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IN THIS ISSUE

### Research Papers

J Biomech Eng. 2009;131(6):061001-061001-6. doi:10.1115/1.3116155.

Understanding the complex relationships between microstructural organization and macromechanical function is fundamental to our knowledge of the differences between normal, diseased/injured, and healing connective tissues. The long-term success of functional tissue-engineered constructs or scaffolds may largely depend on our understanding of the structural organization of the original tissue. Although innovative techniques have been used to characterize and measure the microstructural properties of collagen fibers, a large gap remains in our knowledge of the behavior of intermediate scale (i.e., “mesostructural”) groups of fiber bundles in larger tissue samples. The objective of this study was to develop a system capable of directly measuring deformations of these smaller mesostructures during application of controlled loads. A novel mesostructural testing system (MSTS) has been developed to apply controlled multiaxial loads to medium (meso-) scale tissue specimens, while directly measuring local nonuniform deformations using synchronized digital video capture and “markerless” image correlation. A novel component of the MSTS is the use of elliptically polarized light to enhance collagen fiber contrast, providing the necessary texture for accurate markerless feature tracking of local fiber deformations. In this report we describe the components of the system, its calibration and validation, and the results from two different tissues: the porcine aortic valve cusp and the bovine pericardium. Validation tests on prepared samples showed maximum error of direct strain measurement to be 0.3%. Aortic valve specimens were found to have larger inhomogeneous strains during tensile testing than bovine pericardium. Clamping effects were more pronounced for the valve specimens. A new system for direct internal strain measurement in connective tissues during application of controlled loads has been developed and validated. The results from the two different tissues show that significant inhomogeneous deformations can occur even in simple tensile testing experiments.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2009;131(6):061002-061002-9. doi:10.1115/1.3118771.

When designing a medical device based on lightweight accelerometers, the designer is faced with a number of questions in order to maximize performance while minimizing cost and complexity: Where should the inertial unit be located? How many units are required? How is performance affected if the unit is not correctly located during donning? One way to answer these questions is to use position data from a single trial, captured with a nonportable measurement system (e.g., stereophotogrammetry) to simulate measurements from multiple accelerometers at different locations on the body. In this paper, we undertake a thorough investigation into the applicability of these simulated acceleration signals via a series of interdependent experiments of increasing generality. We measured the dynamics of a reference coordinate frame using stereophotogrammetry over a number of trials. These dynamics were then used to simulate several “virtual” accelerometers at different points on the body segment. We then compared the simulated signals with those directly measured to evaluate the error under a number of conditions. Finally, we demonstrated an example of how simulated signals can be employed in a system design application. In the best case, we may expect an error of $0.028 m/s2$ between a derived virtual signal and that directly measured by an accelerometer. In practice, however, using centripetal and tangential acceleration terms (that are poorly estimated) results in an error that is an order of magnitude greater than the baseline. Furthermore, nonrigidity of the limb can increase error dramatically, although the effects can be reduced considerably via careful modeling. We conclude that using simulated signals has definite benefits when an appropriate model of the body segment is applied.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2009;131(6):061003-061003-10. doi:10.1115/1.3118773.

Cartilage is a hydrated soft tissue whose solid matrix consists of negatively charged proteoglycans enmeshed within a fibrillar collagen network. Though many aspects of cartilage mechanics are well understood today, most notably in the context of porous media mechanics, there remain a number of responses observed experimentally whose prediction from theory has been challenging. In this study the solid matrix of cartilage is modeled with a continuous fiber angular distribution, where fibers can only sustain tension, swelled by the osmotic pressure of a proteoglycan ground matrix. It is shown that this representation of cartilage can predict a number of observed phenomena in relation to the tissue’s equilibrium response to mechanical and osmotic loading, when flow-dependent and flow-independent viscoelastic effects have subsided. In particular, this model can predict the transition of Poisson’s ratio from very low values in compression $(∼0.02)$ to very high values in tension $(∼2.0)$. Most of these phenomena cannot be explained when using only three orthogonal fiber bundles to describe the tissue matrix, a common modeling assumption used to date. The main picture emerging from this analysis is that the anisotropy of the fibrillar matrix of articular cartilage is intimately dependent on the mechanism of tensed fiber recruitment, in the manner suggested by our recent theoretical study (Ateshian, 2007, ASME J. Biomech. Eng., 129(2), pp. 240–249).

