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Gastrointestinal Imaging |
1 From the Russell H. Morgan Department of Radiology and Radiological Sciences (I.R.K., K.M.H., H.J.V.B., E.K.F., D.A.B.) and Department of Surgery (M.A.C.), Johns Hopkins Hospital, 600 N Wolfe St, Rm 100, Baltimore, MD 21287; Department of Radiology, New York University Medical Center, New York (B.A.B.); and Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Md (R.E.T.). Received October 31, 2001; revision requested January 18, 2002; final revision received October 2; accepted November 5. Address correspondence to I.R.K. (e-mail: ikamel@jhmi.edu).
| ABSTRACT |
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MATERIALS AND METHODS: Surgically and histopathologically proven liver lesions were evaluated by three experienced CT readers. These lesions were present in 77 patients who underwent dual-phase helical CT. Images were interpreted separately by the three blinded reviewers. Each lesion was graded on a nine-point scale of confidence, with 1 being definitely benign, 9 being definitely malignant, and 5 being indeterminate. The
2 test was used to determine if the distribution of lesion classifications was different between readers.
RESULTS: There was a total of 237 lesions: 73 were benign and 164 were malignant. Sensitivity for lesion detection was 69%, 70%, and 71% for the three reviewers, respectively. Specificity was 91%, 86%, and 90%, and the area under the curve for the alternative-free response receiver operating characteristic curve was 0.84, 0.83, and 0.85, respectively. The difference in the distributions of lesion classification between the three reviewers was not statistically significant (P = .67) as determined by
2 analysis.
CONCLUSION: Dual-phase CT has sensitivity of 69%71% and high specificity (86%91%) in enabling the detection and characterization of focal liver lesions. Interpretation is highly reproducible, as there is minimal variation between experienced reviewers.
© RSNA, 2003
Index terms: Liver neoplasms, CT, 761.12112 Liver neoplasms, diagnosis, 761.31, 761.32 Liver neoplasms, metastases, 761.33
| INTRODUCTION |
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Helical CT scanners are now the dominant type of CT scanners in the United States (79). Although magnetic resonance (MR) imaging (1013) and positron emission tomography (PET) are available, helical CT is more widely available in aiding presurgical planning for hepatic resection. The sensitivity and specificity of helical CT have not been determined in a large surgical series with multiple independent observers and receiver operating characteristic (ROC) analysis. The purpose of our study was to assess the accuracy and reproducibility of dual-phase helical CT in enabling preoperative detection and characterization of surgically staged focal liver lesions.
| MATERIALS AND METHODS |
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CT Examination
CT was performed with a helical scanner (Somatom Plus 4; Siemens Medical Systems, Iselin, NJ). Scanning parameters were 120 kVp, 210 mA, 5-mm section collimation, and 5-mm image reconstruction. The acquisition length was 2024 seconds, depending on liver size. All patients received 120150 mL of nonionic contrast medium (iohexol, Omnipaque, 350 mg/mL; Nycomed Amersham, Princeton, NJ), which was injected intravenously with a power injector at a rate of 3 mL/sec. Arterial phase and portal venous phase images were obtained at 20 seconds and 70 seconds, respectively, after the start of injection. Images were reviewed with liver windows (center = 80 HU, width = 200 HU), or with abdominal windows (center = 10 HU, width = 410 HU) if liver windows were not available.
Image Analysis
The combined CT images (arterial and portal venous phases) were reviewed on film by three CT readers with 5 or more years of experience at two high-volume academic institutions. CT images were interpreted separately by the blinded reviewers, without prior knowledge of patient history. To ensure accurate correlation between the lesions scored by reviewers and those found at surgery, each reviewer recorded the image number, location (right or left lobe), and size of each lesion.
For CT interpretation, malignant lesions were defined as nodular, low-attenuating lesions without characteristic findings of benign lesions (cysts, hemangiomas, or focal nodular hyperplasia). Cysts were defined as fluid-attenuating lesions with no contrast enhancement. Hemangiomas were defined as low-attenuating lesions with globular peripheral contrast enhancement on the portal venous phase images. Focal nodular hyperplasia was defined by well-defined lesions with intense homogeneous enhancement on the arterial phase images that become nearly isoattenuating with the liver parenchyma on the portal venous phase.
Reviewers scored each lesion by using a nine-point scale of confidence with a score of 1 being definitely benign (100% confidence), a score of 9 being definitely malignant (100% confidence), and a score of 5 being indeterminate (50% possibility of either). Intermediate scores indicated less certainty in the diagnosis. Scores of 2, 3, and 4 reflected confidence of 85%, 75%, and 65%, respectively, that the lesion was benign. Scores of 6, 7, and 8 reflected confidence of 65%, 75%, and 85%, respectively, that the lesion was malignant. For statistical analysis, scores between 1 and 3 were considered benign, scores between 4 and 6 were considered indeterminate, and scores between 7 and 9 were considered malignant. Reviewers added comments to distinguish between lesions and indicate if multiple lesions were found in the same image and lobe. Confidence scores were then reclassified such that 1 and 9 were given the highest confidence value (coded as 1), 2 and 8 were the given the next highest (coded as 2), 3 and 7 were given a lower value (coded as 3), and 4 and 6 were given the lowest confidence value (coded as 4). Therefore, even though the lesions were classified as benign, indeterminate, and malignant, all the data points were used in plotting the ROC curve.
