Mechanobiology of Hyaluronan: Connecting Biomechanics and Bioactivity in Musculoskeletal Tissues.

Hyaluronan (HA) plays well-recognized mechanical and biological roles in articular cartilage and synovial fluid, where it contributes to tissue structure and lubrication. An understanding of how HA contributes to the structure of other musculoskeletal tissues, including muscle, bone, tendon, and intervertebral discs, is growing. In addition, the use of HA-based therapies to restore damaged tissue is becoming more prevalent. Nevertheless, the relationship between biomechanical stimuli and HA synthesis, degradation, and signaling in musculoskeletal tissues remains understudied, limiting the utility of HA in regenerative medicine. In this review, we discuss the various roles and significance of endogenous HA in musculoskeletal tissues. We use what is known and unknown to motivate new lines of inquiry into HA biology within musculoskeletal tissues and in the mechanobiology governing HA metabolism, by suggesting questions that remain regarding the relationship and interaction between biological and mechanical roles of HA in musculoskeletal health and disease. Expected final online publication date for the Annual Review of Biomedical Engineering, Volume 26 is May 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Statistical Characterization of Human Brain Deformation During Mild Angular Acceleration Measured In Vivo by Tagged Magnetic Resonance Imaging.

Understanding of in vivo brain biomechanical behavior is critical in the study of traumatic brain injury (TBI) mechanisms and prevention. Using tagged magnetic resonance imaging, we measured spatiotemporal brain deformations in 34 healthy human volunteers under mild angular accelerations of the head. Two-dimensional (2D) Lagrangian strains were examined throughout the brain in each subject. Strain metrics peaked shortly after contact with a padded stop, corresponding to the inertial response of the brain after head deceleration. Maximum shear strain of at least 3% was experienced at peak deformation by an area fraction (median±standard error) of 23.5±1.8% of cortical gray matter, 15.9±1.4% of white matter, and 4.0±1.5% of deep gray matter. Cortical gray matter strains were greater in the temporal cortex on the side of the initial contact with the padded stop and also in the contralateral temporal, frontal, and parietal cortex. These tissue-level deformations from a population of healthy volunteers provide the first in vivo measurements of full-volume brain deformation in response to known kinematics. Although strains differed in different tissue type and cortical lobes, no significant differences between male and female head accelerations or strain metrics were found. These cumulative results highlight important kinematic features of the brain's mechanical response and can be used to facilitate the evaluation of computational simulations of TBI.

Intervertebral disc internal deformation measured by displacements under applied loading with MRI at 3T.

PURPOSE: Noninvasive assessment of tissue mechanical behavior could enable insights into tissue function in healthy and diseased conditions and permit the development of effective tissue repair treatments. Measurement of displacements under applied loading with MRI (dualMRI) has the potential for such biomechanical characterization on a clinical MRI system. METHODS: dualMRI was translated from high-field research systems to a 3T clinical system. Precision was calculated using repeated tests of a silicone phantom. dualMRI was demonstrated by visualizing displacements and strains in an intervertebral disc and compared to T2 measured during cyclic loading. RESULTS: The displacement and strain precisions were 24 µm and 0.3% strain, respectively, under the imaging parameters used in this study. Displacements and strains were measured within the intervertebral disc, but no correlations were found with the T2 values. CONCLUSION: The translation of dualMRI to a 3T system unveils the potential for in vivo studies in a myriad of tissue and organ systems. Because of the importance of mechanical behavior to the function of a variety of tissues, it's expected that dualMRI implemented on a clinical system will be a powerful tool in assessing the interlinked roles of structure, mechanics, and function in both healthy and diseased tissues.

Pneumatic Non-Equibiaxial Cell Stretching Device With Live-Cell Imaging.

