Precision and Test-Retest Repeatability of Stiffness Measurement with MR Elastography: A Multicenter Phantom Study.

Background MR elastography (MRE) has been shown to have excellent performance for noninvasive liver fibrosis staging. However, there is limited knowledge regarding the precision and test-retest repeatability of stiffness measurement with MRE in the multicenter setting. Purpose To determine the precision and test-retest repeatability of stiffness measurement with MRE across multiple centers using the same phantoms. Materials and Methods In this study, three cylindrical phantoms made of polyvinyl chloride gel mimicking different degrees of liver stiffness in humans (phantoms 1-3: soft, medium, and hard stiffness, respectively) were evaluated. Between January 2021 and January 2022, phantoms were circulated between five different centers and scanned with 10 MRE-equipped clinical 1.5-T and 3-T systems from three major vendors, using two-dimensional (2D) gradient-recalled echo (GRE) imaging and/or 2D spin-echo (SE) echo-planar imaging (EPI). Similar MRE acquisition parameters, hardware, and reconstruction algorithms were used at each center. Mean stiffness was measured by a single observer for each phantom and acquisition on a single section. Stiffness measurement precision and same-session test-retest repeatability were assessed using the coefficient of variation (CV) and the repeatability coefficient (RC), respectively. Results The mean precision represented by the CV was 5.8% (95% CI: 3.8, 7.7) for all phantoms and both sequences combined. For all phantoms, 2D GRE achieved a CV of 4.5% (95% CI: 3.3, 5.7) whereas 2D SE EPI achieved a CV of 7.8% (95% CI: 3.1, 12.6). The mean RC of stiffness measurement was 5.8% (95% CI: 3.7, 7.8) for all phantoms and both sequences combined, 4.9% (95% CI: 2.7, 7.0) for 2D GRE, and 7.0% (95% CI: 2.9, 11.2) for 2D SE EPI (all phantoms). Conclusion MRE had excellent in vitro precision and same-session test-retest repeatability in the multicenter setting when similar imaging protocols, hardware, and reconstruction algorithms were used. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Tang in this issue.

Magnetic resonance elastography for noninvasive detection of liver fibrosis: is there an added value of 3D acquisition?

PURPOSE: (1) Assess the diagnostic performance of liver 3D magnetic resonance elastography (MRE) parameters (including stiffness, storage/loss modulus and damping ratio) compared to liver stiffness measured with 2D MRE for noninvasive detection of advanced liver fibrosis (F3-F4) and cirrhosis (F4) in patients with chronic liver disease. (2) Assess the value of serum markers (FIB-4) in detecting advanced liver fibrosis and cirrhosis in the same patients. METHODS: This was a single center, prospective IRB-approved cross-sectional study that included 49 patients (M/F: 23/26, mean age 50.8 y) with chronic liver disease and concomitant liver biopsy. MRE was acquired at 1.5T using a spin echo-EPI sequence. The following parameters were measured: liver stiffness using 2D MRE (LS-2D) and 3D MRE parameters (LS-3D, liver storage, loss modulus and damping ratio). The Mann-Whitney U test, ROC curve analysis, Spearman correlation and logistic regression were performed to evaluate diagnostic performance of MRE parameters and FIB-4. RESULTS: LS-2D and LS-3D had similar diagnostic performance for diagnosis of F3-F4, with AUCs of 0.87 and 0.88, sensitivity of 0.71 and 0.81, specificity of 0.89 for both. For diagnosis of F4, LS-2D and LS-3D had similar performance with AUCs of 0.81 for both, sensitivity of 0.75 and 0.83, and specificity of 0.84 and 0.73, respectively. Additional 3D parameters (storage modulus, loss modulus, damping ratio) had variable performance, with AUC range of 0.59-0.78 for F3-F4; and 0.52-0.70 for F4. FIB-4 had lower diagnostic performance, with AUCs of 0.66 for F3-F4, and 0.68 for F4. CONCLUSION: Our study shows no added value of 3D MRE compared to 2D MRE for detection of advanced fibrosis and cirrhosis, while FIB-4 had lower diagnostic performance.

