Simon A. Lambert

Prospective Comparison of Spleen and Liver Stiffness by Using Shear-Wave and Transient Elastography for Detection of Portal Hypertension in Cirrhosis

PURPOSE To prospectively compare the technical success rate and accuracy of shear-wave elastography (SWE) and transient elastography (TE) for the detection of clinically significant portal hypertension (PH) in patients with advanced cirrhosis who are undergoing hepatic vein pressure gradient (HVPG) measurements. MATERIALS AND METHODS The institutional ethics committee approved the study, and written informed consent was obtained. Seventy-nine consecutive patients with cirrhosis who were undergoing SWE and TE at the time of HVPG measurement were studied. The technical success rate of SWE and TE was compared with the diagnostic value of liver stiffness (LS) and spleen stiffness (SS) measurements and composite scores (LS spleen-diameter-to-platelet-ratio score [LSPS] and PH risk score) by using SWE and TE to detect clinically significant PH (HVPG ≥ 10 mm Hg) and esophageal varices at high risk of bleeding. Areas under the receiver operating characteristic curve and the DeLong test were used. RESULTS The technical success rate of SWE was significantly better than that of TE for both LS and SS (97% and 97% vs 44% and 42%, respectively; P < .001). LS of more than 24.6 kPa with SWE had a sensitivity, specificity, and accuracy for clinically significant PH of 81%, 88%, and 82%, respectively. Diagnostic performance of LS by using SWE was significantly better than that for SS for the diagnosis of clinically significant PH (area under the receiver operating characteristic curve of 0.87 vs 0.64, P = .003). LS, SS, LSPS, and PH risk score (according to SWE or TE) did not differ between patients with and those without high-risk esophageal varices (P = .09-.42). CONCLUSION In patients with advanced cirrhosis who are undergoing HVPG measurements, LS measurements obtained by using SWE have a higher technical success rate and a better diagnostic value than TE for clinically significant PH.

Assessment of portal hypertension and high-risk oesophageal varices with liver and spleen three-dimensional multifrequency MR elastography in liver cirrhosis

ObjectiveTo assess the value of the liver and spleen viscoelastic parameters at multifrequency MR elastography to determine the degree of portal hypertension and presence of high-risk oesophageal varices in patients with cirrhosis.MethodsFrom January to September 2012, 36 consecutive patients with cirrhosis evaluated for transplantation were prospectively included. All patients underwent hepatic venous pressure gradient (HVPG) measurements and endoscopy to assess oesophageal varices. Multifrequency MR elastography was performed within the liver and spleen. The shear, storage and loss moduli were calculated and compared to the HVPG with Spearman coefficients and multiple regressions. Patients with and without severe portal hypertension and high-risk varices were compared with Mann–Whitney tests, logistic regression and ROC analysis.ResultsThe liver storage and loss moduli and the spleen shear, storage and loss moduli correlated with the HVPG. At multiple regression, only the liver and the spleen loss modulus correlated with the HVPG (r = 0.44, p = 0.017, and r = 0.57, p = 0.002, respectively). The spleen loss modulus was the best parameter for identifying patients with severe portal hypertension (p = 0.019, AUROC = 0.81) or high-risk varices (p = 0.042, AUROC = 0.93).ConclusionsThe spleen loss modulus appears to be the best parameter for identifying patients with severe portal hypertension or high-risk varices.Key points1. Noninvasive HVPG assessment can be performed with liver and spleen MR elastography2. The spleen loss modulus enables the detection of high-risk oesophageal varices3. The spleen loss modulus enables the detection of severe portal hypertension

In Vivo Anisotropic Mechanical Properties of Dystrophic Skeletal Muscles Measured by Anisotropic MR Elastographic Imaging: The mdx Mouse Model of Muscular Dystrophy

PURPOSE To evaluate the utility of mechanical anisotropy (shear storage modulus parallel to fiber/shear storage modulus perpendicular to fiber) measured by combined magnetic resonance (MR) elastography and diffusion-tensor imaging ( DTI diffusion-tensor imaging ) technique (anisotropic MR elastography) to distinguish between healthy and necrotic muscle with different degrees of muscle necrosis in the mdx mouse model of muscular dystrophy. MATERIALS AND METHODS The experimental protocol was approved by the regional animal ethics committee. Twenty-one mdx and 21 wild-type ( WT wild type ) mice were used in our study. Animals were divided into exercised and sedentary groups. Anisotropic MR elastography was used to obtain mechanical anisotropic shear moduli for the lateral gastrocnemius and plantaris muscles in a 7-T MR imager, from which the mechanical anisotropic ratio was calculated. The animals were imaged before and after 10 weeks of a horizontal treadmill running protocol. Spearman rank correlations were used to compare MR elastographic data with muscle necrotic area percentage from histologic analysis. Mechanical anisotropy in WT wild type and mdx mice muscle were compared by using t test and one-way analysis of variance, and receiver operating characteristic curves were constructed by using statistical software. RESULTS Anisotropic MR elastography was able to be used to distinguish between the muscles of mdx and WT wild type mice, with an area under the receiver operating characteristic curve of 0.8. Strong negative correlation (rs = -0.701; P < .001) between the mechanical anisotropic ratio and the percentage of muscle necrotic area was found. By comparing mice with no or mild (0%-5% mean necrotic area) and severe (>5% mean necrotic area) muscle necrosis, an area under the receiver operating characteristic curve of 0.964 was achieved. Diffusion parameters alone were unable to distinguish between the WT wild type and mdx mice at any time point. CONCLUSION The mechanical anisotropic ratio of the shear storage moduli measured by an anisotropic MR elastographic technique can distinguish between healthy muscle and dystrophic muscle.

