Static and dynamic liver stiffness: An ex vivo porcine liver study using MR elastography

Magnetic resonance elastography (MRE) is an MRI-based noninvasive technique for quantitatively assessing tissue stiffness. The hypothesis of this study is that stiffness increases with portal pressure. We further hypothesized that the rate of stiffness change with pressure would be larger in liver tissue treated to simulate the stiffening effects of fibrosis. In agreement with our hypothesis, the formalin-treated livers were stiffer than the untreated livers, and in both groups the liver stiffness increased with portal venous pressure. The rate of stiffness change with portal pressure was significantly greater after formalin treatment. In this study, we have developed an ex vivo liver model incorporating portal venous pressure variations and observed significant changes in liver stiffness due to portal pressure. This model could be useful for understanding and investigating the changes in the static and dynamic components of liver stiffness.     

Assessment of in vitro vs. in vivo lung structure using hyperpolarized helium-3 diffusion magnetic resonance imaging

The purpose of this study was to assess the properties of a model system for hyperpolarized He-3 (HHe) diffusion MR imaging created from the lungs of New Zealand white rabbits by drying the lungs while inflated at constant pressure. The dried lungs were prepared by sacrificing the animal, harvesting the lungs en bloc and dehydrating the lungs for several days using dry compressed air. In four rabbits, the apparent diffusion coefficient (ADC) of HHe gas was measured in vivo and, within 1 week, in vitro in the dried lungs. To assess long-term repeatability, in vitro ADC values were measured again 3 months later. Dried lungs from four additional rabbits were imaged twice on the same day to assess the short-term repeatability of ADC measurements, and tissue samples from these lungs were then removed for histology. In vivo and in vitro ADC maps showed similar features and similar distributions of ADC values; mean in vivo and in vitro ADC values differed by less than 12%. The in vitro mean ADC values were highly reproducible, with no more than 5% difference between measurements for the short-term repeatability and less than 17% difference between measurements for the long-term repeatability. Histological samples from the dried lungs demonstrated that the lung structure remained intact. These results suggest that the dried lungs are a useful and inexpensive alternative to human or in vivo animal studies for HHe diffusion MR sequence development, testing and optimization.     

Short- and midterm repeatability of magnetic resonance elastography in healthy volunteers at 3.0 T

The purpose of this study was to evaluate the short- and midterm repeatability of liver stiffness measurements with magnetic resonance elastography (MRE) in healthy subjects at 3.0 T. Twenty-two healthy volunteers were enrolled in this prospective study. The stiffness measurements were obtained from three slices with three repeated acquisitions for each slice (session 1) by two independent raters. After a mean period of 7 ± 2 days (session 2) and 195 ± 15 days (session 3), each subject was scanned again using the same protocol and MR system. The liver stiffness differences were calculated between sessions or raters. The intraclass correlation coefficient (ICC) was calculated to assess interrater agreement and intersession agreement. The stiffness differences over the short- and midterm intervals was (− 0.004 ± 0.086) kPa for sessions 1–2, lower than (− 0.055 ± 0.150) kPa for sessions 1–3 and (− 0.051 ± 0.173) kPa for sessions 2–3. The liver stiffness was more repeatable for the short-term interval with the mean overall ICC of 0.96 (sessions 1–2) (95% confidence interval [CI]: 0.90–0.98) compared with 0.91 (sessions 1–3) (95% CI: 0.78–0.96) and 0.87 (sessions 2–3) (95% CI: 0.69–0.95) for the midterm intervals. The overall ICC of interrater agreement was excellent at 0.987 (95% CI: 0.983 to 0.990). These results confirm that MRE is a reproducible technique for liver stiffness quantification over short- and midterm intervals up to 6 months in a healthy population at 3.0 T.     

Assessment of pulmonary artery stiffness using velocity-encoding magnetic resonance imaging: evaluation of techniques

