3D Heart Research Articles

His bundle pacing in a patient with complete atrioventricular block and congenitally corrected transposition of the great arteries: potential of the use of extended reality and cardiac electrical activity projected into 3D heart model.

His bundle pacing in a patient with complete atrioventricular block and congenitally corrected transposition of the great arteries: potential of the use of extended reality and cardiac electrical activity projected into 3D heart model.

CardiacField: computational echocardiography for automated heart function estimation using two-dimensional echocardiography probes

Abstract Aims Accurate heart function estimation is vital for detecting and monitoring cardiovascular diseases. While two-dimensional echocardiography (2DE) is widely accessible and used, it requires specialized training, is prone to inter-observer variability, and lacks comprehensive three-dimensional (3D) information. We introduce CardiacField, a computational echocardiography system using a 2DE probe for precise, automated left ventricular (LV) and right ventricular (RV) ejection fraction (EF) estimations, which is especially easy to use for non-cardiovascular healthcare practitioners. We assess the system’s usability among novice users and evaluate its performance against expert interpretations and advanced deep learning (DL) tools. Methods and results We developed an implicit neural representation network to reconstruct a 3D cardiac volume from sequential multi-view 2DE images, followed by automatic segmentation of LV and RV areas to calculate volume sizes and EF values. Our study involved 127 patients to assess EF estimation accuracy against expert readings and two-dimensional (2D) video-based DL models. A subset of 56 patients was utilized to evaluate image quality and 3D accuracy and another 50 to test usability by novice users and across various ultrasound machines. CardiacField generated a 3D heart from 2D echocardiograms with <2 min processing time. The LVEF predicted by our method had a mean absolute error (MAE) of 2.48%, while the RVEF had an MAE of 2.65%. Conclusion Employing a straightforward apical ring scan with a cost-effective 2DE probe, our method achieves a level of EF accuracy for assessing LV and RV function that is comparable to that of three-dimensional echocardiography probes.

Three-Dimensional Heart Modeling of Hypertrophic Obstructive Cardiomyopathy for In Situ Patient-Specific Simulation to Optimize Septal Myectomy.

Hypertrophic obstructive cardiomyopathy (HOCM) develops in at least 1 out of 715 young adults. Patients who are refractory to medical therapy qualify for septal myectomy. Due to anatomy, serious complications such as ventricular septal defect and heart block may occur. Establishing cardiovascular magnetic resonance (CMR)-based 3-dimensional (3D) models as part of preoperative planning and training has the potential to decrease procedure-related complications and improve results. CMR images were used to segment cardiac structures. Left ventricular wall thickness was calculated and projected on top of the in silico model. A 3D model was printed with a red layer indicating a wall thickness exceeding 15 mm and used for preoperative resection planning and patient counseling. To provide preoperative patient-specific in situ simulation, the planned resection volume was replaced with silicone in a second model. For perioperative quality control, resected silicone was compared with resected myocardial tissue. The impact of the models was evaluated descriptively through consultation of both the cardiothoracic surgeon and patients and through patient outcomes. Three-dimensional in silico and 3D-printed heart models of 5 patients were established preoperatively. Since the introduction of the models in October 2020, the surgeon feels better prepared, more confident, and less difficulty with making decisions. In addition, patients feel better informed preoperatively. Using 3D heart models optimized preoperative planning and training, intraoperative quality control, and patient consultation. Reduction of procedure-related complications and clinical outcome should be studied in larger cohorts.

In Vivo Three-Dimensional Geometric Reconstruction of the Mouse Aortic Heart Valve.

Aortic valve (AV) disease is a common valvular lesion in the United States, present in about 5% of the population at age 65 with increasing prevalence with advancing age. While current replacement heart valves have extended life for many, their long-term use remains hampered by limited durability. Non-surgical treatments for AV disease do not yet exist, in large part because our understanding of AV disease etiology remains incomplete. The direct study of human AV disease remains hampered by the fact that clinical data is only available at the time of treatment, where the disease is at or near end stage and any time progression information has been lost. Large animal models, long used to assess replacement AV devices, cannot yet reproduce AV disease processes. As an important alternative mouse animal models are attractive for their ability to perform genetic studies of the AV disease processes and test potential pharmaceutical treatments. While mouse models have been used for cellular and genetic studies of AV disease, their small size and fast heart rates have hindered their use for tissue- and organ-level studies. We have recently developed a novel ex vivo micro-CT-based methodology to 3D reconstruct murine heart valves and estimate the leaflet mechanical behaviors (Feng et al. in Sci Rep 13(1):12852, 2023). In the present study, we extended our approach to 3D reconstruction of the in vivo functional murine AV (mAV) geometry using high-frequency four-dimensional ultrasound (4DUS). From the resulting 4DUS images we digitized the mAV mid-surface coordinates in the fully closed and fully opened states. We then utilized matched high-resolution µCT images of ex vivo mouse mAV to develop mAV NURBS-based geometric model. We then fitted the mAV geometric model to the in vivo data to reconstruct the 3D in vivo mAV geometry in the closed and open states in n = 3 mAV. Results demonstrated high fidelity geometric results. To our knowledge, this is the first time such reconstruction was ever achieved. This robust assessment of in vivo mAV leaflet kinematics in 3D opens up the possibility for longitudinal characterization of murine models that develop aortic valve disease.

