Frequency-domain Optical Coherence Tomography System Research Articles

Methylene blue-filled biodegradable polymer particles as a contrast agent for optical coherence tomography.

Optical coherence tomography (OCT) images largely lack molecular information or molecular contrast. We address that issue here, reporting on the development of biodegradable micro and nano-spheres loaded with methylene blue (MB) as molecular contrast agents for OCT. MB is a constituent of FDA approved therapies and widely used as a dye in off-label clinical applications. The sequestration of MB within the polymer reduced toxicity and improved signal strength by drastically reducing the production of singlet oxygen and leuco-MB. The former leads to tissue damage and the latter to reduced image contrast. The spheres are also strongly scattering which improves molecular contrast signal localization and enhances signal strength. We demonstrate that these contrast agents may be imaged using both pump-probe OCT and photothermal OCT, using a 830 nm frequency domain OCT system and a 1.3 µm swept source OCT system. We also show that these contrast agents may be functionalized and targeted to specific receptors, e.g. the VCAM receptor known to be overexpressed in inflammation.

Frequency-domain optical coherence tomography system in the terahertz region

In this study, a frequency-domain optical coherence tomography (FD-OCT) system in the terahertz frequency range was developed. To generate tunable continuous-wave terahertz radiation, the outputs of two near-infrared external cavity diode lasers were mixed in an antenna-coupled photo-mixer. Using the FD-OCT system, tomographic profiling of the front and back surfaces of a high-resistivity silicon plate was realized.

Measurement of Thickness and Refractive Index of Optical Samples Simultaneously Using Full-Range One-Shot Frequency-Domain Optical Coherence Tomography

This article proposes an improved frequency-domain optical coherence tomography for simultaneously measuring the thickness and refractive index of an unknown sample. In conventional frequency-domain optical coherence tomography systems, the spectrum of interference signals generates mirror signals and autocorrelation terms that result in a restricted measurement range. This study presents an improved method that involves applying a phase-shifting algorithm to orthogonally polarized light beams to increase the measurement range and eliminate unnecessary noise. However, a disadvantage is that the proposed method is suitable for the imaging of no (or very low) birefringent samples and needs to align properly the light’s states of polarization.

The Role of Optical Coherence Tomography in Coronary Intervention

Optical coherence tomography (OCT) is an optical analog of intravascular ultrasound (IVUS) that can be used to examine the coronary arteries and has 10-fold higher resolution than IVUS. Based on polarization properties, OCT can differentiate tissue characteristics (fibrous, calcified, or lipid-rich plaque) and identify thin-cap fibroatheroma. Because of the strong attenuation of light by blood, OCT systems required the removal of blood during OCT examinations. A recently developed frequency-domain OCT system has a faster frame rate and pullback speed, making the OCT procedure more user-friendly and not requiring proximal balloon occlusion. During percutaneous coronary intervention (PCI), OCT can provide detailed information (dissection, tissue prolapse, thrombi, and incomplete stent apposition [ISA]). At follow-up examinations after stent implantation, stent strut coverage and ISA can be assessed. Several OCT studies have demonstrated delayed neointimal coverage following drug-eluting stent (DES) implantation vs. bare metal stent (BMS) placement. While newer DESs promote more favorable vascular healing, the clinical implications remain unknown. Recent OCT studies have provided insights into restenotic tissue characteristics; DES restenotic morphologies differ from those with BMSs. OCT is a novel, promising imaging modality; with more in-depth assessments of its use, it may impact clinical outcomes in patients with symptomatic coronary artery disease.

Pathophysiology of acute coronary syndrome assessed by optical coherence tomography

Optical coherence tomography (OCT) is an optical analogue of intravascular ultrasound (IVUS), which provides high-resolution images of the coronary arteries up to 10microm. OCT allows us to demonstrate clearly culprit lesion morphologies in detail including types of plaque, plaque disruption, thrombus, fibrous cap thickness, and the frequency of thin-capped fibroatheroma (TCFA) in acute coronary syndrome (ACS), as described in previous histological examinations. Furthermore, clinical silent disrupted plaques and non-ruptured TCFAs, which are thought to be precursors of ACS and vulnerable plaques, have also been demonstrated by OCT not only in culprit but also in non-culprit vessels in ACS. OCT also identified the mechanisms of late thrombosis after bare-metal stent and drug-eluting stent implantation. Development of the next-generation frequency-domain OCT system and prospective studies in a large population may allow us to realize the pathophysiology of ACS in detail in vivo in humans, and these may provide us new insights into the etiology and treatment of coronary artery disease in the near future for predicting and preventing ACS.

