The use of preserved tissue in finite element modelling of fresh ovine vertebral behaviour

The aim of this study was to investigate whether the predicted finite element (FE) stiffness of vertebral bone is altered when using images of preserved rather than fresh tissue to generate specimen-specific FE models. Fresh ovine vertebrae were used to represent embalmed (n = 3) and macerated dry-bone (n = 3) specimens and treated accordingly. Specimens were scanned pre- and post-treatment using micro-computed tomography. A constant threshold level derived from these images was used to calculate the respective bone volume fraction (BV/TV) from which the conversion factor validated for fresh tissue was used to determine material properties that were assigned to corresponding FE models. Results showed a definite change in the BV/TV between the fresh and the preserved bone. However, the changes in the predicted FE stiffness were not generally greater than the variations expected from assignment of loading and boundary conditions. In conclusion, images of preserved tissue can be used to generate FE models that are representative of fresh tissue with a tolerable level of error.     

Quantifying whole bladder biomechanics using the novel pentaplanar reflected image macroscopy system

Optimal bladder compliance is essential to urinary bladder storage and voiding functions. Calculated as the change in filling volume per change in pressure, bladder compliance is used clinically to characterize changes in bladder wall biomechanical properties that associate with lower urinary tract dysfunction. But because this method calculates compliance without regard to wall structure or wall volume, it gives little insight into the mechanical properties of the bladder wall during filling. Thus, we developed Pentaplanar Reflected Image Macroscopy (PRIM): a novel ex vivo imaging method to accurately calculate bladder wall stress and stretch in real time during bladder filling. The PRIM system simultaneously records intravesical pressure, infused volume, and an image of the bladder in five distinct visual planes. Wall thickness and volume were then measured and used to calculate stress and stretch during filling. As predicted, wall stress was nonlinear; only when intravesical pressure exceeded ~ 15 mmHg did bladder wall stress rapidly increase with respect to stretch. This method of calculating compliance as stress vs stretch also showed that the mechanical properties of the bladder wall remain similar in bladders of varying capacity. This study demonstrates how wall tension, stress and stretch can be measured, quantified, and used to accurately define bladder wall biomechanics in terms of actual material properties and not pressure/volume changes. This method is especially useful for determining how changes in bladder biomechanics are altered in pathologies where profound bladder wall remodeling occurs, such as diabetes and spinal cord injury.

     

Finite element simulation of interactions between pelvic organs: Predictive model of the prostate motion in the context of radiotherapy

The setting up of predictive models of the pelvic organ motion and deformation may prove an efficient tool in the framework of prostate cancer radiotherapy, in order to deliver doses more accurately and efficiently to the clinical target volume (CTV). A finite element (FE) model of the prostate, rectum and bladder motion has been developed, investigating more specifically the influence of the rectum and bladder repletions on the gland motion. The required organ geometries are obtained after processing the computed tomography (CT) images, using specific softwares. Due to their structural characteristics, a 3D shell discretization is adopted for the rectum and the bladder, whereas a volume discretization is adopted for the prostate. As for the mechanical behavior modelling, first order Ogden hyperelastic constitutive laws for both the rectum and bladder are identified. The prostate is comparatively considered as more rigid and is accordingly modelled as an elastic tissue undergoing small strains. A FE model is then created, accounting for boundary and contact conditions, internal and applied loadings being selected as close as possible to available anatomic data.The order of magnitude of the prostate motion predicted by the FE simulations is similar to the measurements done on a deceased person, accounting for the delineation errors, with a relative error around 8%. Differences are essentially due to uncertainties in the constitutive parameters, pointing towards the need for the setting up of direct measurement of the organs mechanical behavior.     

