Contrast-enhanced ultrasound with perflubutane microbubble agent: evaluation of differentiation of hepatocellular carcinoma.
OBJECTIVE
The aim of this study was to evaluate the effectiveness of contrast-enhanced ultrasound with a perflubutane microbubble agent in the assessment of cellular differentiation of hepatocellular carcinoma (HCC).


METHODS
Continuous harmonic imaging with a low mechanical index (0.21-0.30) was performed 1, 5, and 10 minutes after i.v. contrast injection (0.0075 mL/kg). Tumor enhancement was evaluated by both subjective reading and objective intensity analysis based on the signal distribution in the nontumor parenchyma. Tumor vascularity was assessed with CT during hepatic arteriography.


RESULTS
Sixty-four patients with 77 histologically proved HCCs (mean greatest dimension, 19.1 ± 5.3 mm)--six poorly differentiated HCCs, 45 moderately differentiated HCCs, and 26 well-differentiated HCCs--were enrolled in this prospective study. Among 64 hyperenhancing lesions on peak enhancement sonograms, four poorly differentiated HCCs and eight moderately differentiated HCCs exhibited washout within 1 minute. In addition to these 12 lesions, 36 lesions exhibited washout 5 minutes after injection, resulting in a total of 48 washout lesions. Fifty-four lesions exhibited washout 10 minutes after contrast injection (six poorly differentiated, 38 moderately differentiated, and 10 well-differentiated HCCs). Washout was more frequent in poorly than in moderately differentiated HCC (p = 0.0117) and well-differentiated HCC (p = 0.0003) in the 1-minute phase and was more frequent in moderately differentiated than in well-differentiated HCC in the 5-minute (p = 0.0026) and 10-minute (p = 0.0117) phases. Thirteen lesions were isoenhancing or hypoenhancing on peak enhancement sonograms (three moderately differentiated and 10 well-differentiated HCCs). Contrast-enhanced ultrasound and CT during hepatic arteriography did not differ significantly with respect to rate of detection of hyperenhancing lesions.


CONCLUSIONS
The findings at contrast-enhanced ultrasound with the perflubutane microbubble agent may be predictive of cellular differentiation of HCC without needle biopsy.
Department of Medicine and Clinical Oncology, Chiba University Graduate School of Medicine, 1-8-1, Inohana, Chuou-ku, Chiba 260-8670, Japan.
Masanori
M
Takahashi
Hitoshi
H
Maruyama
Hiroyuki
H
Ishibashi
Masaharu
M
Yoshikawa
Osamu
O
Yokosuka
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000792:Angiography; D006528:Carcinoma, Hepatocellular / Q000098:blood supply / Q000000981:diagnostic imaging* / Q000473:pathology; D002454:Cell Differentiation; D003287:Contrast Media; D005260:Female; D005466:Fluorocarbons; D006499:Hepatic Artery / Q000000981:diagnostic imaging; D006801:Humans; D007089:Image Enhancement / Q000379:methods*; D008113:Liver Neoplasms / Q000098:blood supply / Q000000981:diagnostic imaging* / Q000473:pathology; D008297:Male; D045423:Microbubbles; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D014057:Tomography, X-Ray Computed; D014463:Ultrasonography
D003287:Contrast Media; D005466:Fluorocarbons; C108042:perfluorobutane