Gastrointestinal Imaging Clinical Observations Doo et al. Pseudo Washout Sign on MRI of Hemangioma Gastrointestinal Imaging Clinical Observations Kyung Won Doo 1 Chang Hee Lee Jae Woong Choi Jongmee Lee Kyeong Ah Kim Cheol Min Park Doo KW, Lee CH, Choi JW, Lee J, Kim KA, Park CM Keywords: abdominal imaging, gadoxetic acid, hemangioma, liver, MRI DOI:10.2214/AJR.08.1732 Received August 25, 2008; accepted after revision June 4, 2009. 1 All authors: Department of Radiology, Korea University Guro Hospital, Korea University College of Medicine, 80 Guro-dong, Guro-gu, Seoul 152-703, Korea. Address correspondence to C. H. Lee (chlee86@hanmail.net). WEB This is a Web exclusive article. AJR 2009; 193:W490 W496 0361 803X/09/1936 W490 American Roentgen Ray Society Pseudo Washout Sign in High-Flow Hepatic Hemangioma on Gadoxetic Acid Contrast-Enhanced MRI Mimicking Hypervascular Tumor OBJECTIVE. The purpose of this article is to describe the pseudo washout sign of high-flow hepatic hemangioma that mimics hypervascular tumor on gadoxetic acid enhanced MRI. CONCLUSION. High-flow hemangiomas might show relatively low signal intensity because of gadoxetic acid contrast uptake in the surrounding normal liver parenchyma during the equilibrium (3-minute delay) phase. Such findings are called pseudo washout and can mimic hypervascular hepatic tumors. However, high-flow hemangioma can be diagnosed by observing bright signal intensity on T2-weighted imaging, arterial phase dominant enhancement, pseudo washout sign during the equilibrium phase, and isointense or slightly increased signal intensity on subtraction images. H epatic hemangioma is the most common benign liver tumor, and differentiating it from malignant liver neoplasms is clinically important [1]. The most common MRI pattern shown by hemangiomas is peripheral nodular enhancement, centripetal filling, and delayed contrast enhancement. However, some atypical hemangiomas, especially high-flow hemangiomas, can display rapid, intense homogeneous arterial enhancement and can show isointense or slightly hyperintense signal when compared with the surrounding hepatic parenchyma during the equilibrium phase using extracellular contrast media [1, 2]. Therefore, these early enhancing types of hemangiomas can mimic hypervascular hepatic tumors, such as hepatocellular carcinoma (HCC) or hypervascular metastasis, which show rapid enhancement on the arterial phase and are isointense on the equilibrium phase of extracellular contrast media enhanced MRI [3]. Gadoxetic acid disodium (Primovist, Bayer Schering Pharma) is a recently developed liver-specific MRI contrast agent with combined perfusion and hepatocyte-selective properties [4 6]. Benign lesions containing well-differentiated hepatocytes have been shown to take up gadoxetic acid, whereas malignant tumors, dysplastic tumors, hepatic cysts, hepatic hemangiomas, and some cases of adenomas generally show no uptake [7 9]. Among patients who underwent gadoxetic acid enhanced MRI, we found high-flow hepatic hemangiomas that could be confused with hypervascular tumors. The lesions showed bright signal intensity on unenhanced T2-weighted imaging leading to the suspicion that they were hemangiomas, but they also showed good enhancement on the arterial phase and low signal intensity compared with the surrounding liver parenchyma on the equilibrium phase the washout pattern. Thus, the hemangiomas could be confused with HCC. Therefore, we report the imaging findings of high-flow hemangiomas in three patients who showed a pseudo washout sign using gadoxetic acid enhanced MRI. Materials and Methods Patients The subjects were three men whose imaging findings were retrospectively reviewed at our institution. Of the 400 patients who underwent gadoxetic acid enhanced MRI of the liver from January to September 2008, three were confirmed to have a high-flow hemangioma through biopsy or follow-up imaging studies. Institutional review board approval was obtained before performance of this clinical observation, and informed consent was waived for review of the data. The first patient was a 54-yearold man (patient 1) with a history of variant angina. Routine abdominal sonography had shown a hypoechoic lesion in segment III. Patient 2 was a W490 AJR:193, December 2009
