1-Norm waveform analysis for MR elastography-based quantification of inhomogeneity: Effects of the freeze-thaw cycle and Alzheimer's disease.

BACKGROUND: Despite its success in the mechanical characterization of biological tissues, magnetic resonance elastography (MRE) uses ill-posed wave inversions to estimate tissue stiffness. 1-Norm has been recently introduced as a mathematical measure for the scattering of mechanical waves due to inhomogeneities based on an analysis of the delineated contours of wave displacement. PURPOSE: To investigate 1-Norm as an MRE-based quantitative biomarker of mechanical inhomogeneities arising from microscopic structural tissue alterations caused by the freeze-thaw cycle (FTC) or Alzheimer's disease (AD). METHODS: In this proof-of-concept study, we prospectively investigated excised porcine kidney (n = 6), liver (n = 6), and muscle (n = 6) before vs. after the FTC at 500-2000 Hz and excised murine brain of healthy controls (n = 3) vs. 5xFAD species with AD (n = 3) at 1200-1800 Hz using 0.5 T tabletop MRE. 1-Norm analysis was compared with conventional wave inversion. RESULTS: While the FTC reduced both stiffness and inhomogeneity in kidney, liver, and muscle tissue, AD led to lower brain stiffness but more pronounced mechanical inhomogeneity. CONCLUSION: Our preliminary results show that 1-Norm is sensitive to tissue mechanical inhomogeneity due to FTC and AD without relying on ill-posed wave inversion techniques. 1-Norm has the potential to be used as an MRE-based diagnostic biomarker independent of stiffness to characterize abnormal conditions that involve changes in tissue mechanical inhomogeneity.

Quantifying uniaxial prestress and waveguide effects on dynamic elastography estimates for a cylindrical rod.

Dynamic elastography attempts to reconstruct quantitative maps of the viscoelastic properties of materials by noninvasively measuring mechanical wave motion in them. The target motion is typically transversely-polarized relative to the wave propagation direction, such as bulk shear wave motion. In addition to neglecting waveguide effects caused by small lengths in one dimension or more, many reconstruction strategies also ignore nonzero, non-isotropic static preloads. Significant anisotropic prestress is inherent to the functional role of some biological materials of interest, which also are small in size relative to shear wavelengths in one or more dimensions. A cylindrically shaped polymer structure with isotropic material properties is statically elongated along its axis while its response to circumferentially-, axially-, and radially-polarized vibratory excitation is measured using optical or magnetic resonance elastography. Computational finite element simulations augment and aid in the interpretation of experimental measurements. We examine the interplay between uniaxial prestress and waveguide effects. A coordinate transformation approach previously used to simplify the reconstruction of un-prestressed transversely isotropic material properties based on elastography measurements is adapted with partial success to estimate material viscoelastic properties and prestress conditions without requiring advanced knowledge of either.

Decoupling Uniaxial Tensile Prestress and Waveguide Effects From Estimates of the Complex Shear Modulus in a Cylindrical Structure Using Transverse-Polarized Dynamic Elastography.

Dynamic elastography, whether based on magnetic resonance, ultrasound, or optical modalities, attempts to reconstruct quantitative maps of the viscoelastic properties of biological tissue, properties altered by disease and injury, by noninvasively measuring mechanical wave motion in the tissue. Most reconstruction strategies that have been developed neglect boundary conditions, including quasi-static tensile or compressive loading resulting in a nonzero prestress. Significant prestress is inherent to the functional role of some biological tissues currently being studied using elastography, such as skeletal and cardiac muscle, arterial walls, and the cornea. In the present article a configuration, inspired by muscle elastography but generalizable to other applications, is analytically and experimentally studied. A hyperelastic polymer phantom cylinder is statically elongated in the axial direction while its response to transverse-polarized vibratory excitation is measured. We examine the interplay between uniaxial prestress and waveguide effects in this muscle-like tissue phantom using computational finite element simulations and magnetic resonance elastography measurements. Finite deformations caused by prestress coupled with waveguide effects lead to results that are predicted by a coordinate transformation approach that has been previously used to simplify reconstruction of anisotropic properties using elastography. Here, the approach estimates material viscoelastic properties that are independent of the nonhomogeneous prestress conditions without requiring advanced knowledge of those stress conditions.