Towards Image Guided Magnetic Resonance Elastography via Active Driver Positioning Robot.

Magnetic Resonance Elastography (MRE) is a developing imaging technique that enables non-invasive estimation of tissue mechanical properties through the combination of induced mechanical displacements in the tissue and Magnetic Resonance Imaging (MRI). The mechanical drivers necessary to produce shear waves in the tissue have been a focus of engineering effort in the development and refinement of MRE. The potential targeting of smaller and stiffer tissues calls for increases in actuation frequency and refinement of mechanical driver positioning. Furthermore, the anisotropic nature of soft tissues results in driver position related changes in observed displacement wave patterns. These challenges motivate the investigation and development of the concept of active MRE driver positioning through visual servoing under MR imaging. OBJECTIVE: This work demonstrates the initial prototype of an MRE driver positioning system, allowing capture of displacement wave patterns from various mechanical vibration loading angles under different vibration frequencies through MR imaging. METHODS: Three different configurations of the MRE driver positioning robot are tested with an intervertebral disc (IVD) shaped gel phantom. RESULTS: Both the octahedral shear stress signal to noise ratio (OSS-SNR) and estimated stiffness show statistically significant dependence on driver configuration in each of the three phantom IVD regions. CONCLUSION: This dependence demonstrates that driver configuration is a critical factor in MRE, and that the developed robot is capable of producing a range of configurations. SIGNIFICANCE: This work presents the first demonstration of an active, imaging guided MRE driver positioning system, with significance for the future application of MRE to a wider range of human tissues.

Design, Construction, and Implementation of a Magnetic Resonance Elastography Actuator for Research Purposes.

Magnetic resonance elastography (MRE) is a technique for determining the mechanical response of soft materials using applied harmonic deformation of the material and a motion-sensitive magnetic resonance imaging sequence. This technique can elucidate significant information about the health and development of human tissue such as liver and brain, and has been used on phantom models (e.g., agar, silicone) to determine their suitability for use as a mechanical surrogate for human tissues in experimental models. The applied harmonic deformation used in MRE is generated by an actuator, transmitted in bursts of a specified duration, and synchronized with the magnetic resonance signal excitation. These actuators are most often a pneumatic design (common for human tissues or phantoms) or a piezoelectric design (common for small animal tissues or phantoms). Here, we describe how to design and assemble both a pneumatic and a piezoelectric MRE actuator for research purposes. For each of these actuator types, we discuss displacement requirements, end-effector options and challenges, electronics and electronic-driving requirements and considerations, and full MRE implementation. We also discuss how to choose the actuator type, size, and power based on the intended material and use. © 2022 Wiley Periodicals LLC. Basic Protocol 1: Design, construction, and implementation of a convertible pneumatic MRE actuator for use with tissues and phantom models Basic Protocol 2: Design, construction, and implementation of a piezoelectric MRE actuator for localized excitation in phantom models.

Predictive Helmet Optimization Framework Based on Reduced-Order Modeling of the Brain Dynamics.

Sports-related traumatic brain injuries (TBIs) are among the leading causes of head injuries in the world. Use of helmets is the main protective measure against this epidemic. The design criteria for the majority of the helmets often only consider the kinematics of the head. This approach neglects the importance of regional deformations of the brain especially near the deep white matter structures such as the corpus callosum (CC) which have been implicated in mTBI studies. In this work, we develop a dynamical reduced-order model of the skull-brain-helmet system to analyze the effect of various helmet parameters on the dynamics of the head and CC. Here, we show that the optimal head-helmet coupling values that minimize the CC dynamics are different from the ones that minimize the skull and brain dynamics (at some kinematics, up to two times stiffer for the head motion mitigation). By comparing our results with experimental impact tests performed on seven different helmets for five different sports, we found that the football helmets with an absorption of about 65-75% of the impact energy had the best performance in mitigating the head motion. Here, we found that none of the helmets are effective in protecting the CC from harmful impact energies. Our computational results reveal that the origin of the difference between the properties of a helmet mitigating the CC motion vs. the head motion is nonlinear vs. linear dynamics. Unlike the globally linear behavior of the head dynamics, we demonstrate that the CC exhibits nonlinear mechanical response similar to an energy sink. This means that there are scenarios where, at the instant of impact, the CC does not undergo extreme motions, but these may occur with a time delay as it absorbs shock energy from other parts of the brain. These findings hint at the importance of considering tissue level dynamics in designing new helmets.