Pseudo Washout Sign on MRI of Hemangioma 71-year-old man who underwent sigmoidoscopy for polypectomy. On further examination, a small lowattenuating lesion at segment IV of the liver was detected on a baseline abdominal CT scan. The third patient was a 48-year-old man (patient 3) with chronic hepatitis C. He was referred for abdominal sonography and CT, which showed an approximately 2.5-cm hepatic nodule in segment V that was suspected to be a hemangioma. Imaging Techniques MRI was performed using a 3-T unit (Magnetom Trim Trio, Siemens Healthcare) with a combination of a body matrix coil and a spinal matrix coil (Tim Coil, Siemens Healthcare). Baseline MR images were acquired with the following parameters: fat-suppressed respiratory-triggered T2- weighted turbo spin-echo sequence (TR range/te range, 3,500 5,000/70 85; echo-train length, 10; flip angle, 140 ; matrix, 202 320; and slice thickness, 3 mm), breath-hold T2-weighted turbo spinecho sequence (2,500 4,500/103; flip angle, 140 ; matrix, 202 320; and slice thickness, 5 mm), T2-weighted HASTE sequence (400 500/100 150; flip angle, 150 ; matrix, 166 256; and slice thickness, 3 mm), and a breath-hold T1-weighted fast low-angle shot (FLASH) sequence (TR/TE, 172/2.5; flip angle, 65 ; matrix, 208 256; signal average, 1; acquisitions, 2; and slice thickness, 5 mm). Dynamic imaging (volumetric interpolated breath-hold examination, VIBE, Siemens Healthcare) was performed after IV injection of 0.1 ml/ kg of gadoxetic acid based contrast medium (gadoxetic acid disodium, Primovist), using the following parameters: T1-weighted VIBE fat-suppressed axial series (3.37/1.23), obtained during early arterial (20 seconds), late arterial (40 seconds), portal venous (65 seconds), equilibrium (3 minutes), and hepatobiliary (20 minutes) phases. Another dynamic imaging series with 0.1 ml/kg of gadobutrol (Gadovist, Bayer Schering Pharma) was performed for further evaluation; however, the 20-minute delayed-phase image was not obtained. Contrast media was injected using an automated injector (Spectris MR, Medrad Europe) at a rate of 2 ml/s and flushed with 25 ml of saline solution after the contrast injection. Image Interpretation MR images were interpreted through a consensus of two radiologists with 12 and 6 years of experience in gastrointestinal MRI. The signal intensity of all of the liver lesions was graded on T1-weighted, T2-weighted, and contrast-enhanced images as isointense, hypointense, or hyperintense in relation to normal liver tissue. The MRI data were transferred to a workstation (MRWP, Siemens Healthcare) for analysis. The signal intensities were measured by the radiologists with visual evaluation at first, and ROI (region of interest) measurements of tissue signal intensity were placed by one of the authors in normal hepatic parenchyma, avoiding vessels and motion artifacts. The normal liver and background noise ROI measurements were approximated to the same size and distance from the phased-array coil. The measurements were performed three times and averaged. Signal-to-noise ratio (SNR) was calculated for hepatic parenchyma and for hemangioma using the formula [signal intensity / SD of background noise]. The contrast-to-noise ratio (CNR) was calculated for normal hepatic parenchyma versus hemangioma. The following formula was used: [(signal intensity of the liver signal intensity of the hemangioma) / SD of background]. We measured the percentage change in the SNR with the following formula: [(SNR of each phase SNR of unenhanced) / SNR of unenhanced 100]. The diagnosis of the lesions was confirmed by subtraction images between the unenhanced and equilibrium phase images. The subtraction images were automatically produced by the workstation. We measured the contrast-enhanced proportion of the whole area of the lesions at the center of the longest diameter during the arterial phase using the formula [enhanced area of the lesion on the arterial phase / area of the total lesion] to prove that all of the lesions had enhancement predominantly in the arterial phase. The presence of an arterioportal shunt adjacent to the lesion was used to support the diagnosis of a high-flow hemangioma [2]. Results In patient 1, sonography revealed a 3-cm lobulating hypoechoic lesion in segment III of the liver. On abdominal CT, an arterial, enhancing lesion with a low-density center was noted in the subcapsular portion of segment III of the liver. Liver MRI was then performed, which showed the lesion in segment III to have bright signal intensity similar to that of bile contents in the gallbladder on T2- weighted images and hypointensity in comparison with the normal liver parenchyma on unenhanced T1-weighted images. The lesion was found to have homogeneous contrast uptake on the early and late arterial phases (20 and 40 seconds) and the portal phase (65 seconds). An arterioportal shunt was noted adjacent to the lesion by an irregularly shaped enhancement. On the equilibrium phase (3 minutes) and hepatobiliary phase (20 minutes), the lesion appeared homogeneously hypointense because of