Clinical Science: ReviewRadiofrequency tumor ablation: principles and techniques
Introduction
The purpose of this article is to review the basic principles of radiofrequency (RF) thermal ablation with the goal of providing insights into achieving optimal results (i.e. reproducible large volume tissue coagulation) in the safest possible manner. This article will attempt to provide a better understanding of radiofrequency ablation that can hopefully be applied to clinical practice with favorable results. Overviews of potential clinical applications (Gazelle et al., 2000, McGahan and Dodd, 2001), and specific clinical application in the liver (Solbiati et al., 1997a, Solbiati et al., 1997b, Rossi et al., 1998, Curley et al., 1999, Livraghi et al., 1999, Livraghi et al., 2000) and other organs (Anzai et al., 1995, Zlotta et al., 1997, Birdwell et al., 1998, Lewin et al., 1998, Rosenthal et al., 1998, McGovern et al., 1999, Dupuy et al., 2000a, Dupuy et al., 2000b); and comparison to other thermal ablative therapies (Dodd et al., 2000, Goldberg et al., 2000a) can be found elsewhere.
Preparatory to RF heat ablation of a tumor, thin (usually 21–14 gauge) needle-like electrodes are placed directly into the tumor using US, CT, or MR imaging guidance. The RF electrode typically comprises a metal shaft, which is insulated except for an exposed conductive tip that is in direct electrical contact with the targeted tissue volume (Fig. 1a). The RF generator supplies RF power to the tissue through the electrode. It is connected both to the shaft(s) of the RF electrode (and thus the exposed RF electrode tip) and a reference electrode, usually a large area conductive pad contacting the patient's skin in an area of relatively good electrical and thermal conductivity. The RF generator produces a RF voltage between the active RF electrode and the reference electrode, thereby establishing lines of electric field within the patient's body between the two electrodes. At the low RF frequencies used for this procedure (<1 MHz), the electric field pattern is governed essentially by electrostatic equations (Organ, 1976, Cosman et al., 1984). Essentially, the electric field oscillates with the RF frequency, which causes oscillatory movement of ions in the tissue with a velocity that is proportional to the field intensity. The mechanism of tissue heating with RF ablation is frictional (or resistive) energy loss associated with this ionic current.
The main aim of thermal tumor ablation therapy is to destroy an entire tumor using heat to kill the malignant cells in a minimally invasive fashion without damaging adjacent vital structures (Dodd et al., 2000, Gazelle et al., 2000, Goldberg et al., 2000a, McGahan and Dodd, 2001). This often includes the treatment of a 0.5–1 cm margin of apparently normal tissue adjacent to the lesion (i.e., a ‘surgical’ margin) in order to eliminate microscopic foci of disease and the uncertainty which often exists regarding the precise location of actual tumor margins (Dodd et al., 2000, Goldberg et al., 2000a). The parameter governing tissue destruction is temperature. Thus, it is necessary to understand how heat interacts with tissue to induce cell death.
Essentially, it is the generation of the tissue heating that induces cellular death occurs via thermal coagulation necrosis (Cosman et al., 1984, Goldberg et al., 2000b). The volume of RF heat ablation is therefore governed by the temperature distribution within the tissue. The thermal distribution in a targeted lesion can be modeled by the ‘Bio-heat’ equation as previously described by Pennes (1948). We have previously described a simplified framework of viewing thermal ablation along the lines of this equation reduced to a first approximation as ‘Coagulation necrosis=energy deposited×local tissue interactions-heat lost’ (Goldberg et al., 2000a).
