MR-Guided Liver Interventions
2018-06-01

Image-guided, percutaneous interventions of the liver have rapidly evolved over the last decades and serve as an important tool for diagnosis and therapy of hepatic malignancies.1–3 This applies for technical solutions and available devices as well as possible treatment indications. Although some approaches are still subject to research, others have been embedded into clinical guidelines as routine treatment option.4,5 This accounts in particular for local tumor ablation of primary and secondary hepatic malignancies.1,2 For a safe and effective ablation procedure, a reliable image guidance modality is mandatory. Requirements are good visualization of the target lesion, the applicator, and the surrounding tissue before and during the intervention and the possibility of real-time imaging and multi-planar capabilities.6 In addition, monitoring of the coagulation process is desirable to allow for intraprocedural modifications, if necessary. Moreover, magnetic resonance (MR) image guidance has also proven to serve as a valuable option for liver biopsies, in particular after failure or inconclusive results of previous biopsy approaches.7,8 Although computed tomography (CT) and ultrasound are most commonly used as guidance modalities due to their widespread availability and relatively lower costs in comparison to MRI, they do not fulfill all of the above-mentioned criteria in one way or another, thus making MR imaging (MRI) the most preferable image guidance modality for percutaneous interventions of hepatic malignancies. MR SYSTEMS Using MRI as image guidance modality for interventional procedures offers all MR-specific imaging advantages for planning and monitoring the ablation procedure as well as immediately assessing the treatment response.6 In the beginning, MR-guided interventions were commonly performed with open, low-field (0.2 to 0.6 T) MR systems that enabled adequate access to the patient, however, at the cost of limitations in image quality.9,10 This accounts for both temporal and spatial resolution due to inhomogeneities of the magnetic field and technical restrictions of the gradient systems. In contrast, closed-bore MR systems provided higher field strength allowing for compensation of the shortcomings in image quality, however, with restrictions in patient access.11 This situation has considerably improved over the last decades by introducing open MR systems with higher filed strengths (up to 1 T) or closed-bore systems with a wider bore diameter (typically 1.5 T with a bore diameter up to 70 cm).1,2 In addition, improvements in data acquisition and reconstruction allow for images with higher spatial and temporal resolution—also during free-breathing—using respiration gating strategies and advanced k-space sampling techniques.12,13 This applies for T1-weighted dynamic contrast-enhanced and T2-weighted sequences as well as diffusion-weighted imaging with the potential to improve image quality and reduce motion artifacts.14–16 These developments have paved the way to utilize MRI as a safe and effective image guidance modality for a constantly growing field of indications. ABLATION PROCEDURE MR-guided, percutaneous ablation procedures of primary and secondary hepatic malignancies have become available as a safe and effective treatment option in clinical routine.2,17 Although radiofrequency ablation is the most commonly used ablation technique at present, other approaches are gaining increasing importance and a final evaluation of the different available methods is still outstanding.1,18,19 ABLATION DEVICES The methods used for local tumor ablation are typically divided into chemical and energy-based ablation systems based on the underlying principles causing the tissue destruction. The first comprise all techniques that relay on instillation of chemical agents (eg, acetic acid) into to the index lesion, whereas the second include all methods that transfer energy to the target tissue. The energy-based methods can be further subdivided into thermal (radiofrequency, microwave, ultrasound, cryo-, and laser ablation) and nonthermal systems (irreversible electroporation).20 The decision to use one technique or another depends on the indication and the local expertise at the institution. For MR-guided hepatic tumor ablations, 2 radiofrequency systems, 1 microwave, and 1 cryoablation system are commercially available at present. A summary is provided in Table 1. Although these applicators are specifically designed for MR-guided interventions, no dedicated MR-compatible generators are commercially available. Therefore, appropriate extension cables are necessary to bridge the distance from the generator outside of the MR suite to the MR scanner.TABLE 1: Overview of Commercially Available MR-Compatible Devices for Local Tumor AblationINDICATIONS Indications for local tumor ablation can be subdivided into 2 categories: curative ablation and palliative ablation.20 Curative ablations comprise all indications that aim to totally eradicate the tumor manifestation(s). This most commonly refers to malignant tumors, but also the ablation of benign tumors manifesting with specific symptoms (eg, pain, hormone activity) can be curative when resulting in symptom relief.21,22 In contrast and less frequently, palliative ablation is performed with the intent to control or reduce tumor-related symptoms (such as pain or specific symptoms of neuroendocrine tumors), when total tumor eradication is impossible.23,24 IMAGE GUIDANCE Image guidance is used as assistance during the ablation procedure to ensure safe and complete treatment. Its role can be divided into 