Rapid and Precise Computation of Fractional Flow Reserve from Routine Two-Dimensional Coronary Angiograms Based on Fluid Mechanics: The Pilot FFR2D Study.

Objective: To present a novel pipeline for rapid and precise computation of fractional flow reserve from an analysis of routine two-dimensional coronary angiograms based on fluid mechanics equations (FFR2D). Material and methods: This was a pilot analytical study that was designed to assess the diagnostic performance of FFR2D versus the gold standard of FFR (threshold ≤ 0.80) measured with a pressure wire for the physiological assessment of intermediate coronary artery stenoses. In a single academic center, consecutive patients referred for diagnostic coronary angiography and potential revascularization between 1 September 2020 and 1 September 2022 were screened for eligibility. Routine two-dimensional angiograms at optimal viewing angles with minimal overlap and/or foreshortening were segmented semi-automatically to derive the vascular geometry of intermediate coronary lesions, and nonlinear pressure-flow mathematical relationships were applied to compute FFR2D. Results: Some 88 consecutive patients with a single intermediate coronary artery lesion were analyzed (LAD n = 74, RCA n = 9 and LCX n = 5; percent diameter stenosis of 45.7 ± 11.0%). The computed FFR2D was on average 0.821 ± 0.048 and correlated well with invasive FFR (r = 0.68, p < 0.001). There was very good agreement between FFR2D and invasive-wire FFR with minimal measurement bias (mean difference: 0.000 ± 0.048). The overall accuracy of FFR2D for diagnosing a critical epicardial artery stenosis was 90.9% (80 cases classified correctly out of 88 in total). FFR2D identified 24 true positives, 56 true negatives, 4 false positives, and 4 false negatives and predicted FFR ≤ 0.80 with a sensitivity of 85.7%, specificity of 93.3%, positive likelihood ratio of 13.0, and negative likelihood ratio of 0.15. FFR2D had a significantly better discriminatory capacity (area under the ROC curve: 0.95 [95% CI: 0.91-0.99]) compared to 50%DS on 2D-QCA (area under the ROC curve: 0.70 [95% CI: 0.59-0.82]; p = 0.0001) in predicting wire FFR ≤ 0.80. The median time of image analysis was 2 min and the median time of computation of the FFR2D results was 0.1 s. Conclusion: FFR2D may rapidly derive a precise image-based metric of fractional flow reserve with high diagnostic accuracy based on a single two-dimensional coronary angiogram.

Computation for biomechanical analysis of aortic aneurysms: the importance of computational grid.

Aortic wall stress is the most common variable of interest in abdominal aortic aneurysm (AAA) rupture risk assessment. Computation of such stress has been dominated by finite element analysis. However, the effects of finite element (FE) formulation, element quality, and methods of FE mesh construction on the efficiency, robustness, and accuracy of such computation have attracted little attention. In this study, we fill this knowledge gap by comparing the results of the calculated aortic wall stress for ten AAA patients using tetrahedral and hexahedral meshes when varying the FE formulation (displacement-based and hybrid), FE shape functions, spatial integration scheme, and number of elements through the wall thickness.

Image data and computational grids for computing brain shift and solving the electrocorticography forward problem.

This article describes the dataset applied in the research reported in NeuroImage article "Patient-specific solution of the electrocorticography forward problem in deforming brain" [1] that is available for download from the Zenodo data repository (https://zenodo.org/record/7687631) [2]. Preoperative structural and diffusion-weighted magnetic resonance (MR) and postoperative computed tomography (CT) images of a 12-year-old female epilepsy patient under evaluation for surgical intervention were obtained retrospectively from Boston Children's Hospital. We used these images to conduct the analysis at The University of Western Australia's Intelligent Systems for Medicine Laboratory using SlicerCBM [3], our open-source software extension for the 3D Slicer medical imaging platform. As part of the analysis, we processed the images to extract the patient-specific brain geometry; created computational grids, including a tetrahedral grid for the meshless solution of the biomechanical model and a regular hexahedral grid for the finite element solution of the electrocorticography forward problem; predicted the postoperative MRI and DTI that correspond to the brain configuration deformed by the placement of subdural electrodes using biomechanics-based image warping; and solved the patient-specific electrocorticography forward problem to compute the electric potential distribution within the patient's head using the original preoperative and predicted postoperative image data. The well-established and open-source file formats used in this dataset, including Nearly Raw Raster Data (NRRD) files for images, STL files for surface geometry, and Visualization Toolkit (VTK) files for computational grids, allow other research groups to easily reuse the data presented herein to solve the electrocorticography forward problem accounting for the brain shift caused by implantation of subdural grid electrodes.