Mixed Reality in Medical Education - Introduction of a Practical Course Module.

With increasing digitalization in healthcare, there is growing potential for the use of Mixed Reality (MR) in medicine. In response to this, we developed a course to provide students with hands-on experience in MR and familiarize them with the technology. Utilizing the HoloLens 2, we designed an application enabling multiple users to interact with virtual objects overlaid on the real world and shared across devices. We used 3D heart anatomy models to let students discuss cardiovascular diseases together. We conducted a preliminary evaluation of our prototype, involving ten participants. The first test indicated a positive reception of the course, with students expressing keen interest in MR. With this work we share our experience to contribute to the field of MR applications.

Concordance of left ventricular volumes and function measurements between two human readers, a fully automated AI algorithm, and the 3D heart model.

Echocardiography is essential in cardiovascular medicine for screening, diagnosis, and monitoring. Artificial intelligence (AI) has the potential to improve echocardiography by reducing variability and analysis time. While 3D echocardiography is becoming more accurate, 2D imaging still dominates clinical care. We aimed to evaluate agreement in measures of left ventricular (LV) volumes and function between human readers, a fully automated AI 2D algorithm, and the 3D Heart Model. A retrospective analysis was conducted on 109 patients who underwent 2D and 3D transthoracic echocardiography. LV end-diastolic and end-systolic volumes (LVEDV, LVESV) and ejection fraction (LVEF) were measured by two operators, a commercially available AI algorithm (US2ai), and the 3D Heart Model. Global longitudinal strain (GLS) was measured by the integrated semi-automated software and the AI algorithm. Outcomes included measures of agreement [bias, limit of agreement and Pearson's correlation (R)]. For LV volume measurements, the AI algorithm was strongly correlated with the average of the human operators (r = 0.89 for LVEDV and r = 0.92 for LVESV), which was higher than between the operators (r = 0.74 and r = 0.84, respectively, p < 0.01). The same trend was seen for measures of reliability with respect to LVEDV, but not LVESV. AI demonstrated comparable performance to human operators in measuring LVEF, while the 3D Heart Model had a weaker correlation and reliability compared with human operators and AI measurements. The correlation between human operators and AI for GLS was only moderate. This study demonstrates AI-based echocardiography as a promising tool for accurately assessing LV volumes and LVEF in clinical practice. AI-based measures demonstrated a significantly lower inter-operator variability, thereby improving the consistency and reliability of these assessments. Moreover, AI may prove particularly effective for conducting retrospective bulk analyses, offering a valuable tool for comprehensive evaluations of past data.

Advancements in Finite Element Modeling for Cardiac Device Leads and 3D Heart Models.

The human heart's remarkable vitality necessitates a deep understanding of its mechanics, particularly concerning cardiac device leads. This paper presents advancements in finite element modeling for cardiac leads and 3D heart models, leveraging computational simulations to assess lead behavior over time. Through detailed modeling and meshing techniques, we accurately captured the complex interactions between leads and heart tissue. Material properties were assigned based on ASTM (American Society for Testing and Materials) standards and in vivo exposure data, ensuring realistic simulations. Our results demonstrate close agreement between experimental and simulated data for silicone insulation in pacemaker leads, with a mean force tolerance of 19.6 N ± 3.6 N, an ultimate tensile strength (UTS) of 6.3 MPa ± 1.15 MPa, and a percentage elongation of 125% ± 18.8%, highlighting the effectiveness of simulation in predicting lead performance. Similarly, for polyurethane insulation in ICD leads, we found a mean force of 65.87 N ± 7.1 N, a UTS of 10.7 MPa ± 1.15 MPa, and a percentage elongation of 259.3% ± 21.4%. Additionally, for polyurethane insulation in CRT leads, we observed a mean force of 53.3 N ± 2.06 N, a UTS of 22.11 MPa ± 0.85 MPa, and a percentage elongation of 251.6% ± 13.2%. Correlation analysis revealed strong relationships between mechanical properties, further validating the simulation models. Classification models constructed using both experimental and simulated data exhibited high discriminative ability, underscoring the reliability of simulation in analyzing lead behavior. These findings contribute to the ongoing efforts to improve cardiac device lead design and optimize patient outcomes.

