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.

The mechanical properties of soft tissues are closely associated with a variety of diseases. This motivates the development of elastography techniques in which tissue mechanical properties are quantitatively estimated through imaging. Magnetic resonance elastography (MRE) is a noninvasive phase-contrast MR technique wherein shear modulus of soft tissue can be spatially and temporally estimated. MRE has recently received significant attention due to its capability in noninvasively estimating tissue mechanical properties, which can offer considerable diagnostic potential. In this work, recent technology advances of MRE, its future clinical applications, and the related limitations will be discussed.

Aortic stiffness plays an important role in evaluating and predicting the progression of systemic arterial hypertension (SAH). The aim of this study is to determine the stiffness of aortic wall using MR elastography (MRE) in a hypertensive porcine model and compare it against invasive aortic pressure measurements.

Renal wrapping surgery was performed on eight pigs to induce SAH. Aortic MRE was performed at baseline and 2 months postsurgery using a retrospectively pulse-gated gradient-echo MRE sequence on a 1.5 tesla scanner. Mechanical waves of 70 Hz were introduced into the aorta. Invasive central aortic pressure measurements were obtained prior to each scan to calculate mean arterial pressure (MAP). MRE data were analyzed to obtain effective aortic stiffness. Spearman's rank correlation analysis was performed to assess the relationship between MAP and MRE-derived aortic stiffness.

Significant increase in effective aortic stiffness was observed between baseline and 2 months postsurgery measurements (paired t test; P = 0.004). The average MAP, determined by pooling all animals, was 65.24 ± 9.42 mm Hg at baseline and 92.57 ± 11.80 mm Hg 2 months postsurgery with P < 0.0001. Moderate linear correlation was observed between MAP and effective aortic stiffness (ρ = 0.52; P = 0.046).

This study demonstrated that, in a SAH porcine model, MRE-derived aortic stiffness increased with increase in MAP. Magn Reson Med 78:2315-2321, 2017. © 2017 International Society for Magnetic Resonance in Medicine.

Aortic wall shear stress (WSS_Flow ) alters endothelial function, which in-turn changes aortic wall stiffness leading to remodeling in different disease states. Therefore, the aims of this study are to determine normal physiologic correlations between: (1) Magnetic Resonance Elastography (MRE)-derived aortic wall stiffness (WS_MRE ) and WSS_Flow ; (2) WS_MRE and mean velocity; (3) WS_MRE and pulse wave velocity (PWV);( 4) WS_MRE and mean peak flow; and (5) WS_MRE , WSS_Flow and age using MRE and 4D-flow MRI in the abdominal aorta in healthy human subjects.

Cardiac-gated aortic MRE and 4D-flow MRI data were acquired in 24 healthy volunteers using a 3 Tesla scanner. For MRE, 70 Hz external motion was applied to obtain wave images in all spatial directions in a separate breathhold. Whereas, 4D-flow data was acquired under free-breathing. Wave images in all the directions were processed to obtain three-dimensional-weighted stiffness map at end-systole (ES). WSS_Flow , mean velocity, PWV and mean peak flow were obtained using 4D-flow data. Pearson correlation was performed to determine association between all variables.

A significant negative correlation was observed between: (1) ES WS_MRE and WSS_Flow in both axial (r = -0.62; P = 0.006) and circumferential (r = -0.52; P = 0.016) directions; (2) ES WS_MRE and mean velocity (r = -0.58; P = 0.012); and (3) age and WSS_Flow in both axial (r = -0.71; P < 0.0001) and circumferential (r = -0.58; P = 0.0012) directions. A significant positive correlation was observed between: (1) ES WS_MRE and PWV (r = 0.69; P < 0.0001); (2) ES WS_MRE and mean peak flow (r = 0.53; P = 0.016); and (3) ES WS_MRE and age (r = 0.63;P = 0.006).

The negative significant correlation between aortic WSS_Flow and WS_MRE in normal volunteers demonstrates a relationship between WS_MRE and WSS_Flow .

2 J. Magn. Reson. Imaging 2017;45:771-778.

Abdominal aortic aneurysm (AAA) wall stiffness has been suggested to be an important factor in the overall rupture risk assessment compared with anatomic measure. We hypothesize that AAA diameter will have no correlation to AAA wall stiffness. The aim of this study is to (1) determine magnetic resonance elastography (MRE)-derived aortic wall stiffness in AAA patients and its correlation to AAA diameter; (2) determine the correlation between AAA stiffness and amount of thrombus and calcium; and (3) compare the AAA stiffness measurements against age-matched healthy individuals.

