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Multi-frequency MRE for elasticity quantitation and optimal tissue discrimination: a two-platform liver fibrosis mimicking phantom study

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 Added by Xavier Maitre
 Publication date 2021
  fields Physics
and research's language is English




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In the framework of algebraic inversion, Magnetic Resonance Elastography (MRE) repeatability, reproducibility and robustness were evaluated on extracted shear velocities (or elastic moduli). The same excitation system was implemented at two sites equipped with clinical MR scanners of 1.5 T and 3 T. A set of four elastic, isotropic, homogeneous calibrated phantoms of distinct elasticity representing the spectrum of liver fibrosis severity was mechanically characterized. The repeatability of the measurements and the reproducibility between the two platforms were found to be excellent with mean coefficients of variations of 1.62% for the shear velocity mean values and 1.95% for the associated standard deviations. MRE velocities were robust to the amplitude and pattern variations of the displacement field with virtually no difference between outcomes from both magnets at identical excitation frequencies even when the displacement field amplitude was 6 times smaller. However, MRE outcomes were very sensitive to the number of voxels per wavelength, s, of the recorded displacement field, with relative biases reaching 62% and precision losing up to a factor 23.5. For both magnetic field strengths, MRE accuracy and precision were largely degraded outside of established conditions of validity ($6 lesssim s lesssim 9$) resulting in estimated shear velocity values not significantly different between phantoms of increasing elasticity. When fulfilling the spatial sampling conditions, either prospectively in the acquisition or retrospectively before the reconstruction, MRE produced quantitative measurements that allowed to unambiguously discriminate, with infinitesimal p-values, between the phantoms mimicking increasing severity of liver fibrosis.

