Abstract:

Federated Learning (FL) holds the potential to advance equality in health by enabling diverse institutions to collaboratively train deep learning (DL) models, even with limited data. However, the significant resource requirements of FL often exclude centres with limited computational infrastructure, further widening existing healthcare disparities. To address this issue, we propose a Green AI-oriented adaptive layer-freezing strategy designed to reduce energy consumption and computational load while maintaining model performance. We tested our approach using different federated architectures for Magnetic Resonance Imaging (MRI)-to-Computed Tomography (CT) conversion. The proposed adaptive strategy optimises the federated training by selectively freezing the encoder weights based on the monitored relative difference of the encoder weights from round to round. A patience-based mechanism ensures that freezing only occurs when updates remain consistently minimal. The energy consumption and CO2eq emissions of the federation were tracked using the CodeCarbon library. Compared to equivalent non-frozen counterparts, our approach reduced training time, total energy consumption and CO2eq emissions by up to 23%. At the same time, the MRI-to-CT conversion performance was maintained, with only small variations in the Mean Absolute Error (MAE). Notably, for three out of the five evaluated architectures, no statistically significant differences were observed, while two architectures exhibited statistically significant improvements. Our work aligns with a research paradigm that promotes DL-based frameworks meeting clinical requirements while ensuring climatic, social, and economic sustainability. It lays the groundwork for novel FL evaluation frameworks, advancing privacy, equity and, more broadly, justice in AI-driven healthcare.

Abstract:

Cardiac fibrosis contributes to electrical conduction disturbances, yet its specific impact on conduction remains unclear, hindering predictive insight into cardiac electrophysiology and arrhythmogenesis. Arrhythmogenic cardiomyopathy is associated with fibrotic remodeling, and it accounts for most cases of stress-related arrhythmic sudden death. Here we develop a correlative imaging approach to integrate macroscale cardiac electrophysiology with three-dimensional microscale reconstructions of the ventricles. We apply this tool to a desmoglein-2 mutant mouse model to characterize the dynamics of conduction wavefronts and relate them to the underlying structural substrate. We observed that conduction through fibrotic tissue areas shows a frequency-dependent behavior, where conduction fails at high stimulation frequencies; this promotes reentrant arrhythmias, even in regions that were electrophysiologically inconspicuous at lower stimulation rates. We found that fibrotic areas undergo electrophysiological remodeling that acts as a low-pass filter for conduction, quantitatively explained by computational models informed by structural data. Collectively, our study provides a structure-function mapping pipeline and describes a pro-arrhythmogenic mechanism in arrhythmogenic cardiomyopathy.

Abstract:

Cone-beam computed tomography (CBCT) has become a widely adopted modality for image-guided radiotherapy (IGRT). However, CBCT is characterized by increased noise, limited soft-tissue contrast, and artifacts. These issues result in unreliable Hounsfield unit (HU) values, which limits direct dose calculation. These issues were addressed by generating synthetic CT (sCT) from CBCT, particularly by adopting deep learning (DL) methods. However, existing DL approaches were hindered by institutional heterogeneity, scanner-dependent variations, and data privacy regulations that prevented multi-center data sharing.To overcome these challenges, we proposed a cross-silo federated learning approach for CBCT-to-sCT synthesis in the head and neck region. This approach extended our original FedSynthCT framework to a different image modality and anatomical region. A conditional generative adversarial network (cGAN) was trained using data from three European medical centers within the SynthRAD2025 public challenge dataset while maintaining data privacy at each institution. A combination of the FedAvg and FedProx aggregation strategies, alongside a standardized preprocessing pipeline, was adopted to federate the DL model.The federated model effectively generalized across participating centers, as evidenced by the mean absolute error (MAE) ranging from $64.38\pm13.63$ to $85.90\pm7.10$ HU, the structural similarity index (SSIM) ranging from $0.882\pm0.022$ to $0.922\pm0.039$, and the peak signal-to-noise ratio (PSNR) ranging from $32.86\pm0.94$ to $34.91\pm1.04$ dB. Notably, performance on an external validation dataset of 60 patients yielded comparable metrics: a MAE of $75.22\pm11.81$ HU, an SSIM of $0.904\pm0.034$ and a PSNR of $33.52\pm2.06$, confirming robust cross-center generalization despite differences in imaging protocols and scanner types, without additional training. Furthermore, a visual analysis of the results revealed that the obtained metrics were influenced by registration errors.Our findings demonstrated the technical feasibility of FL for CBCT-to-sCT synthesis task while preserving data privacy, offering a collaborative solution for developing generalizable models across institutions without requiring data sharing or center-specific models.

