Three-Dimensional Multi-Modality Registration for Orthopaedics and Cardiovascular Settings: State-of-the-Art and Clinical Applications.

The multimodal and multidomain registration of medical images have gained increasing recognition in clinical practice as a powerful tool for fusing and leveraging useful information from different imaging techniques and in different medical fields such as cardiology and orthopedics. Image registration could be a challenging process, and it strongly depends on the correct tuning of registration parameters. In this paper, the robustness and accuracy of a landmarks-based approach have been presented for five cardiac multimodal image datasets. The study is based on 3D Slicer software and it is focused on the registration of a computed tomography (CT) and 3D ultrasound time-series of post-operative mitral valve repair. The accuracy of the method, as a function of the number of landmarks used, was performed by analysing root mean square error (RMSE) and fiducial registration error (FRE) metrics. The validation of the number of landmarks resulted in an optimal number of 10 landmarks. The mean RMSE and FRE values were 5.26 ± 3.17 and 2.98 ± 1.68 mm, respectively, showing comparable performances with respect to the literature. The developed registration process was also tested on a CT orthopaedic dataset to assess the possibility of reconstructing the damaged jaw portion for a pre-operative planning setting. Overall, the proposed work shows how 3D Slicer and registration by landmarks can provide a useful environment for multimodal/unimodal registration.

Treatment of multiple valve disease: surgery, structural intervention, or both?

Multiple valve heart disease refers to the simultaneous presence of several valvular anomalies, while mixed valvular heart disease refers to the combination of stenotic lesions or regurgitation affecting the same valve. The pathophysiology of multiple and mixed valvular heart disease depends on the combination of affected valves and the severity of the individual valvular defects. Imaging is essential for diagnosis and assessment of disease severity. The treatment of combined valvular defects currently represents a challenge for both cardiac surgeons and interventional cardiologists since only few data in the literature address the clinical and therapeutic decision-making process related to these complex lesions. These are heterogeneous conditions, which differ from each other in the combination of the valves involved, in the pathogenesis with which they develop, in the severity of the individual lesions, in the associated surgical risk, in the possibility of being repaired, and in the undergoing transcatheter treatments. In addition to the severity of the individual valve defects, the choice of treatment also depends on the ventricular function and the general condition of the patient. This work aims to provide a review of the state of the art regarding the possible management strategies of the most common multiple valve diseases in clinical practice.

3D model-guided transcatheter closure of ascending aorta pseudoaneurysm with the novel Amplatzer Trevisio intravascular delivery system.

Ascending aorta pseudoaneurysm (AAP) is a rare but life-threatening complication of atherosclerosis, endocarditis, chest trauma, transcatheter or cardio-thoracic procedures. Since surgical repair is burdened by high morbidity and mortality, percutaneous closure is nowadays considered a valuable cost-effective therapeutic alternative. Due to unpredictability and complexity of local anatomy, no standardized technique and device are advised. In this setting, 3D printing technology could significantly help in planning trans-catheter approach. This article reports on a 3D printed model-guided percutaneous closure of a huge AAP using an Amplatzer Septal Occluder (Abbott, Plymouth MN) implanted by the recently commercialized Amplatzer Trevisio Intravascular Delivery System.

Penetration capability of near infrared Laguerre-Gaussian beams through highly scattering media.

The higher capability of optical vortex beams of penetrating turbid media (e.g., biological fluids) with respect to the conventional Gaussian beams is, for the first time to our knowledge, demonstrated in the 1.3 µm wavelength range which is conventionally used for optical coherence tomography procedures in endoscopic intravascular scenarios. The effect has been demonstrated by performing transmittance measurements through suspensions of polystyrene microspheres in water with various particulate concentrations and, in reflection, by using samples of human blood with different thicknesses. The reduced backscattering/increased transmittance into such highly scattering media of Laguerre-Gaussian beams with respect to Gaussian ones, in the near infrared wavelength region, could be potentially exploited in clinical applications, leading to novel biomedical diagnoses and/or procedures.

Computational Fluid Dynamic Study for aTAA Hemodynamics: An Integrated Image-Based and Radial Basis Functions Mesh Morphing Approach.

