Accuracy of analytically determined fractional flow reserve derived from coronary angiography for non-invasive assessment of coronary artery stenosis.

BACKGROUND: Fractional flow reserve (FFR) determined invasively has been globally accepted as the gold standard for determining the functional significance of coronary artery stenoses. However, despite its great importance, the invasive method has certain disadvantages, including the risk of vascular injuries, the need for vasodilation, and significant medical costs. That is why great attention was paid to the development of non-invasive methods that would enable reliable diagnosis without exposing patients to the risk of unwanted consequences. OBJECTIVE: This paper aimed to create and verify an alternative, less resource- and time-demanding, non-invasive solution. METHODS: The determination of FFR is based on the application of the fundamental laws of fluid dynamics. All energy losses in the coronary artery with stenosis were identified and analyzed in detail. A three-dimensional model of a coronary artery was generated using the corresponding angiographic images. Finally, the pressure due to stenosis was calculated and the FFR was determined. RESULTS: The results obtained using the proposed analytical method were compared with available experimental data for 40 patients who experienced the invasive coronary angiography. The coefficient of determination, mean difference and standard deviation values are determined to be 0.726, -0.017 and 0.056, respectively. These values were slightly higher for FFR values above 0.80. CONCLUSION: The FFR calculated by the proposed analytical method has a relatively good correlation with clinical data, which leads to the conclusion that it can provide a reliable assessment of the functional significance of coronary stenosis.

Software for optimized virtual stenting of patient-specific coronary arteries reconstructed from angiography images.

Detection of clinically relevant stenosis within coronary arteries as well as planning of treatment (stent implantation) are important topics in clinical cardiology. In this study a thorough methodology for virtual stenting assistance is proposed, that includes the 3D reconstruction of a patient-specific coronary artery from X-ray angiography images, hemodynamic simulations of blood flow, computation of a fractional flow reserve (FFR) equivalent, virtual stenting procedure and an optimization of the virtual stenting, by considering not only the value of computed FFR, but also the low and high WSS regions and the state of arterial wall after stenting. The evaluation of the proposed methodology is performed in two ways: the calculated values of FFR are compared with clinically measured values; and the results obtained for automated optimized virtual stenting are compared with virtual stenting performed manually by an expert clinician for the whole considered dataset. The agreement of the results in almost all cases demonstrates the accuracy of the proposed approach, and the small discrepancies only show the capabilities and benefits this approach can offer. The automated optimized virtual stenting technique can provide information about the most optimal stent position that ensures the maximum achievable FFR, while also considering the distribution of WSS and the state of arterial wall. The proposed methodology and developed software can therefore be used as a noninvasive method for planning of optimal patient-specific treatment strategies before invasive procedures and thus help to improve the clinical outcome of interventions and provide better treatment planning adapted to the particular patient.

Computer simulation of cervical tissue response to a hydraulic dilator device.

BACKGROUND: Classical mechanical dilators for cervical dilation are associated with various complications, such as uterine perforation, cervical laceration, infections and intraperitoneal hemorrhage. A new medical device called continuous controllable balloon dilator (CCBD) was constructed to make a significant reduction in all of the side effects of traditional mechanical dilation. METHOD: In this study we investigated numerically the cervical canal tissue response for Hegar and CCBD using our poroelastic finite element model and in-house software development. Boundary conditions for pressure loading on the tissue for both dilators in vivo were measured experimentally. Material properties of the cervical tissue were fitted with experimental in vivo data of pressure and fluid volume or balloon size. RESULTS: Obtained results for effective stresses inside the cervical tissue clearly showed higher stresses for Hegar dilator during dilation in comparison with our CCBD. CONCLUSION: This study opens a new avenue for the implementation of CCBD device instead of mechanical dilators to prevent cervical injury during cervical dilation.

Numerical vs analytical comparison with experimental fractional flow reserve values of right coronary artery stenosis.