Human cardiomyocyte derived extracellular vesicles regulate cardiac fibroblast activation through miR-24

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Fondazione Leonardo Introduction Cardiovascular diseases are associated with increase in interstitial fibrosis due to cardiac fibroblast (CF) activation into myofibroblast leading to the secretion and deposition of extracellular matrix (ECM). The intricate functional activation of these processes is not well understood, especially concerning the contribution of the microenvironment. One of the most important mechanisms of paracrine communication are due to Extracellular vesicles (EVs). EVs are cell-released nanoparticles carrying proteins, lipids, and nucleic acids, particularly miRs. To note, previous transcriptomic analysis of healthy human heart demonstrated that miR24-3p is one of the most abundant miRs [1], suggesting an important role associated with its expression. Aim of the work Here we aim to investigate the role of miR24-3p as regulator of cardiac fibroblast activation, focusing on healthy and pathological conditions. Materials and methods Bioinformatic analysis of open-data, single-cell RNA sequencing from heart tissue was conducted to assess the expression of miR24-3p and its specific targets in both healthy and infarcted myocardium. To explore the functional role of miR24-3p, loss- and gain-of-function experiments were performed by transfecting cardiac fibroblasts (CF) with specific antimiR or mimic oligonucleotides, respectively. In investigating the influence of cardiomyocytes (CM) on CF regulation, extracellular vesicles (EVs) from human-induced pluripotent stem cell-derived CM were isolated and utilized in in vitro experiments. The expression levels of miRNA24-3p were also evaluated in the plasma of healthy individuals and patients who had experienced myocardial infarction. Finally, cardiac slices from human tissue were employed as ex-vivo microtissues to functionally validate the in vitro findings. Results RealTime analysis of CF, CM and cardiac endothelial cells (EC) revealed a CM specific expression of miR24-3p, not only at cellular level but also in EVs. Upregulation of miR24-3p in CF was able to significantly reduce protein expression of FURIN, CYCLD1 and SMAD4, resulting in decrease of CF activation and ECM secretion. Interestingly, treatment of CF with CM-EVs recapitulate miR24-3p transfection, while EVs derived from hypoxia cultured CM (MI-like) does not. RNAScope and ddPCR analysis on human cardiac slice cultured under hypoxia conditions confirmed decrease in miR24-3p expression upon induction of stress. Ultimately, a significant decrease in miR24-3p in circulating serum EVs of MI patients’ was observed. Conclusions These data demonstrate the role of miR24-3p in CF regulation through the paracrine activity mediated by CM-EVs. Further analysis, including the use of a 3D human heart microtissue, will confirm the mechanism of cross-talk between CM and CF.

Cardiovascular magnetic resonance 3D LGE imaging for atrial fibrillation ablation