OBJECTIVE: Adherent cell behavior is influenced by a complex interplay of factors, including chemical and mechanical signals. In vitro experiments that mimic the mechanical environment experienced by cells in vivo are crucial for understanding cellular behavior and the progression of disease. In this study, we developed and validated a low-cost pneumatically-controlled cell stretcher with independent control of strain in two directions of a membrane, enabling unequal biaxial stretching and real-time microscopy during actuation. METHODS: The stretching was achieved by two independent pneumatic channels controlled by electrical signals. We used finite element simulations to compute the membrane's strain field and particle tracking algorithms based on image processing techniques to validate the strain fields and measure the cell orientation and morphology. RESULTS: The device can supply uniaxial, equibiaxial, and unequal biaxial stretching up to [Formula: see text] strain in each direction at a frequency of [Formula: see text], with a strain measurement error of less than 1%. Through live cell imaging, we determined that distinct stretching patterns elicited differing responses and alterations in cell orientation and morphology, particularly in terms of cell length and area. CONCLUSION: The device successfully provides a large, uniform, and variable strain field for cell experiments, while also enabling real-time, live cell imaging. SIGNIFICANCE: This scalable, low-cost platform provides mechanical stimulation to cell cultures by independently controlling strains in two directions. This could contribute to a deeper understanding of cellular response to bio-realistic strains and could be useful for future in vitro drug testing platforms.

An Accelerated PETALUTE MRI Sequence for In Vivo Quantification of Sodium Content in Human Articular Cartilage at 3T.

In this work, we demonstrate the sodium magnetic resonance imaging (MRI) capabilities of a three-dimensional (3D) dual-echo ultrashort echo time (UTE) sequence with a novel rosette petal trajectory (PETALUTE), in comparison to the 3D density-adapted (DA) radial spokes UTE sequence. We scanned five healthy subjects using a 3D dual-echo PETALUTE acquisition and two comparable implementations of 3D DA-radial spokes acquisitions, one matching the number of k-space projections (Radial-Matched Trajectories) and the other matching the total number of samples (Radial-Matched Samples) acquired in k-space. The PETALUTE acquisition enabled equivalent sodium quantification in articular cartilage volumes of interest (168.8 ± 29.9 mM) to those derived from the 3D radial acquisitions (171.62 ± 28.7 mM and 149.8 ± 22.2 mM, respectively). We achieved a shorter scan time of 2:06 for 3D PETALUTE, compared to 3:36 for 3D radial acquisitions. We also evaluated the feasibility of further acceleration of the PETALUTE sequence through retrospective compressed sensing with 2× and 4× acceleration of the first echo and showed structural similarity of 0.89 ± 0.03 and 0.87 ± 0.03 when compared to non-retrospectively accelerated reconstruction. Together, these results demonstrate improved scan time with equivalent performance of the PETALUTE sequence compared to the 3D DA-radial sequence for sodium MRI of articular cartilage.

Finite element modeling with subject-specific mechanical properties to assess knee osteoarthritis initiation and progression.

Finite element models of the knee can be used to identify regions at risk of mechanical failure in studies of osteoarthritis. Models of the knee often implement joint geometry obtained from magnetic resonance imaging (MRI) or gait kinematics from motion capture to increase model specificity for a given subject. However, differences exist in cartilage material properties regionally as well as between subjects. This paper presents a method to create subject-specific finite element models of the knee that assigns cartilage material properties from T2 relaxometry. We compared our T2 -refined model to identical models with homogeneous material properties. When tested on three subjects from the Osteoarthritis Initiative data set, we found the T2 -refined models estimated higher principal stresses and shear strains in most cartilage regions and corresponded better to increases in KL grade in follow-ups compared to their corresponding homogeneous material models. Measures of cumulative stress within regions of a T2 -refined model also correlated better with the region's cartilage morphology MRI Osteoarthritis Knee Score as compared with the homogeneous model. We conclude that spatially heterogeneous T2 -refined material properties improve the subject-specificity of finite element models compared to homogeneous material properties in osteoarthritis progression studies. Statement of Clinical Significance: T2 -refined material properties can improve subject-specific finite element model assessments of cartilage degeneration.

Can biomechanics turn youth sports into a venue for informal STEM engagement?

A common pitfall of existing Science, Technology, Engineering, and Math (STEM) outreach programs is that they preferentially engage youth with a preexisting interest in STEM. Biomechanics has the unique potential to broaden access to STEM enrichment due to its direct applicability to sports and human performance. In this study we examine whether biomechanics within youth sports can be used as a venue for STEM outreach, and whether recruiting participants through youth sports programs could broaden access to the STEM pipeline. We created a four-hour sports science clinic that was performed as part of National Biomechanics Day and invited two groups of student participants: youth recruited through local high school sports programs ("Sports Cohort", N = 80) and youth recruited through existing STEM enrichment programs ("STEM Cohort", N = 31). We evaluated interest in STEM, Sports Science, and Sports using a pre-post survey. Somewhat expectedly, youth recruited through sports programs (Sports Cohort) had a lower baseline interest in STEM and a higher baseline interest in sports, compared to those recruited through STEM programs (STEM Cohort). The Sports Cohort exhibited a statistically significant increase in STEM interest following participation in the clinic, while youth in the STEM Cohort maintained their high baseline of STEM interest. These findings provide evidence that youth sports programs can serve as an attractive partner for biomechanists engaged in STEM outreach, and that situating STEM within sports through biomechanical analysis has potential to introduce STEM interest to a wider audience and to broaden access to the STEM fields among diverse youth.