Tabletop MR elastography for investigating effects of the freeze-thaw cycle on the mechanical properties of biological tissues.

PURPOSE: We aimed at characterizing the effects of the freeze-thaw cycle (FTC) on ex vivo specimens of porcine muscle, liver, kidney, and brain using tabletop magnetic resonance elastography (MRE) combined with rheological modeling. While frozen tissue banks potentially facilitate access to large amounts of well-preserved biospecimens, the impact of the FTC on their viscoelastic properties remains elusive. METHODS: In this proof-of-concept study, fresh specimens from porcine lumbar muscle (n = 6), liver (n = 6), kidney (n = 6), and brain (n = 6) were examined before and after the FTC using 0.5T tabletop MRE at 500 Hz, 1000 Hz, 1500 Hz, and 2000 Hz. Seven standard rheological models (Maxwell, Springpot, Voigt, Zener, Jeffrey, fractional Voigt, fractional Zener) were employed to calculate frequency independent viscoelastic parameters. RESULTS: The Zener rheological model showed the best fit quality for tissues before and after FTC in the investigated frequency range. Global rheological behavior after the FTC was softer for all tissues. Differences in mechanical parameters between tissues were preserved after the FTC and showed similar trends as before the FTC. Moreover, rheological fit quality improved after the FTC - a result that will be beneficial in investigating frozen tissue bank samples. CONCLUSION: Multifrequency tabletop MRE allows rheological characterization of tissue samples before and after the FTC. Our results encourage further biomechanical characterization of frozen tissue bank samples, which may provide valuable information on the diagnostic potential of elastographic methods.

Optical coherence elastography for assessing the influence of intraocular pressure on elastic wave dispersion in the cornea.

The cornea is a highly specialized organ that relies on its mechanical stiffness to maintain its aspheric geometry and refractive power, and corneal diseases such as keratoconus have been linked to abnormal tissue stiffness and biomechanics. Dynamic optical coherence elastography (OCE) is a clinically promising non-contact and non-destructive imaging technique that can provide measurements of corneal tissue stiffness directly in vivo. The method relies on the concepts of elastography where shear waves are generated and imaged within a tissue to obtain mechanical properties such as tissue stiffness. The accuracy of OCE-based measurements is ultimately dependent on the mathematical theories used to model wave behavior in the tissue of interest. In the cornea, elastic waves propagate as guided wave modes which are highly dispersive and can be mathematically complex to model. While recent groups have developed detailed theories for estimating corneal tissue properties from guided wave behavior, the effects of intraocular pressure (IOP)-induced prestress have not yet been considered. It is known that prestress alone can strongly influence wave behavior, in addition to the associated non-linear changes in tissue properties. This present study shows that failure to account for the effects of prestress may result in overestimations of the corneal shear moduli, particularly at high IOPs. We first examined the potential effects of IOP and IOP-induced prestress using a combination of approximate mathematical theories describing wave behavior in thin plates with observations made from data published in the OCE literature. Through wave dispersion analysis, we deduce that IOP introduces a tensile hoop stress and may also influence an elastic foundational effect that were observable in the low-frequency components of the dispersion curves. These effects were incorporated into recently developed models of wave behavior in nearly incompressible, transversely isotropic (NITI) materials. Fitting of the modified NITI model with ex vivo porcine corneal data demonstrated that incorporation of the effects of IOP resulted in reduced estimates of corneal shear moduli. We believe this demonstrates that overestimation of corneal stiffness occurs if IOP is not taken into consideration. Our work may be helpful in separating inherent corneal stiffness properties that are independent of IOP; changes in these properties and in IOP are distinct, clinically relevant issues that affect the cornea health.