the much stronger gadoxetic acid uptake of the surrounding normal liver parenchyma. On subtraction images, the lesion was isointense relative to the surrounding liver parenchyma, indicating that contrast media still remained in the lesion (Fig. 1). The percentage changes in SNR of the hemangioma were 172.27% during the arterial phase and 108.79% during the equilibrium phase, indicating that contrast media remained in the lesion. The percentage changes in the SNR of the hepatic parenchyma were 87.25% and 351.64% in the arterial and equilibrium phases, respectively. However, the CNRs in the arterial and equilibrium phases were 298.2 and 53.39, respectively. The signal intensity of the lesion was relatively low compared with the surrounding liver parenchyma (Table 1). We performed a sonography-guided biopsy of the lesion, and a cavernous hemangioma was confirmed by the pathology report. Patient 2 underwent an abdominal CT with 75-second single-phase delayed imaging after a polypectomy in the sigmoid colon. An approximately 1.2-cm low-attenuating lesion at segment IV of the liver was detected, and it could not be specifically diagnosed with only single-phase CT. On liver MRI, the lesion in segment IV, which was detected on CT, showed low signal intensity on the T1-weighted image and bright signal intensity on the T2-weighted image without enhancement on the dynamic contrast-enhanced study. Thus, it was confirmed as a cyst. However, there was another incidentally found 0.9-cm lesion in segment II. This lesion showed bright signal intensity on the T2-weighted image, dominant contrast enhancement in the arterial phase, and hypointensity compared with the normal liver parenchyma on the equilibrium phase (3 minutes). The percentage changes in the SNR of the hemangiomas were 355.65% during the arterial phase and 270.55% during the equilibrium phase. The percentage changes in the SNR of the hepatic parenchyma were 102.22% and 177.02% for the arterial phase and the equilibrium phase, respectively. The CNR was 65.6 during the arterial phase and 58.3 during the equilibrium phase (Table 1). A gadobutrol-enhanced study performed 2 weeks later confirmed that the lesion was a hemangioma by showing persistent enhancement on the delayed image. In patient 3, an approximately 2.5-cm illdefined mass was noted in segment V of the liver on dynamic CT. The mass showed peripheral globular enhancement on the arterial and portal phases, with an arterioportal shunt. Liver MRI revealed bright signal intensity of the lesion on the T2-weighted image and faint peripheral enhancement on the early arterial AJR:193, December 2009 W491
Doo et al. Fig. 1 54-year-old man (patient 1) with histologically proven cavernous hemangioma of liver. A C, On gadoxetic acid enhanced T1-weighted images, lesion shows homogeneous enhancement during early arterial phase (20 seconds) (A), relative hypointensity in relation to gadoxetic acid uptake by surrounding normal liver parenchyma during equilibrium phase (3 minutes) (B), and lower signal intensity during hepatobiliary phase (20 minutes) (C). D, On T2-weighted image (fat-suppressed respiratory-triggered T2-weighted turbo spin-echo sequence, TR range/te range, 3,500 5,000/70 85), lesion has bright signal intensity similar to that of bile contents in gallbladder. E, On subtraction image of unenhanced and equilibrium phases, isointensity of lesion is noted. A C B D E W492 AJR:193, December 2009
Pseudo Washout Sign on MRI of Hemangioma TABLE 1: Signal-to-Noise Ratio (SNR) of Hemangioma and Hepatic Parenchyma and Percentage Change of SNR and Contrast-to-Noise Ratio (CNR) of Hemangioma Patient Unenhanced phase (20 seconds), with more prominent enhancement on the late arterial phase (40 seconds). It had slightly low signal intensity on the equilibrium phase (3 minutes) and a significantly lower intensity on the hepatobiliary phase (20 minutes) (Fig. 2). Like the findings in patient 2, the lesion enhanced mainly on the arterial phase, leading to the belief that it was a high-flow hemangioma. After 3 months, we could confirm the lesion as a hemangioma by observing persistent enhancement on the delayed image during the gadobutrol-enhanced study (Fig. 2). On gadoxetic acid enhanced MRI, the percentage changes in the SNR of the hemangioma were 263.73% during the arterial phase and 200.68% during the equilibrium phase. The percentage changes in the SNR of the hepatic parenchyma were 23.68% during the arterial phase and 113.7% during the Arterial SNR a Equilibrium Hepatobiliary equilibrium phase. For gadobutrol-enhanced MRI, the percentage changes in the SNR of the hemangioma were 574% during the arterial phase and 475% during the