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Published October 5, 2022 | Supplemental Material + Published
Journal Article Open

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, for example, 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 h 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

© 2022 The Authors. Advanced Science published by Wiley-VCH GmbH. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. The authors acknowledge Rui Cao, California Institute of Technology for useful discussions. Author Contributions. A.K., C.D.P., J.M.B., S.S.O., and L.V.W. 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 experiments, and analyzed and interpreted 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.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.S.O., and L.V.W. contributed to writing the manuscript. Data Availability Statement. The data that support the findings of this study are available from the corresponding author upon reasonable request. Conflict of Interest. A.K., Y.Z., S.P.X.D., and J.S. declare no conflict of interest. C.D.P., P.G., J.M.B., and S.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.

Attached Files

Published - ADVS-9-2202907.pdf

Supplemental Material - advs4419-sup-0001-suppmat.pdf

Supplemental Material - advs4419-sup-0002-movies1.avi

Supplemental Material - advs4419-sup-0003-movies2.avi

Supplemental Material - advs4419-sup-0004-movies3.avi


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Additional details

August 22, 2023
November 15, 2023