Positional uncertainty of vaginal cuff and feasibility of implementing portable bladder scanner in postoperative cervical cancer patients

PurposeTo propose a geometrical margin for definition of the vaginal cuff PTV using only CT images of the full bladder (CT_full) in postoperative cervical cancer patients.MethodsTwenty-nine operated cervical cancer patients underwent volumetric arc therapy with a bladder filling protocol. This study assessed bladder filling using a portable bladder scanner and cone-beam computed tomography (CBCT) during the entire treatment period. The measured bladder volumes with a BladderScan® were compared with the delineated volume on CBCT. Titanium clips in the vaginal cuff were analysed to assess geometrical uncertainty and the influence of rectal and bladder volume changes.ResultsBladderScan® showed good agreement with the delineated volume (R = 0.80). The volume changes in the bladder have a greater influence on the clip displacements than in the rectum. The 95th percentile of uncertainty of the clips in reference to CT_full in the right-left (RL), the superoinferior (SI), and the anteroposterior (AP) was 0.32, 0.65, and 1.15 cm, respectively. From this result and intra-fractional movements of the vaginal cuff reported by Haripotepornkul, a new geometrical margin was proposed for definition of the vaginal cuff planning target volume (PTV): 0.5, 0.9, and 1.4 cm in the RL, SI, and AP directions, respectively.ConclusionsA new geometrical margin was proposed for definition of the vaginal cuff PTV based on CT_full, which will be needless of empty bladder at the planning CT scan. This method allows patients to reduce the burden and efficient routine CT scans can be improved.     

Variability of a three-dimensional finite element model constructed using magnetic resonance images of a knee for joint contact stress analysis

Magnetic resonance (MR) imaging has been widely used to evaluate the thickness and volume of articular cartilage both in vivo and in vitro. While morphological information on the cartilage can be obtained using MR images, image processing for extracting geometric boundaries of the cartilage may introduce variations in the thickness of the cartilage. To evaluate the variability of using MR images to construct finite element (FE) knee cartilage models, five investigators independently digitized the same set of MR images of a human knee. The topology of cartilage thickness was determined using a minimal distance algorithm. Less than 8 percent variation in cartilage thickness was observed from the digitized data. The effect of changes in cartilage thickness on contact stress analysis was then investigated using five FE models of the knee. One FE model (average FE model) was constructed using the mean values of the digitized contours of the cartilage, and the other four were constructed by varying the thickness of the average FE model by +/- 5 percent and +/- 10 percent, respectively. The results demonstrated that under axial tibial compressive loading (up to 1,400 N), variations of cartilage thickness caused by digitization of MR images may result in a difference of approximately 10 percent in peak contact stresses (surface pressure, von Mises stress, and hydrostatic pressure) in the cartilage. A reduction of cartilage thickness caused increases of contact stresses, while an increase of cartilage thickness reduced contact stresses. Furthermore, the effect of variation of material properties of the cartilage on contact stress analysis was investigated. The peak contact stress increased almost linearly with the Young's modulus of the cartilage. The peak von Mises stress was dramatically reduced when the Poisson,s ratio was increased from 0.05 to 0.49 under an axial compressive load of 1,400 N, while peak hydrostatic pressure was dramatically increased. Peak surface pressure was also increased with the Poisson's ratio, but with a lower magnitude compared to von Mises stress and hydrostatic pressure. In conclusion, the imaging process may cause 10 percent variations in peak contact stress, and the predicted stress distribution is sensitive to the accuracy of the material properties of the cartilage model, especially to the variation of Poisson's ratio.     

Detrusor expulsive strength is preserved, but responsiveness to bladder filling and urinary sensitivity is diminished in the aging mouse