5 distinct and separate steps: planning—imaging before the intervention, targeting—imaging for actual guidance of the applicator to the index lesion, monitoring—evaluation of therapy effects during the ablation process, intraprocedural modification—real-time modification of treatment during the ablation process, assessment of immediate treatment response—evaluation and confirmation of treatment end point before the ablation procedure is finally terminated. PLANNING Imaging for intervention planning is performed in 2 subsequent steps. At first, preinterventional imaging is mandatory for selecting suitable patients. This process includes the evaluation of technical feasibility and disease-specific staging.20 Important aspects that need to be considered to meet the criteria of technical feasibility comprise tumor size, number and location, as well as the spatial relationship to anatomical structures at risk during the intervention (eg, blood vessels, bile ducts, or bowl loops).6,20 Disease-specific staging is required as a decision-making tool to ensure that the ablation procedure is reasonably embedded in an oncological treatment concept. This means that target tumor(s) can either be totally eradicated during the ablation procedure with no extrahepatic tumor manifestations present or if present, that extrahepatic tumors can sufficiently be treated in an alternative way. Therefore, the indication for local tumor ablation should always be made on an interdisciplinary basis after carefully evaluating all available treatment options. If the indication for local tumor ablation has been made, planning imaging is also used at the beginning of the intervention for several reasons. At first, adequate visibility of the target tumor(s) and delineation from the surrounding anatomical structures is mandatory. A major advantage of MR-guided tumor ablation in comparison to other image guidance modalities is the high soft tissue contrast.25,26 This allows for optimal planning of the trajectory, often without the need of additional contrast agent. Moreover, different tissue weightings are available for the case that tumor delineation or identification of anatomical structures remain unclear. Furthermore, the administration of contrast agent is another possibility to improve contrast properties of the tissue and allows for a prolonged interval of contrast enhancement in comparison to CT or ultrasound.3 This applies in particular for hepatocyte-specific contrast agent, which may be especially useful for a precise visualization of small target lesions.27 Finally, planning imaging can reveal new, unexpected small lesions with a higher sensitivity than other image guidance modalities with the possibility to treat the additionally detected lesion(s) within the same ablation session (example provided in Fig. 1). This is important, as it might have fundamental impact on the therapy management, if the primarily intended treatment endpoint—total tumor eradication—cannot be achieved anymore.FIGURE 1: Images [unenhanced T1-weigted flash 2D images (A; C) and T2-weighted images (B; D)] of a 58-year-old male patient with colorectal cancer and partial liver resection due hepatic metastasis. Follow-up imaging revealed a new metastasis in segment VII (A; B), which should be treated with radiofrequency ablation. During preinterventional planning imaging, a new, unexpected small metastasis was detected in segment VI (C; D), which probably would have been missed with a different image guidance modality. The metastasis was treated in the same session, and the patient could be discharged from the hospital on the next day as initially planned.Besides visualization of the target tumor, planning imaging also serves as decision-making tool to plan the final trajectory for the applicator from the cutaneous puncture site to the target lesion.6 Moreover, tumor size and its spatial relation to critical surrounding anatomical structures might have changed since preinterventional planning imaging making an alternative device or applicator the more appropriate tool than initially planned.28 Thus, precise planning imaging before the ablation procedure is important for optimal outcome and patient safety. TARGETING The term targeting refers to the actual process of placing the applicator into the target tumor.20 The optimal image guidance modality for precise and safe targeting has to meet several criteria. First, the target tumor and the surrounding anatomical structures as well as the applicator itself should be clearly visible. Second, real-time imaging during the targeting process is desirable to avoid damage of critical anatomic structures while advancing the applicator towards the target tumor. Moreover, this supports the operator to minimize deviation from the initially planned trajectory, which is of particular importance in a moving target tissue, such as the liver. Third, multiplanar imaging with the possibility of choosing arbitrary imaging planes allows for a simultaneous visualization of the applicator and the target tumor, even in difficult localizations. MRI as image guidance is the modality that best matches these criteria, although the total setup might be more complicated than with ultrasound or CT.6 An image example is given in Fig. 2.FIGURE 2: Images of a 28-year-old female patient with a hepatic metastasis of an inflammatory myofibroblastic tumor originating from the colon. The metastasis was treated with microwave ablation. Image A–C show fluoroscopic images while advancing the applicator to the metastasis, clearly depicting the applicator tip (dashed arrow) and the metastasis (arrow), thus allowing for a safe and