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 7

Therapeutic monitoring of drug-free NIR-II photothermal ablation by high-sensitivity AR-PAM imaging.

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Therapeutic monitoring of drug-free NIR-II photothermal ablation by high...
(A) Viability of BEAS-2B and B16-F10 cells upon 808 or 1064 nm irradiation for the indicated durations. *P < 0.05 by 1-way ANOVA followed by Tukey’s test. (B) Photoablation efficacies at various laser spot sizes. The output laser power was kept constant at 1.5 W. Dead-cell zones from photoablation were detected by trypan blue staining under phase-contrast bright-field microscopy. (C) Cell viability of B16-F10 as a function of melanin content after 2 W/cm2 photoablation for 5 minutes at 1,064 nm. (D) Time-lapse thermographic imaging of B16-F10 MLM mice models receiving NIR-I or NIR-II photoablation at indicated power densities for various durations. (E) Therapeutic planning and imaging verification of allograft mice bearing B16-F10 MLM tumor burdens. (F) AR-PAM images of lungs harvested from MLM allograft mice at the endpoint after the indicated ablation. Corresponding photographic and US images are in Supplemental Figure 13. (G) The correlation between the AR-PAM intensity and the area of MLM nodules (R = 0.86). The inset highlights the smallest detected lung nodules. (H) The number of MLM nodules in mice receiving different photothermal ablations. (I) Quantified PA intensities at 808 nm. **P < 0.01, ***P < 0.001 by 1-way ANOVA followed by Tukey’s test. NS, P > 0.05.