Effect of MRI Versus MDCT on Milan Criteria Scores and Liver Transplantation Eligibility

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1 Gastrointestinal Imaging Original Research Rostambeigi et al. Use of Milan Criteria With Advanced MRI Technology Versus MDCT Gastrointestinal Imaging Original Research Nassir Rostambeigi 1 Andrew J. Taylor 1 Jafar Golzarian 1 Eric H. Jensen 2 Timothy L. Pruett 2 Vikas Dudeja 2 Donna D Souza 1 Rostambeigi N, Taylor AJ, Golzarian J, et al. Keywords: hepatocellular carcinoma, liver transplantation, Milan criteria, MRI DOI: /AJR N. Rostambeigi is the recipient of the ARRS 2015 Residents in Radiology Executive Council Award. Received March 12, 2015; accepted after revision August 29, Based on a presentation at the ARRS 2015 Annual Meeting, Toronto, Canada. 1 Department of Radiology, University of Minnesota, 420 Delaware St SE, Mayo Memorial Bldg, Minneapolis, MN Address correspondence to A. J. Taylor (taylora@umn.edu). 2 Department of Surgery, University of Minnesota, Minneapolis, MN. This article is available for credit. AJR 2016; 206: X/16/ American Roentgen Ray Society Effect of MRI Versus MDCT on Milan Criteria Scores and Liver Transplantation Eligibility OBJECTIVE. The Milan criteria for the selection of patients with hepatocellular carcinoma (HCC) for liver transplantation were originally based on the findings of contrast-enhanced CT examinations. Studies have shown improvement in HCC detection of using contrast-enhanced MRI instead of CT, but they have provided little information on the potential downstream effect on patient management that might result from discrepant imaging findings. We sought to assess the effect of discrepant imaging findings on patient eligibility to undergo liver transplantation. MATERIALS AND METHODS. From 2006 to 2013, patients with a diagnosis of HCC who underwent both MDCT and MRI examinations within a 40-day period were studied retrospectively. All examinations were independently reviewed by two abdominal radiologists who recorded the number, diameter, and location of each lesion. Secondary confirmation of the lesions was made on the basis of histopathologic findings, diffusion restriction on DWI, increased T2 signal intensity, lesion growth, presence of fat, uptake of ethiodized oil, or a combination of these findings. RESULTS. Sixty-four patients (48 men and 16 women; mean age, 62 years) met the criteria for inclusion in the study. Of the 129 lesions identified by MRI, only 102 of these lesions (79%) were identified by MDCT. This discrepancy led to a difference in the Milan criteria scoring for nine patients (14%). There was no statistically significant difference in the mean (± SD) greatest lesion diameter measured using the two modalities, with measurements of 3.52 ± 2.8 cm and 3.46 ± 2.8 cm noted on MDCT and MRI, respectively (p = 0.8). Lesions missed on MDCT studies tended to be smaller, with a mean diameter of 2.7 cm. Of the 129 lesions identified by MRI, 112 (87%) had available histopathologic findings or other confirmatory diagnostic evidence. CONCLUSION. MDCT missed one-fifth of the HCC lesions detected by MRI. Had MDCT been the only imaging examination performed, failure to identify these lesions would have led to a different management plan for 14% of patients. H epatocellular carcinoma (HCC) is the third most common cause of cancer-related death worldwide [1, 2]. The eligibility of patients to undergo liver transplantation (LT) depends in part on the severity of liver disease, patient comorbidities, and the presence and extent of HCC. Cross-sectional imaging, when used in conjunction with guidelinesbased imaging criteria, typically replaces biopsy for the diagnosis and staging of HCC in patients with chronic liver disease. Initial reports of the long-term survival after LT for patients with HCC revealed a poor overall 5-year survival rate of 30 40% [3, 4]. Mazzaferro et al. [5] subsequently proposed the widely accepted Milan criteria, which use findings from contrast-enhanced CT to evaluate patients with HCC and which have led to an improved survival rate after LT for such patients, with the 4-year survival rate increasing to approximately 75%. The Milan criteria deem a patient to be eligible for LT if he or she has a single HCC lesion with a diameter of 5 cm or smaller or no more than three lesions with a diameter of 3 cm or smaller and no macrovascular invasion. A recent prospective study also confirmed the high predictive value of the Milan criteria for tumor recurrence after LT; however, the imaging modalities used in that study were ultrasound, MDCT, MRI, or a combination of those modalities [6]. Moreover, if locoregional therapies reduce the tumor burden (i.e., downstage the tumor) so that it meets the Milan criteria, then survival after LT approaches rates similar to those noted for patients who met the Milan criteria [7]. 726 AJR:206, April 2016

