OpenKBP-Opt: an international and reproducible evaluation of 76 knowledge-based planning pipelines.

Objective.To establish an open framework for developing plan optimization models for knowledge-based planning (KBP).Approach.Our framework includes radiotherapy treatment data (i.e. reference plans) for 100 patients with head-and-neck cancer who were treated with intensity-modulated radiotherapy. That data also includes high-quality dose predictions from 19 KBP models that were developed by different research groups using out-of-sample data during the OpenKBP Grand Challenge. The dose predictions were input to four fluence-based dose mimicking models to form 76 unique KBP pipelines that generated 7600 plans (76 pipelines × 100 patients). The predictions and KBP-generated plans were compared to the reference plans via: the dose score, which is the average mean absolute voxel-by-voxel difference in dose; the deviation in dose-volume histogram (DVH) points; and the frequency of clinical planning criteria satisfaction. We also performed a theoretical investigation to justify our dose mimicking models.Main results.The range in rank order correlation of the dose score between predictions and their KBP pipelines was 0.50-0.62, which indicates that the quality of the predictions was generally positively correlated with the quality of the plans. Additionally, compared to the input predictions, the KBP-generated plans performed significantly better (P< 0.05; one-sided Wilcoxon test) on 18 of 23 DVH points. Similarly, each optimization model generated plans that satisfied a higher percentage of criteria than the reference plans, which satisfied 3.5% more criteria than the set of all dose predictions. Lastly, our theoretical investigation demonstrated that the dose mimicking models generated plans that are also optimal for an inverse planning model.Significance.This was the largest international effort to date for evaluating the combination of KBP prediction and optimization models. We found that the best performing models significantly outperformed the reference dose and dose predictions. In the interest of reproducibility, our data and code is freely available.

Regional left ventricular myocardial contractility and stress in a finite element model of posterobasal myocardial infarction.

Recently, a noninvasive method for determining regional myocardial contractility, using an animal-specific finite element (FE) model-based optimization, was developed to study a sheep with anteroapical infarction (Sun et al., 2009, "A Computationally Efficient Formal Optimization of Regional Myocardial Contractility in a Sheep With Left Ventricular Aneurysm," ASME J. Biomech. Eng., 131(11), p. 111001). Using the methodology developed in the previous study (Sun et al., 2009, "A Computationally Efficient Formal Optimization of Regional Myocardial Contractility in a Sheep With Left Ventricular Aneurysm," ASME J. Biomech. Eng., 131(11), p. 111001), which incorporates tagged magnetic resonance images, three-dimensional myocardial strains, left ventricular (LV) volumes, and LV cardiac catheterization pressures, the regional myocardial contractility and stress distribution of a sheep with posterobasal infarction were investigated. Active material parameters in the noninfarcted border zone (BZ) myocardium adjacent to the infarct (T(max_B)), in the myocardium remote from the infarct (T(max_R)), and in the infarct (T(max_I)) were estimated by minimizing the errors between FE model-predicted and experimentally measured systolic strains and LV volumes using the previously developed optimization scheme. The optimized T(max_B) was found to be significantly depressed relative to T(max_R), while T(max_I) was found to be zero. The myofiber stress in the BZ was found to be elevated, relative to the remote region. This could cause further damage to the contracting myocytes, leading to heart failure.

A computationally efficient formal optimization of regional myocardial contractility in a sheep with left ventricular aneurysm.

A non-invasive method for estimating regional myocardial contractility in vivo would be of great value in the design and evaluation of new surgical and medical strategies to treat and/or prevent infarction-induced heart failure. As a first step towards developing such a method, an explicit finite element (FE) model-based formal optimization of regional myocardial contractility in a sheep with left ventricular (LV) aneurysm was performed using tagged magnetic resonance (MR) images and cardiac catheterization pressures. From the tagged MR images, 3-dimensional (3D) myocardial strains, LV volumes and geometry for the animal-specific 3D FE model of the LV were calculated, while the LV pressures provided physiological loading conditions. Active material parameters (T(max_B) and T(max_R)) in the non-infarcted myocardium adjacent to the aneurysm (borderzone) and in myocardium remote from the aneurysm were estimated by minimizing the errors between FE model-predicted and measured systolic strains and LV volumes using the successive response surface method for optimization. The significant depression in optimized T(max_B) relative to T(max_R) was confirmed by direct ex vivo force measurements from skinned fiber preparations. The optimized values of T(max_B) and T(max_R) were not overly sensitive to the passive material parameters specified. The computation time of less than 5 hours associated with our proposed method for estimating regional myocardial contractility in vivo makes it a potentially very useful clinical tool.

