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AJR 2005; 184:1069-1076
© American Roentgen Ray Society

Ferucarbotran-Enhanced MRI Versus Triple-Phase MDCT for the Preoperative Detection of Hepatocellular Carcinoma

Seong Hyun Kim1,2, Dongil Choi1, Seung Hoon Kim1, Jae Hoon Lim1, Won Jae Lee1, Min Ju Kim1, Hyo K. Lim1 and Soon Jin Lee1

1 Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Gangnam-gu, Seoul 135-710, South Korea.
2 Department of Radiology, Wonju Christian Hospital, Wonju College of Medicine, Yonsei University, 162 Ilsandong, Wonju, Kangwon-do 220-701, South Korea.

Received June 3, 2004; accepted after revision August 10, 2004.

 
Address correspondence to D. Choi.


Abstract
Top
 Abstract
Introduction
 Subjects and Methods
 Results
 Discussion
 References
 
OBJECTIVE. We compared ferucarbotran-enhanced MRI with triple-phase MDCT for the preoperative detection of hepatocellular carcinoma.

SUBJECTS AND METHODS. Seventy-three consecutive patients with 121 hepatocellular carcinomas underwent ferucarbotran-enhanced MRI, including a dynamic study, and triple-phase MDCT before hepatic resection. The diagnosis of hepatocellular carcinoma was confirmed in all patients by means of pathologic examination after surgical resection. Three experienced radiologists independently reviewed the MR and CT images on a segment-by-segment basis. The accuracy of these techniques for the detection of hepatocellular carcinoma was assessed by conducting a receiver operating characteristic (ROC) analysis of the observations of 88 resected hepatic segments with at least one hepatocellular carcinoma each and 121 resected hepatic segments without hepatocellular carcinoma.

RESULTS. The mean values of the area under the ROC curve (Az) for ferucarbotran-enhanced MRI and triple-phase MDCT for all observers were 0.947 and 0.949, respectively; the difference between these two values was not statistically significant (p = 0.799). The mean sensitivities of MRI and triple-phase MDCT were 90.2% and 91.3%, respectively, and their mean specificities were 97.0% and 95.3%, respectively. The differences in the mean sensitivities and specificities of these two imaging techniques were not statistically significant (p > 0.05 in each case).

CONCLUSION. Ferucarbotran-enhanced MRI seems to be as accurate as triple-phase MDCT for the preoperative detection of hepatocellular carcinoma.


Introduction
Top
 Abstract
 Introduction
Subjects and Methods
 Results
 Discussion
 References
 
Hepatocellular carcinoma is the most common primary hepatic malignancy. In patients with hepatocellular carcinoma, surgical resection is considered to be the treatment of choice. In the preoperative evaluation of hepatocellular carcinoma, it is important to detect, characterize, and accurately localize the carcinoma in order to choose the most appropriate surgical procedure. CT, with multiphasic helical scanning, is the most frequently used imaging technique for the preoperative detection of hepatocellular carcinoma [1-3]. Recently, the advent of MDCT scanners, which offer faster speed, thinner slices, and multiphase scanning, has improved the chance of detecting hepatocellular carcinoma [4-8].

Superparamagnetic iron oxide material, such as ferumoxides, has been developed as a liver-specific particulate MR contrast agent. Superparamagnetic iron oxide is primarily taken up by the Kupffer's cells of the liver and the macrophages of the spleen, resulting in signal intensity loss in normal liver tissue because of the susceptibility effects of iron [9, 10]. Some investigators have suggested that ferumoxides-enhanced MRI is more accurate than other imaging techniques, such as multiphase helical CT or gadolinium-enhanced MRI, for the detection of hepatocellular carcinoma [11-14]. Another recently developed superparamagnetic iron oxide material, ferucarbotran (Resovist; Schering) particles coated with carboxydextran, has also been used in clinical practice. This material allows a dynamic study to be performed immediately after an IV bolus injection, as compared with ferumoxides [15, 16]. The purpose of this study was to compare ferucarbotran-enhanced MRI, including a dynamic study, with triple-phase MDCT for the preoperative detection of hepatocellular carcinoma.


Subjects and Methods
Top
 Abstract
 Introduction
 Subjects and Methods
Results
 Discussion
 References
 
Patient Selection
Between August 2002 and October 2003, triple-phase MDCT was performed at our institution in 368 consecutive patients suspected of having hepatocellular carcinoma on the basis of their sonographic findings and elevated {alpha}-fetoprotein level. Ferucarbotran-enhanced MRI was performed in 134 of these patients. Finally, 73 consecutive patients (61 men and 12 women; age range, 32-81 years; mean, 53 years) who had pathologically proven hepatocellular carcinoma according to hepatic resection surgery were selected for this study.

Hepatic resection surgery was performed within 3 weeks after the imaging studies: segmentectomy (n = 13), bisegmentectomy (n = 15), right lobectomy (n = 29), left lobectomy (n = 13), right lobectomy with segment I segmentectomy (n = 1), and liver transplantation (n = 2). A total of 219 hepatic segments were resected. The resected specimens were serially sliced with 5-mm thickness in the transverse or coronal plane, depending on the location of the tumor. The criterion for selecting a patient for partial hepatic resection surgery was the presence of one or more tumors of any size that were limited to one lobe of the liver with Child-Pugh class A function. The two patients who underwent liver transplantation also had Child-Pugh class A cirrhosis. The explanted livers showed grossly minimal changes of cirrhosis.