2 Use of Milan Criteria With Advanced MRI Technology Versus MDCT The imaging criteria component currently used in the selection of patients for LT still follows the Milan criteria, which were first established 2 decades ago on the basis of non-mdct findings. Although previously reported data indicated that use of the Milan criteria has led to better outcomes, recent advancements, particularly improvements in MRI technology, have led to a much greater ability to detect HCC [8]. These advances have not been factored into the critical imaging component of patient management and patient selection to undergo LT. The accuracy of contrast-enhanced MRI in the detection of HCC frequently has been shown to be greater than that of MDCT [8 12]. Similarly, a recent meta-analysis indicated that the perlesion sensitivity of MRI is 80%, compared with 68% for contrast-enhanced MDCT [9]. However, even recent review articles have suggested that MDCT and MRI can be used interchangeably for the evaluation of patients for LT [13, 14]. In contrast to the emphasis on comparing different imaging methods for use in the detection of HCC, there has been relatively little emphasis on the potential downstream effects on the eligibility of patients to undergo LT on the basis of discrepant imaging findings for HCC detection [15, 16]. The present study compares the rate of detection of HCC by contrast-enhanced MRI versus MDCT, subsequently translating discrepant findings into potentially different patient care paths, particularly with regard to patient eligibility for LT. Materials and Methods Patient Selection Criteria Institutional review board approval was obtained for this retrospective study. A database that included all patients who had HCC diagnosed between 2006 and the end of 2013 was reviewed. Overall, 689 patients with the correct diagnostic code were identified. Only patients who had undergone both contrast-enhanced MDCT and MRI studies performed within 40 days of each other were included in the study. This 40-day period was chosen on the basis of the examination period used in previous reports, one of which indicated that the median time for the HCC nodules to double was 127 days [17]. Patients with who had a history of embolization, ablation, or resection before undergoing these imaging examinations were excluded from the study. Finally, patients without an acceptable arterial phase sequence on MDCT or acceptable arterial, portal venous, and delayed phases on MRI were excluded from the study. Imaging Methods The MDCT protocol at our institution consists of using a 64-MDCT scanner (Somatom Sensation 64, Siemens Healthcare) to obtain a triphasic contrast-enhanced scan, with the use of the following imaging parameters: tube voltage, 120 kv; collimation, mm; pitch, 0.8; and reconstruction interval, 2 mm every 1 mm and 5 mm every 2.5 mm in all contrast-enhanced phases. The amount of contrast bolus (Isovue, 370 mg I/mL, Bracco Diagnostics) and the rate of administration were calculated on the basis of patient body weight, with the use of automated contrast medium injection protocol software (Certegra PT3, Bayer HealthCare). A 50-mL saline flush was performed immediately afterward. The first image acquisition through the liver, which produced the late arterial phase, was obtained 15 seconds after attenuation of 200 HU was reached with the use of a bolus-tracking technique. The next image acquisition was the portal venous phase, which was obtained 70 seconds after injection was initiated. Finally, a delayed, or equilibrium, phase image was obtained 3 minutes after injection began. MDCT studies performed during the earlier years of the study consisted of arterial and portal venous phase images only. The use of triphasic protocols, which include a delayed phase, was not common in the early years of the study [18]. Moreover, the practice of needing to use both MDCT and MRI findings to confirm a diagnosis of HCC was also changed during this study period [19]. When only one imaging technique was needed, MRI was usually retained and MDCT discarded. Fortunately, an