution and promises to be a powerful research tool in developmental biology and future clinical studies [10]. OCT is a promising and powerful medical imaging technique because it can permit the in situ visualization of tissue microstructure without the need to remove a specimen excisionally as in conventional biopsy and histopathology. The concept of nonexcisional "optical biopsy" provided by OCT and the ability to visualize tissue architectural morphology in real time under operator guidance can have many applications in several scenarios: 1) For situations where conventional biopsy is either hazardous or impossible, 2) Where biopsy has an unacceptably high false negative rate due to sampling errors, and 3) For guiding surgical intervention. This presentation will discuss technology and applications of this new imaging modality.

On the Horizon From the ORS

Nodular lesions have common clinical appearance but different prognoses. Differential diagnosis between melanoma (MM), basal cell carcinoma (BCC) and dermal naevus (DN) poses a challenge in clinical practice. Reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) are promising non-invasive imaging techniques, potentially able to decrease redundant biopsies. RCM allows invivo visualization of skin down to the papillary dermis at almost histological resolution, while OCT, particularly dynamic OCT (D-OCT), provides images deeper within the dermis and reveals the vascular pattern. To identify correlating features observed with RCM and OCT associated with the different nodular lesion diagnoses. We retrospectively assessed 68 nodular lesions (30 MM, 20 BCC and 18 DN) with RCM and subsequently OCT. At the end of the study, evaluations were matched with histopathological diagnosis and statistical analysis was performed. In MM, 57% (17/30) evidenced both cerebriform nests at RCM and icicle-shaped structures at OCT, with higher average Breslow index. In 80% of BCCs with basaloid islands at RCM, OCT showed ovoid structures. More than half of DN (56%) showed hyporeflective nests at OCT and either dense nests or dense and sparse nests at RCM. The combined use of RCM and OCT offers a better understanding of the morphological architecture of nodular lesions, correlating RCM parameters with OCT and vice versa, assisting in turn with early differential diagnosis of malignant and benign nodular lesions. The correlation between icicle-shaped structures and cerebriform nests in MM and their association with Breslow index requires future research.

Use of optical techniques for biomedical imaging is a topic of considerable current interest. This is motivated by the potential of optical techniques to provide micrometer-scale resolution imaging without the need for ionizing radiation and associated risks. Optical coherence tomography (OCT) can provide non-invasive cross-sectional images of biological tissues in real time with spatial resolutions down to few micrometers. Recent advances in OCT enable rapid image acquisition speeds and 3D volumetric information. There have been increasing applications of 3D-OCT for imaging of biological microstructures such as human retina, human skin and other developmental model systems. The depth of OCT imaging is limited by scattering of the medium that destroys the coherence of the probe beam. Thus while for non-scattering ocular structures, OCT can be used to image the entire structure, imaging of highly scattering tissues like skin is usually limited to a few mm. By taking OCT images for two orthogonal linear polarizations of the scattered light we can get information about the birefringent properties of the tissue. This helps monitor changes in the morphology of the birefringent constituents (collagen, tendon etc) of the tissue. Such Polarisation Senstive OCT (PSOCT) systems have also been developed and are being used for monitoring changes that take place in malignancy or in wounds. Work on the development and utilization of OCT & PSOCT systems for biological tissue imaging is being actively pursued at RRCAT, Indore. The OCT Proceedings of 2010 International Conference on Systems in Medicine and Biology 16–18 December 2010, IIT Kharagpur, India systems have been used for real time, in vivo & in vitro imaging of micro-structures of biological tissues and animal model systems with resolutions of ∼10–20 µm. Even though cytological differences cannot be monitored, the characteristic morphological features (texture) in OCT images can be used to discriminate and classify different tissue types using automated algorithms. In this talk I shall provide an overview of some of these developments and describe a few representative applications carried out in our laboratory.

When the doctor needs an engineer to be the matchmaker

Retinal changes and visual symptoms are present in several inflammatory, degenerative and tumorous disorders of the central nervous system (CNS). Optical coherence tomography (OCT) is a method that can be used in clinical practice to detect and quantify the structural correlates of these visual symptoms in neurological disorders. OCT is a non-invasive imaging technique, based on interferometry, which can create high-resolution images of the retina and measure the thickness and volume of the different retinal layers. The combined ganglion cell- and inner plexiform layer (GCIPL) and the peripapillary retinal nerve fibre layer (pRNFL) are of particular interest in the field of neurological disorders, since they contain the neuronal bodies (ganglion cells) and their axons that form the optic nerve. In acute optic neuritis (ON), initial swelling of the pRNFL can be detected by OCT and this may contribute to the diagnosis and differential diagnosis of ON; moreover, the extent of the GCIPL-thinning within the first 4weeks after an acute ON can contribute to the prediction of the long-term visual recovery. However, the role of OCT in the field of multiple sclerosis (MS) is not restricted in patients with ON, since even eyes without an ON-history show mild thinning of the pRNFL and GCIPL. This thinning seems to be associated with neurodegenerative processes in the entire CNS. Several studies showed correlations between these OCT-parameters and a higher risk of clinical deterioration (disability progression), cognitive deficits and disease activity in patients with MS. However, it is often still unclear how these correlations can be useful in the management of the individual patient. In recent years, OCT has been applied to a greater extent to neurodegenerative diseases, such as Parkinson's disease, amyotrophic lateral sclerosis (ALS) and various forms of dementia. However, routine clinical use is still further away than for inflammatory CNS diseases, since the role of OCT in the diagnosis, differential diagnosis and prediction of the clinical course of neurodegenerative diseases is still unclear. This review article offers a summary of the available study results on OCT parameters and their role in inflammatory, degenerative and tumorous diseases of the central nervous system (CNS).

