Label-free streamlined photoacoustic image guidance facilitates NIR-II photoablation in models of melanoma lung metastases
Wei Xing, Yujia Zhou, Katja Haedicke, Chenyixin Wang, Karla Ximena Vazquez-Prada, Hong Wu, Zhijun Lin, Chrysafis Andreou, Qize Zhang, Ke Shang, Ruoyang Hu, Moritz Kircher, Xingdong Ye, Jan Grimm, Jiang Yang
Wei Xing, Yujia Zhou, Katja Haedicke, Chenyixin Wang, Karla Ximena Vazquez-Prada, Hong Wu, Zhijun Lin, Chrysafis Andreou, Qize Zhang, Ke Shang, Ruoyang Hu, Moritz Kircher, Xingdong Ye, Jan Grimm, Jiang Yang
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Research Article Dermatology Oncology Pulmonology

Label-free streamlined photoacoustic image guidance facilitates NIR-II photoablation in models of melanoma lung metastases

Abstract

Integrative multiscale imaging bridges the gap between macroscopic organ structures and microscopic cellular processes, enabling holistic visualization of anatomy and function across scales. Photoacoustic imaging (PAI) leverages melanin’s potent contrast for label-free melanoma detection, yet its potential in lung imaging, challenged by air-tissue acoustic impedance mismatch, remains unexplored for melanoma lung metastases (MLMs). We used hierarchical multiscale PAI, transitioning from whole-body macroscale to localized mesoscale and single-cell-resolution microscale. PAI also guided photoablation interventions in the first and second near-infrared windows, requiring only 10.4 pg intracellular melanin/cell. Bioinformatic analysis of human MLM tissues revealed perturbed signaling pathways compared with normal skin and lung tissues, accounting for dysfunctional melanogenesis to enable label-free PAI with high sensitivity and specificity. Malignant MLM lesions in living mice, resected mouse lungs, and human lungs were delineated with margins closely conforming to histology. The high sensitivity allowed visualization of low-cellularity microsatellite foci down to a few tens of cell clusters, with sufficient penetration in the lungs of mice and Bama minipigs. The multiscale imaging methodology streamlines a theranostic workflow and specifically identifies MLM burden in a progressive, label-free manner, which may aid real-time tumor ablation in the future.

Authors

Wei Xing, Yujia Zhou, Katja Haedicke, Chenyixin Wang, Karla Ximena Vazquez-Prada, Hong Wu, Zhijun Lin, Chrysafis Andreou, Qize Zhang, Ke Shang, Ruoyang Hu, Moritz Kircher, Xingdong Ye, Jan Grimm, Jiang Yang

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Figure 4

PAI of MLM at mesoscopic and microscopic scales by RSOM and AR-PAM.

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PAI of MLM at mesoscopic and microscopic scales by RSOM and AR-PAM. (A) ...
(A) RSOM images of an MLM lobe with US frequencies split into sub-bands that dictate melanoma-associated major (5–25 MHz low frequencies; red) and minor (25–80 MHz high frequencies; green) vascular structures. (B) H&E and (C) immunofluorescent staining of lung tissue sections from A. Magnified histology views of regions of interest are labeled 1–6. (D) RSOM intensities of 2 × 104 B16-F10 cells/μL in 2% agarose gel phantoms as a function of the imaging depth. (E) Normalized absorption spectra of synthetic melanin, melanogenic B16-F10, and nonmelanogenic BEAS-2B cell suspensions. (F) AR-PAM capillary phantom images and (G) high-resolution cellular images of RBCs, B16-F10, RAW 264.7, and BEAS-2B cells at 532 and 808 nm. US and phase-contrast bright-field images are included as reference frames.