MDCT scan of the chest, obtained soon after the MR image was acquired, was performed to assess for pulmonary metastases. The protocol for obtaining this stand-alone MDCT scan of the chest involved a 35-second delay from the time that injection of the contrast agent began; this delay consistently resulted in a late arterial phase image through the liver. Finally, three examinations performed at an institution other than the study institution were used in the present study; these three examinations included arterial phase and delayed phase images only. The MRI protocol was performed using a 1.5-T superconducting MRI system (Avanto, Siemens Healthcare) with a phased-array body coil. The protocol includes T1-weighted images with inand out-of-phase axial images, a T2-weighted axial turbo spin-echo sequence with spectral fat saturation, a T2-weighted HASTE coronal sequence, T2-weighted spectral adiabatic inversion recovery axial images, and T1-weighted gradient-echo axial fat saturation images. A transverse T1-weighted fat-suppressed 3D volumetric interpolated breathhold sequence was obtained before and after dynamic injection of one of two gadolinium contrast agents: gadobutrol (Gadavist, 0.1 mmol/kg of body weight, Bayer HealthCare) or gadoxetic acid (Eovist, 0.05 mmol/kg of body weight, Bayer HealthCare); this was followed by a 70-mL saline flush (rate of administration, 2 ml/s for both contrast medium and saline) delivered via a power injector (Spectris, Medrad). If gadoxetic acid was used, the hepatobiliary phase image was not used in the interpretation of the examination. Late arterial, portal venous, and delayed (or equilibrium) phase images were acquired. After the late arterial phase image was obtained by bolus tracking, images were obtained during the portal venous phase (after a 60-second delay) and the delayed phase (after a 180-second delay). The imaging parameters used to acquire 23 sections in a breath-hold were as follows: integrated parallel acquisition techniques, 2.0; FOV, 320 mm; slice thickness, 3 mm; and slice gap, 0 mm. Subtracted images from the dynamic phase were used. Finally, a coronal image was acquired 5 minutes after the contrast medium was injected. As with the MDCT studies, the MRI examinations performed during the early years of the study used older technology. Also in the early years of the study, the dynamic phase image slices were slightly larger than the slices obtained in more recent years of the study (5 vs 3 mm), no bolus tracking was used, and no subtraction MRI technique was used. Image Interpretation and Diagnostic Algorithm Two radiology faculty members with 6 and 33 years of experience in abdominal imaging independently and randomly reviewed all MDCT and MRI examinations in a blinded fashion. All the MDCT studies were reviewed first, and the MRI studies were reviewed after a 1-month interval, to avoid any introduction of bias. Any disagreements were resolved by consensus. In the present study, we followed the guidelines for diagnosing HCC on the basis of imaging and laboratory findings, which have been accepted since 2001 by the expert panel of the European Association for the Study of the Liver [13, 20]. The lesion size was denoted by the greatest single diameter. Also, the updated guidelines from the American Association for the Study of Liver Diseases [19] and the European Association for the Study of the Liver [21] were implemented. Various but equivalent IV-administered iodine contrast agents were used in the MDCT examinations. Gadolinium chelates, both interstitial and hepatobiliary, were used in MRI examinations performed at our institution. Both guidelines rely on the presence of hyperenhancement (wash-in) in the arterial phase, followed by wash- AJR:206, April

3 Rostambeigi et al. out in the venous or delayed phase. Also noted was the presence of any capsule developing on the portal venous or delayed phase images, which can also be important in the diagnosis of HCC [14]. When the hepatobiliary gadolinium agent was used, only the dynamic phase images (not the hepatobiliary phase image) were used for the diagnosis of HCC. In the late arterial phase, the maximum dimension in the axial plane and both the location and the total number of lesions were recorded for each patient. Because the specificity of imaging for the detection of small lesions is limited, and in accordance with the guidelines of the American Association for the Study of Liver Diseases, lesions smaller than 