Viscoelasticity of children and adolescent brains through MR elastography.

Magnetic Resonance Elastography (MRE) is an elasticity imaging technique that allows a safe, fast, and non-invasive evaluation of the mechanical properties of biological tissues in vivo. Since mechanical properties reflect a tissue's composition and arrangement, MRE is a powerful tool for the investigation of the microstructural changes that take place in the brain during childhood and adolescence. The goal of this study was to evaluate the viscoelastic properties of the brain in a population of healthy children and adolescents in order to identify potential age and sex dependencies. We hypothesize that because of myelination, age dependent changes in the mechanical properties of the brain will occur during childhood and adolescence. Our sample consisted of 26 healthy individuals (13 M, 13 F) with age that ranged from 7-17 years (mean: 11.9 years). We performed multifrequency MRE at 40, 60, and 80 Hz actuation frequencies to acquire the complex-valued shear modulus G = G' + iG″ with the fundamental MRE parameters being the storage modulus (G'), the loss modulus (G″), and the magnitude of complex-valued shear modulus (|G|). We fitted a springpot model to these frequency-dependent MRE parameters in order to obtain the parameter α, which is related to tissue's microstructure, and the elasticity parameter k, which was converted to a shear modulus parameter (µ) through viscosity (η). We observed no statistically significant variation in the parameter µ, but a significant increase of the microstructural parameter α of the white matter with increasing age (p < 0.05). Therefore, our MRE results suggest that subtle microstructural changes such as neural tissue's enhanced alignment and geometrical reorganization during childhood and adolescence could result in significant biomechanical changes. In line with previously reported MRE data for adults, we also report significantly higher shear modulus (µ) for female brains when compared to males (p < 0.05). The data presented here can serve as a clinical baseline in the analysis of the pediatric and adolescent brain's viscoelasticity over this age span, as well as extending our understanding of the biomechanics of brain development.

MR elastography frequency-dependent and independent parameters demonstrate accelerated decrease of brain stiffness in elder subjects.

OBJECTIVES: To analyze the mechanical properties in different regions of the brain in healthy adults in a wide age range: 26 to 76 years old. METHODS: We used a multifrequency magnetic resonance elastography (MRE) protocol to analyze the effect of age on frequency-dependent (storage and loss moduli, G' and G″, respectively) and frequency-independent parameters (µ1, µ2, and η, as determined by a standard linear solid model) of the cerebral parenchyma, cortical gray matter (GM), white matter (WM), and subcortical GM structures of 46 healthy male and female subjects. The multifrequency behavior of the brain and frequency-independent parameters were analyzed across different age groups. RESULTS: The annual change rate ranged from - 0.32 to - 0.36% for G' and - 0.43 to - 0.55% for G″ for the cerebral parenchyma, cortical GM, and WM. For the subcortical GM, changes in G' ranged from - 0.18 to - 0.23%, and G″ changed - 0.43%. Interestingly, males exhibited decreased elasticity, while females exhibited decreased viscosity with respect to age in some regions of subcortical GM. Significantly decreased values were also found in subjects over 60 years old. CONCLUSION: Values of G' and G″ at 60 Hz and the frequency-independent µ2 of the caudate, putamen, and thalamus may serve as parameters that characterize the aging effect on the brain. The decrease in brain stiffness accelerates in elderly subjects. KEY POINTS: • We used a multifrequency MRE protocol to assess changes in the mechanical properties of the brain with age. • Frequency-dependent (storage moduli G' and loss moduli G″) and frequency-independent (µ1, µ2, and η) parameters can bequantitatively measured by our protocol. • The decreased value of viscoelastic properties due to aging varies in different regions of subcortical GM in males and females, and the decrease in brain stiffness is accelerated in elderly subjects over 60 years old.

