Two-point Dixon and six-point Dixon magnetic resonance techniques in the detection, quantification and grading of hepatic steatosis.

BACKGROUND: Hepatic steatosis is a very common problem worldwide. AIM: To assess the performance of two- and six-point Dixon magnetic resonance (MR) techniques in the detection, quantification and grading of hepatic steatosis. METHODS: A single-center retrospective study was performed in 62 patients with suspected parenchymal liver disease. MR sequences included two-point Dixon, six-point Dixon, MR spectroscopy (MRS) and MR elastography. Fat fraction (FF) estimates on the Dixon techniques were compared to the MRS-proton density FF (PDFF). Statistical tests used included Pearson's correlation and receiver operating characteristic. RESULTS: FF estimates on the Dixon techniques showed excellent correlation (≥ 0.95) with MRS-PDFF, and excellent accuracy [area under the receiver operating characteristic (AUROC) ≥ 0.95] in: (1) Detecting steatosis; and (2) Grading severe steatosis, (P < 0.001). In iron overload, two-point Dixon was not evaluable due to confounding T2* effects. FF estimates on six-point Dixon vs MRS-PDFF showed a moderate correlation (0.82) in iron overload vs an excellent correlation (0.97) without iron overload, (P < 0.03). The accuracy of six-point Dixon in grading mild steatosis improved (AUROC: 0.59 to 0.99) when iron overload cases were excluded. The excellent correlation (> 0.9) between the Dixon techniques vs MRS-PDFF did not change in the presence of liver fibrosis (P < 0.01). CONCLUSION: Dixon techniques performed satisfactorily for the evaluation of hepatic steatosis but with exceptions.

Multiparametric MR assessment of liver fat, iron, and fibrosis: a concise overview of the liver "Triple Screen".

Chronic liver disease (CLD) is a common source of morbidity and mortality worldwide. Non-alcoholic fatty liver disease (NAFLD) serves as a major cause of CLD with a rising annual prevalence. Additionally, iron overload can be both a cause and effect of CLD with a negative synergistic effect when combined with NAFLD. The development of state-of-the-art multiparametric MR solutions has led to a change in the diagnostic paradigm in CLD, shifting from traditional liver biopsy to innovative non-invasive methods for providing accurate and reliable detection and quantification of the disease burden. Novel imaging biomarkers such as MRI-PDFF for fat, R2 and R2* for iron, and liver stiffness for fibrosis provide important information for diagnosis, surveillance, risk stratification, and treatment. In this article, we provide a concise overview of the MR concepts and techniques involved in the detection and quantification of liver fat, iron, and fibrosis including their relative strengths and limitations and discuss a practical abbreviated MR protocol for clinical use that integrates these three MR biomarkers into a single simplified MR assessment. Multiparametric MR techniques provide accurate and reliable non-invasive detection and quantification of liver fat, iron, and fibrosis. These techniques can be combined in a single abbreviated MR "Triple Screen" assessment to offer a more complete metabolic imaging profile of CLD.

Diagnostic accuracy and inter-reader reliability of the MRI Liver Imaging Reporting and Data System (version 2018) risk stratification and management system.

Background: Hepatocellular carcinoma (HCC) can be diagnosed non-invasively, provided certain imaging criteria are met. However, the recent Liver Imaging Reporting and Data System (LI-RADS) version 2018 has not been widely validated. Objectives: This study aimed to evaluate the diagnostic accuracy and reader reliability of the LI-RADS version 2018 lexicon amongst fellowship trained radiologists compared with an expert consensus reference standard. Method: This retrospective study was conducted between 2018 and 2020. A total of 50 contrast enhanced liver magnetic resonance imaging (MRI) studies evaluating focal liver observations in patients with cirrhosis, hepatitis B virus (HBV) or prior HCC were acquired. The standard of reference was a consensus review by three fellowship-trained radiologists. Diagnostic accuracy including sensitivity, specificity, positive predictive value (PPV), negative predictive values (NPV) and area under the curve (AUC) values were calculated per LI-RADS category for each reader. Kappa statistics were used to measure reader agreement. Results: Readers demonstrated excellent specificities (88% - 100%) and NPVs (85% - 100%) across all LI-RADS categories. Sensitivities were variable, ranging from 67% to 83% for LI-RADS 1, 29% to 43% for LI-RADS 2, 100% for LI-RADS 3, 70% to 80% for LI-RADS 4 and 80% to 84% for LI-RADS 5. Readers showed excellent accuracy for differentiating benign and malignant liver lesions with AUC values > 0.90. Overall inter-reader agreement was 'good' (kappa = 0.76, p < 0.001). Pairwise inter-reader agreement was 'very good' (kappa ≥ 0.90, p < 0.001). Conclusion: The LI-RADS version 2018 demonstrates excellent specificity, NPV and AUC values for risk stratification of liver observations by radiologists. Liver Imaging Reporting and Data System can reliably differentiate benign from malignant lesions when used in conjunction with corresponding LI-RADS management recommendations.