The loss of pulmonary artery (PA) compliance has significant pathophysiological effect on the right ventricle. Noninvasive and reliable assessment of PA wall stiffness would be an essential determiner of right heart load and a clinically useful factor to assess cardiovascular risk. Two MRI techniques have been proposed for assessing PA stiffness by measuring pulse wave velocity (PWV): transit time (TT) and flow area (QA). However, no data are available that compares the two techniques and evaluates their performance, especially over a wide range of PWV values or at 3.0-T, which is the purpose of the present study. Thirty-three patients with different heart conditions were imaged using optimized high-temporal resolution and high-spatial resolution velocity-encoding MRI sequences. Statistical analysis was conducted to study intermethod, interobserver and intraobserver variabilities. The PWV measurements using TT and QA techniques showed good agreement (P>0.1). The Bland-Altman analysis showed negligible differences between the two methods (mean±S.D.=0.11±0.35 m/s, correlation coefficient r=0.94). The repeated measurements showed low interobserver and intraobserver variabilities, although the S.D. of the differences was larger in the QA technique. The mean±S.D. of the TT/QA measurement differences were −0.05±0.2/0.0±0.36 m/s and 0.02±0.26/0.02±0.39 m/s for the interobserver and intraobserver differences, respectively. In conclusion, each technique has its own advantages and disadvantages. The two techniques result in similar measurements, although the QA method is more subjective due to its dependency on operator intervention.     

In vivo structural analysis of articular cartilage using diffusion tensor magnetic resonance imaging

Purpose

The articular cartilage is a small tissue with a matrix structure of three layers between which the orientation of collagen fiber differs. A diffusion-weighted twice-refocused spin-echo echo-planar imaging (SE-EPI) sequence was optimized for the articular cartilage, and the structure of the three layers of human articular cartilage was imaged in vivo from diffusion tensor images.

Materials and Methods

The subjects imaged were five specimens of swine femur head after removal of the flesh around the knee joint, five specimens of swine articular cartilage with flesh present and the knee cartilage of five adult male volunteers. Based on diffusion-weighted images in six directions, the mean diffusivity (MD) and the fractional anisotropy (FA) values were calculated.

Results

Diffusion tensor images of the articular cartilage were obtained by sequence optimization. The MD and FA value of the specimens (each of five examples) under different conditions were estimated. Although the articular cartilage is a small tissue, the matrix structure of each layer in the articular cartilage was obtained by SE-EPI sequence with GRAPPA. The MD and FA values of swine articular cartilage are different between the synovial fluid and saline. In human articular cartilage, the load of the body weight on the knee had an effect on the FA value of the surface layer of the articular cartilage.

Conclusion

This method can be used to create images of the articular cartilage structure, not only in vitro but also in vivo. Therefore, it is suggested that this method should support the elucidation of the in vivo structure and function of the knee joint and might be applied to clinical practice.     

Accelerated magnetic resonance imaging using the sparsity of multi-channel coil images

Joint estimation of coil sensitivities and output image (JSENSE) is a promising approach that improves the reconstruction of parallel magnetic resonance imaging (pMRI). However, when acceleration factor increases, the signal to noise ratio (SNR) of JSENSE reconstruction decreases as quickly as that of the conventional pMRI. Although sparse constraints have been used to improve the JSENSE reconstruction in recent years, these constraints only use the sparsity of the output image, which cannot fully exploit the prior information of pMRI. In this paper, we use the sparsity of coil images, instead of the output image, to exploit more prior information for JSENSE. Numerical simulation, phantom and in vivo experiments demonstrate that the proposed method has better performance than the SparseSENSE method and the constrained JSENSE method using the sparsity of the output image only.     

Effect of off-frequency sampling in magnetic resonance elastography

In magnetic resonance elastography (MRE), shear waves at a certain frequency are encoded through bipolar gradients that switch polarity at a controlled encoding frequency and are offset in time to capture wave propagation using a controlled sampling frequency. In brain MRE, there is a possibility that the mechanical actuation frequency is different from the vibration frequency, leading to a mismatch with encoding and sampling frequencies. This mismatch can occur in brain MRE from causes both extrinsic and intrinsic to the brain, such as scanner bed vibrations or active damping in the head. The purpose of this work was to investigate how frequency mismatch can affect MRE shear stiffness measurements. Experiments were performed on a dual-medium agarose gel phantom, and the results were compared with numerical simulations to quantify these effects. It is known that off-frequency encoding alone results in a scaling of wave amplitude, and it is shown here that off-frequency sampling can result in two main effects: (1) errors in the overall shear stiffness estimate of the material on the global scale and (2) local variations appearing as stiffer and softer structures in the material. For small differences in frequency, it was found that measured global stiffness of the brain could theoretically vary by up to 12.5% relative to actual stiffness with local variations of up to 3.7% of the mean stiffness. It was demonstrated that performing MRE experiments at a frequency other than that of tissue vibration can lead to artifacts in the MRE stiffness images, and this mismatch could explain some of the large-scale scatter of stiffness data or lack of repeatability reported in the brain MRE literature.     

