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Objective: A new computer tool is proposed to distinguish between focal nodular hyperplasia (FNH) and an inflammatory hepatocellular adenoma (I-HCA) using contrast-enhanced ultrasound (CEUS). The new method was compared with the usual qualitative analysis., Methods: The proposed tool embeds an "optical flow" algorithm, designed to mimic the human visual perception of object transport in image series, to quantitatively analyse apparent microbubble transport parameters visible on CEUS. Qualitative (visual) and quantitative (computer-assisted) CEUS data were compared in a cohort of adult patients with either FNH or I-HCA based on pathological and radiological results. For quantitative analysis, several computer-assisted classification models were tested and subjected to cross-validation. The accuracies, area under the receiver-operating characteristic curve (AUROC), sensitivity and specificity, positive predictive values (PPVs), negative predictive values (NPVs), false predictive rate (FPRs) and false negative rate (FNRs) were recorded., Results: Forty-six patients with FNH (n = 29) or I-HCA (n = 17) with 47 tumours (one patient with 2 I-HCA) were analysed. The qualitative diagnostic parameters were accuracy = 93.6%, AUROC = 0.94, sensitivity = 94.4%, specificity = 93.1%, PPV = 89.5%, NPV = 96.4%, FPR = 6.9% and FNR = 5.6%. The quantitative diagnostic parameters were accuracy = 95.9%, AUROC = 0.97, sensitivity = 93.4%, specificity = 97.6%, PPV = 95.3%, NPV = 96.7%, FPR = 2.4% and FNR = 6.6%., Conclusions: Microbubble transport patterns evident on CEUS are valuable diagnostic indicators. Machine-learning algorithms analysing such data facilitate the diagnosis of FNH and I-HCA tumours., Key Points: • Distinguishing between focal nodular hyperplasia and an inflammatory hepatocellular adenoma using dynamic contrast-enhanced ultrasound is sometimes difficult. • Microbubble transport patterns evident on contrast-enhanced sonography are valuable diagnostic indicators. • Machine-learning algorithms analysing microbubble transport patterns facilitate the diagnosis of FNH and I-HCA.

Objectives: Local drug delivery by ultrasound (US)-induced cavitation is a promising strategy for increasing the drug concentration at the target location and for decreasing the systemic toxicity effects. The presence of microbubbles during sonication at the targeted location improves the likelihood for cavitation that can be exploited to increase the capillary permeability. The objective of this work was to evaluate the magnetic resonance imaging (MRI) contrast changes in hepatic tissue in vivo, induced by US-triggered cavitation and destruction of microbubbles (Sonovue), in the presence of a coinjected blood pool MRI contrast agent (Vistarem) used as a reporter macromolecule. The potential tissue damage induced by microbubbles destruction was also evaluated by histology., Method: The change in the hepatic distribution of the macromolecular MRI contrast agent associated with cavitation was monitored at 1.5 T with a look-locker fast inversion recovery sequence to map the longitudinal relaxation rates, before and during 1 hour after intravenous administration of Vistarem and Sonovue. In 1 group of rats (n = 5), these microbubbles were immediately destroyed with a clinical echograph, using a high mechanical index (MI = 1.5) at low frequency (2 MHz). The control group (n = 7) received identical injections without application of US. The parametric relaxation rate images were computed, and the changes in time were analyzed to account for the potential effect of microbubble destruction by US on the permeability of the hepatic vessels. The animals were killed 1 day after the experiment for routine histology of the liver., Results: For both groups of animals, after an initial increase, a transient decay of the longitudinal relaxation rate was observed, followed by a constant plateau after 20 minutes. The analysis of the mean relaxation rates in the liver showed significant (P < 0.01) higher values for the group with destruction of microbubbles as compared with the control group. The US-triggered cavitation and destruction of microbubble with the proposed protocol suggests an increased concentration of Vistarem of a factor 2 in the hepatic tissue. No tissue damage was observed at the microscopic analysis., Conclusion: The absence of tissue alterations indicates that the destruction of this US contrast agent could be safe in vivo under an appropriate choice of the sonication parameters. This approach opens new perspectives for translation toward clinical applications of local drug delivery. Ultrasound-mediated microbubble destruction may help in increasing the local concentration of a drug currently limited by the endothelial barrier. In addition, it may help in reducing the systemic toxicity to normal cells in standard chemotherapies, because the enhanced capillary permeability effect can be spatially adjusted by selecting the sonicated region.