All patients underwent exploratory surgery with laparotomy, which was performed by an experienced hepatic surgeon (M.A.C.). Complete assessment of the liver was performed with intraoperative US. Lesions were identified and characterized on an individual basis. Nonresected hepatic segments were thoroughly evaluated for occult hepatic metastases. All patients subsequently underwent either resection or biopsy for histopathologic confirmation. Pathologic evaluation reported whether each recorded lesion was actually detected at surgery and whether it was benign or malignant.
Statistical Analysis
Alternative-free response ROC curves were calculated for each reviewer by plotting the true-positive fraction against the false-positive fraction. Alternative-free response ROC is a modified ROC technique that allows multiple responses per image or patient (14). Conventional ROC methods do not allow observers to record multiple responses per image. As with the ROC method, the area under the curve (AUC) for the alternative-free response ROC is calculated to determine the overall performance of the observers. The true-positive fraction is the number of true-positive responses divided by the number of true lesions present, as determined at pathologic examination. The false-positive fraction is the number of false-positive responses divided by the number of scans examined. The number of scans is used as a denominator because it is a fixed and well-defined quantity, thus confining the specificity to values between 0 and 1. Confidence intervals for the AUC values were obtained by performing a bootstrapping simulation, in which 1,000 simulated samples were created by sampling with replacement from the original data set (Stata 6.0 Statistical Software; Stata, College Station, Tex). Similarly, the corresponding two-sided 95% confidence intervals were calculated empirically by taking the 2.5 and 97.5 percentile AUC values from these 1,000 samples.
A true-positive finding was scored if the reviewer correctly identified a lesion and correctly classified that lesion as benign or malignant. A type I false-positive finding was scored if the reviewer identified a false lesion (ie, a lesion not identified at pathologic examination), while a type II false-positive finding was scored if the reviewer incorrectly classified a true benign lesion as being malignant. Similarly, a type I false-negative finding occurred if the reviewer missed a true lesion, and a type II false-negative finding occurred if the reviewer incorrectly scored a true malignant lesion as being benign.
Sensitivity, specificity, and AUC values with corresponding 95% confidence intervals were determined for each reviewer. Sensitivity and specificity were calculated for the cumulative number of true-positive responses and false-positive responses, respectively, summed over confidence levels of 1, 2, and 3. Scores of 4 and 5 were eliminated because they were considered indeterminate.
2 goodness-of-fit test was used to determine whether the distribution of lesion classifications was different between readers. Statistical significance was associated with a P value of less than .05. Patients were subdivided into two groups depending on whether they had one lesion or more than one lesion at CT. Sensitivity, specificity, and AUC were calculated for the two groups to determine if reviewer performance was affected by the number of liver lesions present.
| RESULTS |
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Curative resection (either segmental resection or partial hepatectomy) was performed in 54 (70%) of the 77 patients, while combined resection and tumor ablation was performed in four (5%) patients. In five patients (6%), cryoablation or radio-frequency ablation alone was performed after tissue diagnosis was obtained, and in the remaining 14 patients (18%) exploratory laparotomy, intraoperative US, and biopsy were performed to confirm a benign lesion or document unresectability.
A total of 237 lesions were confirmed at surgery and pathologic examination. The average lesion size was 2.3 cm, and the range was 0.220 cm. There were 73 benign lesions (31%), including cyst (n = 43), hemangioma (n = 14), adenoma (n = 8), focal nodular hyperplasia (n = 5), focal fat (n = 1), postsurgical scar (n = 1), and chronic inflammation (n = 1). The remaining 164 lesions (69%) were malignant. These included metastasis (n = 154), hepatocellular carcinoma (n = 7), cholangiocarcinoma (n = 2), and adult hepatoblastoma (n = 1). The maximum number of true lesions found in a single patient was 15. Of the 237 total confirmed lesions, 160 lesions were in the right lobe (67.5%) and 68 lesions (28.7%) were in the left lobe. Nine lesions (3.8%) involved both lobes.
Sensitivity, specificity, and AUC values with the corresponding 95% confidence intervals for each of the three reviewers are shown in Table 1. Sensitivity values ranged between 69% and 71% for the three reviewers, and, on the basis of the two-sided 95% confidence intervals, the difference was not statistically significant. Similarly, specificity was not significantly different between the three reviewers. Specificity values ranged between 86% and 91%, with the confidence intervals overlapping for all reviewers. The AUC values were also very close for all three reviewers. AUC values ranged between 0.83 and 0.85 (Fig 1), and, on the basis of the two-sided 95% confidence intervals, the difference between the reviewers was not statistically significant.