We present a novel framework for the fluid dynamics analysis of healthy subjects and patients affected by ascending thoracic aorta aneurysm (aTAA). Our aim is to obtain indications about the effect of a bulge on the hemodynamic environment at different enlargements. Three-dimensional (3D) surface models defined from healthy subjects and patients with aTAA, selected for surgical repair, were generated. A representative shape model for both healthy and pathological groups has been identified. A morphing technique based on radial basis functions (RBF) was applied to mold the shape relative to healthy patient into the representative shape of aTAA dataset to enable the parametric simulation of the aTAA formation. Computational fluid dynamics (CFD) simulations were performed by means of a finite volume solver using the mean boundary conditions obtained from three-dimensional (PC-MRI) acquisition. Blood flow helicity and flow descriptors were assessed for all the investigated models. The feasibility of the proposed integrated approach pertaining the coupling between an RBF morphing technique and CFD simulation for aTAA was demonstrated. Significant hemodynamic changes appear at the 60% of the bulge progression. An impingement of the flow toward the bulge was observed by analyzing the normalized flow eccentricity (NFE) index.

Case Report: Role of numerical simulations in the management of acute aortic syndromes.

Penetrating aortic ulcer (PAU) represents a subset of acute aortic syndromes characterized by high rupture risk and management challenges, particularly in elderly patients with significant comorbidities. This case report showcases a 75-year-old patient with a history of coronary artery bypass graft (CABG) and with multiple PAUs involving the aortic arch, deemed unfit for conventional open surgery. A branched aortic endograft with a pre-cannulated side component for the left subclavian artery (LSA) was employed to preserve the patency of the previous CABG. Two computational fluid dynamics (CFD) simulations and a morphological analysis were performed on the pre- and post-intervention aortic configurations to evaluate changes in flow rate and pressure drop at LSA level and differences in the lumen size. The results revealed a decrease in the flow rate equal to 2.38% after the intervention and an increase in pressure drop of 4.48 mmHg, while the maximum differences in LSA cross-sectional areas and diameters were 1.49 cm2 and 0.64 cm, respectively. Minimal alteration in LSA blood flow due to the chosen intervention approach confirmed the effectiveness of the selected unibody design endograft with LSA preservation, ensuring myocardial perfusion. Therefore, CFD simulations demonstrate to be a powerful tool to evaluate the hemodynamic consequences of interventions by accurately estimating the main fluid dynamic parameters.

Left atrial appendage occlusion: On the need of a numerical model to simulate the implant procedure.

Left atrial appendage occlusion (LAAO) is a percutaneous procedure to prevent thromboembolism in patients affected by atrial fibrillation. Despite its demonstrated efficacy, the LAA morphological complexity hinders the procedure, resulting in postprocedural drawbacks (device-related thrombus and peri-device leakage). Local anatomical features may cause difficulties in the device's positioning and affect the effectiveness of the device's implant. The current work proposes a detailed FE model of the LAAO useful to investigate implant scenarios and derive clinical indications. A high-fidelity model of the Watchman FLX device and simplified parametric conduits mimicking the zone of the LAA where the device is deployed were developed. Device-conduit interactions were evaluated by looking at clinical indicators such as device-wall gap, possible cause of leakage, and device protrusion. As expected, the positioning of the crimped device before the deployment was found to significantly affect the implant outcomes: clinician's choices can be improved if FE models are used to optimize the pre-operative planning. Remarkably, also the wall mechanical stiffness plays an important role. However, this parameter value is unknown for a specific LAA, a crucial point that must be correctly defined for developing an accurate FE model. Finally, numerical simulations outlined how the device's configuration on which the clinician relies to assess the implant success (i.e., the deployed configuration with the device still attached to the catheter) may differ from the actual final device's configuration, relevant for achieving a safe intervention.

Multimodality Imaging Approach for Planning and Guiding Direct Transcatheter Tricuspid Valve Annuloplasty.