SlicerCBM: automatic framework for biomechanical analysis of the brain.

PURPOSE: Brain shift that occurs during neurosurgery disturbs the brain's anatomy. Prediction of the brain shift is essential for accurate localisation of the surgical target. Biomechanical models have been envisaged as a possible tool for such predictions. In this study, we created a framework to automate the workflow for predicting intra-operative brain deformations. METHODS: We created our framework by uniquely combining our meshless total Lagrangian explicit dynamics (MTLED) algorithm for computing soft tissue deformations, open-source software libraries and built-in functions within 3D Slicer, an open-source software package widely used for medical research. Our framework generates the biomechanical brain model from the pre-operative MRI, computes brain deformation using MTLED and outputs results in the form of predicted warped intra-operative MRI. RESULTS: Our framework is used to solve three different neurosurgical brain shift scenarios: craniotomy, tumour resection and electrode placement. We evaluated our framework using nine patients. The average time to construct a patient-specific brain biomechanical model was 3 min, and that to compute deformations ranged from 13 to 23 min. We performed a qualitative evaluation by comparing our predicted intra-operative MRI with the actual intra-operative MRI. For quantitative evaluation, we computed Hausdorff distances between predicted and actual intra-operative ventricle surfaces. For patients with craniotomy and tumour resection, approximately 95% of the nodes on the ventricle surfaces are within two times the original in-plane resolution of the actual surface determined from the intra-operative MRI. CONCLUSION: Our framework provides a broader application of existing solution methods not only in research but also in clinics. We successfully demonstrated the application of our framework by predicting intra-operative deformations in nine patients undergoing neurosurgical procedures.

Hemodynamics of anterior circulation intracranial aneurysms with daughter blebs: investigating the multidirectionality of blood flow fields.

Recent advances in diagnostic neuroradiological imaging, allowed the detection of unruptured intracranial aneurysms (IAs). The shape - irregular or multilobular - of the aneurysmal dome, is considered as a possible rupture risk factor, independently of the size, the location and patient medical background. Disturbed blood flow fields in particular is thought to play a key role in IAs progression. However, there is an absence of widely-used hemodynamic indices to quantify the extent of a multi-directional disturbed flow. We simulated blood flow in twelve patient-specific anterior circulation unruptured intracranial aneurysms with daughter blebs utilizing the spectral/hp element framework Nektar++. We simulated three cardiac cycles using a volumetric flow rate waveform while we considered blood as a Newtonian fluid. To investigate the multidirectionality of the blood flow fields, besides the time-averaged wall shear stress (TAWSS), we calculated the oscillatory shear index (OSI), the relative residence time (RRT) and the time-averaged cross flow index (TACFI). Our CFD simulations suggest that in the majority of our vascular models there is a formation of complex intrasaccular flow patterns, resulting to low and highly oscillating WSS, especially in the area of the daughter blebs. The existence of disturbed multi-directional blood flow fields is also evident by the distributions of the RRT and the TACFI. These findings further support the theory that IAs with daughter blebs are linked to a potentially increased rupture risk.

Patient-specific solution of the electrocorticography forward problem in deforming brain.