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2 analysis (Table 2).
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Lesions that were considered indeterminate by at least one reviewer were evaluated. There were 26 lesions (of 237, 11%) with a mean size of 1.5 cm (range, 0.24.0 cm). Nine of these lesions (35%) were benign and 17 (65%) were malignant.
| DISCUSSION |
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The goal of our study was to determine the accuracy and reproducibility of dual-phase helical CT in enabling the assessment of focal liver lesion. In our study of a large number of patients with careful radiologic-histopathologic correlation, we found that dual-phase helical CT had a sensitivity of 69%71% and specificity of 86%91% in the detection and characterization of both benign and malignant lesions. When reviewers evaluated lesions independently, alternative-free response ROC analysis demonstrated high reproducibility with minimal variations between experienced readers. We also evaluated the effect that the number of lesions had on a reviewers performance. As shown in Table 3, reviewer performance was better in patients with a solitary lesion than in patients with multiple liver lesions. This is partially because of the improved specificity, which reached up to 100% for reviewers 1 and 3.
The sensitivity in our study was slightly lower than that reported by Ward et al (11) for benign and malignant lesions, who performed both biphasic helical CT (75%) and MR imaging after administration of superparamagnetic iron oxide (80%). However, histologic confirmation was available in only 31 of the 51 patients (61%) in that study, compared to all 77 patients in our study. Our sensitivity was also slightly lower than that found in a study by Valls et al (8), which was 85%. In this latter study, however, image analysis was determined by consensus of at least two of four radiologists, and all indeterminate lesions were considered metastatic. These factors could result in increased sensitivity in lesion detection. In our study, however, three radiologists worked independently and without prior knowledge of patient history. It is possible that we have overestimated the sensitivity for lesion detection. This is because all patients enrolled in our study had liver lesions detected with other imaging modalities, and they were referred to undergo CT for confirmation.
CT during arterial portography was previously considered to be the most sensitive imaging technique for use in the detection of hepatic metastases. However, the procedure is invasive and is associated with a high false-positive rate (15). In addition, a number of recent reports have shown that helical CT and contrast materialenhanced MR imaging are highly accurate in the detection of hepatic tumors, with results that may surpass those of CT during arterial portography (10,12,16,17).
Previous results have shown that ferumoxides-enhanced MR imaging (17) and helical CT (10) were as accurate as CT during arterial portography in the detection of hepatic metastases and that they were associated with fewer false-positive findings. These results suggest that adequate preoperative staging may be performed with noninvasive imaging techniques. In addition, prior studies have demonstrated that contrast-enhanced MR imaging with ferumoxides or gadolinium-based contrast agents enables excellent results in the preoperative staging of hepatic metastases (11,16).
The use of the biphasic helical CT in the evaluation of hepatic metastases is controversial. Arterial phase imaging increases the detection of hypervascular tumors such as hepatocellular carcinoma or hypervascular metastases (18,19). Although there have been reports that some hepatic metastases missed on the portal venous phase images were detected on the arterial phase images (20), some authors (19,21) suggest that arterial phase imaging is not necessary for the study of metastases from colorectal cancer.
A limitation of our study is that multidetector row CT was not used. The thin collimation possible with multidetector row CT results in higher image resolution and therefore may improve lesion detection and characterization. In our study, 19 of 237 lesions (8%) were not detected by any of the reviewers or by rereview of the CT studies. All of these lesions were small (up to 1 cm), and the detection of such lesions may improve with use of multidetector row CT. In addition, 26 lesions (11%) were considered indeterminate by at least one reviewer. It is possible that multidetector row CT could better depict those lesions that are poorly characterized with helical CT. However, the rapid advance in imaging technology hinders performing the study on a large number of patients while obtaining strong histopathologic correlation.
In this study we did not evaluate the effect of CT accuracy on disease management and outcome. Many of the patients included in this study had undergone additional imaging and/or biopsy prior to surgery.
In summary, in our experience dual-phase CT has sensitivity of 69%71% and high specificity (86%91%) in enabling the detection and characterization of focal liver lesions. Interpretation is highly reproducible, as there is minimal variation between experienced reviewers.
| FOOTNOTES |
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Author contributions: Guarantors of integrity of entire study, I.R.K., D.A.B.; study concepts, I.R.K., D.A.B.; study design, R.E.T., I.R.K., D.A.B.; literature research, I.R.K.; clinical studies, all authors; data acquisition, I.R.K., K.M.H., B.A.B., E.K.F.; data analysis/interpretation, all authors; statistical analysis, R.E.T.; manuscript preparation, I.R.K.; manuscript definition of intellectual content, I.R.K., D.A.B.; manuscript editing, revision/review, and final version approval, all authors.
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