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Characterization of Focal Liver Lesions with Contrast-specific US Modes and a Sulfur Hexafluoride–filled Microbubble Contrast Agent: Diagnostic Performance and Confidence¹

¹ From the Department of Radiology, Cattinara Hospital, University of Trieste, Strada di Fiume 447, Trieste 34149, Italy (E.Q., M.B., R.P.M.); and Department of Radiology (F.C., L.G.) and Operative Unit of Interventional Ultrasound (S.R., L.R.), San Matteo Hospital, University of Pavia, Italy. From the 2003 RSNA scientific assembly. Received August 31, 2003; revision requested November 11; revision received November 17; accepted January 15, 2004. Address correspondence to E.Q. (e-mail: equaia@yahoo.com).

View larger version (14K): [in a new window]   Figure 1. Different contrast enhancement patterns in focal liver lesions. Absent (A), dotted (B), peripheral rimlike (C), peripheral nodular (D), central with spoke wheel-shaped (E), diffuse homogeneous (F), and diffuse heterogeneous (G) enhancement patterns are shown.

View larger version (165K): [in a new window]   Figure 2a. Transverse contrast-enhanced US scans obtained in contrast-specific mode with contrast-tuned imaging in 65-year-old man show most frequent and typical appearances of HCC. (a) Scan obtained during arterial phase—that is, 20 seconds after microbubble contrast agent injection—shows HCC (arrow) with diffuse, slightly heterogeneous contrast enhancement. (b) Scan obtained during portal venous phase—that is, 70 seconds after the injection—shows the HCC (arrow) to be slightly hypoechoic compared with the adjacent liver. (c) Scan obtained during late phase—that is, 100 seconds after the injection—shows the HCC (arrow) to be hypoechoic.

View larger version (192K): [in a new window]   Figure 2b. Transverse contrast-enhanced US scans obtained in contrast-specific mode with contrast-tuned imaging in 65-year-old man show most frequent and typical appearances of HCC. (a) Scan obtained during arterial phase—that is, 20 seconds after microbubble contrast agent injection—shows HCC (arrow) with diffuse, slightly heterogeneous contrast enhancement. (b) Scan obtained during portal venous phase—that is, 70 seconds after the injection—shows the HCC (arrow) to be slightly hypoechoic compared with the adjacent liver. (c) Scan obtained during late phase—that is, 100 seconds after the injection—shows the HCC (arrow) to be hypoechoic.

View larger version (174K): [in a new window]   Figure 2c. Transverse contrast-enhanced US scans obtained in contrast-specific mode with contrast-tuned imaging in 65-year-old man show most frequent and typical appearances of HCC. (a) Scan obtained during arterial phase—that is, 20 seconds after microbubble contrast agent injection—shows HCC (arrow) with diffuse, slightly heterogeneous contrast enhancement. (b) Scan obtained during portal venous phase—that is, 70 seconds after the injection—shows the HCC (arrow) to be slightly hypoechoic compared with the adjacent liver. (c) Scan obtained during late phase—that is, 100 seconds after the injection—shows the HCC (arrow) to be hypoechoic.

View larger version (144K): [in a new window]   Figure 3a. HCC depicted on longitudinal contrast-enhanced US scans obtained in contrast-specific mode with pulse-inversion imaging in 60-year-old man. (a) Scan obtained during arterial phase—that is, 22 seconds after microbubble contrast agent injection—shows HCC (arrow) with diffuse heterogeneous contrast enhancement. (b, c) The tumor (arrow) appears isoechoic relative to the adjacent liver on scans obtained during both portal venous phase—that is, 65 seconds after the injection (b)—and late phase—that is, 100 seconds after the injection (c).

View larger version (149K): [in a new window]   Figure 3b. HCC depicted on longitudinal contrast-enhanced US scans obtained in contrast-specific mode with pulse-inversion imaging in 60-year-old man. (a) Scan obtained during arterial phase—that is, 22 seconds after microbubble contrast agent injection—shows HCC (arrow) with diffuse heterogeneous contrast enhancement. (b, c) The tumor (arrow) appears isoechoic relative to the adjacent liver on scans obtained during both portal venous phase—that is, 65 seconds after the injection (b)—and late phase—that is, 100 seconds after the injection (c).