1 cm in diameter were not regarded as HCC [19] and were excluded from the study. The contrast washout in the portal phase, the delayed phase, or both phases was also used in the diagnosis of HCC. Therefore, a mass with arterial hyperenhancement and portal venous phase washout was equivalent to a Liver Imaging Reporting and Data System category 4 or 5 lesion, depending on the size of the mass [22]. When a hyperenhancing late arterial phase lesion was visualized on an MDCT examination of the chest for which neither a portal venous phase nor a delayed phase image was available, this lesion was considered to be an HCC if the lesion was identified as an HCC on MRI. Data on patient demographic characteristics at baseline, the cause of the underlying liver disease, liver function test findings, and serum α-fetoprotein levels were all collected. Patient outcomes, including LT, survival, and tumor recurrence at followup, were determined. When available, the histopathologic findings for explanted liver lesion specimens, wedge resection specimens, or biopsy samples were reviewed and correlated with the imaging findings. If patients did not receive a diagnosis on the basis of tissue findings, then one or more of the following four secondary imaging characteristics were used for supplemental confirmation of the HCC: lesion growth ( 50% increase in diameter in 6 months [23], as noted on subsequent imaging studies), uptake of ethiodized oil by the lesion as a result of subsequent chemoembolization [24, 25], increased signal intensity on high-bvalue DWI [26 28] or mild-to-moderate increased signal intensity on T2-weighted imaging [14, 29, 30], or presence of fat in the nodule on MRI [31, 32]. Of note, these secondary imaging characteristics were used only when the lesion met MRI criteria for HCC, and they were only used for confirmation and not for diagnosis of the lesions. For each patient, the length of follow-up was based on the last day of follow-up or the date of death. Statistical Analysis The number of lesions detected was counted for each patient, and the kappa statistic was calculated to determine the agreement between MDCT and MRI for lesion detection. The size of the lesions was measured, and then the correlation between the sizes measured by MDCT and MRI was TABLE 1: Baseline Demographic and Clinical Characteristics of 64 Patients Included in the Study Characteristic Value Age (y), mean ± SD 62 ± 9.3 Male sex 48 (75) Cause of underlying liver disease Hepatitis C infection 38 (60) Alcohol-related liver disease 11 (17) Hepatitis B infection 4 (6) Alcohol use and hepatitis C infection 4 (6) Hepatitis B and C infection 1 (1.6) Cystic fibrosis 1 (1.6) N-acryloxysuccinimide 2 (3.1) Primary biliary cirrhosis 2 (3.1) Alcohol use and hemochromatosis 1 (1.6) Follow-up duration (y) Median 3.5 Range 2 months to 8 years Patients who underwent LT at follow-up, no. 24 Note Except where otherwise indicated, data are number (%) of patients. LT = liver transplantation. calculated using the intraclass correlation coefficient. Logistic regression analysis was performed to determine the possible roots of the discrepancy in lesion detection between MDCT and MRI. The sizes of the lesions were compared using the t test. Survival analysis was performed to compare the survival of patients in different groups of patients who had nonconcordant Milan criteria versus patients who had concordant Milan criteria and groups of patients who underwent transplantation versus those who did not undergo transplantation. Statistical software (Stata, version 11, StataCorp) was used for analysis. Results Overall, 346 of 689 patients (50%) underwent both CT and MRI studies. Of these 346 patients, 80 had both of these imaging studies performed less than 40 days apart. After the exclusion of patients who had previously received therapy (e.g., resection, percutaneous ablation, and chemoembolization) for HCC and patients whose MDCT or MRI examinations were not satisfactory, 64 patients met all the criteria for inclusion in the study. A total of 48 patients (75%) were men, and the mean (± SD) patient age was 62 ± 9.3 years (Table 1). The contrast agents used in the MRI studies were either gadobutrol or another interstitial agent, for 53 patients (83%), and gadoxetic acid, for 11 patients (17%). The interval between the MDCT and MRI examinations varied from 0 to 40 days, with a mean of 16 ± 14 days. The order in which the examinations were performed was evenly distributed between