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2009;131(6):061004-061004-8. doi:10.1115/1.3118774.

Rapid early diastolic left ventricular (LV) filling requires a highly compliant chamber immediately after systole, allowing inflow at low driving pressures. The transmural LV deformations associated with such filling are not completely understood. We sought to characterize regional transmural LV strains during diastole, with focus on early filling, in ovine hearts at 1 week and 8 weeks after myocardial marker implantation. In seven normal sheep hearts, 13 radiopaque markers were inserted to silhouette the LV chamber and a transmural beadset was implanted into the lateral equatorial LV wall to measure transmural strains. Four-dimensional marker dynamics were obtained 1 week and 8 weeks thereafter with biplane videofluoroscopy in closed-chest, anesthetized animals. LV transmural strains in both cardiac and fiber-sheet coordinates were studied from filling onset to the end of early filling (EOEF, 100 ms after filling onset) and at end diastole. At the 8 week study, subepicardial circumferential strain $(ECC)$ had reached its final value already at EOEF, while longitudinal and radial strains were nearly zero at this time. Subepicardial $ECC$ and fiber relengthening $(Eff)$ at EOEF were reduced to 1 compared with 8 weeks after surgery ($ECC:0.02±0.01$ to $0.08±0.02$ and $Eff:0.00±0.01$ to $0.03±0.01$, respectively, both $P<0.05$). Subepicardial $ECC$ during early LV filling was associated primarily with fiber-normal and sheet-normal shears at the 1 week study, but to all three fiber-sheet shears and fiber relengthening at the 8 week study. These changes in LV subepicardial mechanics provide a possible mechanistic basis for regional myocardial lusitropic function, and may add to our understanding of LV myocardial diastolic dysfunction.

Topics: Fibers , Surgery , Inflow
Commentary by Dr. Valentin Fuster
J Biomech Eng. 2009;131(6):061005-061005-9. doi:10.1115/1.3116156.

Characterizing the biomechanical and biotribological properties for articular surfaces in healthy, damaged, and repaired states will both elucidate the understanding of mechanical degradation and lubricating phenomena and enhance the development of functional tissue engineered cartilage and surgical repair techniques. In recent work, a new methodology involving concomitant linear translational and oscillating rotational motion was developed to determine the frictional and wear characteristics of articular cartilage. The impetus of this work was to further characterize the biomechanical characteristics from stress relaxation and dynamic cyclical indentation testing of normal and damaged articular cartilage and to correlate the biotribological characteristic findings with the biomechanical data. Quasilinear viscoelastic (QLV) theory was used to curve fit the stress-relaxation data, while the dynamic data were used both to determine the dynamic properties through fast Fourier transform analysis and to validate the dynamic behavior based on the properties obtained from the QLV theory. Comparisons of the curve-fit parameters showed a significant decrease in pre- versus postwear elastic response, $A$$(p<0.04)$, and viscous response, $c$$(p<0.01)$. In addition, the short term relaxation time, $τ1$$(p<0.0062)$, showed a significant decrease between surfaces with and without a defect. The magnitude of the complex modulus from dynamic tests revealed a decrease due to wear, $lGlpostwear∕lGlprewear<1$$(p<0.05)$. The loss factor, $tanδ$, was generally greater while $lGl$ was less for those specimens experiencing rotation. A linear regression analysis was performed to correlate $μstatic$ and $μinitial$ with the curve-fit QLV parameters, $A$, $B$, $c$, $τ1$, and $τ2$. Increasing coefficients of friction correlated with decreases in the elastic response, $A$, viscous response, $c$, and the short term relaxation time constant, $τ1$, while $B$ became increasingly nonlinear and $τ2$ became shorter postwear. Qualitatively, scanning electron microscopy photographs revealed the mechanical degradation of the tissue surface due to wear. Surfaces with a defect had an increased amount of wear debris, which ultimately contributed to third body wear. Surfaces without a defect had preferentially aligned abrasions, while those surfaces not within the wear path showed no signs of wear. The efficacy of various repair techniques and innovative repair tissue models in comparison to normal and worn articular surface tissue can be determined through experimental designs involving both biomechanical and biotribological parameter characterizations. The development of this comprehensive testing scenario involving both biotribological and biomechanical characteristics is essential to the continued development of potential articular repair tissue.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2009;131(6):061006-061006-9. doi:10.1115/1.3118764.

