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Can We Differentiate Residual Untreated Tumor from Tissue Responses to Heat Following Thermal Tumor Ablation?

¹ Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, 1 Deaconess Rd, WCC 308B, Boston, MA 02215 e-mail: sgoldber@caregroup.harvard.edu

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Regardless of the energy source used with image-guided tumor ablation, the techniques used to ensure destruction of an adequate volume of tissue (eg, creating an ablative margin, the use of cytotoxic adjuvants), and the imaging strategy chosen for targeting and controlling the ablation process, there is always a need for long-term imaging follow-up to ensure that no residual viable tumor has been left untreated (1). In this issue of Radiology, Kim et al (2) address differentiation of residual tumor from benign periablational enhancement.

The Science

Gadopentetate dimeglumine is considered a low-molecular-weight extracellular contrast agent (3). Thus over time, it can leak from the intravascular space into the surrounding tissue, limiting the ability to discriminate between tissues with differing microvascularity, especially tumors and inflammation, where the endovascular epithelium is known to be particularly leaky. Given the higher molecular weight of the blood pool contrast agent 24-gadolinium-tetraazacyclododecane tetraacetic acid dendrimer (SH L 643A, Gadomer-17; Schering, Berlin, Germany), it has a reduced diffusion into the extravascular space and thus should enable differentiation of tissues with differing microvascularity.

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The Practice

Clinical use.—Most clinicians adhere to the philosophic perspective that the earliest detection of residual tumor will give the best chance for repeat or alternative therapy to effectively treat the patient (4). However, such detection is compromised by the body’s physiologic response to ablation heating, including the development of benign periablational enhancement (5). This finding usually manifests as a thin rim peripheral to the zone of ablation and typically measures acutely up to 5 mm, but most often 1–2 mm. It is a relatively concentric, symmetric, and uniform process, with smooth inner margins as differentiated from irregular peripheral enhancement (ie, residual tumor). Benign periablational enhancement represents a physiologic response to thermal injury (initially reactive hyperemia and subsequently fibrosis and giant cell reaction). Depending on the protocol used for contrast material–enhanced imaging (injection rate and scanning delay), it can be seen immediately after ablation and can last for up to 6 months. It is most readily appreciated at the arterial phase of computed tomography, with persistent enhancement often seen on delayed magnetic resonance (MR) images. In clinical practice, it represents a barrier to early detection of disease.

Future opportunities and challenges.—Although Kim et al have shown the noteworthy finding that SH L 643A permits more accurate differentiation of benign periablational enhancement from residual tumor than does gadopentetate dimeglumine, additional animal and clinical studies are necessary to prove the potential utility of this agent. The current study was performed in one tumor type (rabbit VX2) implanted in one particular tissue (muscle). Enhancement characteristics of different tumor types and different background organs may vary according to differences in their microvascularity.

In addition to organ-specific validation, clinical studies will be needed to determine how much earlier these agents can help detect residual disease and whether the use of these agents results in improved outcomes, especially since much of the residual disease detected in clinical practice occurs after 1 month, which was the longest follow-up in the Kim et al study. In addition, the SH L 643A agent used in their study does not have wide-scale availability in many countries, including the United States. Other strategies for differentiation with other contrast agents and other imaging modalities are also being explored along with MR spectroscopy to detect active tumor metabolites.

Summary

Kim et al suggest that the MR blood pool contrast agent SH L 643A may enable more accurate differentiation of benign periablational enhancement from residual viable tumor following radiofrequency ablation. This animal study represents a first step in addressing a clinical issue of great importance.

REFERENCES

1. Nahum Goldberg S, Dupuy DE. Image-guided radiofrequency tumor ablation: challenges and opportunities—part I. J Vasc Interv Radiol 2001; 12:1021-1032.[Medline]
2. Kim TJ, Moon WK, Cha JH, et al. VX2 carcinoma in rabbits after radiofrequency ablation: comparison of MR contrast agents for help in differentiating benign periablational enhancement and residual tumor. Radiology 2004; 234:423-430.
3. Caravan P, Ellison JJ, McMurry TJ, Lauffer RB. Gadolinium(III) chelates as MRI contrast agents: structure, dynamics, and applications. Chem Rev 1999; 99:2293-2352.[CrossRef][Medline]
4. Dupuy DE, Goldberg SN. Image-guided radiofrequency tumor ablation: challenges and opportunities—part II. J Vasc Interv Radiol 2001; 12:1135-1148.[Medline]
5. Goldberg SN, Charboneau JW, Dodd GD, 3rd, et al. for the International Working Group on Image-Guided Tumor Ablation. Image-guided tumor ablation: proposal for standardization of terms and reporting criteria. Radiology 2003; 228:335-345.[Abstract/Free Full Text]

This article has been cited by other articles:

				Y. Ni, F. Chen, G. Marchal, T. J. Kim, W. K. Moon, and S. N. Goldberg Differentiation of Residual Tumor from Benign Periablational Tissues after Radiofrequency Ablation: The Role of MR Imaging Contrast Agents * Drs Kim and Moon respond: * Dr Goldberg responds: Radiology, November 1, 2005; 237(2): 745 - 749. [Full Text] [PDF]

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