Invasive intracranial electroencephalography (iEEG), or electrocorticography (ECoG), measures electric potential directly on the surface of the brain and can be used to inform treatment planning for epilepsy surgery. Combined with numerical modeling it can further improve accuracy of epilepsy surgery planning. Accurate solution of the iEEG forward problem, which is a crucial prerequisite for solving the iEEG inverse problem in epilepsy seizure onset zone localization, requires accurate representation of the patient's brain geometry and tissue electrical conductivity after implantation of electrodes. However, implantation of subdural grid electrodes causes the brain to deform, which invalidates preoperatively acquired image data. Moreover, postoperative magnetic resonance imaging (MRI) is incompatible with implanted electrodes and computed tomography (CT) has insufficient range of soft tissue contrast, which precludes both MRI and CT from being used to obtain the deformed postoperative geometry. In this paper, we present a biomechanics-based image warping procedure using preoperative MRI for tissue classification and postoperative CT for locating implanted electrodes to perform non-rigid registration of the preoperative image data to the postoperative configuration. We solve the iEEG forward problem on the predicted postoperative geometry using the finite element method (FEM) which accounts for patient-specific inhomogeneity and anisotropy of tissue conductivity. Results for the simulation of a current source in the brain show large differences in electric potential predicted by the models based on the original images and the deformed images corresponding to the brain geometry deformed by placement of invasive electrodes. Computation of the lead field matrix (useful for solution of the iEEG inverse problem) also showed significant differences between the different models. The results suggest that rapid and accurate solution of the forward problem in a deformed brain for a given patient is achievable.

Automatic framework for patient-specific modelling of tumour resection-induced brain shift.

Our motivation is to enable non-biomechanical engineering specialists to use sophisticated biomechanical models in the clinic to predict tumour resection-induced brain shift, and subsequently know the location of the residual tumour and its boundary. To achieve this goal, we developed a framework for automatically generating and solving patient-specific biomechanical models of the brain. This framework automatically determines patient-specific brain geometry from MRI data, generates patient-specific computational grid, assigns material properties, defines boundary conditions, applies external loads to the anatomical structures, and solves differential equations of nonlinear elasticity using Meshless Total Lagrangian Explicit Dynamics (MTLED) algorithm. We demonstrated the effectiveness and appropriateness of our framework on real clinical cases of tumour resection-induced brain shift.

Computer simulation of tumour resection-induced brain deformation by a meshless approach.

Tumour resection requires precise planning and navigation to maximise tumour removal while simultaneously protecting nearby healthy tissues. Neurosurgeons need to know the location of the remaining tumour after partial tumour removal before continuing with the resection. Our approach to the problem uses biomechanical modelling and computer simulation to compute the brain deformations after the tumour is resected. In this study, we use meshless Total Lagrangian explicit dynamics as the solver. The problem geometry is extracted from the patient-specific magnetic resonance imaging (MRI) data and includes the parenchyma, tumour, cerebrospinal fluid and skull. The appropriate non-linear material formulation is used. Loading is performed by imposing intra-operative conditions of gravity and reaction forces between the tumour and surrounding healthy parenchyma tissues. A finite frictionless sliding contact is enforced between the skull (rigid) and parenchyma. The meshless simulation results are compared to intra-operative MRI sections. We also calculate Hausdorff distances between the computed deformed surfaces (ventricles and tumour cavities) and surfaces observed intra-operatively. Over 80% of points on the ventricle surface and 95% of points on the tumour cavity surface were successfully registered (results within the limits of two times the original in-plane resolution of the intra-operative image). Computed results demonstrate the potential for our method in estimating the tissue deformation and tumour boundary during the resection.

Simulation of intracranial hemodynamics by an efficient and accurate immersed boundary scheme.

We use computational fluid dynamics (CFD) to simulate blood flow in intracranial aneurysms (IAs). Despite ongoing improvements in the accuracy and efficiency of body-fitted CFD solvers, generation of a high quality mesh appears as the bottleneck of the flow simulation and strongly affects the accuracy of the numerical solution. To overcome this drawback, we use an immersed boundary method. The proposed approach solves the incompressible Navier-Stokes equations on a rectangular (box) domain discretized using uniform Cartesian grid using the finite element method. The immersed object is represented by a set of points (Lagrangian points) located on the surface of the object. Grid local refinement is applied using an automated algorithm. We verify and validate the proposed method by comparing our numerical findings with published experimental results and analytical solutions. We demonstrate the applicability of the proposed scheme on patient-specific blood flow simulations in IAs.

Mathematical modeling and computer simulation of needle insertion into soft tissue.

In this study we present a kinematic approach for modeling needle insertion into soft tissues. The kinematic approach allows the presentation of the problem as Dirichlet-type (i.e. driven by enforced motion of boundaries) and therefore weakly sensitive to unknown properties of the tissues and needle-tissue interaction. The parameters used in the kinematic approach are straightforward to determine from images. Our method uses Meshless Total Lagrangian Explicit Dynamics (MTLED) method to compute soft tissue deformations. The proposed scheme was validated against experiments of needle insertion into silicone gel samples. We also present a simulation of needle insertion into the brain demonstrating the method's insensitivity to assumed mechanical properties of tissue.

