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This study explores the structure characteristics of thick glaze, in terms of the case study of Chinese Southern Song Guan (SSG) ware, focusing on the bubble and its media structure, using a novel focus-tracking optical coherence tomography (OCT) system. The OCT images we obtained not only unveil the structural uniqueness of the thick-glaze SSG sample, but also establish a distinguishable structural pattern for aiding authentication. In addition, information revealed in our images provides a logical explanation for the subtle texture and tone of SSG glaze as well as insights into the technologies used in layering and firing these thick glazes.

Optical coherence tomography (OCT), a new method for ceramics research, is a non-destructive, three-dimensional tomography system, which provides subsurface morphology visualization of samples based on the refractive index or dielectric constant differences in the target specimen. In this study, seven shards from different Chinese kilns of Song and Yuan dynasties (10‐14th centuries) were scanned to visualize the subsurface morphology of their glazes. The images revealed unique phase assemblage modes in different samples. The results suggest that OCT may be used to identify ceramics and provide information about their manufacturing technology.

Ovarian cancer is the fourth leading cause of cancer-related death among women in the US largely due to late detection secondary to unreliable symptomology and screening tools without adequate resolution. Optical coherence tomography (OCT) is a recently emerging imaging modality with promise in ovarian cancer diagnostics, providing non-destructive subsurface imaging at imaging depths up to 2 mm with near-histological grade resolution (10-20 microm). In this study, we developed the first ever laparoscopic OCT (LOCT) device, evaluated the safety and feasibility of LOCT, and characterized the microstructural features of human ovaries in vivo.A custom LOCT device was fabricated specifically for laparoscopic imaging of the ovaries in patients undergoing oophorectomy. OCT images were compared with histopathology to identify preliminary architectural imaging features of normal and pathologic ovarian tissue.Thirty ovaries in 17 primarily peri- or post-menopausal women were successfully imaged with LOCT: 16 normal, 5 endometriosis, 3 serous cystadenoma, and 4 adenocarcinoma. Preliminary imaging features developed for each category reveal qualitative differences in the homogeneous character of normal post-menopausal ovary, the ability to image small subsurface inclusion cysts, and distinguishable features for endometriosis, cystadenoma, and adenocarcinoma.We present the development and successful implementation of the first laparoscopic OCT probe. Comparison of OCT images and corresponding histopathology allowed for the description of preliminary microstructural features for normal ovary, endometriosis, and benign and malignant surface epithelial neoplasms. These results support the potential of OCT both as a diagnostic tool and an imaging modality for further evaluation of ovarian cancer pathogenesis.

Super-resolution microscopy techniques - capable of overcoming the diffraction limit of light - have opened new opportunities to explore subcellular structures and dynamics not resolvable in conventional far-field microscopy. However, relying on staining with exogenous fluorescent markers, these techniques can sometimes introduce undesired artifacts to the image, mainly due to large tagging agent sizes and insufficient or variable labeling densities. By contrast, the use of endogenous pigments allows imaging of the intrinsic structures of biological samples with unaltered molecular constituents. Here, we report label-free photoacoustic (PA) nanoscopy, which is exquisitely sensitive to optical absorption, with an 88 nm resolution. At each scanning position, multiple PA signals are successively excited with increasing laser pulse energy. Because of optical saturation or nonlinear thermal expansion, the PA amplitude depends on the nonlinear incident optical fluence. The high-order dependence, quantified by polynomial fitting, provides super-resolution imaging with optical sectioning. PA nanoscopy is capable of super-resolution imaging of either fluorescent or nonfluorescent molecules.

The fundamental limitations of photoacoustic microscopy for detecting optically absorbing molecules are investigated both theoretically and experimentally. We experimentally demonstrate noise-equivalent detection sensitivities of 160,000 methylene blue molecules (270 zeptomol or 2.7×10^(−19) mol) and 86,000 oxygenated hemoglobin molecules (140 zeptomol) using narrowband continuous-wave photoacoustics. The ultimate sensitivity of photoacoustics is fundamentally limited by thermal noise, which can present in the acoustic detection system as well as in the medium itself. Under the optimized conditions described herein and using commercially available detectors, photoacoustic microscopy can detect as few as 100s of oxygenated hemoglobin molecules. Realizable improvements to the detector may enable single molecule detection of select molecules.