BACKGROUND: The fractional flow reserve (FFR) index has been widely accepted as a standard diagnostic method for identifying functional relevance of coronary stenosis. Since the invasive techniques used for its determination are associated with a certain risk of vascular injury, as well as with an increased cost, several non-invasive procedures have been developed. OBJECTIVE: The aim of this study was to compare FFR values for the coronary artery obtained by computational fluid dynamics (CFD) and coronary computed tomography angiography (CCTA). METHODS: Computation of FFR has been performed using both numerical and the analytical method. The numerical method employs CFD to solve the governing equations which relate to mass and momentum conservation (the continuity equation and the Navier-Stokes equations) as well as CCTA to generate the three-dimensional computational domain. After imposing the appropriate boundary conditions, the values of the pressure change are calculated and the FFR index is determined. Based on Bernoulli's law, the analytical method calculates the overall pressure drop across the stenosis in the coronary artery, enabling FFR determination. RESULTS: The clinical data for twenty patients who underwent invasive coronary angiography are used to validate the results obtained by using CFD (together with CCTA) simulation and analytical solution. The medically measured FFR compared to the analytical one differs by about 4%, while, the difference is about 2.6% when compared to the numerical FFR. For FFR values below 0.8 (which are considered to be associated with myocardial ischemia) the standard error has a value of 0.01201, while the standard deviation is 0.02081. For FFR values above 0.80, these values are slightly higher. Bland-Altman analysis showed that medical measurement and numerical FFR were in good agreement (SD = 0.0292, p< 0.0001). CONCLUSIONS: The analytically calculated FFR has a slightly lower coefficient of determination than the numerically computed FFR when compared with experimental one. However, it can still give a reliable answer to the question of whether patients need a stent, bypass surgery or only drug treatment and it requires a significantly lower computation time.

Application of Machine Learning for Segmentation of the Pulmonary Acinus Imaged by Synchrotron X-Ray Tomography.

Background: To assess the effectiveness of inhalation therapy, it is important to evaluate the lungs' structure; thus, visualization of the entire lungs at the level of the alveoli is necessary. To achieve this goal, the applied visualization technique must satisfy the following two conditions simultaneously: (1) it has to obtain images of the entire lungs, since one part of the lungs is influenced by the other parts, and (2) the images have to capture the detailed structure of the alveolus/acinus in which gas exchange occurs. However, current visualization techniques do not fulfill these two conditions simultaneously. Segmentation is a process in which each pixel of the obtained high-resolution images is simplified (i.e., the representation of an image is changed by categorizing and modifying each pixel) so that we can perform three-dimensional volume rendering. One of the bottlenecks of current approaches is that the accuracy of the segmentation of each image has to be evaluated on the outcome of the process (mainly by an expert). It is a formidable task to evaluate the astronomically large numbers of images that would be required to resolve the entire lungs in high resolution. Methods: To overcome this challenge, we propose a new approach based on machine learning (ML) techniques for the validation step. Results: We demonstrate the accuracy of the segmentation process itself by comparison with previously validated images. In this ML approach, to achieve a reasonable accuracy, millions/billions of parameters used for segmentation have to be optimized. This computationally demanding new approach is achievable only due to recent dramatic increases in computation power. Conclusion: The objective of this article is to explain the advantages of ML over the classical approach for acinar imaging.

Fractional Flow Reserve-Based Patient Risk Classification.

Cardiovascular diseases (CVDs) are a leading cause of death. If not treated in a timely manner, cardiovascular diseases can cause a plethora of major life complications that can include disability and a loss of the ability to work. Globally, acute myocardial infarction (AMI) is responsible for about 3 million deaths a year. The development of strategies for prevention, but also the early detection of cardiovascular risks, is of great importance. The fractional flow reserve (FFR) is a measurement used for an assessment of the severity of coronary artery stenosis. The goal of this research was to develop a technique that can be used for patient fractional flow reserve evaluation, as well as for the assessment of the risk of death via gathered demographic and clinical data. A classification ensemble model was built using the random forest machine learning algorithm for the purposes of risk prediction. Referent patient classes were identified by the observed fractional flow reserve value, where patients with an FFR higher than 0.8 were viewed as low risk, while those with an FFR lower than 0.8 were identified as high risk. The final classification ensemble achieved a 76.21% value of estimated prediction accuracy, thus achieving a mean prediction accuracy of 74.1%, 77.3%, 78.1% and 83.6% over the models tested with 5%, 10%, 15% and 20% of the test samples, respectively. Along with the machine learning approach, a numerical approach was implemented through a 3D reconstruction of the coronary arteries for the purposes of stenosis monitoring. Even with a small number of available data points, the proposed methodology achieved satisfying results. However, these results can be improved in the future through the introduction of additional data, which will, in turn, allow for the utilization of different machine learning algorithms.

In Silico Clinical Trials for Cardiovascular Disease.