Abstract Objective To assess feasibility and reliability of cardiac magnetic resonance (CMR) imaging in visualizing left atrial (LA) structural changes that patients with paroxysmal atrial fibrillation (PAF) undergo acutely and long-term post ablation. Two different ablation methods i.e pulsed filed ablation (PFA) and cryoablation were studied. Background Pulmonary vein (PV) isolation has become the cornerstone technique for catheter ablation in patients with drug-refractory atrial fibrillation (AF). At present, almost all ablation technologies are mediated by a thermal effect. Recently, pulsed field ablation (PFA) has been introduced as a new energy source. PFA is a non-thermal ablative modality in which high voltage ultra-short pulses are applied to target tissue, while preserving the extracellular matrix architecture, nerves, and microvascular structures. Few data exist showing different structural LA changes between the two methods using Three-Dimensional (3D) Late Gadolinium Enhancement (LGE) Imaging. Methods CMR imaging was performed pre-ablation, acutely (&amp;lt;24 h), and 3 months post-ablation in 10 patients with paroxysmal atrial fibrillation (AF) undergoing pulmonary vein (PV) isolation with PFA (n = 5) or cryoablation (n = 5). 3D LGE and T2-weighted images were analysed. We obtained two data sets of 3D whole heart LGE imaging with high resolution, 20minutes post gadolinium injection. Patients underwent two acquisitions: the conventional respiratory navigated, electrocardiographically-gated 3D fast gradient echo (1.3slice thickness, 256x256 matrix acquisition) and the image-navigated isotropic high resolution 3D LGE with Dixon water-fat separation. 3D LGE data were analysed using a dedicated (ADAS LA) software in order to produce a 3D-LA model visualization of LGE areas. Results In the acute stage, LGE volume was 50% larger after PFA vs. cryoablation (P &amp;lt; 0.001), and oedema on T2 imaging was significantly smaller (visual estimation) on PFA cases. LGE rings surrounding PV ostia were more homogeneous after PFA, with no sign of microvascular damage or intramural hemorrhage as compared to cryoablation cases. In the chronic stage, the majority of acute LGE had disappeared after PFA, whereas most LGE persisted after cryo-ablation. The two 3D LGE sequences used for analysis showed complete agreement in the visualization of atrial scar with superior image quality of the novel sequence. The mean acquisition time for 3D LGE imaging was 11±4minutes for the conventional fast gradient echo sequence, and 5±2minutes for the novel 3D self-image navigated LGE sequence. Conclusions CMR imaging may help in visualization and understanding of LA structural remodeling post different ablation techniques.

Cardiac magnetic resonance - aided ventricular tachycardia substrate ablation

Abstract Objectives To assess feasibility and reliability of Cardiac magnetic resonance (CMR)-derived pixel signal intensity (PSI) maps obtained by Three Dimensional (3D)- Late Gadolinium Enhancement (LGE) images for detecting potential targets for VT substrate ablation procedures. Background Parametric imaging with color-coded PSI maps obtained from pre-ablation 3D LGE -CMR imaging can be used for identification and characterization of arrhythmic abnormal substrate. Recent publications have shown that PSI maps permit visualization of border zone areas inside the scar. Specifically, corridors of viable tissue within the scar connecting healthy myocardium define VT corridors that may be the electrical equivalent of the abnormal conducting channels on the electroanatomical mapping (EAM). Methods 8 patients with scar-dependent monomorphic VTs who underwent 3D-LGE CMR imaging prior to substrate ablation were included in the study. The studies were performed at 1.5T scanner. We obtained two data sets of 3D whole heart LGE imaging with high resolution. Patients underwent two acquisitions: the conventional respiratory navigated, electrocardiographically-gated 3D fast gradient echo (1.3slice thickness, 256x256 matrix acquisition) and the image-navigated isotropic high resolution 3D GE with Dixon water-fat separation. 3D LGE-CMR images were processed with ADAS-VT software to produce a 3-dimensional model of the heart with 10 layers from the endocardium to epicardium and PSI maps color-coded from the LGE data projected to each of the shells (Figure 1). In the LGE-CMR PSI maps, VT corridors were obtained automatically by the ADAS VT software. Subsequently, data were given to the electrophysiologists and merged with the CARTO3 system EAM data obtained for the ablation (Figure2). CMR information was used to facilitate the identification of target ablation sites in the areas identified by CMR as abnormal substrate and radiofrequency was applied in the presence of both a pathological electrogram (EGM) and a VT corridor as identified by CMR. Results There was a 95% agreement between the abnormal conducting channels as detected by abnormal electrograms in the EAM and the VT corridors identified by 3D LGE CMR imaging. In two occasions, there was one VT corridor that did not correlate with abnormal electrograms and was not ablated. The two 3D LGE sequences used for ADAS-VT corridors analysis showed complete agreement in the number and location of VT corridors. Mean acquisition time for 3D LGE imaging was 11±4minutes for the conventional fast gradient echo sequence, and 5±2minutes for the novel 3D self-image navigated LGE sequence. The image quality of 3D LGE was superior with the Dixon fat-water separation. Overall CMR-aided VT ablation reduced the procedural and fluoroscopy time by 40%. Conclusions CMR-aided VT ablation is feasible, reliable and significantly reduces the procedural time.

