Bernard E. Van Beers

Primovist, Eovist: What to expect?

Gadolinium ethoxybenzyl dimeglumine (Gd-EOB-DTPA, Primovist in Europe and Eovist in the USA) is a liver-specific magnetic resonance imaging contrast agent that has up to 50% hepatobiliary excretion in the normal liver. After intravenous injection, Gd-EOB-DTPA distributes into the vascular and extravascular spaces during the arterial, portal venous and late dynamic phases, and progressively into the hepatocytes and bile ducts during the hepatobiliary phase. The hepatocyte uptake of Gd-EOB-DTPA mainly occurs via the organic anion transporter polypeptides OATP1B1 and B3 located at the sinusoidal membrane and biliary excretion via the multidrug resistance-associated proteins MRP2 at the canalicular membrane. Because of these characteristics, Gd-EOB-DTPA behaves similarly to non-specific gadolinium chelates during the dynamic phases, and adds substantial information during the hepatobiliary phase, improving the detection and characterization of focal liver lesions and diffuse liver disease. This information is particularly relevant for the detection of metastases, and for the detection and characterization of nodular lesions in liver cirrhosis, including early hepatocellular carcinomas. Finally, GD-EOB-DTPA-enhanced magnetic resonance imaging may provide quantitative assessment regarding liver perfusion and hepatocyte function in diffuse liver diseases. The full potential of GD-EOB-DTPA-enhanced magnetic resonance imaging has to be established further. It is already clear that GD-EOB-DTPA-enhanced magnetic resonance imaging provides anatomic and functional information in the setting of focal and diffuse liver disease that is unattainable with magnetic resonance imaging enhanced with non-specific contrast agents.

New imaging techniques for liver diseases

Newly developed or advanced methods of ultrasonography and MR imaging provide combined anatomical and quantitative functional information about diffuse and focal liver diseases. Ultrasound elastography has a central role for staging liver fibrosis and an increasing role in grading portal hypertension; dynamic contrast-enhanced ultrasonography may improve tumor characterization. In clinical practice, MR imaging examinations currently include diffusion-weighted and dynamic MR imaging, enhanced with extracellular or hepatobiliary contrast agents. Moreover, quantitative parameters obtained with diffusion-weighted MR imaging, dynamic contrast-enhanced MR imaging and MR elastography have the potential to characterize further diffuse and focal liver diseases, by adding information about tissue cellularity, perfusion, hepatocyte transport function and visco-elasticity. The multiparametric capability of ultrasonography and more markedly of MR imaging gives the opportunity for high diagnostic performance by combining imaging biomarkers. However, image acquisition and post-processing methods should be further standardized and validated in multicenter trials.

Rapid acquisition of multifrequency, multislice and multidirectional MR elastography data with a fractionally encoded gradient echo sequence

In MR elastography (MRE), periodic tissue motion is phase encoded using motion‐encoding gradients synchronized to an externally applied periodic mechanical excitation. Conventional methods result in extended scan time for quality phase images, thus limiting the broad application of MRE in the clinic. For practical scan times, researchers have been relying on one‐dimensional or two‐dimensional motion‐encoding, low‐phase sampling and a limited number of slices, and artifact‐prone, single‐shot, echo planar imaging (EPI) readout. Here, we introduce a rapid multislice pulse sequence capable of three‐dimensional motion encoding that is also suitable for simultaneously encoding motion with multiple frequency components. This sequence is based on a gradient‐recalled echo (GRE) sequence and exploits the principles of fractional encoding. This GRE MRE pulse sequence was validated as capable of acquiring full three‐dimensional motion encoding of isotropic voxels in a large volume within less than a minute. This sequence is suitable for monofrequency and multifrequency MRE experiments. In homogeneous paraffin phantoms, the eXpresso sequence yielded similar storage modulus values as those obtained with conventional methods, although with markedly reduced variances (7.11 ± 0.26 kPa for GRE MRE versus 7.16 ± 1.33 kPa for the conventional spin‐echo EPI sequence). The GRE MRE sequence obtained better phase‐to‐noise ratios than the equivalent spin‐echo EPI sequence (matched for identical acquisition time) in both paraffin phantoms and in vivo data in the liver (59.62 ± 11.89 versus 27.86 ± 3.81, 61.49 ± 14.16 versus 24.78 ± 2.48 and 58.23 ± 10.39 versus 23.48 ± 2.91 in the X, Y and Z components, respectively, in the case of liver experiments). Phase‐to‐noise ratios were similar between GRE MRE used in monofrequency or multifrequency experiments (75.39 ± 14.93 versus 86.13 ± 18.25 at 28 Hz, 71.52 ± 24.74 versus 86.96 ± 30.53 at 56 Hz and 95.60 ± 36.96 versus 61.35 ± 26.25 at 84Hz, respectively). Copyright

