Gadoxetic acid‐enhanced MRI versus multiphase multidetector row computed tomography for evaluating the viable tumor of hepatocellular carcinomas treated with image‐guided tumor therapy

To compare the diagnostic performance of gadoxetic acid‐enhanced MRI with that of multi‐phase 40‐ or 64‐multidetector row computed tomography (MDCT) to evaluate viable tumors of hepatocellular carcinomas (HCCs) treated with image‐guided tumor therapy.

HEPATOCELLULAR CARCINOMA (HCC) is the most common primary liver cancer. Although surgery remains the treatment of choice for HCC, several minimally invasive techniques have been used as alternatives to surgery for the treatment of HCCs. These include transcatheter arterial chemoembolization (TACE) and image-guided tumor ablation therapies, including percutaneous ethanol injection therapy (PEIT), percutaneous microwave coagulation therapy, and radiofrequency ablation (RFA) (1). Although several therapeutic options have been proposed, the most widely used image-guided tumor therapies are TACE, RFA, or a combination of these two. After image-guided tumor therapy of HCCs, CT and MRI perform a crucial role in assessing the therapeutic efficacy and monitoring local tumor progression in the treated HCCs during follow-up and early detection of a viable tumor including residual tumor (i.e., incompletely treated tumor on immediate or 1-month followup CT after locoregional therapy) or local tumor progression (i.e., any growing or enhancing tumor in the treated lesion, where there had been no evidence of a residual tumor after locoregional therapy) can facilitate successful retreatment at an early stage (2)(3)(4)(5).
MDCT, which has the advantages of greater speed, thinner slices, and multiphasic scanning, has improved the chances of detecting HCC (6,7). Highfield-strength (3.0 Tesla [T]) MRI has been previously shown to have the advantages of better signal-to-noise ratio and image quality than 1.5T MRI, thereby improving lesion detection (8)(9)(10). Additionally, the use of liver-specific contrast agents such as gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (gadoxetic acid disodium, Primovist, Bayer Schering Pharma) produces both dynamic and liver-specific hepatobiliary MR images, thus improving both detection and characterization of focal liver lesions (11)(12)(13).
To the best of our knowledge, there have been no comparative studies of gadoxetic acid-enhanced 3.0T MRI and multiphase 40-to 64-MDCT for the evaluation of viable tumor of HCCs after TACE or RFA of HCCs in patients with chronic liver disease. The purpose of our study, therefore, was to compare the diagnostic performance of gadoxetic acid-enhanced MRI with that of multiphase 40-or 64-MDCT for the evaluation of viable tumors of HCCs treated with imageguided tumor therapies, such as TACE and RFA, in patients with chronic liver disease.

Patient Selection
This study was conducted with the approval of the institutional review board of our institution. Informed consent was not required for this retrospective study.
Between April 2008 and June 2009, among a total of 2680 consecutive patients with chronic liver disease suspected of having HCC on the basis of their imaging findings: the appearance of a new hypervascular tumor on CT or MRI during follow-up, the characteristic enhancement pattern on contrast-enhanced multi-phase MDCT (hypervascular at arterial phase and wash-out at portal or equilibrium phase) and/or gadoxetic acid-enhanced MRI (hypervascular at arterial phase, wash-out at portal or 3-min late phase, and hypointensity without uptake in hepatobiliary phase), and elevated serum a-fetoprotein level (a-fetoprotein level > 200 ng/mL), one study coordinator retrospectively collected 157 consecutive patients for whom the following criteria were fulfilled: chronic liver disease with HCCs that had been treated with TACE and/or RFA; had undergone both multi-phase CT at 40-or 64-MDCT and gadoxetic acid-enhanced MRI using 3.0T with less than a 3-month time interval (range, 5 -90 days; mean, 52 days) between the two techniques because of a suspicion of viable tumors in HCCs treated with TACE and/or RFA or because of a suspicion of new hypervascular HCC based on previous imaging and/or clinical findings including increased serum a-fetoprotein level; and had undergone follow-up images in 6-month or longer for confirmative diagnosis. Among those 157 