One hundred twenty-one hepatocellular carcinomas (13 well differentiated, 100 moderately differentiated, and eight poorly differentiated) in 88 segments were confirmed by pathologic examination. The tumors ranged from 0.3 to 15.5 cm in diameter (mean, 3.5 cm). In 35 (48%) of the 73 patients, liver cirrhosis was confirmed by the histopathologic examination of the resected specimen. Of these, 29 patients had related hepatitis B and six patients had related hepatitis C. Two patients had alcoholic hepatitis and the remaining seven patients had reactive hepatitis. The study was approved by our institutional review board, and written informed consent was obtained from all patients.

Imaging Methods
Triple-phase CT was performed with an MDCT scanner with four (n = 27) or eight (n = 46) detectors (LightSpeed QX/I or LightSpeed Ultra 8; GE Healthcare). The scanning parameters were 120 kVp, 175-184 mAs, 5-mm slice thickness, and a table speed of 15.0 mm/sec (pitch, 0.75) for the MDCT scanner with four detectors, and 17.5 mm/sec (pitch, 0.875) for the MDCT scanner with eight detectors during a single-breath-hold helical acquisition of 8-10 sec (depending on the liver size). Images were obtained in the craniocaudal direction and were reconstructed every 5 mm to provide contiguous sections. With a bolus-triggered technique, the arterial phase of scanning started 20-35 sec after the start of the IV injection of 120 mL of non-ionic iodinated contrast material ([iopamidol] Iopamiro 300; Bracco) through an antecubital vein at a rate of 4 mL/sec. The portal phase of scanning began 70 sec after the start of contrast material injection. The delayed phase of scanning began 180 sec after the start of contrast material injection.

MRI was performed with 1.5-T MRI units (Signa Horizon; GE Healthcare) within 10 days after CT. All images were obtained in the transverse plane using a phased-array multicoil as the receiver coil. For all pulse sequences, a 6- to 8-mm section thickness (according to the liver volume) was used with a 2-mm intersection gap and a field of view of 30-32 cm. Saturation bands superior and inferior to the imaging volume were applied in all sequences to minimize the number of motion artifacts. The dose of ferucarbotran was 1.4 mL in patients with a body weight of 60 kg or more and 0.9 mL in patients with a body weight of less than 60 kg (range, 8.0-12.0 µmol of iron/kg). The contrast agent was manually administered IV through an in-line 5-µm specific filter with a rapid bolus in 1 sec, immediately followed by a 10-mL saline solution flush. The entire procedure was performed in approximately 5 sec. Before injection of the contrast agent, a fat-suppressed respiratory-triggered fast spin-echo sequence with two TEs (proton density-weighted and T2-weighted images) (TR range/first-echo TE, second-echo TE range, 3,333-8,571/18, 90-117; an echo-train length of 10-18; two signals acquired; a 256 x 256 matrix; and a bandwidth of 120 Hz per pixel), a T2*-weighted fast multiplanar gradient-recalled echo acquisition in the steady state (TR/TE range, 130/8.4-10.4; flip angle, 30°; and bandwidth, 60 Hz per pixel), and a breath-hold in phase T1-weighted fast multiplanar spoiled gradient-recalled echo sequence (TR/TE, 200/4.2; 90° flip angle; and 256 x 160 matrix) were acquired. After the unenhanced images were obtained, enhanced images of the same sequences were obtained 10 min after the injection of the contrast agent. Dynamic enhanced T1-weighted fast multiplanar spoiled gradient-recalled echo images were also obtained with delays of 20 sec and 1, 3, and 5 min after the injection of the contrast agent. Twenty transverse images were obtained during each pulse sequence.

Standard of Reference and Histopathologic Examination
A total of 121 hepatocellular carcinomas were pathologically confirmed in 219 resected segments. However, in 10 patients, two segments were completely occupied by a large single hepatocellular carcinoma and were considered to be a single segment. Therefore, a total of 209 segments (88 with at least one hepatocellular carcinoma and 121 without hepatocellular carcinoma) were ultimately included in the subsequent receiver operating characteristic (ROC) analysis. Among these 88 segments, 62 had only one hepatocellular carcinoma; 17 had two hepatocellular carcinomas; five had three hepatocellular carcinomas; two had four hepatocellular carcinomas; two had one hepatocellular carcinoma with one dysplastic nodule. In the 121 segments with no hepatocellular carcinoma, one segment had one hemangioma and three segments had one adenoma.

Image Analysis
Three observers independently reviewed the CT and MR images in random order and in a blinded fashion. The radiologists were unaware of the patient's identity or clinical history. Any identifying information on the CT and MR images was masked. The interval between the reviews of the CT and MR images was at least 1 month. For each patient, the images were reviewed on a segment-by-segment basis for the entire liver. All images were evaluated using a 2,000 x 2,000 PACS (PACS; GE Healthcare Integrated Imaging Solution) monitor, with adjustment of the optimal window setting in each case. Liver window settings were also used in all patients because the reviewer could adjust the window width and level on the PACS monitor.

