Ting-Ta Chi

Diagnosis of oral precancer with optical coherence tomography

A procedure for computer analyzing an optical coherence tomography (OCT) image of normal and precancerous oral mucosae is demonstrated to reasonably plot the boundary between epithelium (EP) and lamina propria (LP) layers, determine the EP thickness, and estimate the range of dysplastic cell distribution based on standard deviation (SD) mapping. In this study, 54 normal oral mucosa, 39 oral mild dysplasia, and 44 oral moderate dysplasia OCT images are processed for evaluating the diagnosis statistics. Based on SD mapping in an OCT image, it is found that the laterally average range percentages of 70% SD maximum level in the EP layer is a reasonably good threshold for differentiating moderate dysplasia from mild dysplasia oral lesion based on the OCT image analysis. The sensitivity and specificity in diagnosis statistics can reach 82 and 90%, respectively.

Au nanorings for enhancing absorption and backscattering monitored with optical coherence tomography.

Preparation of a high-concentration Au nanoring (NR) water solution and its applications to the enhancement of image contrast in optical coherence tomography (OCT) and the generation of the photothermal effect in a bio-sample through localized surface plasmon (LSP) resonance are demonstrated. Au NRs are first fabricated on a sapphire substrate with colloidal lithography and secondary sputtering of Au, and then transferred into a water solution through a liftoff process. By controlling the NR geometry, the LSP dipole resonance wavelength in tissue can cover a spectral range of 1300 nm for OCT scanning of deep tissue penetration. The extinction cross sections of the fabricated Au NRs in water are estimated to give levels of 10(-10)-10(-9) cm(2) near their LSP resonance wavelengths. The fabricated Au NRs are then delivered into pig adipose samples for OCT scanning. It is observed that, when resonant Au NRs are delivered into such a sample, LSP resonance-induced Au NR absorption results in a photothermal effect, making the opaque pig adipose cells transparent. Also, the delivered Au NRs in the intercellular substance enhance the image contrast of OCT scanning through LSP resonance-enhanced scattering. By continuously OCT scanning a sample, both photothermal and image contrast enhancement effects are observed. However, by continually scanning a sample with a low scan frequency, only the image contrast enhancement effect is observed.

Characterizing the localized surface plasmon resonance behaviors of Au nanorings and tracking their diffusion in bio-tissue with optical coherence tomography

The characterization results of the localized surface plasmon resonance (LSPR) of Au nanorings (NRs) with optical coherence tomography (OCT) are first demonstrated. Then, the diffusion behaviors of Au NRs in mouse liver samples tracked with OCT are shown. For such research, aqueous solutions of Au NRs with two different localized surface plasmon resonance (LSPR) wavelengths are prepared and characterized. Their LSPR-induced extinction cross sections at 1310 nm are estimated with OCT scanning of solution droplets on coverslip to show reasonably consistent results with the data at individual LSPR wavelengths and at 1310 nm obtained from transmission measurements of Au NR solutions and numerical simulations. The resonant and non-resonant Au NRs are delivered into mouse liver samples for tracking Au NR diffusion in the samples through continuous OCT scanning for one hour. With resonant Au NRs, the average A-mode scan profiles of OCT scanning at different delay times clearly demonstrate the extension of strong backscattering depth with time. The calculation of speckle variance among successive OCT scanning images, which is related to the local transport speed of Au NRs, leads to the illustrations of downward propagation and spreading of major Au NR motion spot with time.

Observations of cardiac beating behaviors of wild‐type and mutant Drosophilae with optical coherence tomography

Time-resolved optical coherence tomography (OCT) scanning images of wild-type and mutant fruit flies (Drosophila melanogaster), illustrating the heartbeat patterns for evaluating their cardiac functions, are demonstrated. Based on the heartbeat patterns, the beat rate and the relative phase between the first two heart segments can be evaluated. The OCT scanning results of mutant flies with impaired proteasome function in cardiac muscles show irregular heartbeat patterns and systematically decreased average beat rates, when compared with the regular patterns of ~4.97 beats/s in average beat rate of the wild-type. In both wild-type and proteasome mutant flies, the beatings at different locations in the same heart segment are essentially synchronized. However, between different heart segments, although the beating in the second segment shows a lag in phase behind that of the first segment in a wild-type, in a proteasome mutant, the beating in the second segment becomes significantly leading that of the first segment. Besides the comparison between the wild-type and proteasomal mutant flies, the influences of using different methods for immobilizing flies during OCT scanning on the heart functions are demonstrated.

Microvascular Imaging Using Swept-Source Optical Coherence Tomography with Single-Channel Acquisition

This study proposes a new approach to improve the phase stability for swept-source optical coherence tomography (SS-OCT) with single-channel acquisition. This approach can improve the phase instability due to the A-scan trigger jitter from the swept source, or the asynchronization between the A-scan trigger and high-speed digitizer, which enables the visualization of vascular structures by SS-OCT. Aside from reducing the phase noise of the OCT system, only one channel is required for the A-scan trigger, data storage, and wavelength calibration by implementing the proposed approach. Finally, human skin was scanned in vivo to demonstrate the vascular images.

