Changes in tumor vascularity precede microbubble contrast accumulation deficit in the process of dedifferentiation of hepatocellular carcinoma.
OBJECTIVE
To elucidate the changes in tumor vascularity and microbubble accumulation on contrast-enhanced sonograms, in relation to the dedifferentiation of hepatocellular carcinoma (HCC).


METHODS
This prospective study enrolled 10 patients with histologically proven HCC (14.4-39.0mm, 26.1+/-7.4) showing nodule-in-nodule appearance upon contrast-enhanced computed tomography. Contrast-enhanced ultrasound was performed by harmonic imaging under a low mechanical index (0.22-0.25) during the vascular phase (agent injection to 1 min) and late phase (15 min) following the injection of Sonazoid (0.0075 ml/kg). Contrast enhancement in the inner and outer nodules was assessed in comparison with that in adjacent liver parenchyma as hyper-, iso-, or hypo-enhanced.


RESULTS
Vascular-phase enhancement of all 10 inner nodules was hyper-enhanced, and that of outer nodules was hyper-enhanced in 3, iso-enhanced in 2, and hypo-enhanced in 5. Late-phase enhancement of inner nodules was hypo-enhanced in 8 and iso-enhanced in 2. Furthermore, late-phase enhancement of outer nodules was iso-enhanced in the 7 lesions that showed iso- or hypo-enhancement in the vascular phase, and hypo-enhanced in the 3 with hyper-enhancement in the vascular phase. Late-phase hypo-enhancement was significantly more frequent in the nodules showing early-phase hyper-enhancement (11/13) than in the nodules showing early-phase iso- or hypo-enhancement (0/7) in both the inner and outer nodules.


CONCLUSIONS
Dedifferentiation of HCC may be accompanied by changes in tumor vascularity prior to a reduction in microbubble accumulation. Observation of the vascular phase may be more useful than late-phase imaging for the early recognition of HCC dedifferentiation when using contrast-enhanced ultrasound with Sonazoid.
Maruyama
Hitoshi
H
Department of Medicine and Clinical Oncology, Chiba University Graduate School of Medicine 1-8-1, Inohana, Chuou-ku, Chiba 260-8670, Japan. maru-cib@umin.ac.jp
Takahashi
Masanori
M
Ishibashi
Hiroyuki
H
Okabe
Shinichiro
S
Yoshikawa
Masaharu
M
Yokosuka
Osamu
O
D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000098:blood supply / Q000000981:diagnostic imaging* / Q000378:metabolism; D003287:Contrast Media / Q000493:pharmacokinetics; D003937:Diagnosis, Differential; D005260:Female; D005290:Ferric Compounds / Q000493:pharmacokinetics*; D006801:Humans; D007501:Iron / Q000493:pharmacokinetics*; D008113:Liver Neoplasms / Q000098:blood supply / Q000000981:diagnostic imaging* / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate; D045423:Microbubbles; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging* / Q000378:metabolism; D010087:Oxides / Q000493:pharmacokinetics*; D011856:Radiographic Image Enhancement / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014463:Ultrasonography
D003287:Contrast Media; D005290:Ferric Compounds; D010087:Oxides; C069727:Sonazoid; D007501:Iron