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Improved Detection of Hepatic Metastases with Contrast-enhanced Low Mechanical-index Pulse Inversion Ultrasonography During the Liver-specific Phase of Sonazoid

Posted Jun 30, 2009 Updated Apr 7, 2023
By Katsutoshi Sugimoto MD , Junji Shiraishi PhD , Fuminori Moriyasu MD , Kazuhiro Saito MD , Kunio Doi PhD
11 min read

Rationale and Objectives

To compare B-mode ultrasonography (US) alone with the combination of B-mode and contrast-enhanced (Sonazoid) late-phase pulse-inversion US for the detection of hepatic metastases by use of jackknife free-response receiver-operating characteristic (JAFROC) analysis.

Materials and Methods

Twenty-seven patients with 57 hepatic metastases and 6 patients without hepatic metastases underwent B-mode and contrast-enhanced US. We used the diagnoses established by contrast-enhanced computed tomography and contrast-enhanced US as the standard of reference. All ultrasonographic scanning was performed by an experienced radiologist with a routine clinical procedure. All scanning data were archived with digital cine clips. A review system, which can display pairs of cine clips for B-mode and contrast-enhanced US side by side, was developed for off-site observer study. Seven radiologists interpreted each case individually first by B-mode US only, and then by the combination with contrast-enhanced US by identifying locations of possible candidates for hepatic metastasis with their confidence ratings. The figure-of-merit (FOM) values, sensitivity, and false-positives per case were estimated for B-mode US alone, and for the combination of B-mode and contrast-enhanced US.

Results

The sensitivities of the combined ultrasonographic imaging (mean, 72.2%) were clearly improved from that of B-mode US alone (mean, 41.6%) while reducing the average number of false positives from 1.1 to 0.5 per case. In the jackknife analysis, there was a statistically significant difference between mean FOM values for the combined imaging (0.76) and for B-mode US alone (0.44, P < .00001).

Conclusion

Evaluating cine clips of contrast-enhanced liver US together with B-mode US could improve physicians’ accuracy for detection of hepatic metastases.

The liver is one of the most common sites for metastases, and the detection of metastases is crucially important because of therapeutic and prognostic implications. Accurate staging is a prerequisite for successful surgery and for monitoring of chemotherapy. Because the sensitivity of conventional ultrasonography (US) for hepatic metastases was relatively poor (53%–77%) , contrast material-enhanced computed tomography (CT) and magnetic resonance (MR) imaging have been recommended for the detection of liver metastases.

It has been reported that the advent of the microbubble contrast agent SHU 508A (Levovist; Schering, Berlin, Germany) and the development of a gray-scale microbubble-specific ultrasonographic technique, which was called pulse- or phase-inversion harmonic contrast enhanced US, has remarkably improved the detection of liver metastases by use of US . However, contrast-enhanced US with SHU 508A is limited because prolonged evaluation of liver contrast enhancement cannot be performed due to a technical factor .

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Materials and methods

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Patients and Reference Standards

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Figure 1, Confirmation of 82 hepatic metastases and “gold standard” used in this study. CT, computed tomography; MR, magnetic resonance; US, ultrasonography.

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Table 1

Sizes of 57 Hepatic Metastases

Diameter (mm) No. of Lesions Less than or equal to 5 10 (17.5 %) 6–10 18 (31.6 %) 11–20 16 (28.1 %) Greater than or equal to 21 13 (22.8 %)

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Ultrasonographic Examination Technique

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Other Examination Techniques

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Observer Performance Study

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Figure 2, Overview of the observer study interface.

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Statistical Analysis

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Results

JAFROC Analysis

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Figure 3, The average free-response receiver-operating characterstic curves show the increase in diagnostic performance after review of contrast-enhanced (CE)-ultrasonographic (US) images ( black line ).

Table 2

Sensitivity, FPs/case, and FOM Values in Detection of Hepatic Metastases

B-mode US Alone Combined US Imaging Reader Sensitivity FP / Case FOM Sensitivity FP / Case FOM A 31.6 % (18/57) 0.24 (8/33) 0.33 57.9 % (33/57) 0.21 (7/33) 0.66 B 56.1 % (32/57) 1.97 (65/33) 0.55 79.0% (45/57) 0.45 (15/33) 0.82 C 38.6 % (22/57) 1.30 (43/33) 0.39 64.9 % (37/57) 0.64 (21/33) 0.66 D 36.8 % (21/57) 0.85 (28/33) 0.39 71.9 % (41/57) 0.52 (17/33) 0.78 E 50.9 % (29/57) 1.15 (38/33) 0.51 91.2 % (52/57) 0.55 (18/33) 0.93 F 38.6 % (22/57) 0.94 (31/33) 0.46 64.9 % (37/57) 0.33 (11/33) 0.74 G 38.6 % (22/57) 0.97 (32/33) 0.44 75.4 % (43/57) 0.52 (17/33) 0.76 Average 41.6 % (166/399) 1.06 (245/231) 0.44 72.2 % (288/399) ∗ 0.46 (106/231) † 0.76 ‡

Combined US imaging, combination of B-mode and contrast-enhanced US; FOM, figure of merit; FP, false-positive; US, ultrasonography.