View larger version (148K): [in a new window]   Figure 3c. HCC depicted on longitudinal contrast-enhanced US scans obtained in contrast-specific mode with pulse-inversion imaging in 60-year-old man. (a) Scan obtained during arterial phase—that is, 22 seconds after microbubble contrast agent injection—shows HCC (arrow) with diffuse heterogeneous contrast enhancement. (b, c) The tumor (arrow) appears isoechoic relative to the adjacent liver on scans obtained during both portal venous phase—that is, 65 seconds after the injection (b)—and late phase—that is, 100 seconds after the injection (c).

View larger version (138K): [in a new window]   Figure 4a. Longitudinal contrast-enhanced US scans obtained in contrast-specific mode with pulse-inversion imaging in 55-year-old man show less frequent appearances of HCC, which are similar to appearances of macroregenerative nodules. (a) Scan obtained 25 seconds after the injection (arterial phase) shows HCC (arrow) with dotted contrast enhancement, which consists of tiny separate spots, and a hypoechoic appearance. (b, c) Dotted contrast enhancement (arrow) persists during both portal venous phase—that is, 70 seconds after the injection (b)—and late phase—that is, 120 seconds after the injection (c)—with a progressive isoechoic appearance.

View larger version (126K): [in a new window]   Figure 4b. Longitudinal contrast-enhanced US scans obtained in contrast-specific mode with pulse-inversion imaging in 55-year-old man show less frequent appearances of HCC, which are similar to appearances of macroregenerative nodules. (a) Scan obtained 25 seconds after the injection (arterial phase) shows HCC (arrow) with dotted contrast enhancement, which consists of tiny separate spots, and a hypoechoic appearance. (b, c) Dotted contrast enhancement (arrow) persists during both portal venous phase—that is, 70 seconds after the injection (b)—and late phase—that is, 120 seconds after the injection (c)—with a progressive isoechoic appearance.

View larger version (141K): [in a new window]   Figure 4c. Longitudinal contrast-enhanced US scans obtained in contrast-specific mode with pulse-inversion imaging in 55-year-old man show less frequent appearances of HCC, which are similar to appearances of macroregenerative nodules. (a) Scan obtained 25 seconds after the injection (arterial phase) shows HCC (arrow) with dotted contrast enhancement, which consists of tiny separate spots, and a hypoechoic appearance. (b, c) Dotted contrast enhancement (arrow) persists during both portal venous phase—that is, 70 seconds after the injection (b)—and late phase—that is, 120 seconds after the injection (c)—with a progressive isoechoic appearance.

View larger version (48K): [in a new window]   Figure 5a. Transverse US scans obtained in 66-year-old man show epithelioid hemangioendothelioma with low-grade malignant pattern at histologic analysis. (a) On baseline (left) and color Doppler (right) US scans, the tumor (arrow) appears hypoechoic with a peripheral vessel. (b, c) US scans obtained in contrast-specific mode with pure harmonic detection show diffuse, homogeneous contrast enhancement (arrow) during arterial (b) and portal venous (c) phases. (c) During portal venous phase, the homogeneous enhancement (arrow) persists with a hyperechoic appearance.

View larger version (123K): [in a new window]   Figure 5b. Transverse US scans obtained in 66-year-old man show epithelioid hemangioendothelioma with low-grade malignant pattern at histologic analysis. (a) On baseline (left) and color Doppler (right) US scans, the tumor (arrow) appears hypoechoic with a peripheral vessel. (b, c) US scans obtained in contrast-specific mode with pure harmonic detection show diffuse, homogeneous contrast enhancement (arrow) during arterial (b) and portal venous (c) phases. (c) During portal venous phase, the homogeneous enhancement (arrow) persists with a hyperechoic appearance.

View larger version (100K): [in a new window]   Figure 5c. Transverse US scans obtained in 66-year-old man show epithelioid hemangioendothelioma with low-grade malignant pattern at histologic analysis. (a) On baseline (left) and color Doppler (right) US scans, the tumor (arrow) appears hypoechoic with a peripheral vessel. (b, c) US scans obtained in contrast-specific mode with pure harmonic detection show diffuse, homogeneous contrast enhancement (arrow) during arterial (b) and portal venous (c) phases. (c) During portal venous phase, the homogeneous enhancement (arrow) persists with a hyperechoic appearance.

View larger version (145K): [in a new window]   Figure 6a. Transverse contrast-enhanced US scans obtained in 50-year-old-woman show typical appearances of metastasis. (a) Baseline color Doppler US scan shows slightly heterogeneous metastasis with peripheral vessels. (b, c) Contrast-enhanced US scans obtained in contrast-specific mode with contrast-tuned imaging show persistent peripheral, rimlike contrast enhancement 30 seconds (b, arterial phase) and 75 seconds (c, portal venous phase) after microbubble contrast agent injection, with the center of the lesion remaining hypoechoic.