The prevalence of urinary symptoms increases with age and is a significant source of distress, morbidity, and expense in the elderly. Recent evidence suggests that symptoms in the aged may result from sensory dysfunction, rather than abnormalities of detrusor performance. Therefore, we employed a pressure/flow multichannel urethane-anesthetized mouse cystometry model to test the hypothesis that in vivo detrusor performance does not degrade with aging. Secondarily, we sought to evaluate sensory responsiveness to volume using pressure-volume data generated during bladder filling. Cystometric data from 2-, 12-, 22-, and 26-mo-old female C57BL6 mice were compared. All 2- and 12-mo-old mice, 66% of 22-mo-old mice, and 50% of 26-mo-old mice responded to continuous bladder filling with periodic reflex voiding. Abdominal wall contraction with voiding had a minimal contribution to expulsive pressure, whereas compliance pressure was a significant contributor. Maximum bladder pressure, estimated detrusor pressure, detrusor impulse (pressure-time integral), as well as indices of detrusor power and work, did not decrease with aging. Bladder precontraction pressures decreased, compliance increased, and nonvoiding contraction counts did not change with increasing age. Intervoid intervals, per-void volumes, and voiding flow rates increased with age. Calculations approximating wall stress during filling suggested loss of bladder volume sensitivity with increasing age. We conclude that aging is associated with an impaired ability to respond to the challenge of continuous bladder filling with cyclic voiding, yet among responsive animals, voiding detrusor contraction strength does not degrade with aging in this murine model. Furthermore, indirect measures suggest that bladder volume sensitivity is diminished. Thus, changes in homeostatic reserve and peripheral and/or central sensory mechanisms may be important contributors to aging-associated changes in bladder function.     

Ex vivo deformations of the urinary bladder wall during whole bladder filling: Contributions of extracellular matrix and smooth muscle

As the complete understanding of urinary bladder function requires knowledge of organ level deformations, we conducted ex vivo studies of surface strains of whole bladders during controlled filling. The surface strains derived from displacements of surface markers applied to the posterior surface of excised rat bladders were tracked under slow filling with pressure and volume simultaneously recorded in the passive and completely inactivated states (i.e. with and without smooth muscle tone, respectively). Bladders evaluated in the passive state exhibited spontaneous contractions and larger average peak pressures (16.7 mmHg compared to 6.4 mmHg in the inactive state). Overall, the bladders exhibited anisotropic deformations and were stiffer in the circumferential direction, with average peak stretch values of ～2.3 and ～1.9 in the longitudinal and circumferential directions, respectively, for both states. Although bladders in the passive state were stiffer, they had similar average peak areal stretches of 4.3 in both states. However, differences early in the filling process as a result of a loss in smooth muscle tone in the inactive state resulted in longitudinal lengthening of 36%. Idealizing the bladder as a prolate spheroid, we estimated the wall stress–strain relation during filling and demonstrated that the intact bladder exhibited the classic stress–stretch relation, with a significantly protracted low stress region and peak stresses of 36 and 51 kPa in the longitudinal and circumferential directions, respectively. The present study fills a major gap in the urinary bladder biomechanics literature, wherein knowledge of the pressure–volume–wall stress–wall strain relation was explored for the first time in a functioning organ ex vivo.     

Hypercompliant Apical Membranes of Bladder Umbrella Cells

Urinary bladder undergoes dramatic volume changes during filling and voiding cycles. In the bladder the luminal surface of terminally differentiated urothelial umbrella cells is almost completely covered by plaques. These plaques (500 to 1000 nm) are made of a family of proteins called uroplakins that are known to form a tight barrier to prevent leakage of water and solutes. Electron micrographs from previous studies show these plaques to be interconnected by hinge regions to form structures that appear rigid, but these same structures must accommodate large changes in cell shape during voiding and filling cycles. To resolve this paradox, we measured the stiffness of the intact, living urothelial apical membrane and found it to be highly deformable, even more so than the red blood cell membrane. The intermediate cells underlying the umbrella cells do not have uroplakins but their membranes are an order of magnitude stiffer. Using uroplakin knockout mouse models we show that cell compliance is conferred by uroplakins. This hypercompliance may be essential for the maintenance of barrier function under dramatic cell deformation during filling and voiding of the bladder.     

Hypercompliant Apical Membranes of Bladder Umbrella Cells

Urinary bladder undergoes dramatic volume changes during filling and voiding cycles. In the bladder the luminal surface of terminally differentiated urothelial umbrella cells is almost completely covered by plaques. These plaques (500 to 1000 nm) are made of a family of proteins called uroplakins that are known to form a tight barrier to prevent leakage of water and solutes. Electron micrographs from previous studies show these plaques to be interconnected by hinge regions to form structures that appear rigid, but these same structures must accommodate large changes in cell shape during voiding and filling cycles. To resolve this paradox, we measured the stiffness of the intact, living urothelial apical membrane and found it to be highly deformable, even more so than the red blood cell membrane. The intermediate cells underlying the umbrella cells do not have uroplakins but their membranes are an order of magnitude stiffer. Using uroplakin knockout mouse models we show that cell compliance is conferred by uroplakins. This hypercompliance may be essential for the maintenance of barrier function under dramatic cell deformation during filling and voiding of the bladder.     

