Changes in tumor vascularity precede microbubble contrast accumulation deficit in the process of dedifferentiation of hepatocellular carcinoma

PurposeTo elucidate the changes in tumor vascularity and microbubble accumulation on contrast-enhanced sonograms, in relation to the dedifferentiation of hepatocellular carcinoma (HCC).Materials and methodsThis prospective study enrolled 10 patients with histologically proven HCC (14.4–39.0 mm, 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.ResultsVascular-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.ConclusionDedifferentiation 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.