Integrated Ultrasound and Photoacoustic-Guided Laser Ablation Theranostic Endoscopic System

Abstract

Advancements in ablation techniques have paved the way towards the development of safer and more effective clinical procedures for treating various maladies such as atrial fibrillation (AF). AF is characterized by rapid, chaotic atrial activation and is commonly treated using radiofrequency applicators or laser ablation catheters. However, the lack of thermal lesion formation and temperature monitoring capabilities in these devices prevents them from measuring the treatment outcome directly. In addition, poor differentiation between healthy and ablated tissues leads to incomplete ablation, which reduces safety and causes complications in patients. Hence, a novel photoacoustic (PA)-guided laser ablation theranostic device was developed around a traditional phased-array endoscope. The proposed technology provides lesion formation, tissue distinguishing, and temperature monitoring capabilities. Our results have validated the lesion monitoring capability of the proposed technology through PA correlation maps. The tissue distinguishing capability of the theranostic device was verified by the measurable differences in the PA signal between pre-and post-ablated mice myocardial tissue. The increase in the PA signal with temperature variations caused by the ablation laser confirmed the ability of the proposed device to provide temperature feedback.

Figure 1:

Design and development of the theranostic device. (a-b) Schematic of the developed theranostic device. The theranostic device comprises of the data acquisition, ablation, and imaging laser systems coupled to a theranostic endoscope. (c) Photograph of the theranostic endoscope. The developed US/PA-guided ablation endoscope contains six fibers for PA imaging and one fiber for ablation. The diameter of the endoscope measures as 6.89 mm.

Figure 2:

Tissue distinguishability and temperature monitoring capabilities of the theranostic device: (a) a schematic of the experimental setup for evaluating the tissue distinguishing and temperature monitoring capabilities of the theranostic device. (b). A schematic of staining study procedure: the sliced myocardial tissue was incubated in 0.5 mg/ml nitrotetrazolium blue solution for 15–30 minutes at a temperature of 37°C. Staining studies were performed to evaluate the extent of tissue ablation.

Figure 3:

Ray tracing simulation illustrating the light pattern formed by the imaging and ablation laser beams on the tissue surface. (a) A schematic illustrating the simulation environment. The illumination pattern for PA imaging is shown in red and the ablation laser beam spot is shown in yellow. (b) The simulation illustrates the alignment of the pulsed and CW laser beams. The ablation beam coincides with the center of the pulse laser illumination pattern at a distance of 8 mm from the endoscope.

Figure 4:

tissue distinguishability capability of the theranostic endoscope: PA images indicating the tissue during (a) pre-ablation and (b) post-ablation scenarios, acquired at the imaging wavelength of $\text{λ}$ = 760 nm. (c) The lesion is indicated using the US image corresponding to the PA image in a, b. The orange contour highlights the border of the rabbit heart tissue (a-c). (d) Variation of the mean of PA signal amplitude in the spectrum ($\text{λ}$ = 740–760 nm) acquired from the surface of the tissue. Results indicate a distinguishable trend between ablated and non-ablated tissue regions.

Figure 5:

Correlation maps validate the tissue distinguishing capability and evaluate the extent of tissue ablation: (a) laser energy compensation was applied on PA data at each wavelength and was normalized. (b) The correlated PA signal’s pattern for each pixel to non-ablated or ablated tissue spectra was superimposed on the US image. The red color refers to the ablated region and blue color refers to the non-ablated areas. The lesion measured as 2.46 mm. (c) Staining studies indicated the depth of the lesion as 2.5 mm. The ablated tissue has no color change, but the healthy tissue turned dark blue, post-staining. The red dashed circle outlines the ablated tissue region.

Figure 6:

temperature monitoring capability of the theransotic system (a). Variation of the PA amplitude with tissue-temperature variations caused by the CW laser. A steady increment in the PA signal is observed, which is in accordance the principles of PA imaging (b) Variation of the PA signal with tissue temperature during pre-and post-ablation scenarios indicating the sole dependence of the PA signal on the tissue’s temperature variations. The black circles indicate the temperature values plotted on the right-hand side Y-axis against time. Error bars indicate the PA amplitude plotted on the left-hand side Y-axis against time. A small change in PA signal is observed from the baseline at same temperatures (20°C), which is due to the lesion formed on the tissue.