A patient-based realistic simulation platform to train future electrophysiologists to complex ablation procedures

Abstract Title An immersive catheter ablation platform based on patients’ 3D heart model for the simulation and training of future electrophysiologists. Background Arrhythmias are on the rise worldwide due to the ageing of the population. Projections urge to train the next generation of electrophysiologists (EPs) to perform catheter (CATH) ablation (CA) of arrhythmias. Training of future EPs relies mostly on a companionship, where teaching of CATH steerability is made on patients (pts) referred for procedures. While several other domains have established the utility of simulators to speed up learning process, increase safety and establish procedure road maps, dedicated simulators for EPs based on pts’ real anatomy do not exist yet. Purpose To speed up the handling of steerable CATH on MRI-based 3D heart models to optimize ablation road maps in pts referred for complex arrhythmias. Methods ARTS is an Artificial Intelligence and Augmented Reality-based platform comprising two key components: HeARTS and ARTSim. HeARTS is designed to automatically generate 3D heart models from pts’ MRI scans. ARTSim is a CA simulator that utilizes the 3D heart models of the pts for the planning and simulation of CA procedures. This simulator incorporates innovative techniques for digitizing and tracking the movements of a physical catheter in real time, and enabling its navigation within a completely virtual heart. With this technology, the CATH can be precisely steered to various heart locations, including the right and left (LA) atrium, the coronary sinus, and the right and left (LV) ventricles. Results Panel A of the figure shows the mannequin used for the simulator, where a real ablation CATH is introduced within the pt’s heart through a venous introducer. Panel B shows right anterior oblique (RAO) and modified RAO views of a pt suffering from a typical right atrial flutter. Note the presence of yellow tags positioned along the cavotricuspid isthmus (CTI) that the trainee must reach for a programmable duration using the shaft and the handle of the CATH shown in panel A. Panel C shows the virtual ablation CATH in green positioned on the target dots of the CTI. The pink color indicates that the trainee reached the desired target, which became red when the CATH remained stable at the same location for a duration of 5 sec (i.e. stability) with a force &amp;gt;5g (i.e. efficacy) and &amp;lt;20g (i.e. safety). Conclusions Herein, we present ARTS, a realistic CA simulation platform for the training of future EPs, that offers all the typical characteristics of 3D navigation including steerability, stability measurements and the force applied. Importantly, ARTS is based on the true anatomy of the pts, hence might be used to establish and discuss roadmaps to optimize procedures efficacy and safety. Version 2.0, foreseen early 2024, will include 3D late gadolinium enhancement and transseptal puncture for virtual LA and LV procedures, and later on activation times and myocardial voltage.Figure

The effect of 3D modeling on family quality of life, surgical success, and patient outcomes in congenital heart diseases: objectives and design of a randomized controlled trial.

Understanding the severity of the disease from the parents' perspective can lead to better patient outcomes, improving both the child's health-related quality of life and the family's quality of life. The implementation of 3-dimensional (3D) modeling technology in care is critical from a translational science perspective. The purpose of this study is to determine the effect of 3D modeling on family quality of life, surgical success, and patient outcomes in congenital heart diseases. Additionally, we aim to identify challenges and potential solutions related to this innovative technology. The study is a two-group pretest-posttest randomized controlled trial protocol. The sample size is 15 in the experimental group and 15 in the control group. The experimental group's heart models will be made from their own computed tomography (CT) images and printed using a 3D printer. The experimental group will receive surgical simulation and preoperative parent education with their 3D heart model. The control group will receive the same parent education using the standard anatomical model. Both groups will complete the Sociodemographic Information Form, the Surgical Simulation Evaluation Form - Part I-II, and the Pediatric Quality of Life Inventory (PedsQL) Family Impacts Module. The primary outcome of the research is the average PedsQL Family Impacts Module score. Secondary outcome measurement includes surgical success and patient outcomes. Separate analyses will be conducted for each outcome and compared between the intervention and control groups. Anomalies that can be clearly understood by parents according to the actual size and dimensions of the child's heart will affect the preoperative preparation of the surgical procedure and the recovery rate in the postoperative period.

Comparing fabrication techniques for engineered cardiac tissue.