Case 275: Multiple Hepatic Hydatid Cysts.

HistoryA 61-year-old woman presented to the cardiology service with sinus tachycardia. As part of her work-up, she underwent routine echocardiography that showed a normal heart but incidentally revealed multiple lesions in the liver. An outpatient CT scan was performed to characterize the liver lesions. The patient had emigrated to Canada from the Middle East several years earlier and had no medical history of note; in particular, there was no history of cancer or predisposing factors for chronic liver disease. The patient's clinical examination findings; laboratory test results, including complete blood count; and liver function test results were normal.

Accuracy of findings in the diagnosis of uterine adenomyosis on ultrasound.

PURPOSE: MRI is the current imaging gold standard to diagnose adenomyosis, but access is often limited by high costs and availability. Transvaginal ultrasound provides a cost-effective, accurate and readily available alternative. The objective of our study was to determine the diagnostic accuracy of commonly described sonographic findings in predicting uterine adenomyosis. METHODS: This retrospective study evaluated 649 MRI studies performed to investigate adenomyosis with a preceding transvaginal ultrasound within 12 months between 2013 and 2018. Two blinded reviewers assessed the presence or absence of six sonographic features: bulky uterus, heterogeneous myometrium, streaky myometrium, myometrial cysts, endometrial-myometrial interface ill-definition, and echogenic linear striations. The sensitivity, specificity, positive and negative predictive values of these features were calculated individually and in combination when compared to MRI as the standard of reference. RESULTS: Adenomyosis was found in 315 (48.5%) cases on MRI. Ultrasound had a high specificity of 91.8% (95% CI 88.4 to 94.6%) but was less sensitive (36.8% (95% CI 31.5 to 42.4%)) for detecting adenomyosis. Comorbid fibroids or focal adenomyosis did not affect diagnostic accuracy. All six variables were significantly more common in patients with adenomyosis compared to those without. Individually, 'bulky uterus' and 'heterogenous myometrium' each demonstrated a mean sensitivity and specificity > 50%. The best dual combined variables were 'bulky uterus' + 'ill definition of the endometrial-myometrial interface' (sensitivity 39%, specificity 91%). The best triple combined variables were 'bulky uterus', 'heterogeneous myometrium' + 'ill definition of the endometrial-myometrial interface' (sensitivity 38%, specificity 93%). CONCLUSION: Transvaginal ultrasound is highly specific for diagnosing uterine adenomyosis, providing a cost-effective and readily available alternative to MRI.

Case 273: Pancreatic Duct-to-Portal Vein Fistula with Secondary Portal Vein Pyophlebitis-A Rare Complication of Chronic Pancreatitis.

HistoryA 55-year-old man with a history of chronic pancreatitis secondary to chronic alcohol abuse presented to the hospital with acute abdominal pain, generalized weakness, weight loss, and pyrexia. A clinical examination revealed he was tender to touch in the upper abdomen. Laboratory tests revealed a serum alkaline phosphatase level of 370 U/L (6.1 µkat/L) (normal range, 30-130 U/L [0.5-2.2 µkat/L]), a lipase level of 172 U/L (2.9 µkat/L) (normal range, 0-60 U/L [0-1.0 µkat/L]), a C-reactive protein level of 159 mg/L (1514 nmol/L) (normal value, <8.0 mg/L [76.2 nmol/L]), and a white cell count of 7 × 109/L (normal range, [4-11] × 109/L). During the present admission, the patient underwent urgent CT for his acute symptoms. His relevant medical history included a hospital admission 2 months earlier for abdominal discomfort. Given his history of chronic pancreatitis, baseline abdominal MRI was performed to determine the cause of his symptoms and to assess the pancreas.