On the feasibility of elastic wave visualization within polymeric solids using magnetic resonance elastography

In this paper, the feasibility of extending previously described magnetic resonance elastography (MRE) dynamic displacement (and associated elasticity) measurement techniques, currently used successfully in tissue, to solid materials which have much higher shear rigidity and much lower nuclear spin densities, is considered. Based on these considerations, the MRE technique is modified in a straightforward manner and used to directly visualize shear wave displacements within two polymeric materials, one of which is relatively stiff.     

New technical developments in magnetic resonance imaging of epilepsy

Within the last several years a number of technical developments have been made in magnetic resonance imaging (MRI) that can potentially impact clinical and research MR imaging applications in epilepsy. These include developments in instrumentation and in pulse sequences. Advances in instrumentation include higher capacity gradient systems and multiple receiver coils as directed to brain imaging. Advances in pulse sequence include use of fast or turbo-spin-echo techniques, variants of echo-planar imaging, and sequences such as fluid-attenuation inversion recovery (FLAIR) targeted to specific applications of brain imaging. The purpose of this paper is to review several of these developments.     

Effects of gadoxetic acid on liver elasticity measurement by using magnetic resonance elastography

The purpose of this study was to evaluate the effect of gadoxetic acid (Gd-EOB-DTPA) on measurements of liver stiffness by using magnetic resonance elastography (MRE). In this study, 104 consecutive patients (mean age, 67.7±9.4 years) underwent MRE using a 1.5-T MR scanner equipped with a cylindrical passive driver that was placed across the right chest wall for delivering vibrations. Axial gradient-echo images, which were automatically converted to elastograms that represented stiffness (kPa), were acquired using a continuous sinusoidal vibration of 60 Hz. Two raters independently placed a region of interest on the right lobe of the liver on the elastograms obtained before and after Gd-EOB-DTPA was administered. Liver stiffness was measured using these two elastograms and compared using a paired t test and correlation analysis. No significant difference was observed in liver stiffness before and after Gd-EOB-DTPA was administered (Rater 1, P=.1200; Rater 2, P=.3585). The correlation coefficients were 0.986 (Rater 1) and 0.984 (Rater 2), indicating excellent correlation between the stiffness values before and after Gd-EOB-DTPA was administered. Liver stiffness measured by MRE did not differ before and after Gd-EOB-DTPA was administered.     

In vivo magnetic resonance microscopy of Drosophilae at 9.4 T

In preclinical research, genetic studies have made considerable progress as a result of the development of transgenic animal models of human diseases. Consequently, there is now a need for higher resolution MRI to provide finer details for studies of small animals (rats, mice) or very small animals (insects). One way to address this issue is to work with high-magnetic-field spectrometers (dedicated to small animal imaging) with strong magnetic field gradients. It is also necessary to develop a complete methodology (transmit/receive coil, pulse sequence, fixing system, air supply, anesthesia capabilities, etc.). In this study, we developed noninvasive protocols, both in vitro and in vivo (from coil construction to image generation), for drosophila MRI at 9.4 T. The 10*10*80-μm resolution makes it possible to visualize whole drosophila (head, thorax, abdomen) and internal organs (ovaries, longitudinal and transverse muscles, bowel, proboscis, antennae and optical lobes). We also provide some results obtained with a Drosophila model of muscle degeneration. This opens the way for new applications of structural genetic modification studies using MRI of drosophila.     

Magnetic resonance elastography of the brain in a mouse model of Alzheimer's disease: initial results

The increasing prevalence of Alzheimer's disease (AD) has provided motivation for developing novel methods for assessing the disease and the effects of potential treatments. Magnetic resonance elastography (MRE) is an MRI-based method for quantitatively imaging the shear tissue stiffness in vivo. The objective of this research was to determine whether this new imaging biomarker has potential for characterizing neurodegenerative disease. Methods were developed and tested for applying MRE to evaluate the mouse brain, using a conventional large bore 3.0T MRI system. The technique was then applied to study APP-PS1 mice, a well-characterized model of AD. Five APP-PS1 mice and 8 age-matched wild-type mice were imaged immediately following sacrifice. Brain shear stiffness measurements in APP-PS1 mice averaged 22.5% lower than those for wild-type mice (P = .0031). The results indicate that mouse brain MRE is feasible at 3.0T, and brain shear stiffness has merit for further investigation as a potential new biomarker for Alzheimer's disease.     