View larger version (122K): [in a new window]   Figure 6b. Transverse contrast-enhanced US scans obtained in 50-year-old-woman show typical appearances of metastasis. (a) Baseline color Doppler US scan shows slightly heterogeneous metastasis with peripheral vessels. (b, c) Contrast-enhanced US scans obtained in contrast-specific mode with contrast-tuned imaging show persistent peripheral, rimlike contrast enhancement 30 seconds (b, arterial phase) and 75 seconds (c, portal venous phase) after microbubble contrast agent injection, with the center of the lesion remaining hypoechoic.

View larger version (124K): [in a new window]   Figure 6c. Transverse contrast-enhanced US scans obtained in 50-year-old-woman show typical appearances of metastasis. (a) Baseline color Doppler US scan shows slightly heterogeneous metastasis with peripheral vessels. (b, c) Contrast-enhanced US scans obtained in contrast-specific mode with contrast-tuned imaging show persistent peripheral, rimlike contrast enhancement 30 seconds (b, arterial phase) and 75 seconds (c, portal venous phase) after microbubble contrast agent injection, with the center of the lesion remaining hypoechoic.

View larger version (122K): [in a new window]   Figure 7a. Longitudinal contrast-enhanced US scans obtained in 55-year-old woman show typical appearances of liver hemangioma. (a) Baseline US scan shows hyperechoic and slightly heterogeneous hemangioma (arrow). (b-d) Contrast-enhanced US scans obtained in contrast-specific mode with contrast-tuned imaging show nodular peripheral enhancement 35 seconds after microbubble contrast agent injection (b, arterial phase) and progressive centripetal fill-in (arrow in d) during late phase—that is, 110 seconds (c) and 180 seconds (d) after the injection.

View larger version (122K): [in a new window]   Figure 7b. Longitudinal contrast-enhanced US scans obtained in 55-year-old woman show typical appearances of liver hemangioma. (a) Baseline US scan shows hyperechoic and slightly heterogeneous hemangioma (arrow). (b-d) Contrast-enhanced US scans obtained in contrast-specific mode with contrast-tuned imaging show nodular peripheral enhancement 35 seconds after microbubble contrast agent injection (b, arterial phase) and progressive centripetal fill-in (arrow in d) during late phase—that is, 110 seconds (c) and 180 seconds (d) after the injection.

View larger version (137K): [in a new window]   Figure 7c. Longitudinal contrast-enhanced US scans obtained in 55-year-old woman show typical appearances of liver hemangioma. (a) Baseline US scan shows hyperechoic and slightly heterogeneous hemangioma (arrow). (b-d) Contrast-enhanced US scans obtained in contrast-specific mode with contrast-tuned imaging show nodular peripheral enhancement 35 seconds after microbubble contrast agent injection (b, arterial phase) and progressive centripetal fill-in (arrow in d) during late phase—that is, 110 seconds (c) and 180 seconds (d) after the injection.

View larger version (139K): [in a new window]   Figure 7d. Longitudinal contrast-enhanced US scans obtained in 55-year-old woman show typical appearances of liver hemangioma. (a) Baseline US scan shows hyperechoic and slightly heterogeneous hemangioma (arrow). (b-d) Contrast-enhanced US scans obtained in contrast-specific mode with contrast-tuned imaging show nodular peripheral enhancement 35 seconds after microbubble contrast agent injection (b, arterial phase) and progressive centripetal fill-in (arrow in d) during late phase—that is, 110 seconds (c) and 180 seconds (d) after the injection.

View larger version (83K): [in a new window]   Figure 8a. Transverse contrast-enhanced US scans obtained in contrast-specific mode with pure harmonic detection in 45-year-old woman show typical spoke wheel-shaped contrast enhancement pattern of focal nodular hyperplasia after microbubble contrast agent injection. (a) Central spoke wheel-shaped contrast enhancement (arrow) is evident 15 seconds after the injection (arterial phase). (b) Contrast enhancement (arrow) is diffuse and homogeneous 25 seconds after the injection (arterial phase). (c) Contrast enhancement is hyperechoic 105 seconds after the injection, with a central hypoechoic region that corresponds to the central scar (arrow) that is evident during the late phase.

