Heart failure is an increasing global health problem. Approximately 50% of patients with heart failure have heart failure with preserved ejection fraction (HFpEF) and concomitant diastolic dysfunction (DD), in part caused by increased myocardial stiffness not detectable by standard echocardiography. While elastography can map tissue stiffness, cardiac applications are currently limited, especially in patients with a higher body mass index. Therefore, we developed cardiac time-harmonic elastography (THE) to detect abnormal diastolic myocardial stiffness associated with DD.

Cardiac THE was developed using standard medical ultrasound and continuous external vibration for regionally resolved mapping of diastolic shear wave speed as a proxy for myocardial stiffness. The method was prospectively applied to 54 healthy controls (26 women), 10 patients with moderate left ventricular hypertrophy (mLVH; 5 women), and 45 patients with wild-type transthyretin amyloidosis (wTTR; 4 women), 20 of whom were treated with tafamidis. Ten healthy participants were reinvestigated after 2 to 6 months to analyze test-retest reproducibility by intraclass correlation coefficients.

Myocardial shear wave speed was measured with good reproducibility (intraclass correlation coefficient = 0.82) and showed higher values in wTTR (3.0 ± 0.7 m/sec) than in mLVH (2.1 ± 0.6 m/sec) and healthy controls (1.8 ± 0.3 m/sec, all P < .05). Area under the curve values were 0.991 and 0.737 for discriminating wTTR and mLVH from healthy controls, respectively. Shear wave speed was reduced in patients after tafamidis treatment (2.6 ± 0.6 m/sec, P = .04), suggesting the potential value of THE for therapy monitoring. Shear wave speed was quantified in the septum, posterior wall, and an automatically masked region (here stated for the septal region).

Cardiac THE detects abnormal myocardial stiffness in patients with DD with high penetration depth, independent of body mass index and region selection. Based on standard ultrasound components, cardiac THE is cost-effective and has the potential to become a point-of-care method for stiffness-sensitive echocardiography.

Magnetic resonance elastography (MRE) is an emerging clinical imaging modality for characterizing the viscoelastic properties of soft biological tissues. MRE shows great promise in the noninvasive diagnosis of various diseases, especially those associated with soft tissue changes involving the extracellular matrix, cell density, or fluid turnover including altered blood perfusion - all hallmarks of inflammation from early events to cancer development. This review covers the fundamental principles of measuring tissue viscoelasticity by MRE, which are based on the stimulation and encoding of shear waves and their conversion into parameter maps of mechanical properties by inverse problem solutions of the wave equation. Technical challenges posed by real-world biological tissue properties such as viscosity, heterogeneity, anisotropy, and nonlinear elastic behavior of tissues are discussed. Applications of MRE measurement in both humans and animal models are presented, with emphasis on the detection, characterization, and staging of diseases related to the cascade of biomechanical property changes from early to chronic inflammation in the liver and brain. Overall, MRE provides valuable insights into the biophysics of soft tissues for imaging-based detection and staging of inflammation-associated tissue changes.

Many heart diseases can change the elasticity of myocardial tissues, making elastography a potential medical imaging strategy for heart disease diagnosis and cardiovascular risk assessment. Among the existing elastography methods, ultrasound elastography is an appealing choice because of ultrasound's inherent advantages of low cost, high safety, wide availability, and deep penetration. The existing investigations of cardiac ultrasound elastography were implemented based on a bulk model of heart tissue, treating the waves generated in the myocardial tissues as shear waves. In this pilot study, we considered the distinct geometric characteristics of heart tissue, i.e., being a layered structure and its dispersive nature as biological tissue. Based on these considerations, we modeled heart tissues as a layered-dispersive structure and developed a new ultrasound elastography method, ultrasonic guided wave elastography, to characterize the myocardial elasticity. The validity of this layered-dispersive model and the reliability of the developed guided wave elastography were first verified on tissue-mimicking phantoms. Then, the guided wave elastography was applied to an ex vivo imaging of a rat heart tissue specimen in real-time during the biaxial planar mechanical testing. The comparison of the real-time myocardial elasticity obtained from guided wave elastography and mechanical testing demonstrated strong matching, verifying the reliability of the developed cardiac guided wave elastography as a potential method for characterizing myocardial elasticity.

In vivo MR elastography (MRE) holds promise as a neuroimaging marker. In cerebral MRE, shear waves are introduced into the brain, which also stimulate vibrations in adjacent CSF, resulting in blurring and biased stiffness values near brain surfaces. We here propose inversion-recovery MRE (IR-MRE) to suppress CSF signal and improve stiffness quantification in brain surface areas.