precise targeting. After positioning, T1-weighted control imaging (D; E) showed the applicator at the craniolateral margin of the metastasis to document the correct placement before starting the coagulation process.MONITORING Monitoring is defined as assessment of therapy effects during the ablation procedure.20 Particular attention in this phase of the intervention should be paid to the ablation zone and their spatial relation to the target tumor. This also includes the observation of the surrounding anatomical structures and whether they are affected from the ablation process.20 Methods for monitoring the coagulation procedure comprise the observation of specific changes in the visual appearance of the treated tissue as well as direct measurement of the ablation temperature. Visual Monitoring Energy-based thermal ablation procedures cause tissue damage by coagulation. This can be visualized by MR-imaging, as the underlying changes in tissue environment are responsible for specific alterations of the MR signal.29,30 Although in general pathologic and radiologic findings show a good correlation, it is important to note that there may be differences in the actual size of the ablated tissue and the signal alterations in the MR image, which has to be taken into account to reduce over- or underestimation.31,32 Typically, the ablation zone shows a characteristic zonal structure due to the continuously decreasing temperature towards the periphery. In the center, coagulation leads to complete tissue destruction. This corresponds to the "white zone" in a histological specimen and will appear moderately hypointense in T2-weighted images, most likely due to tissue dehydration, hyperintense on T1-weigthed images and usually lacks the enhancement of contrast agent.31,33 The central "white zone" is surrounded by a "red zone," representing a transitional area between coagulated tissue and normal liver parenchyma, which is histologically characterized by viable and nonviable cells, inflammation, edema, hyperemia, and accumulation of erythrocytes.33 On MR images, this zone corresponds to a hyperintese rim on T2-weigthed sequences and a rather homogeneously contrast enhancement.31 Problems arise, if irregular or nodular contrast enhancement with a corresponding hyperintese signal in T2-weigted images is depicted, as this may reflect residual, nonablated tumor.34,35 Thus, careful monitoring of the ablation margin is necessary to ensure complete tumor coagulation. Thermal Monitoring The MR signal acquired from different tissue properties is susceptible to temperature changes.29,30 This has led to the development of different imaging techniques that allow for visualization and monitoring of alternating temperature in the examined region. Promising results have been reported for MR spectroscopy, equilibrium magnetization M0, diffusion coefficient, T1 longitudinal relaxation, and proton resonance frequency-phase mapping.29,36 Although these techniques are still subject to research, they may have the potential to improve monitoring of the coagulation process and to more accurately estimate the size of the actually ablated tissue.37,38 INTRAPROCEDURAL MODIFICATION Intraprocedural modifications is a newly introduced definition that replaces the formerly used term "controlling" and summarizes the techniques and tools used to control and modify the ablation process.20 The decisions for intraprocedural modifications are based on the information obtained by monitoring, including thermal, electrical, and imaging-based information.39 This allows the operator to reposition the applicator in case of inefficient energy deposition or incomplete coverage of the target tumor by the ablation zone and to terminate the ablation after a satisfactory result has been achieved. Thermal controlling is typically performed by temperature measurements at the tip of the applicator. To facilitate reliable tissue coagulation, a predefined temperature should be measurable for a specific time.40 If the temperature does not exceed a specific threshold, for example, due to the close proximity of large blood vessels, insufficient energy deposition might be the result with the need for repositioning the applicator.28 However, thermal controlling does not provide any information about the size and shape of the ablation zone, as tissue conductivity varies between individuals. Thus, control imaging with a high spatial resolution is desirable for an accurate estimation of the ablation zone. Besides thermal controlling, also, electrical controlling can provide crucial information about the efficiency of the coagulation process by measuring the impedance of the electrical circuit (monopolar ablation systems) or the tissue resistance (bipolar systems).40,41 This is due to the fact that with increasing coagulation accompanied by tissue dehydration, the impedance, respectively, the resistance, constantly increases. Consequently, the electrical conductivity of the tissue decreases and the energy deposition declines.6 However, likewise to thermal monitoring, no information about the actual size and shape of the ablation zone can be derived from these data. Therefore, reliable control imaging is necessary to determine the actual coagulation zone. The most essential tool to evaluate the necessity for intraprocedural modifications is repeated imaging-based controlling of the target area. This is the only possibility that allows for visualizing the actual location, size, and shape of the ablation zone.6,39 This not only facilitates the decision to terminate the coagulation process after a satisfying ablation zone has been created but also helps to detect