Interest in transcatheter treatment of tricuspid regurgitation (TR) has grown significantly in recent years due to increasing evidence correlating TR severity with mortality and to limited availability of surgical options often considered high-risk in these patients. Although edge-to-edge repair is currently the main transcatheter therapeutic strategy, tricuspid valve direct annuloplasty can also be performed safely and effectively to reduce TR and improve heart failure symptoms and quality of life. In the annuloplasty procedure, an adjustable band is implanted around the tricuspid annulus to reduce valvular size and improve TR. Patient selection and careful preoperative imaging, including transthoracic echocardiography, transesophageal echocardiography, and computed tomography, are critical for procedural success and proper device implantation. Compared to edge-to-edge repair, perioperative imaging with transesophageal echocardiography and fluoroscopy is particularly challenging. Alignment and insertion of the anchors are demanding but essential to achieve good results and avoid damaging the surrounding structures. The presence of shadowing artifacts due to cardiac devices makes the acquisition of good-quality images even more challenging. In this review, we discuss the current role of multimodality imaging in planning direct transcatheter tricuspid valve annuloplasty and describe all procedural steps focusing on echocardiographic monitoring.

Spectral Photon-Counting Computed Tomography: Technical Principles and Applications in the Assessment of Cardiovascular Diseases.

Spectral Photon-Counting Computed Tomography (SPCCT) represents a groundbreaking advancement in X-ray imaging technology. The core innovation of SPCCT lies in its photon-counting detectors, which can count the exact number of incoming x-ray photons and individually measure their energy. The first part of this review summarizes the key elements of SPCCT technology, such as energy binning, energy weighting, and material decomposition. Its energy-discriminating ability represents the key to the increase in the contrast between different tissues, the elimination of the electronic noise, and the correction of beam-hardening artifacts. Material decomposition provides valuable insights into specific elements' composition, concentration, and distribution. The capability of SPCCT to operate in three or more energy regimes allows for the differentiation of several contrast agents, facilitating quantitative assessments of elements with specific energy thresholds within the diagnostic energy range. The second part of this review provides a brief overview of the applications of SPCCT in the assessment of various cardiovascular disease processes. SPCCT can support the study of myocardial blood perfusion and enable enhanced tissue characterization and the identification of contrast agents, in a manner that was previously unattainable.

Enabling supra-aortic vessels inclusion in statistical shape models of the aorta: a novel non-rigid registration method.

Statistical Shape Models (SSMs) are well-established tools for assessing the variability of 3D geometry and for broadening a limited set of shapes. They are widely used in medical imaging due to their ability to model complex geometries and their high efficiency as generative models. The principal step behind these techniques is a registration phase, which, in the case of complex geometries, can be a critical issue due to the correspondence problem, as it necessitates the development of correspondence mapping between shapes. The thoracic aorta, with its high level of morphological complexity, poses a multi-scale deformation problem due to the presence of several branch vessels with varying diameters. Moreover, branch vessels exhibit significant variability in shape, making the correspondence optimization even more challenging. Consequently, existing studies have focused on developing SSMs based only on the main body of the aorta, excluding the supra-aortic vessels from the analysis. In this work, we present a novel non-rigid registration algorithm based on optimizing a differentiable distance function through a modified gradient descent approach. This strategy enables the inclusion of custom, domain-specific constraints in the objective function, which act as landmarks during the registration phase. The algorithm's registration performance was tested and compared to an alternative Statistical Shape modeling framework, and subsequently used for the development of a comprehensive SSM of the thoracic aorta, including the supra-aortic vessels. The developed SSM was further evaluated against the alternative framework in terms of generalisation, specificity, and compactness to assess its effectiveness.

Numerical investigation on circular and elliptical bulge tests for inverse soft tissue characterization.

