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 •.
Glycerol-3-phosphate acyltransferase (GPAT) catalyzes the initial step in the synthesis of all glycerolipids. It is the committed and rate-limiting step and is redundant in Saccharomyces cerevisiae, mammals, and plants. GPAT controls the formation of lipid intermediates that serve not only as precursors of more-complex lipids but also as intracellular signaling molecules. Saccharomyces cerevisiae possesses two GPATs, encoded by the GAT1 and GAT2 genes. Metabolic analysis of yeast lacking either GAT1 or GAT2 indicated partitioning of the two main branches of phospholipid synthesis at the initial and rate-limiting GPAT step. We are particularly interested in identifying molecular determinants mediating lipid metabolic pathway partitioning; therefore, as a starting point, we have performed a detailed study of Gat1p and Gat2p cellular localization. We have compared Gat1p and Gat2p localization by fluorescence microscopy and subcellular fractionation using equilibrium density gradients. Our results indicate Gat1p and Gat2p overlap mostly in their localization and are in fact microsomal GPATs, localized to both perinuclear and cortical endoplasmic reticula in actively proliferating cells. A more detailed analysis suggests a differential enrichment of Gat1p and Gat2p in distinct ER fractions. Furthermore, overexpression of these enzymes in the absence of endogenous GPATs induces proliferation of distinct ER arrays, differentially affecting cortical ER morphology and polarized cell growth. In addition, our studies also uncovered a dynamic posttranslational regulation of Gat1p and Gat2p and a compensation mechanism through phosphorylation that responds to a cellular GPAT imbalance.The first step in the synthesis of almost all membrane phospholipids and neutral glycerolipids is catalyzed by glycerol-3-phosphate acyltransferases (GPATs; EC 2.3.1.15). This enzyme transfers a fatty acid from fatty acyl coenzyme A to the sn-1 position of glycerol-3-phosphate to produce lysophosphatidic acid (LysoPA). LysoPA is further acylated at the sn-2 position by a separate acyltransferase to produce phosphatidic acid (PA). PA can be either (i) dephosphorylated to produce diacylglycerol (DAG) or (ii) converted to CDP-DAG. These lipids not only are precursors of all glycerolipids but also are dynamic components of signal transduction systems that control cell physiology. Regulated interconversion of signaling lipids like LysoPA, PA, and DAG transmits information in part by their biophysical properties (5) and through lipid-lipid and lipid-protein interactions (18,23,29). The mechanisms of the regulation of PA biosynthesis, of the rate-limiting GPAT step, and of lipid metabolic pathway partitioning are not known (8,12).GPATs are present in bacteria, fungi, plants, and animals. We and others have previously identified a unique gene pair in Saccharomyces cerevisiae, YKR067W (GAT1/GPT2) and YBL011W (GAT2/SCT1), and demonstrated that they code for the major GPATs in this organism (32, 34). Bioinformatic approaches, using a region conserved betw...
Objectives Following positive surveillance ultrasound (US), magnetic resonance imaging (MRI) is recommended for further characterization. We propose contrast‐enhanced ultrasound (CEUS) shows equivalent efficacy. Methods This prospective institutional review board approved study recruited 195 consecutive at‐risk patients with a positive surveillance US. All had CEUS and MRI. Biopsy (n = 44) and follow‐up are gold standard. MRI and CEUS results are classified according to liver imaging reporting and data system (LI‐RADS) and patient outcome. Results As an US‐based modality, CEUS is superior in confirming findings from surveillance US, correlation in 189/195 (97%) on CEUS compared to 153/195 (79%) on MRI. Within these negative MRI examinations, there are 2 hepatocellular carcinoma (HCC) and 1 cholangiocarcinoma (iCCA) diagnosed on CEUS and proven by biopsy. From 195 patients, there are 71 malignant diagnoses from all sources, including 58 LR‐5 (45 on MRI and 54 on CEUS) and 13 others, including HCC outside of LR‐5 category, and LR‐M with biopsy proven iCCA (3 on MRI and 6 on CEUS). CEUS and MRI show concordant results in the majority of patients (146/195, 75%), including 57/146 malignant and 89/146 benign diagnoses. There are 41/57 concordant LR‐5 and 6/57 concordant LR‐M. When CEUS and MRI are discordant, CEUS upgraded 20 (10 biopsy‐proven) from MRI LR‐3/4 to CEUS LR‐5 or LR‐M by showing washout (WO) that MRI failed to show. Additionally, CEUS characterized time and intensity of WO and diagnosed 13/20 LR‐5 by showing late and weak WO and 7 LR‐M by showing fast and marked WO. CEUS is 81% sensitive and 92% specific in diagnosing malignancy. MRI is 64% sensitive and 93% specific. Conclusions CEUS performance is at least equivalent if not superior to MRI for initial evaluation of lesions from surveillance US.
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