Cellular homeostasis can be maintained with mild elevation of temperature to approx. 40°C. When temperatures are increased to 42–45°C (hyperthermia), cells become more susceptible to damage by other agents such as chemotherapy and radiation (Seegenschmiedt et al., 1990, Trembley et al., 1992). However, even prolonged heating at these temperatures will not kill all cells within a given volume, as continued cellular functioning and tumor growth can be observed following relatively long exposure to these temperatures. When temperatures are increased to 46° C for 60 min, irreversible cellular damage occurs (Larson et al., 1996). Increasing the temperature only several degrees to 50–52°C markedly shortens the time necessary to induce cytotoxicity (4–6 min) (Goldberg et al., 1996a). Between 60–100°C, there is near instantaneous induction of protein coagulation which irreversibly damages key cytosolic and mitochondrial enzymes, as well as nucleic acid–histone protein complexes (Zevas and Kuwayama, 1972, Thomsen, 1991, Goldberg et al., 2000b). Cells experiencing this extent of thermal damage most often, but not always, undergo coagulative necrosis over the course of several days. The term ‘coagulation necrosis’ has therefore been used to denote irreversible thermal damage to cells whether or not the ultimate manifestations of cell death fulfill the strict histologic criteria of coagulative necrosis. This last point has significant implications, as it has limited the use of percutaneous biopsy and histologic interpretation as a reliable method for documenting adequate ablation of a tumor. Temperatures greater than 105°C result in tissue boiling, vaporization, and carbonization. These processes usually retard optimal ablation due to a resultant decrease in energy transmission (Goldberg et al., 1996a). Thus, a key aim for ablative therapies is achieving and maintaining a 50–100°C temperature range throughout the entire target volume.
Section snippets
Conventional monopolar electrodes
Earliest use of radiofrequency ablation techniques was primarily geared toward neurosurgical and cardiac applications such as the treatment of hyperactive neurologic foci (Taha et al., 1995, Van Kleef et al., 1996) and aberrant intracardiac conductive pathways (McGahan et al., 1990, Wagshal et al., 1995, Kay and Plumb, 1996). For these conditions, conventional monopolar RF electrodes are adequate as they can induce the required small, but precise foci of tissue destruction. Initial studies of
The quest for increased coagulation diameter
To adequately destroy an entire tumor, the entire lesion must be subject to cytotoxic temperatures. However, the studies described in the prior section documented that monopolar RF energy does not uniformly deposit heat within tissues surrounding the electrode resulting in an increase in the heterogeneity of the electric field as the surface area of the electrode increases (Goldberg et al., 1996a). Thus, in actuality, the tissue heating profile is very disadvantageous for inducing coagulation
Modification of RF electrodes
One of the main key technologic advances in RF technology has been the development of several, often complimentary, strategies for modifying RF electrode design. These modifications which will be described below have been essential for achieving acceptable tissue tumor coagulation.
Tissue heating
It is important to remember that tumor heating at a distance from the electrode surface requires application of energy for sufficient time to enable the heat to radiate from the high temperature electrode source to deeper into the tissues. These properties of heat conduction are innate to the tissue, and cannot readily be overcome with increased energy deposition. If anything, increased energy usually leads to rapid tissue boiling, and decreased coagulation. As a result, longer ablation times
Factors limiting coagulation necrosis in vivo
The substantial gains achieved for tissue coagulation in laboratory experiments have not translated to the same degree of increase in in vivo or clinical studies (Gazelle et al., 2000, Goldberg et al., 2000a, Goldberg et al., 2000b, Goldberg et al., 2000c, Goldberg et al., 2000d, McGahan and Dodd, 2001). Specifically, there are multiple and often tissue specific limitations which prevent heating of the entire tumor volume. Most importantly, there is heterogeneity of heat deposition throughout a
Strategies which decrease tumor tolerance to heat
Strategies which decrease tumor tolerance to heat have been proposed, but as of yet are not well studied. Theoretically, previous insult to the tumor cells by cellular hypoxia (caused by vascular occlusion or antiangiogenesis factor therapy (i.e., endostatin), or prior tumor cell damage from chemotherapy or radiation could be used to increase tumor sensitivity to heat. Synergy between chemotherapeutic agents and hyperthermic temperatures (42–45°C) have already been established (Seegenschmiedt
Principles to improve the safety of RF techniques
A fundamental understanding of RF principles is necessary to ensure maximal safety when performing this procedure in clinical practice. In addition to well know complications from percutaneous needle procedures such as bleeding, infection and pneumothorax, two broad categories of complications that are specific to this method of thermal ablation therapy, including grounding pads burns and thermal damage to adjacent organs, need to be fully addressed.