Each observer recorded the presence, size (maximum diameter), and number of lesions, and the segmental location (Couinaud segment) of one or more of the lesions. A rating of diagnostic confidence in the overall interpretation was also given for lesion classification regarding the presence of hepatocellular carcinoma: 5, definitely present; 4, probably present; 3, possibly present; 2, probably absent; and 1, definitely absent. In clinical practice at our institute, nodules showing enhancement at the contrast-enhanced arterial phase and then a washout pattern at the contrast-enhanced portal or delayed phase, with or without capsular enhancement, on triple-phase MDCT were regarded as hepatocellular carcinomas. Nodules larger than 2 cm with predominant hypoattenuation at contrast-enhanced portal and delayed phases with no definite enhancement at the contrast-enhanced arterial phase on CT were also regarded as hepatocellular carcinoma [1, 2, 13]. On ferucarbotran-enhanced MRI, any nodule seen as having high signal intensity or any prominent nodule larger than 2 cm in diameter despite the uptake of ferucarbotran was considered to be hepatocellular carcinoma. Of high-signal-intensity lesions seen on ferucarbotran-enhanced MRI other than hepatocellular carcinoma, hemangiomas were diagnosed when they showed high signal intensity on unenhanced proton density-weighted and T2-weighted MR images and peripheral globular enhancement on contrast-enhanced dynamic MR images, and cysts were confirmed when they showed their typical imaging findings on unenhanced T1- and T2-weighted MR images in addition to no enhancement on contrast-enhanced dynamic MR images. To prevent lesion mis-allocation (mismatch), a standardized template form for each examination was completed, on which the interpreter indicated the segmental location of each lesion. When a lesion invaded two or more segments, the lesion was assigned to the segment with the greatest involvement. Two other radiologists analyzed the observers' interpretations in consensus to evaluate the causes of the false-positive or false-negative diagnoses on the basis of all imaging studies and histopathology and surgery reports.

Statistical Analysis
A binominal ROC curve was calculated for each observer's confidence rating data and for each study using a maximum-likelihood estimation. The area under each ROC curve (Az) was used to indicate the overall performance of the imaging techniques and observers. Composite ROC curves for the combined performance of all observers were obtained by applying the maximum-likelihood curve-fitting algorithm to the pooled data of the three observers for each imaging technique. The number of segments with hepatocellular carcinoma assigned a score of 3, 4, or 5 by each observer was considered to represent the number of correctly diagnosed segments with hepatocellular carcinoma.

For each observer and each imaging technique, the sensitivity and specificity were calculated and the statistical analysis of their differences was assessed using the McNemar test. A p value of less than 0.05 was considered statistically significant.

Kappa statistics were used to assess the interobserver agreement for the detection of hepatocellular carcinoma with each imaging technique. The degree of agreement was categorized as follows: kappa values of 0.41-0.60, moderate agreement; 0.61-0.80, good agreement; and 0.81-1.00, excellent agreement [17].


Results
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
Discussion
 References
 
Table 1 shows the Az values for each observer and each imaging technique, on the basis of the pathologic findings in the resected liver specimens used as the standard of reference. The difference in the mean Az values obtained from MRI and CT for all observers was not statistically significant (p = 0.799). The ROC curves constructed on the basis of the pooled data from the three observers for each imaging technique are shown in Figure 1. Table 2 shows the sensitivities and specificities for each observer and each imaging technique. The difference in the mean sensitivities of MRI (90.2%, 238/264 segments) and CT (91.3%, 241/264 segments) was not statistically significant (p = 0.375) (Figs. 2A, 2B, 2C, and 2D), nor was the difference in the mean specificities of MRI (97.0%, 352/363 segments) and CT (95.3%, 346/363 segments) (p = 0.263).


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  		TABLE 1 Az and p values for Ferucarbotran-Enhanced MRI and Triple-Phase MDCT for Detection of Hepatocellular Carcinoma by Three Observers

 


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  		Fig. 1. —Receiver operating characteristic curves for triple-phase MDCT ({diamondsuit}) and ferucarbotran-enhanced MRI ({half_circle}) calculated with mean values from all three observers. Mean values for area under the curve (Az) (an indicator of diagnostic accuracy) for detection of hepatocellular carcinoma on ferucarbotran-enhanced MRI and triple-phase MDCT were 0.947 ± 0.010 and 0.949 ± 0.010, respectively. Difference in mean Az values between the two techniques was not statistically significant (p = 0.799).

 

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  		TABLE 2 Sensitivity and Specificity of Ferucarbotran-Enhanced MRI and Triple-Phase MDCT for Detection of Liver Segments Containing Hepatocellular Carcinoma

 


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  		Fig. 2A. —54-year-old man with three hepatocellular carcinomas in liver. Contrast-enhanced CT scan obtained at arterial phase shows 3.8- and 0.6-cm-diameter hypervascular hepatocellular carcinomas in liver segment VII (arrows) and 0.5-cm-diameter hypervascular hepatocellular carcinoma in segment VIII (arrowhead).

