Non-invasive cardiac pacing with image-guided focused ultrasound

Abstract

Currently, no non-invasive cardiac pacing device acceptable for prolonged use in conscious patients exists. High Intensity Focused Ultrasound (HIFU) can be used to perform remote pacing using reversibility of electromechanical coupling of cardiomyocytes. Here we described an extracorporeal cardiac stimulation device and study its efficacy and safety. We conducted experiments ex vivo and in vivo in a large animal model (pig) to evaluate clinical potential of such a technique. The stimulation threshold was determined in 10 different ex vivo hearts and different clinically relevant electrical effects such as consecutive stimulations of different heart chambers with a single ultrasonic probe, continuous pacing or the inducibility of ventricular tachycardia were shown. Using ultrasonic contrast agent, consistent cardiac stimulation was achievable in vivo for up to 1 hour sessions in 4 different animals. No damage was observed in inversion-recovery MR sequences performed in vivo in the 4 animals. Histological analysis revealed no differences between stimulated and control regions, for all ex vivo and in vivo cases.

Molecular and histological effects of MR-guided pulsed focused ultrasound to the rat heart

“…The main purpose of this study was to examine the molecular and histological changes following pFUS at various PNP to the myocardium. It has recently been shown in preclinical models that image-guided FUS could be used as a noninvasive tool to pace and control heart rate [ 20 – 22 ]. These studies did not evaluate the effects of pFUS on cardiac biomarkers or subsequent molecular or histological changes within the myocardium or adjacent lung [ 29 , 30 ].…”

“…Mechanical forces from pFUS can be modulated by adjusting numerous US parameters such as pulse length, duty cycle, and peak negative pressure (PNP). The potential for pFUS as a noninvasive pacing tool has been superficially explored with promising results [ 20 – 25 ]. Previous reports have superficially examined proteomic and histological changes in ischemic myocardium following ultrasound-mediated microbubble destruction as a means to attract therapeutic stem cells [ 26 – 28 ], but systematic evaluation of pFUS effects on myocardial tissue and the possibility of coincident pulmonary contusion [ 29 , 30 ] is virtually nonexistent.…”

MR‐guided pulsed focused ultrasound improves mesenchymal stromal cell homing to the myocardium

“…39,40 There are several studies demonstrating the potential use of ultrasound (both focused and unfocused) to the heart coupled with MB infusion that generated molecular changes in the myocardium increased tropism of systemically infused stem cells. [16][17][18] It has been reported that pFUS + MB followed by infusion of endothelial progenitor cells in a model of chronic cardiomyopathy in the guinea pig resulted in improvement in LVEF and myocardial perfusion at 20 weeks post-sonication. 19 In acute myocardial infarction rat model, the combination of pFUS + MB results in increased expression of IL-1β, 4, 6, MCP-1 and TNF-α within 15 minutes post-sonication.…”

“…pFUS has been applied for various cardiac applications such as treating cardiac arrhythmias, as a cardiac pacing tool, as a contusion model and as a method to mitigate cardiac diseases. [16][17][18][19] The current study investigates whether pFUS could be used to modify the myocardial microenvironment and increase tropism of IV-injected MSC.…”

Comparison of Combination Stereotactic Body Radiotherapy Plus High-Intensity Focused Ultrasound Ablation Versus Stereotactic Body Radiotherapy Alone for Massive Hepatocellular Carcinoma

“…Thermal high-intensity focused ultrasound (HIFU) ablation has been used as a non-invasive treatment since the mid-twentieth century [11]. This technique uses focused ultrasound beams that are capable of producing complete coagulative necrosis of the target lesions through intact skin [10].…”