Abstract:

The generation of Synthetic Computed Tomography (sCT) images has become a pivotal methodology in modern clinical practice, particularly in the context of Radiotherapy (RT) treatment planning. The use of sCT enables the calculation of doses, pushing towards Magnetic Resonance Imaging (MRI) guided radiotherapy treatments. Moreover, with the introduction of MRI-Positron Emission Tomography (PET) hybrid scanners, the derivation of sCT from MRI can improve the attenuation correction of PET images.Deep learning methods for MRI-to-sCT have shown promising results, but their reliance on single-centre training dataset limits generalisation capabilities to diverse clinical settings. Moreover, creating centralised multi-centre datasets may pose privacy concerns. To address the aforementioned issues, we introduced FedSynthCT-Brain, an approach based on the Federated Learning (FL) paradigm for MRI-to-sCT in brain imaging. This is among the first applications of FL for MRI-to-sCT, employing a cross-silo horizontal FL approach that allows multiple centres to collaboratively train a U-Net-based deep learning model. We validated our method using real multicentre data from four European and American centres, simulating heterogeneous scanner types and acquisition modalities, and tested its performance on an independent dataset from a centre outside the federation.In the case of the unseen centre, the federated model achieved a median Mean Absolute Error (MAE) of 102.0 HU across 23 patients, with an interquartile range of 96.7–110.5 HU. The median (interquartile range) for the Structural Similarity Index (SSIM) and the Peak Signal to Noise Ratio (PNSR) were 0.89 (0.86–0.89) and 26.58 (25.52–27.42), respectively.The analysis of the results showed acceptable performances of the federated approach, thus highlighting the potential of FL to enhance MRI-to-sCT to improve generalisability and advancing safe and equitable clinical applications while fostering collaboration and preserving data privacy.

Abstract:

This review focuses on the computerized modeling of the electrophysiology of the human atria, emphasizing the simulation of common arrhythmias such as atrial flutter (AFlut) and atrial fibrillation (AFib). Which components of the model are necessary to accurately model arrhythmogenic tissue modifications, including remodeling, cardiomyopathy, and fibrosis, to ensure reliable simulations? The central question explored is the level of detail required for trustworthy simulations for a specific context of use. The review discusses the balance between model complexity and computational efficiency, highlighting the risks of oversimplification and excessive detail. It covers various aspects of atrial modeling, from cellular to whole atria levels, including the influence of atrial geometry, fiber direction, anisotropy, and wall thickness on simulation outcomes. The article also examines the impact of different modeling approaches, such as volumetric 3D models, bilayer models, and single surface models, on the realism of simulations. In addition, it reviews the latest advances in the modeling of fibrotic tissue and the verification and validation of atrial models. The intended use of these models in planning and optimization of atrial ablation strategies is discussed, with a focus on personalized modeling for individual patients and cohort-based approaches for broader applications. The review concludes by emphasizing the importance of integrating experimental data and clinical validation to enhance the utility of computerized atrial models to improve patient outcomes.

