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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. 

The generalized contrast-to-noise ratio (gCNR) is a relatively new image quality metric designed to assess the probability of lesion detectability in ultrasound images. Although gCNR was initially demonstrated with ultrasound images, the metric is theoretically applicable to multiple types of medical images. In this paper, the applicability of gCNR to photoacoustic images is investigated. The gCNR was computed for both simulated and experimental photoacoustic images generated by amplitude-based (i.e., delay-and-sum) and coherence-based (i.e., short-lag spatial coherence) beamformers. These gCNR measurements were compared to three more traditional image quality metrics (i.e., contrast, contrast-to-noise ratio, and signal-to-noise ratio) applied to the same datasets. An increase in qualitative target visibility generally corresponded with increased gCNR. In addition, gCNR magnitude was more directly related to the separability of photoacoustic signals from their background, which degraded with the presence of limited bandwidth artifacts and increased levels of channel noise. At high gCNR values (i.e., 0.95-1), contrast, contrast-to-noise ratio, and signal-to-noise ratio varied by up to 23.7-56.2 dB, 2.0-3.4, and 26.5-7.6×10²⁰, respectively, for simulated, experimental phantom, andin vivodata. Therefore, these traditional metrics can experience large variations when a target is fully detectable, and additional increases in these values would have no impact on photoacoustic target detectability. In addition, gCNR is robust to changes in traditional metrics introduced by applying a minimum threshold to image amplitudes. In tandem with other photoacoustic image quality metrics and with a defined range of 0 to 1, gCNR has promising potential to provide additional insight, particularly when designing new beamformers and image formation techniques and when reporting quantitative performance without an opportunity to qualitatively assess corresponding images (e.g., in text-only abstracts).