Small-Animal Compression Models of Osteoarthritis.

The utility of nonsurgical, mechanical compression-based joint injury models to study osteoarthritis pathogenesis and treatments is increasing. Joint injury may be induced via cyclic compression loading or acute overloading to induce anterior cruciate ligament rupture. Models utilizing mechanical testing systems are highly repeatable, require little expertise, and result in a predictable onset of osteoarthritis-like pathology on a rapidly progressing timeline. In this chapter, we describe the procedures and equipment needed to perform mechanical compression-induced initiation of osteoarthritis in mice and rats.

Loss of hyaluronan synthases impacts bone morphology, quality, and mechanical properties.

Hyaluronan, a glycosaminoglycan synthesized by three isoenzymes (Has1, Has2, Has3), is known to play a role in regulating bone turnover, remodeling, and mineralization, which in turn can affect bone quality and strength. The goal of this study is to characterize how the loss of Has1 or Has3 affects the morphology, matrix properties, and overall strength of murine bone. Femora were isolated from Has1-/-, Has3-/-, and wildtype (WT) C57Bl/6 J female mice and were analyzed using microcomputed-tomography, confocal Raman spectroscopy, three-point bending, and nanoindentation. Of the three genotypes tested, Has1-/- bones demonstrated significantly lower cross-sectional area (p = 0.0002), reduced hardness (p = 0.033), and lower mineral-to-matrix ratio (p < 0.0001). Has3-/- bones had significantly higher stiffness (p < 0.0001) and higher mineral-to-matrix ratio (p < 0.0001) but lower strength (p = 0.0014) and bone mineral density (p < 0.0001) than WT. Interestingly, loss of Has3 was also associated with significantly lower accumulation of advanced glycation end-products than WT (p = 0.0478). Taken together, these results demonstrate, for the first time, the impact of the loss of hyaluronan synthase isoforms on cortical bone structure, content, and biomechanics. Loss of Has1 impacted morphology, mineralization, and micron-level hardness, while loss of Has3 reduced bone mineral density and affected organic matrix composition, impacting whole bone mechanics. This is the first study to characterize the effect of loss of hyaluronan synthases on bone quality, suggesting an essential role hyaluronan plays during the development and regulation of bone.

Contrast-enhanced micro-computed tomography of compartment and time-dependent changes in femoral cartilage and subchondral plate in a murine model of osteoarthritis.

A lack of understanding of the mechanisms underlying osteoarthritis (OA) progression limits the development of effective long-term treatments. Quantitatively tracking spatiotemporal patterns of cartilage and bone degeneration is critical for assessment of more appropriately targeted OA therapies. In this study, we use contrast-enhanced micro-computed tomography (µCT) to establish a timeline of subchondral plate (SCP) and cartilage changes in the murine femur after destabilization of the medial meniscus (DMM). We performed DMM or sham surgery in 10-12-week-old male C57Bl/6J mice. Femora were imaged using µCT after 0, 2, 4, or 8 weeks. Cartilage-optimized scans were performed after immersion in contrast agent CA4+. Bone mineral density distribution (BMDD), cartilage attenuation, SCP, and cartilage thickness and volume were measured, including lateral and medial femoral condyle and patellar groove compartments. As early as 2 weeks post-DMM, cartilage thickness significantly increased and cartilage attenuation, SCP volume, and BMDD mean significantly decreased. Trends in cartilage and SCP metrics within each joint compartment reflected those seen in global measurements, and both BMDD and SCP thickness were consistently greater in the lateral and medial condyles than the patellar groove. Sham surgery also resulted in significant changes to SCP and cartilage metrics, highlighting a potential limitation of using surgical models to study tissue morphology or composition changes during OA progression. Contrast-enhanced µCT analysis is an effective tool to monitor changes in morphology and composition of cartilage, and when combined with bone-optimized µCT, can be used to assess the progression of degenerative changes after joint injury.