Abstract:

Since the turn of the millennium, computational modelling of biological systems has evolved remarkably and sees matured use spanning basic and clinical research. While the topic of the peri-millennial debate about the virtues and limitations of 'reductionism and integrationism' seems less controversial today, a new apparent dichotomy dominates discussions: mechanistic vs. data-driven modelling. In light of this distinction, we provide an overview of recent achievements and new challenges with a focus on the cardiovascular system. Attention has shifted from generating a universal model of the human to either models of individual humans (digital twins) or entire cohorts of models representative of clinical populations to enable in silico clinical trials. Disease-specific parameterisation, inter-individual and intra-individual variability, uncertainty quantification as well as interoperable, standardised, and quality-controlled data are important issues today, which call for open tools, data and metadata standards, as well as strong community interactions. The quantitative, biophysical, and highly controlled approach provided by in silico methods has become an integral part of physiological and medical research. In silico methods have the potential to accelerate future progress also in the fields of integrated multi-physics modelling, multi-scale models, virtual cohort studies, and machine learning beyond what is feasible today. In fact, mechanistic and data-driven modelling can complement each other synergistically and fuel tomorrow's artificial intelligence applications to further our understanding of physiology and disease mechanisms, to generate new hypotheses and assess their plausibility, and thus to contribute to the evolution of preventive, diagnostic, and therapeutic approaches.

Abstract:

PurposeIdentifying and quantifying coronary artery calcification (CAC) is crucial for preoperative planning, as it helps to estimate both the complexity of the 2D coronary angiography (2DCA) procedure and the risk of developing intraoperative complications. Despite the relevance, the actual practice relies upon visual inspection of the 2DCA image frames by clinicians. This procedure is prone to inaccuracies due to the poor contrast and small size of the CAC; moreover, it is dependent on the physician’s experience. To address this issue, we developed a workflow to assist clinicians in identifying CAC within 2DCA using data from 44 image acquisitions across 14 patients.MethodsOur workflow consists of three stages. In the first stage, a classification backbone based on ResNet-18 is applied to guide the CAC identification by extracting relevant features from 2DCA frames. In the second stage, a U-Net decoder architecture, mirroring the encoding structure of the ResNet-18, is employed to identify the regions of interest (ROI) of the CAC. Eventually, a post-processing step refines the results to obtain the final ROI. The workflow was evaluated using a leave-out cross-validation.ResultsThe proposed method outperformed the comparative methods by achieving an F1-score for the classification step of 0.87 (0.77-0.94) (median ± quartiles), while for the CAC identification step the intersection over minimum (IoM) was 0.64 (0.46-0.86) (median ± quartiles).ConclusionThis is the first attempt to propose a clinical decision support system to assist the identification of CAC within 2DCA. The proposed workflow holds the potential to improve both the accuracy and efficiency of CAC quantification, with promising clinical applications. As future work, the concurrent use of multiple auxiliary tasks could be explored to further improve the segmentation performance.

Abstract:

BACKGROUND AND OBJECTIVE: Radiomics extracts quantitative features from magnetic resonance images (MRI) and is especially useful in the presence of subtle pathological changes within human soft tissues. This scenario, however, may not cover the effects of intrinsic, e.g., aging-related, (physiological) neurodegeneration of normal brain tissue. The aim of the work was to study the repeatability of radiomic features extracted from an apparently normal area in longitudinally acquired T1-weighted MR brain images using three different intensity normalization approaches typically used in radiomics: Z-score, WhiteStripe and Nyul. METHODS: Fifty-nine images of hearing impaired, yet cognitively intact, patients were repeatedly acquired in two different time points within six months. Ninety-one radiomic features were obtained from an area within the pons region, considered to be a healthy brain tissue according to previous analyses and reports. The Intraclass Correlation Coefficient (ICC) and the Concordance Correlation Coefficient (CCC) in the repeatability study were used as metrics. RESULTS: Features extracted from the MRI normalized with Z-score showed results comparable in both ICC (0.90 (0.82-0.98)) and CCC (0.82 (0.69-0.95)) distribution values, in terms of median and quartiles, with those extracted from the images normalized with WhiteStripe (0.89 (0.84-0.92)) and (0.80 (0.73-0.84)), respectively. CONCLUSION: Our findings underline the importance of, providing useful guidelines for, the intensity normalization of brain MRI prior to a longitudinal radiomic analysis.

