EDIT Software: A tool for the semi-automatic 3D reconstruction of bladder cancer and urinary bladder of animal models.

BACKGROUND AND OBJECTIVE: This study presents the EDIT software, a tool for the visualization of the urinary bladder anatomy in the 3D space and for its semi-automatic 3D reconstruction. METHODS: The inner bladder wall was computed by applying a Region of Interest (ROI) feedback-based active contour algorithm on the ultrasound images while the outer bladder wall was calculated by expanding the inner borders to approach the vascularization area on the photoacoustic images. The validation strategy of the proposed software was divided into two processes. Initially, the 3D automated reconstruction was performed on 6 phantom objects of different volume in order to compare the software computed volumes of the models with the true volumes of phantoms. Secondly, the in-vivo 3D reconstruction of the urinary bladder for 10 animals with orthotopic bladder cancer, which range in different stages of tumor progression was performed. RESULTS: The results showed that the minimum volume similarity of the proposed 3D reconstruction method applied on phantoms is 95.59%. It is noteworthy to mention that the EDIT software enables the user to reconstruct the 3D bladder wall with high precision, even if the bladder silhouette has been significantly deformed by the tumor. Indeed, by taking into account the dataset of the 2251 in-vivo ultrasound and photoacoustic images, the presented software performs segmentation with dice similarity 96.96% and 90.91% for the inner and the outer borders of the bladder wall, respectively. CONCLUSIONS: This study delivers the EDIT software, a novel software tool that uses ultrasound and photoacoustic images to extract different 3D components of the bladder.

SmartFFR, a New Functional Index of Coronary Stenosis: Comparison With Invasive FFR Data.

Aims: In this study, we evaluate the efficacy of SmartFFR, a new functional index of coronary stenosis severity compared with gold standard invasive measurement of fractional flow reserve (FFR). We also assess the influence of the type of simulation employed on smartFFR (i.e. Fluid Structure Interaction vs. rigid wall assumption). Methods and Results: In a dataset of 167 patients undergoing either computed tomography coronary angiography (CTCA) and invasive coronary angiography or only invasive coronary angiography (ICA), as well as invasive FFR measurement, SmartFFR was computed after the 3D reconstruction of the vessels of interest and the subsequent blood flow simulations. 202 vessels were analyzed with a mean total computational time of seven minutes. SmartFFR was used to process all models reconstructed by either method. The mean FFR value of the examined dataset was 0.846 ± 0.089 with 95% CI for the mean of 0.833-0.858, whereas the mean SmartFFR value was 0.853 ± 0.095 with 95% CI for the mean of 0.84-0.866. SmartFFR was significantly correlated with invasive FFR values (RCCTA = 0.86, p CCTA < 0.0001, RICA = 0.84, p ICA < 0.0001, R overall = 0.833, p overall < 0.0001), showing good agreement as depicted by the Bland-Altman method of analysis. The optimal SmartFFR threshold to diagnose ischemia was ≤0.83 for the overall dataset, ≤0.83 for the CTCA-derived dataset and ≤0.81 for the ICA-derived dataset, as defined by a ROC analysis (AUCoverall = 0.956, p < 0.001, AUCICA = 0.975, p < 0.001, AUCCCTA = 0.952, p < 0.001). Conclusion: SmartFFR is a fast and accurate on-site index of hemodynamic significance of coronary stenosis both at single coronary segment and at two or more branches level simultaneously, which can be applied to all CTCA or ICA sequences of acceptable quality.

Spatial relationships among hemodynamic, anatomic, and biochemical plaque characteristics in patients with coronary artery disease.