Inversion-recovery MRE was demonstrated in agar-based phantoms with solid-fluid interfaces and 11 healthy volunteers using 31.25-Hz harmonic vibrations. It was performed by standard single-shot, spin-echo EPI MRE following 2800-ms IR preparation. Wave fields were acquired in 10 axial slices and analyzed for shear wave speed (SWS) as a surrogate marker of tissue stiffness by wavenumber-based multicomponent inversion.

Phantom SWS values near fluid interfaces were 7.5 ± 3.0% higher in IR-MRE than MRE (P = .01). In the brain, IR-MRE SNR was 17% lower than in MRE, without influencing parenchymal SWS (MRE: 1.38 ± 0.02 m/s; IR-MRE: 1.39 ± 0.03 m/s; P = .18). The IR-MRE tissue-CSF interfaces appeared sharper, showing 10% higher SWS near brain surfaces (MRE: 1.01 ± 0.03 m/s; IR-MRE: 1.11 ± 0.01 m/s; P < .001) and 39% smaller ventricle sizes than MRE (P < .001).

Our results show that brain MRE is affected by fluid oscillations that can be suppressed by IR-MRE, which improves the depiction of anatomy in stiffness maps and the quantification of stiffness values in brain surface areas. Moreover, we measured similar stiffness values in brain parenchyma with and without fluid suppression, which indicates that shear wavelengths in solid and fluid compartments are identical, consistent with the theory of biphasic poroelastic media.

Characterisation of soft tissue mechanical properties is a topic of increasing interest in translational and clinical research. Magnetic resonance elastography (MRE) has been used in this context to assess the mechanical properties of tissues in vivo noninvasively. Typically, these analyses rely on linear viscoelastic wave equations to assess material properties from measured wave dynamics. However, deformations that occur in some tissues (e.g. liver during respiration, heart during the cardiac cycle, or external compression during a breast exam) can yield loading bias, complicating the interpretation of tissue stiffness from MRE measurements. In this paper, it is shown how combined knowledge of a material's rheology and loading state can be used to eliminate loading bias and enable interpretation of intrinsic (unloaded) stiffness properties. Equations are derived utilising perturbation theory and Cauchy's equations of motion to demonstrate the impact of loading state on periodic steady-state wave behaviour in nonlinear viscoelastic materials. These equations demonstrate how loading bias yields apparent material stiffening, softening and anisotropy. MRE sensitivity to deformation is demonstrated in an experimental phantom, showing a loading bias of up to twofold. From an unbiased stiffness of [Formula: see text] Pa in unloaded state, the biased stiffness increases to 9767.5 [Formula: see text]1949.9 Pa under a load of [Formula: see text] 34% uniaxial compression. Integrating knowledge of phantom loading and rheology into a novel MRE reconstruction, it is shown that it is possible to characterise intrinsic material characteristics, eliminating the loading bias from MRE data. The framework introduced and demonstrated in phantoms illustrates a pathway that can be translated and applied to MRE in complex deforming tissues. This would contribute to a better assessment of material properties in soft tissues employing elastography.

Cardiovascular diseases are the leading cause of death worldwide. These cardiovascular diseases are associated with mechanical changes in the myocardium and aorta. It is known that stiffness is altered in many diseases, including the spectrum of ischemia, diastolic dysfunction, hypertension and hypertrophic cardiomyopathy. In addition, the stiffness of the aortic wall is altered in multiple diseases, including hypertension, coronary artery disease and aortic aneurysm formation. For example, in diastolic dysfunction in which the ejection fraction is preserved, stiffness can potentially be an important biomarker. Similarly, in aortic aneurysms, stiffness can provide valuable information with regard to rupture potential. A number of studies have addressed invasive and non-invasive approaches to test and measure the mechanical properties of the myocardium and aorta. One of the non-invasive approaches is magnetic resonance elastography (MRE). MRE is a phase-contrast magnetic resonance imaging technique that measures tissue stiffness non-invasively. This review article highlights the technical details and application of MRE in the quantification of myocardial and aortic stiffness in different disease states.