 


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  		Fig. 2B. —54-year-old man with three hepatocellular carcinomas in liver. Contrast-enhanced CT scan obtained at delayed phase at same level as A shows washout pattern in two hepatocellular carcinomas in segment VII (arrows) and one hepatocellular carcinoma in segment VIII (arrowhead).

 


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  		Fig. 2C. —54-year-old man with three hepatocellular carcinomas in liver. Ferucarbotran-enhanced image from fat-suppressed, respiratory-triggered proton density-weighted fast spin-echo MRI (TR/TE, 5,000/18) shows two hyperintense nodules in segment VII (arrows) and one hyperintense nodule in segment VIII (arrowhead).

 


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  		Fig. 2D. —54-year-old man with three hepatocellular carcinomas in liver. Ferucarbotran-enhanced image from T2*-weighted fast multiplanar gradient-recalled echo acquisition in steady state MRI (TR/TE, 130/8.4; 30° flip angle) at same level as C shows two hyperintense nodules (arrows) in liver segment VII and one hyperintense nodule in segment VIII (arrowhead). All three observers interpreted segment VII and segment VIII as segments with hepatocellular carcinoma on both CT and MR images.

 

The total number of segments with hepatocellular carcinomas that were missed by all observers was 26 on MRI (Figs. 3A, 3B, 3C, and 3D) and 23 on CT. For the detection of segments with a hepatocellular carcinoma equal to or less than 1 cm, both imaging techniques showed low sensitivities (29% [7/24 segments] in MRI and CT) compared with those for the larger hepatocellular carcinomas (Table 3). In three (23%) of 13 segments with well-differentiated hepatocellular carcinomas and one (1%) with moderately differentiated hepatocellular carcinoma of 75 segments with the 108 moderately or poorly differentiated hepatocellular carcinomas, hepatocellular carcinomas were not shown on either ferucarbotran-enhanced MRI or triple-phase MDCT. These four of 11 tumors 1.2 cm or smaller in diameter were not detected by any of the observers. In the remaining 10 segments with well-differentiated and 74 segments with moderately or poorly differentiated hepatocellular carcinomas, hepatocellular carcinomas showed hypervascular enhancement on the contrast-enhanced arterial phase and no uptake of ferucarbotran.



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  		Fig. 3A. —51-year-old man with 1.2-cm-diameter hepatocellular carcinoma in segment VIII of liver. Contrast-enhanced CT scan obtained at arterial phase shows hypervascular nodule (arrow) in segment VIII.

 


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  		Fig. 3B. —51-year-old man with 1.2-cm-diameter hepatocellular carcinoma in segment VIII of liver. Contrast-enhanced CT scan obtained at delayed phase at same level as A shows hypoattenuated nodule (arrow). All three observers interpreted this nodule as hepatocellular carcinoma.

 


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  		Fig. 3C. —51-year-old man with 1.2-cm-diameter hepatocellular carcinoma in segment VIII of liver. Ferucarbotran-enhanced image from fat-suppressed, respiratory-triggered T2-weighted fast spin-echo MRI (TR/TE, 4,500/98) shows subtle hyperintense nodule (arrow) overlying vascular structure in segment VIII.

 


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  		Fig. 3D. —51-year-old man with 1.2-cm-diameter hepatocellular carcinoma in segment VIII of liver. Ferucarbotran-enhanced MR image from T2*-weighted fast multiplanar gradient-recalled echo acquisition in steady state (130/8.4; 30° flip angle) at same level as C also shows subtle hyperintense nodule (arrow). Two of three observers did not interpret this nodule as hepatocellular carcinoma.

 

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  		TABLE 3 Sensitivity of Ferucarbotran-Enhanced MRI and Triple-Phase MDCT for Detection of Hepatocellular Carcinoma for Each Observer According to Tumor Size

 

The three observers recorded 11 false-positive MRI results and 17 false-positive CT results (Figs. 4A, and 4B). Seven (64%) of the false-positive MRI results were attributed to the overlying vascular structures such as hepatic and portal veins. The remaining four (36%) false-positive MRI results were attributed to the fact that three hepatic adenomas appeared to be large discrete nodules with the uptake of ferucarbotran. Eight (47%) of the 17 false-positive CT results were attributed to the arterioportal shunt. The remaining nine (53%) false-positive CT results were attributed to three hepatic adenomas appearing to be large discrete hypoattenuated nodules. In our study, two dysplastic nodules smaller than 1 cm did not cause a false-positive result for any of the observers.



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  		Fig. 4A. —48-year-old man with 7.2-cm-diameter hepatocellular carcinoma in liver segment VI and false-positive lesion in segment V. Contrast-enhanced CT scan obtained at arterial phase shows large, ill-defined, heterogeneous enhancing mass (arrows) in segment VI and subtle enhancing nodule (arrowheads) in segment V. Two of three observers considered nodule in segment V to be hepatocellular carcinoma.

