SignificancePhotoacoustic imaging holds promise to provide critical guidance in surgical interventions, but its widespread use is challenged by the absence of applicable safety guidelines across diverse target tissues. The biosafety of this technology is primarily associated with the risk of necrosis generation, which is an irreversible thermal effect that can result from prolonged, high-energy laser applications.AimWe introduce the first known numerical simulation approaches to assess laser-induced necrosis in liver tissue and present a novel microscopy analysis framework to validate performance.ApproachOur simulation methods integrate Monte Carlo simulations of laser-tissue interaction with the COMSOL interface, model local tissue heating, and predict associated tissue damage to quantify the percentage of tissue necrosis resulting from laser application. Our initial predictions are based on 30 and 73 mJ mean laser energies, laser irradiation times of 1, 10, and 20 min, and a 750 nm laser wavelength. Empirical validations with in vivo porcine liver exposed to a mean laser energy of 73 mJ and 750 nm laser wavelength were performed based on H&E and cleaved Caspase-3 immunohistochemistry (IHC) results. Simulation results from the lower 30 mJ laser energy were additionally cross-referenced with previous qualitative H&E-based reports.ResultsNegligible tissue damage was observed with necrosis predictions ≤15.05%, damage thresholds were determined to be within the 15.05% to 66.23% necrosis prediction range, and necrosis predictions deviated from quantitative IHC results by 0.01% to 8.1%.ConclusionsWe successfully demonstrated an in silico alternative to the otherwise time-consuming and expensive empirical assessments that would be required to create tissue-specific laser safety guidelines. The presented methods have the potential to be translated to multiple tissues and additional laser properties.
Flexible transducer arrays have the potential to conform to various organ shapes and sizes during photoacoustic image-guided interventions. However, incorrect sound speeds and array shapes can interfere with photoacoustic target localization and degrade image quality. We propose a metric to estimate the sound speed surrounding a target and the radii of curvature of flexible arrays with approximately concave shapes. The metric is defined as the maximum lag-one spatial coherence of the time-delayed, zero-mean channel data received from a region of interest surrounding a photoacoustic target (which we abbreviate as mLOC). Performance is demonstrated with simulated and experimental phantom data. Three photoacoustic targets were simulated in k-Wave with 1540 m/s medium sound speed, and photoacoustic signals were received by a transducer with a flat shape and an 81.3 mm radius of curvature. To acquire experimental photoacoustic data with the flexible array placed on flat and curved surfaces, an optical fiber paired with a hollow metal needle was inserted into an 83-mm-radius hemispherical plastisol phantom at three locations. When implementing beamforming time delays to calculate mLOC, the associated sound speed and radii of curvature ranged 1080-2000 m/s and 60-120 mm, respectively. The sound speed and array curvature estimated by the maximized mLOC were 1540 m/s and 81 mm, respectively, in simulation, resulting in accuracies of 100% and 99.63%, respectively. The sound speed in the phantom was empirically estimated by the maximum of mLOC as 1543 m/s, which led to the array curvature estimation of 85 mm and the corresponding accuracy of 97.59%. Results demonstrate the potential of mLOC to approximate sound speeds and array radii when these variables are unknown in future flexible array imaging scenarios.
Photoacoustic imaging has recently demonstrated strong viability for tool tip visualization in surgical guidance. The rigidity of conventional transducers requires applied pressure for complete tissue contact when placed on curved organs while flexible arrays are able to conform to different geometries. This work presents photoacoustic images acquired with a rigid laparoscopic transducer and a flexible array transducer on different curved surfaces and provides quantitative comparisons on image quality and transducer characterization. The wider field-of-view and correct target depth in images make the flexible array advantageous for tool tip identification in photoacoustic-guided surgery over the laparoscopic transducer.
With different states of two intrinsic fluorophores, nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) and flavin adenine dinucleotide (FAD), we developed a single-layer autoencoder (AE) for feature extraction, which outputs condensed features representing the full metabolic FLIM information with lower dimensionality. We also described distributions of AE features and fluorescence lifetime redox ratio (FLIRR) from single cells by Gaussian mixture models (GMM), and predicted the values of FLIRR based on feature data from each time point for the HeLa cell lines and Caucasian-American (LNCaP) prostate cancer cell lines by the polynomial regression model and the random forest regression model.
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