BACKGROUND AND AIMS: We aimed to characterize the spatial proximity of plaque destabilizing features local endothelial shear stress (ESS), minimal luminal area (MLA), plaque burden (PB), and near-infrared spectroscopy (NIRS) lipid signal in high- vs. low-risk plaques. METHODS: Coronary arteries imaged with angiography and NIRS-intravascular ultrasound (IVUS) underwent 3D reconstruction and computational fluid dynamics calculations of local ESS. ESS, PB, MLA, and lipid core burden index (LCBI), for each 3-mm arterial segment were obtained in arteries with large lipid-rich plaque (LRP) vs. arteries with smaller LRP. The locations of the MLA, minimum ESS (minESS), maximum ESS (maxESS), maximum PB (maxPB), and maximum LCBI in a 4-mm segment (maxLCBI4mm) were determined along the length of each plaque. RESULTS: The spatial distributions of minESS, maxESS, maxPB, and maxLCBI4mm, in reference to the MLA, were significantly heterogeneous within and between each variable. The location of maxLCBI4mm was spatially discordant from sites of the MLA (p<0.0001), minESS (p = 0.003), and maxESS (p = 0.003) in arteries with large LRP (maxLCBI4mm ≥ 400) and non-large LRP. Large LRP arteries had higher maxESS (9.31 ± 4.78 vs. 6.32 ± 5.54 Pa; p = 0.023), lower minESS (0.41 ± 0.16 vs. 0.61 ± 0.26 Pa; p = 0.007), smaller MLA (3.54 ± 1.22 vs. 5.14 ± 2.65 mm2; p = 0.002), and larger maxPB (70.64 ± 9.95% vs. 56.70 ± 13.34%, p<0.001) compared with non-large LRP arteries. CONCLUSIONS: There is significant spatial heterogeneity of destabilizing plaque features along the course of both large and non-large LRPs. Large LRPs exhibit significantly more abnormal destabilizing plaque features than non-large LRPs. Prospective, longitudinal studies are required to determine which patterns of heterogeneous destabilizing features act synergistically to cause plaque destabilization.

Local Low Shear Stress and Endothelial Dysfunction in Patients With Nonobstructive Coronary Atherosclerosis.

BACKGROUND: Local hemodynamic factors are important determinants of atherosclerotic plaque development and progression. OBJECTIVES: The goal of this study was to determine the association between low endothelial shear stress (ESS) and microvascular and epicardial endothelial dysfunction in patients with early atherosclerosis. METHODS: Sixty-five patients (mean age 52 ± 11 years) with nonobstructive coronary atherosclerosis (luminal diameter stenosis <30%) were included. Microvascular and epicardial coronary endothelial function was assessed by using intracoronary acetylcholine infusion. Vascular profiling, using 2-plane coronary angiography and intravascular ultrasound, was used to reconstruct the three-dimensional anatomy of the left anterior descending artery. Each reconstructed artery was divided into sequential 3-mm segments and analyzed for local ESS with computational fluid dynamics; that is, lower ESS levels at both a 3-mm regional level (average ESS and low ESS) and at a vessel level (lowest ESS per artery) and for plaque characteristics (plaque area, plaque thickness, and plaque burden). RESULTS: Coronary segments in arteries with abnormal microvascular function exhibited lower ESS compared with segments in arteries with normal microvascular function (average ESS: 1.67 ± 1.04 Pa vs. 2.03 ± 1.72 Pa [p = 0.050]; lowest ESS: 0.54 ± 0.25 Pa vs. 0.72 ± 0.32 Pa [p = 0.014]). Coronary segments in arteries with abnormal epicardial endothelial function also exhibited significantly lower ESS compared with segments in arteries with normal epicardial function (average ESS: 1.49 ± 0.89 Pa vs. 1.93 ± 1.50 Pa [p < 0.0001]; low ESS: 1.26 ± 0.81 Pa vs. 1.56 ± 1.30 Pa [p = 0.001]; lowest ESS: 0.51 ± 0.27 Pa vs. 0.65 ± 0.29 Pa [p = 0.080]). Patients with abnormal microvascular endothelial function exhibited a progressive decrease in average and low ESS, starting from patients with normal epicardial endothelial function to those with both microvascular and epicardial endothelial dysfunction (p < 0.0001 and p = 0.004, respectively). CONCLUSIONS: These data indicate an association between dysfunction of the microvascular and epicardial endothelium and local ESS at the early stages of coronary atherosclerosis in humans.