Adjustable passive stiffness in mouse bladder: regulated by Rho kinase and elevated following partial bladder outlet obstruction

Detrusor smooth muscle (DSM) contributes to bladder wall tension during filling, and bladder wall deformation affects the signaling system that leads to urgency. The length-passive tension (L-T(p)) relationship in rabbit DSM can adapt with length changes over time and exhibits adjustable passive stiffness (APS) characterized by a L-T(p) curve that is a function of both activation and strain history. Muscle activation with KCl, carbachol (CCh), or prostaglandin E(2) at short muscle lengths can increase APS that is revealed by elevated pseudo-steady-state T(p) at longer lengths compared with prior T(p) measurements at those lengths, and APS generation is inhibited by the Rho Kinase (ROCK) inhibitor H-1152. In the current study, mouse bladder strips exhibited both KCl- and CCh-induced APS. Whole mouse bladders demonstrated APS which was measured as an increase in pressure during passive filling in calcium-free solution following CCh precontraction compared with pressure during filling without precontraction. In addition, CCh-induced APS in whole mouse bladder was inhibited by H-1152, indicating that ROCK activity may regulate bladder compliance during filling. Furthermore, APS in whole mouse bladder was elevated 2 wk after partial bladder outlet obstruction, suggesting that APS may be relevant in diseases affecting bladder mechanics. The presence of APS in mouse bladder will permit future studies of APS regulatory pathways and potential alterations of APS in disease models using knockout transgenetic mice.     

A prospective observational study to analyse the influence of bladder and rectal volume changes on prostate radiotherapy using IMRT

AimTo analyse the interfractional bladder and rectal volume changes and the influence on prostate position.BackgroundInterfractional displacement of prostate due to variation in bladder and rectal volume is usual. It is only rational to study the bladder and rectal volume changes and their effects on prostate position during intensity modulated radiotherapy of prostate cancer.Materials and MethodsA prospective study was conducted on twenty patients with localized prostate cancer during the first phase of radiotherapy, where 50 gray in 25 fractions was delivered by the IMRT technique with daily cone beam computed tomography Bladder and rectum volumes were delineated on CBCT images and their volumes were noted. Prostate position was noted on each set of CBCT images with respect to specific reference points defined on the ileum and coccyx, and daily prostate displacement was noted.ResultsMean setup errors in vertical, longitudinal and lateral directions were noted as 1.49, 0.498 and 0.17 cm, respectively. Mean change in bladder and rectal volumes in daily CBCT images with respect to that on the first day CT images was noted as 101.94 and 10.22, respectively. Mean lateral and vertical displacement in prostate position was noted as 0.53 and 0.49 cm respectively. No considerable changes in dosimetric parameters were observed because of bladder and rectal volume changes.ConclusionsDaily CBCT should be done for accurate treatment delivery by the IMRT technique for prostate radiotherapy as prostate shifts physiologically with changes in rectal and bladder volumes.     

A simple fluid-mechanical model for the prediction of the stress-strain relation of the male urinary bladder

The non-linear, viscoelastic behavior of the male urinary bladder complicates the formulation of suitable stress-strain relations for the quasi-static filling process and the unsteady voiding process. In particular, the voiding process-which, in addition, is affected by contraction of muscles leading to generation of bladder wall tension-makes it difficult to obtain quantitative results. In the present study, a simple model is developed that uses certain urological data from cystometry and uroflowmetry to determine the stress-strain relations of the bladder wall during both filling and voiding.     