The SILICOFCM project mainly aims to develop a computational platform for in silico clinical trials of familial cardiomyopathies (FCMs). The unique characteristic of the platform is the integration of patient-specific biological, genetic, and clinical imaging data. The platform allows the testing and optimization of medical treatment to maximize positive therapeutic outcomes. Thus, adverse effects and drug interactions can be avoided, sudden cardiac death can be prevented, and the time between the commencement of drug treatment and the desired result can be shortened. This article presents a parametric model of the left ventricle automatically generated from patient-specific ultrasound images by applying an electromechanical model of the heart. Drug effects were prescribed through specific boundary conditions for inlet and outlet flow, ECG measurements, and calcium function for heart muscle properties. Genetic data from patients were incorporated through the material property of the ventricle wall. Apical view analysis involves segmenting the left ventricle using a previously trained U-net framework and calculating the bordering rectangle based on the length of the left ventricle in the diastolic and systolic cycle. M-mode view analysis includes bordering of the characteristic areas of the left ventricle in the M-mode view. After extracting the dimensions of the left ventricle, a finite elements mesh was generated based on mesh options, and a finite element analysis simulation was run with user-provided inlet and outlet velocities. Users can directly visualize on the platform various simulation results such as pressure-volume, pressure-strain, and myocardial work-time diagrams, as well as animations of different fields such as displacements, pressures, velocity, and shear stresses.

A study on the accuracy and efficiency of the improved numerical model for stent implantation using clinical data.

BACKGROUND AND OBJECTIVES: Stent implantation procedure should be carefully planned and adapted to the particular patient in order to minimize possible complications. Numerical simulations can provide useful quantitative data about the state of the artery after the implantation, as well as information about the benefits of the intervention from the hemodynamical point of view. METHODS: In this paper, a numerical model for stent implantation is presented. This numerical model simulates the stent expansion, the interaction of the stent with arterial wall and the deformation of the arterial wall under the influence of the stent. FE method was used to perform CFD simulations and the effects of stenting were analyzed by comparing the hemodynamic parameters before and after stent implantation. RESULTS: Clinical data for overall 34 patients was used for the simulations, and for 9 of them data from follow up examinations was used to validate the results of simulations of stent implantation. CONCLUSIONS: The good agreement of results (less than 4.1% of SD error for all the 9 validation cases) demonstrated the accuracy of the presented numerical model. The developed approach can be a valuable tool for the improvement of pre-operative planning and patient-specific treatment optimization.

Numerical simulation of stent deployment within patient-specific artery and its validation against clinical data.

BACKGROUND AND OBJECTIVE: One of the most widely adopted endovascular treatment procedures is the stent implantation. The effectiveness of the treatment depends on the appropriate stent expansion. However, it is difficult to accurately predict the outcome of such an endovascular intervention. Numerical simulations represent a useful tool to study the complex behavior of the stent during deployment. This study presents a numerical model capable of simulating this process. METHODS: The numerical model consists of three parts: modeling of stent expansion, modeling the interaction of the stent with the arterial wall and the deformation of the arterial wall. The model is able to predict the shapes of both stent and arterial wall during the entire deployment process. Simulations are performed using patient-specific clinical data that ensures more realistic results. RESULTS: The numerical simulations of stent deployment are performed using the extracted geometry of the coronary arteries of two patients. The obtained results are validated against clinical data from the follow up examination and both quantitative and qualitative analysis of the results is presented. The areas of several slices of the arterial wall are calculated for all the three states (before, after and follow up) and the standard error of the area when comparing simulation and follow up examination is 5.27% for patient #1 and 4.5% for patient #2. CONCLUSIONS: The final goal of numerical simulations in stent deployment should be to provide a clinical tool that is capable of reliably predicting the treatment outcome. This study showed through the good agreement of results of the numerical simulations and clinical data that the presented numerical model represents a step towards this final goal. These simulations can also provide valuable information about distribution of forces and stress in the arterial wall that can improve pre-operative planning and treatment optimization.

Computational and experimental model of transdermal iontophorethic drug delivery system.

The concept of iontophoresis is often applied to increase the transdermal transport of drugs and other bioactive agents into the skin or other tissues. It is a non-invasive drug delivery method which involves electromigration and electroosmosis in addition to diffusion and is shown to be a viable alternative to conventional administration routs such as oral, hypodermic and intravenous injection. In this study we investigated, experimentally and numerically, in vitro drug delivery of dexamethasone sodium phosphate to porcine skin. Different current densities, delivery durations and drug loads were investigated experimentally and introduced as boundary conditions for numerical simulations. Nernst-Planck equation was used for calculation of active substance flux through equivalent model of homogeneous hydrogel and skin layers. The obtained numerical results were in good agreement with experimental observations. A comprehensive in-silico platform, which includes appropriate numerical tools for fitting, could contribute to iontophoretic drug-delivery devices design and correct dosage and drug clearance profiles as well as to perform much faster in-silico experiments to better determine parameters and performance criteria of iontophoretic drug delivery.