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Different clinical elastography devices show different liver-stiffness values in the same subject, hindering comparison of values and establishment of system-independent thresholds for disease detection. Therefore, authorities request standardized phantoms that address the viscosity-related dispersion of stiffness over frequency. A linear polymerized polyacrylamide phantom (PAAm) was calibrated to the viscoelastic properties of healthy human liver in vivo. Shear-wave speed as a surrogate of stiffness was quantified between 5 Hz and 3000 Hz frequency-range by shear rheometry, ultrasound-based time-harmonic elastography, clinical MR elastography (MRE), and tabletop MRE. Imaging parameters for ultrasound were close to those of liver in vivo. Reproducibility, aging behavior and temperature dependency were assessed and fulfilled requirements for quantitative elastography. In addition, the phantom was used to characterize the frequency bandwidth of shear-wave speed of several clinical elastography methods. The liquid-liver phantom has favorable properties for standardization and development of liver elastography: first, it can be used across clinical and experimental elastography devices in ultrasound and MRI. Second, being a liquid, it can easily be adapted in size and shape to specific technical requirements, and by adding inclusions and scatterers. Finally, since the phantom is based on non-crosslinked linear PAA constituents, it is easy to produce, indicating potential widespread use among researchers and vendors to standardize liver-stiffness measurements.
Objective: Realistic tissue-mimicking phantoms are essential for the development, the investigation and the calibration of medical imaging techniques and protocols. Because it requires taking both mechanical and imaging properties into account, the development of robust, calibrated phantoms is a major challenge in elastography. Soft polyvinyl chloride gels in a liquid plasticizer (plastisol or PVCP) have been proposed as soft tissue-mimicking phantoms (TMP) for elasticity imaging. PVCP phantoms are relatively low-cost and can be easily stored over long time periods without any specific requirements. In this work, the preparation of a PVCP gel phantom for both MR and ultrasoundelastography is proposed and its acoustic, NMR and mechanical properties are studied.Material and methods: The acoustic and magnetic resonance imaging properties of PVCP are measured for different mass ratios between ultrasound speckle particles and PVCP solution, and between resin and plasticizer. The linear mechanical properties of plastisol samples are then investigated over time using not only indentation tests, but also MR and ultrasound-elastography clinical protocols. These properties are compared to typical values reported for biological soft tissues and to the values found in the literature for PVCP gels.Results and conclusions: After a period of two weeks, the mechanical properties of the plastisol samples measured with indentation testing are stable for at least the following 4 weeks (end of follow-up period 43 days after gelation-fusion). Neither the mechanical nor the NMR properties of plastisol gels were found to be affected by the addition of cellulose as acoustic speckle. Mechanical properties of the proposed gels were successfully characterized by clinical, commercially-available MR Elastography and sonoelastography protocols. PVCP with a mass ratio of ultrasound speckle particles of 0.6% to 0.8% and a mass ratio between resin and plasticizer between 50 and 70% appears as a good TMP candidate that can be used with both MR and ultrasound-based elastography methods.
Hepatic fibrosis causes an increase in liver stiffness, a parameter measured by elastography and widely used as a diagnosis method. The concomitant presence of portal vein thrombosis (PVT) implies a change in hepatic portal inflow that could also affect liver elasticity. The main objective of this study is to determine the extent to which the presence of portal occlusion can affect the mechanical properties of the liver and potentially lead to misdiagnosis of fibrosis and hepatic cirrhosis by elastography. Portal vein occlusion was generated by insertion and inflation of a balloon catheter in the portal vein of four swines. The portal flow parameters peak flow (PF) and peak velocity magnitude (PVM) and liver mechanical properties (shear modulus) were then investigated using 4D-flow MRI and MR elastography, respectively, for progressive obstructions of the portal vein. Experimental results indicate that the reduction of the intrahepatic venous blood flow (PF/PVM decreases of 29.3%/8.5%, 51.0%/32.3% and 83.3%/53.6%, respectively) measured with 50%, 80% and 100% obstruction of the portal vein section results in a decrease of liver stiffness by $0.8%pm0.1%$, $7.7%pm0.4%$ and $12.3%pm0.9%$, respectively. While this vascular mechanism does not have sufficient influence on the elasticity of the liver to modify the diagnosis of severe fibrosis or cirrhosis (F4 METAVIR grade), it may be sufficient to attenuate the increase in stiffness due to moderate fibrosis (F2-F3 METAVIR grades) and consequently lead to false-negative diagnoses with elastography in the presence of PVT.
Over the past few decades, researchers have developed several approaches such as the Reference Phantom Method (RPM) to estimate ultrasound attenuation coefficient (AC) and backscatter coefficient (BSC). AC and BSC can help to discriminate pathology from normal tissue during in-vivo imaging. In this paper, we propose a new RPM model to simultaneously compute AC and BSC for harmonic imaging and a normalized score that combines the two parameters as a measure of disease progression. The model utilizes the spectral difference between two regions of interest, the first, a proximal, close to the probe and second, a distal, away from the probe. We have implemented an algorithm based on the model and shown that it provides accurate and stable estimates to within 5% of AC and BSC for simulated received echo from post-focal depths of a homogeneous liver-like medium. For practical applications with time gain and time frequency compensated in-phase and quadrature (IQ) data from ultrasound scanner, the method has been approximated and generalized to estimate AC and BSC for tissue layer underlying a more attenuative subcutaneous layer. The angular spectrum approach for ultrasound propagation in biological tissue is employed as a virtual Reference Phantom (VRP). The VRP is calibrated with a fixed probe and scanning protocol for application to liver tissue. In a feasibility study with 16 subjects, the method is able to separate 9/11 cases of progressive non-alcoholic fatty liver disease from 5 normal. In particular, it is able to separate 4/5 cases of non-alcoholic steato-hepatitis and early fibrosis (F<=2) from normal tissue. More extensive clinical studies are needed to assess the full capability of this model for screening and monitoring disease progression in liver and other tissues.
The quantification of liver fat as a diagnostic assessment of steatosis remains an important priority for noninvasive imaging systems. We derive a framework in which the unknown fat volume percentage can be estimated from a pair of ultrasound measurements. The precise estimation of ultrasound speed of sound and attenuation within the liver are shown to be sufficient for estimating fat volume assuming a classical model of the properties of a composite elastic material. In this model, steatosis is represented as a random dispersion of spherical fat vacuoles with acoustic properties similar to those of edible oils. Using values of speed of sound and attenuation from the literature where normal and steatotic livers were studied near 3.5 MHz, we demonstrate agreement of the new estimation method with independent measures of fat. This framework holds the potential for translation to clinical scanners where the two ultrasound measurements can be made and utilized for improved quantitative assessment of steatosis.
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