Investigating the heterogeneity of viscoelastic properties in prostate cancer using MR elastography at 9.4T in fresh prostatectomy specimens.

PURPOSE: To quantify the heterogeneity of viscoelastic tissue properties in prostatectomy specimens from men with prostate cancer (PC) using MR elastography (MRE) with histopathology as reference. METHODS: Twelve fresh prostatectomy specimens were examined in a preclinical 9.4T MRI scanner. Maps of the complex shear modulus (|G*| in kPa) with its real and imaginary part (G' and G" in kPa) were calculated at 500 Hz. Prostates were divided into 12 segments for segment-wise measurement of viscoelastic properties and histopathology. Coefficients of variation (CVs in %) were calculated for quantification of heterogeneity. RESULTS: Group-averaged values of cancerous vs. benign segments were significantly increased: |G*| of 12.13 kPa vs. 6.14 kPa, G' of 10.84 kPa vs. 5.44 kPa and G" of 5.45 kPa vs. 2.92 kPa, all p < 0.001. In contrast, CVs were significantly increased for benign segments: 23.59% vs. 26.32% (p = 0.014) for |G*|, 27.05% vs. 37.84% (p < 0.003) for G', and 36.51% vs. 50.37% (p = 0.008) for G". DISCUSSION: PC is characterized by a stiff yet homogeneous biomechanical signature, which may be due to the unique nondestructive growth pattern of PC with intervening stroma, providing a rigid scaffold in the affected area. In turn, increased heterogeneity in benign prostate segments may be attributable to the presence of different prostate zones with involvement by specific nonmalignant pathology.

Concurrent OCT and OCT angiography of retinal neurovascular degeneration in the 5XFAD Alzheimer's disease mice.

Significance: As one part of the central nervous system, the retina manifests neurovascular defects in Alzheimer's disease (AD). Quantitative imaging of retinal neurovascular abnormalities may promise a new method for early diagnosis and treatment assessment of AD. Previous imaging studies of transgenic AD mouse models have been limited to the central part of the retina. Given that the pathological hallmarks of AD frequently appear in different peripheral quadrants, a comprehensive regional investigation is needed for a better understanding of the retinal degeneration associated with AD-like pathology. Aim: We aim to demonstrate concurrent optical coherence tomography (OCT) and OCT angiography (OCTA) of retinal neuronal and vascular abnormalities in the 5XFAD mouse model and to investigate region-specific retinal degeneration. Approach: A custom-built OCT system was used for retinal imaging. Retinal thickness, vessel width, and vessel density were quantitatively measured. The artery and vein (AV) were classified for differential AV analysis, and trilaminar vascular plexuses were segmented for depth-resolved density measurement. Results: It was observed that inner and outer retinal thicknesses were explicitly reduced in the dorsal and temporal quadrants, respectively, in 5XFAD mice. A significant arterial narrowing in 5XFAD mice was also observed. Moreover, overall capillary density consistently showed a decreasing trend in 5XFAD mice, but regional specificity was not identified. Conclusions: Quadrant- and layer-specific neurovascular degeneration was observed in 5XFAD mice. Concurrent OCT and OCTA promise a noninvasive method for quantitative monitoring of AD progression and treatment assessment.

Measuring viscoelastic parameters in Magnetic Resonance Elastography: a comparison at high and low magnetic field intensity.

Magnetic Resonance Elastography (MRE) is a non-invasive imaging technique which involves motion-encoding MRI for the estimation of the shear viscoelastic properties of soft tissues through the study of shear wave propagation. The technique has been found informative for disease diagnosis, as well as for monitoring of the effects of therapies. The development of MRE and its validation have been supported by the use of tissue-mimicking phantoms. In this paper we present our new MRE protocol using a low magnetic field tabletop MRI device at 0.5 T and sinusoidal uniaxial excitation in a geometrical focusing condition. Results obtained for gelatin are compared to those previously obtained using high magnetic field MRE at 11.7 T. A multi-frequency investigation is also provided via a comparison of commonly used rheological models: Maxwell, Springpot, Voigt, Zener, Jeffrey, fractional Voigt and fractional Zener. Complex shear modulus values were comparable when processed from images acquired with the tabletop low field scanner and the high field scanner. This study serves as a validation of the presented tabletop MRE protocol and paves the way for MRE experiments on ex-vivo tissue samples in both normal and pathological conditions.