Computational modeling of drug transport across the in vitro cornea.

A novel quasi-3D (Q3D) modeling approach was developed to model networks of one dimensional structures like tubes and vessels common in human anatomy such as vascular and lymphatic systems, neural networks, and respiratory airways. Instead of a branching network of the same tissue type, this approach was extended to model an interconnected stack of different corneal tissue layers with membrane junction conditions assigned between the tissues. The multi-laminate structure of the cornea presents a unique barrier design and opportunity for investigation using Q3D modeling. A Q3D model of an in vitro rabbit cornea was created to simulate the drug transport across the cornea, accounting for transcellular and paracellular pathways of passive and convective drug transport as well as physicochemistry of lipophilic partitioning and protein binding. Lipophilic Rhodamine B and hydrophilic fluorescein were used as drug analogs. The model predictions for both hydrophilic and lipophilic tracers were able to match the experimental measurements along with the sharp discontinuities at the epithelium-stroma and stroma-endothelium interfaces. This new modeling approach was successfully applied towards pharmacokinetic modeling for use in topical ophthalmic drug design.

Clinical evaluation of a model-updated image-guidance approach to brain shift compensation: experience in 16 cases.

PURPOSE: Brain shift during neurosurgical procedures must be corrected for in order to reestablish accurate alignment for successful image-guided tumor resection. Sparse-data-driven biomechanical models that predict physiological brain shift by accounting for typical deformation-inducing events such as cerebrospinal fluid drainage, hyperosmotic drugs, swelling, retraction, resection, and tumor cavity collapse are an inexpensive solution. This study evaluated the robustness and accuracy of a biomechanical model-based brain shift correction system to assist with tumor resection surgery in 16 clinical cases. METHODS: Preoperative computation involved the generation of a patient-specific finite element model of the brain and creation of an atlas of brain deformation solutions calculated using a distribution of boundary and deformation-inducing forcing conditions (e.g., sag, tissue contraction, and tissue swelling). The optimum brain shift solution was determined using an inverse problem approach which linearly combines solutions from the atlas to match the cortical surface deformation data collected intraoperatively. The computed deformations were then used to update the preoperative images for all 16 patients. RESULTS: The mean brain shift measured ranged on average from 2.5 to 21.3 mm, and the biomechanical model-based correction system managed to account for the bulk of the brain shift, producing a mean corrected error ranging on average from 0.7 to 4.0 mm. CONCLUSIONS: Biomechanical models are an inexpensive means to assist intervention via correction for brain deformations that can compromise surgical navigation systems. To our knowledge, this study represents the most comprehensive clinical evaluation of a deformation correction pipeline for image-guided neurosurgery.

Residual Stress Impairs Pump Function After Surgical Ventricular Remodeling: A Finite Element Analysis.

BACKGROUND: Surgical ventricular restoration (Dor procedure) is generally thought to reduce left ventricular (LV) myofiber stress (FS) but to adversely affect pump function. However, the underlying mechanism is unclear. The goal of this study was to determine the effect of residual stress (RS) on LV FS and pump function after the Dor procedure. METHODS: Previously described finite element models of the LV based on magnetic resonance imaging data obtained in 5 sheep 16 weeks after anteroapical myocardial infarction were used. Simulated polyethylene terephthalate fiber (Dacron) patches that were elliptical and 25% of the infarct opening area were implanted using a virtual suture technique (VIRTUAL-DOR). In each case, diastole and systole were simulated, and RS, FS, LV volumes, systolic and diastolic function, and pump (Starling) function were calculated. RESULTS: VIRTUAL-DOR was associated with significant RS that was tensile (2.89 ± 1.31 kPa) in the remote myocardium and compressive (234.15 ± 65.53 kPa) in the border zone. VIRTUAL-DOR+RS (compared with VIRTUAL-DOR-NO-RS) was associated with further reduction in regional diastolic and systolic FS, with the greatest change in the border zone (43.5-fold and 7.1-fold, respectively; p < 0.0001). VIRTUAL-DOR+RS was also associated with further reduction in systolic and diastolic volumes (7.9%; p = 0.0606, and 10.6%; p = 0.0630, respectively). The resultant effect was a further reduction in pump function after VIRTUAL-DOR+RS. CONCLUSIONS: Residual stress that occurs after the Dor procedure is positive (tensile) in the remote myocardium and negative (compressive) in the border zone and associated with reductions in FS and LV volumes. The resultant effect is a further reduction in LV pump (Starling) function.