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.

Can we justify not doing liver perfusion imaging in 2013

Liver perfusion imaging is a quantitative functional investigation. Liver perfusion imaging is complicated because of the livers dual vascular supply, artefacts due to respiratory movements and the fenestrated sinusoidal capillaries which allow the contrast medium to diffuse out. Liver perfusion can be examined by ultrasound, CT or MRI: each technique has its limitations and specific features. The major indications in hepatology are oncology (detection, characterization and tumor response) and non-invasive investigation of patients with chronic liver disease. Work is needed to standardize acquisition and modeling methods to allow wider use of results and more widespread use of the technique.

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.

Microvasculature alters the dispersion properties of shear waves - a multi-frequency MR elastography study

Magnetic Resonance Elastography (MRE) uses macroscopic shear wave propagation to quantify mechanical properties of soft tissues. Micro‐obstacles are capable of affecting the macroscopic dispersion properties of shear waves. Since disease or therapy can change the mechanical integrity and organization of vascular structures, MRE should be able to sense these changes if blood vessels represent a source for wave scattering. To verify this, MRE was performed to quantify alteration of the shear wave speed cs due to the presence of vascular outgrowths using an aortic ring model. Eighteen fragments of rat aorta included in a Matrigel matrix (n=6 without outgrowths, n=6 with a radial outgrowth extent of ~600µm and n=6 with ~850µm) were imaged using a 7 Tesla MR scanner (Bruker, PharmaScan). High resolution anatomical images were acquired in addition to multi‐frequency MRE (ν = 100, 115, 125, 135 and 150 Hz). Average cs was measured within a ring of ~900µm thickness encompassing the aorta and were normalized to cs0 of the corresponding Matrigel. The frequency dependence was fit to the power law model cs ~νy. After scanning, optical microscopy was performed to visualize outgrowths. Results demonstrated that in presence of vascular outgrowths (1) normalized cs significantly increased for the three highest frequencies (Kruskal‐Wallis test, P = 0.0002 at 125 Hz and P = 0.002 at 135 Hz and P = 0.003 at 150 Hz) but not for the two lowest (Kruskal‐Wallis test, P = 0.63 at 100 Hz and P = 0.87 at 115 Hz), and (2) normalized cs followed a power law behavior not seen in absence of vascular outgrowths (ANOVA test, P < 0.0001). These results showed that vascular outgrowths acted as micro‐obstacles altering the dispersion relationships of propagating shear waves and that MRE could provide valuable information about microvascular changes. Copyright

Simultaneous MR quantification of hepatic fat content, fatty acid composition, transverse relaxation time and magnetic susceptibility for the diagnosis of non‐alcoholic steatohepatitis

Non‐alcoholic steatohepatitis (NASH) is characterized at histology by steatosis, hepatocyte ballooning and inflammatory infiltrates, with or without fibrosis. Although diamagnetic material in fibrosis and inflammation can be detected with quantitative susceptibility imaging, fatty acid composition changes in NASH relative to simple steatosis have also been reported. Therefore, our aim was to develop a single magnetic resonance (MR) acquisition and post‐processing scheme for the diagnosis of steatohepatitis by the simultaneous quantification of hepatic fat content, fatty acid composition, T2* transverse relaxation time and magnetic susceptibility in patients with non‐alcoholic fatty liver disease. MR acquisition was performed at 3.0 T using a three‐dimensional, multi‐echo, spoiled gradient echo sequence. Phase images were unwrapped to compute the B0 field inhomogeneity (ΔB0) map. The ΔB0‐demodulated real part images were used for fat–water separation, T2* and fatty acid composition quantification. The external and internal fields were separated with the projection onto dipole field method. Susceptibility maps were obtained after dipole inversion from the internal field map with single‐orientation Bayesian regularization including spatial priors. Method validation was performed in 32 patients with biopsy‐proven, non‐alcoholic fatty liver disease from which 12 had simple steatosis and 20 NASH. Liver fat fraction and T2* did not change significantly between patients with simple steatosis and NASH. In contrast, the saturated fatty acid fraction increased in patients with NASH relative to patients with simple steatosis (48 ± 2% versus 44 ± 4%; p < 0.05) and the magnetic susceptibility decreased (−0.30 ± 0.27 ppm versus 0.10 ± 0.14 ppm; p < 0.001). The area under the receiver operating characteristic curve for magnetic susceptibility as NASH marker was 0.91 (95% CI: 0.79–1.0). Simultaneous MR quantification of fat content, fatty acid composition, T2* and magnetic susceptibility is feasible in the liver. Our preliminary results suggest that quantitative susceptibility imaging has a high diagnostic performance for the diagnosis of NASH.