patients, patients with following criteria were excluded: (a) patients with multi-focal (more than 10) accumulations of iodized oil (n ¼ 33) rendering analysis difficult; (b) patients with diffuse (i.e., multiple small foci of HCC throughout the liver in a diffuse manner) or massive (i.e., a large tumor occupying more than one segment of the liver) HCCs (n ¼ 16). Finally, 108 patients (81 men, 27 women; age range, 37-86 years) with 162 HCCs (59 HCCs treated with TACE, 96 HCCs treated with RFA, 7 HCC treated with both TACE and RFA) were included in this study. Sixty-nine patients had one treated HCC, 25 patients had two treated HCCs, 13 patients had three treated HCCs, and one patient had four treated HCCs. All patients underwent a follow-up CT 1 month after the procedure to evaluate technical effectiveness. If residual tumor was found in the treated lesion, it was treated with additional RFA or TACE. In the cases of no residual tumor, with no appearance of a new tumor in other sites of the liver at the 1-month follow-up CT, subsequent CT or MRI examinations were repeated usually every 3 months as a part of the follow-up protocol. However, the interval of the follow-up CT or MRI examinations was occasionally changed to somewhere between 2 and 6 months because of suspected complications or the clinician's decision. Underlying liver cirrhosis was associated with viral hepatitis B in 86 patients, viral hepatitis C in 16 patients, and alcoholic cirrhosis in six patients. The initial diagnosis of the 162 HCCs (mean, 1.8 cm; range, 1.2-9.5 cm) before imageguided tumor therapy in patients with chronic liver disease were confirmed by means of ultrasonographyguided percutaneous needle biopsy for 24 tumors, and the remaining 138 tumors were identified as HCC by a combination of the characteristic imaging findings and laboratory findings.
Among 162 treated HCCs, 56 lesions were proved to have the viable tumors in treated HCC, as follows: compared with CT/MRI enrolled in the study, viable tumors that were diagnosed depending on the followup imaging findings of increase in size of enhancing area which is suspected of viable tumor in the treated lesion and/or sustained iodized-oil accumulations in the hypervascular area corresponding to suspected viable tumor of treated lesions seen on CT and MRI on the hepatic arteriography with repeated TACE. The size of viable tumors in 56 treated lesions ranged from 0.7 to 5.1 cm in diameter (mean diameter, 1.6 cm). For 56 treated lesions with viable tumors, the time interval between two techniques was less than 1-month (range, 5 -30 days; mean, 21 days). The remaining 106 lesions were proved to have no viable tumors in the treated HCCs, as follows: compared with CT/MRI enrolled in the study, stable lesion (no change or decrease in size of treated lesion with no hypervascular portion) or disappearance or decrease in size of hypervascular pseudolesions at the periphery of treated lesions on CT or MRI in 6-month or longer follow-up images, in addition to the negative findings on the follow-up iodized-oil CT after repeated TACE.

Imaging Methods
Multiphase (contrast-enhanced hepatic arterial, portal venous and equilibrium phases) CT was conducted with a 40-MDCT scanner (Brilliance 40, Philips Healthcare) in 15 patients, and with a 64-MDCT scanner (Aquilion 64, Toshiba Medical, and light speed VCT 64, GE healthcare) in 93 patients. Unenhanced CT scans were also obtained in all patients with HCCs treated with TACE. The scanning parameters were as follows: 120 kVp, 189-200 mAs, 5-mm slice thickness with an increment (overlap) of 2.5 mm, table speed of 26.5-39.37 mm/rotation (pitch, 0.828-1.07), and a single-breath-hold helical acquisition of 4-6 s depending on liver size. Images were obtained in the craniocaudal direction. Hepatic arterial phase scanning began 30-40 s after the injection of 120 mL of a nonionic iodinated contrast agent (iopamidol, Iopamiro 300, Bracco) at a rate of 3-4 mL/s by means of a bolus-triggered technique (120 kVp; 40-60 mA; monitoring frequency from 12 s after the contrast injection, 1 s; trigger threshold, 100 HU in descending aorta; delay from trigger to initiation of scan, 18 s). The contrast agent was administered through the antecubital vein with a power injector. The portal and equilibrium phases of scanning began 70 s and 180 s after the injection of the contrast agent, respectively.