Convertible pneumatic actuator for magnetic resonance elastography of the brain

Here we present a novel pneumatic actuator design for brain magnetic resonance elastography (MRE). Magnetic resonance elastography is a phase contrast technique capable of tracing strain wave propagation and utilizing this information for the calculation of mechanical properties of materials and living tissues. In MRE experiments, the acoustic waves are generated in a synchronized way with respect to image acquisition, using various types of mechanical actuators. The unique feature of the design is its simplicity and flexibility, which allows reconfiguration of the actuator for different applications ranging from in vivo brain MRE to experiments with phantoms. Phantom and in vivo data are presented to demonstrate actuator performance.     

In vivo characterization of the aortic wall stress-strain relationship

Arterial stiffness has been shown to be a good indicator of arterial wall disease. However, a single parameter is insufficient to describe the complex stress-strain relationship of a multi-component, non-linear tissue such as the aorta. We therefore propose a new approach to measure the stress-strain relationship locally in vivo noninvasively, and present a clinically relevant parameter describing the mechanical interaction between aortic wall constituents. The slope change of the circumferential stress-strain curve was hypothesized to be related to the contribution of elastin and collagen, and was defined as the transition strain (). A two-parallel spring model was employed and three Young’s moduli were accordingly evaluated, i.e., corresponding to the: elastic lamellae (E₁), elastin-collagen fibers (E₂) and collagen fibers (E₃). Our study was performed on normal and Angiotensin II (AngII)-treated mouse abdominal aortas using the aortic pressure after catheterization and the local aortic wall diameters change from a cross-correlation technique on the radio frequency (RF) ultrasound signal at 30 MHz and frame rate of 8 kHz. Using our technique, the transition strain and three Young’s moduli in both normal and pathological aortas were mapped in 2D. The slope change of the circumferential stress-strain curve was first observed in vivo under physiologic conditions. The transition strain was found at a lower strain level in the AngII-treated case, i.e., 0.029 ± 0.006 for the normal and 0.012 ± 0.004 for the AngII-treated aortas. E₁, E₂ and E₃ were equal to 69.7 ± 18.6, 214.5 ± 65.8 and 144.8 ± 55.2 kPa for the normal aortas, and 222.1 ± 114.8, 775.0 ± 586.4 and 552.9 ± 519.1 kPa for the AngII-treated aortas, respectively. This is because of the alteration of structures and content of the wall constituents, the degradation of elastic lamella and collagen formation due to AngII treatment. While such values illustrate the alteration of structure and content of the wall constituents related to AngII treatment, limitations regarding physical assumptions (isotropic, linear elastic) should be kept in mind. The transition strain, however, was shown to be a pressure independent parameter that can be clinically relevant and noninvasively measured using ultrasound-based motion estimation techniques. In conclusion, our novel methodology can assess the stress-strain relationship of the aortic wall locally in vivo and quantify important parameters for the detection and characterization of vascular disease.     

Characterization of water distribution in bread during storage using magnetic resonance imaging

A soy bread of fully acceptable quality and containing 49% soy ingredients (with or without 5% almond powder) has been recently developed in our laboratory.

An investigation on water distribution and mobility, as probed by proton signal intensity and T₂ magnetic resonance images, during storage was designed to examine possible relations between water states and hindered staling rate upon soy or soy–almond addition.

Water proton distribution throughout soy-containing loaves was found to be very homogeneous in fresh breads with and without almond, with minimal water migration occurring during prolonged storage. In contrast, traditional wheat bread displayed an inhomogeneous water proton population that tended to change (with higher moisture migration towards the outer perimeter of the slice) during storage. Similar results were found for water mobility throughout the loaves, as depicted in T₂ images. On intensity images of all considered bread varieties, the outer perimeter corresponding to the crust exhibited lower signal intensity due to decreased water content. Higher T₂ values were found in the crust of soy breads with and without almond, which were attributed to lipids.

The results indicated that the addition of soy to bread improved the homogeneous distribution of water molecules, which may hinder the staling rate of soy-containing breads. However, incorporation of almond had little effect on the water proton distribution or mobility of soy breads.     