Case 275.

HistoryA 61-year-old woman presented to the cardiology service with sinus tachycardia. As part of her work-up, she underwent routine echocardiography that showed a normal heart but incidentally revealed multiple lesions in the liver (Fig 1). An outpatient CT scan was performed to characterize the liver lesions (Figs 2-5). The patient had emigrated to Canada from the Middle East several years earlier and had no medical history of note; in particular, there was no history of cancer or predisposing factors for chronic liver disease. The patient's clinical examination findings; laboratory test results, including complete blood count; and liver function test results were normal.[Figure: see text][Figure: see text][Figure: see text][Figure: see text][Figure: see text].

Case 273.

HistoryA 55-year-old man with a history of chronic pancreatitis secondary to chronic alcohol abuse presented to the hospital with acute abdominal pain, generalized weakness, weight loss, and pyrexia. A clinical examination revealed he was tender to touch in the upper abdomen. Laboratory tests revealed a serum alkaline phosphatase level of 370 U/L (6.1 µkat/L) (normal range, 30-130 U/L [0.5-2.2 µkat/L]), a lipase level of 172 U/L (2.9 µkat/L) (normal range, 0-60 U/L [0-1.0 µkat/L]), a C-reactive protein level of 159 mg/L (1514 nmol/L) (normal value, <8.0 mg/L [76.2 nmol/L]), and a white cell count of 7 × 109/L (normal range, [4-11] × 109/L). During the present admission, the patient underwent urgent CT for his acute symptoms. His relevant medical history included a hospital admission 2 months earlier for abdominal discomfort. Given his history of chronic pancreatitis, baseline abdominal MRI was performed to determine the cause of his symptoms and to assess the pancreas (Figs 1-3).Figure 1a:(a, b) Images from axial fat-suppressed T2-weighted MRI (repetition time msec/echo time msec, 1000/87; section thickness, 6 mm) of the upper abdomen obtained 2 months prior to admission. (c, d) Images from axial fat-suppressed T1-weighted MRI (3.69/1.62; section thickness, 4 mm) of the upper abdomen acquired 60 seconds after intravenous administration of gadopentetate dimeglumine (0.1 mL per kilogram of body weight; Magnevist; Bayer Healthcare, East Mississauga, Ontario) during the current admission.Figure 1b:(a, b) Images from axial fat-suppressed T2-weighted MRI (repetition time msec/echo time msec, 1000/87; section thickness, 6 mm) of the upper abdomen obtained 2 months prior to admission. (c, d) Images from axial fat-suppressed T1-weighted MRI (3.69/1.62; section thickness, 4 mm) of the upper abdomen acquired 60 seconds after intravenous administration of gadopentetate dimeglumine (0.1 mL per kilogram of body weight; Magnevist; Bayer Healthcare, East Mississauga, Ontario) during the current admission.Figure 1c:(a, b) Images from axial fat-suppressed T2-weighted MRI (repetition time msec/echo time msec, 1000/87; section thickness, 6 mm) of the upper abdomen obtained 2 months prior to admission. (c, d) Images from axial fat-suppressed T1-weighted MRI (3.69/1.62; section thickness, 4 mm) of the upper abdomen acquired 60 seconds after intravenous administration of gadopentetate dimeglumine (0.1 mL per kilogram of body weight; Magnevist; Bayer Healthcare, East Mississauga, Ontario) during the current admission.Figure 1d:(a, b) Images from axial fat-suppressed T2-weighted MRI (repetition time msec/echo time msec, 1000/87; section thickness, 6 mm) of the upper abdomen obtained 2 months prior to admission. (c, d) Images from axial fat-suppressed T1-weighted MRI (3.69/1.62; section thickness, 4 mm) of the upper abdomen acquired 60 seconds after intravenous administration of gadopentetate dimeglumine (0.1 mL per kilogram of body weight; Magnevist; Bayer Healthcare, East Mississauga, Ontario) during the current admission.Figure 2:Coronal T2-weighted MRI (repetition time msec/echo time msec, 1000/89; section thickness, 4 mm) of the upper abdomen obtained 2 months prior to admission.Figure 3:Coronal CT image of the abdomen acquired 60 seconds after administration of intravenous contrast material (100 mL of iohexol, Omnipaque 350; GE Healthcare, Princeton, NJ). This CT examination was performed during the current admission.