Spatial heterogeneity of hepatic fibrosis in primary sclerosing cholangitis vs. viral hepatitis assessed by MR elastography.

Spatial heterogeneity of hepatic fibrosis in primary sclerosing cholangitis (PSC) in comparison to viral hepatitis was assessed as a potential new biomarker using MR elastography (MRE). In this proof-of-concept study, we hypothesized a rather increased heterogeneity in PSC and a rather homogeneous distribution in viral hepatitis. Forty-six consecutive subjects (PSC: n = 20, viral hepatitis: n = 26) were prospectively enrolled between July 2014 and April 2017. Subjects underwent multifrequency MRE (1.5 T) using drive frequencies of 35-60 Hz and generating shear-wave speed (SWS in m/s) maps as a surrogate of stiffness. The coefficient of variation (CV in %) was determined to quantify fibrosis heterogeneity. Mean SWS and CV were 1.70 m/s and 21% for PSC, and 1.84 m/s and 18% for viral hepatitis. Fibrosis heterogeneity was significantly increased for PSC (P = 0.04) while no difference was found for SWS of PSC and viral hepatitis (P = 0.17). Global hepatic stiffness was similar in PSC and viral hepatitis groups, but spatial heterogeneity may reveal spatial patterns of stiffness changes towards enhanced biophysics-based diagnosis by MRI.

Axially- and torsionally-polarized radially converging shear wave MRE in an anisotropic phantom made via Embedded Direct Ink Writing.

Magnetic Resonance Elastography (MRE) is a non-invasive imaging method to quantitatively map the shear viscoelastic properties of soft tissues. In this study, Embedded Direct Ink Writing is used to fabricate a muscle mimicking anisotropic phantom that may serve as a standard for imaging studies of anisotropic materials. The technique allowed us to obtain a long shelf life silicone-based phantom expressing transverse isotropic mechanical properties. Another goal of the present investigation is to introduce a torsionally-polarized, radially-converging shear wave actuation method for MRE. The implemented design for this novel setup was first validated via its application to isotropic and homogeneous gelatin phantoms. Then, a comparison of the resulting complex wave images from axially- and torsionally-polarized MRE on the developed anisotropic phantom and on a skeletal muscle murine sample is presented, highlighting the value of using multiple actuation and motion encoding polarization directions when studying anisotropic materials.

Longitudinal study of sub-regional cerebral viscoelastic properties of 5XFAD Alzheimer's disease mice using multifrequency MR elastography.

PURPOSE: To study sub-regional, longitudinal changes occurring inside brains of 5XFAD mice, an Alzheimer's disease (AD) model, based on viscoelastic parameters derived using MR elastography and their spatial variation. METHODS: Female 5XFAD and non-transgenic B6SJLF1/J mice as controls (n = 9 for both groups) were used for the study. Scans were performed inside a 9.4T preclinical MRI scanner using SampLe Interval Modulation-magnetic resonance elastography (SLIM-MRE). Experiments were performed at ages 2, 4, and 6 mo, and by using three actuation frequencies: 900, 1000, and 1100 Hz. Multifrequency dual elasto-visco (MDEV) reconstruction was used to combine 3D multifrequency MRE data and calculate magnitude G∗ , and phase angle φ, of the complex shear modulus G∗ . Mean values were measured for the overall brain and sub-regions associated with the early onset of AD, to check for the effect of aging and mouse model. Spatial coefficient of variation (CV) of both parameters across different age-groups were analyzed. RESULTS: G∗ and φ values reduced with age for overall brain in 5XFAD mice with significant difference in mean G∗ between 5XFAD and control mice at 6 mo (P = .029). Analyzing values from the hippocampal region highlighted drop in mean G∗ and φ values. The CV of G∗ inside hippocampus enabled differentiation at 4 mo with it being significantly lower in 5XFAD mice (P = .0007). CONCLUSION: Multifrequency 3D MRE revealed longitudinal viscoelastic changes in 5XFAD mice and the CV of G∗ in brain sub-regions may qualify as biomarker for early diagnosis of AD.

