Magnetic resonance imaging (MRI) has an established or developing role in the evaluation of post-therapy assessment for oncologic imaging in many organ systems, most notably the brain and liver.1–5 Virtually every organ system can be effectively evaluated in the post-treatment period by MRI. Magnetic resonance, however, possesses the ability to image metabolic activity, through MR spectroscopy (MRS), while providing detailed imaging with MRI. The combination of MRI with MRS has been most extensively used in the post-treatment assessment of brain cancer, and more recently in prostate cancer.6,7 Breast cancer is on the horizon for this evaluation.8 Most evaluations, however, are generally done using MRI alone, but incorporating the use of intravenous gadolinium contrast agents.

Generally, images are acquired early following contrast to provide information on blood delivery, and later (1 to 2 minutes) to provide information on interstitial space. In conjunction with standard noncontrast T1 and T2 weighted images, MRI provides comprehensive information on post-treatment change of cancer.

Our greatest experience with post-treatment evaluation of cancer is with the assessment of liver cancer. We will use the liver as a model to illustrate changes of post-therapeutic intervention.

Resection

Surgical resection causes areas of edema and granulation tissue along the resection margin. On MR imaging, these linear, circular, oval, or serpiginous shaped resection areas are characterized by high signal intensity on T2-weighted images, low signal intensity on T1-weighted images, and homogeneously mild to moderate enhancement on arterial-dominant phase images that fade on interstitial phase images, which tends to resolve in 3 to 5 months.3,9 Residual/recurrent malignancies may occur along the resected margin or in the remainder parenchyma. (Figures 1a–1d) They appear more nodular or masslike with relatively high T2-weighted signal intensity. (Figure 1a) Often they demonstrate imaging findings and enhancement characteristic similar to the pretreatment lesion.10 (Figures 1c–1d)

Figure 1. Recurrent hepatocellular carcinoma (arrows) after the right hepatectomy. The recurrent tumor is detected in the left hepatic lobe close to the resection margin. The tumor, which is moderately hyperintense on T2-weighted fat-suppressed single shot echo train spin echo (a) and hypointense on T1-weighted spoiled gradient echo (b) sequences, demonstrates heterogenous enhancement and delayed washout on the postgadolinium early arterial (c) and late venous (d) phases, respectively.

After radical nephrectomy for kidney cancer, recurrences are common in the renal fossa and commonly associated with distant metastases.11

Systemic Chemotherapy

After effective chemotherapy, decrease in size, number, and vascularity of lesions is observed, and central necrosis may develop.12,13 Decrease of lesional and/or perilesional enhancement of liver metastases is an indicator of response to systemic therapy and shows good correlation with prognosis.12,13 On T2-weighted images, early in the course of therapy, responsive tumor may exhibit high signal intensity reflecting necrosis; but progressively, they show decrease in signal intensity caused by cellular dehydration and reduction in vascularity.5 In the long term, tumors may either disappear or become fibrotic, leaving areas of irregular, angular-shaped foci often with distortion or capsule retraction. (Figures 2a–2e) Mature fibrosis appears as isointensity or low signal intensity on T2-weighted images and moderately low signal intensity on T1-weighted images. On initial postcontrast images, mature fibrosis exhibits negligible enhancement, but tends to enhance progressively on interstitial phase images. Increase in number, size, and/or extent of enhancement on early postcontrast images of tumors after systemic chemotherapy is suggestive of nonresponse.14

Figure 2. Successful treatment of a colon carcinoma metastasis after chemotherapy. In the liver, a colon carcinoma metastasis (arrows), which is mildly hyperintense on T2-weighted fat-suppressed single shot echo train spin echo (a) and hypointense on T1-weighted spoiled gradient echo sequences, is detected. The metastasis demonstrates peripheral enhancement on the postgadolinium SGE sequence (c). The metastasis is successfully treated with the chemotherapy, and it is not detected on corresponding T2-weighted (d), T1-weighted (e), and postgadolinium (f) sequences.

