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Original Article

Characterization of hyperintense nodules on T1-weighted liver magnetic

resonance imaging: Comparison of Ferucarbotran-enhanced MRI with

accumulation-phase FS-T1WI and gadolinium-enhanced MRI

Chen-Te Chou

a,c

, Ran-Chou Chen

a,b,

*

, Wei-Tsung Chen

b

, Jiunn-Ming Lii

b

a

Department of Biomedical Imaging and Radiological Science, National Yang-Ming University, Taipei, Taiwan, ROC

b

Department of Radiology, Taipei City Hospital, Taipei, Taiwan, ROC

c

Department of Radiology, Chang-Hua Christian Hospital, Er-lin branch, Chang-Hua, Taiwan, ROC Received February 19, 2010; accepted November 2, 2010

Abstract

Background: T1-weighted (T1W) hyperintense nodules against a background of cirrhosis are diagnostically challenging in daily practice. All regenerative nodules, dysplastic nodules and hepatocellular carcinoma (HCC) might present hyperintense on T1W imaging (T1WI), so T1W hyperintense nodules cannot be definitively characterized as dysplastic nodules or HCC before biopsy, resection or transplantation. The purpose of our study was to evaluate Ferucarbotran-enhanced Magnetic Resonance Imaging (MRI) with accumulation-phase fat suppression T1-weighted imaging (FS-T1WI) in comparison with gadolinium-enhanced MRI for characterization of hyperintense nodules on unenhanced T1WI within cirrhotic liver.

Methods: Two separate groups of patients with histologically-proven T1W hyperintense nodule on MRI were retrospectively identified. The Ferucarbotran group consisted of 17 T1W hyperintense nodules in 12 patients. The gadolinium group consisted of 22 T1W hyperintense nodules in 21 patients. All of the patients had liver cirrhosis. Finally, 11 HCC nodules, and six benign nodules were included in the Ferucarbotran group; 15 HCC nodules and seven benign nodules were included in the gadolinium group.

Results: With the conventional criteria, in the gadolinium-enhanced group, the sensitivity, specificity, and accuracy were 53%, 100%, and 73%, respectively. Using the conventional criteria in the Ferucarbotran group, the sensitivity, specificity, and accuracy were 73%, 100%, 82%, respectively. Using the conventional criteria plus hyperintense on the accumulation-phase FS-T1WI in the Ferucarbotran group for character-ization of the T1W hyperintense nodules, the sensitivity, specificity, and accuracy were 100%, 83%, 94%, respectively. The sensitivity of Ferucarbotran-enhanced MR with accumulation-phase FS-T1WI was better than that of gadolinium-enhanced MRI ( p¼ 0.01).

Conclusion: Ferucarbotran-enhanced MRI with accumulation-phase FS-T1WI is superior to gadolinium-enhanced MRI in characterization of T1W hyperintense nodules within cirrhotic liver. T1W hyperintense nodule within cirrhotic liver depicting hyperintense on Ferucarbotran-enhanced accumulation-phase FS-T1WI should be investigated aggressively.

CopyrightÓ 2011 Elsevier Taiwan LLC and the Chinese Medical Association. All rights reserved.

Keywords: Dysplastic nodule; Ferucarbotran; Gadolinium; Hepatocellular carcinoma; T1-weighted hyperintense nodule

1. Introduction

Cirrhosis is a diffuse liver disease that is characterized by fibrosis and nodular regeneration. Hepatocellular carcinoma

(HCC) develops by means of a multi-step dedifferentiation process that progresses from regenerative nodule to dysplastic nodule and then to HCC.1Hepatic resection or transplantation is the most effective treatment for HCC if the diagnosis is made at an early stage.2Accurate preoperative imaging for the detection of HCC or dysplastic nodule is therefore crucial. T1-weighted (T1W) hyperintense nodules on unenhanced T1W imaging (T1WI) against a background of cirrhosis are * Corresponding author. Dr. Ran Chou Chen, Department of Radiology,

Taipei City Hospital, 10, Section 4, Renai Road, Taipei 106, Taiwan, ROC. E-mail address:chenranchou@yahoo.com.tw(R.-C. Chen).

