Multi-functional Optical Coherence Tomography Research Articles

多機能OCTを用いた力学特徴量マイクロ断層可視化の産業・技術への展開

多機能OCTを用いた力学特徴量マイクロ断層可視化の産業・技術への展開

Structural and functional human retinal imaging with a fiber-based visible light OCT ophthalmoscope.

The design of a multi-functional fiber-based Optical Coherence Tomography (OCT) system for human retinal imaging with < 2 micron axial resolution in tissue is described. A detailed noise characterization of two supercontinuum light sources with different pulse repetition rates is presented. The higher repetition rate and lower noise source is found to enable a sensitivity of 96 dB with 0.15 mW light power at the cornea and a 98 microsecond exposure time. Using a broadband (560 ± 50 nm), 90/10, fused single-mode fiber coupler designed for visible wavelengths, the sample arm is integrated into an ophthalmoscope platform, similar to current clinical OCT systems. To demonstrate the instrument's range of operation, in vivo structural retinal imaging is also shown at 0.15 mW exposure with 10,000 and 70,000 axial scans per second (the latter comparable to commercial OCT systems), and at 0.03 mW exposure and 10,000 axial scans per second (below maximum permissible continuous exposure levels). Lastly, in vivo spectroscopic imaging of anatomy, saturation, and hemoglobin content in the human retina is also demonstrated.

Multi-Functional OCT Enables Longitudinal Study of Retinal Changes in a VLDLR Knockout Mouse Model.

We present a multi-functional optical coherence tomography (OCT) imaging approach to study retinal changes in the very-low-density-lipoprotein-receptor (VLDLR) knockout mouse model with a threefold contrast. In the retinas of VLDLR knockout mice spontaneous retinal-chorodoidal neovascularizations form, having an appearance similar to choroidal and retinal neovascularizations (CNV and RNV) in neovascular age-related macular degeneration (AMD) or retinal angiomatous proliferation (RAP). For this longitudinal study, the mice were imaged every 4 to 6 weeks starting with an age of 4 weeks and following up to the age of 11 months. Significant retinal changes were identified by the multi-functional imaging approach offering a threefold contrast: reflectivity, polarization sensitivity (PS) and motion contrast based OCT angiography (OCTA). By use of this intrinsic contrast, the long-term development of neovascularizations was studied and associated processes, such as the migration of melanin pigments or retinal-choroidal anastomosis, were assessed in vivo. Furthermore, the in vivo imaging results were validated with histological sections at the endpoint of the experiment. Multi-functional OCT proves as a powerful tool for longitudinal retinal studies in preclinical research of ophthalmic diseases. Intrinsic contrast offered by the functional extensions of OCT might help to describe regulative processes in genetic animal models and potentially deepen the understanding of the pathogenesis of retinal diseases such as wet AMD.

Birefringence imaging of posterior eye by multi-functional Jones matrix optical coherence tomography.

A clinical grade prototype of posterior multifunctional Jones matrix optical coherence tomography (JM-OCT) is presented. This JM-OCT visualized depth-localized birefringence in addition to conventional cumulative phase retardation imaging through local Jones matrix analysis. In addition, it simultaneously provides a sensitivity enhanced scattering OCT, a quantitative polarization uniformity contrast, and OCT-based angiography. The probe beam is at 1-μm wavelength band. The measurement speed and the depth-resolution were 100,000 A-lines/s, and 6.6 μm in tissue, respectively. Normal and pathologic eyes are examined and several clinical features are revealed, which includes high birefringence in the choroid and lamina cribrosa, and birefringent layered structure of the sclera. The theoretical details of the depth-localized birefringence imaging and conventional phase retardation imaging are formulated. This formulation indicates that the birefringence imaging correctly measures a depth-localized single-trip phase retardation of a tissue, while the conventional phase retardation can provide correct single-trip phase retardation only for some specific types of samples.

Optically buffered Jones-matrix-based multifunctional optical coherence tomography with polarization mode dispersion correction.

