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Published May 20, 2022 | Submitted + Supplemental Material
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Long-duration and non-invasive photoacoustic imaging of multiple anatomical structures in a live mouse using a single contrast agent


Long-duration in vivo simultaneous imaging of multiple anatomical structures is useful for understanding physiological aspects of diseases, informative for molecular optimization in preclinical models, and has potential applications in surgical settings to improve clinical outcomes. Previous studies involving simultaneous imaging of multiple anatomical structures, e.g., blood and lymphatic vessels as well as peripheral nerves and sebaceous glands, have used genetically engineered mice, which require expensive and time-consuming methods. Here, an IgG4 isotype control antibody is labeled with a near-infrared dye and injected into a mouse ear to enable simultaneous visualization of blood and lymphatic vessels, peripheral nerves, and sebaceous glands for up to 3 hours using photoacoustic microscopy. For multiple anatomical structure imaging, peripheral nerves and sebaceous glands are imaged inside the injected dye-labeled antibody mass while the lymphatic vessels are visualized outside the mass. The efficacy of the contrast agent to label and localize deep medial lymphatic vessels and lymph nodes using photoacoustic computed tomography is demonstrated. The capability of a single injectable contrast agent to image multiple structures for several hours will potentially improve preclinical therapeutic optimization, shorten discovery timelines, and enable clinical treatments.

Additional Information

The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license. Version 1 - May 19, 2022; Version 2 - July 1, 2022. Data availability: The data that support the conclusions are mentioned in the main draft or the supplementary information. Author contributions: L.V.W., S.O., J.M.B, C.D.P., and A.K. conceived the project and the ideas. C.D.P. and A.K. designed the chemistry and parameters for dye labeling. P.G. labeled the antibody with the dye and characterized them. P.G. and A.K. prepared the antibody and dye buffer solutions. A.K. and K.M. designed and built the scanning photoacoustic microscope. A.K. designed and performed all the PAM experiments and analyzed the data. Y.Z. designed the PACT system and data reconstruction algorithm. A.K. and Y.Z. performed the PACT experiments. S.P.X.D. performed the image segmentation for the PAM data and vessel segmentation for the PACT data. J.S. wrote the LabVIEW software for photoacoustic data acquisition. L.V.W., S.O., and J.M.B. supervised the project. A.K. wrote the manuscript. C.D.P., Y.Z., S.P.X.D., J.M.B., S.O., and LV.W. contributed to writing the manuscript. Competing interests: A.K., Y.Z., S.P.X.D., and J.S. declare no competing interests. C.D.P., P.G, J.M.B, and S.O. are employees and stockholders of Eli Lilly and Company. L.V.W. and K.M. have financial interests in Microphotoacoustics, Inc., CalPACT, LLC, and Union Photoacoustic Technologies, Ltd, which did not support this work.

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Submitted - 2022.05.17.491718v2.full.pdf

Supplemental Material - media-1.pdf


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Additional details

August 20, 2023
November 15, 2023