Assessment of tissue stiffness is desirable for clinicians and researchers, as it is well established that pathophysiological mechanisms often alter the structural properties of tissue. Magnetic resonance elastography (MRE) provides an avenue for measuring tissue stiffness and has a long history of clinical application, including staging liver fibrosis and stratifying breast cancer malignancy. A vital component of MRE consists of the reconstruction algorithms used to derive stiffness from wave-motion images by solving inverse problems. A large range of reconstruction methods have been presented in the literature, with differing computational expense, required user input, underlying physical assumptions, and techniques for numerical evaluation. These differences, in turn, have led to varying accuracy, robustness, and ease of use. While most reconstruction techniques have been validated against in silico or in vitro phantoms, performance with real data is often more challenging, stressing the robustness and assumptions of these algorithms. This article reviews many current MRE reconstruction methods and discusses the aforementioned differences. The material assumptions underlying the methods are developed and various approaches for noise reduction, regularization, and numerical discretization are discussed. Reconstruction methods are categorized by inversion type, underlying assumptions, and their use in human and animal studies. Future directions, such as alternative material assumptions, are also discussed.

Many cardiovascular diseases are associated with abnormal function of myocardial contractility or dilatability, which is related to elasticity changes of the myocardium over the cardiac cycle. The mouse is a common animal model in studies of the progression of various cardiomyopathies. We introduce a novel noninvasive approach using microscopic scale MR elastography (MRE) to measure the myocardium stiffness change during the cardiac cycle on a mouse model.

A harmonic mechanical wave of 400 Hz was introduced into the mouse body. An electrocardiograph-gated and respiratory-gated fractional encoding cine-MRE pulse sequence was applied to encode the resulting oscillatory motion on a short-axis slice of the heart. Five healthy mice (age range, 3-13.5 mo) were examined. The weighted summation effective stiffness of the left ventricle wall during the cardiac cycle was estimated.

The ratio of stiffness at end diastole and end systole was 0.5-0.67. Additionally, variation in shear wave amplitude in the left ventricle wall throughout the cardiac cycle was measured and found to correlate with estimates of stiffness variation.

This study demonstrates the feasibility of implementing cardiac MRE on a mouse model. Magn Reson Med 76:1879-1886, 2016. © 2016 International Society for Magnetic Resonance in Medicine.

Myocardial stiffness is an important determinant of cardiac function and is currently invasively and indirectly assessed by catheter angiography. This study aims to demonstrate the feasibility of quantifying right ventricular (RV) stiffness noninvasively using cardiac magnetic resonance elastography (CMRE) in dogs with severe congenital pulmonary valve stenosis (PVS) causing RV hypertrophy, and compare it to remote myocardium in the left ventricle (LV). Additionally, correlations between stiffness and selected pathophysiologic indicators from transthoracic echocardiography (TTE) and cardiac magnetic resonance imaging were explored.

In-vivo CMRE was performed on nine dogs presenting severe congenital PVS using a 1.5T MRI scanner. T1-MOLLI, T2-prepared-bSSFP, gated-cine GRE-MRE and LGE (PSIR) sequences were used to acquire a basal short-axis slice. RV and LV-free-wall (FW) stiffness measurements were compared against each other and also correlated to ventricular mass, RV and LV FW thickness, T1 and T2 relaxation times, and extracellular volume fraction (ECV). Peak transpulmonary pressure gradient and myocardial strain were also acquired on eight dogs by TTE and correlated to RV-FW systolic stiffness. Potential correlations were evaluated by Spearman's rho (rs).

RV-FW stiffness was found to be significantly higher than the LV-FW stiffness both during end-systole (ES) (p=0.002) and end-diastole (ED) (p=0.029). Significant correlations were observed between RV-FW ES and LV-FW ED stiffness versus ECV (rs=0.75; p-value=0.05). Non-significant moderate correlations were found between LV-FW ES (rs=0.54) and RV-FW ED (rs=0.61) stiffness versus ECV. Furthermore, non-significant correlations were found between RV or LV-FW stiffness and the remaining variables (rs<0.54; p-value>0.05).

This study demonstrates the feasibility of determining RV stiffness. The positive correlations between stiffness and ECV might indicate some interdependence between stiffness and myocardial extracellular matrix alterations. However, further studies are warranted to validate our initial observations.

To assess reproducibility in measuring left ventricular (LV) myocardial stiffness in volunteers throughout the cardiac cycle using MR elastography (MRE) and to determine its correlation with age.

Cardiac MRE (CMRE) was performed on 29 normal volunteers, with ages ranging from 21 to 73 years. For assessing reproducibility of CMRE-derived stiffness measurements, scans were repeated per volunteer. Wave images were acquired throughout the LV myocardium, and were analyzed to obtain mean stiffness during the cardiac cycle. CMRE-derived stiffness values were correlated to age.