In vivo abdominal aortic MRE was performed on 36 individuals (24 patients with AAA measuring 3-10 cm and 12 healthy volunteers), aged 36 to 78 years, after obtaining written informed consent under the approval of the Institutional Review Board. MRE images were processed to obtain spatial stiffness maps of the aorta. AAA diameter, amount of thrombus, and calcium score were reported by experienced interventional radiologists. Spearman correlation, Wilcoxon signed rank test, and Mann-Whitney test were performed to determine the correlation between AAA stiffness and diameter and to determine the significant difference in stiffness measurements between AAA patients and healthy individuals.

No significant correlation (P > .1) was found between AAA stiffness and diameter or amount of thrombus or calcium score. AAA stiffness (mean 13.97 ± 4.2 kPa) is significantly (P ≤ .02) higher than remote normal aorta in AAA (mean 8.87 ± 2.2 kPa) patients and in normal individuals (mean 7.1 ± 1.9 kPa).

Our results suggest that AAA wall stiffness may provide additional information independent of AAA diameter, which may contribute to our understanding of AAA pathophysiology, biomechanics, and risk for rupture.

The clinical diagnosis of atherosclerosis via the measurement of stenosis size is widely acknowledged as an imperfect criterion. The vulnerability of an atherosclerotic plaque to rupture is associated with its mechanical properties. The potential to image these mechanical properties using magnetic resonance elastography (MRE) was investigated through synthetic datasets. An image of the steady state wave propagation, equivalent to the first harmonic, can be extracted directly from finite element analysis. Inversion of this displacement data yields a map of the shear modulus, known as an elastogram. The variation of plaque composition, stenosis size, Gaussian noise, filter thresholds and excitation frequency were explored. A decreasing mean shear modulus with an increasing lipid composition was identified through all stenosis sizes. However the inversion algorithm showed sensitivity to parameter variation leading to artefacts which disrupted both the elastograms and quantitative trends. As noise was increased up to a realistic level, the contrast was maintained between the fully fibrous and lipid plaques but lost between the interim compositions. Although incorporating a Butterworth filter improved the performance of the algorithm, restrictive filter thresholds resulted in a reduction of the sensitivity of the algorithm to composition and noise variation. Increasing the excitation frequency improved the techniques ability to image the magnitude of the shear modulus and identify a contrast between compositions. In conclusion, whilst the technique has the potential to image the shear modulus of atherosclerotic plaques, future research will require the integration of a heterogeneous inversion algorithm.

MR Elastography (MRE) is a noninvasive technique for measuring tissue stiffness that has been used to assess the average stiffness of the abdominal aorta. The utility of aortic MRE would be improved if it could provide information about local variations in aortic stiffness. We hypothesize that regional variations in aortic stiffness can also be measured with MRE and the purpose of this work was to demonstrate that MRE can measure regional stiffness variations in a vascular phantom and in ex vivo porcine aortas. A vascular phantom was fabricated, containing two silicone tubes embedded in gel. A segment of one of the tubes was modified to increase its stiffness. MRE was performed on the phantom with a continuous flow of water through the tubes. The stiffness distribution along the modified tube was measured and compared to the reference tube. MRE was also performed in porcine aortas embedded in gel with segments treated with saline or formalin for 4 days. The stiffness difference between saline- and formalin-treated aortic segments was measured by MRE and mechanical tests. A positive correlation was found between the regional stiffnesses measured by MRE and mechanical tests. The results indicate that MRE can be used to evaluate the local stiffness distribution in silicone tubes and ex vivo porcine aortas. It may therefore be possible to apply MRE to measure regional stiffness variations of the aorta in vivo.