Continuous flow left ventricular pump support and its effect on regional left ventricular wall stress: finite element analysis study.

Left ventricular assist device (LVAD) support unloads left ventricular (LV) pressure and volume and decreases wall stress. This study investigated the effect of systematic LVAD unloading on the 3-dimensional myocardial wall stress by employing finite element models containing layered fiber structure, active contractility, and passive stiffness. The HeartMate II(®) (Thoratec, Inc., Pleasanton, CA) was used for LV unloading. The model geometries and hemodynamic conditions for baseline (BL) and LVAD support (LVsupport) were acquired from the Penn State mock circulatory cardiac simulator. Myocardial wall stress of BL was compared with that of LVsupport at 8,000, 9,000, 10,000 RPM, providing mean pump flow (Q(mean)) of 2.6, 3.2, and 3.7 l/min, respectively. LVAD support was more effective at unloading during diastole as compared to systole. Approximately 40, 50, and 60% of end-diastolic wall stress reduction were achieved at Q(mean) of 2.6, 3.2, and 3.7 l/min, respectively, as compared to only a 10% reduction of end-systolic wall stress at Q(mean) of 3.7 l/min. In addition, there was a stress concentration during systole at the apex due to the cannulation and reduced boundary motion. This modeling study can be used to further understand optimal unloading, pump control, patient management, and cannula design.

Near Real-Time Computer Assisted Surgery for Brain Shift Correction Using Biomechanical Models.

Conventional image-guided neurosurgery relies on preoperative images to provide surgical navigational information and visualization. However, these images are no longer accurate once the skull has been opened and brain shift occurs. To account for changes in the shape of the brain caused by mechanical (e.g., gravity-induced deformations) and physiological effects (e.g., hyperosmotic drug-induced shrinking, or edema-induced swelling), updated images of the brain must be provided to the neuronavigation system in a timely manner for practical use in the operating room. In this paper, a novel preoperative and intraoperative computational processing pipeline for near real-time brain shift correction in the operating room was developed to automate and simplify the processing steps. Preoperatively, a computer model of the patient's brain with a subsequent atlas of potential deformations due to surgery is generated from diagnostic image volumes. In the case of interim gross changes between diagnosis, and surgery when reimaging is necessary, our preoperative pipeline can be generated within one day of surgery. Intraoperatively, sparse data measuring the cortical brain surface is collected using an optically tracked portable laser range scanner. These data are then used to guide an inverse modeling framework whereby full volumetric brain deformations are reconstructed from precomputed atlas solutions to rapidly match intraoperative cortical surface shift measurements. Once complete, the volumetric displacement field is used to update, i.e., deform, preoperative brain images to their intraoperative shifted state. In this paper, five surgical cases were analyzed with respect to the computational pipeline and workflow timing. With respect to postcortical surface data acquisition, the approximate execution time was 4.5 min. The total update process which included positioning the scanner, data acquisition, inverse model processing, and image deforming was ~11-13 min. In addition, easily implemented hardware, software, and workflow processes were identified for improved performance in the near future.

Evaluation of conoscopic holography for estimating tumor resection cavities in model-based image-guided neurosurgery.

Surgical navigation relies on accurately mapping the intraoperative state of the patient to models derived from preoperative images. In image-guided neurosurgery, soft tissue deformations are common and have been shown to compromise the accuracy of guidance systems. In lieu of whole-brain intraoperative imaging, some advocate the use of intraoperatively acquired sparse data from laser-range scans, ultrasound imaging, or stereo reconstruction coupled with a computational model to drive subsurface deformations. Some authors have reported on compensating for brain sag, swelling, retraction, and the application of pharmaceuticals such as mannitol with these models. To date, strategies for modeling tissue resection have been limited. In this paper, we report our experiences with a novel digitization approach, called a conoprobe, to document tissue resection cavities and assess the impact of resection on model-based guidance systems. Specifically, the conoprobe was used to digitize the interior of the resection cavity during eight brain tumor resection surgeries and then compared against model prediction results of tumor locations. We should note that no effort was made to incorporate resection into the model but rather the objective was to determine if measurement was possible to study the impact on modeling tissue resection. In addition, the digitized resection cavity was compared with early postoperative MRI scans to determine whether these scans can further inform tissue resection. The results demonstrate benefit in model correction despite not having resection explicitly modeled. However, results also indicate the challenge that resection provides for model-correction approaches. With respect to the digitization technology, it is clear that the conoprobe provides important real-time data regarding resection and adds another dimension to our noncontact instrumentation framework for soft-tissue deformation compensation in guidance systems.