Trauma of the Frontal Region Is Influenced by the Volume of Frontal Sinuses. A Finite Element Study.

Anatomy of frontal sinuses varies individually, from differences in volume and shape to a rare case when the sinuses are absent. However, there are scarce data related to influence of these variations on impact generated fracture pattern. Therefore, the aim of this study was to analyse the influence of frontal sinus volume on the stress distribution and fracture pattern in the frontal region. The study included four representative Finite Element models of the skull. Reference model was built on the basis of computed tomography scans of a human head with normally developed frontal sinuses. By modifying the reference model, three additional models were generated: a model without sinuses, with hypoplasic, and with hyperplasic sinuses. A 7.7 kN force was applied perpendicularly to the forehead of each model, in order to simulate a frontal impact. The results demonstrated that the distribution of impact stress in frontal region depends on the frontal sinus volume. The anterior sinus wall showed the highest fragility in case with hyperplasic sinuses, whereas posterior wall/inner plate showed more fragility in cases with hypoplasic and undeveloped sinuses. Well-developed frontal sinuses might, through absorption of the impact energy by anterior wall, protect the posterior wall and intracranial contents.

Modeling the Behavior of Red Blood Cells within the Caudal Vein Plexus of Zebrafish.

Due to the important biological role of red blood cells (RBCs) in vertebrates, the analysis of reshaping and dynamics of RBCs motion is a critical issue in physiology and biomechanics. In this paper the behavior of RBCs within the immature capillary plexus during embryonic development of zebrafish has been analyzed. Relying on the fact that zebrafish embryos are small and optically transparent, it is possible to image the blood flow. In this way the anatomy of blood vessels is monitored along with the circulation throughout their development. Numerical simulations were performed using a specific numerical model that combines fluid flow simulation, modeling of the interaction of individual RBCs immersed in blood plasma with the surrounding fluid and modeling the deformation of individual cells. The results of numerical simulations are in accordance with the in vivo observed region of interest within the caudal vein plexus of the zebrafish embryo. Good agreement of results demonstrates the capabilities of the developed numerical model to predict and analyze the motion and deformation of RBCs in complex geometries. The proposed model (methodology) will help to elucidate different rheological and hematological related pathologies and finally to design better treatment strategies.

Computational and experimental model of electroporation for human aorta.

PURPOSE: In this study the computational and experimental electroporation model with human aorta tissue is made in order to examine the reduction of smooth muscle cells. METHODS: The segments in native state of the aorta are treated by electroporation method through a series of electrical impulses from 50 V/cm to 2500 V/cm. For each patient we analyzed one sample with and one sample without electroporation as a control. In the computational study, electrical field distribution is solved by the Laplace equation. The Pennes Bioheat equation without metabolism and blood perfusion heating is used to solve heat transfer problems. Different conductivity values are used in order to fit the experimental results. RESULTS: Experimental histology has shown us that there are a smaller number of vascular smooth muscle cells (VSMC) nuclei at the tunica media, while the elastic fibre morphology is maintained 24 h after electroporation. In the computational model, heat generation coupled with electrical field is included. The fitting procedure is applied for conductivity values in order to make material properties of the aorta tissue. The fitting procedure gives tissue conductivity of 0.44 [S/m] for applied electrical field of 2500 V/cm. CONCLUSIONS: Future studies are necessary for investigation of a new device for in-vivo ablation with electroporation of plaque stenosis. It will open up a new avenue for stenosis treatment without stent implantation.

Computational modeling of shear forces and experimental validation of endothelial cell responses in an orbital well shaker system.