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False-positive Findings

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Table 3

Averaged Number of False-positive Lesions by Seven Readers

False-positive Lesions B-mode Combined US Imaging No. No. Fibrosis or sequelae 23.9 (167/7) 5.0 (35/7) Focal fatty sparing and focal fatty change 2.4 (17/7) 0 (0/7) Cyst 5.9 (41/7) 9.9 (69/7) Hemangioma 2.9 (20/7) 0.3 (2/7) Total 35.0 (245/7) 15.1 (106/7)

Data in parentheses are the numbers used for calculating the averaged number of false-positive lesions per reader.

Figure 4, Liver hemangioma in a 65-year-old man. At follow-up computed tomography (CT) 6 months later, the lesion showed no change in size and typical enhancement on dynamic contrast-enhanced CT. Hence, the lesion was considered to be a liver hemangioma. (a) B-mode ultrasonographic (US) image obtained in the right lobe of the liver shows a hypoechoic lesion with marginal hyperechoic area. (b) Contrast-enhanced US image in the same region shows a slightly hypoechoic lesion compared to surrounding liver parenchyma, but shows late-phase uptake of contrast agent. (c) Transverse contrast-enhanced computed tomographic scan shows a hyperattenuating lesion. With B-mode US images alone, four readers detected the lesion as liver metastasis with high confidence level. With the combination of B-mode ultrasonography and contrast-enhanced US images, only one reader detected the lesion as liver metastasis with low confidence level.

Figure 5, Liver cyst in a 73-year-old woman. At follow-up magnetic resonance (MR) imaging 6 months later, the lesion showed no change in size and typical findings on contrast-enhanced computed tomography. Hence, the lesion was considered to be a liver cyst. (a) B-mode ultrasonographic (US) image obtained in the right lobe of the liver shows a typical hepatic cyst with sharp margins and increased transmission through the lesion. (b) Contrast-enhanced US image in the same region shows subtle endocystic enhancing septa and slightly hyperechoic content. (c) Transverse precontrast heavy T2-weighted fast spin echo MR image shows the cyst as a very bright lesion. With B-mode US images alone, no reader detected the lesion as liver metastasis. Conversely, with the combination of B-mode US and contrast-enhanced US images, five readers detected the lesion as liver metastasis with high confidence level.

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False-negative Findings

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Figure 6, Liver metastasis from stomach cancer in a 78-year-old man. At follow-up computed tomography 2 months later, the lesion showed growth. Hence, the lesion was considered to be a true metastatic tumor. (a) B-mode ultrasonographic image obtained in the left lobe of the liver shows a small hypoechoic lesion in segment 4. (b) Contrast-enhanced ultrasonographic image in the same region shows a small and subtle signal void without enhancement in segment 4. (c) Transverse contrast-enhanced computed tomographic scan shows a small hypoattenuating lesion. All readers overlooked this nodule on both B-mode ultrasonography alone and the combination of B-mode ultrasonography and contrast-enhanced ultrasonography.

Figure 7, Histologically proved liver metastasis from ovarian cancer in a 73-year-old woman. (a) B-mode ultrasonographic image obtained in the right lobe of the liver shows a small and slightly hypoechoic lesion in segment 6. (b) Contrast-enhanced ultrasonographic image in the same region shows a small and clear signal void without enhancement in segment 6. (c) Transverse contrast-enhanced computed tomographic scan shows a small hypoattenuating lesion. All readers overlooked this nodule at B-mode ultrasonography alone. Conversely, six readers detected the lesion as liver metastasis with high confidence level.

Figure 8, Histologically proved liver metastasis from ovarian cancer in a 74-year-old woman. (a) B-mode ultrasonographic image obtained in the right lobe of the liver shows a slightly hyperechoic lesion in segment 1 ( arrows ) and a typical hepatic cyst with sharp margins and increased transmission through the lesion ( arrowheads ). (b) Contrast-enhanced ultrasonographic image in the same region shows a clear signal void without enhancement in segment 1 ( arrows ) and a typical hepatic cyst with sharp margins and increased transmission through the lesion ( arrowheads ). (c) Transverse contrast-enhanced computed tomographic scan shows a small hypoattenuating lesion ( arrow ). All readers overlooked this nodule at B-mode ultrasonography alone. Conversely, five readers detected the lesion as liver metastasis with high confidence level.

Figure 9, The number of false-negative lesions with and without contrast-enhanced ultrasonography (US) for the seven physicians.

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Discussion

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Acknowledgments

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Academic Radiology, Volume 16, Issue 7
Journals General Radiology
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