Journal of the Chinese Medical Association 74 (2011) 62e68

www.jcma-online.com

1726-4901/$ - see front matter CopyrightÓ 2011 Elsevier Taiwan LLC and the Chinese Medical Association. All rights reserved. doi:10.1016/j.jcma.2011.01.013

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diagnostically challenging in daily practice. All regenerative nodules, dysplastic nodules, and HCC might present hyper-intense on unenhanced T1WI, so T1W hyperhyper-intense nodules cannot be definitively characterized as dysplastic nodules or HCC before biopsy, resection or transplantation.3e5

Positive arterial enhancement during dynamic Magnetic Resonance Imaging (MRI) is a well-known criterion in diag-nosis of HCC.6,7 Gadolinium-enhanced multiphase dynamic imaging has generally been used for the vascular assessment of focal lesions in cirrhotic liver.6e8 However, determination of contrast enhancement is not always easy to accomplish for T1W hyperintense lesions in arterial phase during dynamic imaging.9

Superparamagnetic iron oxide (SPIO) is a liver-specific particulate MRI contrast agent that is primarily taken up by the Kupffer cells of the liver. SPIO-enhanced MRI reflects Kupffer-cell numbers in HCCs and is useful for estimation of histological grading in HCCs.10The uptake clustered particles can produce the susceptibility effect and cause loss of signal intensity on both postcontrast T2W and T1W images.11 We hypothesized that Ferucarbotran-enhanced MRI might be superior to gadolinium-enhanced MRI in characterization of T1W hyperintense nodules within cirrhotic liver. To our knowledge, this had not been investigated previously. The purpose of our study was to evaluate the Ferucarbotran-enhanced MRI with accumulation-phase fat suppression T1WI in comparison with gadolinium-enhanced MRI for characterization of hyperintense nodules on unenhanced T1WI within cirrhotic liver.

2. Methods

2.1. Patient population

Approval for retrospective study was obtained from our institutional review board. Two separate groups of patients with focal hepatic lesions who had received liver biopsy or surgery from January 2004 to December 2006 were retro-spectively identified from medical records. One patient group had undergone Ferucarbotran-enhanced MRI, and the other group underwent gadolinium-enhanced MRI. An attending radiologist with more than 10 years’ experience in hepatic MRI retrieved the images and conducted a prelimi-nary review on the picture archiving and communication system (PACS) monitor for the initial selection of patients and lesions among the patients. The criteria for entry into the analysis were as follows: (1) The nodule which under-went histological examination should present hyperintense on T1W opposed-phase imaging; (2) The time interval between initial MR study and histological examination should be less than one month; and (3) The diagnosis of HCCs should be based on histological examination. For nodules with benign histological result, follow-up imaging study should be performed for at least one year. When the benign nodule was stable in size for at least one year, it was confirmed as a benign lesion. When the benign nodule was enlarged or depicted arterial enhancement during the

follow-up period, it was considered as a benign nodule with malignant potential.

2.2. Ferucarbotran patient group

The Ferucarbotran patient population consisted of 17 T1W hyperintense nodules (mean size, 2.0 1.1 cm) in 12 patients (10 men and 2 women) who ranged in age from 28 to 83 years (mean age: 56 years). The other nodules of the 12 patients without histological examination were ignored. All patients had liver cirrhosis and chronic hepatitis (hepatitis B, eight patients; hepatitis C, two patients; hepatitis B and C, two patients). Seven patients had a solitary lesion, five patients had two lesions. Two nodules in two patients underwent surgical resection. Fifteen nodules in 10 patients received needle biopsy. One benign nodule (1.3 cm in size) was enlarged and depicted arterial enhancement during dynamic study on the follow-up Computed tomography (CT) and MRI. The other five histologically benign nodules showed no obvious changes on the follow-up MRI studies (mean period, 20 months). Finally, 11 HCC nodules, five benign nodules, and one benign nodule with malignant potential were diagnosed.

2.3. Gadolinium patient group

The gadolinium patient population consisted of 22 T1W hyperintense nodules (mean size, 2.1 0.7 cm) in 21 patients (13 men and 8 women) who ranged in age from 30 to 78 years (mean age: 62 years). The other nodules of the 21 patients without histological examination were ignored. Eighteen patients had liver cirrhosis and chronic hepatitis (hepatitis B, 9 patients; hepatitis C, 5 patients; hepatitis B and C, 4 patients), and 3 patients had alcoholic cirrhosis. Twenty patients had a solitary lesion, and one patient had two lesions. Two nodules in two patients underwent surgical resection. Twenty nodules in 19 patients received needle biopsy. The seven benign nodules showed no obvious changes on the follow-up MRI studies (mean period, 17 months). Finally, 15 HCC nodules and 7 benign nodules were diagnosed.