residual untreated tumor with the need for repositioning the applicator as well as preventing the involvement of critical anatomical structures adjacent to the ablation site.35 ASSESSMENT OF IMMEDIATE TREATMENT RESPONSE Assessment of immediate treatment response is defined as imaging immediately after the ablation procedure and is done with the purpose to document the successful achievement of the originally intended end point.20 Depending on the indication, this is most common total tumor eradication. In this case, imaging should depict an ablation zone with an appropriate safety margin (5 to 10 mm) around the target tumor.42 Immediate treatment response imaging is often performed with contrast agent and fluid-sensitive sequences, not only for a more accurate delineation of the ablation zone but also to detect possible complications, such as damage of blood vessels, bile ducts, or bleeding. For an image example, refer to Fig. 3.FIGURE 3: Images of a 74-year-old male patient with hepatocellular carcinoma in segment VIII. The tumor is clearly visible as T1-weighted moderately hypointense (A) and T2-weighted hyperintense (B) lesion in preinterventional imaging without contrast agent. Control imaging for assessing immediate treatment response revealed an oval-shaped ablation zone in multiphase contrast-enhanced images (C) and T2-weighted images completely covering the target tumor with an appropriate safety margin.COMPARISON OF DIFFERENT IMAGE GUIDANCE MODALITIES Local tumor ablation can be performed with different image guidance modalities, including ultrasound, CT, and MRI all offering distinct advantages and shortcomings. Ultrasound is a comparably cheap and widely available modality that likewise to MR allows for real-time and multi-planar imaging in arbitrary planes; however, its successful use is dependent on the experience of the operator and the constitution of the patent, which may limit a reliable visualization of the applicator and/or the target tumor.43–45 Moreover, immediate evaluation of treatment effects during and after the ablation is only possible to a limited extent, given the fact that the coagulation process generates gas bubbles.46 Consequently, ultrasound waves are scattered and reflected causing areas of hyperechogenic signal that disguises the actual size and shape of the ablation zone and makes a reliable intraprocedural therapy assessment impossible.45,47 Therefore, subsequent follow-up imaging is necessary to evaluate the treatment response and to decide whether the tumor has been successfully ablated or if an additional session is needed for final tumor eradication.48 CT imaging, likewise to MRI, allows for a more operator and patient-independent image acquisition, including real-time fluoroscopy and the possibility for reconstructing multi-planar reformations.49,50 However, image contrast may be a limiting factor for both reliable visualization of the target tumor and the differentiation of residual tumor and successfully ablated tissue. Even after the administration of contrast agent, the period of improved contrast is relatively short8 and repeated imaging for monitoring and treatment evaluation should be kept at a minimum due to the harmful effects of ionizing radiation.51 COMPLICATIONS Like any other interventional procedure, local tumor ablations in the liver contain the risk of certain complications.52 Although the overall rate, especially of major complications, is relatively low, both the operator and the patient should be aware of them.53 Per definition, major complications include all events that cause severe morbidity requiring hospital admission or increasing/lengthening hospital stay and should be reported as such, following the SIR classification system.20,54 All complications not meeting these criteria are defined as minor complications. Ideally, all complications should be reliably detectable with the modality used for image guidance and the expertise needed to handle them should be readily available at the institution where the procedure is performed to allow for an immediate initiation of adequate therapeutic measures. FOLLOW-UP Follow-up after local tumor ablation therapy is crucial to evaluate technical success as well as technique efficacy and to detect residual unablated tumor or local tumor progression as early as possible. The term technical success describes whether the ablative treatment was successful according to the primary intention.20 Most often, this means complete tumor coverage by the ablation zone with an appropriate safety margin.42,55 If ablative treatment is planned for only 1 session, evaluation of technical success falls under the concept of "assessment of immediate treatment response." If the ablative treatment is divided into several sessions, primary technical success is ought to be evaluated after the final ablation procedure.20 In contrast, technique efficacy can only be evaluated after a certain (usually predefined) time frame of clinical follow-up, in which the tumor is completely ablated.20 As subsequent ablation procedures are not uncommon in an individual patient depending on the course of the disease, a distinction between primary and secondary efficacy rate is important. In this concept, the primary efficacy rate refers to the tumors successfully treated as originally intended, whereas the secondary efficacy rate summarizes successfully reablated tumors after local tumor progression has occurred.20 Residual unablated tumor is defined as any tumor tissue at the ablation margin that can be detected on the first contrast-enhanced follow-up examination. 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