Tumor response for image-guided interventions: ASSESSMENT AND VALIDATION

Radiofrequency ablation

Much of the literature on locoregional tumor treatment focuses on the effects of radiofrequency ablation (RFA) on liver tumors. The concepts are largely applicable to other thermal ablative treatments and to other organ systems. In essence, successful targeted treatment of tumor entails the induction of cell necrosis or programmed cell death (apoptosis) using extreme heat.

Gross pathologic evaluation of the thermally ablated tissue typically reveals a localized hardening of the parenchyma, with a central “white zone” of coagulation and a surrounding “red zone” of hyperemia ( Figure 5-1 ). The zone of coagulation mostly consists of coagulative necrosis, wherein intact nuclei are absent within cells, a finding that is consistent with cell death. Capsular retraction can be seen if the tumor is subcapsular. In the chronic stage, the necrotic tissue hardens, undergoes volume loss, and is often surrounded by a thick fibrous capsule.

RFA functions by imparting frictional energy to a tissue causing destruction (coagulative necrosis) through heat energy. In the most common system, a monopolar system, this energy is created by a rapidly alternating voltage current between the electrode placed within the target lesion (active electrode) and dispersive pads (reference electrode) placed on the patient’s skin. This alternating electrical current, with frequencies in the range of 375–500 kHz, results in agitation of the surrounding tissue ions, resulting in tissue heating. ^, The density of this electrical current is greatest immediately surrounding the electrode, and diminishes with distance. Coagulation necrosis will occur if the tissue temperature is elevated and maintained at 60°C for several seconds. Therapeutic RFA strives to heat tissues in the range of 60–100°C.

Immediately following RFA, conventional hematoxylin and eosin stain will not demonstrate significant change to the tissue other than subtle distortion of sinusoidal architecture. This apparent false negative can be mediated by the use of specialized staining agents, such as the nicotinamide adenine dinucleotide stain, which will highlight devitalized tissue. ^, In the chronic phase, cytolysis and obscuration of the nucleus will result in an amorphous eosinophilic hepatocyte. Infiltration by fibroblasts and mononuclear cells are also seen. Eventually, a capsule of granulation and fibrous tissue forms around the ablation zone. ^,

Cryoablation

The mechanism of tissue injury in percutaneous cryoablation is variable and depends on several factors, including the rate and extent of freezing. Fast freezing rates result in direct tissue injury, whereby ice crystals form within cells. Slower rates result in ice crystals forming in the extracellular spaces resulting in cellular dehydration, leading to membrane damage. ^, Another mechanism of cryoablation-induced tissue injury is expansion of the microvasculature, leading to endothelial damage and subsequent thrombosis. ^, Additionally, sublethal freezing temperatures can lead to apoptosis (programmed cell death), a finding often seen in the periphery of the ablation zone. ^,

Like other thermal ablative technologies, coagulation necrosis is the desired histopathologic endpoint. Lethal temperature is considered to be within −40° to −50°C, although tumor cell survival has been reported after freezing to less than 50°C. Most cryoablation protocols entail two freeze–thaw cycles, which compared to a single cycle, have been shown to result in a larger area of coagulation necrosis on pathologic specimens and in a larger ice ball on imaging.

Conceptually similar to the heat sink phenomenon described in RFA, cryoablation is limited by the delivery of warm blood by vessels adjacent to tumors, resulting in higher than desired temperatures. This is sometimes referred to as the “cold sink,” and it can likewise result in variable size of the ablation zone and extent of the coagulation necrosis. ^,

Microwave ablation

A relatively new treatment option for locoregional control of unresectable tumor is microwave ablation, which employs electromagnetic wavelengths in the frequency range of 900–2450 MHz. Rapid directional current changes in the microwave electrode causes surrounding water dipoles to oscillate, resulting in heat generation leading to cellular coagulative necrosis. Unlike RFA, microwave ablation is not limited by the conductive properties of tissues, and therefore temperatures higher than 100°C can be more easily achieved, theoretically resulting not only in a larger area of coagulation necrosis but also in a more uniform ablation zone as the heat sink effect by regional vessels is less a factor. ^,

Percutaneous ethanol injection

Owing to its ease of use and cost-effectiveness, percutaneous ethanol injection (PEI) remains a viable option in many parts of the world, particularly for the treatment of hepatocellular carcinoma (HCC) in cirrhotic livers. Coagulation necrosis is achieved by both direct and indirect mechanisms. Alcohol instillation will result in immediate cytoplasmic dehydration and protein denaturation. Indirectly, tumor death results following alcohol-induced vascular endothelial necrosis and subsequent thrombosis. Although it is not affected by heat sink, its success is largely limited by the difficulty in obtaining a uniform distillation of ethanol over a large tumor volume. As such, PEI is often not used in tumors with large size, heterogenous or dense composition, and in those without a capsule or pseudocapsule (the latter theoretically would aid in increasing intratumor concentration of alcohol). ^, Given the effectiveness and safety profile of RFA and other thermal ablative technologies, PEI has largely been replaced by these modalities in the treatment of HCC. ^,

Transcatheter embolization

Exploiting the dual blood supply of the liver, transarterial therapy offers a unique adjunct to surgery and systemic chemotherapy. Most often described for nonresectable primary and secondary malignancies in the liver, transcatheter embolization can be further divided into three categories: arterial embolization, chemoembolization, and radioembolization. Extensive discussion of these techniques and their respective indications, risk profiles, and success rates is beyond the scope of this section. Detailed peer-reviewed literature abounds for the interested interventionalist. For our purposes, a short review of their mechanisms and imaging findings will be discussed.