Integrating Retraction Modeling Into an Atlas-Based Framework for Brain Shift Prediction.

In recent work, an atlas-based statistical model for brain shift prediction, which accounts for uncertainty in the intraoperative environment, has been proposed. Previous work reported in the literature using this technique did not account for local deformation caused by surgical retraction. It is challenging to precisely localize the retractor location prior to surgery and the retractor is often moved in the course of the procedure. This paper proposes a technique that involves computing the retractor-induced brain deformation in the operating room through an active model solve and linearly superposing the solution with the precomputed deformation atlas. As a result, the new method takes advantage of the atlas-based framework's accounting for uncertainties while also incorporating the effects of retraction with minimal intraoperative computing. This new approach was tested using simulation and phantom experiments. The results showed an improvement in average shift correction from 50% (ranging from 14 to 81%) for gravity atlas alone to 80% using the active solve retraction component (ranging from 73 to 85%). This paper presents a novel yet simple way to integrate retraction into the atlas-based brain shift computation framework.

The benefit of enhanced contractility in the infarct borderzone: a virtual experiment.

OBJECTIVES: Contractile function in the normally perfused infarct borderzone (BZ) is depressed. However, the impact of reduced BZ contractility on left ventricular (LV) pump function is unknown. As a consequence, there have been no therapies specifically designed to improve BZ contractility. We tested the hypothesis that an improvement in borderzone contractility will improve LV pump function. METHODS: From a previously reported study, magnetic resonance imaging (MRI) images with non-invasive tags were used to calculate 3D myocardial strain in five sheep 16 weeks after anteroapical myocardial infarction. Animal-specific finite element (FE) models were created using MRI data and LV pressure obtained at early diastolic filling. Analysis of borderzone function using those FE models has been previously reported. Chamber stiffness, pump function (Starling's law) and stress in the fiber, cross fiber, and circumferential directions were calculated. Animal-specific FE models were performed for three cases: (a) impaired BZ contractility (INJURED); (b) BZ-contractility fully restored (100% BZ IMPROVEMENT); or (c) BZ-contractility partially restored (50% BZ IMPROVEMENT). RESULTS: 100% BZ IMPROVEMENT and 50% BZ IMPROVEMENT both caused an upward shift in the Starling relationship, resulting in a large (36 and 26%) increase in stroke volume at LVP(ED) = 20 mmHg (8.0 ml, p < 0.001). Moreover, there were a leftward shift in the end-systolic pressure volume relationship, resulting in a 7 and 5% increase in LVP(ES) at 110 mmHg (7.7 ml, p < 0.005). It showed that even 50% BZ IMPROVEMENT was sufficient to drive much of the calculated increase in function. CONCLUSION: Improved borderzone contractility has a beneficial effect on LV pump function. Partial improvement of borderzone contractility was sufficient to drive much of the calculated increase in function. Therapies specifically designed to improve borderzone contractility should be developed.

Comparison of the Young-Laplace law and finite element based calculation of ventricular wall stress: implications for postinfarct and surgical ventricular remodeling.

BACKGROUND: Both the Young-Laplace law and finite element (FE) based methods have been used to calculate left ventricular wall stress. We tested the hypothesis that the Young-Laplace law is able to reproduce results obtained with the FE method. METHODS: Magnetic resonance imaging scans with noninvasive tags were used to calculate three-dimensional myocardial strain in 5 sheep 16 weeks after anteroapical myocardial infarction, and in 1 of those sheep 6 weeks after a Dor procedure. Animal-specific FE models were created from the remaining 5 animals using magnetic resonance images obtained at early diastolic filling. The FE-based stress in the fiber, cross-fiber, and circumferential directions was calculated and compared to stress calculated with the assumption that wall thickness is very much less than the radius of curvature (Young-Laplace law), and without that assumption (modified Laplace). RESULTS: First, circumferential stress calculated with the modified Laplace law is closer to results obtained with the FE method than stress calculated with the Young-Laplace law. However, there are pronounced regional differences, with the largest difference between modified Laplace and FE occurring in the inner and outer layers of the infarct borderzone. Also, stress calculated with the modified Laplace is very different than stress in the fiber and cross-fiber direction calculated with FE. As a consequence, the modified Laplace law is inaccurate when used to calculate the effect of the Dor procedure on regional ventricular stress. CONCLUSIONS: The FE method is necessary to determine stress in the left ventricle with postinfarct and surgical ventricular remodeling.