Four commercially available stent designs (two balloon expandable—Bx Velocity and NIR, and two self-expanding—Wallstent and Aurora) were modeled to compare the near-wall flow characteristics of stented arteries using computational fluid dynamics simulations under pulsatile flow conditions. A flat rectangular stented vessel model was constructed and simulations were carried out using rigid walls and sinusoidal velocity input (nominal wall shear stress of $10±5 dyn/cm2$). Mesh independence was determined from convergence $(<10%)$ of the axial wall shear stress (WSS) along the length of the stented model. The flow disturbance was characterized and quantified by the distributions of axial and transverse WSS, WSS gradients, and flow separation parameters. Normalized time-averaged effective WSS during the flow cycle was the smallest for the Wallstent $(2.9 dyn/cm2)$ compared with the others ($5.8 dyn/cm2$ for the Bx Velocity stent, $5.0 dyn/cm2$ for the Aurora stent, and $5.3 dyn/cm2$ for the NIR stent). Regions of low mean WSS $(<5 dyn/cm2)$ and elevated WSS gradients $(>20 dyn/cm3)$ were also the largest for the Wallstent compared with the others. WSS gradients were the largest near the struts and remained distinctly nonzero for most of the region between the struts for all stent designs. Fully recirculating regions (as determined by separation parameter) were the largest for the Bx Velocity stent compared with the others. The most hemodynamically favorable stents from our computational analysis were the Bx Velocity and NIR stents, which were slotted-tube balloon-expandable designs. Since clinical data indicate lower restenosis rates for the Bx Velocity and NIR stents compared with the Wallstent, our data suggest that near-wall hemodynamics may predict some aspects of in vivo performance. Further consideration of biomechanics, including solid mechanics, in stent design is warranted.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2009;131(6):061007-061007-11. doi:10.1115/1.3118765.

The objective of this modeling and simulation study was to establish the role of stress wave interactions in the genesis of traumatic brain injury (TBI) from exposure to explosive blast. A high resolution ($1 mm3$ voxels) five material model of the human head was created by segmentation of color cryosections from the Visible Human Female data set. Tissue material properties were assigned from literature values. The model was inserted into the shock physics wave code, CTH , and subjected to a simulated blast wave of 1.3 MPa (13 bars) peak pressure from anterior, posterior, and lateral directions. Three-dimensional plots of maximum pressure, volumetric tension, and deviatoric (shear) stress demonstrated significant differences related to the incident blast geometry. In particular, the calculations revealed focal brain regions of elevated pressure and deviatoric stress within the first 2 ms of blast exposure. Calculated maximum levels of 15 KPa deviatoric, 3.3 MPa pressure, and 0.8 MPa volumetric tension were observed before the onset of significant head accelerations. Over a 2 ms time course, the head model moved only 1 mm in response to the blast loading. Doubling the blast strength changed the resulting intracranial stress magnitudes but not their distribution. We conclude that stress localization, due to early-time wave interactions, may contribute to the development of multifocal axonal injury underlying TBI. We propose that a contribution to traumatic brain injury from blast exposure, and most likely blunt impact, can occur on a time scale shorter than previous model predictions and before the onset of linear or rotational accelerations traditionally associated with the development of TBI.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2009;131(6):061008-061008-5. doi:10.1115/1.3118776.