patients, with MRI performed first for 28 patients and with MDCT performed first for 29 patients. Seven patients had both studies performed on the same date. A total of 129 lesions met the imaging criteria for detection of HCC on MRI. In contrast, only 102 lesions met such criteria on MDCT; 27 lesions (21%) in 18 patients were missed on MDCT (Table 2). Figures 1 and 2 provide examples of images of lesions in two patients. None of the lesions that were detected by MDCT were missed by MRI. The kappa agreement between MDCT and MRI was 71.8%, which denotes moderate agreement. The number of lesions noted in each patient was variable, with 0 5 lesions detected by MDCT and 1 8 lesions identified by MRI in each patient. The mean size of the lesions was 3.46 ± 2.8 cm (range, cm) on MRI and 3.52 ± 2.8 cm (range, cm) on MDCT. There was no statistically significant difference between the mean size of lesions detect- 728 AJR:206, April 2016

4 Use of Milan Criteria With Advanced MRI Technology Versus MDCT TABLE 2: MDCT and MRI Findings in Terms of the Number and Size of the Lesions Detected Finding ed on MDCT and MRI examinations (p = 0.8) (Table 2). Similarly, the intraclass correlation coefficient for lesion size was 0.9 (50% CI, ), which indicated a high correlation between the sizes of the lesions detected by MDCT versus MRI (Fig. 3). Logistic regression analysis of disagreement in lesion detection between MDCT and MRI showed higher disagreement in the detection of smaller lesions (odds ratio [OR], 0.74 [i.e., with each 1-centimeter increase in the size of the lesion, there was a 74% lower Value Total lesions detected by MDCT 102 Total lesions detected by MRI 129 Patients with discrepant number of lesions (n = 27 lesions) on MDCT and MRI studies a 18 Patients with nonconcordant Milan criteria on MDCT and MRI 4 Patients with no lesions identified on MDCT but with 1 3 lesion(s) identified on MRI 5 Diameter of lesions seen on MDCT images (cm) Mean 3.52 Range Diameter of lesions seen on MR images (cm) Mean 3.46 Range Diameter of lesions seen on MRI but not on MDCT (cm) Mean 2.7 Range Note Except where otherwise indicated, data are number of patients or lesions. a MRI missed no lesions, compared with MDCT. chance of the lesion being missed]; p = 0.03). The mean diameter of the lesions missed by MDCT was 2.7 cm (range, cm). Similarly, the greatest dimension of 80% of the lesions missed by MDCT was less than 3 cm. The 18 patients who had discrepant findings on MDCT and MRI examinations were distributed throughout the study period ( ), with 61% of lesions with discrepant findings noted in studies performed before 2009 and 39% noted in studies performed after Even though MDCT and MRI technology changed throughout the 8-year study, there was no change in the continued superiority of MRI versus MDCT for the detection of lesions. Thirty-one patients (48%) underwent biphasic liver MDCT, 13 (21%) underwent triphasic MDCT, and 20 (31%) underwent chest MDCT with arterial phase image acquisition. The quality of CT (i.e., biphasic liver MDCT vs triphasic liver MDCT vs chest CT with arterial phase image acquisition) was again unrelated to the number of lesions with discrepant findings. Multivariate logistic regression analysis did not show any statistically significant effect resulting from the type of MDCT used (p = 0.4), the year when the imaging studies were performed (p = 0.4), or any difference in the date on which MDCT and MRI examinations were conducted (p = 0.3). Similarly, whether MRI was performed with the use of either gadobutrol or gadoxetic acid as the contrast agent did not make a statistically significant difference with regard to lesions with discrepant findings (p = 0.4). Fifty-five of the 64 patients had concordant Milan criteria when MDCT was compared with MRI: 29 patients were found to have Milan criteria indicating possible patient eligibility for LT, according to results of both MDCT and MRI techniques, whereas 26 patients had evidence of an HCC tumor load that would disqualify them for LT, according to the results of both MDCT and MRI. For the remaining nine patients, Milan criteria were nonconcordant. Five of these remaining nine patients had no lesions visualized on MDCT, but MRI demonstrated one to three lesions per A B Fig year-old man with hepatocellular carcinomas (HCCs). MDCT shows only some HCCs found by MRI. A, Late arterial phase MDCT scan. Two subtle but visible HCCs (arrows) are shown. B, Late arterial phase MR image obtained at the same level used in MDCT scan shows lesions (asterisks) that were visualized on MDCT, but it also shows another lesion (arrow) that, even in retrospect, is not noted on MDCT. Fourth subtle HCC in segment III (arrowhead) was seen in next slice on MDCT, thereby matching the MRI finding. AJR:206, April