Vascular endothelial cells are continuously exposed to hemodynamic shear stress. Intensity and type of shear stress are highly relevant to vascular physiology and pathology. Here, we modeled shear stress distribution in a tissue culture well (R = 17.5 mm, fill volume 2 ml) under orbital translation using computational fluid dynamics with the finite element method. Free surface distribution, wall shear stress, inclination angle, drag force, and oscillatory index on the bottom surface were modeled. Obtained results predict nonuniform shear stress distribution during cycle, with higher oscillatory shear index, higher drag force values, higher circular component, and larger inclination angle of the shear stress at the periphery of the well compared with the center of the well. The oscillatory index, inclination angle, and drag force are new quantitative parameters modeled in this system, which provide a better understanding of the hydrodynamic conditions experienced and reflect the pulsatile character of blood flow in vivo. Validation experiments revealed that endothelial cells at the well periphery aligned under flow and increased Kruppel-like Factor 4 (KLF-4), cyclooxygenase-2 (COX-2) expression and endothelial nitric oxide synthase (eNOS) phosphorylation. In contrast, endothelial cells at the center of the well did not show clear directional alignment, did not induce the expression of KLF-4 and COX-2 nor increased eNOS phosphorylation. In conclusion, this improved computational modeling predicts that the orbital shaker model generates different hydrodynamic conditions at the periphery versus the center of the well eliciting divergent endothelial cell responses. The possibility of generating different hydrodynamic conditions in the same well makes this model highly attractive to study responses of distinct regions of the same endothelial monolayer to different types of shear stresses thereby better reflecting in vivo conditions.

Pharmacological Modulation of Hemodynamics in Adult Zebrafish In Vivo.

INTRODUCTION: Hemodynamic parameters in zebrafish receive increasing attention because of their important role in cardiovascular processes such as atherosclerosis, hematopoiesis, sprouting and intussusceptive angiogenesis. To study underlying mechanisms, the precise modulation of parameters like blood flow velocity or shear stress is centrally important. Questions related to blood flow have been addressed in the past in either embryonic or ex vivo-zebrafish models but little information is available for adult animals. Here we describe a pharmacological approach to modulate cardiac and hemodynamic parameters in adult zebrafish in vivo. MATERIALS AND METHODS: Adult zebrafish were paralyzed and orally perfused with salt water. The drugs isoprenaline and sodium nitroprusside were directly applied with the perfusate, thus closely resembling the preferred method for drug delivery in zebrafish, namely within the water. Drug effects on the heart and on blood flow in the submental vein were studied using electrocardiograms, in vivo-microscopy and mathematical flow simulations. RESULTS: Under control conditions, heart rate, blood flow velocity and shear stress varied less than ± 5%. Maximal chronotropic effects of isoprenaline were achieved at a concentration of 50 µmol/L, where it increased the heart rate by 22.6 ± 1.3% (n = 4; p < 0.0001). Blood flow velocity and shear stress in the submental vein were not significantly increased. Sodium nitroprusside at 1 mmol/L did not alter the heart rate but increased blood flow velocity by 110.46 ± 19.64% (p = 0.01) and shear stress by 117.96 ± 23.65% (n = 9; p = 0.03). DISCUSSION: In this study, we demonstrate that cardiac and hemodynamic parameters in adult zebrafish can be efficiently modulated by isoprenaline and sodium nitroprusside. Together with the suitability of the zebrafish for in vivo-microscopy and genetic modifications, the methodology described permits studying biological processes that are dependent on hemodynamic alterations.

Occlusal load distribution through the cortical and trabecular bone of the human mid-facial skeleton in natural dentition: a three-dimensional finite element study.

Understanding of the occlusal load distribution through the mid-facial skeleton in natural dentition is essential because alterations in magnitude and/or direction of occlusal forces may cause remarkable changes in cortical and trabecular bone structure. Previous analyses by strain gauge technique, photoelastic and, more recently, finite element (FE) methods provided no direct evidence for occlusal load distribution through the cortical and trabecular bone compartments individually. Therefore, we developed an improved three-dimensional FE model of the human skull in order to clarify the distribution of occlusal forces through the cortical and trabecular bone during habitual masticatory activities. Particular focus was placed on the load transfer through the anterior and posterior maxilla. The results were presented in von Mises stress (VMS) and the maximum principal stress, and compared to the reported FE and strain gauge data. Our qualitative stress analysis indicates that occlusal forces distribute through the mid-facial skeleton along five vertical and two horizontal buttresses. We demonstrated that cortical bone has a priority in the transfer of occlusal load in the anterior maxilla, whereas both cortical and trabecular bone in the posterior maxilla are equally involved in performing this task. Observed site dependence of the occlusal load distribution may help clinicians in creating strategies for implantology and orthodontic treatments. Additionally, the magnitude of VMS in our model was significantly lower in comparison to previous FE models composed only of cortical bone. This finding suggests that both cortical and trabecular bone should be modeled whenever stress will be quantitatively analyzed.