Tissue engineering can provide in vitro models for drug testing, disease modeling, and perhaps someday, tissue/organ replacements. For building 3D heart tissue, the alignment of cardiac cells or cardiomyocytes (CMs) is important in generating a synchronously contracting tissue. To that end, researchers have generated several fabrication methods for building heart tissue, but direct comparisons of pros and cons using the same cell source is lacking. Here, we derived cardiomyocytes (CMs) from human induced pluripotent stem cells (hiPSCs) and compare the assembly of these cells using three fabrication methods: cardiospheres, muscle rings, and muscle strips. All three protocols successfully generated compacted tissue comprised of hiPSC-derived CMs stable for at least 2 weeks. The percentage of aligned cells was greatest in the muscle strip (55%) and the muscle ring (50%) compared with the relatively unaligned cardiospheres (35%). The iPSC-derived CMs within the muscle strip also exhibited the greatest elongation, with elongation factor at 2.0 compared with 1.5 for the muscle ring and 1.2 for the cardiospheres. This is the first direct comparison of various fabrication techniques using the same cell source.

Remodeling of Ventricular Catecholaminergic Axons Following Chronic Intermittent Hypoxia in Mice

Chronic intermittent hypoxia (CIH) is a widely employed model for sleep apnea. The imbalance of autonomic control may contribute to CIH-induced cardiovascular diseases. Previously, we demonstrated that CIH increases sympathetic innervation of the atria. In this study, we determined whether CIH remodels peripheral cardiac tyrosine hydroxylase (TH, a marker for sympathetic efferent axons) innervation in the whole ventricles. The two challenges here were: 1) labeling the entire TH-IR axon innervation in the full thickness (~500 μm) of whole flat-mount ventricles. 2) Quantifying the topographical distribution of TH-IR axons through the thick ventricular walls at the single axon/varicosity scale. In this study, C57BL/6J mice (male, 2 months old, n=7/group) were exposed to room air (RA, 21% O2) or CIH (alternating between 21% and 5.7% O2 every 6 minutes for 10 hours/day) for 8-10 weeks. We prepared flat-mounts of the whole ventricles and septum and processed them with immunohistochemical labeling for TH. Using the Zeiss M2 Imager, confocal microscope, Zeiss Arivis Vision 4D, and Neurolucida system, we traced and digitized the TH-IR axons. We found that: 1) In RA and CIH mice, several large TH-immunoreactive (TH-IR) bundles from the base area entered the ventricles and septum. These large bundles branched into numerous smaller bundles as they traveled downward toward the apex and finally developed into fine varicose axons and terminals in the epicardial and myocardial layers. 2) Using Vision 4D, we were able to accurately detect, trace, and digitize all TH-IR axons in the ventricle walls with high accuracy. 3) CIH increased overall TH-IR axon density and network complexity of the whole ventricles and septum. 3) Abnormal CIH TH-IR axon terminal structures were frequently seen. 4) We geometrically and precisely registered the tracing data into a scaffold map for presentation and comparison in 3D. Altogether, CIH increased sympathetic innervation of the heart which may contribute to the augmented sympathetic drive. Our success in mapping data in the 3D heart scaffold will establish a heart-brain connectome/atlas. Supported by NIH 1 U01 NS113867-01 NIH R15 1R15HL137143-01A1, 2R01HL137832-05 and Carl Zeiss. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Modeling acute myocardial infarction and cardiac fibrosis using human induced pluripotent stem cell-derived multi-cellular heart organoids.

Heart disease involves irreversible myocardial injury that leads to high morbidity and mortality rates. Numerous cell-based cardiac in vitro models have been proposed as complementary approaches to non-clinical animal research. However, most of these approaches struggle to accurately replicate adult human heart conditions, such as myocardial infarction and ventricular remodeling pathology. The intricate interplay between various cell types within the adult heart, including cardiomyocytes, fibroblasts, and endothelial cells, contributes to the complexity of most heart diseases. Consequently, the mechanisms behind heart disease induction cannot be attributed to a single-cell type. Thus, the use of multi-cellular models becomes essential for creating clinically relevant in vitro cell models. This study focuses on generating self-organizing heart organoids (HOs) using human-induced pluripotent stem cells (hiPSCs). These organoids consist of cardiomyocytes, fibroblasts, and endothelial cells, mimicking the cellular composition of the human heart. The multi-cellular composition of HOs was confirmed through various techniques, including immunohistochemistry, flow cytometry, q-PCR, and single-cell RNA sequencing. Subsequently, HOs were subjected to hypoxia-induced ischemia and ischemia-reperfusion (IR) injuries within controlled culture conditions. The resulting phenotypes resembled those of acute myocardial infarction (AMI), characterized by cardiac cell death, biomarker secretion, functional deficits, alterations in calcium ion handling, and changes in beating properties. Additionally, the HOs subjected to IR efficiently exhibited cardiac fibrosis, displaying collagen deposition, disrupted calcium ion handling, and electrophysiological anomalies that emulate heart disease. These findings hold significant implications for the advancement of in vivo-like 3D heart and disease modeling. These disease models present a promising alternative to animal experimentation for studying cardiac diseases, and they also serve as a platform for drug screening to identify potential therapeutic targets.