2.4. MRI

All MRI (for both Ferucarbotran and gadolinium study groups) was performed with a 1.5-T MR system (Philips Gyroscan ACS-NT, Best, The Netherlands), equipped with a body phased-array coil. Unenhanced MRI was performed with T2W turbo spin-echo (TSE) axial imaging (T2WI, TR/TE: 2500/90 ms; turbo spin-echo factor, 23; slice thickness 8 mm, gap 0.8 mm) without and with fat suppression (FS) under respiratory trigger, T2*-echo planar imaging (EPI) (TR/TE 500/13.8 ms; angle, 35) obtained during one-breath hold, T1-weighted dual echo imaging (TR/TE: 210/2.3 ms and 4.6 ms; slice thickness 8 mm, gap 0.8 mm) during one or two breath-holdings according to the liver size of the patients. Automatic shimming was applied for fat saturation imaging to maximize magnetic field homogeneity. Flow compensation was also used.

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2.5. Ferucarbotran-enhanced MRI

Ferucarbotran (Resovist, Schering, Germany), consisting of SPIO microparticles coated with carboxydextran, was pre-loaded at volume of 1.4 mL (>50 kg body weight) into a connecting intravenous tube and manually injected rapidly through a filter with a 5-mm pore size. Dynamic T1W fast field echo (FFE) imaging (175e210/1.3e2.1; flip angle, 80) was carried out before, 18e20 seconds and 50e55 seconds after the contrast agent injection. An equilibrium-phase T1W with FS imaging (FS-T1WI, TR/TE 241e344/2.7 ms, flip angle, 70; slice thickness 8 mm, gap 0.8 mm) with breath-holding was performed 180 seconds after the contrast agent injection. Approximately 10 minutes after intravenous injection of the SPIO agent, the postcontrast accumulation-phase images, including T2W axial imaging without and with FS, T2*-EPI, were performed using the same parameters as the precontrast sequences. Finally, FS-T1WI was performed after completion of the postcontrast T2WI.

2.6. Gadolinium-enhanced MRI

Gadopentetate dimeglumine (Magnevist; Schering, Berlin, Germany) at 0.1 mmol Gd/kg body weight was manually injected rapidly. Dynamic T1W FFE imaging (175e210/ 1.3e2.1; flip angle, 80) was carried out before, 18e20 seconds and 50e55 seconds after the contrast agent injection. An equilibrium-phase FS-T1W (TR/TE 241e344/2.7 ms, flip angle, 70; slice thickness 8 mm, gap 0.8 mm) was performed with breath-holding 180 seconds after the contrast agent injection.

2.7. Data analysis

Imaging analysis was performed on a dual-screen diag-nostic workstation (GE Healthcare, Milwaukee, WI, USA). All images were reviewed retrospectively by two radiologists who had more than 10 years of experience in liver MRI. They did not know the final diagnosis.

Only histologically-proven nodules which presented hyperintense on the opposed-phase T1W images of the initial MR study according to the position of ultrasonography-guiding biopsy were reviewed. Signal intensity on T2WI and enhancement patterns of the corresponding lesions on contrast-enhanced dynamic images were also recorded. The presence of arterial enhancement of the lesion was detected by automatic subtraction of multiphasic dynamic study using the software of the MR machine. The follow-up MR images of the patients with benign T1W hyperintense nodule were reviewed by the two same radiologists to assess the serial changes based on viewing of both MR images. When the interpretations of the two radiologists differed, a third radiologist joined the discussion until consensus was reached.

The reviewers used the following criteria for characteriza-tion of the T1W hyperintense nodules. The convencharacteriza-tional HCC diagnostic criteria for gadolinium-enhanced MR images were nodule presented hyperintense on the precontrast T2WI or

presence of early arterial enhancement during dynamic MRI.6 The conventional HCC diagnostic criteria for Ferucarbotran-enhanced MR images were nodule presented hyperintense on the precontrast or postcontrast T2WI/T2*EPI or presence of early arterial enhancement during dynamic MRI.6,7,10Besides the conventional criteria, when a nodule showed hyperintense on the Ferucarbotran-enhanced accumulation-phase FS-T1WI, the nodule was also diagnosed as HCC.12,13

2.8. Statistical analysis

An independent t test was used to compare continuous variable, such as the patient’s age and tumor size, between the Ferucarbotran-enhanced and gadolinium-enhanced groups. Categorical variables, such as patient gender, background liver disease (hepatitis, Child-Pugh class) were carried out using the chi-square test. Chi-square test was also used to compare the diagnostic difference between Ferucarbotran-enhanced and gadolinium-enhanced groups and to compare the difference between histological results of T1W hyperintense nodules. Wilcoxon signed ranks test was used to compare the diag-nostic difference between conventional criteria and accumu-lation-phase FS-T1WI within Ferucarbotran-enhanced group. The results were considered significant at p< 0.05. Kappa statistic was performed to evaluate the inter-observer differ-ence. The result was expressed as k values and could be classified according to a scale, (poor, <0; slight, 0.0e0.20; fair, 0.21e0.40; moderate, 0.41e0.60; good, 0.61e0.80; and excellent, 0.81e1.00).