View larger version (129K): [in a new window]   Figure 8b. Transverse contrast-enhanced US scans obtained in contrast-specific mode with pure harmonic detection in 45-year-old woman show typical spoke wheel-shaped contrast enhancement pattern of focal nodular hyperplasia after microbubble contrast agent injection. (a) Central spoke wheel-shaped contrast enhancement (arrow) is evident 15 seconds after the injection (arterial phase). (b) Contrast enhancement (arrow) is diffuse and homogeneous 25 seconds after the injection (arterial phase). (c) Contrast enhancement is hyperechoic 105 seconds after the injection, with a central hypoechoic region that corresponds to the central scar (arrow) that is evident during the late phase.

View larger version (133K): [in a new window]   Figure 8c. Transverse contrast-enhanced US scans obtained in contrast-specific mode with pure harmonic detection in 45-year-old woman show typical spoke wheel-shaped contrast enhancement pattern of focal nodular hyperplasia after microbubble contrast agent injection. (a) Central spoke wheel-shaped contrast enhancement (arrow) is evident 15 seconds after the injection (arterial phase). (b) Contrast enhancement (arrow) is diffuse and homogeneous 25 seconds after the injection (arterial phase). (c) Contrast enhancement is hyperechoic 105 seconds after the injection, with a central hypoechoic region that corresponds to the central scar (arrow) that is evident during the late phase.

View larger version (71K): [in a new window]   Figure 9a. Hepatocellular adenoma depicted on transverse US scans obtained in 50-year-old man. (a) Baseline color Doppler US scan shows lesion (arrow) with peripheral vessels. (b-d) Contrast-enhanced US scans obtained in contrast-specific mode with cadence contrast pulse sequencing during arterial phase. The lesion (arrow) has diffuse and homogeneous enhancement 17 seconds after microbubble contrast agent injection (b) and becomes progressively isoechoic relative to the adjacent liver parenchyma 25 seconds (c) and 35 seconds (d) after the injection.

View larger version (117K): [in a new window]   Figure 9b. Hepatocellular adenoma depicted on transverse US scans obtained in 50-year-old man. (a) Baseline color Doppler US scan shows lesion (arrow) with peripheral vessels. (b-d) Contrast-enhanced US scans obtained in contrast-specific mode with cadence contrast pulse sequencing during arterial phase. The lesion (arrow) has diffuse and homogeneous enhancement 17 seconds after microbubble contrast agent injection (b) and becomes progressively isoechoic relative to the adjacent liver parenchyma 25 seconds (c) and 35 seconds (d) after the injection.

View larger version (117K): [in a new window]   Figure 9c. Hepatocellular adenoma depicted on transverse US scans obtained in 50-year-old man. (a) Baseline color Doppler US scan shows lesion (arrow) with peripheral vessels. (b-d) Contrast-enhanced US scans obtained in contrast-specific mode with cadence contrast pulse sequencing during arterial phase. The lesion (arrow) has diffuse and homogeneous enhancement 17 seconds after microbubble contrast agent injection (b) and becomes progressively isoechoic relative to the adjacent liver parenchyma 25 seconds (c) and 35 seconds (d) after the injection.

View larger version (124K): [in a new window]   Figure 9d. Hepatocellular adenoma depicted on transverse US scans obtained in 50-year-old man. (a) Baseline color Doppler US scan shows lesion (arrow) with peripheral vessels. (b-d) Contrast-enhanced US scans obtained in contrast-specific mode with cadence contrast pulse sequencing during arterial phase. The lesion (arrow) has diffuse and homogeneous enhancement 17 seconds after microbubble contrast agent injection (b) and becomes progressively isoechoic relative to the adjacent liver parenchyma 25 seconds (c) and 35 seconds (d) after the injection.

View larger version (28K): [in a new window]   Figure 10a. Graphs illustrate the increase in diagnostic confidence after review of contrast-enhanced US scans. Receiver operating characteristic curves are plotted to discriminate between benign and malignant focal liver lesions after review of baseline US scans (continuous line) and after review of contrast-enhanced US scans (dotted line) for (a) reader 1 and (b) reader 2. The curves are shown against a diagonal (right) line, which represents a review method with which malignant and benign lesions cannot be differentiated.

View larger version (29K): [in a new window]   Figure 10b. Graphs illustrate the increase in diagnostic confidence after review of contrast-enhanced US scans. Receiver operating characteristic curves are plotted to discriminate between benign and malignant focal liver lesions after review of baseline US scans (continuous line) and after review of contrast-enhanced US scans (dotted line) for (a) reader 1 and (b) reader 2. The curves are shown against a diagonal (right) line, which represents a review method with which malignant and benign lesions cannot be differentiated.