Concordance correlation coefficient revealed good interscan agreement with rc of 0.77, with P-value < 0.0001. Significantly higher myocardial stiffness was observed during end-systole (ES) compared with end-diastole (ED) across all subjects. Additionally, increased deviation between ES and ED stiffness was observed with increased age.

CMRE-derived stiffness is reproducible, with myocardial stiffness changing cyclically across the cardiac cycle. Stiffness is significantly higher during ES compared with ED. With age, ES myocardial stiffness increases more than ED, giving rise to an increased deviation between the two.

To test whether shear-wave amplitudes (SWAs) in the myocardium measured with cardiac magnetic resonance (MR) elastography enable diagnosis of myocardial relaxation abnormalities in patients with diastolic dysfunction.

Each subject gave written informed consent to participate in this institutional review board-approved prospective study. Electrocardiographically triggered SWA-based cardiac MR elastography with 24.13-Hz external vibration frequency was performed in 50 subjects grouped into asymptomatic young (n = 10, 18-39 years) and asymptomatic old (n = 10, 40-68 years) subjects and patients with echocardiographically proved mild, moderate, or severe diastolic dysfunction (n = 30, 44-73 years). SWA images were analyzed in the left ventricular (LV) region and were normalized against reference SWA of the thoracic wall. Analysis of variance with Bonferroni-corrected pairwise comparison and Pearson correlation were used for statistical evaluation.

Young and old control subjects had normalized mean LV SWA of 0.67 ± 0.04 (standard error of the mean) and 0.56 ± 0.04 (P = .18, F test), respectively. Compared with the control groups, patients with mild, moderate, and severe diastolic dysfunction displayed significantly reduced normalized mean LV SWA of 0.37 ± 0.04, 0.34 ± 0.04, and 0.29 ± 0.04 (P < .001, F test), respectively, which was inversely correlated to the severity of diastolic dysfunction (R = -0.61, P < .001). The best cutoff value to differentiate between asymptomatic volunteers and patients was 0.43, yielding an area under the receiver operating characteristic curve of 0.92, with 90% sensitivity and 89.7% specificity.

LV SWA measured with cardiac MR elastography provides image contrast sensitive to myocardial relaxation abnormalities and shows significantly lower values in patients with diastolic dysfunction.

Time harmonic elastography (THE) has recently been introduced for measurement of the periodic alteration in myocardial shear modulus based on externally induced low-frequency acoustic vibrations produced by a loudspeaker. In this study, we propose further developments of cardiac THE toward a clinical modality including integration of the vibration source into the patient bed and automated parameter extraction from harmonic shear wave amplitudes, wall motion profiles and synchronized electrocardiographic records. This method has enabled us to evaluate the delay between wall motion and wave amplitude alteration for the measurement of isovolumetric times of elasticity alteration during contraction (τ(C)) and relaxation (τ(R)) in a group of 32 healthy volunteers. On average, the wave amplitudes changed between systole and diastole by a factor of 1.7 ± 0.3, with a τ(C) of 137 ± 61 ms and a τ(R) of 68 ± 73 ms, which agrees with results obtained with the more time-consuming and expensive cardiac magnetic resonance elastography. Furthermore, because of the high sampling rate, elasto-morphometric parameters such as transition times and the area of wave amplitude-cardiac motion cycles can be processed in an automated way for the future clinical detection of myocardial relaxation abnormalities.

Viscoelastic properties of the myocardium are important for normal cardiac function and may be altered by disease. Thus, quantification of these properties may aid with evaluation of the health of the heart. Lamb wave dispersion ultrasound vibrometry (LDUV) is a shear wave-based method that uses wave velocity dispersion to measure the underlying viscoelastic material properties of soft tissue with plate-like geometries. We tested this method in eight pigs in an open-chest preparation. A mechanical actuator was used to create harmonic, propagating mechanical waves in the myocardial wall. The motion was tracked using a high frame rate acquisition sequence, typically 2500 Hz. The velocities of wave propagation were measured over the 50-400 Hz frequency range in 50 Hz increments. Data were acquired over several cardiac cycles. Dispersion curves were fit with a viscoelastic, anti-symmetric Lamb wave model to obtain estimates of the shear elasticity, μ(1), and viscosity, μ(2) as defined by the Kelvin-Voigt rheological model. The sensitivity of the Lamb wave model was also studied using simulated data. We demonstrated that wave velocity measurements and Lamb wave theory allow one to estimate the variation of viscoelastic moduli of the myocardial walls in vivo throughout the course of the cardiac cycle.