Recently, a number of optical imaging modalities have achieved single molecule sensitivity, including photothermal imaging, stimulated emission microscopy, ground state depletion microscopy, and transmission microscopy. These optical techniques are based on optical absorption contrast, extending single-molecule detection to non-fluorescent chromophores. Photoacoustics is a hybrid technique that utilizes optical excitation and ultrasonic detection, allowing it to scale both the optical and acoustic regimes with 100% sensitivity to optical absorption. However, the sensitivity of photoacoustics is limited by thermal noise, inherent in the medium itself in the form of acoustic black body radiation. In this paper, we investigate the molecular sensitivity of photoacoustics in the context of the thermal noise limit. We show that single molecule sensitivity is achievable theoretically at room temperature for molecules with sufficiently fast relaxation times. Hurdles to achieve single molecule sensitivity in practice include development of detection schemes that work at short working distance

Optical polarimetry is used in pharmaceutical drug testing and quality control for saccharide-containing products (juice, honey). More recently, it has been proposed as a method for noninvasive glucose sensing for diabetic patients. Sagnac interferometry is commonly used in optical gyroscopes, measuring minute Doppler shifts resulting from mechanical rotation. In this work, we demonstrate that Sagnac interferometers are also sensitive to optical rotation, or the rotation of linearly polarized light, and are therefore useful in optical polarimetry. Results from simulation and experiment show that Sagnac interferometers are advantageous in optical polarimetry as they are insensitive to net linear birefringence and alignment of polarization components.

Optical coherence tomography (OCT) can provide new insight into disease progression and therapy by enabling nondestructive, serial imaging of in vivo cancer models. In previous studies, we have shown the utility of endoscopic OCT for identifying adenomas in the azoxymethane-treated mouse model of colorectal cancer and tracking disease progression over time. Because of improved imaging speed made possible through Fourier domain imaging, three-dimensional imaging of the entire mouse colon is possible. Increased amounts of data can facilitate more accurate classification of tissue but require more time on the part of the researcher to sift through and identify relevant data. We present quantitative software for automatically identifying potentially diseased areas that can be used to create a two-dimensional "disease map" from a three-dimensional Fourier domain OCT data set. In addition to sensing inherent changes in tissue that occur during disease development, the algorithm is sensitive to exogeneous highly scattering gold nanoshells that can be targeted to disease biomarkers. The results of the algorithm were compared to histological diagnosis. The algorithm was then used to assess the ability of gold nanoshells targeted to epidermal growth factor receptor in vivo to enable functional OCT imaging.

Polarimetric glucose sensing is a promising method for noninvasive estimation of blood glucose concentration. Published methods of polarimetric glucose sensing generally rely on measuring the rotation of light as it traverses the aqueous humor of the eye. In this article, an interferometer is described that can detect polarization changes due to glucose without the use of polarization control or polarization analyzing elements. Without polarizers, this system is sensitive to optical activity, inherent to glucose, but minimally sensitive to linear retardance, inherent to the cornea. The underlying principle of the system was experimentally verified using spectral domain optical coherence tomography. A detection scheme involving amplitude modulation was simulated, demonstrating sensitivity to clinically relevant glucose concentrations and an acceptable error due to time varying linear birefringence of the cornea using Clarke Error Grid Analysis.

