This Exploratory/Developmental Research (R21) application proposes a new Optical Coherence Tomography (OCT) method that is capable of imaging the concentration and distribution of a specific contrast agent within a biological subject. This method, termed Spectral Triangulation Molecular Contrast Optical Coherence Tomography (MCOCT), will represent a very important advancement in the development of a hybridized imaging modality that combines the advantages of fluorescence contrast microscopy and optical coherence tomography (OCT) - molecular imaging specificity and deeper depth penetration. The method detects contrast agents by seeking their absorption spectrum signatures within the sample. The generality and passivity of the technique implies that it can be used with a very wide range of absorptive dyes. We have already demonstrated that the method is capable of imaging the presence of indocyanine green (ICG), an FDA approved dye, within a biological target. In the research outlined in this application, we propose to dramatically improve upon the technique's implementation and sensitivity. With the completion of the proposed research, we expect that the technology will be sufficiently refined to tackle a wide range of basic research and clinical imaging challenges. The improved penetration depth of our proposed contrast agent based technique will dramatically improve the biologist's capability to trace molecular contrast agents within living tissues by providing optical imaging access through the entire thickness of small animals such as xenopus laevis tadpoles and zebrafish. Immediate examples of applications for basic research include developmental biology study of flow dynamics in zebrafish gills and blood circulatory systems. While potential clinical applications can be found in extensions of current clinical procedures using ICG, such as eneratering 3 dimension mapping of contrast agent distribution in fluorescence angiography and hepatic function diagnosis.
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