Conclusions
Preliminary clinical studies encourage optimism about the future of percutaneous minimally-invasive, image-guided RF thermal ablation techniques, particularly for the treatment of hepatic neoplasms. Because the goal of tumor eradication necessitates ablating the entire tumor and a 0.5–1 cm peripheral margin of grossly normal tissue, complete ablation of the entire neoplasm requires the induction of large volumes of coagulation necrosis. Modification of RF energy delivery and/or modulation of
References (59)
- et al.
Radiofrequency tissue ablation: importance of local temperature along the electrode tip exposure in determining lesion shape and size
Acad. Radiol.
(1996) - et al.
Percutaneous radiofrequency tissue ablation: does perfusion-mediated tissue cooling limit coagulation necrosis?
JVIR
(1998) - et al.
Percutaneous radiofrequency tissue ablation: optimization of pulsed-RF technique to increase coagulation necrosis
JVIR
(1999) - et al.
Variables affecting proper system grounding for radiofrequency ablation in an animal model
JVIR
(2000) - et al.
Temperature-correlated histopathologic changes following microwave thermoablation of obstructive tissue in patients with benign prostatic hyperplasia
Urology
(1996) A cooled needle electrode for radiofrequency tissue ablation: thermodynamic aspects of improved performance compared with conventional needle design
Acad. Radiol.
(1996)- et al.
Ex vivo experiment on radiofrequency liver ablation with saline infusion through a screw-tip cannulated electrode
JSR
(1997) - et al.
Hepatic ablation using bipolar radiofrequency electrocautery
Acad. Radiol.
(1996) - et al.
Radiofrequency ablation of renal cell carcinoma via image guided needle electrodes
J. Urol.
(1999) - et al.
Preliminary experience with MR-guided thermal ablation of brain tumors
AJNR
(1995)
Preliminary experience with intraoperative radiofrequency breast tumor ablation
Radiology
Theoretical aspects of radiofrequency lesions in the dorsal root entry zone
Neurosurg
Radiofrequency ablation of unresectable primary and metastatic hepatic malignancies: results in 123 patients
Ann Surg.
Interstitial bipolar RF-thermotherapy (REITT) Therapy planning by computer simulation and MRI-monitoring — a new concept for minimally invasive procedures
Proc SPIE
Minimally invasive treatment of malignant hepatic tumors: at the threshold of a major breakthrough
Radiographics
Percutaneous RF ablation of malignancies in the lung
AJR
Radiofrequency ablation of spinal tumors: temperature distribution in the spinal canal
Am. J. Radiol.
Tumor ablation with radio-frequency energy
Radiology
Tissue ablation with radiofrequency: effect of probe size, ablation duration, and temperature on lesion volume
Acad. Radiol.
Radiofrequency tissue ablation using multiprobe arrays: greater tissue destruction than multiple probes operating alone
Acad. Radiol.
Radiofrequency tissue ablation: increased lesion diameter with a perfusion electrode
Acad. Radiol.
Large volume radiofrequency tissue ablation: increased coagulation with cooled-tip electrodes
Radiology
Large-volume tissue ablation with radiofrequency by using a clustered, internally cooled electrode technique: laboratory and clinical experience in liver metastases
Radiology
Radiofrequency tissue ablation: effect of pharmacologic modulation of blood flow on coagulation diameter
Radiology
Thermal ablation therapy for focal malignancy: a unified approach to underlying principles, techniques, and diagnostic imaging guidance
Am. J. Radiol.
Treatment of intrahepatic malignancy with radiofrequency ablation: radiologic-pathologic correlation
Cancer
Percutaneous tumor ablation: increased coagulation by combining radio-frequency ablation and ethanol instillation in a rat breast tumor model
Radiology
Cited by (355)
Radiofrequency Ablation for Benign Nodules and for Cancer, Too?
2024, Otolaryngologic Clinics of North AmericaOptoresponsive Pheophorbide-Silver based organometallic nanomaterials for high efficacy multimodal theranostics in Melanoma
2023, Chemical Engineering JournalNonsurgical Therapy for Early-Stage Lung Cancer
2023, Hematology/Oncology Clinics of North AmericaRadiofrequency ablation for metastatic bone lesions with vertebral augmentation
2023, Vertebral Augmentation TechniquesEndoscopic ultrasound-guided radiofrequency ablation of pancreatic insulinoma: a state of the art review
2024, Expert Review of Gastroenterology and Hepatology