Chung-Chieh Yu - Academia.edu (original) (raw)

Papers by Chung-Chieh Yu

Optics Letters, 2006

We describe azimuthal light scattering spectroscopy ͑ / LSS͒, a novel technique for assessing epi... more We describe azimuthal light scattering spectroscopy ͑ / LSS͒, a novel technique for assessing epithelial-cell nuclear morphology. The difference between the spectra measured at azimuthal angles =0°and = 90°p referentially isolates the single backscattering contribution due to large ͑ϳ10 m͒ structures such as epithelial cell nuclei by discriminating against scattering from smaller organelles and diffusive background. We demonstrate the feasibility of using / LSS for cancer detection by showing that spectra from cancerous colon tissue exhibit significantly greater azimuthal asymmetry than spectra from normal colonic tissues.

This dissertation reports experimental observations of the fluorescence spectrum of a two-level a... more This dissertation reports experimental observations of the fluorescence spectrum of a two-level atom under a bichromatic optical field excitation. The bichromatic driving field consists of two components with, in general, different field strengths and detunings. Both fields are nearly resonant with the atomic transition. This research is carried out in the resonance fluorescence sub-field of quantum optics. The experiment is

Biomedical Optics and 3-D Imaging, 2012

An algorithm to generate synthesized holograms is described, and the results are validated by com... more An algorithm to generate synthesized holograms is described, and the results are validated by comparing them with an experiment. The system’s axial resolution is analyzed using the algorithm as an example of the algorithm’s capabilities.

Optics Express, 2009

We report a method of assessing the contribution of whole cell body and its nucleus to the clinic... more We report a method of assessing the contribution of whole cell body and its nucleus to the clinically most relevant backward light scattering. We first construct an experimental system that can measure forward scattering and use the system to precisely extract the optical properties of a specimen such as the refractive index contrast, size distribution, and their density. A system that can simultaneously detect the backscattered light is installed to collect the backscattering for the same specimen. By comparing the measured backscattering spectrum with that estimated from the parameters determined by the forward scattering experiment, the contribution of cell body and nucleus to the backward light scattering is quantitatively assessed. For the HeLa cells in suspension, we found that the cell body contributes less than 10% and cell nucleus on the order of 0.1% to the total backscattering signal. Quantitative determination of the origin of backscattered light may help design a system that aims for detecting particular structure of biological tissues.

Biomedical Optics and 3-D Imaging, 2012

A spatial-filtering method for demodulating interlace-sampled off-axis digital holograms is appli... more A spatial-filtering method for demodulating interlace-sampled off-axis digital holograms is applied to holograms made in monochromatic illumination using a color sensor. The end results are high dynamic-range images. Includes experimental results.

Biomedical Optics, 2008

... Michael S. Feld, Condon Lau, Obrad Scepanovic, Sasha McGee, Jelena Mircovic, ChungChieh Yu, S... more ... Michael S. Feld, Condon Lau, Obrad Scepanovic, Sasha McGee, Jelena Mircovic, ChungChieh Yu, Steve Fulghum1, James Tunnell2, Vadim Backman3, Irene ... 1] Perelman, LT, Backman, V, Wallace, M, Zonios, G, Manoharan, R, Nusrat, A, Shields, S, Seiler, M, Lima, C, Hamano ...

Biomedical Optics, 2008

ABSTRACT We have extended quantitative spectroscopy from a single pixel, contact probe to a wide ... more ABSTRACT We have extended quantitative spectroscopy from a single pixel, contact probe to a wide area, non-contact imaging system. Quantitative Spectroscopic Imaging is used to distinguish high grade from low grade dysplasia and non-dysplastic tissue.