During temporomandibular joint (TMJ) function, the mandibular condylar cartilage plays a prime role in the distribution and absorption of stresses generated over the condyle. Biomechanical characterization of the tissue under compression, however, is still incomplete. The present study investigates the regional variations in the elastic and equilibrium moduli of the condylar cartilage under high strains using unconfined compression and stress relaxation, with aims to facilitate future tissue engineering studies. Porcine condylar cartilages from five regions (anterior, central, lateral, medial, and posterior) were tested under unconfined compression. Elastic moduli were obtained from the linear regions of the stress-strain curves corresponding to the continuous deformation. Equilibrium moduli were obtained from the stress relaxation curves using the Kelvin model. The posterior region was the stiffest, followed by the middle (medial, central, and lateral) regions and the anterior region, respectively. Specifically, in terms of the equilibrium modulus, the posterior region was 1.4 times stiffer than the middle regions, which were in turn 1.7 times stiffer than the anterior region, although only the difference between anterior and posterior regions was statistically significant. No significant differences in stiffness were observed among the medial, central, lateral, and posterior regions. A positive correlation between the thickness and stiffness of the cartilage was observed, reflecting that their regional variations may be related phenomena caused in response to cartilage loading patterns. Condylar cartilage was less stiff under compression than in tension. In addition, condylar cartilage under compression appears to behave in a manner similar to the TMJ disc in terms of the magnitude of moduli and drastic initial drop in stress after a ramp strain.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2009;131(6):061009-061009-9. doi:10.1115/1.3118767.

Cell-substrate interaction is implicated in many physiological processes. Dynamical monitoring of cellular tractions on substrate is critical in investigating a variety of cell functions such as contraction, migration, and invasion. On account of the inherent ill-posed property as an inverse problem, cellular traction recovery is essentially sensitive to substrate displacement noise and thus likely produces unstable results. Therefore, some additional constraints must be applied to obtain a reliable traction estimate. By integrating the classical Boussinesq solution over a small rectangular area element, we obtain a new analytical solution to express the relation between tangential tractions and induced substrate displacements, and then form an alternative discrete Green’s function matrix to set up a new framework of cellular force reconstruction. Deformation images of flexible substrate actuated by a single cardiac myocyte are processed by digital image correlation technique and the displacement data are sampled with a regular mesh to obtain cellular tractions by the proposed solution. Numerical simulations indicate that the 2-norm condition number of the improved coefficient matrix typically does not exceed the order of 100 for actual computation of traction recovery, and that the traction reconstruction is less sensitive to the shift or subdivision of the data sampling grid. The noise amplification arising from ill-posed inverse problem can be restrained and the stability of inverse solution is improved so that regularization operations become less relevant to the present force reconstruction with economical sampling density. The traction recovery for a single cardiac myocyte, which is in good agreement with that obtained by the Fourier transform traction cytometry, demonstrates the feasibility of the proposed method. We have developed a simple and efficient method to recover cellular traction field from substrate deformation. Unlike previous force reconstructions that numerically employ some regularization schemes, the present approach stabilizes the traction recovery by analytically improving the Green’s function such that the intricate regularizations can be avoided under proper conditions. The method has potential application to a real-time traction force microscopy in combination with a high-efficiency displacement acquisition technique.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2009;131(6):061010-061010-11. doi:10.1115/1.3127253.