Polarization mode dispersion (PMD) degrades the performance of Jones-matrix-based polarization-sensitive multifunctional optical coherence tomography (JM-OCT). The problem is specially acute for optically buffered JM-OCT, because the long fiber in the optical buffering module induces a large amount of PMD. This paper aims at presenting a method to correct the effect of PMD in JM-OCT. We first mathematically model the PMD in JM-OCT and then derive a method to correct the PMD. This method is a combination of simple hardware modification and subsequent software correction. The hardware modification is introduction of two polarizers which transform the PMD into global complex modulation of Jones matrix. Subsequently, the software correction demodulates the global modulation. The method is validated with an experimentally obtained point spread function with a mirror sample, as well as by in vivo measurement of a human retina.

Simultaneous investigation of vascular and retinal pigment epithelial pathologies of exudative macular diseases by multifunctional optical coherence tomography.

To investigate exudative macular disease, multifunctional optical coherence tomography (MF-OCT) using a 1-μm probe band was developed. The clinical utility of MF-OCT was examined in a descriptive case series. Ten eyes of nine subjects with exudative macular disease, including one eye with age-related macular degeneration (AMD), one eye with idiopathic neovascular maculopathy, and eight eyes with polypoidal choroidal vasculopathy (PCV), were investigated. Areas of 6 × 6 mm(2) around the pathologic region were scanned with 512 × 1024 depth scans in 6.6 seconds. Structural OCT, Doppler optical coherence angiography (OCA), and cumulative phase retardation images were obtained with a single measurement. Each MF-OCT image visualized the structure, vasculature, and birefringence. Degree of polarization uniformity values were also obtained for selective visualization of the retinal pigment epithelium (RPE). The MF-OCT images were compared with conventional ophthalmic images. Abnormal vasculatures were observed with Doppler OCA in all eyes, which presented high similarity to indocyanine green angiography in the midphase. The RPE and exudation in the pathologic regions were discriminated in one eye with AMD and five of eight eyes with PCV. Cumulative phase retardation visualized fibrosis scars in two of the PCV cases. Multifunctional OCT revealed depth-resolved abnormal vasculatures, the integrity of the RPE and choroid, discrimination of the RPE and exudation, and existence of fibrosis scars in exudative macular diseases. Interpretation of MF-OCT examination is well matched with conventional ophthalmic examination. These results suggest that MF-OCT can be used as a noninvasive ophthalmic examination tool prior to conventional examinations in clinical routines.

SY34 再生医療実現のための非侵襲マイクロ診断技術 : 多機能OCT(S3:再生医療実現のための工学的基盤技術)

SY34 再生医療実現のための非侵襲マイクロ診断技術 : 多機能OCT(S3:再生医療実現のための工学的基盤技術)

GPU accelerated real-time multi-functional spectral-domain optical coherence tomography system at 1300nm

We present a GPU accelerated multi-functional spectral domain optical coherence tomography system at 1300nm. The system is capable of real-time processing and display of every intensity image, comprised of 512 pixels by 2048 A-lines acquired at 20 frames per second. The update rate for all four images with size of 512 pixels by 2048 A-lines simultaneously (intensity, phase retardation, flow and en face view) is approximately 10 frames per second. Additionally, we report for the first time the characterization of phase retardation and diattenuation by a sample comprised of a stacked set of polarizing film and wave plate. The calculated optic axis orientation, phase retardation and diattenuation match well with expected values. The speed of each facet of the multi-functional OCT CPU-GPU hybrid acquisition system, intensity, phase retardation, and flow, were separately demonstrated by imaging a horseshoe crab lateral compound eye, a non-uniformly heated chicken muscle, and a microfluidic device. A mouse brain with thin skull preparation was imaged in vivo and demonstrated the capability of the system for live multi-functional OCT visualization.

Passive component based multifunctional Jones matrix swept source optical coherence tomography for Doppler and polarization imaging

We present a fiber based multifunctional Jones matrix swept source optical coherence tomography (SS-OCT) system for Doppler and polarization imaging. Jones matrix measurement without using active components such as electro-optic modulators is realized by incident polarization multiplexing based on independent delay of two orthogonal polarization states and polarization diversity detection. In addition to polarization sensitivity, this system measures Doppler flow without extra hardware for phase stabilized SS-OCT detection. An eighth-wave plate was measured to demonstrate the polarization detection accuracy. The optic nerve head of a retina was measured in vivo. Detailed vasculature and birefringent structures were investigated simultaneously.

