Ehman, Richard L.

Chronic passive hepatic congestion (congestive hepatopathy) leads to hepatic fibrosis; however, the mechanisms involved in this process are not well understood. We developed a murine experimental model of congestive hepatopathy through partial ligation of the inferior vena cava (pIVCL). C57BL/6 and transgenic mice overexpressing tissue factor pathway inhibitor (SM22α‐TFPI) were subjected to pIVCL or sham. Liver and blood samples were collected and analyzed in immunohistochemical, morphometric, real‐time polymerase chain reaction, and western blot assays. Hepatic fibrosis and portal pressure were significantly increased after pIVCL concurrent with hepatic stellate cell (HSC) activation. Liver stiffness, as assessed by magnetic resonance elastography, correlated with portal pressure and preceded fibrosis in our model. Hepatic sinusoidal thrombosis as evidenced by fibrin deposition was demonstrated both in mice after pIVCL as well as in humans with congestive hepatopathy. Warfarin treatment and TFPI overexpression both had a protective effect on fibrosis development and HSC activation after pIVCL. In vitro studies show that congestion stimulates HSC fibronectin (FN) fibril assembly through direct effects of thrombi as well as by virtue of mechanical strain. Pretreatment with either Mab13 or Cytochalasin‐D, to inhibit β‐integrin or actin polymerization, respectively, significantly reduced fibrin and stretch‐induced FN fibril assembly. Conclusion : Chronic hepatic congestion leads to sinusoidal thrombosis and strain, which in turn promote hepatic fibrosis. These studies mechanistically link congestive hepatopathy to hepatic fibrosis. (H epatology 2015;61:648‐659)

Purpose To evaluate the feasibility of using three‐dimensional (3D) MR elastography (MRE) to determine the stiffness of the pancreas in healthy volunteers. Materials and Methods Twenty healthy volunteers underwent 1.5 Tesla MRE exams using an accelerated echo planar imaging (EPI) pulse sequence with low‐frequency vibrations (40 and 60 Hz). Stiffness was calculated with a 3D direct inversion algorithm. The mean shear stiffness in five pancreatic subregions (uncinate, head, neck, body, and tail) and the corresponding liver stiffness were calculated. The intrasubject coefficient of variation (CV) was calculated as a measure of the reproducibility for each volunteer. Results The mean shear stiffness (average of values obtained in different pancreatic subregions) was (1.15 ± 0.17) kPa at 40 Hz, and (2.09 ± 0.33) kPa at 60 Hz. The corresponding liver stiffness was higher than the pancreas stiffness at 40 Hz ([1.60 ± 0.21] kPa, mean pancreas‐to‐liver stiffness ratio: 0.72), but similar at 60Hz ([2.12 ± 0.23) kPa, mean ratio: 0.95). The mean intrasubject CV for each pancreatic subregion was lower at 40 Hz than 60 Hz ( P < 0.05 for all subregions, range: 11.9–15.7% at 40 Hz and 16.5–19.6% at 60 Hz). Conclusion The 3D pancreatic MRE can provide promising and reproducible stiffness measurements throughout the pancreas, with more consistent data acquired at 40 Hz. J. Magn. Reson. Imaging 2015;41:369–375. © 2013 Wiley Periodicals, Inc .

Purpose To develop a rapid proton MR elastography (MRE) technique that can quantify the absolute shear stiffness of lung parenchyma, to investigate the ability to differentiate respiration‐dependent stiffness variations of the lung, and to demonstrate clinical feasibility. Materials and Methods A spin‐echo echo planar imaging MRE sequence (SE‐EPI MRE) with a very short echo time was developed and tested in a series of five healthy volunteers at three different lung volumes: (i) residual volume (RV), (ii) total lung capacity (TLC), (iii) and midway between RV and TLC (MID). At each volume, lung density was quantified using a MR‐based density mapping sequence. For reference, data were acquired using the previously described spin‐echo lung MRE sequence (SE‐MRE). MRE data were also acquired in a patient with proven Idiopathic Pulmonary Fibrosis (IPF) to test clinical feasibility. Results The SE‐EPIMRE sequence reduced total acquisition time by a factor of 2 compared with the SE‐MRE sequence. Lung parenchyma median shear stiffness for the 5 volunteers quantified with the SE‐EPI MRE sequence was 0.9 kPa, 1.1 kPa, and 1.6 kPa at RV, MID, and TLC, respectively. The corresponding values obtained with the SE‐MRE sequence were 0.9 kPa, 1.1 kPa, and 1.5 kPa. Absolute shear stiffness was also successfully measured in the IPF patient. Conclusion The results indicate that stiffness variations due to respiration could be measured with the SE‐EPIMRE technique and were equivalent to values generated by the previously described SE‐MRE approach. Preliminary data obtained from the patient demonstrate clinical feasibility. J. Magn. Reson. Imaging 2014;40:1230–1237 . © 2013 Wiley Periodicals, Inc .

In this paper, we present recent developments in the characterization of anisotropic, biological media utilizing displacements measured with dynamic MRE. In one approach, a waveguide constrained analysis is applied to physical structures (such as muscle), which evaluates the velocities of wave propagation along arbitrarily oriented fibers or fiber bundles in a local fashion, utilizing a spectral filter and a sliding window, spatial Fourier transform. In a second approach, the anisotropic equations of elasticity, in variational form, are inverted for a determination of the complex moduli comprising the medium. Issues concerning ill-conditioning, the effects of boundary conditions, and multiaspect excitation requirements will be addressed, as well as a discussion concerning the models which are appropriate for various physical situations. These two complementary methods of analysis will be demonstrated utilizing both phantom as well as in vivo dynamic displacement measurements.

The goal of our research is to develop MRI-based methods for assessing the mechanical properties of tissues in vivo. We have focused on a novel MRI technique for visualizing propagating acoustic shear waves [Science 269, 1854–1857 (1995)]. Suitable dynamic shear stress for Magnetic Resonance Elastography (MRE) can be generated by surface drivers, inertial effects, acoustic radiation pressure, or endogenous physiologic mechanisms. The MRE acquisition sequence is capable of visualizing cyclic tissue motion of less than 1 micron in displacement amplitude, with imaging times ranging from 100 ms to several minutes. Inversion algorithms based on continuum mechanics are used to process the acquired data to generate maps of mechanical properties such as depict stiffness, viscosity, attenuation, and anisotropic behavior. We have applied MRE to assess specimens of a variety of tissues, ranging in stiffness from lung to cartilage. Human studies have demonstrated that it is feasible to apply MRE to quantitatively image the mechanical properties of skeletal muscles, gray and white matter in the brain, thyroid, kidney, liver, and skin. Our preliminary clinical studies have to date applied MRE to observe changes in tissue mechanical properties in patients with breast, brain, and thyroid tumors, liver fibrosis, and diffuse diseases of skeletal muscle.