5 Rostambeigi et al. A Fig year-old woman with moderately large hepatocellular carcinoma (HCC) that would not have been diagnosed by MDCT alone. A, Slice from late arterial phase MDCT scan did not show any lesion prospectively, but lesion is subtly present in retrospect. B, Late arterial phase MR image shows 3.7-cm HCC (arrow). patient, with lesion diameters ranging from 1.3 to 4.8 cm. Of the last four patients with nonconcordant Milan criteria, one patient had six lesions detected by MRI but had only three lesions detected by MDCT. A second patient had a moderately large lesion visualized by both MDCT (diameter, 4.5 cm) and MRI (diameter, 4.2 cm), but MRI showed a second lesion that was not seen on MDCT. Similarly, a third patient had two lesions (measuring 3.5 and 2.2 cm) identified by MRI but had a single lesion (measuring 3.0 cm) detected by MDCT. The fourth patient had a large 7-cm lesion identified by MRI that subsequently underwent chemoembolization; however, this lesion was not identified by MDCT. Explanted tissues samples, resected lesion specimens, or percutaneous biopsy specimens were available for 42 patients (66%). Of these 42 patients, 28 underwent explantation or wedge resection of liver specimens, and 14 patients underwent percutaneous needle biopsies. Five patients for whom no tissue specimens were available subsequently underwent chemoembolization, with avid uptake of ethiodized oil, which was used for confirmation of the diagnosis of HCC. For four patients, subsequent contrast-enhanced imaging examinations showed an appropriate increase in lesion diameter that supported the diagnosis of HCC. Fourteen patients had mild-tomoderate T2 signal intensity, diffusion restriction on DWI, or the presence of fat within the nodule, findings that all provided supplemental confirmation of the HCC diagnosis. Therefore, 62 of 64 patients (97%) had one type of secondary confirmation of the HCC diagnosis in addition to confirmation made on the basis of standard imaging criteria. Biopsy, wedge resection, or tissue explantation was performed on 57 of 129 lesions (44%). Another 55 lesions (43%) had other indicators that confirmed the diagnosis of HCC, including uptake of ethiodized oil, diffusion restriction on DWI, lesion growth of more than 50% in 6 months, presence of fat within the nodule, a mild-to-moderate increase in T2 signal intensity, or a combination of these indicators. Of these 55 lesions, 37 were diagnosed on the basis of both tissue findings and other secondary confirmatory indicators. Overall, for 112 lesions (87%), Fig. 3 Comparison of size of each lesion identified on both MRI and MDCT examinations. Note that although correlation of size estimates is high, considerable number of smaller lesions were missed by MDCT (as depicted by lesions in red dashed oval). Diameter of Lesion, as Measured by MDCT (cm) there was one or more supplemental piece of evidence that supported the diagnosis of HCC. Of note, secondary confirmation was achieved for 25 of the 27 lesions with discrepant findings (93%) (nine with diagnostic tissue findings and the remaining 16 with other secondary indicators). The size and number of all 27 lesions in these 18 patients were closely correlated with the MRI findings. The median patient follow-up was 3.5 years (range, 2 months to 8 years). There was no difference in survival for patients who met the Milan criteria on the basis of MRI findings versus patients who met the criteria on the basis of MDCT findings but not MRI findings (1.8 years for patients with concor Diameter of Lesion, as Measured by MRI (cm) B 730 AJR:206, April 2016