Breast cancer is one of the most common cancers, and recognized as the third leading cause of mortality in women. Optical coherence tomography (OCT) enables three dimensional visualization of biological tissue with micrometer level resolution at high speed, and can play an important role in early diagnosis and treatment guidance of breast cancer. In particular, ultra-high resolution (UHR) OCT provides images with better histological correlation. This paper compared UHR OCT performance with standard OCT in breast cancer imaging qualitatively and quantitatively. Automatic tissue classification algorithms were used to automatically detect invasive ductal carcinoma in ex vivo human breast tissue. Human breast tissues, including non-neoplastic/normal tissues from breast reduction and tumor samples from mastectomy specimens, were excised from patients at Columbia University Medical Center. The tissue specimens were imaged by two spectral domain OCT systems at different wavelengths: a home-built ultra-high resolution (UHR) OCT system at 800 nm (measured as 2.72 μm axial and 5.52 μm lateral) and a commercial OCT system at 1,300 nm with standard resolution (measured as 6.5 μm axial and 15 μm lateral), and their imaging performances were analyzed qualitatively. Using regional features derived from OCT images produced by the two systems, we developed an automated classification algorithm based on relevance vector machine (RVM) to differentiate hollow-structured adipose tissue against solid tissue. We further developed B-scan based features for RVM to classify invasive ductal carcinoma (IDC) against normal fibrous stroma tissue among OCT datasets produced by the two systems. For adipose classification, 32 UHR OCT B-scans from 9 normal specimens, and 28 standard OCT B-scans from 6 normal and 4 IDC specimens were employed. For IDC classification, 152 UHR OCT B-scans from 6 normal and 13 IDC specimens, and 104 standard OCT B-scans from 5 normal and 8 IDC specimens were employed. We have demonstrated that UHR OCT images can produce images with better feature delineation compared with images produced by 1,300 nm OCT system. UHR OCT images of a variety of tissue types found in human breast tissue were presented. With a limited number of datasets, we showed that both OCT systems can achieve a good accuracy in identifying adipose tissue. Classification in UHR OCT images achieved higher sensitivity (94%) and specificity (93%) of adipose tissue than the sensitivity (91%) and specificity (76%) in 1,300 nm OCT images. In IDC classification, similarly, we achieved better results with UHR OCT images, featured an overall accuracy of 84%, sensitivity of 89% and specificity of 71% in this preliminary study. In this study, we provided UHR OCT images of different normal and malignant breast tissue types, and qualitatively and quantitatively studied the texture and optical features from OCT images of human breast tissue at different resolutions. We developed an automated approach to differentiate adipose tissue, fibrous stroma, and IDC within human breast tissues. Our work may open the door toward automatic intraoperative OCT evaluation of early-stage breast cancer. Lasers Surg. Med. 49:258-269, 2017. © 2017 Wiley Periodicals, Inc.

Early detection of gastrointestinal cancer is essential for the patient treatment and medical care. Endoscopically guided biopsy is currently the gold standard for the diagnosis of early esophageal cancer, but can suffer from high false negative rates due to sampling errors. Optical coherence tomography (OCT) is an emerging medical imaging technology which can generate high resolution, cross-sectional images of tissue in situ and in real time, without the removal of tissue specimen. Although endoscopic OCT has been used successfully to identify certain pathologies in the gastrointestinal tract, the resolution of current endoscopic OCT systems has been limited to 10 - 15 m for clinical procedures. In this study, in vivo imaging of the gastrointestinal tract is demonstrated at a three-fold higher resolution (< 5 m), using a portable, broadband, Cr4+:Forsterite laser as the optical light source. Images acquired from the esophagus, gastro-esophageal junction and colon on animal model display tissue microstructures and architectural details at high resolution, and the features observed in the OCT images are well-matched with histology. The clinical feasibility study is conducted through delivering OCT imaging catheter using standard endoscope. OCT images of normal esophagus, Barrett's esophagus, and esophageal cancers are demonstrated with distinct features. The ability of high resolution endoscopic OCT to image tissue morphology at an unprecedented resolution in vivo would facilitate the development of OCT as a potential imaging modality for early detection of neoplastic changes.

Excision biopsy and histology represent the gold standard for morphological investigation of the skin, in particular for cancer diagnostics. Nevertheless, a biopsy may alter the original morphology, usually requires several weeks for results, is non-repeatable on the same site and always requires an iatrogenic trauma. Hence, diagnosis and clinical management of diseases may be substantially improved by new non-invasive imaging techniques. Optical Coherence Tomography (OCT) is a non-invasive depth-resolved optical imaging modality based on low coherence interferometry that enables high-resolution, cross-sectional imaging in biological tissues and it can be used to obtain both structural and functional information. Beyond the resolution limit, it is not possible to detect structural and functional information using conventional OCT. In this paper, we present a recently developed technique, nanosensitive OCT (nsOCT), improved using broadband supercontinuum laser, and demonstrate nanoscale sensitivity to structural changes within ex vivo human skin tissue. The extended spectral bandwidth permitted access to a wider distribution of spatial frequencies and improved the dynamic range of the nsOCT. Firstly, we demonstrate numerical and experimental detection of a few nanometers structural difference using the nsOCT method from single B-scan images of phantoms with sub-micron periodic structures, acting like Bragg gratings, along the depth. Secondly, our study shows that nsOCT can distinguish nanoscale structural changes at the skin cancer margin from the healthy region in en face images at clinically relevant depths. Finally, we compare the nsOCT en face image with a high-resolution confocal microscopy image to confirm the structural differences between the healthy and lesional/cancerous regions, allowing the detection of the skin cancer margin.