Abstract:

Radiotherapy (RT) is a cancer treatment technique that involves exposing cells to ionizing radiation, including X-rays, electrons, or protons. RT offers promise to treat cancer, however, some inherent limitations can hamper its performance. Radio-resistance, whether innate or acquired, refers to the ability of tumor cells to withstand treatment, making it a key factor in RT failure. This perspective hypothesizes that nanoscale surface topography can impact on the topology of cancer cells network under radiation, and that this understanding can possibly advance the assessment of cell radio-resistance in RT applications. An experimental plan is proposed to test this hypothesis, using cancer cells exposed to various RT forms. By examining the influence of 2D surface and 3D scaffold nanoscale architecture on cancer cells, this approach diverges from traditional methodologies, such as clonogenic assays, offering a novel viewpoint that integrates fields such as tissue engineering, artificial intelligence, and nanotechnology. The hypotheses at the base of this perspective not only may advance cancer treatment but also offers insights into the broader field of structural biology. Nanotechnology and label-free Raman phenotyping of biological samples are lenses through which scientists can possibly better elucidate the structure-function relationship in biological systems.

Abstract:

Regular activation of the heart originates from cyclic spontaneous depolarisations of sinoatrial node cells (SANCs). Variations in electrolyte levels, commonly observed in haemodialysis (HD) patients, and the autonomic nervous system (ANS) profoundly affect the SANC function. Thus we investigated the effects of hypocalcaemia and sympathetic stimulation on the SANC beating rate (BR). The β-adrenergic receptor (β-AR) signalling cascade, as described by Behar et al., was incorporated into the SANC models of Severi et al. (rabbit) and Fabbri et al. (human). Simulations were conducted across various extracellular calcium ([Ca]) (0.6-1.8 mM) and isoprenaline concentrations [ISO] (0-1000 nM) for a sufficient period of time to allow transient oscillations to equilibrate and reach a limit cycle. The β-AR cell response of the extended models was validated against new Langendorff-perfused rabbit heart experiments and literature data. The extended models revealed that decreased [Ca] necessitated an exponential-like increase in [ISO] to restore the basal BR. Specifically at 1.2 mM [Ca], the Severi and Fabbri models required 28.0 and 9.6 nM [ISO], respectively, to restore the initial BR. Further reduction in [Ca] to 0.6 mM required 170.0 and 43.6 nM [ISO] to compensate for hypocalcaemia. A sudden loss of sympathetic tone at low [Ca] resulted in a loss of automaticity within seconds. These findings suggest that hypocalcaemic bradycardia can be compensated for by an elevated sympathetic tone. The integration of the β-AR pathways led to a logarithmic BR increase and offers insights into potential pathomechanisms underlying sudden cardiac death (SCD) in HD patients. KEY POINTS: We extended the sinoatrial node cell (SANC) models of Severi et al. (rabbit) and Fabbri et al. (human) using the β-adrenergic receptor (β-AR) signalling cascade Behar et al. described. Simulations were conducted across various extracellular calcium ([Ca]) (0.6-1.8 mM) and isoprenaline concentrations [ISO] (0-1000 nM) to reflect conditions in haemodialysis (HD) patients. An exponential-like increase in [ISO] compensated for hypocalcaemia-induced bradycardia in both models, whereas interspecies differences increased the sensitivity of the extended Fabbri model towards hypocalcaemia and increased sympathetic tone. The extended models may help to further understand the pathomechanisms of several cardiovascular diseases affecting pacemaking, such as the high occurrence of sudden cardiac death (SCD) in chronic kidney disease (CKD) patients.