Role of Low Endothelial Shear Stress and Plaque Characteristics in the Prediction of Nonculprit Major Adverse Cardiac Events: The PROSPECT Study.

OBJECTIVES: This study sought to determine whether low endothelial shear stress (ESS) adds independent prognostication for future major adverse cardiac events (MACE) in coronary lesions in patients with high-risk acute coronary syndrome (ACS) from the United States and Europe. BACKGROUND: Low ESS is a proinflammatory, proatherogenic stimulus associated with coronary plaque development, progression, and destabilization in human-like animal models and in humans. Previous natural history studies including baseline ESS characterization investigated low-risk patients. METHODS: In the PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study, 697 patients with ACS underwent 3-vessel intracoronary imaging. Independent predictors of MACE attributable to untreated nonculprit (nc) coronary lesions during 3.4-year follow-up were large plaque burden (PB), small minimum lumen area (MLA), and thin-cap fibroatheroma (TCFA) morphology. In this analysis, baseline ESS of nc lesions leading to new MACE (nc-MACE lesions) and randomly selected control nc lesions without MACE (nc-non-MACE lesions) were calculated. A propensity score for ESS was constructed for each lesion, and the relationship between ESS and subsequent nc-MACE was examined. RESULTS: A total of 145 lesions were analyzed in 97 patients: 23 nc-MACE lesions (13 TCFAs, 10 thick-cap fibroatheromas [ThCFAs]), and 122 nc-non-MACE lesions (63 TCFAs, 59 ThCFAs). Low local ESS (<1.3 Pa) was strongly associated with subsequent nc-MACE compared with physiological/high ESS (≥1.3 Pa) (23 of 101 [22.8%]) versus (0 of 44 [0%]). In propensity-adjusted Cox regression, low ESS was strongly associated with MACE (hazard ratio: 4.34; 95% confidence interval: 1.89 to 10.00; p < 0.001). Categorizing plaques by anatomic risk (high risk: ≥2 high-risk characteristics PB ≥70%, MLA ≤4 mm2, or TCFA), high anatomic risk, and low ESS were prognostically synergistic: 3-year nc-MACE rates were 52.1% versus 14.4% versus 0.0% in high-anatomic risk/low-ESS, low-anatomic risk/low-ESS, and physiological/high-ESS lesions, respectively (p < 0.0001). No lesion without low ESS led to nc-MACE during follow-up, regardless of PB, MLA, or lesion phenotype at baseline. CONCLUSIONS: Local low ESS provides incremental risk stratification of untreated coronary lesions in high-risk patients, beyond measures of PB, MLA, and morphology.

Art care: A multi-modality coronary 3D reconstruction and hemodynamic status assessment software.

BACKGROUND: Due to the incremental increase of clinical interest in the development of software that allows the 3-dimensional (3D) reconstruction and the functional assessment of the coronary vasculature, several software packages have been developed and are available today. OBJECTIVE: Taking this into consideration, we have developed an innovative suite of software modules that perform 3D reconstruction of coronary arterial segments using different coronary imaging modalities such as IntraVascular UltraSound (IVUS) and invasive coronary angiography images (ICA), Optical Coherence Tomography (OCT) and ICA images, or plain ICA images and can safely and accurately assess the hemodynamic status of the artery of interest. METHODS: The user can perform automated or manual segmentation of the IVUS or OCT images, visualize in 3D the reconstructed vessel and export it to formats, which are compatible with other Computer Aided Design (CAD) software systems. We employ finite elements to provide the capability to assess the hemodynamic functionality of the reconstructed vessels by calculating the virtual functional assessment index (vFAI), an index that corresponds and has been shown to correlate well to the actual fractional flow reserve (FFR) value. RESULTS: All the modules of the proposed system have been thoroughly validated. In brief, the 3D-QCA module, compared to a successful commercial software of the same genre, presented very good correlation using several validation metrics, with a Pearson's correlation coefficient (R) for the calculated volumes, vFAI, length and minimum lumen diameter of 0.99, 0.99, 0.99 and 0.88, respectively. Moreover, the automatic lumen detection modules for IVUS and OCT presented very high accuracy compared to the annotations by medical experts with the Pearson's correlation coefficient reaching the values of 0.94 and 0.99, respectively. CONCLUSIONS: In this study, we have presented a user-friendly software for the 3D reconstruction of coronary arterial segments and the accurate hemodynamic assessment of the severity of existing stenosis.