The technique of MR elastography (MRE) has emerged as a useful modality for quantitatively imaging the mechanical properties of soft tissues in vivo. Recently, MRE has been introduced as a clinical tool for evaluating chronic liver disease, but many other potential applications are being explored. These applications include measuring tissue changes associated with diseases of the liver, breast, brain, heart, and skeletal muscle including both focal lesions (e.g., hepatic, breast, and brain tumors) and diffuse diseases (e.g., fibrosis and multiple sclerosis). The purpose of this review article is to summarize some of the recent developments of MRE and to highlight some emerging applications.

To determine whether increasing epinephrine infusion in an in vivo pig model is associated with an increase in end-systolic magnetic resonance elastography (MRE)-derived effective stiffness.

Finite element modeling (FEM) was performed to determine the range of myocardial wall thicknesses that could be used for analysis. Then MRE was performed on five pigs to measure the end-systolic effective stiffness with epinephrine infusion. Epinephrine was continuously infused intravenously in each pig to increase the heart rate in increments of 20%. For each such increase end-systolic effective stiffness was measured using MRE. In each pig, Student's t-test was used to compare effective end-systolic stiffness at baseline and at initial infusion of epinephrine. Least-square linear regression was performed to determine the correlation between normalized end-systolic effective stiffness and increase in heart rate with epinephrine infusion.

FEM showed that phase gradient inversion could be performed on wall thickness ≈≥1.5 cm. In pigs, effective end-systolic stiffness significantly increased from baseline to the first infusion in all pigs (P = 0.047). A linear correlation was found between normalized effective end-systolic stiffness and percent increase in heart rate by epinephrine infusion with R(2) ranging from 0.86-0.99 in four pigs. In one of the pigs the R(2) value was 0.1. A linear correlation with R(2) = 0.58 was found between normalized effective end-systolic stiffness and percent increase in heart rate when pooling data points from all pigs.

Noninvasive MRE-derived end-systolic effective myocardial stiffness may be a surrogate for myocardial contractility.

Noninvasive image-based measurement of intrinsic tissue pressure is of great interest in the diagnosis and characterization of diseases. Therefore, we propose to exploit the capability of phase-contrast MRI to measure three-dimensional vector fields of tissue motion for deriving volumetric strain induced by external vibration. Volumetric strain as given by the divergence of mechanical displacement fields is related to tissue compressibility and is thus sensitive to the state of tissue pressure. This principle is demonstrated by the measurement of three-dimensional vector fields of 50-Hz oscillations in a compressible agarose phantom and in the lungs of nine healthy volunteers. In the phantom, the magnitude of the oscillating divergence increased by about 400% with 4.8 bar excess air pressure, corresponding to an effective-medium compression modulus of 230 MPa. In lungs, the averaged divergence magnitude increased in all volunteers (N = 9) between 7 and 78% from expiration to inspiration. Measuring volumetric strain by MRI provides a compression-sensitive parameter of tissue mechanics, which varies with the respiratory state in the lungs. In future clinical applications for diagnosis and characterization of lung emphysema, fibrosis, or cancer, divergence-sensitive MRI may serve as a noninvasive marker sensitive to disease-related alterations of regional elastic recoil pressure in the lungs.

Time harmonic elastography is introduced as a modality for assessing myocardial elasticity changes during the cardiac cycle. It is based on external stimulation and real-time analysis of 30-Hz harmonic shear waves in axial direction of a parasternal line of sight through the lateral heart wall. In 20 healthy volunteers, the externally induced waves showed smaller amplitudes during systole (76.0 ± 30.8 μm) and higher amplitudes during diastole (126.7 ± 52.1 μm). This periodic wave amplitude alteration preceded ventricular contraction and dilation by about 100 ms. The amplitude ratio of 1.75 ± 0.49 indicates a relative change in myocardial shear elasticity on the order of 14 ± 11. These results well agree with observations made by cardiac magnetic resonance elastography for a similar displacement component and region of the heart. The proposed method provides reproducible elastodynamic information on the heart in real-time and may help in diagnosing myocardial relaxation abnormalities in the future.