 


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  		Fig. 4B. —48-year-old man with 7.2-cm-diameter hepatocellular carcinoma in liver segment VI and false-positive lesion in segment V. Ferucarbotran-enhanced MR image from fat-suppressed, respiratory-triggered T2-weighted fast spin-echo sequence (TR/TE, 4,500/98) at same level as A shows no mass in segment V other than hyperintense mass (arrows) in segment VI. None of three observers interpreted segment V as segment with hepatocellular carcinoma.

 

For the dynamic study of ferucarbotran-enhanced MRI, all three observers had little additional values for the detection of hepatocellular carcinomas because of the low contrast between the tumor and the surrounding liver (Figs. 5A, 5B, 5C, 5D, 5E, and 5F). However, one hemangioma was not interpreted as hepatocellular carcinoma because of peripheral enhancement and subsequent filling-in on the dynamic study (Figs. 5A, 5B, 5C, 5D, 5E, and 5F).



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  		Fig. 5A. —45-year-old man with 2.5-cm-diameter hepatocellular carcinoma in liver segment VI and hemangioma in segment V. Contrast-enhanced CT scan obtained at arterial phase shows hypervascular hepatocellular carcinoma (arrow) in segment VI and hemangioma with peripheral enhancement (arrowhead) in segment V.

 


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  		Fig. 5B. —45-year-old man with 2.5-cm-diameter hepatocellular carcinoma in liver segment VI and hemangioma in segment V. Contrast-enhanced CT scan obtained at delayed phase at same level as A shows hepatocellular carcinoma with washout (arrow) and persistent enhancing hemangioma (arrowhead). All three observers interpreted these nodules as hepatocellular carcinoma and hemangioma, respectively.

 


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  		Fig. 5C. —45-year-old man with 2.5-cm-diameter hepatocellular carcinoma in liver segment VI and hemangioma in segment V. MR image from breath-hold in-phase T1-weighted fast multiplanar spoiled gradient-recalled echo sequence (TR/TE, 200/4.2; 90° flip angle) before injection of contrast agent shows nodule (arrow) in segment VI that is less hypointense than hypointense nodule (arrowhead) in segment V.

 


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  		Fig. 5D. —45-year-old man with 2.5-cm-diameter hepatocellular carcinoma in liver segment VI and hemangioma in segment V. Ferucarbotran-enhanced dynamic MR images from breath-hold in-phase T1-weighted fast multiplanar spoiled gradient-recalled echo sequence (200/4.2; 90° flip angle). Image obtained 20 sec after injection of contrast agent (D) shows hypointense hepatocellular carcinoma (arrow, D) and early peripheral enhancement of hemangioma (arrowhead, D). At 1 min after injection of contrast agent (E), image shows less hypointense nodule (arrow, E) than in D and subsequent filling-in of hemangioma (arrowhead, E). At 5 min after injection of contrast agent (F), image shows hyperintense hepatocellular carcinoma (arrow, F) and hemangioma (arrowhead, F). Liver shows decrease in signal intensity compared with E.

 


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  		Fig. 5E. —45-year-old man with 2.5-cm-diameter hepatocellular carcinoma in liver segment VI and hemangioma in segment V. Ferucarbotran-enhanced dynamic MR images from breath-hold in-phase T1-weighted fast multiplanar spoiled gradient-recalled echo sequence (200/4.2; 90° flip angle). Image obtained 20 sec after injection of contrast agent (D) shows hypointense hepatocellular carcinoma (arrow, D) and early peripheral enhancement of hemangioma (arrowhead, D). At 1 min after injection of contrast agent (E), image shows less hypointense nodule (arrow, E) than in D and subsequent filling-in of hemangioma (arrowhead, E). At 5 min after injection of contrast agent (F), image shows hyperintense hepatocellular carcinoma (arrow, F) and hemangioma (arrowhead, F). Liver shows decrease in signal intensity compared with E.

 


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  		Fig. 5F. —45-year-old man with 2.5-cm-diameter hepatocellular carcinoma in liver segment VI and hemangioma in segment V. Ferucarbotran-enhanced dynamic MR images from breath-hold in-phase T1-weighted fast multiplanar spoiled gradient-recalled echo sequence (200/4.2; 90° flip angle). Image obtained 20 sec after injection of contrast agent (D) shows hypointense hepatocellular carcinoma (arrow, D) and early peripheral enhancement of hemangioma (arrowhead, D). At 1 min after injection of contrast agent (E), image shows less hypointense nodule (arrow, E) than in D and subsequent filling-in of hemangioma (arrowhead, E). At 5 min after injection of contrast agent (F), image shows hyperintense hepatocellular carcinoma (arrow, F) and hemangioma (arrowhead, F). Liver shows decrease in signal intensity compared with E.

 

The kappa values among the three observers showed excellent agreement for both imaging techniques (Table 4).


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  		TABLE 4 Interobserver Agreement for the Presence of Hepatocellular Carcinoma

 


Discussion
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
References
 
Contrast-enhanced dynamic CT is still the most commonly used technique for the evaluation of patients with suspected hepatocellular carcinoma [5, 18]. The recently developed MDCT technology has successfully replaced single-detector helical CT in many institutions. MDCT has been shown to have higher sensitivity for the detection of focal liver lesions and is therefore expected to improve the diagnosis of hepatocellular carcinoma because of the advantage afforded by its providing thinner section collimation with higher temporal and spatial resolution than single-detector helical CT provides [4, 19-22]. We performed triple-phase (contrast-enhanced arterial, portal, and delayed phases) MDCT for improving the detection of hypovascular and hypervascular hepatocellular carcinomas [2, 13, 23-25].