Error propagation in the characterization of atheromatic plaque types based on imaging.

Imaging systems transmit and acquire signals and are subject to errors including: error sources, signal variations or possible calibration errors. These errors are included in all imaging systems for atherosclerosis and are propagated to methodologies implemented for the segmentation and characterization of atherosclerotic plaque. In this paper, we present a study for the propagation of imaging errors and image segmentation errors in plaque characterization methods applied to 2D vascular images. More specifically, the maximum error that can be propagated to the plaque characterization results is estimated, assuming worst-case scenarios. The proposed error propagation methodology is validated using methods applied to real datasets, obtained from intravascular imaging (IVUS) and optical coherence tomography (OCT) for coronary arteries, and magnetic resonance imaging (MRI) for carotid arteries. The plaque characterization methods have recently been presented in the literature and are able to detect the vessel borders, and characterize the atherosclerotic plaque types. Although, these methods have been extensively validated using as gold standard expert annotations, by applying the proposed error propagation methodology a more realistic validation is performed taking into account the effect of the border detection algorithms error and the image formation error into the final results. The Pearson's coefficient of the detected plaques has changed significantly when the method was applied to IVUS and OCT, while there was not any variation when the method was applied to MRI data.

Patient-specific simulation of coronary artery pressure measurements: an in vivo three-dimensional validation study in humans.

Pressure measurements using finite element computations without the need of a wire could be valuable in clinical practice. Our aim was to compare the computed distal coronary pressure values with the measured values using a pressure wire, while testing the effect of different boundary conditions for the simulation. Eight coronary arteries (lumen and outer vessel wall) from six patients were reconstructed in three-dimensional (3D) space using intravascular ultrasound and biplane angiographic images. Pressure values at the distal and proximal end of the vessel and flow velocity values at the distal end were acquired with the use of a combo pressure-flow wire. The 3D lumen and wall models were discretized into finite elements; fluid structure interaction (FSI) and rigid wall simulations were performed for one cardiac cycle both with pulsatile and steady flow in separate simulations. The results showed a high correlation between the measured and the computed coronary pressure values (coefficient of determination [r(2)] ranging between 0.8902 and 0.9961), while the less demanding simulations using steady flow and rigid walls resulted in very small relative error. Our study demonstrates that computational assessment of coronary pressure is feasible and seems to be accurate compared to the wire-based measurements.

Modeling of blood flow through sutured micro-vascular anastomoses.

Microanastomosis is a surgical procedure used to reconnect two blood vessels using sutures. The optimal microanastomosis may be predicted by assessing the factors that influence this invasive procedure. Blood flow and hemodynamics following microanastomosis are important factors for the successful longevity of this operation. How is the blood flow affected by the presence of sutures? Computational Fluid Dynamics (CFD) is a powerful tool that permits the estimation of specific quantities, such as fluid stresses, that are hardly measurable in vivo. In this study, we propose a methodology which evaluates the alterations in the hemodynamic status due to microanastomosis. A CFD model of a reconstructed artery has been developed, based on anatomical information provided by intravascular ultrasound and angiography, and was used to simulate blood flow after microanastomosis. The 3D reconstructed arterial segments are modeled as non-compliant 1.24 - 1.47 mm diameter ducts, with approximately 0.1 mm arterial thickness. The blood flow is considered laminar and the no-slip condition is imposed on the boundary wall, which is assumed to be rigid. In analyzing the results, the distribution of the wall shear stress (WSS) is presented in the region of interest, near the sutures. The results indicate that high values of WSS appear in the vicinity of sutures. Such regions may promote thrombus formation and subsequently anastomotic failure, therefore their meticulous study is of high importance.