Heart attack and stroke are often caused by atherosclerotic plaque rupture, which happens without warning most of the time. Magnetic resonance imaging (MRI)-based atherosclerotic plaque models with fluid-structure interactions (FSIs) have been introduced to perform flow and stress/strain analysis and identify possible mechanical and morphological indices for accurate plaque vulnerability assessment. For coronary arteries, cyclic bending associated with heart motion and anisotropy of the vessel walls may have significant influence on flow and stress/strain distributions in the plaque. FSI models with cyclic bending and anisotropic vessel properties for coronary plaques are lacking in the current literature. In this paper, cyclic bending and anisotropic vessel properties were added to 3D FSI coronary plaque models so that the models would be more realistic for more accurate computational flow and stress/strain predictions. Six computational models using one ex vivo MRI human coronary plaque specimen data were constructed to assess the effects of cyclic bending, anisotropic vessel properties, pulsating pressure, plaque structure, and axial stretch on plaque stress/strain distributions. Our results indicate that cyclic bending and anisotropic properties may cause 50–800% increase in maximum principal stress $(Stress-P1)$ values at selected locations. The stress increase varies with location and is higher when bending is coupled with axial stretch, nonsmooth plaque structure, and resonant pressure conditions (zero phase angle shift). Effects of cyclic bending on flow behaviors are more modest (9.8% decrease in maximum velocity, 2.5% decrease in flow rate, 15% increase in maximum flow shear stress). Inclusion of cyclic bending, anisotropic vessel material properties, accurate plaque structure, and axial stretch in computational FSI models should lead to a considerable improvement of accuracy of computational stress/strain predictions for coronary plaque vulnerability assessment. Further studies incorporating additional mechanical property data and in vivo MRI data are needed to obtain more complete and accurate knowledge about flow and stress/strain behaviors in coronary plaques and to identify critical indicators for better plaque assessment and possible rupture predictions.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2009;131(6):061011-061011-8. doi:10.1115/1.3127262.

Human embryonic stem cells (hESCs) possess an immense potential in a variety of regenerative applications. A firm understanding of hESC mechanics, on the single cell level, may provide great insight into the role of biophysical forces in the maintenance of cellular phenotype and elucidate mechanical cues promoting differentiation along various mesenchymal lineages. Moreover, cellular biomechanics can provide an additional tool for characterizing stem cells as they follow certain differentiation lineages, and thus may aid in identifying differentiated hESCs, which are most suitable for tissue engineering. This study examined the viscoelastic properties of single undifferentiated hESCs, chondrogenically differentiated hESC subpopulations, mesenchymal stem cells (MSCs), and articular chondrocytes (ACs). hESC chondrogenesis was induced using either transforming growth factor-$β1$$(TGF-β1)$ or knock out serum replacer as differentiation agents, and the resulting cell populations were separated based on density. All cell groups were mechanically tested using unconfined creep cytocompression. Analyses of subpopulations from all differentiation regimens resulted in a spectrum of mechanical and morphological properties spanning the range of hESCs to MSCs to ACs. Density separation was further successful in isolating cellular subpopulations with distinct mechanical properties. The instantaneous and relaxed moduli of subpopulations from $TGF-β1$ differentiation regimen were statistically greater than those of undifferentiated hESCs. In addition, two subpopulations from the $TGF-β1$ group were identified, which were not statistically different from native articular chondrocytes in their instantaneous and relaxed moduli, as well as their apparent viscosity. Identification of a differentiated hESC subpopulation with similar mechanical properties as native chondrocytes may provide an excellent cell source for tissue engineering applications. These cells will need to withstand any mechanical stimulation regimen employed to augment the mechanical and biochemical characteristics of the neotissue. Density separation was effective at purifying distinct populations of cells. A differentiated hESC subpopulation was identified with both similar mechanical and morphological characteristics as ACs. Future research may utilize this cell source in cartilage regeneration efforts.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2009;131(6):061012-061012-9. doi:10.1115/1.3128673.