MRI was conducted using a 3.0T whole-body MRI system (Intera Achieva 3.0 T, Philips Healthcare) with a 16-channel phased-array coil as the receiver coil. The liver was imaged in the axial plane in all patients both before and after the administration of gadoxetic acid at a dose of 0.1 mL/kg (0.25 mmol/mL). The contrast agent was administered through the antecubital vein with a power injector at a rate of 2 mL/s, followed by a 20 mL saline flush.

Image Analysis
Two blinded gastrointestinal radiologists with at least 5 years' experience in interpretation of MR images of the liver independently reviewed the CT and MR images in random order. The observers knew that the patients had HCCs treated with image-guided tumor therapy such as TACE, RFA, or both. However, the observers were unaware of the results of final diagnoses. All images were evaluated with a 2000 Â 2000 PACS (GE Healthcare) monitor with adjustment of the optimal window setting in each case. Liver window settings were used in all cases, because the observers were free to adjust the window width and level on the PACS monitor.
Each observer independently recorded the presence of viable tumor of the treated lesions using a 5-point confidence scale to assign a confidence level to each lesion. The confidence level was defined as follows: 1, no viable tumor; 2, probably no viable tumor; 3, possibly a viable tumor; 4, probably a viable tumor; 5, definitely a viable tumor. Upon review of the image, the observers were aware that sensitivity was calculated with the number of lesions assigned a confidence level of 4 or 5. In clinical practice at our institution, viable tumors after RFA were considered as any enhancing lesions within or abutting the treated lesion at the arterial phase with washout pattern at the delayed phase of the CT examination based on previous reports (14,15). The definition for viable tumor on gadoxetic acid-enhanced dynamic MRI was similar to that on CT. In addition to the foregoing features, an area with moderate hyperintensity on T2weighted MR images and hypointensity on gadoxetic acid-enhanced hepatobiliary phase MR image compared with surrounding liver parenchyma was considered a viable tumor based on previous reports (3,5,6,13). The criteria for viable tumors on CT and gadoxetic acid-enhanced MRI after TACE were similar to those for viable tumors after RFA, and these criteria were based on previous reports (2,4,6,(16)(17)(18).
To avoid a mismatch between the findings on the scored lesions and the findings of treated lesions, each observer recorded the individual image number, the segmental location of all lesions, and the entire size of each treated lesion. For patients with two or more lesions in one segment, detailed descriptions of the location of the lesion in each segment were added to avoid confusion in the data analysis. The time interval between reviews of CT and MR images was established as at least 4 weeks to minimize any learning bias.
After the two observers had completed the review, the study coordinator with three years of experience in abdominal imaging with two observers compared the scoring results of each observer with the reference standard, and devised a possible explanation for the causes of the consensus false-positive and false-negative findings made by the observers.