Recently, a variety of parenterally administered iron oxides has also been developed for contrast-enhanced MRI of the liver. Superparamagnetic iron oxide-based MR contrast agents such as ferumoxides and ferucarbotran are currently being used in clinical practice. Of these, ferucarbotran has some advantages compared with ferumoxides. Ferucarbotran is used with an IV bolus injection, and thus a dynamic study can be performed with the acquisition of accumulation-phase images. Moreover, complications, such as cardiovascular changes and lumbar pain, occur at a low rate [15].

Many investigators have compared the detection rates of hepatic tumors, particularly hepatocellular carcinoma, using a variety of imaging techniques such as CT during arterial portography, contrast-enhanced multiphase helical CT, gadolinium-enhanced MRI, and ferumoxides-enhanced MRI [11-14, 16, 26-30]. Several investigators have reported that ferumoxides-enhanced MRI appears to be superior to CT during arterial portography or dual-phase or triple-phase helical CT for the detection of hepatocellular carcinoma [13, 16, 26, 27]. However, to our knowledge, no comparison of the detection rates between triple-phase MDCT and ferucarbotran-enhanced MRI has been reported for the preoperative evaluation of hepatocellular carcinoma.

Our results of each imaging technique for the detection of hepatocellular carcinoma are comparable to those recently reported by other investigators [8, 13, 16, 31]. We evaluated the accuracy of CT and MRI for the detection of hepatocellular carcinoma in patients whose liver function was relatively good and who were able to endure surgery, rather than in patients with advanced or end-stage liver cirrhosis with hepatocellular carcinoma that had been proven by histopathologic analysis. Several investigators reported that the detection rates of hepatocellular carcinoma in explanted livers with advanced or end-stage liver cirrhosis were 50-80% on contrast-enhanced CT and MRI [32, 33]. In advanced or end-stage liver cirrhosis, the detection of hepatocellular carcinoma is difficult because the cirrhotic liver parenchyma contains fibrosis, regenerative nodules, fatty infiltration, and parenchymal necrosis, and is accompanied by a variety of hemodynamic changes, such collateral flow as a result of portal hypertension and transient attenuation difference, including arterioportal shunt [13, 27, 29].

In our study, several factors caused false-positive or false-negative results. We concluded that very small hepatocellular carcinomas could be difficult to differentiate from overlying portal or hepatic veins on ferucarbotran-enhanced MRI and from an arterioportal shunt on contrast-enhanced CT, which might therefore cause false-positive or false-negative results. In our study, 64% of the false-positive MRI results were primarily attributed to the presence of overlying vascular structures such as hepatic and portal veins, and 47% of the false-positive CT results were due to arterioportal shunt. We believe that the high signal intensity of overlying vascular structures relative to the signal intensity of the liver parenchyma is the most frequent cause of false-positive results. On the other hand, MDCT can distinguish peripheral hepatic vessels from small hepatocellular carcinomas because of its thinner slice thickness and higher resolution in comparison with those of MRI. And, in our study, small arterioportal shunts were commonly seen on MDCT but seldom observed on ferucarbotran-enhanced MRI. Small arterioportal shunts hardly influenced the change of the signal intensity at ferucarbotran-enhanced MRI, because they have little effect on the number and activity of Kupffer's cells. Some nodules, such as regenerative or dysplastic nodules or even hepatic adenoma, may show predominant hypoattenuation during the contrast-enhanced portal or delayed phase on contrast-enhanced CT [2, 13], which may not be differentiated from hypovascular hepatocellular carcinoma. Some prior reports [13, 15] have pointed out that a variety of hepatic tumors, such as focal nodular hyperplasia, regenerative nodules, hepatic adenoma, dysplastic nodules, and well-differentiated hepatocellular carcinomas, can show variable uptake because these tumors contain a variable number of Kupffer's cells. Therefore, it may be difficult to distinguish well-differentiated hepatocellular carcinoma from other benign hepatic tumors. In our study, three well-differentiated hepatocellular carcinomas and one moderately differentiated hepatocellular carcinoma showed definite Kupffer's cell activity, and thus these HCCs were not visible on ferucarbotran-enhanced MRI. Three hepatic adenomas showed large discrete masses with uptake of ferucarbotran on ferucarbotran-enhanced MRI, which caused false-positive results in two observers.

Kang et al. [13] reported that ferumoxides-enhanced MRI is superior to triple-phase helical CT for depicting hepatocellular carcinoma. Those authors administered ferumoxides at a dose of 15 µmol/kg, and the result was reported to be different from the results obtained by other investigators with the administration of 10 µmol/kg of ferumoxides [29, 34]. We administered ferucarbotran at a dose of 8.0-12.0 µmol/kg. Although Kang et al. used triple-phase helical CT with 7-mm section collimation and the injection of 100 mL of contrast material at a rate of 3 mL/sec, we used triple-phase MDCT with 5-mm section thickness, the injection of 120 mL of contrast material at a rate of 4 mL/sec, and acquisition of contrast-enhanced arterial phase images with a bolus-triggered technique.

