As few incisions and as small as possible is the overwhelming trend in current surgical treatments, a trend strongly driven by robotic-assisted surgery but also by the rapid improvements in ablation technologies and their delivery methods. By delivering high levels of energy — thermal, electrical, mechanical — ablation causes local cell death in order to meet a therapeutic need. With indications spanning cancer, irregular heartbeats (atrial fibrillation), nerve pain, and chronic bronchitis, it has become a widely used and critical treatment method. Alongside this, the ability to transmit ablation energies along catheters, via long needle tips, or even safely through intermediary tissue provides both minimally and non-invasive techniques, reducing the burden on patients and leading to faster recovery times. With so many options and some clear benefits, is there still room for improvement? Almost definitely, but knowing where to go requires an understanding of where we are.
The established technologies
The workhorses of ablation technologies have historically been thermal-based, as with cryogenic and radio frequency (RF) ablation. In cryo-ablation, extremely cold temperatures, typically minus 40 degrees C or less, are used to stress the cells during both freezing and thawing, whereas RF uses resistive electrical heating to reach temperatures of around 60 degrees C. Both result in cell death. These methods each have their champions, with multiple companies offering both options — such as Boston Scientific’s POLARx or BLAZER catheters. Cryo balloons can present shorter surgical times, particularly for pulmonary vein isolation; however, they may increase the risks of bleeding due to a lack of active coagulation during the cold ablation process. Alongside this, RF probes have seen continual advancement to offer force sensing, irrigation (to minimize bubble formation and conduction loss from overheating), and power control (to counteract changes in tissue conductivity during the ablation), but their typical point probe method requires lengthy surgical times. Inherent to both techniques is the reliance on thermal conduction to achieve significant lesion size and a successful ablation. Thermal conductivity in the body is typically good, in some cases too good, and heat loss to the vascular system can reduce ablation effectiveness, whereas heat conduction to adjacent organs can lead to unwanted complications.
The recent advances
In the last decade, a number of new technologies have emerged. These are the result of a dual approach, as researchers further our understanding of cells’ responses to different energy stimuli and develop better methods to control and direct ablation energies, while users push for greater control and selectivity to minimize collateral damage from treatments.
Laser ablation uses high-intensity light, in the near-infrared, delivered through a fiber optic system to apply thermal ablation. As a result, it suffers similar limitations as RF ablation. However, novel balloon-like catheters are in development, such as HeartLight from CardioFocus, that aim to produce ring-shaped lesions in a single application — combining the surgical speed of a cryo-balloon with the clotting benefits of high-temperature thermal ablation, with better energy control. Additionally, these laser ablation optical systems generally have the benefit of being MRI-compatible, making them particularly suitable for neurosurgical ablation, such as Medtronic’s Visualase and Monteris’ NeuroBlate systems.
Microwave ablation, such as the Neuwave from Ethicon, delivers high-temperature thermal ablation with a twist. In the microwave region of the electromagnetic spectrum, the higher frequencies cause direct excitation of polar molecules, resulting in thermal dissipation in the tissue. As this is not a resistive process, the conductivity of the tissue is less important, and microwave ablation can be more effective at immediately increasing the target’s temperature. However, ultimately most of the heat will be conducted to adjacent tissue.
The overall prevalent issue behind thermal ablation techniques is the generally unavoidable heat leak into adjacent tissues. This can be of significant concern during cardiac ablation due to the proximity to the esophagus and the rare but dangerous complication of atrial-esophageal fistula.
The emerging technologies
This issue with thermal ablation has driven researchers to find alternatives, and many believe pulsed-electric-field ablation (PFA) to be the answer. With the major players (Medtronic and Boston Scientific) having acquired PFA catheter companies and multiple startups developing their own solutions for an expanding list of indications, this ablation technology deserves its own discussion. In brief, this technology uses the phenomenon of electroporation, where large electric fields can disrupt a cell’s wall, causing pores to form. Depending on the exact parameters, these pores may heal, or, in the case of irreversible electroporation (IRE) they remain and lead to cell death. The leading advantage here is the flexibility and selectivity of this method. By varying the profile of the applied field, different tissues can be treated (and thus indications met) and, in particular for atrial fibrillation treatments, myocardium tissue appears more sensitive than the esophagus. Finally, as a non-thermal method, there isn’t the worry of heat leaks or the need to overcome the vascular heat bath. PFA is not without issues, though; the human body does not care for large DC electric fields and procedures are needed to account for convulsions and protect the heart’s regular electric signals.
Ultimately, the holy grail is a non-invasive treatment, and high-intensity focused ultrasound (HIFU) is making progress along this line. Focusing ultrasound extra-corporally causes a combined effect of heating and mechanical ablation through microbubble formation. The development of systems, such as the Edison platform from HistoSonics, could lead to a non-invasive tumor treatment without ionizing radiation. With the potential to be a completely non-invasive technique and combine both ablation and imaging systems, HIFU has significant promise. However, investigations of the technology are still early and limitations on treatment position and depth might restrict its adoption.
Is there a non-invasive, highly selective technology?
With so many options, finding the one that gives patients the best results will involve time and a significant number of trials. The ablation space is continually growing with new innovative methods and improvements to existing technologies. With an already crowded space, is there still room for improvement? Two aspects of ablation treatments high on the improvement list are selectivity and non-invasiveness, both hard to fully achieve with any current technology. However, could the next generation of ablation treatments be on the horizon? Nanotechnology has provided huge advancements in the last 40 years and continued efforts with functionalized nanoparticles could outperform all of the above methods. Already used in hyperthermia treatments, could future methods utilize self-locating nanoparticles remotely activated to produce heat, light, or electric fields triggering localized ablation? One thing is clear: transferring intense thermal, electric, or optical energies from source to ablation site through a minimally invasive means is not easy. And new technologies, such as HIFU and PFA, still require significant studies and parameter optimization. So, a true non-invasive, highly selective treatment isn’t here, but it might be just around the corner.
Written by Joe Batley, Senior Physicist