Prostate cancer assessment using MR elastography of fresh prostatectomy specimens at 9.4 T.

PURPOSE: Despite its success in the assessment of prostate cancer (PCa), in vivo multiparametric MRI has limitations such as interobserver variability and low specificity. Several MRI methods, among them MR elastography, are currently being discussed as candidates for supplementing conventional multiparametric MRI. This study aims to investigate the detection of PCa in fresh ex vivo human prostatectomy specimens using MR elastography. METHODS: Fourteen fresh prostate specimens from men with clinically significant PCa without formalin fixation or prior radiation therapy were examined by MR elastography at 500 Hz immediately after radical prostatectomy in a 9.4T preclinical scanner. Specimens were divided into 12 segments for both calculation of storage modulus (G' in kilopascals) and pathology (Gleason score) as reference standard. Sensitivity, specificity, and area under the receiver operating characteristic curve were calculated to assess PCa detection. RESULTS: The mean G' and SD were as follows: all segments, 8.74 ± 5.26 kPa; healthy segments, 5.44 ± 4.40 kPa; and cancerous segments, 10.84 ± 4.65 kPa. The difference between healthy and cancerous segments was significant with P ≤ .001. Diagnostic performance assessed with the Youden index was as follows: sensitivity, 69%; specificity, 79%; area under the curve, 0.81; and cutoff, 10.67 kPa. CONCLUSION: Our results suggest that prostate MR elastography has the potential to improve diagnostic performance of multiparametric MRI, especially regarding its 2 major limitations: interobserver variability and low specificity. Particularly the high value for specificity in PCa detection is a stimulating result and encourages further investigation of this method.

Diagnostic performance of tomoelastography of the liver and spleen for staging hepatic fibrosis.

OBJECTIVES: To determine the diagnostic performance, cut-off values, and optimal drive frequency range for staging hepatic fibrosis using tomoelastography by multifrequency MR elastography of the liver and spleen. METHODS: This prospective study consecutively enrolled a total of 61 subjects between June 2014 and April 2017: 45 patients with chronic liver disease and proven stage of fibrosis and 16 healthy volunteers. Tomoelastography was performed at 1.5 T using six drive frequencies from 35 to 60 Hz. Cut-off values and AUC were calculated. Shear wave speed (in m/s) of the liver and spleen was assessed separately and in combination as a surrogate of stiffness. RESULTS: For compound multifrequency processing of the liver, cut-off and AUC values by fibrosis stage were as follows: F1, 1.52 m/s and 0.89; F2, 1.55 m/s and 0.94; F3, 1.67 m/s and 0.98; and F4, 1.72 m/s and 0.98. Diagnostic performance of the best single drive frequencies (45 Hz, 55 Hz, 60 Hz) was similar (mean AUC = 0.95, respectively). Combined analysis of the liver and spleen slightly improved performance at 60 Hz in F4 patients (mean AUC = 0.97 vs. 0.95, p = 0.03). Full-field-of-view elastograms displayed not only the liver and spleen but also small anatomical structures including the pancreas and major vessels. CONCLUSION: Tomoelastography provides full-field-of-view elastograms with unprecedented detail resolution and excellent diagnostic accuracy for staging hepatic fibrosis. Our analysis of single-frequency tomoelastography suggests that scan time can be further reduced in future studies, making tomoelastography easier to implement in clinical routine. KEY POINTS: • Tomoelastography provides full-field-of-view elastograms of the abdomen with unprecedented detail resolution and excellent diagnostic accuracy for staging hepatic fibrosis. • Diagnostic performance of single-frequency tomoelastography at higher frequencies (45 Hz, 55 Hz, 60 Hz) and compound multifrequency processing are equivalent for staging hepatic fibrosis. • Combined assessment of hepatic and splenic stiffness slightly improves diagnostic performance for staging hepatic fibrosis.