Hormone therapy for prostate cancer results in prostate tissue atrophy and low signal intensity within the prostate in MR imaging.15, 16 Recurrent cancer may be difficult to distinguish from fibrosis, based on the MR imaging alone. In this setting, MRS is helpful, as cancer does not reveal a citrate peak as found in prostate tissue. MRS studies revealed loss of the prostatic metabolites choline, creatine, citrate, and polyamines during hormone-deprivation therapy.7

Radiation Therapy

The most prominent finding of radiation therapy is a well-demarcated area with linear margins conforming to the radiation portal. These areas are moderately high and low signal intensity on T2 and T1 weighted images, respectively. These areas represent acute inflammatory changes and are gradually replaced with fibrosis after 3 months. Recent fibrosis is characterized by a moderate enhancement on early postcontrast images that tends to persist on late images. Chronic fibrosis has the tendency to demonstrate lack of enhancement on all phases. On the other hand, residual or recurrent lesions are nodular or mass-like, have irregular and poorly defined contours, and demonstrate moderately high signal on T2-weighted images and moderate or intense enhancement on arterial phase images.10 The distinction between postradiation non-neoplastic areas and residual or recurrent disease is feasible commencing at 3 months post procedure and can be most accurately determined beyond 1 year after intervention. Between 3 months and 1 year, serial follow-up images generally are required; recurrence commonly increases in size, and radiation changes often regress over time. In most cases, imaging at 3-month intervals is sufficient.

In the abdomen and pelvis, rectal cancer, cervical cancer, and prostate cancer are the malignancies in which radiation therapy is commonly employed. Radiation therapy is generally used in more advanced conditions. Like chemotherapy, radiation induces cell death, resulting in decrease in size and number of malignant lesions and inhibits neovascularization.17,18 Radiation therapy for prostate cancer causes atrophy and fibrosis of glandular tissue and reduction on T2-weighted signal intensity.16,19,20

Ablation

Although complete surgical resection remains the treatment of choice for tumors, minimally invasive interventional techniques have been developed for the treatment of primary and secondary solid parenchymal organ tumors in which complete resection is not feasible or where the less invasive technique is adequate for at least temporary tumor control. Accurate imaging evaluation is important in determining whether a tumor is completely treated or needs additional treatment. Early detection of residual or locally recurrent tumor after ablation is critical and can facilitate successful retreatment at an early stage. Late diagnosis results in potentially extensive regrowth and makes retreatment difficult owing to unfavorable geometry and limited access. Follow-up imaging studies performed at relatively frequent intervals, at least early post-treatment, have been used successfully for early detection of recurrence. Imaging also plays a crucial role in the evaluation of therapy-induced complications.

Although the main purpose of ablation is total cure, these therapies are commonly performed to alleviate clinical symptoms, to achieve tumor regression that enabled subsequent surgical resection, to treat recurrent or metastatic tumors, or to lengthen patient survival until transplantation.21,22 Ablative therapies provide direct tumor destruction. The manner through which the tumor is ablated can be classified as either chemical or thermal ablation. Chemical ablation refers to the use of ethanol injection. Thermal ablation can be subcategorized as follows: by heat (radiofrequency [RF] ablation, microwave ablation, laser ablation, focused ultrasound); and by cold (cryoablation).23 Among all these therapeutic options, RF ablation is currently the most commonly employed approach.23–25

With the reported success of ablative therapies for liver tumors, an increasing number of investigators have applied ablation for the treatment of neoplasms in other abdominal organs, including the kidney, adrenal glands, and lungs.26–28 Ethanol ablation is performed predominantly in the treatment of hepatocellular carcinoma (HCC).24,25

Evolution of Ablated Lesion on MRI

Most thermal therapies induce a central “white zone” of necrosis, a pathologic finding that is generally accepted to represent coagulated tissue, surrounded by a variable inflammatory “red zone” of hyperemia that is usually absent in ex vivo specimens.29 This peripheral zone surrounding the necrotic zone immediately after ablation shows intense inflammatory reaction and hemorrhage on histopathologic examinations, which are progressively replaced by granulation tissue and fibrosis.30–32 The completely necrotic zone usually demonstrates a slow reduction in size with time, but may stay unchanged.31 Small necrotic cavities may result in focal hepatic atrophy with capsule retraction or may disappear completely.

