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The development of high-performance photoacoustic (PA) probes that can monitor disease biomarkers in deep tissue has the potential to replace invasive medical procedures such as a biopsy. However, such probes must be optimized for in vivo performance and exhibit an exceptional safety profile. In this study, we have developed PACu-1, a PA probe designed for biopsy-free assessment (BFA) of hepatic Cu via photoacoustic imaging. PACu-1 features a Cu(I)-responsive trigger appended to an aza-BODIPY dye platform that has been optimized for ratiometric sensing. Owing to its excellent performance, we were able to detect basal levels of Cu in healthy wild-type mice as well as elevated Cu in a Wilson’s disease model and in a liver metastasis model. To showcase the potential impact of PACu-1 for BFA, we conducted two blind studies in which we were able to successfully identify Wilson’s disease animals from healthy control mice in each instance.
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Empirical assessment of laser safety for photoacoustic-guided liver surgeries
Photoacoustic imaging is a promising technique to provide guidance during multiple surgeries and procedures. One challenge with this technique is that major blood vessels in the liver are difficult to differentiate from surrounding tissue within current safety limits, which only exist for human skin and eyes. In this paper, we investigate the safety of raising this limit for liver tissue excited with a 750 nm laser wavelength and approximately 30 mJ laser energy (corresponding to approximately 150 mJ/cm2fluence). Laparotomies were performed on six swine to empirically investigate potential laser-related liver damage. Laser energy was applied for temporal durations of 1 minute, 10 minutes, and 20 minutes. Lasered liver lobes were excised either immediately after laser application (3 swine) or six weeks after surgery (3 swine). Cell damage was assessed using liver damage blood biomarkers and histopathology analyses of 41 tissue samples total. The biomarkers were generally normal over a 6 week post-surgicalin vivostudy period. Histopathology revealed no cell death, although additional pathology was present (i.e., hemorrhage, inflammation, fibrosis) due to handling, sample resection, and fibrous adhesions as a result of the laparotomy. These results support a new protocol for studying laser-related liver damage, indicating the potential to raise the safety limit for liver photoacoustic imaging to approximately 150 mJ/cm2with a laser wavelength of 750 nm and for imaging durations up to 10 minutes without causing cell death. This investigation and protocol may be applied to other tissues and extended to additional wavelengths and energies, which is overall promising for introducing new tissue-specific laser safety limits for photoacoustic-guided surgery.
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- Award ID(s):
- 1751522
- PAR ID:
- 10371687
- Publisher / Repository:
- Optical Society of America
- Date Published:
- Journal Name:
- Biomedical Optics Express
- Volume:
- 12
- Issue:
- 3
- ISSN:
- 2156-7085
- Format(s):
- Medium: X Size: Article No. 1205
- Size(s):
- Article No. 1205
- Sponsoring Org:
- National Science Foundation
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