The relationship between microstructural features and macroscopic mechanical properties of engineered tissues was investigated in pure and mixed composite scaffolds consisting of collagen Type I and fibrin proteins containing embedded smooth muscle cells. In order to vary the matrix microstructure, fibrin polymerization in mixed constructs was initiated using either the blood-derived enzyme thrombin or the snake venom-derived enzyme ancrod, each at low and high concentrations. Microstructural features of the matrix were quantified by analysis of high resolution scanning electron micrographs. Mechanical properties of the scaffolds were assessed by uniaxial tensile testing as well as creep testing. Viscoelastic parameters were determined by fitting creep data to Burger’s four-parameter model. Oscillatory dynamic mechanical testing was used to determine the storage modulus, loss modulus, and phase shift of each matrix type. Mixed composite scaffolds exhibited improved tensile stiffness and strength, relative to pure collagen matrices, as well as decreased deformation and slower relaxation in creep tests. Storage and loss moduli were increased in mixed composites compared with pure collagen, while phase shift was reduced. A correlation analysis showed that the number of fiber bundles per unit volume was positively correlated with matrix modulus, strength, and dynamic moduli, though this parameter was negatively correlated with phase shift. Fiber diameter also was negatively correlated with scaffold strength. This study demonstrates how microstructural features can be related to the mechanical function of protein matrices and provides insight into structure-function relationships in such materials. This information can be used to identify and promote desirable microstructural features when designing biomaterials and engineered tissues.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2009;131(6):061013-061013-7. doi:10.1115/1.3127252.

A variety of hemodynamic wall parameters (HWP) has been proposed over the years to quantify hemodynamic disturbances as potential predictors or indicators of vascular wall dysfunction. The aim of this study was to determine whether some of these might, for practical purposes, be considered redundant. Image-based computational fluid dynamics simulations were carried out for $N=50$ normal carotid bifurcations reconstructed from magnetic resonance imaging. Pairwise Spearman correlation analysis was performed for HWP quantifying wall shear stress magnitudes, spatial and temporal gradients, and harmonic contents. These were based on the spatial distributions of each HWP and, separately, the amount of the surface exposed to each HWP beyond an objectively-defined threshold. Strong and significant correlations were found among the related trio of time-averaged wall shear stress magnitude (TAWSS), oscillatory shear index (OSI), and relative residence time (RRT). Wall shear stress spatial gradient (WSSG) was strongly and positively correlated with TAWSS. Correlations with Himburg and Friedman’s dominant harmonic (DH) parameter were found to depend on how the wall shear stress magnitude was defined in the presence of flow reversals. Many of the proposed HWP were found to provide essentially the same information about disturbed flow at the normal carotid bifurcation. RRT is recommended as a robust single metric of low and oscillating shear. On the other hand, gradient-based HWP may be of limited utility in light of possible redundancies with other HWP, and practical challenges in their measurement. Further investigations are encouraged before these findings should be extrapolated to other vascular territories.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2009;131(6):061014-061014-7. doi:10.1115/1.3128672.