Biomarkers in abdominal imaging

Imaging biomarkers are parameters measurable with imaging methods used to detect, stage or grade disease or assess the response to treatment. Compared with biochemical or histological markers, imaging biomarkers have the advantage of remaining non-invasive and being spatially and temporally resolved. Imaging biomarkers are used in multiple abdominal diseases, including cancer. Anatomical imaging biomarkers such as the RECIST criteria are often insufficient for the early assessment of treatment response. Molecular imaging biomarkers may be used when targeting a receptor or enzyme overexpressed in a given disease. Their use remains limited because of their narrow target specificity. Functional biomarkers are increasingly used with positron-emission tomography, perfusion MRI, diffusion-weighted MRI and MR spectroscopy. They have an important potential to help in selecting the patients and assessing the response to new treatments. However, important efforts of validation and standardization remain to be done before the wide use of imaging biomarkers in abdominal diseases.

Quantification of the triglyceride fatty acid composition with 3.0 T MRI.

The aim of this work was to validate a sequential method for quantifying the triglyceride fatty acid composition with 3.0 T MRI.

Advanced fibrosis: Correlation between pharmacokinetic parameters at dynamic gadoxetate-enhanced MR imaging and hepatocyte organic anion transporter expression in rat liver

PURPOSE To compare the value of enhancement and pharmacokinetic parameters measured at dynamic gadoxetate-enhanced magnetic resonance (MR) imaging in determining hepatic organic anion transporter expression in control rats and rats with advanced liver fibrosis. MATERIALS AND METHODS Institutional animal review board approval was received before the study began. Advanced liver fibrosis was created in rats by means of carbon tetrachloride injections over an 8-week period. In 17 rats with liver fibrosis and eight control rats, dynamic gadoxetate-enhanced MR images of the liver were obtained during 1 hour after injection of 0.025 mmol gadoxetate per kilogram of body weight. Enhancement parameters (maximum enhancement [Emax], time to peak [Tmax], and elimination half-life) were measured on enhancement-versus-time curves, and pharmacokinetic parameters (hepatic extraction fraction [HEF] and mean residence time [MRT]) were obtained by means of deconvolution analysis of the concentration-versus-time curves in the liver and the portal vein. The parameters were correlated at simple and multiple regression analysis with the expression of the hepatic anion uptake transporter organic anion-transporting polypeptide 1A1 (Oatp1a1), the hepatobiliary transporter multidrug resistance-associated protein 2 (Mrp2), and the backflux transporter Mrp4, as determined with reverse transcription polymerase chain reaction. RESULTS In rats with advanced liver fibrosis, the Emax, Tmax, HEF, and MRT decreased significantly relative to those in control rats, whereas the elimination half-life increased significantly. The enhancement and pharmacokinetic parameters correlated significantly with the expression of the transporters at simple regression analysis. At multiple regression analysis, HEF was the only parameter that was significantly associated with the expression of Oatp1a1 and Mrp2 (P < .001, r = 0.74 and P < .001, r = 0.70, respectively). CONCLUSION The pharmacokinetic parameter HEF at dynamic gadoxetate-enhanced MR imaging is independently correlated with hepatic organic anion transporter expression.

