Characterization of Focal Liver Masses: A Multicenter Comparison of Contrast-Enhanced Ultrasound, Computed Tomography, and Magnetic Resonance Imaging.

OBJECTIVES: To demonstrate the usefulness of contrast-enhanced ultrasound (CEUS) for the evaluation of focal liver masses via a direct comparison to standard ultrasound and computed tomography/magnetic resonance imaging (CT/MRI). METHODS: A cohort of 214 patients with previously undiagnosed focal liver masses were included from 5 different centers. Each patient was imaged using CEUS and CT and/or MRI. Anonymized and randomized images were interpreted by 4 separate blind readers from 3 of the participating centers (2 readers for CEUS and 2 readers for CT/MRI). Readers were blinded to patient demographics and past medical history. Readers were asked to decide if the lesion was benign or malignant, provide a final diagnosis for the lesion, and provide a confidence interval. Results were compared to truth standard from pathology or expert consensus. RESULTS: In determination of malignancy, CEUS had a sensitivity of 95%, specificity of 82%, PPV of 82%, NPV of 95%, statistically better than standard ultrasound (sensitivity 82%, specificity 56%, PPV 60%, NPV 78%) with P < .01 and not statistically different from CT (sensitivity 90%, specificity 73% PPV 81%, NPV 86%) or MRI (sensitivity 85%, specificity 79%, PPV 68%, NPV 91%) with P ≥ .01. In assigning a final diagnosis, CEUS had an accuracy of 78% statistically better than standard ultrasound (46%) with P < .01 and not statistically different from CT (68%) or MRI (71%) with P > .01. CONCLUSIONS: In the evaluation of focal liver lesions, both for determination of malignancy and in accuracy of final diagnosis, CEUS performs better than standard ultrasound and at least equivalent to both CT and MRI.

GDNF drives rapid tubule morphogenesis in a novel 3D in vitro model for ADPKD.

Cystogenesis is a morphological consequence of numerous genetic diseases of the epithelium. In the kidney, the pathogenic mechanisms underlying the program of altered cell and tubule morphology are obscured by secondary effects of cyst expansion. Here, we developed a new 3D tubuloid system to isolate the rapid changes in protein localization and gene expression that correlate with altered cell and tubule morphology during cyst initiation. Mouse renal tubule fragments were pulsed with a cell differentiation cocktail including glial-derived neurotrophic factor (GDNF) to yield collecting duct-like tubuloid structures with appropriate polarity, primary cilia, and gene expression. Using the 3D tubuloid model with an inducible Pkd2 knockout system allowed the tracking of morphological, protein, and genetic changes during cyst formation. Within hours of inactivation of Pkd2 and loss of polycystin-2, we observed significant progression in tubuloid to cyst morphology that correlated with 35 differentially expressed genes, many related to cell junctions, matrix interactions, and cell morphology previously implicated in cystogenesis.This article has an associated First Person interview with the first author of the paper.

Contrast-enhanced US Approach to the Diagnosis of Focal Liver Masses.

Focal liver lesions are commonly encountered and often demonstrate nonspecific findings at initial imaging. Although most incidentally discovered liver lesions are benign, their noninvasive diagnosis is necessary, especially if they are large or atypical. Imaging characterization of focal liver lesions and exclusion of malignancy are of prime importance, particularly in high-risk populations. Contrast agent-enhanced ultrasonography of liver lesions is both accurate and reproducible for evaluation of benign and malignant liver tumors. Use of an imaging algorithm and a controlled sonographic technique, including dedicated arterial phase cine imaging and imaging every 30 seconds in the portal venous phase and the delayed (or late) phase, is essential for accurate characterization. This algorithmic analysis of focal liver lesions focuses first on the determination of malignancy by imaging the portal venous phase and the late phase; washout in these phases correlates with a malignant tumor, and sustained enhancement in these phases is suggestive that a lesion is benign. In addition, the timing and the intensity of washout differentiate hepatocellular malignancies from nonhepatocellular malignancies. Nonhepatocellular tumors demonstrate early and strong washout, whereas hepatocellular malignancies show delayed and weak washout. Subsequent analysis of dynamic real-time enhancement patterns in the arterial phase demonstrates specific enhancement patterns of common benign and malignant focal liver lesions. Hemangiomas show classic peripheral nodular enhancement, and spoke-wheel centrifugal enhancement is suggestive of focal nodular hyperplasia. Hepatic adenomas may show centripetal filling. However, arterial phase enhancement in malignancy has less specificity. Online supplemental material is available for this article. ©RSNA, 2017 •.