The failure of endovascular treatments of peripheral arterial disease represents a critical clinical issue. Specialized data are required to tailor such procedures to account for the mechanical response of the diseased femoral arterial tissue to medical device deployment. The purpose of this study is to characterize the mechanical response of atherosclerotic femoral arterial tissue to large deformation, the conditions typical of angioplasty and stenting, and also to determine the mechanically induced failure properties and to relate this behaviour to biological content and structural composition using uniaxial testing, Fourier transform infrared spectroscopy and scanning electron microscopy. Mechanical and biological characterization of 20 plaque samples obtained from femoral endarterectomy identified three distinct classifications. "Lightly calcified" samples display linear mechanical responses and fail at relatively high stretch. "Moderately calcified" samples undergo an increase in stiffness and ultimate strength coupled with a decrease in ductility. Structural characterization reveals calcified nodules within this group that may be acting to reinforce the tissue matrix, thus increasing the stiffness and ultimate strength. "Heavily calcified" samples account for the majority of samples tested and exhibit significantly reduced ultimate strength and ductility compared to the preceding groups. Structural characterization of this group reveals large areas of calcified tissue dominating the failure cross-sections of the samples. The frequency and structural dominance of these features solely within this group offers an explanation as to the reduced ultimate strength and ductility and highlights the need for modern peripheral endovascular devices to account for this behaviour during novel medical device design.

Characterization of blood vessel elastic properties can help in detecting thrombosis and preventing life-threatening conditions such as acute myocardial infarction or stroke. Vascular elastic photoacoustic tomography (VE-PAT) is proposed to measure blood vessel compliance in humans. Implemented on a linear-array-based photoacoustic computed tomography system, VE-PAT can quantify blood vessel compliance changes due to simulated thrombosis and occlusion. The feasibility of the VE-PAT system was first demonstrated by measuring the strains under uniaxial loading in perfused blood vessel phantoms and quantifying their compliance changes due to the simulated thrombosis. The VE-PAT system detected a decrease in the compliances of blood vessel phantoms with simulated thrombosis, which was validated by a standard compression test. The VE-PAT system was then applied to assess blood vessel compliance in a human subject. Experimental results showed a decrease in compliance when an occlusion occurred downstream from the measurement point in the blood vessels, demonstrating VE-PAT’s potential for clinical thrombosis detection.

The pathological changes associated with the development of atherosclerotic plaques within arterial vessels result in significant alterations to the mechanical properties of the diseased arterial wall. There are several methods available to characterise the mechanical behaviour of atherosclerotic plaque tissue, and it is the aim of this paper to review the use of uniaxial mechanical testing. In the case of atherosclerotic plaques, there are nine studies that employ uniaxial testing to characterise mechanical behaviour. A primary concern regarding this limited cohort of published studies is the wide range of testing techniques that are employed. These differing techniques have resulted in a large variance in the reported data making comparison of the mechanical behaviour of plaques from different vasculatures, and even the same vasculature, difficult and sometimes impossible. In order to address this issue, this paper proposes a more standardised protocol for uniaxial testing of diseased arterial tissue that allows for better comparisons and firmer conclusions to be drawn between studies. To develop such a protocol, this paper reviews the acquisition and storage of the tissue, the testing approaches, the post-processing techniques and the stress-strain measures employed by each of the nine studies. Future trends are also outlined to establish the role that uniaxial testing can play in the future of arterial plaque mechanical characterisation.

To investigate the feasibility of using MR elastography (MRE) for the evaluation of the stiffness of in vivo aortic wall.

To validate the experimental approach for imaging the aorta in vivo, a gel phantom with an embedded porcine aorta was imaged in the presence of fluid flow within the aorta. The potential changes in the elasticity of the vessel wall with changes in pressure were investigated. The feasibility of performing MRE of abdominal aorta was assessed in five volunteers (age, 22-40 years; body mass index, 21.5-25.2 kg/m(2) ). The pulse-gated cine MRE technique was used to study the wave propagation along the aorta throughout the cardiac cycle and provide estimates of aortic stiffness in diastole.

In the phantom study, the wave propagation was well visualized within the porcine aorta embedded in the gel phantom. An increase of the Young's modulus-wall thickness (E*t) product with the increase in static pressure was observed. In the in vivo study, the waves were well visualized within the lumen of abdominal aorta in the five volunteers in diastolic phase, but they were not well visualized during systole.

MRE is feasible for noninvasively assessing the stiffness of the abdominal aorta and merits further investigation.

To determine the correlation in abdominal aortic stiffness obtained using magnetic resonance elastography (MRE) (μ(MRE)) and MRI-based pulse wave velocity (PWV) shear stiffness (μ(PWV)) estimates in normal volunteers of varying age, and also to determine the correlation between μ(MRE) and μ(PWV).