Ferucarbotran can be used to perform dynamic imaging with the rapid IV bolus injection, in contrast to ferumoxides. Reimer and Balzer [15] reported that the ferucarbotran-enhanced dynamic study improved the differentiation of benign and malignant focal liver lesions. In our study, the ferucarbotran-enhanced dynamic study usually did not help to detect the hepatocellular carcinoma itself because of the low contrast between hepatocellular carcinoma and the surrounding liver. However, a hemangioma or cyst could be diagnosed with the dynamic study. We believe that the ferucarbotran-enhanced dynamic study may be effective in the differentiation and characterization of benign and malignant hepatic tumors, rather than in the detection of hepatic tumors.

Our study had some limitations. First, all three observers were aware that all patients had been found to have hepatocellular carcinoma at histopathologic examination after hepatic resection surgery, which resulted in a positive bias. Second, our study used resected liver specimens for the segment-based analysis instead of explanted liver for nodule-based analysis as the diagnostic standard, and this factor could lead to higher sensitivity. Third, in our study, the sizes of the tumor were relatively large, with only a small number of the nodules smaller than 2 cm in diameter. This factor influenced the detection rate.

In summary, the results of our study show that ferucarbotran-enhanced MRI seems to be as accurate as triple-phase MDCT for the preoperative evaluation of hepatocellular carcinoma. We believe that ferucarbotran-enhanced MRI may be reserved for complementary use when the results of triple-phase MDCT are equivocal.


References
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 Abstract
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 References
 

