Long‐Duration and Non‐Invasive Photoacoustic Imaging of Multiple Anatomical Structures in a Live Mouse Using a Single Contrast Agent

• Published in: Advanced science 2022-10, Vol.9 (28), p.e2202907-n/a
• Main Authors: Khadria, Anjul, Paavola, Chad D., Zhang, Yang, Davis, Samuel P. X., Grealish, Patrick F., Maslov, Konstantin, Shi, Junhui, Beals, John M., Oladipupo, Sunday S., Wang, Lihong V.
• Format: Article
• Language: English
• Subjects: Animals; Antibodies; Blood vessels; Contrast agents; Contrast Media - chemistry; Diagnostic Imaging; Dyes; Hemoglobin; Immunoglobulin G; lymphatic imaging; Lymphatic Vessels - diagnostic imaging; Lymphatic Vessels - pathology; Mice; Microscopy; nerve imaging; Nervous system; photoacoustic imaging; Photoacoustic Techniques - methods; Skin; Visualization
• ISSN: 2198-3844; 2198-3844
• DOI: 10.1002/advs.202202907

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. This work shows simultaneous imaging of blood and lymphatic vessels, peripheral nerves, and sebaceous glands in a live mouse for several hours through photoacoustic microscopy using sulfo‐cy7.5 dye‐labeled IgG4 antibody as a single contrast agent. The authors also perform photoacoustic computed tomography to visualize deep (0.4 cm) lymphatic vessels in a live mouse for up to 3 h.