Influence of age and sex on aortic distensibility assessed by MRI in healthy subjects

Magnetic resonance imaging (MRI) is particularly well adapted to the evaluation of aortic distensibility. The calculation of this parameter, based on the change in vessel cross-sectional area per unit change in blood pressure, requires precise delineation of the aortic wall on a series of cine-MR images. Firstly, the study consisted in validating a new automatic method to assess aortic elasticity. Secondly, aortic distensibility was studied for the ascending and descending thoracic aortas in 26 healthy subjects. Two homogeneous groups were available to evaluate the influence of sex and age (with an age limit value of 35 years). The automatic postprocessing method proved to be robust and reliable enough to automatically determine aortic distensibility, even on artefacted images. In the 26 healthy volunteers, a marked decrease in distensibility appears with age, although this decrease is only significant for the ascending aorta (8.97±2.69 10⁻³ mmHg⁻¹ vs. 5.97±2.02 10⁻³ mmHg⁻¹). Women have a higher aortic distensibility than men but only significantly at the level of the descending aorta (7.20±1.61 10⁻³ mmHg⁻¹ vs. 5.05±2.40 10⁻³ mmHg⁻¹). Through our automatic contouring method, the aortic distensibility from routine cine-MRI has been studied on a healthy subject population providing reference values of aortic stiffness. The aortic distensibility calculation shows that age and sex are causes of aortic stiffness variations in healthy subjects.     

Discrimination of components in atherosclerotic plaques from human carotid endarterectomy specimens by magnetic resonance imaging ex vivo

Specific MRI techniques have been used to determine the dimensional and compositional properties of atherosclerotic lesions in carotid endarterectomy tissues. A quantitative comparison of areas of specific features in typical tissue segments was performed using MR images and histologic images. The mean difference for the measurements by the two methods was 4.5% for the total vessel, 5.3% for the internal carotid artery lumen, and 5.0% for the external carotid lumen. For other less abundant components, the mean difference was 14.2%. For direct characterization, individual tissue components were isolated by microdissection and their T1 and T2 relaxation times measured. Highly calcified areas typically had rather short T1 (452-837 ms) and short T2 (10.4-18.4 ms). In contrast, regions enriched in lipid had much longer T1 (1,380-1,480 ms) and longer T2 (35.3-49.0 ms). Other components such as thrombus had intermediate T1 (1,180 ms) and short T2 (15.4 ms). T2 parametric imaging was used as a complementary approach for segmentation and quantitation of tissue components. In fresh tissue, several different components exhibited different T2 ranges: calcified/solid lipid (13-18 ms). cellular/ECM (9-30 ms), fluid lipid (35-40 ms): fibrous (50-60 ms). These results demonstrate the utility of MRI for identifying and quantifying specific components of atherosclerotic plaque ex vivo, and suggest its value for these measurements in vivo as well.     

Characterisation of magnetic resonance imaging (MRI) contrast agents using NMR relaxometry

ABSTRACT

This contribution describes the use of Fast Field-cycling relaxometry (FFC-NMR) for the characterisation of Gd(III)- and Mn(II)-based contrast agents for MRI. Through a series of selected examples, we analyse the role of different structural and dynamic parameters on ¹H relaxivity and on the shape of the ¹H Nuclear Magnetic Relaxation Dispersion (NMRD) profiles. The amplitude and shape of the profiles is affected by the number of water molecules coordinated to the metal ion, the water exchange rate, the rotational correlation time of the complex and the relaxation of the electron spin. As a result, ¹H NMRD profiles represent a powerful tool for the understanding of the properties of MRI contrast agent candidates at the molecular level.     

Co-registration of the distribution of wall shear stress and 140 complex plaques of the aorta

Previous studies provide evidence that atherosclerosis develops in vascular regions exposed to low wall shear stress (WSS) and high oscillatory shear index (OSI). 4D flow MRI was analyzed in 70 stroke patients with complex plaques (≥ 4 mm thickness, ulcerated or superimposed thrombi) and in 12 young healthy volunteers. The segmental distribution of peak systolic WSS_systole and OSI was quantified in analysis planes positioned directly at the location of 140 complex plaques found in the 70 patients. In addition, WSS_systole and OSI were evaluated in 8 standard analysis planes distributed along the aorta. Complex plaques were predominantly found at the inner curvature of the aortic arch and of the descending aorta. High OSI was co-located with the segments mostly affected by complex plaque while WSS_systole demonstrated a homogenous distribution. In standard analysis planes, patients demonstrated significantly (p < 0.01) altered distribution of wall parameters compared to volunteers (reduced WSS_systole in 91% of aortic wall segments, increased OSI in 48% of segments). OSI distribution was asymmetric with higher values at the inner curvature of the aorta. While WSS and OSI showed expected changes in patients compared to healthy controls, their distribution pattern at complex plaques indicated a more complex and heterogeneous relationship than previously anticipated.