Numerical simulation of blood flow and plaque progression in carotid-carotid bypass patient specific case.

This study describes computer simulation of blood flow and plaque progression pattern in a patient who underwent surgical treatment for infected carotid prosthetic tube graft using carotid-carotid cross-over bypass. The 3D blood flow is governed by the Navier-Stokes equations, together with the continuity equation. Mass transfer within the blood lumen and through the arterial wall is coupled with the blood flow and is modelled by the convection-diffusion equation. Low-density lipoprotein (LDL) transport in lumen of the vessel is described by Kedem-Katchalsky equations. The inflammatory process is solved using three additional reaction-diffusion partial differential equations. Calculation based on a computer simulation showed that flow distribution in the left carotid artery (CA) was around 40-50% of the total flow in the right common CA. Also, the left CA had higher pressure gradient after surgical intervention. Plaque progression simulation predicted development of the atherosclerotic plaque in the position of the right common CA and the left internal CA. A novel way of atherosclerotic plaque progression modelling using computer simulation shows a potential clinical benefit with significant impact on the treatment strategy optimization.

Impact of the lower third molar presence and position on the fragility of mandibular angle and condyle: A Three-dimensional finite element study.

The aim of the present study was to investigate the influences of the presence and position of a lower third molar (M3) on the fragility of mandibular angle and condyle, using finite element analysis. From computed tomographic scans of a human mandible with normally erupted M3, two additional virtual models were generated: a mandibular model with partially impacted M3 and a model without M3. Two cases of impact were considered: a frontal and a lateral blow. The results are based on the chromatic analysis of the distributed von Mises and principal stresses, and calculation of their failure indices. In the frontal blow, the angle region showed the highest stress in the case with partially impacted M3, and the condylar region in the case without M3. Compressive stresses were dominant but caused no failure. Tensile stresses were recorded in the retromolar areas, but caused failure only in the case with partially impacted M3. In the lateral blow, the stress concentrated at the point of impact, in the ipsilateral and contralateral angle and condylar regions. The highest stresses were recorded in the case with partially impacted M3. Tensile stresses caused the failure on the ipsilateral side, whereas compressive stresses on the contralateral side.

Modeling of liver metastatic disease with applied drug therapy.

Colorectal carcinoma is acknowledged as the second leading cause of total cancer-related death in the European Region. The majority of deaths related to colorectal carcinoma are connected with liver metastatic disease. Approximately, in 25% of all patients, liver metastatic disease is diagnosed at the same time as the primary diagnosis, while up to a quarter of others would develop liver metastases in the course of the illness. In this study, we developed reaction-diffusion model and analyzed the effect of drug therapy on liver metastatic disease for a specific patient. Tumor volumes in specific time points were obtained using CT scan images. The nonlinear function for cell proliferation rate as well as data about clinically applied drug therapy was included in the model. Fitting procedure was used for parameter estimation. Good agreement of numerical and experimental results shows the feasibility and efficacy of the proposed system.

Microstructural properties of the mid-facial bones in relation to the distribution of occlusal loading.

Although the concept of the occlusal load transfer through the facial skeleton along the buttresses has been extensively studied, there has been no study to link microarchitecture of the mid-facial bones to the occlusal load distribution. The aim of this study was to analyze micro-structural properties of the mid-facial bones in relation to occlusal stress. The study was performed by combining the three-dimensional finite element analysis (3D FEA) and micro-computed tomography analysis (micro-CT). Clenching was simulated on the computer model of the adult male human skull which was also used as a source of bone specimens. After the FEA was run, stress was measured at the specific sites in cortical shell and trabecular bone of the model along and between the buttresses. From the corresponding sites on the skull, twenty-five cortical and thirteen cancellous bone specimens were harvested. The specimens were classified into high stress or low stress group based on the stress levels measured via the FEA. Micro-architecture of each specimen was assessed by micro-CT. In the high stress group, cortical bone showed a tendency toward greater thickness and density, lower porosity, and greater pore separation. Stress-related differences in microstructure between the groups were more pronounced in trabecular bone, which showed significantly greater bone volume fraction (BV/TV) and trabecular thickness (Tb.Th) in the high stress group. Our results suggest that the mid-facial bones in the adult dentate male skull exhibit regional variations in cortical and trabecular bone micro-architecture that could be a consequence of different occlusal stress.