Method for suppressing the mirror image in Fourier-domain optical coherence tomography

A method, novel to our knowledge, for effective mirror image suppression in Fourier-domain optical coherence tomography based on a phase shift between neighboring A-mode scans is demonstrated. By realizing that the phase shifts of the real and mirror images are mutually reversed and assuming that the real image intensities of the two successive A-mode scans are the same, we can solve a set of two coupled equations to obtain the real image signals. The images based on the scanning of a high-resolution spectral-domain optical coherence tomography system are processed to show effective mirror image suppression results. Compared with a similar method of broad application, our approach has the advantages of shorter process time and higher flexibility in selecting the concerned image portions for processing.

Photothermal optical coherence tomography based on the localized surface plasmon resonance of Au nanoring

The conventional optical coherence tomography (OCT) images based on enhanced scattering and the photothermal (PT) images based on enhanced absorption of the localized surface plasmon (LSP) resonance of Au nanorings (NRIs) in a bio-tissue sample are demonstrated with the scans of an OCT system (1310-nm system), in which the spectral range covers the LSP resonance peak wavelength, and another OCT system (1060-nm system), in which the spectral range is away from the LSP resonance peak wavelength. A PT image is formed by evaluating the modulation frequency (400 Hz) response of an excitation laser with its wavelength (1308 nm) close to the LSP resonance peak at 1305 nm of the Au NRI solution. With the scan of the 1310-nm OCT system, the Au NRI distribution in the bio-tissue sample can be observed in both conventional OCT and PT images. However, with the scan of the 1060-nm OCT system, the Au NRI distribution can be clearly observed only in the PT image. The diffusion process of Au NRIs in the bio-tissue sample can be traced with the scan of either OCT system. Based on phantom experiments, it is shown that the PT image can help in resolving the ambiguity of a conventional OCT image between the enhanced scattering of Au NRIs and the strong scattering of a tissue structure in the 1310-nm OCT scanning. Also, under the condition of weak intrinsic sample scattering, particularly in the scan of the 1060-nm system, the PT signal can be lower than a saturating level, which is determined by the excitation power. By increasing OCT system signal-to-noise ratio or M-mode scan time, the PT signal level can be enhanced.

Noninvasive imaging of heart chamber in Drosophila with dual-beam optical coherence tomography.

The heart chamber of an adult Drosophila is approximately 2 mm long and 0.5 mm wide, and the interwall separation of different heart portions during systole and diastole range from tens of micrometers to hundreds of micrometers. Furthermore, the heart chamber has a curved structure, which results in the larger differences in depth between the different heart portions. However, applying the wavelength calibration process before Fourier transform in an optical coherence tomography (OCT) system may cause degradation in system sensitivity and longitudinal resolution when the optical path difference between the reference and sample arms increases, which makes imaging the entire heart chamber difficult with OCT system. Additionally, since the heartbeat rate of Drosophila is approximately 6 beats/s, a high-speed OCT system is necessary to record the dynamics of the heat beats. In this study, we propose a new approach to visualize the entire heart chamber including the conical chamber and four ostia portions, and to observe the retrograde and anterograde beats. A buffered Fourier-domain mode-locked (FDML) laser is implemented to provide a high imaging speed. Two output ports of the buffered FDML laser are used simultaneously to scan the different heart portions of Drosophila, and the effective A-scan rate of the OCT system can be doubled. Then, the two scanned images are merged into a single B-mode scan. Furthermore, with dual-beam OCT system, the beating behaviors of the different heart portions from 7-day-old and 21-day-old flies are compared.

Computation time-saving mirror image suppression method in Fourier-domain optical coherence tomography.

The theory and experimental results of a computation time-saving mirror image suppression method in Fourier-domain optical coherence tomography, which utilizes the property of reversed system phase shift between the real and mirror images, for differentiating one from the other are demonstrated. By solving a set of two equations based on a reasonable approximation, the real image signal can be obtained. The theoretical backgrounds and the improved real image quality of the average and iteration procedures in this method are particularly illustrated. Also, the mirror image suppression ratios under various process conditions, including different process iteration numbers and different system phase shifts between two neighboring A-mode scans, are evaluated. Meanwhile, the mirror image suppression results based on our method are compared with those obtained from the widely used BM-scan technique. It is found that when a process procedure of two iterations is used, the mirror image suppression quality based on our method can be higher than that obtained from the BM-scan technique. The computation time of our method is significantly shorter than that of the BM-scan technique.

Motion-insensitive optical coherence tomography based micro-angiography

An improved image processing procedure for suppressing the phase noise due to a motion artifact acquired during optical coherence tomography scanning and effectively illustrating the blood vessel distribution in a living tissue is demonstrated. This new processing procedure and the widely used procedure for micro-angiography application are based on the selection of high-frequency components in the spatial-frequency spectrum of B-mode scanning (x-space), which are contributed from the image portions of moving objects. However, by switching the processing order between the x-space and k-space, the new processing procedure shows the superior function of effectively suppressing the phase noise due to a motion artifact. After the blood vessel positions are precisely acquired based on the new processing procedure, the projected blood flow speed can be more accurately calibrated based on a previously reported method. The demonstrated new procedure is useful for clinical micro-angiography application, in which a stepping motor of generating motion artifacts is usually used in the scanning probe.