Abstract

Diagnosis and resection of indeterminate pulmonary nodules (IPNs) is a growing challenge with increased utilization of chest computed tomography. Photoacoustic (PA) -guided surgical resection with local injection of indocyanine green (ICG) may have utility for IPNs that are suspicious for lung cancer. This preclinical study explores the potential of PA imaging (PAI) to detect ICG-labeled tumors. ICG uptake by H460 lung cancer cells was evaluated in vitro. A phantom study was performed to analyze PA signal intensity according to ICG concentration and tissue thickness/depth using chicken breast. PA signals were measured up to 48 hours after injection of ICG (mixed with 5% agar) into healthy subcutaneous tissue, subcutaneous H460 tumors and right healthy lung in nude mice. Intracellular ICG fluorescence was detected in H460 cells co-incubated with ICG in vitro. The concentration dependence of the PA signal was logarithmic, and PA signal decline was exponential with increasing tissue depth. The PA signal of 2 mg/mL ICG was still detectable at a depth of 22 mm in chicken breast. The PA signal from ICG mixed with agar was detectable 48 hours post injection into subcutaneous tissue and subcutaneous H460 tumors in nude mice. Similar features of PA signals from ICG-agar in mice lung were obtained. The results from this preclinical study suggests that PAI of injected ICG-agar may be beneficial for identifying deeply located tumors. These features may be valuable for IPNs.

Highlights

  • With continuing improvements of imaging modalities and the increased application of lowdose computed tomography (CT) for lung cancer screening, more pathology with uncertain significance is detected in the lung parenchyma [1]

  • Fluorescence-guided lung resection has improved with the injection of agents such as indocyanine green (ICG) under preoperative guidance with navigation bronchoscopy [9,10], but it is hampered by limited penetration depth [11,12] and dispersion of injected contrast agents [13,14]

  • No signal was detected in H460 cells without ICG incubation under the IR wavelength while ICG uptake in the cell membrane or cytoplasm were detected in ICG incubated H460 cells under the IR wavelength (Fig 1)

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Summary

Materials and methods

ICG uptake by H460 lung cancer cells was evaluated in vitro. A phantom study was performed to analyze PA signal intensity according to ICG concentration and tissue thickness/ depth using chicken breast. PA signals were measured up to 48 hours after injection of ICG (mixed with 5% agar) into healthy subcutaneous tissue, subcutaneous H460 tumors and right healthy lung in nude mice

Results
Introduction
Discussion
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