These postablation findings observed on histopathologic examinations are recognized as either changes in perfusion or alterations in the signal intensity on MR imaging. On T2-weighted images, the ablation zones are observed as central hypointense regions, which reliably correspond to the areas of actual cell death and necrosis.33 (Figure 3a.) The appearance of thermal ablation zones on precontrast T1-weighted MR imaging scans is variable, where an ablation zone may appear hypointense, isointense, or slightly or markedly hyperintense.34 (Figures 3b and 3c.) In the immediate postablation period, a uniform, smooth inflammatory rim completely surrounds this necrotic cavity and can be observed as high signal intensity on T2-weighted and moderate to intense enhancement on early postcontrast images.31,32,35 (Figures 3d and 3e.) For the first week to 1 month, the rim width is up to 5 mm. The thickness decreases as the parenchymal inflammatory reaction resolves over time, and is appreciated on MR images as a decrease in the intensity and thickness of the rim enhancement, until it disappears by 6 months after ablation.23,31,32,36 This imaging finding is better appreciated on MRI than on CT because of the greater sensitivity of MRI for contrast enhancement. Up to 1 week after ablation, the necrotic cavity is completely replaced by hemorrhage and liquefactive or coagulative necrosis and shows a wide variation in signal intensity from high to low on T1- and T2-weighted images. The signal intensity on T1-weighted images is determined by the stage of the hemorrhage, whereas the signal intensity on T2-weighted images is influenced by the presence of either coagulative necrosis or liquefactive necrosis.23,31,32 Coagulative necrosis appears as low signal intensity and liquefactive necrosis as high signal intensity on T2-weighted images.32 After contrast administration, the necrotic cavity shows no, or negligible, enhancement on all phases. Within 6 to 12 months of ablation, the necrotic cavity may demonstrate considerable reduction in size and may result in focal hepatic atrophy with capsule retraction or disappear completely, which are findings well demonstrated on MRI.31

Figure 3. Successfully treated hepatocellular carcinoma (arrows) with radiofrequency ablation therapy. Short tau inversion recovery (STIR) (a) and T1-weighted in-phase (b) and out-of-phase (c) spoiled gradient echo (SGE) sequences demonstrate hypointense and hyperintense signal intensity changes, respectively, at the ablation site. These signal changes are consistent with the blood products. Postgadolinium early arterial phase (d) and late venous phase (e) SGE sequences show a thin rim of enhancement that is consistent with the inflammatory response to the therapy. There is no residual tumor.

Thermal ablation zones in the kidneys have a similar appearance to those in the liver, in terms of the temporal evolution of the ablation zone, with some differences. It is reported that RF ablation of kidney tumors resulted in significantly smaller coagulation diameters, probably due to its high perfusion rates.37

Cryoablation zones in liver, kidney, and prostate can also be monitored well with MR imaging. Unlike those after heating, the margins of necrosis following cryoablation are relatively sharp, and the MR imaging–depicted boundaries of the treatment also correlate well with necrosis. The iceballs have been reported as sharply marginated, teardrop-shaped, or ellipsoid regions of signal loss on T1 and T2 weighted images.38–40

Assessment of Treatment Effectiveness on MRI

The evaluation of signal intensity, size, and internal contours of the ablated zone gives important clues about the success of therapy. Complete tumor necrosis is considered to have occurred when follow-up dynamic MRI examination shows a smooth-walled ablated zone with no foci of enhancement within the lesion or at its periphery. The residual or recurrent unablated tumor often grows in a scattered pattern, or intracavitary or eccentric nodular patterns. Local tumor progression areas show enhancement similar to the enhancement patterns of the pretreatment lesion (ie, hypervascular tumors often show moderate to intense enhancement on arterial dominant phase images that persists on late-phase images; hypovascular tumors demonstrate negligible enhancement on early-phase images that progress in intensity over time).10 On postgadolinium scans, only uniform marginal enhancement is a normal finding, whereas any focal nodular enhancement along the margin of the ablation zone should be interpreted as residual tumor or recurrence.36,41,42 (Figures 4b–4d) Peripheral enhancing rims that are inflammatory may sometimes be irregular, but in distinction from cancer they usually appear as transient phenomena on early postcontrast images. Successful ablation is usually shown as an area of thermal necrosis volume exceeding that of the original lesion, with at least a 0.5 to 0.7-cm safety margin of coagulation necrosis in the liver parenchyma surrounding the lesion.43

