Early detection of neoplastic changes remains a critical challenge in clinical cancer diagnosis and treatment. Many cancers arise from epithelial layers such as those of the gastrointestinal (GI) tract. Current standard endoscopic technology is unable to detect those subsurface lesions. Since cancer development is associated with both morphological and molecular alterations, imaging technologies that can quantitative image tissue’s morphological and molecular biomarkers and assess the depth extent of a lesion in real time, without the need for tissue excision, would be a major advance in GI cancer diagnostics and therapy. In this research, we investigated the feasibility of multi-modal optical imaging including high-resolution optical coherence tomography (OCT) and depth-resolved high-sensitivity fluorescence laminar optical tomography (FLOT) for structural and molecular imaging. APC (adenomatous polyposis coli) mice model were imaged using OCT and FLOT and the correlated histopathological diagnosis was obtained. Quantitative structural (the scattering coefficient) and molecular imaging parameters (fluorescence intensity) from OCT and FLOT images were developed for multi-parametric analysis. This multi-modal imaging method has demonstrated the feasibility for more accurate diagnosis with 87.4% (87.3%) for sensitivity (specificity) which gives the most optimal diagnosis (the largest area under receiver operating characteristic (ROC) curve). This project results in a new non-invasive multi-modal imaging platform for improved GI cancer detection, which is expected to have a major impact on detection, diagnosis, and characterization of GI cancers, as well as a wide range of epithelial cancers.
Point spread function (PSF) phantoms based on unstructured distributions of sub-resolution particles in a transparent matrix have proven effective for evaluating resolution and its spatial variation in optical coherence tomography (OCT) systems. Measurements based on PSF phantoms have the potential to become a standard test method for consistent, objective and quantitative inter-comparison of OCT system performance. Towards this end, we have evaluated three PSF phantoms and investigated their ability to compare the performance of four OCT systems. The phantoms are based on 260-nm-diameter gold nanoshells, submicron-diameter iron oxide particles and 1.5-micron-diameter silica particles. The OCT systems included spectral-domain and swept source systems in free-beam geometries as well as a time-domain system in both free-beam and fiberoptic probe geometries. Results indicated that iron oxide particles and gold nanoshells were most effective for measuring spatial variations in the magnitude and shape of PSFs across the image volume. The intensity of individual particles was also used to evaluate spatial variations in signal intensity uniformity. Significant system-to-system differences in resolution and signal intensity and their spatial variation were readily quantified. The phantoms proved useful for identification and characterization of irregularities such as astigmatism. Particle concentrations of 5000 per cubic millimeter or greater provided accurate determination of performance metrics. Our multi-system inter-comparison provides evidence of the effectiveness of PSF-phantom-based test methods for comparison of OCT system resolution and signal uniformity.
We have developed a line-scanning angled fluorescent laminar optical tomography (LS-aFLOT) system. This system
enables three-dimensional imaging of fluorescent-labeled stem cell distribution within engineered tissue scaffold over a
several-millimeter field-of-view.
Macroporous EH-PEG hydrogels fabricated by porogen-leaching method are characterized by optical coherence
tomography (OCT). High-resolution OCT visualizes the microstructures of the engineered tissue scaffolds in threedimensions.
It also enables subsequent image processing to investigate several key morphological design parameters for
macroporous scaffolds. Image processing algorithms are then presented to automatically quantify the pore size, porosity,
and pore interconnectivity. The results indicated that those parameters highly depend on the porogen size. Further,
fluorescence imaging was conducted to monitor the population of labeled human mesenchymal stem cells (hMSCs)
loaded on the surface of the scaffolds. The results revealed the hMSCs' viability as well as their infiltration into the
scaffold. The effect of infiltration is more profound in the scaffold of larger pore sizes, in accordance with the result
suggested by image analysis.
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