Biomechanical modeling and computer simulation of the brain during neurosurgery.

Computational biomechanics of the brain for neurosurgery is an emerging area of research recently gaining in importance and practical applications. This review paper presents the contributions of the Intelligent Systems for Medicine Laboratory and its collaborators to this field, discussing the modeling approaches adopted and the methods developed for obtaining the numerical solutions. We adopt a physics-based modeling approach and describe the brain deformation in mechanical terms (such as displacements, strains, and stresses), which can be computed using a biomechanical model, by solving a continuum mechanics problem. We present our modeling approaches related to geometry creation, boundary conditions, loading, and material properties. From the point of view of solution methods, we advocate the use of fully nonlinear modeling approaches, capable of capturing very large deformations and nonlinear material behavior. We discuss finite element and meshless domain discretization, the use of the total Lagrangian formulation of continuum mechanics, and explicit time integration for solving both time-accurate and steady-state problems. We present the methods developed for handling contacts and for warping 3D medical images using the results of our simulations. We present two examples to showcase these methods: brain shift estimation for image registration and brain deformation computation for neuronavigation in epilepsy treatment.

Suite of meshless algorithms for accurate computation of soft tissue deformation for surgical simulation.

The ability to predict patient-specific soft tissue deformations is key for computer-integrated surgery systems and the core enabling technology for a new era of personalized medicine. Element-Free Galerkin (EFG) methods are better suited for solving soft tissue deformation problems than the finite element method (FEM) due to their capability of handling large deformation while also eliminating the necessity of creating a complex predefined mesh. Nevertheless, meshless methods based on EFG formulation, exhibit three major limitations: (i) meshless shape functions using higher order basis cannot always be computed for arbitrarily distributed nodes (irregular node placement is crucial for facilitating automated discretization of complex geometries); (ii) imposition of the Essential Boundary Conditions (EBC) is not straightforward; and, (iii) numerical (Gauss) integration in space is not exact as meshless shape functions are not polynomial. This paper presents a suite of Meshless Total Lagrangian Explicit Dynamics (MTLED) algorithms incorporating a Modified Moving Least Squares (MMLS) method for interpolating scattered data both for visualization and for numerical computations of soft tissue deformation, a novel way of imposing EBC for explicit time integration, and an adaptive numerical integration procedure within the Meshless Total Lagrangian Explicit Dynamics algorithm. The appropriateness and effectiveness of the proposed methods is demonstrated using comparisons with the established non-linear procedures from commercial finite element software ABAQUS and experiments with very large deformations. To demonstrate the translational benefits of MTLED we also present a realistic brain-shift computation.

Modeling Proteolytically Driven Tumor Lymphangiogenesis.

With the exception of a limited number of sites in the body, primary tumors infrequently lead to the demise of cancer patients. Instead, mortality and a significant degree of morbidity result from the growth of secondary tumors in distant organs. Tumor survival, growth and dissemination are associated with the formation of both new blood vessels (angiogenesis) and new lymph vessels (lymphagenesis or lymphangiogenesis). Although intensive research in tumor angiogenesis has been going on for the past four decades, experimental results in tumor lymphangiogenesis began to appear only in the last 10 years. In this chapter we expand the models proposed by Friedman, Lolas and Pepper on tumor lymphangiogenesis mediated by proteolytically and un-proteolytically processed growth factors (Friedman and Lolas G, Math Models Methods Appl Sci 15(01):95-107, 2005; Pepper and Lolas G, Selected topics in cancer modeling: genesis, evolution, immune competition, and therapy. In: The lymphatic vascular system in lymphangiogenesis invasion and metastasis a mathematical approach. Birkhäuser Boston, Boston, pp 1-22, 2008). The variables represent different cell densities and growth factors concentrations, and where possible the parameters are estimated from experimental and clinical data. The results obtained from computational simulations carried out on the model equations produce dynamic heterogeneous ("anarchic") spatio-temporal solutions. More specifically, we observed coherent masses of tumor clusters migrating around and within the lymphatic network. Our findings are in line with recent experimental evidence that associate cluster formation with the minimization of cell loss favoring high local extracellular matrix proteolysis and thus protecting cancer invading cells from an immunological assault driven by the lymphatic network.