From times immemorial manual palpation served as a source of information on the state of soft tissues and allowed detection of various diseases accompanied by changes in tissue elasticity. During the last two decades, the ancient art of palpation gained new life due to numerous emerging elasticity imaging (EI) methods. Areas of applications of EI in medical diagnostics and treatment monitoring are steadily expanding. Elasticity imaging methods are emerging as commercial applications, a true testament to the progress and importance of the field.In this paper we present a brief history and theoretical basis of EI, describe various techniques of EI and, analyze their advantages and limitations, and overview main clinical applications. We present a classification of elasticity measurement and imaging techniques based on the methods used for generating a stress in the tissue (external mechanical force, internal ultrasound radiation force, or an internal endogenous force), and measurement of the tissue response. The measurement method can be performed using differing physical principles including magnetic resonance imaging (MRI), ultrasound imaging, X-ray imaging, optical and acoustic signals.Until recently, EI was largely a research method used by a few select institutions having the special equipment needed to perform the studies. Since 2005 however, increasing numbers of mainstream manufacturers have added EI to their ultrasound systems so that today the majority of manufacturers offer some sort of Elastography or tissue stiffness imaging on their clinical systems. Now it is safe to say that some sort of elasticity imaging may be performed on virtually all types of focal and diffuse disease. Most of the new applications are still in the early stages of research, but a few are becoming common applications in clinical practice.

To assess the potential of cardiac magnetic resonance elastography (MRE) for elasticity-based detection of abnormal left ventricular (LV) relaxation.

Cardiac MRE was performed in 3 groups: young volunteers (n = 11; mean age, 31.7 years), older volunteers (n = 5; mean age, 54.8 years), and a group with relaxation abnormalities (n = 11; mean age, 58 years) identified by transthoracic echocardiography. Cine MR imaging served to measure LV volumes and global LV systolic function. Wave-amplitude-sensitive electrocardiograph-gated steady-state MRE was performed using an extended piston driver attached to the anterior chest wall. Phase contrast shear wave images were acquired in all 3 Cartesian components and combined to generate amplitude maps. This was done using the time-gradient operator for linear high-pass filtering and phase unwrapping followed by temporal Fourier transformation for extracting externally induced 24.13-Hz shear oscillations from intrinsic motion and blood flow. Amplitudes were evaluated in the left ventricle and normalized by wave amplitudes outside the heart, adjacent to the right ventricle.

One patient and 1 young volunteer had to be excluded from final analysis because of considerable body movement during the acquisition of the MRE scans. Mean wave amplitudes in the remaining subjects were 0.22 ± 0.05 mm in young volunteers, 0.23 ± 0.09 in older volunteers, and 0.14 ± 0.03 mm in patients. The mean ratio of amplitudes inside the ventricle to the anterior chest wall was 0.62 ± 0.15 for young volunteers, 0.50 ± 0.09 for older volunteers, and 0.33 ± 0.08 for patients.

MRE identifies significantly reduced LV shear wave amplitudes in patients with mild relaxation abnormality. Thus, cardiac MRE provides a promising modality for an elasticity-based diagnosis of dysfunctional myocardial relaxation.

: Magnetic resonance elastography (MRE) allows noninvasive assessment of tissue stiffness in vivo. Renal arterial stenosis (RAS), a narrowing of the renal artery, promotes irreversible tissue fibrosis that threatens kidney viability and may elevate tissue stiffness. However, kidney stiffness may also be affected by hemodynamic factors. This study tested the hypothesis that renal blood flow (RBF) is an important determinant of renal stiffness as measured by MRE.

: In 6 anesthetized pigs MRE studies were performed to determine cortical and medullary elasticity during acute graded decreases in RBF (by 20%, 40%, 60%, 80%, and 100% of baseline) achieved by a vascular occluder. Three sham-operated swine served as time control. Additional pigs were studied with MRE 6 weeks after induction of chronic unilateral RAS (n = 6) or control (n = 3). Kidney fibrosis was subsequently evaluated histologically by trichrome staining.

: During acute RAS the stenotic cortex stiffness decreased (from 7.4 ± 0.3 to 4.8 ± 0.6 kPa, P = 0.02 vs. baseline) as RBF decreased. Furthermore, in pigs with chronic RAS (80% ± 5.4% stenosis) in which RBF was decreased by 60% ± 14% compared with controls, cortical stiffness was not significantly different from normal (7.4 ± 0.3 vs. 7.6 ± 0.3 kPa, P = 0.3), despite histologic evidence of renal tissue fibrosis.

: Hemodynamic variables modulate kidney stiffness measured by MRE and may mask the presence of fibrosis. These results suggest that kidney turgor should be considered during interpretation of elasticity assessments.

To compare magnetic resonance elastography (MRE) effective stiffness to end-diastolic pressure at different loading conditions to demonstrate a relationship between myocardial MRE effective stiffness and end-diastolic left ventricular (LV) pressure.