Intervertebral Disc Elastography to Relate Shear Modulus and Relaxometry in Compression and Bending.

Intervertebral disc degeneration is the most recognized cause of low back pain, characterized by the decline of tissue structure and mechanics. Image-based mechanical parameters (e.g., strain, stiffness) may provide an ideal assessment of disc function that is lost with degeneration but unfortunately remains underdeveloped. Moreover, it is unknown whether strain or stiffness of the disc may be predicted by MRI relaxometry (e.g. T1 or T2), an increasingly accepted quantitative measure of disc structure. In this study, we quantified T1 and T2 relaxation times and in-plane strains using displacement-encoded MRI within the disc under physiological levels of compression and bending. We then estimated shear modulus in orthogonal image planes and compared these values to relaxation times and strains within regions of the disc. Intratissue strain depended on the loading mode, and shear modulus in the nucleus pulposus was typically an order of magnitude lower than the annulus fibrosis, except in bending, where the apparent stiffness depended on the loading. Relative shear moduli estimated from strain data derived under compression generally did not correspond with those from bending experiments, with no correlations in the sagittal plane and only 4 of 15 regions correlated in the coronal plane, suggesting that future inverse models should incorporate multiple loading conditions. Strain imaging and strain-based estimation of material properties may serve as imaging biomarkers to distinguish healthy and diseased discs. Additionally, image-based elastography and relaxometry may be viewed as complementary measures of disc structure and function to assess degeneration in longitudinal studies.

Endogenous production of hyaluronan, PRG4, and cytokines is sensitive to cyclic loading in synoviocytes.

Synovial fluid is composed of hyaluronan and proteoglycan-4 (PRG4 or lubricin), which work synergistically to maintain joint lubrication. In diseases like osteoarthritis, hyaluronan and PRG4 concentrations can be altered, resulting in lowered synovial fluid viscosity, and pro-inflammatory cytokine concentrations within the synovial fluid increase. Synovial fibroblasts within the synovium are responsible for contributing to synovial fluid and can be targeted to improve endogenous production of hyaluronan and PRG4 and to alter the cytokine profile. We cyclically loaded SW982 synoviocytes to 0%, 5%, 10%, or 20% strain for three hours at 1 Hz. To assess the impact of substrate stiffness, we compared the 0% strain group to cells grown on tissue culture plastic. We measured the expression of hyaluronan turnover genes, hyaluronan localization within the cell layer, hyaluronan concentration, PRG4 concentration, and the cytokine profile within the media. Our results show that the addition of cyclic loading increased HAS3 expression, but not in a magnitude-dependent response. Hyaluronidase expression was impacted by strain magnitude, which is exemplified by the decrease in hyaluronan concentration due to cyclic loading. We also show that PRG4 concentration is increased at 5% strain, while higher strain magnitude decreases overall PRG4 concentration. Finally, 10% and 20% strain show a distinct, more pro-inflammatory cytokine profile when compared to the unloaded group. Multivariate analysis showed distinct separation between certain strain groups in being able to predict strain group, hyaluronan concentration, and PRG4 concentration from gene expression or cytokine concentration data, highlighting the complexity of the system. Overall, this study shows that cyclic loading can be used tool to modulate the endogenous production of hyaluronan, PRG4, and cytokines from synovial fibroblasts.

T2 Mapping Refined Finite Element Modeling to Predict Knee Osteoarthritis Progression.

This paper presents a novel method for informing cartilage material properties in finite element models from T2 relaxometry. In the developed pipeline, T2 relaxation values are mapped to elements in subject-specific finite element models of the cartilage and menisci. The Young's modulus for each element within the cartilage is directly calculated from its corresponding T2 relaxation voxel value. Our model was tested on a single subject (Subject ID 9932809, Kellgren-Lawrence grade 2) from the Osteoarthritis Initiative dataset at baseline imaging. For comparison, an identical finite element model was built with homogeneous material properties. Kinematics of the stance phase of a standard gait cycle were used as model constraints. Simulation results were compared qualitatively to the MRI Osteoarthritis Knee Score (MOAKS) from the same baseline timepoint. Our T2-refined material model showed higher maximum shear strain in regions with moderate cartilage loss as compared to the homogeneous material model, and the homogeneous model showed higher maximum principal stress and maximum shear strain in regions with no cartilage loss. These results show that a homogeneous material model likely underestimates tissue strains in regions with cartilage damage while overestimating strains in regions with healthy cartilage. This preliminary study demonstrates that T2-refined material properties are more appropriate than assumptions of homogeneity in predictive models of cartilage damage.Clinical relevance- The proposed pipeline demonstrates a computationally efficient way to improve the subject-specificity of finite element models used for evaluation of osteoarthritis.