The acquisition of insights concerning the mechanobiology of aneurysmatic aortic tissues is an important field of investigation. The complete characterization of aneurysm mechanical behaviour can be carried out by biaxial experimental tests on ex vivo specimens. In literature, several works proposed bulge inflation tests as a valid method to analyse aneurysmatic tissue. Bulge test data processing requires the adoption of digital image correlation and inverse analysis approaches to estimate strain and stress distributions, respectively. In this context, however, the accuracy of inverse analysis method has not been evaluated yet. This aspect appears particularly interesting given the anisotropic behaviour of the soft tissue and the possibility to adopt different die geometries. The goal of this study is to provide an accuracy characterization of the inverse analysis applied to the bulge test technique using a numerical approach. In particular, different cases of bulge inflation were simulated in a finite element environment as a reference. To investigate the effect of tissue anisotropic degree and bulge die geometries (circular and elliptical), different input parameters were considered to obtain multiple test cases. The specimen deformed shapes, resulting from the reference finite element simulations, were then analysed through an inverse analysis approach to produce an estimation of stress distributions. The estimated stresses were, at last, compared with the values from the reference finite element simulations. The results demonstrated that the circular die geometry produces a satisfactory estimation accuracy only under certain conditions of material quasi-isotropy. On the other hand, the choice of an elliptical bulge die was proven to be more suitable for the analysis of anisotropic tissues.

A Hybrid Mock Circulatory Loop for Fluid Dynamic Characterization of 3D Anatomical Phantoms.

GOAL: This work presents the development of a Hybrid Mock Circulatory Loop (HMCL) to simulate hemodynamics at patient-specific level in terms of both 3D geometry and inlet/outlet boundary conditions. METHODS: Clinical data have been processed to define the morphological and functional patient-specific settings. A piston pump is used to impose a parametric flow rate profile at the inlet of the hemodynamic circuit. In order to guarantee the physiological pressure and flow conditions, a specific hybrid chamber system including a real-time control has been designed and implemented. The developed system was validated firstly in a single outlet branch model and, secondly, on a 3D printed patient-specific multi-branch phantom. Finally, for the 3D phantom, the outlet flow profiles were compared with the corresponding in-vivo flow data. RESULTS: Results showed that the root mean squared error between the prescribed setpoint and the measured pressures was always below 3 mmHg (about 2.5%) for all cases. The obtained flow profiles for the patient-specific model were in agreement with the related functional in-vivo data. SIGNIFICANCE: The capability to reproduce physiological hemodynamics condition, with high-fidelity, plays a significant role in the cardiovascular research. The developed platform can be used to assess the performances of cardiovascular devices, to validate numerical simulations, and to test imaging systems.

Impact of the Spatial Velocity Inlet Distribution on the Hemodynamics of the Thoracic Aorta.

The impact of the distribution in space of the inlet velocity in the numerical simulations of the hemodynamics in the thoracic aorta is systematically investigated. A real healthy aorta geometry, for which in-vivo measurements are available, is considered. The distribution is modeled through a truncated cone shape, which is a suitable approximation of the real one downstream of a trileaflet aortic valve during the systolic part of the cardiac cycle. The ratio between the upper and the lower base of the truncated cone and the position of the center of the upper base are selected as uncertain parameters. A stochastic approach is chosen, based on the generalized Polynomial Chaos expansion, to obtain accurate response surfaces of the quantities of interest in the parameter space. The selected parameters influence the velocity distribution in the ascending aorta. Consequently, effects on the wall shear stress are observed, confirming the need to use patient-specific inlet conditions if interested in the hemodynamics of this region. The surface base ratio is globally the most important parameter. Conversely, the impact on the velocity and wall shear stress in the aortic arch and descending aorta is almost negligible.

Uncertainty Quantification in the In Vivo Image-Based Estimation of Local Elastic Properties of Vascular Walls.

INTRODUCTION: Patient-specific computational models are a powerful tool for planning cardiovascular interventions. However, the in vivo patient-specific mechanical properties of vessels represent a major source of uncertainty. In this study, we investigated the effect of uncertainty in the elastic module (E) on a Fluid-Structure Interaction (FSI) model of a patient-specific aorta. METHODS: The image-based χ-method was used to compute the initial E value of the vascular wall. The uncertainty quantification was carried out using the generalized Polynomial Chaos (gPC) expansion technique. The stochastic analysis was based on four deterministic simulations considering four quadrature points. A deviation of about ±20% on the estimation of the E value was assumed. RESULTS: The influence of the uncertain E parameter was evaluated along the cardiac cycle on area and flow variations extracted from five cross-sections of the aortic FSI model. Results of stochastic analysis showed the impact of E in the ascending aorta while an insignificant effect was observed in the descending tract. CONCLUSIONS: This study demonstrated the importance of the image-based methodology for inferring E, highlighting the feasibility of retrieving useful additional data and enhancing the reliability of in silico models in clinical practice.