Malignant transformation of hepatic adenoma complicated by rupture and hemorrhage: An extremely rare clinical entity.

Hepatic adenomas (HAs) are rare benign tumors of the liver and comprise 2% of all liver tumors with an annual incidence of 3-4/100,000 per year in Europe and North America. These tumors may be clinically silent or present with abdominal pain. Although rare, the most important complications associated with this tumor is haemorrhage and malignant transformation to hepatocellular carcinoma. The reported risk of malignant transformation is believed to be 4.2%. We present an extremely rare case report of a young woman on the oral contraceptive pill (OCP) with malignant transformation of a hepatic adenoma complicated additionally by tumor rupture and intraperitoneal bleed. This article therefore highlights the need to carefully evaluate any liver lesion in a young female on the OCP to be a possible adenoma and if confirmed to be so, to consider the potential risks associated with it as well as the need for follow-up imaging in order to avoid life threatening complications.

Arf3 is activated uniquely at the trans-Golgi network by brefeldin A-inhibited guanine nucleotide exchange factors.

It is widely assumed that class I and II Arfs function interchangeably throughout the Golgi complex. However, we report here that in vivo, Arf3 displays several unexpected properties. Unlike other Golgi-localized Arfs, Arf3 associates selectively with membranes of the trans-Golgi network (TGN) in a manner that is both temperature-sensitive and uniquely dependent on guanine nucleotide exchange factors of the BIGs family. For example, BIGs knockdown redistributed Arf3 but not Arf1 from Golgi membranes. Furthermore, shifting temperature to 20 degrees C, a temperature known to block cargo in the TGN, selectively redistributed Arf3 from Golgi membranes. Arf3 redistribution occurred slowly, suggesting it resulted from a change in membrane composition. Arf3 knockdown and overexpression experiments suggest that redistribution is not responsible for the 20 degrees C block. To investigate in more detail the mechanism for Arf3 recruitment and temperature-dependent release, we characterized several mutant forms of Arf3. This analysis demonstrated that those properties are readily separated and depend on pairs of residues present at opposite ends of the protein. Furthermore, phylogenetic analysis established that all four critical residues were absolutely conserved and unique to Arf3. These results suggest that Arf3 plays a unique function at the TGN that likely involves recruitment by a specific receptor.

Distinct functions for Arf guanine nucleotide exchange factors at the Golgi complex: GBF1 and BIGs are required for assembly and maintenance of the Golgi stack and trans-Golgi network, respectively.

We examined the relative function of the two classes of guanine nucleotide exchange factors (GEFs) for ADP-ribosylation factors that regulate recruitment of coat proteins on the Golgi complex. Complementary overexpression and RNA-based knockdown approaches established that GBF1 regulates COPI recruitment on cis-Golgi compartments, whereas BIGs appear specialized for adaptor proteins on the trans-Golgi. Knockdown of GBF1 and/or COPI did not prevent export of VSVGtsO45 from the endoplasmic reticulum (ER), but caused its accumulation into peripheral vesiculotubular clusters. In contrast, knockdown of BIG1 and BIG2 caused loss of clathrin adaptor proteins and redistribution of several TGN markers, but had no impact on COPI and several Golgi markers. Surprisingly, brefeldin A-inhibited guanine nucleotide exchange factors (BIGs) knockdown prevented neither traffic of VSVGtsO45 to the plasma membrane nor assembly of a polarized Golgi stack. Our observations indicate that COPII is the only coat required for sorting and export from the ER exit sites, whereas GBF1 but not BIGs, is required for COPI recruitment, Golgi subcompartmentalization, and cargo progression to the cell surface.