A proof-of-concept study for predicting the region of atherosclerotic plaque development based on plaque growth modeling in carotid arteries.

In this work, we present a computational model for plaque growth utilizing magnetic resonance data of a patient's carotid artery. More specifically, we model blood flow utilizing the Navier-Stokes equations, as well as LDL and HDL transport using the convection-diffusion equation in the arterial lumen. The accumulated LDL in the arterial wall is oxidized considering the protective effect of HDL. Macrophages recruitment and foam cells formation are the final step of the proposed multi-level modeling approach of the plaque growth. The simulated results of our model are compared with the follow-up MRI findings in 12 months regarding the change to the arterial wall thickness. WSS and LDL may indicate potential regions of plaque growth (R(2)=0.35), but the contribution of foam cells formation, macrophages and oxidized LDL increased the prediction significantly (R(2)=0.75).

Validation study of a 3D-QCA coronary reconstruction method using a hybrid intravascular ultrasound and angiography reconstruction method and patient-specific Fractional Flow Reserve data.

The estimation of the severity of coronary lesions is of utmost importance in today's clinical practice, since Cardiovascular diseases often have fatal consequences. The most efficient method to estimate the severity of a lesion is the calculation of the Fractional Flow Reserve. The necessary use of a pressure wire, however, makes this method invasive and strenuous for the patient. In this work, we present a novel 3-Dimensional Quantitative Coronary Analysis coronary reconstruction method and a framework for the computation of the virtual Functional Assessment Index (vFAI). In a dataset of 5 coronary arterial segments, we use the aforementioned method to reconstruct them in 3D, and compare them to the respective 3D models reconstructed from our already validated hybrid IVUS-angiography reconstruction method [2]. The obtained results indicate a high correlation between the two methods in terms of the calculated FFR values, presenting a difference of 3.19% in the worst case scenario. Furthermore, when compared to the actual FFR values that derive from a pressure wire, the differences were statistically insignificant.

A dynamic Bayesian network approach for time-specific survival probability prediction in patients after ventricular assist device implantation.

In this work we present a decision support tool for the calculation of time-dependent survival probability for patients after ventricular assist device implantation. Two different models have been developed, a short term one which predicts survival for the first three months and a long term one that predicts survival for one year after implantation. In order to model the time dependencies between the different time slices of the problem, a dynamic Bayesian network (DBN) approach has been employed. DBNs order to capture the temporal events of the patient disease and the temporal data availability. High accuracy results have been reported for both models. The short and long term DBNs reached an accuracy of 96.97% and 93.55% respectively.

Finite element analysis of stent implantation in a three-dimensional reconstructed arterial segment.

Endovascular stent deployment is a mechanical procedure used to rehabilitate a diseased arterial segment by restoring blood flow in occluded regions. The success or failure of the stent implantation depends on the stent device and the deployment technique. The optimal stent deployment can be predicted by investigating the factors that influence this minimally invasive procedure. In this study, we propose a methodology which evaluates the alterations in the arterial environment caused by stent deployment. A finite element model of a reconstructed right coronary artery with a stenosis was created based on anatomical information provided by intravascular ultrasound and angiography. The model was used to consider placement and performance after intervention with a commercially available Leader Plus stent. The performance of the stent, within this patient-specific arterial segment is presented, as well as the induced arterial deformation and straightening. The arterial stress distribution is analyzed with respect to possible regions of arterial injury. Our approach can be used to optimize stent deployment and to provide cardiologists with a valuable tool to visually select the position and deploy stents in patient-specific reconstructed arterial segments, thereby enabling new methods for optimal cardiovascular stent positioning.

Assessing the hemodynamic influence between multiple lesions in a realistic right coronary artery segment: A computational study.