While mechanical stimulation of cells seeded within scaffolds is widely thought to be beneficial, the amount of benefit observed is highly variable between experimental systems. Although studies have investigated specific experimental loading protocols thought to be advantageous for cartilage growth, less is known about the physical stimuli (e.g., pressures, velocities, and local strains) cells experience during these experiments. This study used results of a literature survey, which looked for patterns in the efficacy of mechanical stimulation of chondrocyte seeded scaffolds, to inform the modeling of spatial patterns of physical stimuli present in mechanically stimulated constructs. The literature survey revealed a large variation in conditions used in mechanical loading studies, with a peak to peak strain of 10% (i.e., the maximum amount of deformation experienced by the scaffold) at 1 Hz on agarose scaffolds being the most frequently studied parameters and scaffold. This loading frequency was then used as the basis for simulation in the finite element analyses. 2D axisymmetric finite element models of $2×4 mm2$ scaffolds with 360 modulus/permeability combinations were constructed using COMSOL MULTIPHYSICS software. A time dependent coupled pore pressure/effective stress analysis was used to model fluid/solid interactions in the scaffolds upon loading. Loading was simulated using an impermeable frictionless loader on the top boundary with fluid and solid displacement confined to the radial axis. As expected, all scaffold materials exhibited classic poro-elastic behavior having pressurized cores with low fluid flow and edges with high radial fluid velocities. Under the simulation parameters of this study, PEG scaffolds had the highest pressure and radial fluid velocity but also the lowest shear stress and radial strain. Chitosan and KLD-12 simulated scaffold materials had the lowest radial strains and fluid velocities, with collagen scaffolds having the lowest pressures. Parametric analysis showed maximum peak pressures within the scaffold to be more dependent on scaffold modulus than on permeability and velocities to depend on both scaffold properties similarly. The dependence of radial strain on permeability or modulus was more complex; maximum strains occurred at lower permeabilities and moduli, and the lowest strain occurred at the stiffest most permeable scaffold. Shear stresses within all scaffolds were negligible. These results give insight into the large variations in metabolic response seen in studies involving mechanical stimulation of cell-seeded constructs, where the same loading conditions produce very different results due to the differences in material properties.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2009;131(6):061015-061015-11. doi:10.1115/1.3127256.

The clinical assessment of abdominal aortic aneurysm (AAA) rupture risk is based on the quantification of AAA size by measuring its maximum diameter from computed tomography (CT) images and estimating the expansion rate of the aneurysm sac over time. Recent findings have shown that geometrical shape and size, as well as local wall thickness may be related to this risk; thus, reliable noninvasive image-based methods to evaluate AAA geometry have a potential to become valuable clinical tools. Utilizing existing CT data, the three-dimensional geometry of nine unruptured human AAAs was reconstructed and characterized quantitatively. We propose and evaluate a series of 1D size, 2D shape, 3D size, 3D shape, and second-order curvature-based indices to quantify AAA geometry, as well as the geometry of a size-matched idealized fusiform aneurysm and a patient-specific normal abdominal aorta used as controls. The wall thickness estimation algorithm, validated in our previous work, is tested against discrete point measurements taken from a cadaver tissue model, yielding an average relative difference in AAA wall thickness of 7.8%. It is unlikely that any one of the proposed geometrical indices alone would be a reliable index of rupture risk or a threshold for elective repair. Rather, the complete geometry and a positive correlation of a set of indices should be considered to assess the potential for rupture. With this quantitative parameter assessment, future research can be directed toward statistical analyses correlating the numerical values of these parameters with the risk of aneurysm rupture or intervention (surgical or endovascular). While this work does not provide direct insight into the possible clinical use of the geometric parameters, we believe it provides the foundation necessary for future efforts in that direction.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2009;131(6):061016-061016-7. doi:10.1115/1.3130454.

Each year, between $1.6×106$ and $3.8×106$ concussions are sustained by athletes playing sports, with football having the highest incidence. The high number of concussions in football provides a unique opportunity to collect biomechanical data to characterize mild traumatic brain injury. Human head acceleration data for a range of impact severities were collected by instrumenting the helmets of collegiate football players with accelerometers. The helmets of ten Virginia Tech football players were instrumented with measurement devices for every game and practice for the 2007 football season. The measurement devices recorded linear and angular accelerations about each of the three axes of the head. Data for each impact were downloaded wirelessly to a sideline data collection system shortly after each impact occurred. Data were collected for 1712 impacts, creating a large and unbiased data set. While a majority of the impacts were of relatively low severity ($<30 g$ and $<2000 rad/s2$), 172 impacts were greater than 40 g and 143 impacts were greater than $3000 rad/s2$. No instrumented player sustained a clinically diagnosed concussion during the 2007 season. A large and unbiased data set was compiled by instrumenting the helmets of collegiate football players. Football provides a unique opportunity to collect head acceleration data of varying severity from human volunteers. The addition of concurrent concussive data may advance the understanding of the mechanics of mild traumatic brain injury. With an increased understanding of the biomechanics of head impacts in collegiate football and human tolerance to head acceleration, better equipment can be designed to prevent head injuries.