Premature adjacent vertebral fracture after vertebroplasty: a biomechanical study.

BACKGROUND: There is an increased incidence of fractures in untreated adjacent vertebrae after vertebroplasty. OBJECTIVE: To introduce unconstrained 6 degrees of freedom biomechanical testing to investigate whether vertebroplasty lowered the fracture strength of adjacent untreated vertebrae under physiological loading conditions and to describe the observed fracture pattern. METHODS: Three-level spinal segments (T10-12 and L1-3) from 6 spines were tested under unconstrained axial compression in which shear forces and torque were minimized using a 6-degrees of freedom robotic arm. Fracture initiation loads and ultimate failure loads of lumbar segments were predicted from the corresponding thoracic segments by assuming constant fracture stress along the spinal column. The predicted values were compared with postvertebroplasty experimental values of the lumbar spine segments. Plain radiographs were taken at 600-N increments to record the developing fracture pattern. RESULTS: All 6 vertebroplasty group specimens experienced reductions in fracture strengths ranging from 27.4% to 47.6% with an average decrease of 32.6% (P < .002) and reductions in ultimate failure load ranging from 1.6% to 47.3%, with an average decrease of 34.7% (P < .003) compared with predicted values from the nonvertebroplasty group. In all vertebroplasty group specimens, the superior and inferior endplates of the untreated middle vertebral body (L2) were deflected, whereas 5 of the 6 nonvertebroplasty group specimens did not show any evidence of endplate deflection. CONCLUSION: Vertebroplasty altered the load transfer along the anterior spinal column, thereby statistically significantly increasing fracture risk and ultimate failure load of the untreated adjacent vertebrae. The radiographic findings support the endplate deflection fracture mechanism as the cause of adjacent fractures after vertebroplasty.

Dor procedure for dyskinetic anteroapical myocardial infarction fails to improve contractility in the border zone.

BACKGROUND: Endoventricular patch plasty (Dor) is used to reduce left ventricular volume after myocardial infarction and subsequent left ventricular remodeling. METHODS AND RESULTS: End-diastolic and end-systolic pressure-volume and Starling relationships were measured, and magnetic resonance images with noninvasive tags were used to calculate 3-dimensional myocardial strain in 6 sheep 2 weeks before and 2 and 6 weeks after the Dor procedure. These experimental results were previously reported. The imaging data from 1 sheep were incomplete. Animal specific finite element models were created from the remaining 5 animals using magnetic resonance images and left ventricular pressure obtained at early diastolic filling. Finite element models were optimized with 3-dimensional strain and used to determine systolic material properties, T(max,skinned-fiber), and diastolic and systolic stress in remote myocardium and border zone. Six weeks after the Dor procedure, end-diastolic and end-systolic stress in the border zone were substantially reduced. However, although there was a slight increase in T(max,skinned-fiber) in the border zone near the myocardial infarction at 6 weeks, the change was not significant. CONCLUSIONS: The Dor procedure decreases end-diastolic and end-systolic stress but fails to improve contractility in the infarct border zone. Future work should focus on measures that will enhance border zone function alone or in combination with surgical remodeling.

Effect of adjustable passive constraint on the failing left ventricle: a finite-element model study.