Statistical Analysis
On the basis of the two observers' reviews, a receiver operating characteristic (ROC) curve was generated on a tumor-by-tumor basis. The diagnostic performance of each technique for each observer was assessed by measuring the area under the ROC curve (Az), in accordance with the methods of Hanley and McNeil (19). The diagnostic accuracy, sensitivity, and specificity of each observer and technique in the detection of viable tumors were calculated. The true-positive lesions were identified as those that were assigned a confidence level of 4 or 5 by the observers, and were proved to have viable tumors. False-negative lesions were those assigned a confidence level of 1, 2, or 3, but which were actually determined to have viable tumors. False-positive lesions were those assigned a confidence level of 4 or 5, but which were actually determined to have no viable tumors. The differences in the diagnostic accuracy, sensitivity and specificity were statistically analyzed by means of McNemar's test. Statistical analyses of differences in the calculated positive and negative predictive values for each observer and technique were based on a previous report (20). A value of P < 0.05 was considered statistically significant. An analysis of all false-positive and false-negative observations was also undertaken. To evaluate interobserver agreements in the evaluation of the viable tumor with each technique, kappa statistics were used. The degree of agreement was categorized as follows: kappa values of 0.00-0.20 were considered indicative of poor agreement; 0.21-0.40, fair agreement; 0.41-0.60, moderate agreement; 0.61-0.80, good agreement; and 0.81-1.00, excellent agreement (21). Table 1 shows the Az values for each observer and each technique for the evaluation of the viable tumors of HCCs treated with image-guided tumor therapy. Az values for gadoxetic acid-enhanced MRI were significantly higher than those for MDCT in two observers (P < 0.05). Table 2 shows diagnostic predictive values between the two techniques for each observer. Two observers achieved significantly higher diagnostic accuracy and sensitivity with gadoxetic acid-enhanced MRI than with MDCT (P < 0.001). The specificity of the two techniques for each observer was similar (P > 0.05). The negative predictive values of gadoxetic acid-enhanced MRI in two observers were higher than those of MDCT with significant difference (P < 0.001). The positive predictive values of gadoxetic acidenhanced MRI in two observers tended to be higher than those of MDCT, although this difference was not significant (P > 0.05).

RESULTS
Two observers recorded 52 false-negative CT (22 HCCs treated with TACE and 28 HCCs treated with RFA, two HCC treated with both TACE and RFA) and six false-negative MRI (four HCCs treated with TACE and two HCCs treated with RFA) results. Forty-six of 52 false-negative CT findings were detected by MRI and none of six false-negative MRI findings were detected by CT. False-negative CT findings were attributed to viable tumors with hypervascular enhancement on arterial phase images with no washout pattern in 26 cases (mean size of viable tumors,   (2) a Numbers in parentheses in diagnostic accuracy, sensitivity, specificity, and positive and negative predictive values are the numbers of correctly interpreted lesions, true-positive, true-negative, false-positive, and false-negative lesions, respectively. For positive predictive value, numbers in brackets are the number of true-positive lesions divided by the total number of lesions assigned a confidence level of 4 or 5. For negative predictive value, numbers in brackets are the number of true-negative lesions divided by the total number of lesions assigned a confidence level of 1, 2, or 3. The diagnostic accuracies, sensitivities, and negative predictive values of two techniques for each observer were statistically significant (P < 0.05). The specificities and positive predictive values of two techniques for each observer were not statistically significant (P > 0.05).
1.1 cm; size range of viable tumors, 0.7-2.6 cm) (50%), small size of viable tumor (hypervascular at arterial phase and wash-out at equilibrium phase) in 15 cases (mean, 0.8 cm; range, 0.7-0.9 cm) (29%), heterogeneous uptake of iodized oil in the treated lesion in 10 cases (19%), and interpretation error due to adjacent vessels in one case (2%). False-negative MRI findings were attributed to small size of viable tumor (hypervascular at arterial phase, wash-out at 3-min late phase and hypointensity on hepatobiliary phase) in four cases (mean, 0.8 cm; range, 0.7-0.9 cm) (67%) and isointensity of the viable tumor compared with the surrounding liver on gadoxetic acid-enhanced hepatobiliary phase MR images in two cases (33%).
There were 14 viable tumors (four HCCs treated with TACE and 10 HCCs treated with RFA) in 13 patients that were not detected by any of two observers on MDCT but were detected on gadoxetic acid-enhanced MRI by all of two observers. In the retrospective review, eight viable tumors showed faint hypervascularity on arterial phase CT images and no washout pattern on equilibrium phase with poor conspicuity (Fig. 1). Two viable tumors (each 1.9 cm and 0.7 cm in diameter) in two treated lesions were masked due to heterogeneous uptake of iodized oil in the treated lesions, which interfered with contrastenhanced assessment on arterial phase CT images. However, the viable tumors showed enhancement on gadoxetic acid-enhanced arterial phase MR images and hypointensity on the hepatobiliary phase without the influence of iodized oil (Fig. 2). The remaining four viable tumors were less than 1 cm in diameter.
