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.

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.

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.

Characterization of cancellous and cortical bone strain in the in vivo mouse tibial loading model using microCT-based finite element analysis.

The in vivo mouse tibial loading model has been increasingly used to understand the mechanisms governing the mechanobiological responses of cancellous and cortical bone tissues to physical stimuli. Accurate characterization of the strain environment throughout the tibia is fundamental in relating localized mechanobiological processes to specific strain stimuli in the skeleton. MicroCT-based finite element analysis, together with diaphyseal strain gauge measures, was conducted to quantify the strain field in the tibiae of 16-wk-old female C57Bl/6 mice during in vivo dynamic compressive loading. Despite a strong correlation between the experimentally-measured and computationally-modeled strains at the gauge site, no correlations existed between the strain at the gauge site and the peak strains in the proximal cancellous and midshaft cortical bone, indicating the limitations of using a single diaphyseal strain gauge to estimate strain in the entire tibia. The peak compressive and tensile principal strain magnitudes in the proximal cancellous bone were 10% and 34% lower than those in the midshaft cortical bone. Sensitivity analyses showed that modeling bone tissue as a heterogeneous material had a strong effect on cancellous strain characterization while cortical strain and whole-bone stiffness were primarily affected by the presence of the fibula and the proximal boundary conditions. These results show that microCT-based finite element analysis combined with strain gauge measures provides detailed resolution of the tissue-level strain in both the cancellous and cortical bones of the mouse tibia during in vivo compression loading, which is necessary for interpreting localized patterns of modeling/remodeling and, potentially, gene and protein expression in skeletal mechanobiology studies.

Prestress as an optimal biomechanical parameter for needle penetration.

Drug delivery requires precise intradermal and subcutaneous injections of formulations to clinically relevant penetration depths. However, penetration depth is confounded by skin deflection, which occurs prior to and during penetration as the skin surface deforms axially with the needle, and which varies profoundly due to differing intrinsic mechanical (e.g. viscoelastic) tissue properties, disease state, aging, and ethnicity. Herein, an ex vivo model was utilized to study factors that affect skin deflection and the efficacy of injection, including prestress applied at the tissue surface, needle gauge, velocity, and actuation depth. The application of prestress minimized skin deflection during needle penetration and allowed for needle actuation to the targeted penetration depths with minimum variability. The force required to achieve target penetration depths was found to increase with prestress and decrease with needle gauge. Our findings emphasize the need for prestress applied to the skin surface to minimize variation in skin properties and administer formulations for intradermal and subcutaneous treatments with maximum precision.

A biomechanical analysis of finger joint forces and stresses developed during common daily activities.

The problem of modelling stresses incurred at the finger joints is critical to the design of durable joint replacements in the hand. The goal of this study was to characterise the forces and stresses at the finger and thumb joints occurring during activities such as typing at a keyboard, playing piano, gripping a pen, carrying a weight and opening a jar. The metacarpal and proximal phalanx were modelled using a COMSOL-based finite element analysis. Analysis of these activities indicates that joint forces in excess of 100 N may be common at the metacarpophalangeal joint (MCP) due to carrying objects such as groceries or while opening jars. The model predicted that stresses in excess of 2 MPa, similar to stresses at the hip, occur at the MCP with the properties of cancellous bone playing a significant role in the magnitude and distribution of stress.

A three-dimensional finite element analysis of finger joint stresses in the MCP joint while performing common tasks.

The goal of this study was to develop a three-dimensional finite element model of the metacarpophalangeal (MCP) joint to characterize joint contact stresses incurred during common daily activities. The metacarpal and proximal phalanx were modeled using a COMSOL-based finite element analysis. Muscle forces determined from a static force analysis of two common activities (pen grip and carrying a weight) were applied to the simulation to characterize the surface stress distributions at the MCP joint. The finite element analysis predicted that stresses as high as 1.9 MPa, similar in magnitude to stresses experienced at the hip, may be experienced by the subchondral bone in the MCP joint. The internal structure and material properties of the phalanges were found to play a significant role in both the magnitude and distribution of stresses, but the dependence on cancellous bone modulus was not as severe as predicted by previous two dimensional models.

Stress distributions and material properties determined in articular cartilage from MRI-based finite strains.

The noninvasive measurement of finite strains in biomaterials and tissues by magnetic resonance imaging (MRI) enables mathematical estimates of stress distributions and material properties. Such methods allow for non-contact and patient-specific modeling in a manner not possible with traditional mechanical testing or finite element techniques. Here, we employed three constitutive (i.e. linear Hookean, and nonlinear Neo-Hookean and Mooney-Rivlin) relations with known loading conditions and MRI-based finite strains to estimate stress patterns and material properties in the articular cartilage of tibiofemoral joints. Displacement-encoded MRI was used to determine two-dimensional finite strains in juvenile porcine joints, and an iterative technique estimated stress distributions and material properties with defined constitutive relations. Stress distributions were consistent across all relations, although the stress magnitudes varied. Material properties for femoral and tibial cartilage were found to be consistent with those reported in literature. Further, the stress estimates from Hookean and Neo-Hookean, but not Mooney-Rivlin, relations agreed with finite element-based simulations. A nonlinear Neo-Hookean relation provided the most appropriate model for the characterization of complex and spatially dependent stresses using two-dimensional MRI-based finite strain. These results demonstrate the feasibility of a new and computationally efficient technique incorporating MRI-based deformation with mathematical modeling to non-invasively evaluate the mechanical behavior of biological tissues and materials.