6 Use of Milan Criteria With Advanced MRI Technology Versus MDCT dant Milan criteria, 2.6 years for those with nonconcordant Milan criteria; p = 0.6, by the log-rank test). A total of 24 patients underwent LT by the end of the study. Patients who underwent LT had a statistically significantly better overall survival than did patients who did not undergo LT (45 vs 10 months, respectively; p = 0.002). During follow-up, within a median of 26 months after LT, tumor recurrence occurred in five (four patients with concordant Milan criteria and one with nonconcordant Milan criteria) of the 24 patients who had undergone transplantation (21%). Discussion This retrospective study, which assessed 64 patients with HCC and temporally matched contrast-enhanced MDCT and MRI examinations, revealed that 21% of lesions would be missed if MDCT findings only were considered. Moreover, additional confirmation of the diagnosis of HCC in patients with indicators such as available histopathologic findings, follow-up chemoembolization, restricted diffusion on high-b-value DWI, presence of fat within the lesion, appropriate lesion growth, mild-to-moderate increased T2 signal intensity, or a combination of these factors revealed that 87% of lesions were correlated with HCC detected on MRI. The difference in HCC detection could have changed the management path for 14% of patients. If MDCT only had been performed, four patients (6%) would not have been given any option for HCC treatment because lesions would have been missed on MDCT. On the other hand, if MRI only had been performed, five of the 64 patients (8%) could have been denied LT because of the additionally detected lesions. When the 27 lesions with discrepant findings on MDCT and MRI were evaluated using supplemental verification, as reported in the Results section of the present study, 25 of these lesions had one or more confirmatory findings. The present study amplifies the findings of prior studies in suggesting that MRI is superior to MDCT for the detection of HCC in patients with chronic liver disease. Other series have looked at the downstream effect of this difference in detection by the two imaging modalities. Lee et al. [16] compared the findings of MDCT versus those of MRI enhanced with superparamagnetic iron oxide agent alone versus the combination of superparamagnetic iron oxide agent enhanced MRI followed immediately by MRI enhanced with IV injection of an interstitial gadolinium agent. According to that study, MRI using a combination of contrast agents detected lesions better than did the other two imaging protocols, but it did not lead to a change in the LT status of the 38 patients with HCC who were studied. However, use of the superparamagnetic iron oxide contrast agent is not recommended in any of the major guidelines for the diagnosis of HCC. Another study evaluated MRI performed using gadoxetic acid as the contrast agent, compared with MDCT [15], and found that MRI detected 18.5% more HCCs than did MDCT. This finding resulted in a change in the LT status of 5.4% of the patient population. However, that study included only those patients who already had one lesion diagnosed by MDCT, and a considerable proportion of patients had already received some type of HCC treatment. Moreover, that study did not have any pathologic correlate for the findings. The approach to the diagnosis of HCC in patients with chronic liver disease is a unique practice in medicine, with diagnosis of malignancy preferably being made by imaging without biopsy confirmation. Although diagnosing HCC on the basis of MDCT and MRI findings is not without some concerns [33], the complications, complexities, and cost associated with biopsy confirmation are considered too great [14]. At present, either contrast-enhanced MDCT or MRI is accepted as an appropriate modality for the diagnosis of HCC. In patients with chronic liver disease, the presence of nodules that measure 1 cm or larger and display late arterial hyperenhancement with washout in the portal venous phase, equilibrium phase, or both, have a specificity of close to 100% for the detection of HCC [34]. Although some authors suggest that MDCT is more readily available and that its findings are easier to interpret [12], many studies support the preference for using MRI [8, 9, 11]. Not only does MRI provide better contrast resolution in the dynamic study, but its other capabilities, such as T2-weighted images, DWI, correlation with T2 signal characteristics, the ability to detect the presence of lesion fat, the hepatobiliary component with the use of gadoxetic acid, and, possibly, MRI perfusion all can potentially help in the detection and confirmation of HCC [34]. Although all major clinical practice guidelines [19, 21, 24, 35, 36] currently recommend the use of extracellular contrast agents only for contrast-enhanced dynamic MRI, there is great interest in promoting the use of hepatobiliary agents, particularly gadoxetic acid, as the contrast agent to use in MRI examinations performed for the detection of HCC [11, 37]. The