Figure 4. Hepatocellular carcinoma recurrence after the radiofrequency ablation therapy. T2-weighted fat-suppressed single shot echo train spin echo (a) and T1-weighted spoiled gradient echo (SGE) (b) sequences demonstrate mixed hyper-hypointense and hyperintense signal changes (arrows), respectively, at the ablation site. These signal changes are consistent with the blood products. Adjacent to the ablation site (thin arrows), the recurrent tumor shows nodular increased enhancement (thick arrow) and delayed washout (thick arrow) on the early arterial (c) and late venous (d) phases of postgadolinium SGE sequences, respectively.

After ablative interventions, follow-up examinations are performed to evaluate the treatment effectiveness and the extent of potential complications. The best current approach is contrast-enhanced MR imaging within 6 weeks, and thereafter every 3 to 4 months to determine technique effectiveness, until 2 years, with less frequent imaging beyond that (annually).31 In follow-up studies, the ablated zone should decrease in size with time or stay unchanged.36,44 Similarly, the peripheral inflammatory rim should decrease in thickness and enhance less intensely. Any enlarging lesion or persistent, thick, and irregular enhancing rim should raise the suspicion of local recurrence. Regrowth at the periphery of the ablated lesion can occur beyond l year after intervention, therefore long-term follow-up studies are necessary.36,44,45

Malignant tumor may develop not only at the resection site but also at the other locations in the liver. The general success rate of RF ablation decreases with increasing tumor size. Lesions adjacent to major vessels may not be completely ablated because of a “heat sink” effect (ie, the dissipation of heat by flow in contiguous vessels).46 Lesions close to anatomical structures like gall bladder and bowel may not be ablated completely by choice, to provide the necessary safety margin so as not to compromise these organs.

Transcatheter Arterial Chemoembolization (TACE)

TACE usually is selected for patients who have multiple masses or large tumor. Although most tumors show necrosis in a significant portion of the tumor, total necrosis after TACE has been reported to be as low as 10% to 20%, depending on the embolization method, therefore the presence of residual or recurrent tumor is very common.47,48 For these reasons, TACE has recently been used in combination with ablative therapies.49,50 Therefore, evaluation after TACE is focused mainly on the change in tumor volume and gathering information relevant to the technique and time interval of the next TACE. Peripheral enhancement is seen in early follow-up images, representing granulation tissue. (Figures 5a–5d) TACE does not typically cause an intense reaction at the tumor periphery, as seen in ablative therapies.51 Signal intensity on T2-weighted images is often low immediately following therapy, distinct from the appearance following local ablative therapy, which is high. This reflects the devascularization of the tumor that occurs with TACE.52 Tumors that respond best to TACE therapy are small, uniformly enhancing hypervascular tumors, as the chemoembolic agent will be preferentially delivered to the lesions, rather than the liver, and uniform deposition of the agent is likely to occur throughout the lesions.52

Figure 5. Successful chemoembolization of a hepatocellular carcinoma. The treated tumor (arrows) demonstrates hypointense and mildly hyperintense signal intensity changes on T2-weighted fat-suppressed single shot echo train spin echo (a) and T1-weighted spoiled gradient echo (SGE) (b) sequences, respectively, following the chemoembolization. On the postgadolinium early arterial (c) and late venous (d) phases, there is no tumoral enhancement and the tumor is totally devascularized. A thin rim of enhancement, which is consistent with the inflammatory response, is detected on the late venous phase.

Conclusion

We have examined the role of MRI for the evaluation of post-therapeutic changes focusing on the liver, as the organ that practitioners have the most experience with. Important features of MRI include the safety of the modality and the high sensitivity of gadolinium-enhanced images for the presence of recurrence.

Richard C. Semelka, MD, is professor of radiology, director of MR services, and vice chair of clinical research in the Department of Radiology, and Birsen Unal, MD, and Ersan Altun, MD, are MRI clinical research fellows with the Department of Radiology at the University of North Carolina at Chapel Hill.

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