An investigation into the relationship between inhomogeneity and wave shapes in phantoms and ex vivo skeletal muscle using Magnetic Resonance Elastography and finite element analysis.

Soft biological tissues such as skeletal muscle and brain white matter can be inhomogeneous and anisotropic due to the presence of fibers. Unlike biological tissue, phantoms with known microstructure and defined mechanical properties enable a quantitative assessment and systematic investigation of the influence of inhomogeneities on the nature of shear wave propagation. This study introduces a mathematical measure for the wave shape, which the authors call as the 1-Norm, to determine the conditions under which homogenization may be a valid approach. This is achieved through experimentation using the Magnetic Resonance Elastography technique on 3D printed inhomogeneous fiber phantoms as well as on ex-vivo porcine lumbus muscle. In addition, Finite Element Analysis is used as a tool to decouple the effects of directional anisotropy from those of inhomogeneity. A correlation is then established between the values of 1-Norm derived from the wave front geometry, and the spacing (d) between neighboring inhomogeneities (spherical inclusions or fibers and fiber intersections in phantoms and muscle). Smaller values of 1-Norm indicate less wave scattering at the locations of fiber intersections, which implies that the wave propagation may be approximated to that of a homogeneous medium; homogenization may not be a valid approximation when significant scattering occurs at the locations of inhomogeneities. In conclusion, the current study proposes 1-Norm as a quantitative measure of the magnitude of wave scattering in a medium, which can potentially be used as a homogeneity index of a biological tissue.

Anisotropic composite material phantom to improve skeletal muscle characterization using magnetic resonance elastography.

The presence and progression of neuromuscular pathology, including spasticity, Duchenne's muscular dystrophy and hyperthyroidism, has been correlated with changes in the intrinsic mechanical properties of skeletal muscle tissue. Tools for noninvasively measuring and monitoring these properties, such as Magnetic Resonance Elastography (MRE), could benefit basic research into understanding neuromuscular pathologies, as well as translational research to develop therapies, by providing a means of assessing and tracking their efficacy. Dynamic elastography methods for noninvasive measurement of tissue mechanical properties have been under development for nearly three decades. Much of the technological development to date, for both Ultrasound (US)-based and Magnetic Resonance Imaging (MRI)-based strategies, has been grounded in assumptions of local homogeneity and isotropy. Striated skeletal and cardiac muscle, as well as brain white matter and soft tissue in some other organ regions, exhibit a fibrous microstructure which entails heterogeneity and anisotropic response; as one seeks to improve the accuracy and resolution in mechanical property assessment, heterogeneity and anisotropy need to be accounted for in order to optimize both the dynamic elastography experimental protocol and the interpretation of the measurements. Advances in elastography methodology at every step have been aided by the use of tissue-mimicking phantoms. The aim of the present study was to develop and characterize a heterogeneous composite phantom design with uniform controllable anisotropic properties meant to be comparable to the frequency-dependent anisotropic properties of skeletal muscle. MRE experiments and computational finite element (FE) studies were conducted on a novel 3D-printed composite phantom design. The displacement maps obtained from simulation and experiment show the same elliptical shaped wavefronts elongated in the plane where the structure presents higher shear modulus. The model exhibits a degree of anisotropy in line with literature data from skeletal muscle tissue MRE experiments. FE simulations of the MRE experiments provide insight into proper interpretation of experimental measurements, and help to quantify the importance of heterogeneity in the anisotropic material at different scales.

Simultaneous magnetic resonance and optical elastography acquisitions: Comparison of displacement images and shear modulus estimations using a single vibration source.

