Why Standardization Matters in Pulsed Electric Field Generation for Clinical Electroporation

PFA is a promising technology for treating various medical conditions, including cancer and arrhythmias. (Credit: Advanced Energy)

Pulsed field ablation (PFA) is a nonthermal method of tissue ablation technology that uses high amplitude pulsed electrical fields (PEF) to create irreversible electroporation (IRE) in tissues. Unlike traditional thermal ablation technologies, PFA does not rely on heating to damage and destroy tissue. Instead, PFA creates nanopores in cell membranes due to transient, high-voltage exposure that disrupts cell wall integrity, which leads to cell death.¹

“The emerging field of PFA has the potential to alter the future of ablation therapy,” says Kenneth Stein, MD, senior vice president and chief medical officer, Rhythm Management and Global Health Policy, Boston Scientific.

PFA is a promising technology for treating various medical conditions, including cancer and arrhythmias. These therapies use the pulsed output voltage from a clinical electroporator to induce the biological phenomenon of electroporation in precisely targeted tissue.

Clinical benefits and positive patient outcomes of electroporation are gaining recognition. While this is good news for patients and clinicians, this proliferation is driving the need for a better understanding of PFA waveforms. Standardizing key aspects of the electrical specifications of this technology and the creation of accepted and widely used definitions is important to ensure the optimized, safe and expanded use of this important technology.

Accurately Describing Pulsed Outputs

Pulsed output of PFA (or PEF) generators has poorly defined technical descriptions, leading to practitioners and various research groups commonly applying unclear, confusing or ambiguous descriptions of the pulsed output waveform. In addition, terms such as pulse, burst, and packet are often used interchangeably by various groups and individuals.

A common definition or standard is needed, and a good first step is to fully understand the current situation of the lack of standardization of terms and the issues associated with this.

Fig. 1 - The meaning of *duration* in the specification of an electroporator is often ambiguous and can be interpreted differently.

One example is of a technical specification of one leading clinical electroporation device, in which ‘pulse amplitude’ is described as having possible values of 400, 730 and 900 V. While this sounds straightforward, a definition of ‘pulse amplitude’ is not included. Therefore, there is the risk of different interpretations or assumptions. Without a standard definition, one reader may think the term means maximum pulse amplitude, while another might assume it is a midpoint value. In addition, without adequate definitions, the assertion and definition of more complex parameters such as distortion or accuracy are also hard to ascertain.

A similar problem exists with time-related definitions. For instance, in a typical specification, a pulse duration may be given as 100 μs. However, the term duration is highly ambiguous and can be understood in several ways, as shown in Figure 1.

Uncertainty in defining the pulsed output voltage of a clinical electroporator also affects the waveforms themselves. The term biphasic is a commonly used term but is open to several possible interpretations when used in the context of describing a burst - the most employed waveform from a PEF generator within a clinical electroporator.

The term biphasic — as well as monophasic and triphasic — is regularly used in the specifications of medical defibrillators. But in this application, there is no ambiguity as the terms refer to the number of distinct functions in the clear intervals when the defibrillator is supplying energy. However, holding true to the meaning of biphasic, as applied to defibrillators when describing PEF generator outputs, can lead to issues and confusion.

A so-called biphasic waveform with a burst comprising two separate pulses may or may not include a time separation between the two pulses. So, in the latter, three, not two, separate continuous functions are required to define the waveform, making it unclear if the waveform is classed as biphasic or triphasic. The existence, or not, of pulse separation can lead to the same type of confusion in the case of bursts with more than two pulses in the pulse train.

Standardizing Definitions

A common set of definitions is necessary for the sector to support clear communication between professionals working in the field of electroporation therapy. These definitions are also important to facilitate simple and correct comparison and selection of the optimal electroporator for clinical requirements by those tasked with researching and then procuring equipment.

In addition, clear and logical definitions could provide the basis for definitions to be included in IEC 60601— the series of standards published by the International Electrotechnical Commission covering medical electrical equipment, including electroporators.

To this end, Advanced Energy has been working on a standard set of definitions and terms to describe the pulsed output of PFA generators.^1,2 These provide a clear, unambiguous and measurable set of definitions covering the key technical power parameters, with a particular focus on the typical voltage-controlled burst train output of a PFA generator where each pulse waveform is rectangular in shape. A useful and relatively straightforward potential extension would be to cover current-controlled pulses and other pulse waveforms.

Some of the important parameters covered are pulse amplitude accuracy, distortion and overshoot, plus detailed, robust and unequivocal magnitude, waveform and time definitions. By way of illustration, the set of definitions is used to describe some standard outputs of clinical pulsed field ablation generators.

For example, the pulsed output for high-frequency irreversible electroporation (HFIRE) has been shown to reduce patient pain when under local anesthetic. The term HFIRE does not mean a specific set of pulse parameters but, instead, a burst train waveform with high pulse frequency and low pulse width.

Ensuring an accurate understanding of the relevant related terms is essential to delivering an optimized system, including:

Burst period – the period between the start of a burst with a burst train and the start of the next burst with identical features,

Burst width – the period between the start and end of the burst, and

Burst separation – time duration between the burst stop of a burst and the burst start of the following burst within the burst train.

Table 1. Important parameters for a cardiac PFA.

The same is true when describing the pulsed output for a cardiac PFA using switched bipolar pulses, for which key parameters are shown in Table 1. This table illustrates the need for consistent and well understood definitions and underscores the need for more comprehensive data. As the table indicates, information on certain parameters is not available and leads to uncertainty and interpretation.

Conclusion

PFA generator-related key terms, without unequivocal definitions — including those relating to pulse output and those covering accuracy and distortion— are open to different interpretations or misinterpretation. This has an impact on all aspects of electroporator design and development, not least when it comes to the specification and control of the power supplies that are at the heart of electroporators and other sophisticated electrosurgery equipment.

Advanced Energy has produced two reference documents that are designed to eliminate confusion and simplify the design and development of medical equipment based on pulsed outputs. The first describes the pulsed output voltage of medical PEF generators, while the second outlines a comprehensive range of definitions and terms for these pulsed outputs.^2,³

References

Bradley CJ, Haines DE. “Pulsed field ablation for pulmonary vein isolation in the treatment of atrial fibrillation.” J Cardiovasc Electrophysiol. (2020) 31:2136–47.10.1111/jce.14414.
Robert Ryan. “Describing the Pulsed Output Voltage of a Medical Pulsed-Electric-Field Generator,” AE Technical Journal 2023.
Robert Ryan. “A Standard Set of Definitions and Terms to Describe the Pulsed Output of PEF Generators,” AE Technical Journal 2023.

This article was written by Todd Hudson, Director of Strategic Marketing for Electrosurgery at Advanced Energy, Denver, CO. For more information, visit here .