HR-pQCT-based homogenised finite element models provide quantitative predictions of experimental vertebral body stiffness and strength with the same accuracy as μFE models

This study validated two different high-resolution peripheral quantitative computer tomography (HR-pQCT)-based finite element (FE) approaches, enhanced homogenised continuum-level (hFE) and micro-finite element (μFE) models, by comparing them with compression test results of vertebral body sections. Thirty-five vertebral body sections were prepared by removing endplates and posterior elements, scanned with HR-pQCT and tested in compression up to failure. Linear hFE and μFE models were created from segmented and grey-level CT images, and apparent model stiffness values were compared with experimental stiffness as well as strength results. Experimental and numerical apparent elastic properties based on grey-level/segmented CT images (N=35) correlated well for μFE (r2=0.748/0.842) and hFE models (r2=0.741/0.864). Vertebral section stiffness values from the linear μFE/hFE models estimated experimental ultimate apparent strength very well (r2=0.920/0.927). Calibrated hFE models were able to predict quantitatively apparent stiffness with the same accuracy as μFE models. However, hFE models needed no back-calculation of a tissue modulus or any kind of fitting and were computationally much cheaper.     

Differences in 3D vs. 2D analysis in lumbar spinal fusion simulations

Lumbar interbody fusion is currently the gold standard in treating patients with disc degeneration or segmental instability. Despite it having been used for several decades, the non-union rate remains high. A failed fusion is frequently attributed to an inadequate mechanical environment after instrumentation. Finite element (FE) models can provide insights into the mechanics of the fusion process. Previous fusion simulations using FE models showed that the geometries and material of the cage can greatly influence the fusion outcome. However, these studies used axisymmetric models which lacked realistic spinal geometries. Therefore, different modeling approaches were evaluated to understand the bone-formation process.Three FE models of the lumbar motion segment (L4–L5) were developed: 2D, Sym-3D and Nonsym-3D. The fusion process based on existing mechano-regulation algorithms using the FE simulations to evaluate the mechanical environment was then integrated into these models. In addition, the influence of different lordotic angles (5, 10 and 15°) was investigated. The volume of newly formed bone, the axial stiffness of the whole segment and bone distribution inside and surrounding the cage were evaluated.In contrast to the Nonsym-3D, the 2D and Sym-3D models predicted excessive bone formation prior to bridging (peak values with 36 and 9% higher than in equilibrium, respectively). The 3D models predicted a more uniform bone distribution compared to the 2D model.The current results demonstrate the crucial role of the realistic 3D geometry of the lumbar motion segment in predicting bone formation after lumbar spinal fusion.     

Postfailure modulus strongly affects microcracking and mechanical property change in human iliac cancellous bone: a study using a 2D nonlinear finite element method

A two-dimensional (2D) finite element (FE) method was used to estimate the ability of bone tissue to sustain damage as a function of postfailure modulus. Briefly, 2D nonlinear compact-tension FE models were created from quantitative back-scattered electron images taken of human iliac crest bone specimens. The effects of different postfailure moduli on predicted microcrack propagation were examined. The 2D FE models were used as surrogates for real bone tissues. The crack number was larger in models with higher postfailure modulus, while mean crack length and area were smaller in these models. The rate of stiffness reduction was greater in the models with lower postfailure modulus. Hence, the current results supported the hypothesis that hard tissue postfailure properties have strong effects on bone microdamage morphology and the rate of change in apparent mechanical properties.     

Stretch-regulated exocytosis/endocytosis in bladder umbrella cells

The epithelium of the urinary bladder must maintain a highly impermeable barrier despite large variations in urine volume during bladder filling and voiding. To study how the epithelium accommodates these volume changes, we mounted bladder tissue in modified Ussing chambers and subjected the tissue to mechanical stretch. Stretching the tissue for 5 h resulted in a 50% increase in lumenal surface area (from approximately 2900 to 4300 microm(2)), exocytosis of a population of discoidal vesicles located in the apical cytoplasm of the superficial umbrella cells, and release of secretory proteins. Surprisingly, stretch also induced endocytosis of apical membrane and 100% of biotin-labeled membrane was internalized within 5 min after stretch. The endocytosed membrane was delivered to lysosomes and degraded by a leupeptin-sensitive pathway. Last, we show that the exocytic events were mediated, in part, by a cyclic adenosine monophosphate, protein kinase A-dependent process. Our results indicate that stretch modulates mucosal surface area by coordinating both exocytosis and endocytosis at the apical membrane of umbrella cells and provide insight into the mechanism of how mechanical forces regulate membrane traffic in non-excitable cells.     

