Precancerous esophageal epithelia are associated with significantly increased scattering coefficients.

The progression of epithelial precancers into cancer is accompanied by changes of tissue and cellular structures in the epithelium. Correlations between the structural changes and scattering coefficients of esophageal epithelia were investigated using quantitative phase images and the scattering-phase theorem. An ex vivo study of 14 patients demonstrated that the average scattering coefficient of precancerous epithelia was 37.8% higher than that of normal epithelia from the same patient. The scattering coefficients were highly correlated with morphological features including the cell density and the nuclear-to-cytoplasmic ratio. A high interpatient variability in scattering coefficients was observed and suggests identifying precancerous lesions based on the relative change in scattering coefficients.

Cephalochromin induces G0/G1 cell cycle arrest and apoptosis in A549 human non-small-cell lung cancer cells by inflicting mitochondrial disruption.

The fungus-derived compound cephalochromin, isolated from the fermented broth of Cosmospora vilior YMJ89051501, shows growth-inhibitory and apoptotic activity against human lung cancer A549 cells in a concentration-dependent manner with an IC50 value of 2.8 µM at 48 h. Cephalochromin induced cell cycle arrest at the G0/G1 phase through down-regulation of cyclin D1, cyclin E, Cdk 2, and Cdk 4 expressions. Cephalochromin markedly increased the hypodiploid sub-G1 phase (apoptosis) of the cell cycle at 48 h as measured by flow cytometric analysis. Reactive oxygen species generation and loss of the mitochondrial membrane potential (MMP) were also markedly induced by cephalochromin. Moreover, the immunoblotting assays showed that cephalochromin reduced survivin and Bcl-xL expression and induced the activation of caspase-8, -9, and -3 and the cleavage of poly(ADP-ribose) polymerase, indicating the involvement of a caspase signaling cascade. The caspase inhibitor Z-VAD-fmk significantly suppressed cephalochromin-induced apoptosis. Cephalochromin also triggered LC3 II, autophagic marker, expression. Taken together, this is the first report that cephalochromin induced an antiproliferative effect on human lung cancer cells through mitochondrial disruption and down-regulation of survivin, leading to cell cycle arrest at the G0/G1 phase, loss of MMP, and subsequently apoptotic cell death.

Comparative study of protoporphyrin IX fluorescence image enhancement methods to improve an optical imaging system for oral cancer detection.

Optoelectronics techniques to induce protoporphyrin IX fluorescence with topically applied 5-aminolevulinic acid on the oral mucosa have been developed to noninvasively detect oral cancer. Fluorescence imaging enables wide-area screening for oral premalignancy, but the lack of an adequate fluorescence enhancement method restricts the clinical imaging application of these techniques. This study aimed to develop a reliable fluorescence enhancement method to improve PpIX fluorescence imaging systems for oral cancer detection. Three contrast features, red-green-blue reflectance difference, R∕B ratio, and R∕G ratio, were developed first based on the optical properties of the fluorescence images. A comparative study was then carried out with one negative control and four biopsy confirmed clinical cases to validate the optimal image processing method for the detection of the distribution of malignancy. The results showed the superiority of the R∕G ratio in terms of yielding a better contrast between normal and neoplastic tissue, and this method was less prone to errors in detection. Quantitative comparison with the clinical diagnoses in the four neoplastic cases showed that the regions of premalignancy obtained using the proposed method accorded with the expert's determination, suggesting the potential clinical application of this method for the detection of oral cancer.

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.

Enhanced visualization of oral cavity for early inflamed tissue detection.

We describe a color image reconstruction method that enables both direct visualization and direct digital image acquisition from one oral tissue by using various light sources and color compensating filters. In this method, the image of the oral tissue with white light emitting diodes (LEDs) with blue color compensating filter has a larger color difference between the normal and inflamed tissues. The enhanced visualization comes from the white light color mixing between the red normal tissue and bluish white light from the LEDs. With our method, we evaluate the perceived tissue reflectance in each pixel of the image and color reproduction with different illuminated spectra. Our approach to enhancement of visually perceived color difference between normal and inflamed oral tissue involves optimization of illumination and observation conditions by allowing a significant optical contrast of illuminated spectrum to reach the observer's eyes. In comparison with a conventional daylight LED flashlight, a LED with blue filter as the illuminant for oral cavity detection enhances the color difference between normal and inflamed tissues by 32%.

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.

Oral cancer diagnosis with optical coherence tomography.

We use an optical coherence tomography system with a specially designed probe to image the structures of tissues within the oral cavity for the diagnosis of oral precancer and cancer. Various types of oral mucosa, such as gingiva and buccal mucosa, normal and abnormal, can be well distinguished.

Resolution improvement with dispersion manipulation and a retrieval algorithm in optical coherence tomography.

We propose and demonstrate what is to our knowledge a novel technique of improving the spatial resolution of an optical coherence tomography (OCT) system given a non-Gaussian light source spectrum. By using dispersive materials in the reference arm of the OCT system, the resultant dispersion variation led to a full-width at half maximum (FWHM) of the interference fringe envelope smaller than the Fourier transform-limited value of a Gaussian spectral shape with the same spectral FWHM, at the expense of significant tails. The effects of the tails, which would blur the OCT images, were tremendously reduced with a retrieval algorithm. Simulation results and processed OCT scanning images have shown the capability of the proposed technique.