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 3

Macroscale tomographic detection of MLM lesions in living mice by MSOT.

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Macroscale tomographic detection of MLM lesions in living mice by MSOT. ...
(A) Establishment of MLM mouse models by intravenous injection of murine B16-F10-Luc cells. Metastatic melanoma growth patterns in the lungs were tracked dynamically using BLI. (B) Organ weight of healthy and MLM lung tissues harvested from mice 19 days after implantation (n = 5). *P < 0.05 by 2-tailed Student’s t test. (C) Cross-sectional atlas from ex vivo mouse cryosection as an anatomic reference. Noninvasive MSOT imaging of (D) healthy and (E) B16-F10 MLM mouse models. Maximum intensity projection (MIP) images are shown in the lower right corners. Associated unmixed mapping images for Hb and HbO2 are provided in Supplemental Figure 1. (F) Representative histology of healthy and MLM lung tissues by H&E staining. An enlarged region shows typical tumor histopathology and intratumoral melanin deposition. (G) Aligned photograph, BLI, 3D reconstructed MSOT, and 3D H&E images of MLM lung tissues. (H) Ex vivo MSOT images of MLM lung tissues spectrally unmixed for melanin, Hb, and HbO2. (I) MSOT intensities of 2 × 104 B16-F10 cells/μL in 2% agarose gel phantoms at different imaging depths.