PLoS ONE, 2012

There continues to be a significant clinical need for rapid and reliable intraoperative margin as... more There continues to be a significant clinical need for rapid and reliable intraoperative margin assessment during cancer surgery. Here we describe a portable, quantitative, optical fiber probe-based, spectroscopic tissue scanner designed for intraoperative diagnostic imaging of surgical margins, which we tested in a proof of concept study in human tissue for breast cancer diagnosis. The tissue scanner combines both diffuse reflectance spectroscopy (DRS) and intrinsic fluorescence spectroscopy (IFS), and has hyperspectral imaging capability, acquiring full DRS and IFS spectra for each scanned image pixel. Modeling of the DRS and IFS spectra yields quantitative parameters that reflect the metabolic, biochemical and morphological state of tissue, which are translated into disease diagnosis. The tissue scanner has high spatial resolution (0.25 mm) over a wide field of view (10 cm610 cm), and both high spectral resolution (2 nm) and high spectral contrast, readily distinguishing tissues with widely varying optical properties (bone, skeletal muscle, fat and connective tissue). Tissue-simulating phantom experiments confirm that the tissue scanner can quantitatively measure spectral parameters, such as hemoglobin concentration, in a physiologically relevant range with a high degree of accuracy (,5% error). Finally, studies using human breast tissues showed that the tissue scanner can detect small foci of breast cancer in a background of normal breast tissue. This tissue scanner is simpler in design, images a larger field of view at higher resolution and provides a more physically meaningful tissue diagnosis than other spectroscopic imaging systems currently reported in literatures. We believe this spectroscopic tissue scanner can provide real-time, comprehensive diagnostic imaging of surgical margins in excised tissues, overcoming the sampling limitation in current histopathology margin assessment. As such it is a significant step in the development of a platform technology for intraoperative management of cancer, a clinical problem that has been inadequately addressed to date.

Optics Express, 2008

We report a fully quantitative spectroscopy imaging instrument for wide area detection of early c... more We report a fully quantitative spectroscopy imaging instrument for wide area detection of early cancer (dysplasia). This instrument provides quantitative maps of tissue biochemistry and morphology, making it a potentially powerful surveillance tool for objective early cancer detection. We describe the design, construction, calibration, and first clinical application of this new system. We demonstrate its accuracy using physical tissue models. We validate its diagnostic ability on a resected colon adenoma, and demonstrate feasibility of in vivo imaging in the oral cavity.

Journal of Biomedical Optics, 2008

In order to evaluate the impact of anatomy on the spectral properties of oral tissue, we used ref... more In order to evaluate the impact of anatomy on the spectral properties of oral tissue, we used reflectance and fluorescence spectroscopy to characterize nine different anatomic sites. All spectra were collected in vivo from healthy oral mucosa. We analyzed 710 spectra collected from the oral cavity of 79 healthy volunteers. From the spectra, we extracted spectral parameters related to the morphological and biochemical properties of the tissue. The parameter distributions for the nine sites were compared, and we also related the parameters to the physical properties of the tissue site.

Journal of Biomedical Optics, 2009

Model-based light scattering spectroscopy ͑LSS͒ seemed a promising technique for in-vivo diagnosi... more Model-based light scattering spectroscopy ͑LSS͒ seemed a promising technique for in-vivo diagnosis of dysplasia in multiple organs. In the studies, the residual spectrum, the difference between the observed and modeled diffuse reflectance spectra, was attributed to single elastic light scattering from epithelial nuclei, and diagnostic information due to nuclear changes was extracted from it. We show that this picture is incorrect. The actual single scattering signal arising from epithelial nuclei is much smaller than the previously computed residual spectrum, and does not have the wavelength dependence characteristic of Mie scattering. Rather, the residual spectrum largely arises from assuming a uniform hemoglobin distribution. In fact, hemoglobin is packaged in blood vessels, which alters the reflectance. When we include vessel packaging, which accounts for an inhomogeneous hemoglobin distribution, in the diffuse reflectance model, the reflectance is modeled more accurately, greatly reducing the amplitude of the residual spectrum. These findings are verified via numerical estimates based on light propagation and Mie theory, tissue phantom experiments, and analysis of published data measured from Barrett's esophagus. In future studies, vessel packaging should be included in the model of diffuse reflectance and use of model-based LSS should be discontinued.