3. Results

In characterization of the T1W hyperintense nodules, an excellent agreement of inter-observer agreement between the two reviewers was noted in the Ferucarbotran-enhanced group (k ¼ 0.86) and the gadolinium-enhanced group (k ¼ 0.81). Overall, a consensus reading was necessary for one (1/17) lesion in the Ferucarbotran group, and this was necessary for two (2/22) lesions in the gadolinium-enhanced group.

With regard to patient’s age ( p¼ 0.54), gender ( p ¼ 0.2), background liver disease ( p¼ 0.94), and tumor size ( p¼ 0.28), there were no statistically significant differences between the Ferucarbotran-enhanced and gadolinium-enhanced groups. The histological grading of the T1W hyperintense nodules in both groups is shown in Table 1. When only HCCs were considered, the percentage of well-differentiated HCC (20/26) was significantly higher than that of moderately-differentiated HCC (6/26) ( p< 0.001). Seventy-three percent (8/11) in the Ferucarbotran-enhanced group, and 80% (12/15) in the gadolinium-enhanced group were well-differentiated HCCs.

The tumor numbers, sizes, signal intensities on precontrast T2WI and enhancing patterns for both groups are shown in

Table 2 and Table 3. In the Ferucarbotran-enhanced group,

seven nodules showed hyperintense on precontrast T2WI, four nodules showed arterial enhancement during dynamic study

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postcontrast T2WI/T2*EPI. The other nodules showed hypo-intense or isohypo-intense on T2WI and no arterial enhancement during dynamic study (Fig. 2). With the conventional HCC diagnostic criteria, 8 of 11 HCC nodules in the Ferucarbotran-enhanced group were correctly diagnosed. All of the HCC nodules and the benign nodule with malignant potential showed hyperintense on the accumulation-phase FS-T1WI. There were three additional HCC nodules detected by the accumulation-phase FS-T1WI.

In the gadolinium-enhanced group, five nodules showed hyperintense on T2WI and eight nodules showed arterial enhancement during dynamic study. With the conventional HCC diagnostic criteria, 8 of 15 HCC nodules in the gadoli-nium-enhanced group were correctly diagnosed. The other nodules showed hypointense or isointense on T2WI and no arterial enhancement during dynamic study.

The results of conventional HCC diagnostic criteria for characterization of the T1W hyperintense nodules in the gadolinium/Ferucarbotran-enhanced groups and conventional criteria plus additional accumulation-phase FS-T1WI in the Ferucarbotran group are shown in Table 4. Using the conventional criteria in the gadolinium-enhanced group, the sensitivity, specificity, and accuracy were 53%, 100%, and 73%, respectively. Using the conventional criteria in the Ferucarbotran group, the sensitivity, specificity, and accuracy were 73%, 100%, and 82%, respectively. Using the conventional criteria plus accumulation-phase FS-T1WI for characterization of the T1W hyperintense nodules, the sensitivity, specificity and accuracy were 100%, 83%, and 94%, respectively. The sensitivity of Ferucarbotran-enhanced MR with accumulation-phase FS-T1WI was significantly higher than that of gadolinium-enhanced ( p¼ 0.01) and

Ferucarbotran-enhanced MRI with conventional criteria ( p¼ 0.002).