Articular cartilage deformation determined in an intact tibiofemoral joint by displacement-encoded imaging.

This study demonstrates the in vitro displacement and strain of articular cartilage in a cyclically-compressed and intact joint using displacement-encoded imaging with stimulated echoes (DENSE) and fast spin echo (FSE). Deformation and strain fields exhibited complex and heterogeneous patterns. The displacements in the loading direction ranged from -1688 to -1481 microm in the tibial cartilage and from -1601 to -764 microm in the femoral cartilage. Corresponding strains ranged from -9.8% to 0.7% and from -4.3% to 0.0%. The displacement and strain precision were determined to be 65 microm and less than 0.2%, respectively. Displacement-encoded magnetic resonance imaging is capable of determining the nonuniform displacements and strains in the articular cartilage of an intact joint to a high precision. Knowledge of these nonuniform strains is critical for the in situ characterization of normal and diseased tissue, as well as the comprehensive evaluation of repair constructs designed using regenerative medicine.

Functional MRI can detect changes in intratissue strains in a full thickness and critical sized ovine cartilage defect model.

Functional imaging of tissue biomechanics can reveal subtle changes in local softening and stiffening associated with disease or repair, but noninvasive and nondestructive methods to acquire intratissue measures in well-defined animal models are largely lacking. We utilized displacement encoded MRI to measure changes in cartilage deformation following creation of a critical-sized defect in the medial femoral condyle of ovine (sheep) knees, a common in situ and large animal model of tissue damage and repair. We prioritized visualization of local, site-specific variation and changes in displacements and strains following defect placement by measuring spatial maps of intratissue deformation. Custom data smoothing algorithms were developed to minimize propagation of noise in the acquired MRI phase data toward calculated displacement or strain, and to improve strain measures in high aspect ratio tissue regions. Strain magnitudes in the femoral, but not tibial, cartilage dramatically increased in load-bearing and contact regions especially near the defect locations, with an average 6.7% ±â€¯6.3%, 13.4% ±â€¯10.0%, and 10.0% ±â€¯4.9% increase in first and second principal strains, and shear strain, respectively. Strain heterogeneity reflected the complexity of the in situ mechanical environment within the joint, with multiple tissue contacts defining the deformation behavior. This study demonstrates the utility of displacement encoded MRI to detect increased deformation patterns and strain following disruption to the cartilage structure in a clinically-relevant, large animal defect model. It also defines imaging biomarkers based on biomechanical measures, in particular shear strain, that are potentially most sensitive to evaluate damage and repair, and that may additionally translate to humans in future studies.

Pirfenidone reduces subchondral bone loss and fibrosis after murine knee cartilage injury.

Pirfenidone is an anti-inflammatory and anti-fibrotic drug that has shown efficacy in lung and kidney fibrosis. Because inflammation and fibrosis have been linked to the progression of osteoarthritis, we investigated the effects of oral Pirfenidone in a mouse model of cartilage injury, which results in chronic inflammation and joint-wide fibrosis in mice that lack hyaluronan synthase 1 (Has1-/- ) in comparison to wild-type. Femoral cartilage was surgically injured in wild-type and Has1-/- mice, and Pirfenidone was administered in food starting after 3 days. At 4 weeks, Pirfenidone reduced the appearance, on micro-computed tomography, of pitting in subchondral bone at, and cortical bone surrounding, the site of cartilage injury. This corresponded with a reduction in fibrotic tissue deposits as observed with gross joint surface photography. Pirfenidone resulted in significant recovery of trabecular bone parameters affected by joint injury in Has1-/- mice, although the effect in wild-type was less pronounced. Pirfenidone also increased Safranin-O staining of growth plate cartilage after cartilage injury and sham operation in both genotypes. Taken together with the expression of selected extracellular matrix, inflammation, and fibrosis genes, these results indicate that Pirfenidone may confer chondrogenic and bone-protective effects, although the well-known anti-fibrotic effects of Pirfenidone may occur earlier in the wound-healing response than the time point examined in this study. Further investigations to identify the specific cell populations in the joint and signaling pathways that are responsive to Pirfenidone are warranted, as Pirfenidone and other anti-fibrotic drugs may encourage tissue repair and prevent progression of post-traumatic osteoarthritis. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:365-376, 2018.