equilibrium phase. However, the percentage changes in the SNR of the hepatic parenchyma were 224% and 106% for each phase (Table 1). Therefore, we could find the difference in the percentage change in the SNR of the surrounding liver between the gadoxetic acid and gadobutrolenhanced studies. The findings of the hemangiomas in all three patients are summarized in Tables 1 and 2. Discussion Hemangiomas are common benign liver lesions. The majority of hemangiomas show a characteristic enhancement pattern after a bolus injection of contrast material: early Unenhanced Arterial CNR b Equilibrium Hepatobiliary 1 69.1 298.2 53.39 91.76 Hemangioma 160.56 437.16 335.24 71.2 Percentage change in SNR 172.27 108.79 55.65 Liver 90.36 169.2 408.1 129.2 Percentage change in SNR 87.25 351.64 42.98 2 40.9 65.6 58.3 195.9 Hemangioma 58.4 266.1 216.4 104.9 Percentage change in SNR 355.65 270.55 79.62 Liver 99.2 200.6 274.8 300.8 Percentage change in SNR 102.22 177.02 203.23 3 19.95 65.11 10.46 55.52 Hemangioma 36.89 134.18 110.92 55.13 Percentage change in SNR 263.73 200.68 49.44 Liver 56.8 70.25 121.38 110.65 Percentage change in SNR 23.68 113.70 94.81 Extracellular contrast media in patient 3 c 37.6 72.25 127.48 Hemangioma 55.59 374.63 319.39 Percentage change in SNR 574 475 Liver 93.21 302.29 191.9 Percentage change in SNR 224 106 Note Percentage change in SNR = [(SNR of each phase SNR of unenhanced phase) / SNR of unenhanced phase x 100]. a SNR = [signal intensity (SI) of the hemangioma or liver / SD noise]. b CNR = [(SI of hemangioma SI of liver) / SD noise]. c Gadobutrol-enhanced MRI. peripheral nodular enhancement with centripetal progression [2, 3, 10, 11]. However, the patterns displayed for hemangiomas can vary. Yamashita et al. [11] described three contrast-enhancement patterns of hemangiomas: characteristic progressive fill-in after peripheral globular contrast enhancement, diffuse enhancement throughout the tumor in the arterial-dominant phase, and enhancement only in the periphery of the tumor when enhancement of the majority of the area is less than 10 HU. It has been shown that dynamic enhancement patterns of cavernous hemangiomas are related to the internal architecture or collective size of their constituent vascular spaces and differ from tumor to tumor [11]. Because of their histologic appearance, some atypical hemangiomas show immediate homogeneous enhancement and AJR:193, December 2009 W493
Doo et al. others show minimal enhancement or completely lack enhancement [2]. Therefore, the high-flow hemangioma shows rapid arterialphase dominant contrast enhancement and frequently shows an accompanying adjacent arterioportal shunt because of hyperdynamic status with large arterial inflow [1, 2]. Gadoxetic acid disodium (Primovist) is a hepatobiliary contrast agent that has an efficient extracellular phase and a liver-specific phase in a clinically acceptable time frame. This contrast agent may also enable the image interpreter to detect lesions at a higher rate and to characterize focal liver lesions [8, 12, 13]. Hammerstingl et al. [14] reported TABLE 2: Findings of High-Flow Hepatic Hemangiomas in Three Patients Patient No. Signal Intensity on MRI T2-Weighted Imaging Arterial Equilibrium 1 Hyperintense (as bright as gallbladder contents) Arterial-Dominant Enhancement a Homogeneous, hyperintense Hypointense 0.97 Biopsy, CT Confirmation 2 Hyperintense Homogeneous, hyperintense Hypointense 0.99 Extracellular contrast media enhanced MRI, follow-up MRI 3 Hyperintense Peripheral, hyperintense Hypointense 0.70 Extracellular contrast media enhanced MRI, CT, follow-up MRI a Enhanced proportion of the lesion on arterial phase [enhanced area of lesion / area of total lesion]. A C Fig. 2 48-year-old man (patient 3) with chronic hepatitis C and hepatic hemangioma in segment V, confirmed by follow-up gadobutrol-enhanced MRI. A C, On gadoxetic acid enhanced T1-weighted images, lesion in segment V shows dominant enhancement during late arterial phase (40 seconds) (A), relatively hypointense signal during equilibrium phase (3 minutes) (B), and definite low intensity during hepatobiliary phase (20 minutes) (C). D, Note bright signal intensity of lesion on T2-weighted image (fat-suppressed respiratory-triggered T2-weighted turbo spin-echo sequence, TR range/te range, 3,500 5,000/70 85, 3-mm slice thickness). (Fig. 2 continues on next page) B D W494 AJR:193, December 2009