Dual detection full range frequency domain optical coherence tomography

It has been shown that frequency domain optical coherence tomography (FD-OCT) systems achieve higher sensitivities compared to time domain optical coherence tomography (OCT) systems. However, the obscure object structure due to the mirror image generated by the Fourier transform is one of the remaining issues in the FD-OCT. We designed and developed what we believe to be a novel full range FD-OCT system that we refer to as the dual detection full range frequency domain optical coherence tomography (DD-FDOCT) that enables the instantaneous retrieval of quadrature components of the complex interferometric signal. The DD-FDOCT system enables full range imaging without loss of speed, and it may be less sensitive to phase error generated by involuntary movements of the subject compared to the other established full range OCT systems, because it uses two signals with a phase difference of pi/2 obtained simultaneously from two detection arms to remove mirror images at all depths.

Multispectral in vivo three-dimensional optical coherence tomography of human skin

The capability of optical coherence tomography (OCT) to perform "optical biopsy" of tissues within a depth range of 1 to 2 mm with micron-scale resolution in real time makes it a promising biomedical imaging modality for dermatologic applications. Three high-speed, spectrometer-based frequency-domain OCT systems operating at 800 nm (20,000 A-scans/s), 1060 nm, and 1300 nm (both 47,000 A-scans/s) at comparable signal-to-noise ratio (SNR), SNR roll-off with scanning depth, and transverse resolution (<15 microm) were used to acquire 3-D tomograms of glabrous and hairy human skin in vivo. Images obtained using these three systems were compared in terms of penetration depth, resolution, and contrast. Normal as well as abnormal sites like moles and scar tissue were examined. In this preliminary study, skin pigmentation had little effect on penetration accomplished at three different wavelengths. The epidermis and dermal-epidermal junction could be properly delineated using OCT at 800 nm, and this wavelength offered better contrast over the other two wavelength regions. OCT at 1300 nm permits imaging of deeper dermal layers, critical for detecting deeper tumor boundaries and other deeper skin pathologies. The performance at 1060 nm compromises between the other wavelengths in terms of penetration depth and image contrast.

Evaluating choroidal neovascularization in exudative age-related macular degeneration by fluorescein angiography combined with frequency-domain optical coherence tomography

Objective To evaluate the diagnostic value of Heidelberg retinal angiography(HRA) combined with optical coherence tomography (OCT) to detect neovascularization (CNV) in exudative age-related macular degeneration (AMD) patients. Methods This is a cross-sectional study of a series of clinical cases. AMD diagnosis was established by international standard vision chart, Slit lamp microscope, direct or indirect ophthalmoscope examination. A total of 50 eyes (42 cases) of exudative AMD received HRA and frequency domain OCT scan. All 50 eyes received fundus fluorescein angiography (FFA) and frequency-domain OCT simultaneously, and among them 15 eyes also received indocyanine green angiography (ICGA) at the same time. FFA and ICGA were carried out by conventional methods, CNV was localized by real-time Localization technology of frequency domain OCT. In the radial and grid-like section from the areas with strong fluorescence, image acquisition settings are 7 μm fault for each frame, 30° intervals for radialsection, 10 vertical and 10 horizontal scan lines for grid-like section. CNV can be divided into 4 types (typical CNV, partial typical CNV, occult CNV, CNV scarring) according to their boundaries demonstrated in FFA. Based on the features of the OCT images, there were 3 types of integrated image (sub-RPE type, sub-retinal type and mixed type). Results CNV was detected in all 50 eyes. There were 4 eyes (8%) of typical CNV, 11 eyes (22%) of partial typical CNV, 32 eyes (64 %, including 27 eyes of RPE detachment and 5 eyes of passive late leakage) of occult CNV and 3 eyes (6%) of CNV scarring. There were 4 eyes (8%) of sub-RPE type (CNV under the RPE light band) , 16 eyes (32%) of sub-retinal type(interrupted light band of RPE and choroid capillary layer) and 30 eyes (60%) of mixed type of integrated image. Conclusion The image integration technology of the HRA and frequency domain OCT system provide a valuable tool to classify and measure CNV, which will benefit the clinical treatment of AMD patients. Key words: Macular Degeneration/ diagnosis; Choroidal Neovascularization/ diagnosisTomography, optical coherence; Fluorescein angiography; Diagnostic imaging