Development of residual strains in human vertebral trabecular bone after prolonged static and cyclic loading at low load levels.

Development of irreversible residual strains in trabecular bone may be a mechanism by which age-related non-traumatic vertebral fractures occur. To investigate this concept, static and cyclic loading tests were conducted at low loading levels for cylindrical cores of cadaveric vertebral trabecular bone. Stresses were applied equivalent to elastic strains of either 750 or 1,500 microstrain. Creep strains were measured during the tests, which lasted for 125,000 seconds (about 35 h), and for an additional 125,000 seconds after complete unloading. Emphasis was placed on the residual strains that developed, defined as the strain remaining at the end of the unloading phase. The results indicated that appreciable residual strains did develop, and were similar for static and cyclic loading. Irrespective of the applied load levels and loading modes, the residual strains that remained after the unloading phase were similar in magnitude to the originally applied elastic strain. Extrapolation of the observed residual strains to full recovery indicated that the time that would be required for full recovery was over 20 times longer than the duration of the applied loads. These results indicate that human vertebral trabecular bone does not creep in a linear viscoelastic fashion at low stress levels, and that creep mechanisms dominate the residual strains regardless of the loading mode. Taken together, these findings support the concept that non-traumatic vertebral fractures may be related to long-term creep effects because the trabecular bone does not have sufficient time to recover mechanically from creep deformations accumulated by prolonged static or cyclic loading.

In vivo articular cartilage deformation: noninvasive quantification of intratissue strain during joint contact in the human knee.

The in vivo measurement of articular cartilage deformation is essential to understand how mechanical forces distribute throughout the healthy tissue and change over time in the pathologic joint. Displacements or strain may serve as a functional imaging biomarker for healthy, diseased, and repaired tissues, but unfortunately intratissue cartilage deformation in vivo is largely unknown. Here, we directly quantified for the first time deformation patterns through the thickness of tibiofemoral articular cartilage in healthy human volunteers. Magnetic resonance imaging acquisitions were synchronized with physiologically relevant compressive loading and used to visualize and measure regional displacement and strain of tibiofemoral articular cartilage in a sagittal plane. We found that compression (of 1/2 body weight) applied at the foot produced a sliding, rigid-body displacement at the tibiofemoral cartilage interface, that loading generated subject- and gender-specific and regionally complex patterns of intratissue strains, and that dominant cartilage strains (approaching 12%) were in shear. Maximum principle and shear strain measures in the tibia were correlated with body mass index. Our MRI-based approach may accelerate the development of regenerative therapies for diseased or damaged cartilage, which is currently limited by the lack of reliable in vivo methods for noninvasive assessment of functional changes following treatment.

Comparison of intervertebral disc displacements measured under applied loading with MRI at 3.0 T and 9.4 T.

The purpose of this study was to compare displacement behavior of cyclically loaded cadaveric human intervertebral discs as measured noninvasively on a clinical 3.0 T and a research 9.4 T MRI system. Intervertebral discs were cyclically compressed at physiologically relevant levels with the same MRI-compatible loading device in the clinical and research systems. Displacement-encoded imaging was synchronized to cyclic loading to measure displacements under applied loading with MRI (dual MRI). Displacements from the two systems were compared individually using linear regression and, across all specimens, using Bland-Altman analysis. In-plane displacement patterns measured at 3.0 T and 9.4 T were qualitatively comparable and well correlated. Bland-Altman analyses showed that over 90% of displacement values within the intervertebral disc regions of interest lay within the limits of agreement. Measurement of displacement using dual MRI using a 3.0 T clinical system is comparable to that of a 9.4 T research system. Additional refinements of software, technique implementation, and image processing have potential to improve agreement between different MRI systems. Despite differences in MRI systems in this initial implementation, this work demonstrates that dual MRI can be reliably implemented at multiple magnetic field strengths, permitting translation of dual MRI for a variety of applications in the study of tissue and biomaterial biomechanics.