Diastolic ventricular aspiration: a mechanism supporting the rapid filling phase of the human ventricles

During the rapid filling phase of the heart cycle, the internal volumes of the two ventricular cavities approximately double, while the intraventricular pressures rise typically only by an amount of less than 1 kPa. Such a small pressure increase cannot be the sole driving mechanism for the large inflow of blood associated with ventricular expansion during this period. Instead, the rapid filling phase is to be interpreted as being mediated primarily by the heart recoiling elastically from its contracted state, causing blood to be aspirated rapidly into the ventricles. In order to study the role of this mechanism, elastic finite element (FE) simulations of ventricular expansion were performed, taking into account the large deformations occurring during this period and the effective compressibility of the myocardium due to intramural fluid flow. Thereby, a realistic three-dimensional geometry derived from magnetic resonance imaging (MRI) measurements of both human ventricles was used. To validate our FE analyses, the results were compared with published measurements relating to the rapid filling phase of the human left ventricle. Our study shows that, under normal physiological conditions, ventricular aspiration plays a key role in the ventricular filling process.     

The peculiar properties of the falx and tentorium in brain injury biomechanics

The influence of the falx and tentorium on brain injury biomechanics during impact was studied with finite element (FE) analysis. Three detailed 3D FE head models were created based on the images of a healthy, normal size head. Two of the models contained the addition of falx and tentorium with material properties from previously published experiments. Impact loadings from a reconstructed concussive case in a sport accident were applied to the two players involved. The results suggested that the falx and tentorium could induce large strains to the surrounding brain tissues, especially to the corpus callosum and brainstem. The tentorium seemed to constrain the motion of the cerebellum while inducing large strain in the brainstem in both players involved in the accident (one player had mainly coronal head rotation and the other had both coronal and transversal rotations). Since changed strain levels were observed in the brainstem and corpus callosum, which are classical sites for diffuse axonal injuries (DAI), we confirmed the importance of using accurate material properties for falx and tentorium in a FE head model when studying traumatic brain injuries.     

The influence of material property and morphological parameters on specimen-specific finite element models of porcine vertebral bodies

The use of finite element (FE) methods in spinal research is increasing, but there is only limited information available on the influence of different input parameters on the model predictions. The aim of this study was to investigate the role of these parameters in FE models of the vertebral body. Experimental tests were undertaken on porcine lumbar vertebral bodies and scans of the specimens were used to create specimen-specific FE models. Three models were created for each specimen with combinations of generic and specimen-specific parameters. Stiffness and strength predictions were also made directly from the specimen trabecular bone volume fraction (BVF) and cross-sectional area (CSA). The agreement between the experimental results and the FE models with generic morphology was poorer (concordance coefficients = 0.058, 0.125 for stiffness, strength) than those made from the BVF and CSA (concordance coefficients = 0.638, 0.609). The greatest levels of agreement were found with the morphologically specific models including element-specific material properties (concordance coefficients = 0.881, 0.752). This indicates that highly specific models, both in terms of morphology and bone quality, are necessary if the FE tool is to be used effectively for spinal research and clinical practice.     

A novel approach to estimate trabecular bone anisotropy using a database approach

Continuum finite element (FE) models of bones have become a standard pre-clinical tool to estimate bone strength. These models are usually based on clinical CT scans and material properties assigned are chosen as isotropic based only on the density distribution. It has been shown, however, that trabecular bone elastic behavior is best described as orthotropic. Unfortunately, the use of orthotropic models in FE analysis derived from CT scans is hampered by the fact that the measurement of a trabecular orientation (fabric) is not possible from clinical CT images due to the low resolution of such images. In this study, we explore the concept of using a database (DB) of high-resolution bone models to derive the fabric information that is missing in clinical images. The goal of this study was to investigate if models with fabric derived from a relatively small database can already produce more accurate results than isotropic models.