Transcatheter Treatment of Native Idiopathic Multiloculated Aortic Aneurysm Guided by 3D Printing Technology.

Pediatric idiopathic aortic aneurysm is rare. Single saccular malformation can complicate native or recurrent aortic coarctation; however, multiloculated dilatations of the descending thoracic aorta, associated with aortic coarctation, have so far never been described in literature. In our case, printed 3D model technology was crucial in planning transcatheter treatment. (Level of Difficulty: Intermediate.).

An image-based approach for the estimation of arterial local stiffness in vivo.

The analysis of mechanobiology of arterial tissues remains an important topic of research for cardiovascular pathologies evaluation. In the current state of the art, the gold standard to characterize the tissue mechanical behavior is represented by experimental tests, requiring the harvesting of ex-vivo specimens. In recent years though, image-based techniques for the in vivo estimation of arterial tissue stiffness were presented. The aim of this study is to define a new approach to provide local distribution of arterial stiffness, estimated as the linearized Young's Modulus, based on the knowledge of in vivo patient-specific imaging data. In particular, the strain and stress are estimated with sectional contour length ratios and a Laplace hypothesis/inverse engineering approach, respectively, and then used to calculate the Young's Modulus. After describing the method, this was validated by using a set of Finite Element simulations as input. In particular, idealized cylinder and elbow shapes plus a single patient-specific geometry were simulated. Different stiffness distributions were tested for the simulated patient-specific case. After the validation from Finite Element data, the method was then applied to patient-specific ECG-gated Computed Tomography data by also introducing a mesh morphing approach to map the aortic surface along the cardiac phases. The validation process revealed satisfactory results. In the simulated patient-specific case, root mean square percentage errors below 10% for the homogeneous distribution and below 20% for proximal/distal distribution of stiffness. The method was then successfully used on the three ECG-gated patient-specific cases. The resulting distributions of stiffness exhibited significant heterogeneity, nevertheless the resulting Young's moduli were always contained within the 1-3 MPa range, which is in line with literature.

3D Printed Model-Guided Neonatal Transcatheter Closure of Left Main Coronary Artery-to-Right Ventricle Fistula.

We report on a 2-week-old infant with huge left main coronary artery-to-right ventricular outflow tract fistula causing myocardial ischemia due to global coronary steal who was successfully submitted to percutaneous closure guided by a 3-dimensional-printed model using a duct-occluder vascular plug. (Level of Difficulty: Advanced.).

Coupling synthetic and real-world data for a deep learning-based segmentation process of 4D flow MRI.

BACKGROUND AND OBJECTIVE: Phase contrast magnetic resonance imaging (4D flow MRI) is an imaging technique able to provide blood velocity in vivo and morphological information. This capability has been used to study mainly the hemodynamics of large vessels, such as the thoracic aorta. However, the segmentation of 4D flow MRI data is a complex and time-consuming task. In recent years, neural networks have shown great accuracy in segmentation tasks if large datasets are provided. Unfortunately, in the context of 4D flow MRI, the availability of these data is limited due to its recent adoption in clinical settings. In this study, we propose a pipeline for generating synthetic thoracic aorta phase contrast magnetic resonance angiography (PCMRA) to expand the limited dataset of patient-specific PCMRA images, ultimately improving the accuracy of the neural network segmentation even with a small real dataset. METHODS: The pipeline involves several steps. First, a statistical shape model is used to synthesize new artificial geometries to improve data numerosity and variability. Secondly, computational fluid dynamics simulations are employed to simulate the velocity fields and, finally, after a downsampling and a signal-to-noise and velocity limit adjustment in both frequency and spatial domains, volumes are obtained using the PCMRA formula. These synthesized volumes are used in combination with real-world data to train a 3D U-Net neural network. Different settings of real and synthetic data are tested. RESULTS: Incorporating synthetic data into the training set significantly improved the segmentation performance compared to using only real data. The experiments with synthetic data achieved a DICE score (DS) value of 0.83 and a better target reconstruction with respect to the case with only real data (DS = 0.65). CONCLUSION: The proposed pipeline demonstrated the ability to increase the dataset in terms of numerosity and variability and to improve the segmentation accuracy for the thoracic aorta using PCMRA.