Journal of Biomedical Optics, 2009

It has long been speculated that underlying variations in tissue anatomy affect in vivo spectrosc... more It has long been speculated that underlying variations in tissue anatomy affect in vivo spectroscopic measurements. We investigate the effects of cervical anatomy on reflectance and fluorescence spectroscopy to guide the development of a diagnostic algorithm for identifying high-grade squamous intraepithelial lesions ͑HSILs͒ free of the confounding effects of anatomy. We use spectroscopy in both contact probe and imaging modes to study patients undergoing either colposcopy or treatment for HSIL. Physical models of light propagation in tissue are used to extract parameters related to tissue morphology and biochemistry. Our results show that the transformation zone, the area in which the vast majority of HSILs are found, is spectroscopically distinct from the adjacent squamous mucosa, and that these anatomical differences can directly influence spectroscopic diagnostic parameters. Specifically, we demonstrate that performance of diagnostic algorithms for identifying HSILs is artificially enhanced when clinically normal squamous sites are included in the statistical analysis of the spectroscopic data. We conclude that underlying differences in tissue anatomy can have a confounding effect on diagnostic spectroscopic parameters and that the common practice of including clinically normal squamous sites in cervical spectroscopy results in artificially improved performance in distinguishing HSILs from clinically suspicious non-HSILs.

Journal of Biomedical Optics, 2013

Quantitative spectroscopy has recently been extended from a contact-probe to wide-area spectrosco... more Quantitative spectroscopy has recently been extended from a contact-probe to wide-area spectroscopic imaging to enable mapping of optical properties across a wide area of tissue. We train quantitative spectroscopic imaging (QSI) to identify cervical high-grade squamous intraepithelial lesions (HSILs) in 34 subjects undergoing the loop electrosurgical excision procedure (LEEP subjects). QSI's performance is then prospectively evaluated on the clinically suspicious biopsy sites from 47 subjects undergoing colposcopic-directed biopsy. The results show the per-subject normalized reduced scattering coefficient at 700 nm (A n) and the total hemoglobin concentration are significantly different (p < 0.05) between HSIL and non-HSIL sites in LEEP subjects. A n alone retrospectively distinguishes HSIL from non-HSIL with 89% sensitivity and 83% specificity. It alone applied prospectively on the biopsy sites distinguishes HSIL from non-HSIL with 81% sensitivity and 78% specificity. The findings of this study agree with those of an earlier contact-probe study, validating the robustness of QSI, and specifically A n , for identifying HSIL. The performance of A n suggests an easy to use and an inexpensive to manufacture monochromatic instrument is capable of early cervical cancer detection, which could be used as a screening and diagnostic tool for detecting cervical cancer in low resource countries.

Biomedical …, 2008

Journal of Biomedical Optics, 2009

Model-based light scattering spectroscopy (LSS) seemed a promising technique for in-vivo diagnosi... more Model-based light scattering spectroscopy (LSS) seemed a promising technique for in-vivo diagnosis of dysplasia in multiple organs. In the studies, the residual spectrum, the difference between the observed and modeled diffuse reflectance spectra, was attributed to single elastic light scattering from epithelial nuclei, and diagnostic information due to nuclear changes was extracted from it. We show that this picture is incorrect. The actual single scattering signal arising from epithelial nuclei is much smaller than the previously computed residual spectrum, and does not have the wavelength dependence characteristic of Mie scattering. Rather, the residual spectrum largely arises from assuming a uniform hemoglobin distribution. In fact, hemoglobin is packaged in blood vessels, which alters the reflectance. When we include vessel packaging, which accounts for an inhomogeneous hemoglobin distribution, in the diffuse reflectance model, the reflectance is modeled more accurately, greatl...

Journal of biomedical …, 2009

We report the observation of multiple laser thresholds in the microlaser. Atom-cavity coupling st... more We report the observation of multiple laser thresholds in the microlaser. Atom-cavity coupling strength and interaction time are well-defined due to traveling-wave interaction and a supersonic atom beam. The number of intra-cavity atoms is large, up to N ˜ 10^3. Experimental data is in good agreement with a rate equation theory. Cavity scanning lineshapes exhibit hysteresis and asymmetry due to

Optics Letters, 2006

Biomedical Optics and 3-D Imaging, 2012

Optics Express, 2009

Biomedical Optics and 3-D Imaging, 2012

Biomedical Optics, 2008

PLoS ONE, 2012

Optics Express, 2008

Journal of Biomedical Optics, 2008

Journal of Biomedical Optics, 2009

Journal of Biomedical Optics, 2013

Biomedical …, 2008

Journal of Biomedical Optics, 2009

Journal of biomedical …, 2009