All of two observers were unable to detect a viable tumor in only one lesion treated with TACE on both gadoxetic acid-enhanced MRI and MDCT (Fig. 3). Upon retrospective analysis, the viable tumor was Figure 1. A 38-year-old man with a 1.2-cm-diameter viable HCC tumor treated with RFA in the right lobe of the liver. a: Contrast-enhanced CT scan obtained at arterial phase shows perilesional enhancement (arrow) around the treated lesion without washout pattern on equilibrium phase (not shown). All observers did not recognize a viable tumor in the treated lesion. b: On T2-weighted MR image, a hyperintense nodule (arrow) is seen at the margin of isointense ablated lesion (asterisk). c,d: On gadoxetic acid-enhanced arterial (c) and (d) hepatobiliary phase MR images, a viable tumor (arrow) shows hypervascular enhancement and hypointensity, respectively, at the margin of the treated lesion (asterisk). All observers recognized a viable tumor in the treated lesion. e: Unenhanced CT scan obtained after TACE reveals iodized-oil accumulation of the corresponding viable tumor (arrow) at the margin of treated lesion (asterisk). small in size (1.2 cm) and located in the liver dome, which resulted in poor conspicuity with the isointense viable tumor on gadoxetic acid-enhanced hepatobiliary phase MR images and a faint hypervascularity with no washout on CT images.
For all observers, seven false-positive CT findings (two HCCs treated with TACE, four HCCs treated with RFA and one HCC treated with both TACE and RFA) and six false-positive MRI findings (three HCCs treated with TACE and three HCCs treated with RFA) were detected. False-positive CT findings were attributed to two heterogeneous uptake of iodized oil (29%), two arterioportal shunts (29%), and four interpretation errors (42%). False-positive MRI findings were attributed to four arterioportal shunts (Fig. 4) (67%) and heterogeneity of two treated lesions (33%).
The kappa values between the two observers showed excellent agreement with MRI and moderate agreement with CT (Table 3).

DISCUSSION
After image-guided tumor therapy in patients with HCCs, precise imaging evaluation for the viable tumor in treated HCCs is important because early detection of residual tumors or local tumor progression after image-guided tumor therapy is critical, and can facilitate successful retreatment at an early stage.
A variety of imaging techniques have been introduced for the evaluation of therapeutic efficacy after performing TACE and RFA for HCC (2)(3)(4)(5). Several investigators suggested that dynamic MRI using 1.5T Figure 2. A 56-year-old man with a 1.9-cm-diameter viable HCC tumor treated with TACE in the right lobe of the liver. a: Unenhanced CT scan shows heterogeneous uptake of iodized-oil in HCC (arrow) treated with TACE. b: Contrast-enhanced CT scan obtained at arterial phase shows a faint enhancement (arrows) in the periphery of the treated lesion with heterogeneous uptake of iodized-oil with no washout pattern at equilibrium phase (not shown). All observers did not recognize a viable tumor in the treated lesion. c: T2-weighted MR image shows a hyperintense area (arrows) in the treated lesion. d: Gadoxetic acid-enhanced arterial phase MR image shows a viable tumor (arrows) with rim-like enhancement in the treated lesion compared with unenhanced T1-weighted image (not shown). e: On gadoxetic acid-enhanced hepatobiliary phase MR image, the enhancing viable tumor shows hypointensity (arrow). All observers recognized a viable tumor in the treated lesion. f: Unenhanced CT scan obtained after TACE shows a rim-like uptake of iodized-oil at the corresponding viable tumor (arrows) of the periphery of the treated lesion.
was the best modality for evaluating the therapeutic effect of TACE and RFA on HCC (4,5).