Impact of wall displacements on the large-scale flow coherence in ascending aorta.

In the context of aortic hemodynamics, uncertainties affecting blood flow simulations hamper their translational potential as supportive technology in clinics. Computational fluid dynamics (CFD) simulations under rigid-walls assumption are largely adopted, even though the aorta contributes markedly to the systemic compliance and is characterized by a complex motion. To account for personalized wall displacements in aortic hemodynamics simulations, the moving-boundary method (MBM) has been recently proposed as a computationally convenient strategy, although its implementation requires dynamic imaging acquisitions not always available in clinics. In this study we aim to clarify the real need for introducing aortic wall displacements in CFD simulations to accurately capture the large-scale flow structures in the healthy human ascending aorta (AAo). To do that, the impact of wall displacements is analyzed using subject-specific models where two CFD simulations are performed imposing (1) rigid walls, and (2) personalized wall displacements adopting a MBM, integrating dynamic CT imaging and a mesh morphing technique based on radial basis functions. The impact of wall displacements on AAo hemodynamics is analyzed in terms of large-scale flow patterns of physiological significance, namely axial blood flow coherence (quantified applying the Complex Networks theory), secondary flows, helical flow and wall shear stress (WSS). From the comparison with rigid-wall simulations, it emerges that wall displacements have a minor impact on the AAo large-scale axial flow, but they can affect secondary flows and WSS directional changes. Overall, helical flow topology is moderately affected by aortic wall displacements, whereas helicity intensity remains almost unchanged. We conclude that CFD simulations with rigid-wall assumption can be a valid approach to study large-scale aortic flows of physiological significance.

Fabrication of deformable patient-specific AAA models by material casting techniques.

Background: Abdominal Aortic Aneurysm (AAA) is a balloon-like dilatation that can be life-threatening if not treated. Fabricating patient-specific AAA models can be beneficial for in-vitro investigations of hemodynamics, as well as for pre-surgical planning and training, testing the effectiveness of different interventions, or developing new surgical procedures. The current direct additive manufacturing techniques cannot simultaneously ensure the flexibility and transparency of models required by some applications. Therefore, casting techniques are presented to overcome these limitations and make the manufactured models suitable for in-vitro hemodynamic investigations, such as particle image velocimetry (PIV) measurements or medical imaging. Methods: Two complex patient-specific AAA geometries were considered, and the related 3D models were fabricated through material casting. In particular, two casting approaches, i.e. lost molds and lost core casting, were investigated and tested to manufacture the deformable AAA models. The manufactured models were acquired by magnetic resonance, computed tomography (CT), ultrasound imaging, and PIV. In particular, CT scans were segmented to generate a volumetric reconstruction for each manufactured model that was compared to a reference model to assess the accuracy of the manufacturing process. Results: Both lost molds and lost core casting techniques were successful in the manufacturing of the models. The lost molds casting allowed a high-level surface finish in the final 3D model. In this first case, the average signed distance between the manufactured model and the reference was (-0.2±0.2) mm. However, this approach was more expensive and time-consuming. On the other hand, the lost core casting was more affordable and allowed the reuse of the external molds to fabricate multiple copies of the same AAA model. In this second case, the average signed distance between the manufactured model and the reference was (0.1±0.6) mm. However, the final model's surface finish quality was poorer compared to the model obtained by lost molds casting as the sealing of the outer molds was not as firm as the other casting technique. Conclusions: Both lost molds and lost core casting techniques can be used for manufacturing patient-specific deformable AAA models suitable for hemodynamic investigations, including medical imaging and PIV.