Only 1 of 11 HCC nodules in the Ferucarbotran-enhanced group and 3 of 15 HCC nodules in the gadolinium-enhanced group showed the washout phenomenon in the equilibrium-phase T1WI. None of the benign nodules in either group showed washout phenomenon in the equilibrium-phase T1WI. 4. Discussion

Hyperintense nodules on unenhanced T1WI against a background of cirrhosis are a diagnostic challenge in daily practice. In our results, the sensitivity was significantly higher in Ferucarbotran-enhanced MRI with accumulation-phase FS-T1WI than gadolinium-enhanced ( p¼ 0.01) and Fer-ucarbotran-enhanced MRI ( p¼ 0.002) in characterization of the hyperintense nodules on unenhanced T1WI. The statistical difference was because of the low sensitivity for HCC with the conventional criteria of gadolinium-enhanced and Ferucarbo-tran-enhanced MRI. Using the conventional criteria in dis-tinguishing HCC from benign nodules, the sensitivity was only 53% in the gadolinium-enhanced group and 73% in the conventional criteria of Ferucarbotran-enhanced group. There are two possible reasons to explain this. First, 77% of the HCCs (20/26) in both groups were well-differentiated HCCs and only 23% (6/26) were moderately HCC in our study ( p< 0.001). This might be because of well-differentiated HCC frequently presenting hyperintense on the unenhanced T1WI.14 Li et al. also reported the MR appearance of well-differentiated HCCs was diverse; only 36% showed hyperin-tense on T2WI, and 51% showed arterial enhancement during dynamic study.14Second, hyperintensity on precontrast T1WI might mask subtle arterial enhancement and decreased diag-nostic performance of the dynamic MR study. These two reasons might explain the low sensitivity for HCC with the conventional criteria of gadolinium-enhanced MRI in char-acterization of the T1W hyperintense nodules.

Yu et al. reported dynamic subtraction MR imaging could be useful for the characterization of T1W hyperintense lesions.9However, poor subtraction imaging quality because of misregistration artifact was encountered in our study. New MR software with the function of auto-registration might be needed. Using Ferucarbotran-enhanced accumulation-phase FS-T1WI in characterization of the T1W hyperintense nodules, the accumulation-phase FS-T1WI can be obtained

Table 2

Number, size, and signal intensity on T2-weighted imaging and enhancing pattern for T1-weighted hyperintense nodules in Ferucarbotran-enhanced group Lesion type Tumor number Size (cm) Hyper on T2WI/T2*EPI Arterial enhancement

during dynamic study

“Washout” on EP F S-T1WI Hyper on AP FS-T1WI Precontrast Postcontrast HCC 11 2.3 1.3 7 8 4 1 11 Benign nodule 6 1.6 0.4 0 0 0 0 1a a

The nodules was enlarged in follow-up computed tomography and magnetic resonance imaging.

AP¼ accumulation phase; EP ¼ equilibrium phase; FS-T1WI ¼ T1-weighted imaging with fat suppression; HCC ¼ hepatocellular carcinoma; Hyper ¼ hyperintense; T2*EPI¼ T2*-echo planar imaging; T2WI ¼ T2-weighted imaging.

Values are depicted as mean standard deviation. Table 1

Histological results of T1-weighted hyperintense nodules in both ferucarbo-tran-enhanced and gadolinium-enhanced groups

Lesion type Pathology Ferucarbotran group Gadolinium group Total

HCC wHCC 8 12 20

mHCC 3 3 6

Benign nodule DN or RN 6a 7 13

a

One of the nodules was enlarged with arterial enhancement in follow-up computed tomography and magnetic resonance.

DN¼ dysplastic nodule; HCC ¼ hepatocellular carcinoma; mHCC ¼ moderately-differentiated HCC; RN¼ regenerative nodule; wHCC ¼ well-differentiated HCC.

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without additional body positioning or hardware preparation. The scan time for the accumulation-phase FS-T1WI with breath-holding is short (18e21 seconds for one breath-holding, 28e31 seconds for two breath-holdings) and can be performed immediately after the postcontrast T2WI.

Several studies have shown that the characteristic HCC profile includes intense arterial uptake but is followed by contrast washout in the late phase of dynamic imaging tech-niques including contrast-enhanced US, CT, and MRI.15e17 For the washout phenomenon, only one HCC nodule (1/11) in the Ferucarbotran-enhanced group and three HCC nodules (3/15) in the gadolinium-enhanced group depicted washout phenomenon in equilibrium-phase T1WI in our study. Mean-while, all of the HCC nodules in the Ferucarbotran-enhanced group showed hyperintense on accumulation-phase FS-T1WI. According to our results, the washout phenomenon for HCC diagnosis seemed to be inappropriate in characterization of T1W hyperintense nodules.

