Developing an experimental-computational workflow to study the biomechanics of the human conventional aqueous outflow pathway.

The aqueous humor actively interacts with the trabecular meshwork (TM), juxtacanalicular tissue (JCT), and Schlemm's canal (SC) through a dynamic fluid-structure interaction (FSI) coupling. Despite the fact that intraocular pressure (IOP) undergoes significant fluctuations, our understanding of the hyperviscoelastic biomechanical properties of the aqueous outflow tissues is limited. In this study, a quadrant of the anterior segment from a normal human donor eye was dynamically pressurized in the SC lumen, and imaged using a customized optical coherence tomography (OCT). The TM/JCT/SC complex finite element (FE) with embedded collagen fibrils was reconstructed based on the segmented boundary nodes in the OCT images. The hyperviscoelastic mechanical properties of the outflow tissues' extracellular matrix with embedded viscoelastic collagen fibrils were calculated using an inverse FE-optimization method. Thereafter, the 3D microstructural FE model of the TM, with adjacent JCT and SC inner wall, from the same donor eye was constructed using optical coherence microscopy and subjected to a flow load-boundary from the SC lumen. The resultant deformation/strain in the outflow tissues was calculated using the FSI method, and compared to the digital volume correlation (DVC) data. TM showed larger shear modulus (0.92 MPa) compared to the JCT (0.47 MPa) and SC inner wall (0.85 MPa). Shear modulus (viscoelastic) was larger in the SC inner wall (97.65 MPa) compared to the TM (84.38 MPa) and JCT (56.30 MPa). The conventional aqueous outflow pathway is subjected to a rate-dependent IOP load-boundary with large fluctuations. This necessitates addressing the biomechanics of the outflow tissues using hyperviscoelastic material-model. STATEMENT OF SIGNIFICANCE: While the human conventional aqueous outflow pathway is subjected to a large-deformation and time-dependent IOP load-boundary, we are not aware of any studies that have calculated the hyperviscoelastic mechanical properties of the outflow tissues with embedded viscoelastic collagen fibrils. A quadrant of the anterior segment of a normal humor donor eye was dynamically pressurized from the SC lumen with relatively large fluctuations. The TM/JCT/SC complex were OCT imaged and the mechanical properties of the tissues with embedded collagen fibrils were calculated using the inverse FE-optimization algorithm. The resultant displacement/strain in the FSI outflow model was validated versus the DVC data. The proposed experimental-computational workflow may significantly contribute to understanding of the effects of different drugs on the biomechanics of the conventional aqueous outflow pathway.

Characterisation of Single-Phase Fluid-Flow Heterogeneity Due to Localised Deformation in a Porous Rock Using Rapid Neutron Tomography.

The behaviour of subsurface-reservoir porous rocks is a central topic in the resource engineering industry and has relevant applications in hydrocarbon, water production, and CO2 sequestration. One of the key open issues is the effect of deformation on the hydraulic properties of the host rock and, specifically, in saturated environments. This paper presents a novel full-field data set describing the hydro-mechanical properties of porous geomaterials through in situ neutron and X-ray tomography. The use of high-performance neutron imaging facilities such as CONRAD-2 (Helmholtz-Zentrum Berlin) allows the tracking of the fluid front in saturated samples, making use of the differential neutron contrast between "normal" water and heavy water. To quantify the local hydro-mechanical coupling, we applied a number of existing image analysis algorithms and developed an array of bespoke methods to track the water front and calculate the 3D speed maps. The experimental campaign performed revealed that the pressure-driven flow speed decreases, in saturated samples, in the presence of pre-existing low porosity heterogeneities and compactant shear-bands. Furthermore, the observed complex mechanical behaviour of the samples and the associated fluid flow highlight the necessity for 3D imaging and analysis.

Dual modality neutron and x-ray tomography for enhanced image analysis of the bone-metal interface.

The bone tissue formed at the contact interface with metallic implants, particularly its 3D microstructure, plays a pivotal role for the structural integrity of implant fixation. X-ray tomography is the classical imaging technique used for accessing microstructural information from bone tissue. However, neutron tomography has shown promise for visualising the immediate bone-metal implant interface, something which is highly challenging with x-rays due to large differences in attenuation between metal and biological tissue causing image artefacts. To highlight and explore the complementary nature of neutron and x-ray tomography, proximal rat tibiae with titanium-based implants were imaged with both modalities. The two techniques were compared in terms of visualisation of different material phases and by comparing the properties of the individual images, such as the contrast-to-noise ratio. After superimposing the images using a dedicated image registration algorithm, the complementarity was further investigated via analysis of the dual modality histogram, joining the neutron and x-ray data. From these joint histograms, peaks with well-defined grey value intervals corresponding to the different material phases observed in the specimens were identified and compared. The results highlight differences in how neutrons and x-rays interact with biological tissues and metallic implants, as well as the benefits of combining both modalities. Future refinement of the joint histogram analysis could improve the segmentation of structures and tissues, and yield novel information about specimen-specific properties such as moisture content.