Coronary artery disease is the primary cause of morbidity and mortality worldwide. Therefore, detailed assessment of lesions in the coronary vasculature is critical in current clinical practice. Fractional flow reserve (FFR) has been proven as an efficient method for assessing the hemodynamic severity of a coronary stenosis. However, functional assessment of a coronary segment with multiple stenoses (≥ 2) remains complex for guiding the strategy of percutaneous coronary intervention due to the hemodynamic interplay between adjacent stenoses. In this work, we created four 3-dimensional (3D) arterial models that derive from a healthy patient-specific right coronary artery segment. The initial healthy model was reconstructed using fusion of intravascular ultrasound (IVUS) and biplane angiographic patient data. The healthy 3D model presented a measured FFR value of 0.96 (pressure-wire) and a simulated FFR value of 0.98. We then created diseased models with two artificial sequential stenoses of 90% lumen area reduction or with the proximal and distal stenosis separately. We calculated the FFR value for each case: 0.65 for the case with the two stenoses, 0.73 for the case with the distal stenosis and 0.90 for the case with the proximal stenosis. This leads to the conclusion that although both stenoses had the same degree of lumen area stenosis, there was a large difference in hemodynamic severity, thereby indicating that angiographic lumen assessment by itself is often not adequate for accurate assessment of coronary lesions.

Computational assessment of the fractional flow reserve from intravascular ultrasound and coronary angiography data: a pilot study.

Cardiovascular disease is one of the primary causes of morbidity and mortality around the globe. Thus, the diagnosis of critical lesions in coronary arteries is of utmost importance in clinical practice. One useful and efficient method to assess the functional severity of one or multiple lesions in a coronary artery is the calculation of the fractional flow reserve (FFR). In the current work, we present a method which allows the calculation of the FFR value computationally, without the use of a pressure wire and the induction of hyperemia, using intravascular ultrasound (IVUS) and biplane angiography images for three-dimensional (3D) coronary artery reconstruction and measurements of the volumetric flow rate derived from angiographic sequences. The simulated FFR values were compared to the invasively measured FFR values in 7 cases, presenting high correlation (r=0.85) and good agreement (mean difference=0.002). FFR assessment without employing a pressure wire and the induction of hyperemia is feasible using 3D reconstructed coronary artery models from angiographic and IVUS data coupled with computational fluid dynamics.

Novel methodology for 3D reconstruction of carotid arteries and plaque characterization based upon magnetic resonance imaging carotid angiography data.

In this study, we present a novel methodology that allows reliable segmentation of the magnetic resonance images (MRIs) for accurate fully automated three-dimensional (3D) reconstruction of the carotid arteries and semiautomated characterization of plaque type. Our approach uses active contours to detect the luminal borders in the time-of-flight images and the outer vessel wall borders in the T(1)-weighted images. The methodology incorporates the connecting components theory for the automated identification of the bifurcation region and a knowledge-based algorithm for the accurate characterization of the plaque components. The proposed segmentation method was validated in randomly selected MRI frames analyzed offline by two expert observers. The interobserver variability of the method for the lumen and outer vessel wall was -1.60%±6.70% and 0.56%±6.28%, respectively, while the Williams Index for all metrics was close to unity. The methodology implemented to identify the composition of the plaque was also validated in 591 images acquired from 24 patients. The obtained Cohen's k was 0.68 (0.60-0.76) for lipid plaques, while the time needed to process an MRI sequence for 3D reconstruction was only 30 s. The obtained results indicate that the proposed methodology allows reliable and automated detection of the luminal and vessel wall borders and fast and accurate characterization of plaque type in carotid MRI sequences. These features render the currently presented methodology a useful tool in the clinical and research arena.

Patient specific cardiovascular risk assessment and treatment decision support based on multiscale modelling and medical guidelines.

In this work we present an enhanced medical workflow and a decision support system for atherosclerotic risk assessment and treatment, that is based both on existing medical guidelines and on patient specific multiscale data. The medical expert that uses the system is able to apply both existing medical guidelines as well as to take into account additional information for the patient by inspecting the 3D geometry of an arterial segment or the arterial tree, model the blood flow in the patient specific arterial model and predict the progression of the plaque. Moreover, the user is able to apply plaque characterization techniques in Intravascular Ultrasound images (IVUS) and Tomography Images (CT). The combination of the medical guidelines with the patient specific multiscale data provides a detailed view in the patient status for risk assessment and treatment suggestion.