However, there have been no comparative studies of gadoxetic acid-enhanced 3.0T MRI and multiphase 40-to 64-MDCT for the evaluation of viable tumors of HCCs treated with TACE and RFA. In our study, two observers achieved significantly higher Az values, diagnostic accuracies, sensitivities and negative predictive values when using gadoxetic acid-enhanced 3.0T MRI as compared to MDCT. The previously reported sensitivity of CT and MRI for the detection of small foci of residual or recurrent tumors after RFA ranged from 36-89% in the published literature (22). Several investigators have reported a sensitivity of 45-49% for the detection of HCC recurrence after TACE with CT scans combined with serum a-fetoprotein level (18,23). Kubota et al (4) reported a sensitivity of 100% with dynamic MRI for the detection of viable tumors after TACE. Although the study design was different, our results (sensitivity 53.6% with MDCT and 92.9-96.4% with MRI) were comparable to those of previous reports.
In our study, several factors caused false-negative and false-positive results. The majority (50%) of falsenegative CT findings were attributed to atypical enhancement pattern (hypervascular at arterial phase and no wash-out at portal and/or equilibrium phases), which may be confused with arterioportal shunt or reactive hyperemia around the treated lesion. Several investigators reported that, when HCCs are small, they Figure 3. A 57-year-old man with a 1.2-cm-diameter viable HCC tumor treated with TACE in the dome of the right lobe of the liver. a: Unenhanced CT scan shows two foci of iodized-oil accumulation (arrows) in treated HCCs after TACE. b: Contrast-enhanced CT scan obtained at arterial phase at the same level as (a) shows a faint enhancement between two foci of iodized-oil accumulation (arrow) with no washout pattern at equilibrium phase (not shown). All observers did not recognize a viable tumor in the treated lesion. c: T2-weighted MR image shows a viable tumor (arrow) with moderate hyperintensity at the anterior margin of relatively hypointense treated lesion (arrowhead) with iodized-oil accumulation. d: Gadoxetic acidenhanced arterial phase MR image shows a viable tumor (arrow) with enhancement at the anterior margin of the treated lesion (arrowhead). e: Gadoxetic acid-enhanced hepatobiliary phase MR image shows a viable tumor (arrow) with isointensity relative to surrounding liver parenchyma at the anterior margin of the treated lesion (arrowhead). All observers did not recognize a viable tumor in the treated lesion. f: Unenhanced CT scan obtained after TACE shows iodized-oil accumulation at the corresponding viable tumor (arrow) of the treated lesion.
have high chance of atypical enhancement pattern other than typical enhancement pattern of HCC (hypervascular at arterial phase and wash-out at portal and/or equilibrium phases) (24,25). In our study, the viable tumors in treated lesions that showed atypical enhancement pattern on MDCT were small (mean, 1.1 cm), which might be the main reason of false-negative CT results. We concluded that multiphase MDCT continues to be limited in terms of its ability to detect viable tumors with atypical enhancement in treated HCCs as in our cases, although this technique has high spatial and temporal resolution. On the other hand, we believe that additional information for differentiating the viable tumor with atypical enhancement from arterioportal shunt or reactive hyperemia can be acquired by means of gadoxetic acid-enhanced dynamic and hepatobiliary-phase MR images in addition to unenhanced MR images in some cases.
In our study, 29% of false-negative CT findings and 67% of false-negative MRI findings were attributed to small viable tumors in treated lesions, although they showed typical imaging findings of HCCs on retrospective review. We concluded that small viable tumors in treated lesions could be difficult to easily recognize from treated lesions, which may be obscured by inflammatory enhancement related to the procedure.