Bone Damage Evolution Around Integrated Metal Screws Using X-Ray Tomography - in situ Pullout and Digital Volume Correlation.

Better understanding of the local deformation of the bone network around metallic implants subjected to loading is of importance to assess the mechanical resistance of the bone-implant interface and limit implant failure. In this study, four titanium screws were osseointegrated into rat tibiae for 4 weeks and screw pullout was conducted in situ under x-ray microtomography, recording macroscopic mechanical behavior and full tomographies at multiple load steps before failure. Images were analyzed using Digital Volume Correlation (DVC) to access internal displacement and deformation fields during loading. A repeatable failure pattern was observed, where a ∼300-500 µm-thick envelope of bone detached from the trabecular structure. Fracture initiated close to the screw tip and propagated along the implant surface, at a distance of around 500 µm. Thus, the fracture pattern appeared to be influenced by the microstructure of the bone formed closely around the threads, which confirmed that the model is relevant for evaluating the effect of pharmacological treatments affecting local bone formation. Moreover, cracks at the tibial plateau were identified by DVC analysis of the tomographic images acquired during loading. Moderate strains were first distributed in the trabecular bone, which localized into higher strains regions with subsequent loading, revealing crack-formation not evident in the tomographic images. The in situ loading methodology followed by DVC is shown to be a powerful tool to study internal deformation and fracture behavior of the newly formed bone close to an implant when subjected to loading. A better understanding of the interface failure may help improve the outcome of surgical implants.

Sub-trabecular strain evolution in human trabecular bone.

To comprehend the most detrimental characteristics behind bone fractures, it is key to understand the material and tissue level strain limits and their relation to failure sites. The aim of this study was to investigate the three-dimensional strain distribution and its evolution during loading at the sub-trabecular level in trabecular bone tissue. Human cadaver trabecular bone samples were compressed in situ until failure, while imaging with high-resolution synchrotron radiation X-ray tomography. Digital volume correlation was used to determine the strains inside the trabeculae. Regions without emerging damage were compared to those about to crack. Local strains in close vicinity of developing cracks were higher than previously reported for a whole trabecular structure and similar to those reported for single isolated trabeculae. Early literature on bone fracture strain thresholds at the tissue level seem to underestimate the maximum strain magnitudes in trabecular bone. Furthermore, we found lower strain levels and a reduced ability to capture detailed crack-paths with increased image voxel size. This highlights the dependence between the observed strain levels and the voxel size and that high-resolution is needed to investigate behavior of individual trabeculae. Furthermore, low trabecular thickness appears to be one predictor of developing cracks. In summary, this study investigated the local strains in whole trabecular structure at sub-trabecular resolution in human bone and confirmed the high strain magnitudes reported for single trabeculae under loading and, importantly extends its translation to the whole trabecular structure.

Investigating the Mechanical Characteristics of Bone-Metal Implant Interface Using in situ Synchrotron Tomographic Imaging.

Long-term stability of endosseous implants depends on successful bone formation, ingrowth and adaptation to the implant. Specifically, it will define the mechanical properties of the newly formed bone-implant interface. 3D imaging during mechanical loading tests (in situ loading) can improve the understanding of the local processes leading to bone damage and failure. In this study, titanium screws were implanted into rat tibiae and were allowed to integrate for 4 weeks with or without the addition of the growth factor Bone Morphogenetic Protein and the bisphosphonate Zoledronic Acid. Samples were subjected to in situ pullout using high-resolution synchrotron x-ray tomography at the Tomcat beamline (SLS, PSI, Switzerland) at 30 keV with 25 ms exposure time, resulting in a total acquisition time of 45 s per scan, with a 3.6 µm isotropic voxel size. Using a custom-made loading device positioned inside the beamline, screws were pulled out with 0.05 mm increment, acquiring multiple scans until rupture of the sample. The in situ loading protocol was adapted to ensure short imaging time, which enabled multiple samples to be tested with short loading steps, while keeping the total testing time low and reducing dose deposition. Higher trabecular bone content was quantified in the surrounding of the screw in the treated groups, which correlated with increased mechanical strength and stiffness. Differences in screw implantation, such as contact between threads and cortex as well as minor tilt of the screw were also correlated to the mechanical parameters. In situ loading enabled the investigation of crack propagation during the pullout, highlighting the mechanical behavior of the interface. Three typical crack types were observed: (1) rupture at the interface of trabecular and cortical bone tissues, close to the screw, (2) large crack inside the cortex connected to the implant, and (3) first failure away from the screw with cracks propagating toward the screw-bone interface. Mechanical properties of in vivo integrated bone-metal screws rely on a combination of multiple parameters that are difficult to identify and separate one from the other.

Characterization of the bone-metal implant interface by Digital Volume Correlation of in-situ loading using neutron tomography.