Real-time tumor ablation simulation based on the dynamic mode decomposition method.

PURPOSE: The dynamic mode decomposition (DMD) method is used to provide a reliable forecasting of tumor ablation treatment simulation in real time, which is quite needed in medical practice. To achieve this, an extended Pennes bioheat model must be employed, taking into account both the water evaporation phenomenon and the tissue damage during tumor ablation. METHODS: A meshless point collocation solver is used for the numerical solution of the governing equations. The results obtained are used by the DMD method for forecasting the numerical solution faster than the meshless solver. The procedure is first validated against analytical and numerical predictions for simple problems. The DMD method is then applied to three-dimensional simulations that involve modeling of tumor ablation and account for metabolic heat generation, blood perfusion, and heat ablation using realistic values for the various parameters. RESULTS: The present method offers very fast numerical solution to bioheat transfer, which is of clinical significance in medical practice. It also sidesteps the mathematical treatment of boundaries between tumor and healthy tissue, which is usually a tedious procedure with some inevitable degree of approximation. The DMD method provides excellent predictions of the temperature profile in tumors and in the healthy parts of the tissue, for linear and nonlinear thermal properties of the tissue. CONCLUSIONS: The low computational cost renders the use of DMD suitable for in situ real time tumor ablation simulations without sacrificing accuracy. In such a way, the tumor ablation treatment planning is feasible using just a personal computer thanks to the simplicity of the numerical procedure used. The geometrical data can be provided directly by medical image modalities used in everyday practice.

Automatic vessel lumen segmentation and stent strut detection in intravascular optical coherence tomography.

PURPOSE: Optical coherence tomography (OCT) is a catheter-based imaging method that employs near-infrared light to produce high-resolution cross-sectional intravascular images. The authors propose a segmentation technique for automatic lumen area extraction and stent strut detection in intravascular OCT images for the purpose of quantitative analysis of neointimal hyperplasia (NIH). METHODS: A clinical dataset of frequency-domain OCT scans of the human femoral artery was analyzed. First, a segmentation method based on the Markov random field (MRF) model was employed for lumen area identification. Second, textural and edge information derived from local intensity distribution and continuous wavelet transform (CWT) analysis were integrated to extract the inner luminal contour. Finally, the stent strut positions were detected via the introduction of each strut wavelet response across scales into a feature extraction and classification scheme in order to optimize the strut position detection. RESULTS: The inner lumen contour and the position of stent strut were extracted with very high accuracy. Compared with manual segmentation by an expert vascular physician the automatic segmentation had an average overlap value of 0.937 ± 0.045 for all OCT images included in the study. The strut detection accuracy had an area under the curve (AUC) value of 0.95, together with sensitivity and specificity average values of 0.91 and 0.96, respectively. CONCLUSIONS: A robust automatic segmentation technique integrating textural and edge information for vessel lumen border extraction and strut detection in intravascular OCT images was designed and presented. The proposed algorithm may be employed for automated quantitative morphological analysis of in-stent neointimal hyperplasia.

Computational representation and hemodynamic characterization of in vivo acquired severe stenotic renal artery geometries using turbulence modeling.

The present study reports on computational fluid dynamics in the case of severe renal artery stenosis (RAS). An anatomically realistic model of a renal artery was reconstructed from CT scans, and used to conduct CFD simulations of blood flow across RAS. The recently developed shear stress transport (SST) turbulence model was pivotally applied in the simulation of blood flow in the region of interest. Blood flow was studied in vivo under the presence of RAS and subsequently in simulated cases before the development of RAS, and after endovascular stent implantation. The pressure gradients in the RAS case were many orders of magnitude larger than in the healthy case. The presence of RAS increased flow resistance, which led to considerably lower blood flow rates. A simulated stent in place of the RAS decreased the flow resistance at levels proportional to, and even lower than, the simulated healthy case without the RAS. The wall shear stresses, differential pressure profiles, and net forces exerted on the surface of the atherosclerotic plaque at peak pulse were shown to be of relevant high distinctiveness, so as to be considered potential indicators of hemodynamically significant RAS.