Increased vascular endothelial growth factor (VEGF) receptor expression has been found at the sites of angiogenesis, particularly in tumor growth areas, as compared with quiescent vasculature. An increase in VEGF receptor-2 is associated with colon cancer progression. The in vivo detection of VEGF receptor is of interest for the purposes of studying basic mechanisms of carcinogen esis, monitoring the efficacy of chemopr eventive and therapeutic agents, and clinical diagnosis. In this study, a novel single chain (sc) VEGF-based molecular probe is utilized in the AOM-treated mouse model of colorectal cancer to stud y delivery route and specificity for disease. The probe was constructed by site-specific conjugation of a near-infrared fluorescent dye, Cy5.5, to scVEGF and detected in vivo with a dual-modality optical coherence tomography / laser-induced fluorescence (OCT/LIF) endoscopic system. The LIF excitation source was a 633 nm He:Ne laser and red/near-infrared fluorescence wa s detected with a spectrometer. OCT was used to obtain two-dimensional longitudinal tomograms at eight rotations in the distal colon. Fluorescence emission levels were correlated with OCT-detected disease in vivo and H&E stained histology slides ex vivo. Specificity for disease was found to be highly dependent on the delivery route. Intravenous injection resulted in poor specificity due to many extra-colon confounders, while colon lavage eliminated most of the non-tumor uptake. High fluorescence emission intensity was correlated with tumor presence as detected using OCT. Re sults suggest potential for clinical use to facilitate earlier diagnosis of cancer. Keywords: optical coherence tomography, laser-induced fluorescence, angiogenesis, vascular endothelial growth factor receptor, colon cancer

Ovarian cancer is the fourth leading cause of cancer-related death among women in the United States. If diagnosed at an early stage, the 5-year survival rate is 94%, but drops to 68% for regional disease and 29% for distant metastasis; only 19% of all cases are diagnosed at the early, localized stage. Optical coherence tomography is a recently emerging nondestructive imaging technology, achieving high axial resolutions (10-20 microns) at imaging depths up to 2 mm. Previously, we studied OCT imaging in normal and diseased human ovary ex vivo to determine the features OCT is capable of resolving. Changes in collagen were suggested with several of the images that correlated with changes in collagen seen in malignancy. Areas of necrosis and blood vessels were also visualized using OCT, indicative of an underlying tissue abnormality. We recently developed a custom side-firing laparoscopic OCT (LOCT) probe fabricated specifically for in vivo laparoscopic imaging. The LOCT probe consists of a 38 mm diameter handpiece terminated in an 280 mm long, 4.6 mm diameter tip for insertion into the laparoscopic trocar and is capable of obtaining up to 9.5 mm image lengths at 10 micron axial resolution. In this study, we utilize the LOCT probe to image one or both ovaries of 20 patients undergoing laparotomy or transabdominal endoscopy and oophorectomy to determine if OCT is capable of identifying and/or differentiating normal and neoplastic ovary. To date, we have laparoscopically imaged the ovaries of ten patients successfully with no known complications.

In previous work we have demonstrated the utility of laser-induced fluorescence (LIF) and optical coherence tomography (OCT) to identify adenoma in mouse models of colorectal cancer with high sensitivity and specificity. However, improved sensitivity to early disease, as well as the ability to distinguish confounders (e.g. fecal contamination, natural variations in mucosal thickness), is desired. In this study, we investigated the signal enhancement of fluorescent and scattering contrast agents in the colons of AOM-treated mice. The fluorescent tracer scVEGF/Cy, targeted to receptors for vascular endothelial growth factor, was visualized on a dual modality OCT/LIF endoscopic system with 1300-nm center wavelength OCT source and 635-nm LIF excitation. Scattering agents were tested with an 890-nm center wavelength endoscopic OCT system. Agents included nanoshells, 120-nm in diameter, and nanorods, 20-nm in diameter by 80-nm in length. Following imaging, colons were excised. Tissue treated with fluorophore was imaged on an epifluorescence microscope. Histological sections were obtained and stained with H&E and silver enhancer to verify disease and identify regions of gold uptake, respectively. Non-specific signal enhancement was observed with the scattering contrast agents. Specificity for adenoma was seen with the scVEGF/Cy dye.

Depth dependent broadening of the axial point spread function due to dispersion in the imaged media, and algorithms for postprocess correction, have been previously described for both time domain and frequency domain optical coherence tomography. We show that homogeneous media dispersion artifacts disappear when frequency domain samples are acquired with uniform spacing in circular wavenumber, as opposed to uniform sampling in optical frequency. We further explicate the source of this point spread broadening and simulate its magnitude in aqueous media. We experimentally demonstrate media dispersion compensation in high dispersion glass by choosing sample frequencies at equal intervals of media index of refraction divided by vacuum wavelength, and we recover unbroadened reflections without an additional postprocessing step.