3D whole heart k-space-based super-resolution cardiac T1 mapping using rotated stacks

Objective. To provide three-dimensional (3D) whole-heart high-resolution isotropic cardiac T1 maps using a k-space-based through-plane super-resolution reconstruction (SRR) with rotated multi-slice stacks. Approach. Due to limited SNR and cardiac motion, often only 2D T1 maps with low through-plane resolution (4–8 mm) can be obtained. Previous approaches used SRR to calculate 3D high-resolution isotropic cardiac T1 maps. However, they were limited to the ventricles. The proposed approach acquires rotated stacks in long-axis orientation with high in-plane resolution but low through-plane resolution. This results in radially overlapping stacks from which high-resolution T1 maps of the whole heart are reconstructed using a k-space-based SRR framework considering the complete acquisition model. Cardiac and residual respiratory motion between different breath holds is estimated and incorporated into the reconstruction. The proposed approach was evaluated in simulations and phantom experiments and successfully applied to ten healthy subjects.Main results. 3D T1 maps of the whole heart were obtained in the same acquisition time as previous methods covering only the ventricles. T1 measurements were possible even for small structures, such as the atrial wall. The proposed approach provided accurate (P > 0.4; R 2 > 0.99) and precise T1 values (SD of 64.32 ± 22.77 ms in the proposed approach, 44.73 ± 31.9 ms in the reference). The edge sharpness of the T1 maps was increased by 6.20% and 4.73% in simulation and phantom experiments, respectively. Contrast-to-noise ratios between the septum and blood pool increased by 14.50% in in vivo measurements with a k-space compared to an image-space-based SRR. Significance. The proposed approach provided whole-heart high-resolution 1.3 mm isotropic T1 maps in an overall acquisition time of approximately three minutes. Small structures, such as the atrial and right ventricular walls, could be visualized in the T1 maps.

A Novel Approach to Cardiac Magnetic Resonance Scar Characterization in Patients Affected by Cardiac Amyloidosis: A Pilot Study.

Background and Objectives: Cardiac magnetic resonance (CMR) imaging has become an essential instrument in the study of cardiomyopathies; it has recently been integrated into the diagnostic workflow for cardiac amyloidosis (CA) with remarkable results. An additional emerging role is the stratification of the arrhythmogenic risk by scar analysis and the possibility of merging these data with electro-anatomical maps. This is made possible by using a software (ADAS 3D, Galgo Medical, Barcelona, Spain) able to provide 3D heart models by detecting fibrosis along the whole thickness of the myocardial walls. Little is known regarding the applications of this software in the wide spectrum of cardiomyopathies and the potential benefits have yet to be discovered. In this study, we tried to apply the ADAS 3D in the context of CA. Materials and Methods: This study was a retrospectively analysis of consecutive CMR imaging of patients affected by CA that were treated in our center (Marche University Hospital). Wherever possible, the data were processed with the ADAS 3D software and analyzed for a correlation between the morphometric parameters and follow-up events. The outcome was a composite of all-cause mortality, unplanned cardiovascular hospitalizations, sustained ventricular arrhythmias (VAs), permanent reduction in left ventricular ejection fraction, and pacemaker implantation. The secondary outcomes were the need for a pacemaker implantation and sustained VAs. Results: A total of 14 patients were deemed eligible for the software analysis: 8 patients with wild type transthyretin CA, 5 with light chain CA, and 1 with transthyretin hereditary CA. The vast majority of imaging features was not related to the composite outcome, but atrial wall thickening displayed a significant association with both the primary (p = 0.003) and the secondary outcome of pacemaker implantation (p = 0.003). The software was able to differentiate between core zones and border zones of scars, with the latter being the most extensively represented in all patients. Interestingly, in a huge percentage of CMR images, the software identified the highest degree of core zone fibrosis among the epicardial layers and, in those patients, we found a higher incidence of the primary outcome, without reaching statistical significance (p = 0.18). Channels were found in the scar zones in a substantial percentage of patients without a clear correlation with follow-up events. Conclusions: CMR imaging plays a pivotal role in cardiovascular diagnostics. Our analysis shows the feasibility and applicability of such instrument for all types of CA. We could not only differentiate between different layers of scars, but we were also able to identify the presence of fibrosis channels among the different scar zones. None of the data derived from the ADAS 3D software seemed to be related to cardiac events in the follow-up, but this might be imputable to the restricted number of patients enrolled in the study.