The mechanical properties of tissue are sensitive to pathological changes, which is the basis for using dynamic elastography as a diagnostic tool. The purpose of this study is a concurrent cross-modality comparison of two dynamic elastography methods, Magnetic Resonance Elastography (MRE) and Scanning Laser Doppler Vibrometry (SLDV) using a single vibration source method. Cylindrical soft tissue mimicking specimens of Plastisol and Ecoflex are stimulated with 60, 100, 150, and 250 Hz sinusoidal vibration during imaging. Specimen stiffness was also varied by adjusting the softener amount in each material. Displacement fields acquired using the two methods show similarity in wave front geometry at all frequencies. Magnetic Resonance Elastography (MRE) with 3D inversion and Optical Elastography (OE) with averaged 1D curve fitting were used to derive complex shear moduli from each imaging modality. MRE and OE shear storage modulus (n = 3) results were closest at 150 Hz with Plastisol G' (MRE) = 9.03 ±â€¯0.43 kPa and G' (OE) = 8.46 ±â€¯0.14 kPa while Ecoflex was G' (MRE) = 15.71 ±â€¯0.95 kPa and G' (OE) = 13.71 ±â€¯0.03 kPa. Correlation between MRE and OE complex shear moduli related by all 36 coupled scans performed during this study yield a Pearson's correlation of ρ = 0.88 with p < 0.001 for G' (storage modulus) and ρ = 0.85 with p < 0.001 for G" (loss modulus). The simultaneous imaging approach yields stiffness values within the same range and acceptable error margins for MRE and OE.

Comparison of non-invasive assessment of liver fibrosis in patients with alpha1-antitrypsin deficiency using magnetic resonance elastography (MRE), acoustic radiation force impulse (ARFI) Quantification, and 2D-shear wave elastography (2D-SWE).

PURPOSE: Although it has been known for decades that patients with alpha1-antitrypsin deficiency (AATD) have an increased risk of cirrhosis and hepatocellular carcinoma, limited data exist on non-invasive imaging-based methods for assessing liver fibrosis such as magnetic resonance elastography (MRE) and acoustic radiation force impulse (ARFI) quantification, and no data exist on 2D-shear wave elastography (2D-SWE). Therefore, the purpose of this study is to evaluate and compare the applicability of different elastography methods for the assessment of AATD-related liver fibrosis. METHODS: Fifteen clinically asymptomatic AATD patients (11 homozygous PiZZ, 4 heterozygous PiMZ) and 16 matched healthy volunteers were examined using MRE and ARFI quantification. Additionally, patients were examined with 2D-SWE. RESULTS: A high correlation is evident for the shear wave speed (SWS) determined with different elastography methods in AATD patients: 2D-SWE/MRE, ARFI quantification/2D-SWE, and ARFI quantification/MRE (R = 0.8587, 0.7425, and 0.6914, respectively; P≤0.0089). Four AATD patients with pathologically increased SWS were consistently identified with all three methods-MRE, ARFI quantification, and 2D-SWE. CONCLUSION: The high correlation and consistent identification of patients with pathologically increased SWS using MRE, ARFI quantification, and 2D-SWE suggest that elastography has the potential to become a suitable imaging tool for the assessment of AATD-related liver fibrosis. These promising results provide motivation for further investigation of non-invasive assessment of AATD-related liver fibrosis using elastography.

Simultaneous 3D MR elastography of the in vivo mouse brain.

