Cheng-Kuang Lee

Effective indicators for diagnosis of oral cancer using optical coherence tomography

A swept-source optical coherence tomography system is used to clinically scan oral precancer and cancer patients for statistically analyzing the effective indicators of diagnosis. Three indicators are considered, including the standard deviation (SD) of an A-mode scan signal profile, the exponential decay constant (alpha) of an A-mode-scan spatial-frequency spectrum, and the epithelium thickness (T) when the boundary between epithelium and lamina propria can still be identified. Generally, in abnormal mucosa, the standard deviation becomes larger, the decay constant of the spatial-frequency spectrum becomes smaller, and epithelium becomes thicker. The sensitivity and specificity of the three indicators are discussed based on universal and individual relative criteria. It is found that SD and alpha are good diagnosis indicators for moderate dysplasia and squamous cell carcinoma. On the other hand, T is a good diagnosis indicator for epithelia hyperplasia and moderate dysplasia.

Measurement of the hemoglobin oxygen saturation level with spectroscopic spectral-domain optical coherence tomography

We report the measurement of the hemoglobin (Hb) oxygen saturation level in human blood with a spectroscopic spectral-domain optical coherence tomography (SSD-OCT) system based on the crossover behavior of Hb and oxyhemoglobin (HbO(2)) absorption coefficients around 800 nm. By calculating the ratio of the exponential decay constant of A-mode scan signal in the long-wavelength range (>800 nm) over that in the short-wavelength range (<800 nm), the relative oxygen saturation level of Hb can be calibrated. Such a relative level can be used for practical diagnosis application after a golden standard is built by comparing the variation of the OCT result with that of a conventional method, such as the use of a blood gas analyzer. In our experiment, the variation curve based on the SSD-OCT measurement, which has the advantages of noninvasive, real-time, and high-resolution measurements, is coincident with that of using a commercial blood gas analyzer.

Differentiating oral lesions in different carcinogenesis stages with optical coherence tomography

A swept-source optical coherence tomography (SS-OCT) system is used to clinically scan oral lesions in different oral carcinogenesis stages, including normal oral mucosa control, mild dysplasia (MiD), moderate dysplasia (MoD), early-stage squamous cell carcinoma (ES-SCC), and well-developed SCC (WD-SCC), for diagnosis purpose. On the basis of the analyses of the SS-OCT images, the stages of dysplasia (MiD and MoD), and SCC (ES-SCC and WD-SCC) can be differentiated from normal control by evaluating the depth-dependent standard deviation (SD) values of lateral variations. In the dysplasia stage, the boundary between the epithelium (EP) and lamina propria (LP) layers can still be identified and the EP layer becomes significantly thicker than that of normal control. Also, in a certain range of the EP layer above the EP/LP boundary, the SD value becomes larger than a certain percentage of the maximum level, which is observed around the EP/LP boundary. On the other hand, in the ES-SCC and WD-SCC stages, the EP/LP boundary disappears. Because of the higher density of connective tissue papillae in the ES-SCC stage, the SD values of the slowly varying lateral scan profiles in the ES-SCC samples are significantly larger than those in the WD-SCC sample. Also, ES-SCC can be differentiated from WD-SCC by comparing the exponential decay constants of averaged A-mode scan profiles. Because of the higher tissue absorption in the WD-SCC lesion, the decay constants in the WD-SCC samples are significantly higher than those in the ES-SCC samples.

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.

Diagnosis of oral submucous fibrosis with optical coherence tomography

The epithelium (EP) thickness and the standard deviation (SD) of A-mode scan intensity in the laminar propria (LP) layer are used as effective indicators for the diagnosis of oral submucous fibrosis (OSF) based on the noninvasive clinical scanning of a swept-source optical coherence tomography (OCT) system of approximately 6 mum in axial resolution (in tissue) and 103 dB in sensitivity. Compared with the corresponding parameters in healthy oral mucosal mucosa, in OSF mucosa, the EP thickness becomes smaller and the SD of A-mode scan intensity in the LP layer (LP SD) also becomes smaller. The LP SD can also be used for effectively differentiating OSF (small LP SD) from lesion (large LP SD). This application is particularly useful in the case of a lesion without a clear surface feature. Meanwhile, the use of the SD of A-mode scan intensity in the EP layer (EP SD) can further help in differentiating OSF (medium EP SD) from healthy oral mucosal (small EP SD) and lesion (large EP SD) conditions. Compared with the conventional method of maximum mouth opening measurement, the use of the proposed OCT scanning results can be a more effective technique for OSF diagnosis.

Study of photon migration with various source-detector separations in near-infrared spectroscopic brain imaging based on three-dimensional Monte Carlo modeling.

We have simulated photon migration with various sourcedetector separations based on a three-dimensional Monte Carlo code. Whole brain MRI structure images are introduced in the simulation, and the brain model is more accurate than in previous studies. The brain model consists of the scalp, skull, CSF layer, gray matter, and white matter. We demonstrate dynamic propagating movies under different source-detector separations. The multiple backscattered intensity from every layer of the brain model is obtained by marking the deepest layer that every photon can reach. Also, the influences of an absorption target on the brain cortex are revealed.

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.