Tailored and universal parallel transmit broadband pulses for homogeneous 3D excitation of the human heart at 7T.

To research and evaluate the performance of broadband tailored kT-point pulses (TP) and universal pulses (UP) for homogeneous excitation of the human heart at 7T. Relative 3D -maps of the thorax were acquired from 29 healthy volunteers. TP and UP were designed using the small-tip-angle approximation for a different composition of up to seven resonance frequencies. TP were computed for each of the 29 -maps, and UPs were calculated using 22 -maps and tested in seven testcases. The performance of the pulses was analyzed using the coefficient of variation (CV) in the 3D heart volumes. The 3D gradient-echo (GRE) scans were acquired for the seven testcases to qualitatively validate the -predictions. Single- and double-frequency optimized pulses achieved homogeneity in flip angle (FA) for the frequencies they were optimized for, while the broadband pulses achieved uniformity in FA across a 1300 Hz frequency range. Broadband TP and UP can be used for homogeneous excitation of the heart volume across a 1300 Hz frequency range, including the water and the main six fat peaks, or with longer pulse durations and higher FAs for a smaller transmit bandwidth. Moreover, despite large inter-volunteer variations, broadband UP can be used for calibration-free 3D heart FA homogenization in time-critical situations.

Deep learning from latent spatiotemporal information of the heart: Identifying advanced bioimaging markers from echocardiograms.

A key strength of echocardiography lies in its integration of comprehensive spatiotemporal cardiac imaging data in real-time, to aid frontline or bedside patient risk stratification and management. Nonetheless, its acquisition, processing, and interpretation are known to all be subject to heterogeneity from its reliance on manual and subjective human tracings, which challenges workflow and protocol standardization and final interpretation accuracy. In the era of advanced computational power, utilization of machine learning algorithms for big data analytics in echocardiography promises reduction in cost, cognitive errors, and intra- and inter-observer variability. Novel spatiotemporal deep learning (DL) models allow the integration of temporal arm information based on unlabeled pixel echocardiographic data for convolution of an adaptive semantic spatiotemporal calibration to construct personalized 4D heart meshes, assess global and regional cardiac function, detect early valve pathology, and differentiate uncommon cardiovascular disorders. Meanwhile, data visualization on spatiotemporal DL prediction models helps extract latent temporal imaging features to develop advanced imaging biomarkers in early disease stages and advance our understanding of pathophysiology to support the development of personalized prevention or treatment strategies. Since portable echocardiograms have been increasingly used as point-of-care imaging tools to aid rural care delivery, the application of these new spatiotemporal DL techniques show the potentials in streamlining echocardiographic acquisition, processing, and data analysis to improve workflow standardization and efficiencies, and provide risk stratification and decision supporting tools in real-time, to prompt the building of new imaging diagnostic networks to enhance rural healthcare engagement.

The new era of cardiovascular research: revolutionizing cardiovascular research with 3D models in a dish.

Cardiovascular research has heavily relied on studies using patient samples and animal models. However, patient studies often miss the data from the crucial early stage of cardiovascular diseases, as obtaining primary tissues at this stage is impracticable. Transgenic animal models can offer some insights into disease mechanisms, although they usually do not fully recapitulate the phenotype of cardiovascular diseases and their progression. In recent years, a promising breakthrough has emerged in the form of invitro three-dimensional (3D) cardiovascular models utilizing human pluripotent stem cells. These innovative models recreate the intricate 3D structure of the human heart and vessels within a controlled environment. This advancement is pivotal as it addresses the existing gaps in cardiovascular research, allowing scientists to study different stages of cardiovascular diseases and specific drug responses using human-origin models. In this review, we first outline various approaches employed to generate these models. We then comprehensively discuss their applications in studying cardiovascular diseases by providing insights into molecular and cellular changes associated with cardiovascular conditions. Moreover, we highlight the potential of these 3D models serving as a platform for drug testing to assess drug efficacy and safety. Despite their immense potential, challenges persist, particularly in maintaining the complex structure of 3D heart and vessel models and ensuring their function is comparable to real organs. However, overcoming these challenges could revolutionize cardiovascular research. It has the potential to offer comprehensive mechanistic insights into human-specific disease processes, ultimately expediting the development of personalized therapies.