Hepatic heterogeneity on CT in Budd-Chiari syndrome: correlation with regional disturbances in portal flow.

A comparative study of the imaging findings of computed tomography (CT), selective arteriography, CT arteriography, and/or CT portography is presented in 4 patients with Budd-Chiari syndrome. Hepatic differences in attenuation and morphologic changes were generally found to be closely related with regional disturbances in portal flow. Areas with complete hepatic vein obstruction were hypodense on pre- and postcontrast scans, probably due to portal flow inversion. In 2 of 4 cases, these were subsequently atrophied, while areas receiving the remaining venous outflow appeared hypertrophied. They were markedly enhanced on postcontrast scans. Enhancement may be patchy due to portal and sinusoidal stasis.

Insights into the diagnosis of hepatocellular carcinomas with hepatobiliary MRI

The incidence of hepatocellular carcinomas (HCCs) has increased worldwide in line with an improved screening by high-resolution imaging of cirrhotic livers. Besides abdominal ultrasonography and computerised tomography, magnetic resonance imaging (MRI) is an important tool to detect HCCs. With commercialisation of MR hepatobiliary contrast agents that cross membrane transporters in hepatocytes or tumour cells, MRI adds new information to detect and characterise HCCs. When tumour cells lose organic anion transporting polypeptides (OATP1B1/B3) in cell membranes facing sinusoidal blood, tumours appear hypointense (decreased contrast agent concentrations) in comparison to surrounding normal or cirrhotic liver that retains OATP1B1/B3 expression. However, expression, regulation, and prognostic significance of transporter evolution along carcinogenesis are not completely known. Moreover, understanding signal intensities in focal lesions also relies on transport functions of cellular efflux transporters. This manuscript reviews all the publications that associate liver imaging with hepatobiliary contrast agents and expression of transporters. The regulation of transporters along carcinogenesis to anticipate the prognosis of focal lesions is also included.

Viscoelastic parameters for quantifying liver fibrosis: three-dimensional multifrequency MR elastography study on thin liver rat slices

Objective To assess in a high-resolution model of thin liver rat slices which viscoelastic parameter at three-dimensional multifrequency MR elastography has the best diagnostic performance for quantifying liver fibrosis. Materials and Methods The study was approved by the ethics committee for animal care of our institution. Eight normal rats and 42 rats with carbon tetrachloride induced liver fibrosis were used in the study. The rats were sacrificed, their livers were resected and three-dimensional MR elastography of 5±2 mm liver slices was performed at 7T with mechanical frequencies of 500, 600 and 700 Hz. The complex shear, storage and loss moduli, and the coefficient of the frequency power law were calculated. At histopathology, fibrosis and inflammation were assessed with METAVIR score, fibrosis was further quantified with morphometry. The diagnostic value of the viscoelastic parameters for assessing fibrosis severity was evaluated with simple and multiple linear regressions, receiver operating characteristic analysis and Obuchowski measures. Results At simple regression, the shear, storage and loss moduli were associated with the severity of fibrosis. At multiple regression, the storage modulus at 600 Hz was the only parameter associated with fibrosis severity (r = 0.86, p<0.0001). This parameter had an Obuchowski measure of 0.89+/−0.03. This measure was significantly larger than that of the loss modulus (0.78+/−0.04, p = 0.028), but not than that of the complex shear modulus (0.88+/−0.03, p = 0.84). Conclusion Our high resolution, three-dimensional multifrequency MR elastography study of thin liver slices shows that the storage modulus is the viscoelastic parameter that has the best association with the severity of liver fibrosis. However, its diagnostic performance does not differ significantly from that of the complex shear modulus.

Hepatic fat fraction and visceral adipose tissue fatty acid composition in mice: Quantification with 7.0T MRI.

To develop an MRI method for quantifying hepatic fat content and visceral adipose tissue fatty acid composition in mice on a 7.0T preclinical system.