Abstract:

Background: Computer models for simulating cardiac electrophysiology are valuable tools for research and clinical applications. Traditional reaction-diffusion (RD) models used for these purposes are computationally expensive. While eikonal models offer a faster alternative, they are not well-suited to study cardiac arrhythmias driven by reentrant activity. The present work extends the diffusion-reaction eikonal alternant model (DREAM), incorporating conduction velocity (CV) restitution for simulating complex cardiac arrhythmias. Methods: The DREAM modifies the fast iterative method to model cyclical behavior, dynamic boundary conditions, and frequency-dependent anisotropic CV. Additionally, the model alternates with an approximated RD model, using a detailed ionic model for the reaction term and a triple-Gaussian to approximate the diffusion term. The DREAM and monodomain models were compared, simulating reentries in 2D manifolds with different resolutions. Results: The DREAM produced similar results across all resolutions, while experiments with the monodomain model failed at lower resolutions. CV restitution curves obtained using the DREAM closely approximated those produced by the monodomain simulations. Reentry in 2D slabs yielded similar results in vulnerable window and mean reentry duration for low CV in both models. In the left atrium, most inducing points identified by the DREAM were also present in the high-resolution monodomain model. DREAM's reentry simulations on meshes with an average edge length of 1600$\mu$m were 40x faster than monodomain simulations at 200$\mu$m. Conclusion: This work establishes the mathematical foundation for using the accelerated DREAM simulation method for cardiac electrophysiology. Cardiac research applications are enabled by a publicly available implementation in the openCARP simulator.

Abstract:

BACKGROUND: Longitudinal Displacement (LD) is the relative motion of the intima-media upon adventitia of the arterial wall during the cardiac cycle, probably linked to atherosclerosis. It has a direction, physiologically first backward in its main components with respect to the arterial flow. Here, LD was investigated in various disease and in presence of a unilateral carotid stent. METHODS: Carotid acquisitions were performed by ultrasound imaging on both body sides of 75 participants (150 Arteries). LD was measured in its percent quantity and direction. RESULTS: Obesity (p = 0.001) and carotid plaques (p = 0.01) were independently associated to quantity decrease of LD in the whole population. In a subgroup analysis, it was respectively 143% in healthy (n = 48 carotids), 129% (n = 34) in presence of cardiovascular risk factors, 121% (n = 20) in MACE patients, 119% (n = 24) in the carotid contralateral to a stent, 110% (n = 24) in carotids with stents. Regarding the direction of LD, in a subgroup analysis an inverted movement was identified in aged (p = 0.001) and diseased (p = 0.001) participants who also showed less quantity of LD (p = 0.001), but independently with age only (p = 0.002) in the whole population. CONCLUSIONS: This observational study suggests that LD within carotid wall layers is lower additively with ageing, cardiovascular risk factors, cardiovascular diseases, and stent. Even if stent is surely beneficial, these data might shed some light on stent restenosis, emphasising the need for interventional studies.

Abstract:

In recent years, synthetic Computed Tomography (CT) images generated from Magnetic Resonance (MR) or Cone Beam Computed Tomography (CBCT) acquisitions have been shown to be comparable to real CT images in terms of dose computation for radiotherapy simulation. However, until now, there has been no independent strategy to assess the quality of each synthetic image in the absence of ground truth. In this work, we propose a Deep Learning (DL)-based framework to predict the accuracy of synthetic CT in terms of Mean Absolute Error (MAE) without the need for a ground truth (GT). The proposed algorithm generates a volumetric map as an output, informing clinicians of the predicted MAE slice-by-slice. A cascading multi-model architecture was used to deal with the complexity of the MAE prediction task. The workflow was trained and tested on two cohorts of head and neck cancer patients with different imaging modalities: 27 MR scans and 33 CBCT. The algorithm evaluation revealed an accurate HU prediction (a median absolute prediction deviation equal to 4 HU for CBCT-based synthetic CTs and 6 HU for MR-based synthetic CTs), with discrepancies that do not affect the clinical decisions made on the basis of the proposed estimation. The workflow exhibited no systematic error in MAE prediction. This work represents a proof of concept about the feasibility of synthetic CT evaluation in daily clinical practice, and it paves the way for future patient-specific quality assessment strategies.