Detecting precancerous lesions in the hamster cheek pouch using spectroscopic white-light optical coherence tomography to assess nuclear morphology via spectral oscillations

We have developed a novel dual-window approach for spectroscopic optical coherence tomography (OCT) measurements and applied it to probe nuclear morphology in tissue samples drawn from the hamster cheek pouch carcinogenesis model. The dual-window approach enables high spectral and depth resolution simultaneously, allowing detection of spectral oscillations, which we isolate to determine the structure of cell nuclei in the basal layer of the epithelium. The measurements were executed with our parallel frequency domain OCT system, which uses light from a thermal source, providing high bandwidth and access to the visible portion of the spectrum. The structural measurements show a highly statistically significant difference between untreated (normal) and treated (hyperplastic/dysplastic) tissues, indicating the potential utility of this approach as a diagnostic method.

Analyses and calculations of noise in optical coherence tomography systems

Significant progress has been made in the study of optical coherence tomography (OCT) - a non-invasive, high resolution, and in vivo diagnostic method for medical imaging applications. In this paper, the principles of noise analyses for OCT systems have been described. Comparisons are made of signal-to-noise ratios for both balanced and unbalanced detection schemes under the ideal no-stray light situation as well as the non-ideal situation where residual reflections and scatterings are presented. Numerical examples of noise calculation accompanied by detailed comparison of the main characteristics of both time-domain and frequency-domain OCT systems are also presented. It is shown that a larger dynamic range can be achieved for a Fourier-domain OCT system even under the circumstances of high-speed image acquisition. The main results presented in this paper should be useful for the development of high performance OCT systems.

Evaluation of Morphological Changes in Degenerative Cartilage Using 3-D Optical Coherence Tomography

Optical Coherence Tomography (OCT) is an important noninvasive medical imaging technique that can reveal subsurface structures of biological tissue. OCT has demonstrated a good correlation with histology in sufficient resolution to identify morphological changes in articular cartilage to differentiate normal through progressive stages of degenerative joint disease. Current OCT systems provide individual cross-sectional images that are representative of the tissue directly under the scanning beam, but they may not fully demonstrate the degree of degeneration occurring within a region of a joint surface. For a full understanding of the nature and degree of cartilage degeneration within a joint, multiple OCT images must be obtained and an overall assessment of the joint surmised from multiple individual images. This study presents frequency domain three-dimensional (3-D) OCT imaging of degenerative joint cartilage extracted from bovine knees. The 3-D OCT imaging of articular cartilage enables the assembly of 126 individual, adjacent, rapid scanned OCT images into a full 3-D image representation of the tissue scanned, or these may be viewed in a progression of successive individual two-dimensional (2-D) OCT images arranged in 3-D orientation. A fiber-based frequency domain OCT system that provides cross-sectional images was used to acquire 126 successive adjacent images for a sample volume of <TEX>$6{\times}3.2{\times}2.5\;mm^3$</TEX>. The axial resolution was <TEX>$8\;{\mu}m$</TEX> in air. The 3-D OCT was able to demonstrate surface topography and subsurface disruption of articular cartilage consistent with the gross image as well as with histological cross-sections of the specimen. The 3-D OCT volumetric imaging of articular cartilage provides an enhanced appreciation and better understanding of regional degenerative joint disease than may be realized by individual 2-D OCT sectional images.

Wavelength-Tunable Broadband Frequency-Domain OCT Source Based on Spatially Filtered Sub-10-fs Pulsed Laser

A wavelength swept broadband source based on a sub-10-femtosecond (fs) pulse laser and a spatial filtering method was developed for the application to frequency-domain optical coherence tomography (FD-OCT). The use of the sub-10-fs laser with a galvano scanner operating at a high repetition rate provided a fast tunable broadband light source, which tuned the spectral component across the spectral bandwidth of 110 nm at 1-kHz repetition rate. The spectrally filtered light beam had 0.5-nm instantaneous spectral linewidths at 1-mW average output power. The implemented FD-OCT system clearly imaged a narrow air gap between glass plates with an axial resolution of 5 mum, which proved a potential for the application of a short pulse laser source to the FD-OCT system. The proposed wavelength swept source scheme can secure mode-hopping-free operation at fast tuning speed, which could be applicable for the FD-OCT system properly.

