Dan Dragomir-Daescu

Validated finite element models of the proximal femur using two-dimensional projected geometry and bone density

Two-dimensional finite element models of cadaveric femoral stiffness were developed to study their suitability as surrogates of bone stiffness and strength, using two-dimensional representations of femoral geometry and bone mineral density distributions. If successfully validated, such methods could be clinically applied to estimate patient bone stiffness and strength using simpler and less costly radiographs. Two-dimensional femur images were derived by projection of quantitative computed tomography scans of 22 human cadaveric femurs. The same femurs were fractured in a fall on the hip configuration. Femoral stiffness and fracture load were measured, and high speed video was recorded. Digital image correlation analysis was used to calculate the strain distribution from the high speed video recordings. Two-dimensional projection images were segmented and meshed with second-order triangular elements for finite element analysis. Elastic moduli of the finite elements were calculated based on the projected mineral density values inside the elements. The mapping of projection density values to elastic modulus was obtained using optimal parameter identification in a set of nine of the 22 specimens, and validated on the remaining 13 specimens. Finite element calculated proximal stiffness and strength correlated much better with experimental data than areal bone mineral density alone. In addition, finite element calculated strain distributions compared very well with strains obtained from digital image processing of the high speed video recordings, further validating the two-dimensional projected subject-specific finite element models.

In situ parameter identification of optimal density-elastic modulus relationships in subject-specific finite element models of the proximal femur.

Quantitative computed tomography based finite element analysis of the femur is currently being investigated as a method for non-invasive stiffness and strength predictions of the proximal femur. The specific objective of this study was to determine better conversion relationships from QCT-derived bone density to elastic modulus, in order to achieve accurate predictions of the overall femoral stiffness in a fall-on-the-hip loading configuration. Twenty-two femurs were scanned, segmented and meshed for finite element analysis. The elastic moduli of the elements were assigned according to the average density in the element. The femurs were then tested to fracture and force-displacement data were collected to calculate femoral stiffness. Using a training set of nine femurs, finite element analyses were performed and the parameters of the density-elastic modulus relationship were iteratively adjusted to obtain optimal stiffness predictions in a least-squares sense. The results were then validated on the remaining 13 femurs. Our novel procedure resulted in parameter identification of both power and sigmoid functions for density-elastic modulus conversion for this specific loading scenario. Our in situ estimated power law achieved improved predictions compared to published power laws, and the sigmoid function yielded even smaller prediction errors. In the future, these results will be used to further improve the femoral strength predictions of our finite element models.

Grid convergence errors in hemodynamic solution of patient-specific cerebral aneurysms

Computational fluid dynamics (CFD) has become a cutting-edge tool for investigating hemodynamic dysfunctions in the body. It has the potential to help physicians quantify in more detail the phenomena difficult to capture with in vivo imaging techniques. CFD simulations in anatomically realistic geometries pose challenges in generating accurate solutions due to the grid distortion that may occur when the grid is aligned with complex geometries. In addition, results obtained with computational methods should be trusted only after the solution has been verified on multiple high-quality grids. The objective of this study was to present a comprehensive solution verification of the intra-aneurysmal flow results obtained on different morphologies of patient-specific cerebral aneurysms. We chose five patient-specific brain aneurysm models with different dome morphologies and estimated the grid convergence errors for each model. The grid convergence errors were estimated with respect to an extrapolated solution based on the Richardson extrapolation method, which accounts for the degree of grid refinement. For four of the five models, calculated velocity, pressure, and wall shear stress values at six different spatial locations converged monotonically, with maximum uncertainty magnitudes ranging from 12% to 16% on the finest grids. Due to the geometric complexity of the fifth model, the grid convergence errors showed oscillatory behavior; therefore, each patient-specific model required its own grid convergence study to establish the accuracy of the analysis.

Computational fluid dynamics simulation of an anterior communicating artery ruptured during angiography

We present a computational fluid dynamics (CFD) analysis of the hemodynamic environment of an anterior communicating artery that spontaneously ruptured immediately following three-dimensional rotational angiography. Subsequent digital subtraction angiography allowed for the localization of the point of rupture within the aneurysm dome. CFD analysis demonstrated a concentrated jet that impinged directly at the site of rupture. Peak systolic pressure and wall shear stress were both maximal near the rupture location.