Our study showed that 19% of false-negative CT findings and 29% of false-positive CT findings were attributed to beam hardening artifacts of iodized oil. When evaluating the viable tumor on contrast-enhanced CT, it Figure 4. A 76-year-old man with no viable tumor in HCC treated with TACE in the right lobe of the liver. a: Contrast-enhanced CT scan obtained at arterial phase shows a treated lesion (arrow) with iodized-oil accumulation with no enhancement around the treated lesion as compared to unenhanced CT scan (not shown). All observers recognized no viable tumor in the treated lesion. b: T2-weighted MR image shows a treated lesion with a faint hyperintensity (arrows). c: Gadoxetic acidenhanced arterial phase MR image shows a small nodular enhancement (arrow) in the periphery of the treated lesion. d: Gadoxetic acidenhanced hepatobiliary phase MR image shows a treated lesion with hypointensity (arrow). The lesion was misinterpreted as the lesion with a viable tumor by two observers (false-positive result). has been thought that after TACE, assessment of contrast enhancement may prove difficult because of partial uptake of iodized oil within a tumor on contrastenhanced CT, which results in beam-hardening artifacts due to the high attenuation of iodized oil. However, we believe that the contrast enhancement of MRI is not affected by the presence of iodized oil, which is one of the advantages of MRI improving diagnostic accuracy for detecting viable tumors, as previously reported (26) and our results.
In our study, 33% of false-negative MRI findings were attributed to isointensity of the viable tumor on gadoxetic acid-enhanced hepatobiliary phase images. We believe that correct interpretation may be limited for viable tumors with gadoxetic acid uptake on gadoxetic acid-enhanced hepatobiliary phase images as reported previously (6).
In our study, 29% of false-positive CT findings and 67% of false-positive MRI findings were attributed to arterioportal shunts. Hemodynamic alteration, such as microscopic arterioportal shunting around the treated HCC after RFA or TACE, or hypervascular enhancement around RFA representing inflammatory reactions to thermal injury, can occur (22,27). As described in several previous reports (2,3), we believe that this hemodynamic alteration owing to imageguided tumor therapy can resemble or mask HCCs. However, as in a previous report (6), and our retrospective review, none of this hemodynamic alteration showed hypointensity on gadoxetic acid-enhanced hepatobiliary phase images, which may prove helpful in the differentiation of those from viable tumor with typical hypointensity on hepatobiliary phase images.
In our study, 33% of false-positive MRI findings were attributed to the heterogeneity of the treated lesion. HCCs treated with TACE or RFA have been known to have variable signal intensity on unenhanced T1-and T2-weighted images due to coagulative necrosis and/or iodized oil (15,27,28). Generally, the hypointensity on T2-weighted images is representative of coagulation necrosis. Conversely, the hyperintensity corresponds to hemorrhage or residual tumor (4). Dromain et al (5) reported that moderate hyperintensity on T2-weighted images corresponded to the presence of viable tumors in all cases, and suggested that T2-weighed imaging is highly specific. However, we believe that the presence of areas of hyperintensity on T2-weighted images does not consistently correspond to the viable tumor, as in our cases and a previous report (3).
Our study has several limitations. First, not all of the included patients underwent surgical resection after TACE and RFA. Therefore, the lack of pathological correlation is one limitation of this study. However, it is not possible to obtain lesion-by-lesion histopathologic proof, because hepatic resection is not generally performed in patients who have been treated with image-guided tumor therapies such as TACE and RFA. Additionally, post-treatment biopsies cannot substitute for a resected specimen, as the material retrieved at biopsy does not represent the entire tumor, and small portion of the viable tumor can go undetected. Second, to exclude the possibility of false-negative results, all of the patients considered not to harbor viable tumors in treated HCCs were followed up for more than 6 months. Nevertheless, the followup period may have been insufficient to detect late tumor recurrences in the treated lesions. Third, we used state-of-the-art 3.0T MRI and standard CT technique with a relatively low iodine concentration (300 mg/ mL) and a slow injection rate (3-4 mL/s). State-ofthe-art CT technique with higher iodine concentration and a faster injection rate may yield results superior to those achieved using our study protocol.
In conclusion, gadoxetic acid-enhanced MRI shows better diagnostic performance than that of MDCT for the evaluation of viable tumors of HCCs treated with image-guided tumor therapies such as TACE and RFA. Therefore, when MDCT is inconclusive in detecting viable tumors of HCC treated with image-guided tumor therapy in patients with chronic liver disease, gadoxetic acid-enhanced MRI can provide more confident information regarding the viability of treated HCCs than can MDCT.