The feasibility of sample interval modulation (SLIM) magnetic resonance elastography (MRE) for the in vivo mouse brain is assessed, and an alternative SLIM-MRE encoding method is introduced. In SLIM-MRE, the phase accumulation for each motion direction is encoded simultaneously by varying either the start time of the motion encoding gradient (MEG), SLIM-phase constant (SLIM-PC), or the initial phase of the MEG, SLIM-phase varying (SLIM-PV). SLIM-PC provides gradient moment nulling, but the mutual gradient shift necessitates increased echo time (TE). SLIM-PV requires no increased TE, but exhibits non-uniform flow compensation. Comparison was to conventional MRE using six C57BL/6 mice. For SLIM-PC, the Spearman's rank correlation to conventional MRE for the shear storage and loss modulus images were 80% and 76%, respectively, and likewise for SLIM-PV, 73% and 69%, respectively. The results of the Wilcoxon rank sum test showed that there were no statistically significant differences between the spatially averaged shear moduli derived from conventional-MRE, SLIM-PC, and SLIM-PV acquisitions. Both SLIM approaches were comparable to conventional MRE scans with Spearman's rank correlation of 69%-80% and with 3 times reduction in scan time. The SLIM-PC method had the best correlation, and SLIM-PV may be a useful tool in experimental conditions, where both measurement time and T2 relaxation is critical.

Concurrent 3D acquisition of diffusion tensor imaging and magnetic resonance elastography displacement data (DTI-MRE): Theory and in vivo application.

PURPOSE: To introduce a newly developed technique (DTI-MRE) for the simultaneous acquisition of diffusion tensor imaging (DTI) and 3D-vector field magnetic resonance elastography (MRE) data, and to demonstrate its feasibility when applied in vivo to the mouse brain. METHODS: In DTI-MRE, simultaneous encoding is achieved by using a series of diffusion/motion-sensitizing gradients (dMSGs) with specific timing and directions. By adjusting the duration of the dMSGs with the diffusion time and with the mechanical vibration frequency, the shear wave motion and diffusion are encoded into the MR phase and MR magnitude signals, respectively. The dMSGs are applied in a noncollinear and noncoplanar manner that optimizes the capture of both the DTI signal attenuation and the three-dimensional MRE displacements. In this work, the feasibility of the DTI-MRE technique was demonstrated on in vivo mouse brains (n=3) using a 9.4T animal MRI scanner. The DTI-MRE derived parameters (MD, mean diffusivity; FA, fractional anisotropy; MRE displacement fields; and shear modulus |G|) were compared with those acquired using conventional, separate MRE and diffusion methods. RESULTS: The averaged (MD, FA, and |G|) values for three mice are (0.580 ± 0.050 µm2 /ms, 0.43 ± 0.02, and 4.80 ± 0.06 kPa) and (0.583 ± 0.035 µm2 /ms, 0.46 ± 0.02, and 4.91 ± 0.19 kPa) for DTI-MRE, and conventional DTI and 3D-vector field MRE measurements, respectively. All derived parameters (MD, FA, |G|, and displacement) obtained using the combined DTI-MRE method and conventional methods were significantly correlated with P < 0.05. CONCLUSION: Simultaneous acquisition of DTI and 3D-vector field MRE is feasible in vivo and reduces the scan time by up to 50% compared with conventional, separate acquisitions, while providing an immediate co-registration of maps of diffusion properties and stiffness. Magn Reson Med 77:273-284, 2017. © 2016 Wiley Periodicals, Inc.

Demonstration of concurrent tensile testing and magnetic resonance elastography.

Magnetic Resonance Elastography (MRE) is a technique used to measure the mechanical properties of soft tissues and has already shown its diagnostic potential for pathologies involving fibrogenesis and neurodegeneration. Experimental investigation of loading during MRE is fairly unexplored and may help to better understand changing mechanical properties in relation to organ function. Tensile testing is a common technique for examining mechanical properties of materials and is used as the simultaneous comparison method with MRE in this study. 3D MRE data was acquired during quasistatic uniaxial tensile loading of an Ecoflex 0010 cylindrical specimen. Individual MRE scans at 1.5, 2.0, and 2.5kHz where performed on engineering strain increments of 20% from 0% to 140% while tensile reaction force was recorded using a load cell attached to an adjustable elongation slide. Tensile stress-strain relation resembled the Fung hyperelastic strain energy model. We observe that the MRE shear storage modulus is related to the state of tensile deformation. This study demonstrates the feasibility of simultaneous tensile testing during MRE and the new design can potentially be used for MRE calibration using pre-tension.