There are two possible reasons to explain HCC nodules instead of benign nodules presenting hyperintensity on the Fer-ucarbotran-enhanced accumulation-phase FS-T1WI. First, the Kupffer-cell density of the HCC was lower and the benign nodule was higher than that of the adjacent normal liver paren-chyma.10,13,18The difference of Kupffer-cell density resulted in the signal intensity loss being higher in liver parenchyma than HCC nodules on accumulation-phase FS-T1WI. In contrast to HCC nodules, signal intensity loss of benign nodules was higher than or similar to that of liver parenchyma on accumulation-phase FS-T1WI. Second, HCC nodule was enhanced by the T1 effect of the residual circulating SPIO particles.19 These two reasons might explain why the HCC nodules depicted hyperin-tense on Ferucarbotran-enhanced accumulation-phase FS-T1WI. According to our results, the use of the Ferucarbotran-enhanced MR with accumulation-phase FS-T1WI was superior to the conventional criteria of gadolinium-enhanced MR imaging in distinguishing HCC from benign nodule among the T1W

Fig. 1. A 49-y/o man with well-differentiated hepatocellular carcinoma at S3 of the liver (arrow) underwent Ferucarbotran-enhanced magnetic resonance study. (A) T1-weighted opposed-phase image showed a hyperintense nodule on S3 of the liver. (B) The nodule was slightly hyperintense on fat suppression T2WI. (C) Arterial enhancement of the S3 nodule during dynamic T1WI was noted. (D) The nodule depicted hyperintense on the accumulation-phase FS-T1WI. FS-T1WI¼ T1-weighted imaging with fat suppression; T2WI ¼ T2-weighted imaging.

Table 3

Number, size, and signal intensity on T2-weighted imaging and enhancing pattern for T1-weighted hyperintense nodules in gadolinium-enhanced group Lesion type Tumor number Size (cm)a T2WI Arterial enhancement

during dynamic study

“Washout” on

equilibrium-phase T1WI Hyper Hypo or iso

HCC 15 2.1 0.8 5 10 8 3

Benign nodule 7 1.8 0.4 0 7 0 0

a

Values are depicted as mean standard deviation.

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hyperintense nodules. At the same time, one benign nodule with malignant potential also showed hyperintense on the Ferucarbotran-enhanced accumulation-phase FS-T1WI in the Ferucarbotran-enhanced group. Sampling error of the liver biopsy and high-grade differentiation of the benign (dysplastic) nodule were possible explanations.20e22However, that benign nodule might present hyperintense on accumulation-phase FS-T1WI should be kept in mind.

This study had several limitations. First, the study was retrospective. Imaging with Ferucarbotran and gadolinium was not performed in the same patient population. However, the histological classification and tumor size of T1W hyperintense nodules in the two populations was similar in our study.

Second, a majority of the tumor diagnoses were based on needle biopsy. Problems of sampling error and sampling variation are always inherent in this kind of examination. It is a known shortcoming in most comparative studies. Third, the patient population of both imaging groups in our study was small. Further investigations with larger patient population and prospective studies are needed.

In conclusion, Ferucarbotran-enhanced MRI with accumu-lation-phase FS-T1WI is superior to gadolinium-enhanced MRI in characterization of T1W hyperintense nodule within cirrhotic liver. T1W hyperintense nodule within cirrhotic liver depicting hyperintense on Ferucarbotran-enhanced accumulation-phase FS-T1WI should be investigated aggressively.

Table 4

The results of HCC diagnosis for characterization of the T1-weighted hyperintense nodules in the Ferucarbotran-enhanced and gadolinium-enhanced groups are shown

Histological diagnosis Ferucarbotran group (n¼ 17) Gadolinium group (n¼ 22) Conventional criteria Conventional criteria plus

accumulation-phase FS-T1WI Conventional criteria þ  þ  þ  HCC 8 3 11 0 8 7 DN 0 6 1 5 0 7 Sensitivity 73% 100% 53% Specificity 100% 83% 100% Accuracy 82% 94% 73%

DN¼ dysplastic nodule; FS-T1WI ¼ T1-weighted imaging with fat suppression; HCC ¼ hepatocellular carcinoma; þ ¼ nodule was diagnosed as HCC;  ¼ nodule was diagnosis as dysplastic nodule.

Fig. 2. A 54-y/o man with dysplastic nodules (arrow) at S3 of the liver underwent Ferucarbotran-enhanced MR study. (A) T1W opposed-phase image revealed a hyperintense nodule on S3 of the liver. (B) The nodule was isointense on fat suppression T2WI. (C) No arterial enhancement of the tumor during dynamic T1W imaging was noted. (D) The nodule depicted hypointense on the accumulation-phase FS-T1WI.

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It should be also noted that the LTM is based on the Cauchy(-Poincare) theorem, which states that in- tegral of an analytic (holomorphic) function is independent of the integral path