In vivo aortic MRE and MRI were performed on 21 healthy volunteers with ages ranging from 18 to 65 years to obtain wave and velocity data along the long axis of the abdominal aorta. The MRE wave images were analyzed to obtain mean stiffness and the phase contrast images were analyzed to obtain PWV measurements and indirectly estimate stiffness values from the Moens-Korteweg equation.

Both μ(MRE) and μ(PWV) measurements increased with age, demonstrating linear correlations with R(2) values of 0.81 and 0.67, respectively. Significant difference (P ≤ 0.001) in mean μ(MRE) and μ(PWV) between young and old healthy volunteers was also observed. Furthermore, a poor linear correlation of R(2) value of 0.43 was determined between μ(MRE) and μ(PWV) in the initial pool of volunteers.

The results of this study indicate linear correlations between μ(MRE) and μ(PWV) with normal aging of the abdominal aorta. Significant differences in mean μ(MRE) and μ(PWV) between young and old healthy volunteers were observed.

The proteasome prevents the intracellular accumulation of proteins and its impairment can lead to structural and functional alterations, as noted for the coronary vasculature in a previous study. Utilizing the same model, this study was designed to test the hypothesis that chronic proteasome inhibition (PSI) also leads to structural and functional changes of the heart.

Female domestic pigs were randomized to a normal diet without (N) or with twice-weekly subcutaneous injections of the proteasome inhibitor MLN-273 (0.08 mg/kg, N + PSI, n = 5 each group). In vivo data on cardiac structure and function as well as myocardial perfusion and microvascular permeability response to adenosine and dobutamine were obtained by electron beam computed tomography after 11 weeks. Subsequent ex vivo myocardial analyses included immunoblotting, immunostaining, TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labelling), Masson trichrome, and Congo red staining. Compared with N, an increase in LV mass was observed in N + PSI (106.5 ± 16.4 g vs. 183.1 ± 24.2 g, P < 0.05). The early to late diastolic filling ratio was increased in N + PSI vs. N (3.5 ± 0.6 vs. 1.8 ± 0.1, P < 0.05). The EF tended to be lower (46 ± 12% and 53 ± 9%, respectively) and cardiac output was significantly lower in N + PSI than in N (2.9 ± 1.1 vs. 4.7 ± 1.1 L/min, P < 0.05). Tissue analyses demonstrated an accumulation of proteasome substrates, apoptosis, and fibrosis in the PSI group. Compared with N, the myocardial perfusion response was reduced and microvascular permeability was increased in N + PSI.

The current study demonstrates that chronic proeasome inhibition affects the cardiovascular system, leading to functional and structural alteration of the heart consistent with a hypertrophic-restrictive cardiomyopathy phenotype.

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.

To demonstrate feasibility of using MR elastography (MRE) to identify hypertensive changes in the abdominal aorta when compared with normotensives based on the stiffness measurements.

MRE was performed on eight volunteers (four normotensives and four hypertensives) to measure the effective stiffness of the abdominal aorta. MRE wave images are directionally filtered and phase gradient analysis was performed to determine the stiffness of the aorta. Student's t-test was performed to determine significant difference in stiffness measurements between normotensives and hypertensives.

The normotensive group demonstrated a mean abdominal aortic stiffness of 3.7 ± 0.8 kPa, while the controlled-hypertensive demonstrated a mean abdominal aortic stiffness of 9.3 ± 1.9 kPa. MRE effective stiffness of abdominal aorta in hypertensives was significantly greater than that of normotensives with p = 0.02.

Feasibility of in vivo aortic MRE is demonstrated. Hypertensives have significantly higher aortic stiffness assessed through MRE than normotensives.

Magnetic resonance elastography (MRE) is a noninvasive phase-contrast technique for estimating the mechanical properties of tissues by imaging propagating mechanical waves within the tissue. In this study, we hypothesize that changes in arterial wall stiffness, experimentally induced by formalin fixation, can be measured using MRE in ex vivo porcine aortas. In agreement with our hypothesis, the significant stiffness increase after sample fixation was clearly demonstrated by MRE and confirmed by mechanical testing. The results indicate that MRE can be used to examine the stiffness changes of the aorta. This study has provided evidence of the effectiveness of using MRE to directly assess the stiffness change in aortic wall. The results offer motivation to pursue MRE as a noninvasive method for the evaluation of arterial wall mechanical properties.

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.