Apelinergic system in endothelial cells and its role in angiogenesis in myocardial ischemia

Apelin is a peptide known to have a vital role in cardiovascular diseases. It has been proven to induce proliferation and tube formation in endothelial cells, stabilise contacts between endothelial cells, and mediate pericyte recruitment. Since apelin level is reduced early after myocardial infarction, a supportive therapy with apelin is being investigated for its beneficial effect on blood vessel formation. It is becoming apparent, however, that the final effect of apelin often depends on stimuli the cell receives and the cross-talk with other molecules inside the cell. Hence, understanding the apelin pathway potentially can help us to improve angiogenic therapy. This review summarises recent knowledge regarding molecules involved in apelin signalling while focusing on their roles in angiogenesis within the ischemic environment after myocardial infarction.

Quantitative computed tomography-based finite element analysis predictions of femoral strength and stiffness depend on computed tomography settings

The aim of the present study was to compare proximal femur strength and stiffness obtained experimentally with estimations from Finite Element Analysis (FEA) models derived from Quantitative Computed Tomography (QCT) scans acquired at two different scanner settings. QCT/FEA models could potentially aid in diagnosis and treatment of osteoporosis but several drawbacks still limit their predictive ability. One potential reason is that the models are still sensitive to scanner settings which could lead to changes in assigned material properties, thus limiting their results accuracy and clinical effectiveness. To find the mechanical properties we fracture tested 44 proximal femora in a sideways fall-on-the-hip configuration. Before testing, we CT scanned all femora twice, first at high resolution scanner settings, and second at low resolution scanner settings and built 88 QCT/FEA models of femoral strength and stiffness. The femoral set neck bone mineral density, as measured by DXA, uniformly covered the range from osteoporotic to normal. This study showed that the femoral strength and stiffness values predicted from high and low resolution scans were significantly different (p<0.0001). Strength estimated from high resolution QCT scans was larger for osteoporotic, but smaller for normal and osteopenic femora when compared to low resolution scans. In addition, stiffness estimated from high resolution scans was consistently larger than stiffness obtained from low resolution scans over the entire femoral dataset. While QCT/FEA techniques hold promise for use in clinical settings we provided evidence that further improvements are required to increase robustness in their predictive power under different scanner settings and modeling assumptions.

The Effect of Quantitative Computed Tomography Acquisition Protocols on Bone Mineral Density Estimation

Osteoporosis is characterized by bony material loss and decreased bone strength leading to a significant increase in fracture risk. Patient-specific quantitative computed tomography (QCT) finite element (FE) models may be used to predict fracture under physiological loading. Material properties for the FE models used to predict fracture are obtained by converting grayscale values from the CT into volumetric bone mineral density (vBMD) using calibration phantoms. If there are any variations arising from the CT acquisition protocol, vBMD estimation and material property assignment could be affected, thus, affecting fracture risk prediction. We hypothesized that material property assignments may be dependent on scanning and postprocessing settings including voltage, current, and reconstruction kernel, thus potentially having an effect in fracture risk prediction. A rabbit femur and a standard calibration phantom were imaged by QCT using different protocols. Cortical and cancellous regions were segmented, their average Hounsfield unit (HU) values obtained and converted to vBMD. Estimated vBMD for the cortical and cancellous regions were affected by voltage and kernel but not by current. Our study demonstrated that there exists a significant variation in the estimated vBMD values obtained with different scanning acquisitions. In addition, the large noise differences observed utilizing different scanning parameters could have an important negative effect on small subregions containing fewer voxels.