MRE was performed on four pigs to measure the end-diastolic effective stiffness under different loading conditions. End-diastolic pressure was increased by infusing Dextran-40 (20% of blood volume). For each infusion of Dextran-40, end-diastolic pressure was recorded and end-diastolic effective stiffness was measured using MRE. In each pig, least-square linear regression was performed to determine the correlation between end-diastolic effective stiffness and end-diastolic LV pressure.

A linear correlation was found between end-diastolic LV pressure and end-diastolic effective stiffness with R(2) ranging from 0.73-0.9. A linear correlation with R(2) = 0.26 was found between end-diastolic LV pressure and end-diastolic effective stiffness when pooling data points from all pigs.

End-diastolic effective myocardial stiffness increases linearly with end-diastolic LV pressure.

Viscoelastic properties of mouse brain tissue were estimated non-invasively, in vivo, using magnetic resonance elastography (MRE) at 4.7 T to measure the dispersive properties of induced shear waves. Key features of this study include (i) the development and application of a novel MR-compatible actuation system which transmits vibratory motion into the brain through an incisor bar, and (ii) the investigation of the mechanical properties of brain tissue over a 1200 Hz bandwidth from 600-1800 Hz. Displacement fields due to propagating shear waves were measured during continuous, harmonic excitation of the skull. This protocol enabled characterization of the true steady-state patterns of shear wave propagation. Analysis of displacement fields obtained at different frequencies indicates that the viscoelastic properties of mouse brain tissue depend strongly on frequency. The average storage modulus (G') increased from approximately 1.6 to 8 kPa over this range; average loss modulus (G″) increased from approximately 1 to 3 kPa. Both moduli were well approximated by a power-law relationship over this frequency range. MRE may be a valuable addition to studies of disease in murine models, and to pre-clinical evaluations of therapies. Quantitative measurements of the viscoelastic parameters of brain tissue at high frequencies are also valuable for modeling and simulation of traumatic brain injury.

To investigate the feasibility of quantitative in vivo ultrahigh field magnetic resonance elastography (MRE) of the human brain in a broad range of low-frequency mechanical vibrations.

Mechanical vibrations were coupled into the brain of a healthy volunteer using a coil-driven actuator that either oscillated harmonically at single frequencies between 25 and 62.5 Hz or performed a superimposed motion consisting of multiple harmonics. Using a motion sensitive single-shot spin-echo echo planar imaging sequence shear wave displacements in the brain were measured at 1.5 and 7 T in whole-body MR scanners. Spatially averaged complex shear moduli were calculated applying Helmholtz inversion.

Viscoelastic properties of brain tissue could be reliably determined in vivo at 1.5 and 7 T using both single-frequency and multifrequency wave excitation. The deduced dispersion of the complex modulus was consistent within different experimental settings of this study for the measured frequency range and agreed well with literature data.

MRE of the human brain is feasible at 7 T. Superposition of multiple harmonics yields consistent results as compared to standard single-frequency based MRE. As such, MRE is a system-independent modality for measuring the complex shear modulus of in vivo human brain in a wide dynamic range.

BACKGROUND/MOTIVATION: To directly determine isovolumetric cardiac time intervals by magnetic resonance elastography (MRE) using the magnitude of the complex signal for deducing morphological information combined with the phase of the complex signal for tension-relaxation measurements.

Thirty-five healthy volunteers and 11 patients with relaxation abnormalities were subjected to transthoracic wave stimulation using vibrations of approximately 25 Hz. A k-space-segmented, ECG-gated gradient-recalled echo steady-state sequence with a 500-Hz bipolar motion-encoding gradient was used for acquiring a series of 360 complex images of a short-axis view of the heart at a frame rate of less than 5.2 ms. Magnitude images were employed for measuring the cross-sectional area of the left ventricle, while phase images were used for analyzing the amplitudes of the externally induced waves. The delay between the decrease in amplitude and onset of ventricular contraction was determined in all subjects and assigned to the time of isovolumetric tension. Conversely, the delay between the increase in wave amplitude and ventricular dilatation was used for measuring the time of isovolumetric elasticity relaxation.

Wave amplitudes decreased during systole and increased during diastole. The variation in wave amplitude occurred ahead of morphological changes. In healthy volunteers the time of isovolumetric elasticity relaxation was 75 ± 31 ms, which is significantly shorter than the time of isovolumetric tension of 136 ± 36 ms (P < 0.01). In patients with relaxation abnormalities (mild diastolic dysfunction, n = 11) isovolumetric elasticity relaxation was significantly prolonged, with 133 ± 57 ms (P < 0.01), whereas isovolumetric tension time was in the range of healthy controls (161 ± 45 ms; P = 0.053).