Optical coherence tomography of the choroid at 1050nm

Abstract Purpose: Optical coherence tomography is a well established imaging modality for the retina at 800 nm, but is limited in its capability to visualize through scattering tissue, like through cataract or into the choroid. Methods: Utilizing the lower scattering at longer wavelengths (1050 nm) high speed (&gt;17 kHz), high axial resolution (~7 μm) optical coherence tomography (OCT) demonstrates its abil‐ity to exploit the three dimensional anatomic microstructure of the choroid. Volumetric images, obtained with spectrometer based frequency domain OCT system are presented and compared with their counterparts acquired at the commonly used 800 nm range. Results: Tomograms of normals and patients with pathologic morphological changes of the retinal structure as well as with cataract depict improved signal strength and image contrast at the longer wavelength. The deeper penetration allows reconstruction of the choroidal vascular structure despite strong scattering of superficial tissues at the retinal pigment epithelium, the choriocapillaris also including pathologic retinal thickening. Visualisation of modifications in the choroidal vascular structure associated with wet age related macu‐lar degeneration or diabetic retinopathy indicate the diagnostic potential of this technique. Furthermore, being well outside the spectral sensitivity of the eye the wavelength band at 1050 nm also allows for depth resolved profiling of reflectivity changes to directly moni‐tor light stimulus related retinal activity, without interference due to the sampling OCT beam. Conclusions: Imaging at 1050 nm enables not only to track morphological but also functional changes of the retina.

Three-dimensional optical coherence tomography at 1050 nm versus 800 nm in retinal pathologies: enhanced performance and choroidal penetration in cataract patients

Frequency domain optical coherence tomography (FD-OCT), based on an all-reflective high-speed InGaAs spectrometer, operating in the 1050 nm wavelength region for retinal diagnostics, enables high-speed, volumetric imaging of retinal pathologies with greater penetration into choroidal tissue is compared to conventional 800 nm three-dimensional (3-D) ophthalmic FD-OCT systems. Furthermore, the lower scattering at this wavelength significantly improves imaging performance in cataract patients, thereby widening the clinical applicability of ophthalmic OCT. The clinical performance of two spectrometer-based ophthalmic 3-D OCT systems compared in respect to their clinical performance, one operating at 800 nm with 150 nm bandwidth (approximately 3 microm effective axial resolution) and the other at 1050 nm with 70 nm bandwidth (approximately 7 microm effective axial resolution). Results achieved with 3-D OCT at 1050 nm reveal, for the first time, decisive improvements in image quality for patients with retinal pathologies and clinically significant cataract.

Minimum-phase-function-based processing in frequency-domain optical coherence tomography systems

We present a simple processing technique that uses the concept of minimum-phase functions to improve frequency-domain optical coherence tomography systems. Our approach removes the autocorrelation noise and therefore increases both the accessible depth range and the recovery accuracy. To our knowledge, this is the first time that the concept of minimum-phase functions has been applied to improve optical coherence tomography.

Endoscope-tip interferometer for ultrahigh resolution frequency domain optical coherence tomography in mouse colon

Frequency domain optical coherence tomography (FD-OCT) allows interferometer topologies with simplified system construction and handling. Problems of dispersion and polarization matching between the sample and reference arms, as well as beamsplitter spectral non-uniformity, are mitigated when the interferometer is wholly contained in the endoscope tip. A common path set-up, using a reference reflection originating from the inside surface of the glass envelope at the distal end of the endoscope, and an alternative approach with more efficient collection of the reference light using a novel beamsplitter design have been developed. High speed (20,000 A-lines/s) ultrahigh axial resolution (2.4 mum) tomograms of mouse colon have been acquired using a 2 mm outer diameter endoscope in vivo. The FD-OCT system uses a compact mode-locked Ti:Al(2)O(3) laser emitting a broad spectrum (160 nm full-width-half-maximum) centered at 800 nm in combination with a CCD based, spectrally sensitive detector.