Pseudo Washout Sign on MRI of Hemangioma Fig. 2 (continued) 48-year-old man (patient 3) with chronic hepatitis C and hepatic hemangioma in segment V, confirmed by follow-up gadobutrol-enhanced MRI. E, On gadobutrol-enhanced image after 3 minutes, lesion shows persistent enhancement, proven to be high-flow hemangioma. F, Subtraction image shows enhancement of lesion, confirming diagnosis. sensitivities of 77.1% for CT and 87.42% for gadoxetic acid enhanced MRI for the detection and localization of lesions. Halavaara et al. [15] reported that gadoxetic acid enhanced MRI was able to correctly characterize lesions in 89% of cases. This was significantly better than the use of helical CT, which had a sensitivity of 80% [14, 15]. However, problematic issues might occur in the differentiation of high-flow hemangiomas from HCC after gadoxetic acid enhanced MRI if the lesion shows a pseudo washout sign. Previous reports have described gadoxetic-acid enhancement in hepatic hemangiomas as an early peripheral nodular enhancement with subsequent partial or complete filling and persisting enhancement during the equilibrium phases [8]. To the best of our knowledge, no previous report on gadoxetic acid enhanced MRI findings of high-flow hemangiomas has been published. We were also unable to find literature regarding the incidence of high-flow hemangiomas. However, among approximately 400 patients who underwent MRI with gadoxetic-acid enhancement in our institution, there were three cases of confirmed highflow hemangiomas (0.75%). In our three patients, hepatic lesions showed bright signal intensity, as high as the gallbladder contents on T2-weighted imaging; rapid, intense homogeneous arterial enhancement; and relatively low signal intensity compared with the liver parenchyma on the equilibrium and delayed phases. Presentations with equilibrium phase washouts and arterial-dominant phase E enhancement patterns did not permit a confident diagnosis of hepatic hemangioma and mimicked HCC in our patients. The first patient underwent a sonography-guided liver biopsy, and the lesion was confirmed to be a cavernous hemangioma. When the findings for the other two patients were similar to this first experience, we considered the previously mentioned findings to be hemangiomas on gadoxetic acid enhanced MRI. A high-flow hemangioma on gadoxetic acid enhanced MRI could show bright signal on a T2-weighted image; a rapid, intense homogeneous or dominant portion enhancement on the arterial phase; or a pseudo washout pattern on the equilibrium phase. The pseudo washout sign was not considered a true contrast washout as occurs in HCC. Rather, it was thought to be due to contrast uptake in the surrounding normal liver parenchyma; the lesion itself might have low signal intensity. We measured SNR, CNR, and percentage change of SNR. These measurements revealed a slightly decreased SNR for hemangioma between the arterial and equilibrium phases and increased SNR of the hepatic parenchyma during the same phases. The CNR of the hemangioma was relatively low during the equilibrium phase because of increased parenchymal signal intensity. The percentage change in the SNR of the hemangioma showed a value similar to that of gadoxetic-acid enhancement on the gadobutrol-enhanced image in patient 3. However, the SNR of the hepatic parenchyma was decreased during the equilibrium phase of the gadobutrolenhanced study. Conversely, the SNR was increased on the gadoxetic acid enhanced study. Therefore, it can be concluded that the contrast agent remained in the hemangioma on the equilibrium phase, and the pseudo washout sign is caused by gadoxetic-acid uptake in the surrounding hepatic parenchyma. In conclusion, high-flow hemangiomas may show similar characteristics to those seen in hypervascular tumors on gadoxetic acid enhanced MRI. We observed the pseudo washout sign of high-flow hemangiomas, which showed relatively low signal intensity because of continuous contrast uptake in the surrounding normal hepatic parenchyma during the equilibrium phase. Therefore, high-flow hemangiomas should be considered when the following are observed: bright signal intensity on T2-weighted imaging, arterial-phase dominant enhancement, pseudo washout sign during the equilibrium phase, frequent perilesional arterioportal shunt, and isointensity or slightly increased signal intensity on the subtraction images between the unenhanced phase and the equilibrium phase. References 1. Jang HJ, Kim TK, Lim HK, et al. Hepatic hemangioma: atypical appearances on CT, MR imaging, and sonography. AJR 2003; 180:135 141 2. Kim KW, Kim TK, Han JK, Kim AY, Lee HJ, Choi BI. Hepatic hemangiomas with arterioportal shunt: findings at two-phase CT. Radiology 2001; 219:707 711 3. Burkholz KJ, Silva AC. AJR teaching file: hypervascular metastasis or hepatic hemangioma? AJR 2008; 190[6 suppl]:s53 S56 F AJR:193, December 2009 W495
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