Metallic implants are commonly used as surgical treatments for many orthopedic conditions. The long-term stability of implants relies on an adequate integration with the surrounding bone. Unsuccessful integration could lead to implant loosening. By combining mechanical loading with high-resolution 3D imaging methods, followed by image analysis such as Digital Volume Correlation (DVC), we aim at evaluating ex vivo the mechanical resistance of newly formed bone at the interface. X-rays tomography is commonly used to image bone but induces artefacts close to metallic components. Utilizing a different interaction with matter, neutron tomography is a promising alternative but has not yet been used in studies of bone mechanics. This work demonstrates that neutron tomography during in situ loading is a feasible tool to characterize the mechanical response of bone-implant interfaces, especially when combined with DVC. Experiments were performed where metal screws were implanted in rat tibiae during 4 weeks. The screws were pulled-out while the samples were sequentially imaged in situ with neutron tomography. The images were analyzed to quantify bone ingrowth around the implants. DVC was used to track the internal displacements and calculate the strain fields in the bone during loading. The neutron images were free of metal-related artefacts, which enabled accurate quantification of bone ingrowth on the screw (ranging from 60% to 71%). DVC allowed successful identification of the deformation and cracks that occurred during mechanical loading and led to final failure of the bone-implant interface.

Neutron tomographic imaging of bone-implant interface: Comparison with X-ray tomography.

Metal implants, in e.g. joint replacements, are generally considered to be a success. As mechanical stability is important for the longevity of a prosthesis, the biological reaction of the bone to the mechanical loading conditions after implantation and during remodelling determines its fate. The bone reaction at the implant interface can be studied using high-resolution imaging. However, commonly used X-ray imaging suffers from image artefacts in the close proximity of metal implants, which limit the possibility to closely examine the bone at the bone-implant interface. An alternative ex vivo 3D imaging method is offered by neutron tomography. Neutrons interact with matter differently than X-rays; therefore, this study explores if neutron tomography may be used to enrich studies on bone-implant interfaces. A stainless steel screw was implanted in a rat tibia and left to integrate for 6weeks. After extracting the tibia, the bone-screw construct was imaged using X-ray and neutron tomography at different resolutions. Artefacts were visible in all X-ray images in the close proximity of the implant, which limited the ability to accurately quantify the bone around the implant. In contrast, neutron images were free of metal artefacts, enabling full analysis of the bone-implant interface. Trabecular structural bone parameters were quantified in the metaphyseal bone away from the implant using all imaging modalities. The structural bone parameters were similar for all images except for the lowest resolution neutron images. This study presents the first proof-of-concept that neutron tomographic imaging can be used for ex-vivo evaluation of bone microstructure and that it constitutes a viable, new tool to study the bone-implant interface tissue remodelling.

Quantifying Bulk Electrode Strain and Material Displacement within Lithium Batteries via High-Speed Operando Tomography and Digital Volume Correlation.

Tracking the dynamic morphology of active materials during operation of lithium batteries is essential for identifying causes of performance loss. Digital volume correlation (DVC) is applied to high-speed operando synchrotron X-ray computed tomography of a commercial Li/MnO2 primary battery during discharge. Real-time electrode material displacement is captured in 3D allowing degradation mechanisms such as delamination of the electrode from the current collector and electrode crack formation to be identified. Continuum DVC of consecutive images during discharge is used to quantify local displacements and strains in 3D throughout discharge, facilitating tracking of the progression of swelling due to lithiation within the electrode material in a commercial, spiral-wound battery during normal operation. Displacement of the rigid current collector and cell materials contribute to severe electrode detachment and crack formation during discharge, which is monitored by a separate DVC approach. Use of time-lapse X-ray computed tomography coupled with DVC is thus demonstrated as an effective diagnostic technique to identify causes of performance loss within commercial lithium batteries; this novel approach is expected to guide the development of more effective commercial cell designs.

Timelapse ultrasonic tomography for measuring damage localization in geomechanics laboratory tests.

Variation of mechanical properties in materials can be detected non-destructively using ultrasonic measurements. In particular, changes in elastic wave velocity can occur due to damage, i.e., micro-cracking and particles debonding. Here the challenge of characterizing damage in geomaterials, i.e., rocks and soils, is addressed. Geomaterials are naturally heterogeneous media in which the deformation can localize, so that few measurements of acoustic velocity across the sample are not sufficient to capture the heterogeneities. Therefore, an ultrasonic tomography procedure has been implemented to map the spatial and temporal variations in propagation velocity, which provides information on the damage process. Moreover, double beamforming has been successfully applied to identify and isolate multiple arrivals that are caused by strong heterogeneities (natural or induced by the deformation process). The applicability of the developed experimental technique to laboratory geomechanics testing is illustrated using data acquired on a sample of natural rock before and after being deformed under triaxial compression. The approach is then validated and extended to time-lapse monitoring using data acquired during plane strain compression of a sample including a well defined layer with different mechanical properties than the matrix.