BACKGROUND: Passive constraint is used to prevent left ventricular dilation and subsequent remodeling. However, there has been concern about the effect of passive constraint on diastolic left ventricular chamber stiffness and pump function. This study determined the relationship between constraint, diastolic wall stress, chamber stiffness, and pump function. We tested the hypothesis that passive constraint at 3 mm Hg reduces wall stress with minimal change in pump function. METHODS: A three-dimensional finite-element model of the globally dilated left ventricle based on left ventricular dimensions obtained in dogs that had undergone serial intracoronary microsphere injection was created. The model was adjusted to match experimentally observed end-diastolic left ventricular volume and midventricular wall thickness. The experimental results used to create the model were previously reported. A pressure of 3, 5, 7, and 9 mm Hg was applied to the epicardium. Fiber stress, end-diastolic pressure-volume relationship, end-systolic pressure-volume relationship, and the stroke volume-end-diastolic pressure (Starling) relationship were calculated. RESULTS: As epicardial constraint pressure increased, fiber stress decreased, the end-diastolic pressure-volume relationship shifted to the left, and the Starling relationship shifted down and to the right. The end-systolic pressure-volume relationship did not change. A constraining pressure of 2.3 mm Hg was associated with a 10% reduction in stroke volume, and mean end-diastolic fiber stress was reduced by 18.3% (inner wall), 15.3% (mid wall), and 14.2% (outer wall). CONCLUSIONS: Both stress and cardiac output decrease in a linear fashion as the amount of passive constraint is increased. If the reduction in cardiac output is to be less than 10%, passive constraint should not exceed 2.3 mm Hg. On the other hand, this amount of constraint may be sufficient to reverse eccentric hypertrophy after myocardial infarction.

Biomechanics of prophylactic vertebral reinforcement.

STUDY DESIGN: The effects of bone cement placement, volume, and bone density on the degree of biomechanical reinforcement on cadaveric vertebral bodies were studied using experimentally calibrated detailed finite element models. OBJECTIVES: To investigate the efficacy of prophylactic vertebroplasty on intact vertebral bodies with respect to biomechanical recovery and fracture risk reduction. SUMMARY OF BACKGROUND DATA: Vertebroplasty is a potentially effective fracture prevention treatment, but the risk of complications due to cement leakage must be minimized. Therefore, the least amount of bone cement required to improve vertebral strengths to low fracture risk levels need to be determined. METHODS: Six different polymethyl methacrylate volumes--1, 2.5, 3.5, 5, 7.5 and 9 cm--were virtually implanted into previously validated vertebral body finite element models, following bipedicular and posterolateral vertebroplasty approaches. Stiffness and fracture load of the treated and untreated vertebral body models under uniaxial compression were determined. RESULTS: Greater augmentation effects were observed for vertebral bodies with average quantitative computed tomography densities below 0.1 g/cm injected with polymethyl methacrylate volumes higher than 20% compared to lower injection volumes and higher bone densities, as well as for the bipedicular approach versus posterolateral. Vertebral bodies at high risk of fracture required at least 20% fill of polymethyl methacrylate to improve the mechanical integrity of vertebral bodies to low fracture risk levels, whereas 5% to 15% polymethyl methacrylate volumes were needed for the medium-risk vertebral bodies. CONCLUSION: Prophylactic vertebroplasty can be effective in reducing fracture risk. However, for the polymethyl methacrylate volume (20%) required for the successful reinforcement of high-risk vertebral bodies, the risk of complications will be as high as that for current vertebroplasty procedure for fracture repair. Therefore, alternative materials have to be investigated for prophylactic vertebroplasty. Furthermore, bipedicular vertebroplasty is the recommended approach due to its higher strengthening effect and easier surgical access than the posterolateral case.

Evolution of vertebroplasty: a biomechanical perspective.

This paper is a collection of computational, finite element studies on vertebroplasty performed in our laboratory, which attempts to provide new biomechanical evidence and a fresh perspective into how the procedure can be implemented more effectively toward the goal of preventing osteoporosis-related fractures. The percutaneous application of a bone cement to vertebral defects associated with osteoporotic vertebral compression fracture has proven clinical successful in alleviating back pain. When the biomechanical efficacy of the procedure was examined, however, vertebroplasty was found to be limited in its ability to provide sufficient augmentation to prevent further fractures without risking complications arising from cement extravasations. The procedure may instead be more efficient biomechanically as a prophylactic treatment, to mechanically reinforce osteoporotic vertebrae at risk for fracture. Patient selection for such intervention may be reliably achieved with the more accurate fracture risk assessments based on vertebral strength, predicted using geometrically detailed, specimen-specific finite element models, rather than on bone density alone. Optimal cement volume, placement, and material properties were also recommended. The future of vertebroplasty involving biodegradable augmentation material laced with osteogenic agents that upon release will stimulate new bone growth and increase bone mass was proposed.