Commentary by Dr. Valentin Fuster

### Technical Briefs

J Biomech Eng. 2009;131(6):064501-064501-8. doi:10.1115/1.3118770.

The mechanical behavior of human tympanic membrane (TM) has been investigated extensively under quasistatic loading conditions in the past. The results, however, are sparse for the mechanical properties (e.g., Young's modulus) of the TM at high strain rates, which are critical input for modeling the mechanical response under blast wave. The property data at high strain rates can also potentially be converted into complex modulus in frequency domain to model acoustic transmission in the human ear. In this study, we developed a new miniature split Hopkinson tension bar to investigate the mechanical behavior of human TM at high strain rates so that a force of up to half of a newton can be measured accurately under dynamic loading conditions. Young’s modulus of a normal human TM is reported as 45.2–58.9 MPa in the radial direction, and 34.1–56.8 MPa in the circumferential direction at strain rates $300–2000 s−1$. The results indicate that Young’s modulus has a strong dependence on strain rate at these high strain rates.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2009;131(6):064502-064502-6. doi:10.1115/1.3127249.

Quantification of bone strain can be used to better understand fracture risk, bone healing, and bone turnover. The objective of this work was to develop and validate an intensity matching image registration method to accurately measure and spatially resolve strain in vertebrae using $μCT$ imaging. A strain quantification method was developed that used two sequential $μCT$ scans, taken in loaded and unloaded configurations. The image correlation algorithm implemented was a multiresolution intensity matching deformable registration that found a series of affine mapping between the unloaded and loaded scans. Once the registration was completed, the displacement field and strain field were calculated from the mappings obtained. Validation was done in two distinct ways: the first was to look at how well the method could quantify zero strain; the second was to look at how the method was able to reproduce a known applied strain field. Analytically defined strain fields that linearly varied in space and strain fields resulting from finite element analysis were used to test the strain measurement algorithm. The deformable registration method showed very good agreement with all cases imposed, establishing a detection limit of 0.0004 strain and displaying agreement with the imposed strain cases (average $R2=0.96$). The deformable registration routine developed was able to accurately measure both strain and displacement fields in whole rat vertebrae. A rigorous validation of any strain measurement method is needed that reports on the ability of the routine to measure strain in a variety of strain fields with differing spatial extents, within the structure of interest.

Commentary by Dr. Valentin Fuster
J Biomech Eng. 2009;131(6):064503-064503-4. doi:10.1115/1.3128718.

Microgravity (micro-g) environments have been shown to elicit dysregulation of specific genes in a wide assay of cell types. It is known that the activation of transcription factors and molecular signaling pathways influence various physiological outcomes associated with stress and adaptive responses. Nuclear factor-kappa B $(NF-κB)$ is one of the most prevailing oxidation-sensitive transcription factors. It is hypothesized that simulated microgravity would activate $NF-κB$ and its downstream transcriptional networks, thus suggesting a role for $NF-κB$ in microgravity induced muscle atrophy. To investigate the activation of $NF-κB$ in a rat cardiac cell line (H9c2) under micro-g, rotating wall vessel bioreactors were used to simulate micro-g conditions. Western blotting revealed that mean nuclear translocation of $NF-κB$ p65 subunit was 69% for micro-g and 46% for unit-g dynamic control as compared with a 30 min $TNF-α$ positive control $(p<0.05, n=3)$. The results from western blots were confirmed by enzyme-linked immunosorbent assay, which showed 66% for micro-g and 45% for dynamic control as compared with positive control $(p<0.05, n=3)$. These results show significant differential translocation of $NF-κB$ p65 under simulated micro-g. These results may be expanded upon to explain physiological changes such as muscle atrophy and further identify the regulatory pathways and effector molecules activated under exposure to micro-g.

Commentary by Dr. Valentin Fuster