Transmural Ultrasound Imaging of Thermal Lesion and Action Potential Changes in Perfused Canine Cardiac Wedge Preparations by High Intensity Focused Ultrasound Ablation

Abstract

Intra-procedural imaging is important for guiding cardiac arrhythmia ablation. It is difficult to obtain intra-procedural correlation of thermal lesion formation with action potential (AP) changes in the transmural plane during ablation. This study tested parametric ultrasound imaging for transmural imaging of lesion and AP changes in high intensity focused ultrasound (HIFU) ablation using coronary perfused canine ventricular wedge preparations (n = 13). The preparations were paced from epi/endocardial surfaces and subjected to HIFU application (3.5 MHz, 11 Hz pulse-repetition-frequency, 70% duty cycle, duration 4 s, 3500 W/cm2), during which simultaneous optical mapping (1 kframes/s) using di-4-ANEPPS and ultrasound imaging (30 MHz) of the same transmural surface of the wedge were performed. Spatiotemporally correlated AP measurements and ultrasound imaging allowed quantification of the reduction of AP amplitude (APA), shortening of AP duration at 50% repolarization, AP triangulation, decrease of optical AP rise, and change of conduction velocity along tissue depth direction within and surrounding HIFU lesions. The threshold of irreversible change in APA correlating to lesions was determined to be 43±1% with a receiver operating characteristic (ROC) area under curve (AUC) of 0.96±0.01 (n = 13). Ultrasound imaging parameters such as integrated backscatter, Rayleigh (α) and log-normal (σ) parameters, cumulative extrema of σ were tested, with the cumulative extrema of σ performing the best in detecting lesion (ROC AUC 0.89±0.01, n = 13) and change of APA (ROC AUC 0.79±0.03, n = 13). In conclusion, characteristic tissue and AP changes in HIFU ablation were identified and spatiotemporally correlated using optical mapping and ultrasound imaging. Parametric ultrasound imaging using cumulative extrema of σ can detect HIFU lesion and APA reduction.

Electrophysiological Changes Correlated with Temperature Increases Induced by High-Intensity Focused Ultrasound Ablation

“…For example, the APD 50 is longest at endocardium but shortest at epicardium. However, our previous work demonstrated that the changes of APD 50 across the depth direction of myocardium during HIFU ablation were similar (Wu et al 2013), suggesting the temperature-EP correlation derived from the surface measurement can still be applicable for subsurface condition. Nevertheless, the surface measurements in this study where the EP and temperatures were obtained from the same tissue layer can be correlated.…”

“…For the first time, the thermal dose threshold (log 10 ( CEM 43 )) for causing significant APA changes was calculated to be greater than −5.30 ± 0.13. Since APA changes are predominantly affected by the kinetics of sodium ion channels, the slight APA reduction at the early stage is likely due to the changes in diffusion rate of sodium upon HIFU induced temperature increases, whereas multiple effects including rises of RMP, blocking of fast sodium channels (Wu et al 2013), and structural changes of cellular membrane (Jin et al 2006) were potentially involved when temperature was further increased by HIFU and drastic APA reduction occurred.…”

High-intensity Focused Ultrasound In Interventricular Septal Myocardial Ablation: Effects Of Coronary Flow

“…Therefore, the abundant blood ow in the myocardium seriously affects the ablation effect of HIFU. Previous studies have found that under the conditions of the same HIFU intensity and irradiation time, the heat generated in the blood-rich tissues would be quickly removed by the blood ow, and the extent of tissue necrosis would be affected [27] . An abundant vascular bed can not only reduce the peak temperature rise caused by HIFU, but also reduce the size and change the shape of the injury.…”

The Future of Arrhythmias and Electrophysiology

“…The next step is real time assessment of lesion creation which can be potentially provided by methods to measure tissue temperature and assess necrosis. 29–31 High resolution recording methods also have the potential to better define effective ablation lesions. While radiofrequency current will remain a simple, safe and easily applied energy source for ablation, a number of other energy sources for ablation will find applications for difficult arrhythmia substrates.…”

“…The inadequate lesion depth for some intramural substrates will be addressed with bipolar ablation from electrodes bracketing the target area, intramural needle ablation, and alternative energy sources, such as microwave and ultrasound energy, which do not require tissue contact to produce deep tissue heating. 31–34 …”