Optimization of a Multifrequency Magnetic Resonance Elastography Protocol for the Human Brain.

BACKGROUND AND PURPOSE: The brain's stiffness measurements from magnetic resonance elastography (MRE) strongly depend on actuation frequencies, which makes cross-study comparisons challenging. We performed a preliminary study to acquire optimal sets of actuation frequencies to accurately obtain rheological parameters for the whole brain (WB), white matter (WM), and gray matter (GM). METHODS: Six healthy volunteers aged between 26 and 72 years old went through MRE with a modified single-shot spin-echo echo planar imaging pulse sequence embedded with motion encoding gradients on a 3T scanner. Frequency-independent brain material properties and best-fit material model were determined from the frequency-dependent brain tissue response data (20 -80 Hz), by comparing four different linear viscoelastic material models (Maxwell, Kelvin-Voigt, Springpot, and Zener). During the material fitting, spatial averaging of complex shear moduli (G*) obtained under single actuation frequency was performed, and then rheological parameters were acquired. Since clinical scan time is limited, a combination of three actuation frequencies that would provide the most accurate approximation and lowest fitting error was determined for WB, WM, and GM by optimizing for the lowest Bayesian information criterion (BIC). RESULTS: BIC scores for the Zener and Springpot models showed these models approximate the multifrequency response of the tissue best. The best-fit frequency combinations for the reference Zener and Springpot models were identified to be 30-60-70 and 30-40-80 Hz, respectively, for the WB. CONCLUSIONS: Optimal sets of actuation frequencies to accurately obtain rheological parameters for WB, WM, and GM were determined from shear moduli measurements obtained via 3-dimensional direct inversion. We believe that our study is a first-step in developing a region-specific multifrequency MRE protocol for the human brain.

Magnetic resonance elastography of the brain: A comparison between pigs and humans.

Magnetic resonance elastography holds promise as a non-invasive, easy-to-use, in vivo biomarker for neurodegenerative diseases. Throughout the past decade, pigs have gained increased popularity as large animal models for human neurodegeneration. However, the volume of a pig brain is an order of magnitude smaller than the human brain, its skull is 40% thicker, and its head is about twice as big. This raises the question to which extent established vibration devices, actuation frequencies, and analysis tools for humans translate to large animal studies in pigs. Here we explored the feasibility of using human brain magnetic resonance elastography to characterize the dynamic properties of the porcine brain. In contrast to humans, where vibration devices induce an anterior-posterior displacement recorded in transverse sections, the porcine anatomy requires a dorsal-ventral displacement recorded in coronal sections. Within these settings, we applied a wide range of actuation frequencies, from 40Hz to 90Hz, and recorded the storage and loss moduli for human and porcine brains. Strikingly, we found that optimal actuation frequencies for humans translate one-to-one to pigs and reliably generate shear waves for elastographic post-processing. In a direct comparison, human and porcine storage and loss moduli followed similar trends and increased with increasing frequency. When translating these frequency-dependent storage and loss moduli into the frequency-independent stiffnesses and viscosities of a standard linear solid model, we found human values of µ1=1.3kPa, µ2=2.1kPa, and η=0.025kPas and porcine values of µ1=2.0kPa, µ2=4.9kPa, and η=0.046kPas. These results suggest that living human brain is softer and less viscous than dead porcine brain. Our study compares, for the first time, magnetic resonance elastography in human and porcine brains, and paves the way towards systematic interspecies comparison studies and ex vivo validation of magnetic resonance elastography as a whole.