Meng-Tsan Tsai

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.

Delineation of an oral cancer lesion with swept-source optical coherence tomography

We demonstrate the ex vivo imaging of an oral cancerous sample with a swept-source optical coherence tomography (SS-OCT) system. With the axial resolution of 8 microm in free space and system sensitivity of 108 dB, we can well distinguish the normal and abnormal tissue portions in a sample. In particular, we analyze the lateral variation of A-scan profiles to show two parameters of SS-OCT signal for delineating an oral cancer lesion. One of the parameters is the decay constant in the exponential fitting of the SS-OCT signal intensity along depth. This decay constant decreases as the A-scan point moves laterally across the margin of a lesion. The other parameter is the standard deviation of the SS-OCT signal intensity fluctuation in an A-scan. This parameter increases significantly when the A-scan point is moved across the transition region between the normal and abnormal portions. Such parameters are useful for determining the margins of oral cancer.

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.

Fabrication of a novel partially dissolving polymer microneedle patch for transdermal drug delivery

Polymer microneedles (MNs) have gained increasing attention as a minimally invasive method for efficiently delivering drugs and vaccines in a patient-friendly manner. Herein, an easy and mild process with O2 plasma treatment was used to fabricate polyvinylpyrrolidone (PVP)-polyvinyl alcohol (PVA) MN patches, and efficient, sustained transdermal delivery was achieved. The diffusion rate of the entrained molecules could be controlled by adjusting the ratio of PVP-PVA. Optical coherence tomography was used to monitor the in vitro penetration in real time and to measure the penetration depth. Rhodamine 6G and fluorescein isothiocyanate-labeled bovine serum albumin (BSA-FITC) were used to explore the potential for using partially dissolving MNs as a transdermal delivery device. Confocal microscopy images revealed that the model drug can gradually diffuse from the puncture sites to a deeper depth. The drug-release profile also demonstrated that the PVP-PVA MNs can provide a successful and sustained release and that the transdermal delivery rate was regulated by the PVP-PVA ratio. Furthermore, the two-stage processing strategy developed in this study provides a simple and easy method for localizing the drug in the needle. The partially dissolving MNs developed in this study may serve as a promising device for controlled drug release and for biological storage applications.

Myocardial tissue characterization based on a polarization-sensitive optical coherence tomography system with an ultrashort pulsed laser

A polarization-sensitive optical coherence tomography (PSOCT) system using a femtosecond-laser as the broadband light source is implemented with the axial resolution of 5 microm in free space. Through the design of path-length difference between the two polarization inputs and the modulation of one of the polarization inputs, the PSOCT images of various input and output polarization combinations can be distinguished and simultaneously collected. The PSOCT system is then used for in vitro scanning of the myocardium tissues of normal and infarcted rat hearts. The destruction of the birefringence nature of the fiber muscle in the infarcted heart can be clearly observed.

Visual perception enhancement for detection of cancerous oral tissue by multi-spectral imaging

Color reproduction systems based on the multi-spectral imaging technique (MSI) for both directly estimating reflection spectra and direct visualization of oral tissues using various light sources are proposed. Images from three oral cancer patients were taken as the experimental samples, and spectral differences between pre-cancerous and normal oral mucosal tissues were calculated at three time points during 5-aminolevulinic acid photodynamic therapy (ALA-PDT) to analyze whether they were consistent with disease processes. To check the successful treatment of oral cancer with ALA-PDT, oral cavity images by swept source optical coherence tomography (SS-OCT) are demonstrated. This system can also reproduce images under different light sources. For pre-cancerous detection, the oral images after the second ALA-PDT are assigned as the target samples. By using RGB LEDs with various correlated color temperatures (CCTs) for color difference comparison, the light source with a CCT of about 4500 K was found to have the best ability to enhance the color difference between pre-cancerous and normal oral mucosal tissues in the oral cavity. Compared with the fluorescent lighting commonly used today, the color difference can be improved by 39.2% from 16.5270 to 23.0023. Hence, this light source and spectral analysis increase the efficiency of the medical diagnosis of oral cancer and aid patients in receiving early treatment.