Multifunctional optical imaging reveals tissue properties of the anterior eye

Corneal and anterior-segment optical coherence tomography (CAS-OCT) is an imaging mode used to obtain cross-sectional images of the anterior eye segment in a noncontact and noninvasive manner.1 CAS-OCT has been used in clinics for diagnosis and basic research of ocular diseases such as glaucoma. Although conventional OCT helps to visualize the distribution of backscattering intensities from tissues, unlike histological techniques it does not guarantee clear differentiation of individual tissues. To enhance the contrast of OCT images, the birefringence and Doppler flow of tissues have been measured as functional extensions of OCT.2–5 We have demonstrated that this multifunctional CAS-OCT (MF-CAS-OCT) can accurately visualize fibrous tissues and blood flow in the anterior eye segment. For biomedical imaging, it is important to have good imageacquisition speeds to avoid image distortion due to the motion of the sample. Swept-source optical coherence tomography (SS-OCT), also known as optical frequency-domain imaging, demonstrates high-speed and highly sensitive acquisition, owing to the use of a wavelength-swept laser.6 This technique has been used for CAS-OCT to obtain 3D images.7 A technical challenge for using polarization-sensitive and Doppler-flow imaging in combination with SS-OCT is to apply these additional functions without compromising imaging speed. In previous studies exploring the use of MF-OCT, the effective imaging speed had to be reduced to accommodate the additional functions of OCT. This is because two incident states of polarization are required to compensate for birefringence of the fiberoptic components.2–5 To avoid this, we used a method involving continuous polarization modulation to multiplex the two polarization states into the signal frequency.8 Figure 1. Simplified schematic of multifunctional corneal and anteriorsegment optical coherence tomography. EOM: Electrooptic modulator, PS: polarization sensitive.

Optical Coherence Straingraphy using Low Coherence Intereferometer

Optical Coherence Tomography (OCT) has been developed as a cross-sectional imaging method of microstructural biological tissue with high resolution 1-10μm. Recently, multifunctional OCT system has been promising, e. g. estimator of bio-mechanical characteristics. In this study, presented is Optical Coherence Straingraphy (OCS) on the basis of OCT system, which can diagnose tissue strain distribution. This is composed of the recursive cross-correlation method, resulting in deformation vector distribution with high resolution. In addition, the spatial vector interpolation by local least square method is introduced to remove erroneous vectors and smooth the vector distribution. This was experimentally applied to compressed homogeneous and heterogeneous samples. Conse-quently, the deformation vector distribution has less erroneous vectors and better agreement with the estimation of ideal uniform compression than that obtained by the conventional direct cross-correlation method. Therefore, the proposed method was validated with the smooth strain map having the same high resolution 20μm as that defined by optical system.

Real-time fiber-based multi-functional spectral-domain optical coherence tomography at 13 µm

We demonstrate a high-speed multi-functional spectral-domain optical coherence tomography system, using a broadband light source centered at 1.3 microm and two InGaAs line scan cameras capable of acquiring individual axial scans in 24.4 micros, at a rate of 18,500 axial scans per second. Fundamental limitations on the accuracy of phase determination as functions of signal-to-noise ratio and lateral scan speed are presented and their relative contributions are compared. The consequences of phase accuracy are discussed for both Doppler and polarization-sensitive OCT measurements. A birefringence artifact and a calibration procedure to remove this artifact are explained. Images of a chicken breast tissue sample acquired with the system were compared to those taken with a time-domain OCT system for birefringence measurement verification. The ability of the system to image pulsatile flow in the dermis and to perform functional imaging of large volumes demonstrates the clinical potential of multifunctional spectral-domain OCT.

Real-time multi-functional optical coherence tomography

We demonstrate real-time acquisition, processing, and display of tissue structure, birefringence, and blood flow in a multi-functional optical coherence tomography (MF-OCT) system. This is accomplished by efficient data processing of the phase-resolved inteference patterns without dedicated hardware or extensive modification to the high-speed fiber-based OCT system. The system acquires images of 2048 depth scans per second, covering an area of 5 mm in width x 1.2 mm in depth with real-time display updating images in a rolling manner 32 times each second. We present a video of the system display as images from the proximal nail fold of a human volunteer are taken.