Artery Length Sensitivity in Patient-Specific Cerebral Aneurysm Simulations

BACKGROUND AND PURPOSE: The reconstruction of aneurysm geometry is a main factor affecting the accuracy of hemodynamics simulations in patient-specific aneurysms. We analyzed the effects of the inlet artery length on intra-aneurysmal flow estimations by using 10 ophthalmic aneurysm models. MATERIALS AND METHODS: We successively truncated the inlet artery of each model, first at the cavernous segment and second at the clinoid segment. For each aneurysm, we obtained 3 models with different artery lengths: the originally segmented geometry with the longest available inlet from scans and 2 others with successively shorter artery lengths. We analyzed the velocity, wall shear stress, and the oscillatory shear index inside the aneurysm and compared the 2 truncations with the original model. RESULTS: We found that eliminating 1 arterial turn resulted in root mean square errors of <18% with no visual differences for the contours of the flow parameters in 8 of the 10 models. In contrast, truncating at the second turn led to root mean square errors between 18% and 32%, with consistently large errors for wall shear stress and the oscillatory shear index in 5 of the 10 models and visual differences for the contours of the flow parameters. For 3 other models, the largest errors were between 43% and 55%, with large visual differences in the contour plots. CONCLUSIONS: Excluding 2 arterial turns from the inlet artery length of the ophthalmic aneurysm resulted in large quantitative differences in the calculated velocity, wall shear stress, and oscillatory shear index distributions, which could lead to erroneous conclusions if used clinically.

Magnetizable stent-grafts enable endothelial cell capture.

Emerging nanotechnologies have enabled the use of magnetic forces to guide the movement of magnetically-labeled cells, drugs, and other therapeutic agents. Endothelial cells labeled with superparamagnetic iron oxide nanoparticles (SPION) have previously been captured on the surface of magnetizable 2205 duplex stainless steel stents in a porcine coronary implantation model. Recently, we have coated these stents with electrospun polyurethane nanofibers to fabricate prototype stent-grafts. Facilitated endothelialization may help improve the healing of arteries treated with stent-grafts, reduce the risk of thrombosis and restenosis, and enable small-caliber applications. When placed in a SPION-labeled endothelial cell suspension in the presence of an external magnetic field, magnetized stent-grafts successfully captured cells to the surface regions adjacent to the stent struts. Implantation within the coronary circulation of pigs (n=13) followed immediately by SPION-labeled autologous endothelial cell delivery resulted in widely patent devices with a thin, uniform neointima and no signs of thrombosis or inflammation at 7 days. Furthermore, the magnetized stent-grafts successfully captured and retained SPION-labeled endothelial cells to select regions adjacent to stent struts and between stent struts, whereas the non-magnetized control stent-grafts did not. Early results with these prototype devices are encouraging and further refinements will be necessary in order to achieve more uniform cell capture and complete endothelialization. Once optimized, this approach may lead to more rapid and complete healing of vascular stent-grafts with a concomitant improvement in long-term device performance.

Femoral Strength Changes Faster With Age Than BMD in Both Women and Men: A Biomechanical Study

Although a large number of studies have addressed the age‐related changes in bone mineral density (BMD), there is a paucity of data for the assessment of femoral strength loss with age in both genders. We determined the variation of strength with age in femurs of women and men by mechanical tests on a cohort of 100 cadaveric femurs. In addition, the age‐related neck BMD loss in our cadaveric cohort was found to be similar with BMD loss of four published population‐based studies. Given the strong correlation found in our cadaveric study between BMD and femoral strength, we also estimated the femoral strength of the four populations based on their reported neck BMDs. Our study showed that mens femurs in our cadaveric cohort were stronger than womens femurs by about 800 N at the same BMD level, and by 1750 N at the same age. The strength differences were not explained satisfactorily by the size difference between mens and womens bones. Similar to the findings of clinical studies, the BMD values of men at all ages were larger than that of women. The age‐related loss rates in BMD and strength were not statistically different between the two genders of our cadaveric cohort. After normalization, strength decreased more than 40% faster than BMD. On average, men reached a certain BMD value about 16 years later than women, and for strength about 23 years later, which may explain the higher rate of hip fracture in postmenopausal women. In patient population cohorts men reached a similar BMD value about 16 to 25 years later than women, whereas for estimated strength, sometimes more than 40 years later.