  1. Baron RL, Oliver JH III, Dodd GD III, Nalesnik M, Holbert BL, Carr B. Hepatocellular carcinoma: evaluation with biphasic, contrast-enhanced, helical CT. Radiology1996; 199:505 -511[Abstract/Free Full Text]
  2. Jang HJ, Lim JH, Lee SJ, Park CK, Park HS, Do YS. Hepatocellular carcinoma: are combined CT during arterial portography and CT hepatic arteriography in addition to triple-phase helical CT all necessary for preoperative evaluation? Radiology2000; 215:373 -380[Abstract/Free Full Text]
  3. Hollett MD, Jeffrey RB Jr, Nino-Murcia M, Jorgensen MJ, Harris DP. Dual-phase helical CT of the liver: value of early hepatic arterial phase scans in the detection of small (1.5 cm) malignant hepatic neoplasms. AJR 1995;164:879 -884[Abstract/Free Full Text]
  4. Murakami T, Kim T, Takahashi S, Nakamura H. Hepatocellular carcinoma: multidetector row helical CT. Abdom Imaging2002; 27:139 -146[Medline]
  5. Kopp AF, Heuschmid M, Claussen CD. Multidetector helical CT of the liver for tumor detection and characterization. Eur Radiol 2002;12:745 -752[Medline]
  6. Foley WD. Multidetector CT: abdominal visceral imaging. RadioGraphics2002; 22:701 -719[Abstract/Free Full Text]
  7. Kawata S, Murakami T, Kim T, et al. Multidetector CT: diagnostic impact of slice thickness on detection of hypervascular hepatocellular carcinoma. AJR2002; 179:61 -66[Abstract/Free Full Text]
  8. Laghi A, Iannaccone R, Rossi P, et al. Hepatocellular carcinoma: detection with triple-phase multi-detector row helical CT in patients with chronic hepatitis. Radiology2003; 226:543 -549[Abstract/Free Full Text]
  9. Weissleder R, Stark DD, Engelstad BL, et al. Superparamagnetic iron oxide: pharmacokinetics and toxicity. AJR1989; 152:167 -173[Abstract/Free Full Text]
  10. Saini S, Stark DD, Hahn PF, et al. Ferrite particles: a superparamagnetic MR contrast agent for enhanced detection of liver carcinoma. Radiology1987; 162:217 -222[Abstract/Free Full Text]
  11. Ward J, Naik KS, Guthrie JA, Wilson D, Robinson PJ. Hepatic lesion detection: comparison of MR imaging after the administration of superparamagnetic iron oxide with dual-phase CT by using alternative-free response receiver operating characteristic analysis. Radiology1999; 210:459 -466[Abstract/Free Full Text]
  12. Bluemke DA, Paulson EK, Choti MA, DeSena S, Clavien PA. Detection of hepatic lesions in candidates for surgery: comparison of ferumoxides-enhanced MR imaging and dual-phase helical CT. AJR 2000;175:1653 -1658[Abstract/Free Full Text]
  13. Kang BK, Lim JH, Kim SH, et al. Preoperative depiction of hepatocellular carcinoma: ferumoxides-enhanced MR imaging versus triple-phase helical CT. Radiology2003; 226:79 -85[Abstract/Free Full Text]
  14. Vogl TJ, Hammerstingl R, Schwarz W, et al. Superparamagnetic iron oxide-enhanced versus gadolinium-enhanced MR imaging for differential diagnosis of focal liver lesions. Radiology1996; 198:881 -887[Abstract/Free Full Text]
  15. Reimer P, Balzer T. Ferucarbotran (Resovist): a new clinically approved RES-specific contrast agent for contrast-enhanced MRI of the liver: properties, clinical development, and applications. Eur Radiol 2003;13:1266 -1276[Medline]
  16. Reimer P, Jahnke N, Fiebich M, et al. Hepatic lesion detection and characterization: value of non-enhanced MR imaging, superparamagnetic iron oxide-enhanced MR imaging, and spiral CT—ROC analysis. Radiology2000; 217:152 -158[Abstract/Free Full Text]
  17. Fleiss JL. The measurement of interrater agreement. In: Fleiss JL, ed. Statistical methods for rates and proportions, 2nd ed. New York, NY: Wiley, 1981:212 -236
  18. Ohashi I, Hanafusa K, Yoshida T. Small hepatocellular carcinomas: two-phase dynamic incremental CT in detection and evaluation. Radiology1993; 189:851 -855[Abstract/Free Full Text]
  19. Weg N, Scheer MR, Gabor MP. Liver lesions: improved detection with dual-detector-array CT and routine 2.5-mm thin collimation. Radiology1998; 209:417 -426[Abstract/Free Full Text]
  20. Foley WD, Mallisee TA, Hohenwalter MD, Wilson CR, Quiroz FA, Taylor AJ. Multiphase hepatic CT with a multirow detector CT scanner. AJR 2000;175:679 -685[Abstract/Free Full Text]
  21. Murakami T, Kim T, Takamura M, et al. Hypervascular hepatocellular carcinoma: detection with double arterial phase multidetector helical CT. Radiology2001; 218:763 -767[Abstract/Free Full Text]
  22. Wong K, Paulson EK, Nelson RC. Breath-hold three-dimensional CT of the liver with multidetector helical CT. Radiology2001; 219:75 -79[Abstract/Free Full Text]
  23. Van Leeuwen MS, Noordzij J, Feldberg MA, Hennipman AH, Doornewaard H. Focal liver lesions: characterization with triphasic spiral CT. Radiology1996; 201:327 -336[Abstract/Free Full Text]
  24. Hwang GJ, Kim MJ, Yoo HS, Lee JT. Nodular hepatocellular carcinoma: detection with arterial-, portal-, and delayed-phase images at spiral CT. Radiology1997; 202:383 -388[Abstract/Free Full Text]
  25. Kato H, Kanematsu M, Kondo H, et al. Ferumoxide-enhanced MR imaging of hepatocellular carcinoma: correlation with histologic tumor grade and tumor vascularity. J Magn Reson Imaging2004; 19:76 -81[Medline]
  26. Choi D, Kim SH, Lim JH, et al. Preoperative detection of hepatocellular carcinoma: ferumoxides-enhanced MR imaging versus combined helical CT during arterial portography and CT hepatic arteriography. AJR 2001;176:475 -482[Abstract/Free Full Text]
  27. Lee JM, Kim IH, Kwak HS, Youk YM, Kim CS. Detection of small hypervascular hepatocellular carcinomas in cirrhotic patients: comparison of superparamagnetic iron oxide-enhanced MR imaging with dual-phase spiral CT. Korean J Radiol2003; 4:1 -8[Medline]
  28. Kim MJ, Kim JH, Chung JJ, Park MS, Lim JS, Oh YT. Focal hepatic lesions: detection and characterization with combination gadolinium- and superparamagnetic iron oxide-enhanced MR imaging. Radiology2003; 228:719 -726[Abstract/Free Full Text]
  29. Tang Y, Yamashita Y, Arakawa A, et al. Detection of hepatocellular carcinoma arising in cirrhotic livers: comparison of gadolinium- and ferumoxides-enhanced MR imaging. AJR1999; 172:1547 -1554[Abstract/Free Full Text]
  30. Pauleit D, Textor J, Bachmann R, et al. Hepatocellular carcinoma: detection with gadolinium- and ferumoxides-enhanced MR imaging of the liver. Radiology2002; 222:73 -80[Abstract/Free Full Text]
  31. Zhao H, Zhou KR, Yan FH. Role of multiphase scans by multirow-detector helical CT in detecting small hepatocellular carcinoma. World J Gastroenterol2003; 9:2198 -2201[Medline]
  32. Peterson MS, Baron RL, Marsh JW, Oliver JH, Confer SR, Hunt LE. Pretransplantation surveillance for possible hepatocellular carcinoma in patients with cirrhosis: epidemiology and CT-based tumor detection rate in 430 cases with surgical pathologic correlation. Radiology2000; 217:743 -749[Abstract/Free Full Text]
  33. Krinsky GA, Lee VS, Theise ND, et al. Hepatocellular carcinoma and dysplastic nodules in patients with cirrhosis: prospective diagnosis with MR imaging and explantation correlation. Radiology2001; 219:445 -454[Abstract/Free Full Text]
  34. Matsuo M, Kanematsu M, Itoh K, et al. Detection of malignant hepatic tumors: comparison of gadolinium- and ferumoxide-enhanced MR imaging. AJR 2001;177:637 -643[Abstract/Free Full Text]

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