lack of hepatobiliary phase images in the present study could diminish the diagnostic value of MRI, compared with studies in which a hepatobiliary agent, with the availability of hepatobiliary phase images, was exclusively used. In our small study population, the difference in imaging results did not result in a change in survival rates. This lack of improvement in the survival rate could be interpreted as a lack of importance of MDCT results versus MRI results. However, even though imaging is an important part of the workup for transplantation, it is only one facet that helps to determine the eligibility of an individual patient to undergo transplantation. There are a variety of other factors, including organ availability and patient comorbidities, that are critical in determining patient eligibility for transplantation. These factors, along with the relatively small sample size of the present study and the fact that patients underwent both imaging studies on the basis of which clinical decisions could be made, blunts the argument that the lack of survival means that the difference in imaging findings is not important. Given the aforementioned results, revisiting of the Milan criteria on the basis of MRI findings might better serve patients and the process of patient selection for LT. Because the study in which the Milan criteria were originally proposed by Mazzaferro et al. [5] noted a 27% discrepancy between CT and pathologic findings, it is not definitely known whether the detection of three lesions versus four lesions (on MRI) would make a difference in survival. For patients in the present study who underwent LT, the length of follow-up (median, 3.5 years) extended beyond the period (i.e., 2 years) in which most recurrences of HCC occur after transplantation [38, 39]. The judicious patient selection used in the present study, as exemplified by inclusion of only those patients who underwent both MDCT and MRI examinations in less than 40 days and patients who had no prior procedural distortion of liver tissue, should increase the credibility of the imaging results. We also correlated the MRI findings with liver tissue findings as well as with four other literaturesupported imaging characteristics in the detection of HCC, yielding supplemental verification of 97% per patient and 87% per lesion. Our study had several limitations. First, it was a retrospective single-institution analysis. Selection bias was present because the AJR:206, April

7 Rostambeigi et al. study involved patients who were limited by undergoing closely timed MDCT and MRI examinations. The MDCT studies did not always include equilibrium phase images, because the importance of obtaining such images was not appreciated before 2007 [18]. Therefore, these biphasic MDCT examinations of the liver consisted of arterial and venous phase images only. Also, during the early portion of the examination, standard timing for the phases, as opposed to the bolus timing technique, was used. Later in the study period, multiphasic CT was dropped and only late arterial phase images through the liver were obtained on MDCT examination of the chest. This was a technically poorer examination, compared with multiphasic MRI. Nevertheless, when hyperenhancement of the lesion was noted in the arterial phase on a single-phase CT scan, we correlated this finding with the complete criteria for the detection of HCC on MRI, and only then was this MDCT lesion considered to be an HCC. This approach would be, if anything, in favor of the MDCT results. In conclusion, the present study confirmed previous findings that indicated the superiority of MRI for the detection of HCC, compared with MDCT. This superiority translated into approximately 20% more lesions being defined in this patient population. This difference would theoretically lead to a change in the management of 14% of our patients. The data suggest that there is a need to reconsider the assumption that MDCT and MRI results are interchangeable. A case could be made for performing a prospective study, similar to that conducted by Mazzaferro et al. [5], except with the use of an optimal present-day MRI technique, to better assess the tumor load, thus leading to better selection of patients to undergo LT and better patient survival. References 1. Mazzaferro V, Chun YS, Poon RT, et al. Liver transplantation for hepatocellular carcinoma. Ann Surg Oncol 2008; 15: Botha JF, Langnas AN. 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