The complex MRE signal conveys complementary information on cardiac morphology and elasticity, which can be combined for directly measuring isovolumetric tension and elasticity relaxation in the human heart.

MR elastography (MRE) is a noninvasive technique in which images of externally generated waves propagating in tissue are used to measure stiffness. The first aim is to determine, from a range of driver configurations, the optimal driver for the purpose of generating waves within the heart in vivo. The second aim is to quantify the shear stiffness of normal myocardium throughout the cardiac cycle using MRE and to compare MRE stiffness to left ventricular chamber pressure in an in vivo pig model. MRE was performed in six pigs with six different driver setups, including no motion, three noninvasive drivers, and two invasive drivers. MRE wave displacement amplitudes were calculated for each driver. During the same MRI examination, left ventricular pressure and MRI-measured left ventricular volume were obtained, and MRE myocardial stiffness was calculated for 20 phases of the cardiac cycle. No discernible waves were imaged when no external motion was applied, and a single pneumatic drum driver produced higher amplitude waves than the other noninvasive drivers (P < 0.05). Pressure-volume loops overlaid onto stiffness-volume loops showed good visual agreement. Pressure and MRE-measured effective stiffness showed good correlation (R(2) = 0.84). MRE shows potential as a noninvasive method for estimating effective myocardial stiffness throughout the cardiac cycle.

Magnetic resonance elastography (MRE) has been developed over the last few years as a non-invasive means of evaluating the elasticity of biological tissues. The presence of the skull has always prevented semeiotic palpation of the brain, but MRE now offers the possibility of "palpating by imaging" in order to detect brain consistency under physiological and pathological conditions. The aim of this article is to review the current state-of-the-art of MRE imaging and discuss its possible future diagnostic applications in neuroscience.

To compare magnetic resonance elastography (MRE) with ventricular pressure changes in an animal model.

Three pigs of different cardiac physiology (weight, 25 to 53 kg; heart rate, 61 to 93 bpm; left ventricular [LV] end-diastolic volume, 35 to 70 ml) were subjected to invasive LV pressure measurement by catheter and noninvasive cardiac MRE. Cardiac MRE was performed in a short-axis view of the heart and applying a 48.3-Hz shear-wave stimulus. Relative changes in LV-shear wave amplitudes during the cardiac cycle were analyzed. Correlation coefficients between wave amplitudes and LV pressure as well as between wave amplitudes and LV diameter were determined.

A relationship between MRE and LV pressure was observed in all three animals (R2 >or= 0.76). No correlation was observed between MRE and LV diameter (R2

CONCLUSION

Externally induced shear waves provide information reflecting intraventricular pressure changes which, if substantiated in further experiments, has potential to make cardiac MRE a unique noninvasive imaging modality for measuring pressure-volume function of the heart.

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The aims of this study were to validate stiffness estimates of a phantom undergoing cyclic deformation obtained using a multiphase magnetic resonance elastography (MRE) imaging sequence by comparison with those obtained using a single-phase MRE sequence and to quantify the stability of the multiphase-derived stiffness estimates as a function of deformation frequency and imaging parameters. A spherical rubber shell of 10 cm diameter and 1 cm thickness was connected to a computerized flow pump to produce cyclic pressure variations within the phantom. The phantom was imaged at cyclic pressures between 18-72 bpm using single-phase and multiphase MRE acquisitions. The shear stiffness of the phantom was resolved using a spherical shell wave inversion algorithm. Shear stiffness was averaged over the slice of interest and plotted against pressure within the phantom. A linear correlation was observed between stiffness and pressure. Good correlation (R(2) = 0.98) was observed between the stiffness estimates obtained using the standard single-phase and the multiphase pulse sequences. Stiffness estimates obtained using multiphase MRE were stable when the fraction of the deformation period required for acquisition of a single image was not greater than 42%. The results demonstrate the potential of multiphase MRE technique for imaging dynamic organs, such as the heart.

Current advances in magnetic resonance, as a diagnostic modality, are discussed in the context of publications from Investigative Radiology during 2007 and 2008. The articles relating to this topic, published during the past 2 years, are reviewed by anatomic region. The discussion concludes with a consideration of magnetic resonance contrast media, focusing on studies published in the journal, and examining in particular the potential impact of nephrogenic systemic fibrosis.