Abstract:

Limited medical image data hinders the training of deep learning (DL) models in the biomedical field. Image augmentation can reduce the data-scarcity problem by generating variations of existing images. However, currently implemented methods require coding, excluding non-programmer users from this opportunity.We therefore present ImageAugmenter, an easy-to-use and open-source module for 3D Slicer imaging computing platform. It offers a simple and intuitive interface for applying over 20 simultaneous MONAI Transforms (spatial, intensity, etc.) to medical image datasets, all without programming.ImageAugmenter makes accessible medical image augmentation, enabling a wider range of users to improve the performance of DL models in medical image analysis by increasing the number of samples available for training.

Abstract:

Monocular depth estimation is an important topic in minimally invasive surgery, providing valuable information for downstream application, like navigation systems. Deep learning for this task requires high amount of training data for an accurate and robust model. Especially in the medical field acquiring ground truth depth information is rarely possible due to patient security and technical limitations. This problem is being tackled by many approaches including the use of syn- thetic data. This leads to the question, how well does the syn- thetic data allow the prediction of depth information on clini- cal data. To evaluate this, the synthetic data is used to train and optimize a U-Net, including hyperparameter tuning and aug- mentation. The trained model is then used to predict the depth on clinical image and analyzed in quality, consistency over the same scene, time and color. The results demonstrate that syn- thetic data sets can be used for training, with an accuracy of over 77% and a RMSE below 10 mm on the synthetic data set, do well on resembling clinical data, but also have limitations due to the complexity of clinical environments. Synthetic data sets are a promising approach allowing monocular depth esti- mation in fields with otherwise lacking data.

Abstract:

Efficient personalized ablation strategies for treating atrial arrhythmias remain challenging. Discrepancies in identifying arrhythmogenic areas using characterization methods, such as late gadolinium enhanced magnetic resonance imaging (LGE-MRI) and electroanatomical mapping, require a comparative analysis of local impedance (LI) and LGE-MRI data. This study aims to analyze correlations as basis for im- provement of treatment strategies. 16 patients undergoing left atrium (LA) ablation with LGE-MRI acquisition and LI data recording were recruited. LGE-MRI data and LI measurements were normalized to patient- and modality-specific blood pool references. A global mean shape was generated based on all patient geometries, and normalized local impedance (LIN) and LGE-MRI image intensity ratio (IIR) data points were co- registered for comparison.Data analysis comprised intra-patient and inter-patient assess- ments, evaluating differences in LIN values among datasets categorized by their IIR. Due to substantial deviations in LIN values, even within the same patient and IIR-category, discern- ing the presence or absence of a correlation was challenging, and no statistically significant correlation could be identified. Our findings underscore the necessity for standardized proto- cols in data acquisition, processing, and comparison, to mini- mize unquantified confounding effects. While immediate substitution of LI for LGE-MRI seems improbable given the significant LIN variations, this preliminary study lays the ground- work for systematic data acquisition. By ensuring data quality, a meaningful comparison between LI and LGE-MRI data can be facilitated, potentially shaping future strategies for atrial ar- rhythmia treatment.

Abstract:

In laparoscopic liver surgery, image-guided navigation systems provide crucial support to surgeons by supply- ing information about tumor and vessel positions. For this purpose, these information from a preoperative CT or MRI scan is overlaid onto the laparoscopic video. One option is performing a registration of preoperative 3D data and 3D reconstructed laparoscopic data. A robust registration is challenging due to factors like limited field of view, liver deformations, and 3D reconstruction errors. Since in reality various influencing factors always intertwine, it is crucial to analyze their combined effects. This paper assesses registration accuracy under various synthetically simulated influences: patch size, spatial dis- placement, Gaussian deformations, holes, and downsampling. The objective is to provide insights into the required quality of the intraoperative 3D surface patches. LiverMatch serves as the feature descriptor, and registration employs the RANSAC algorithm. The results of this paper show that ensuring a large field of view of at least 15-20% of the liver surface is necessary, allowing tolerance for less accurate depth estimation.

Abstract:

The lack of labeled, intraoperative patient data in medical scenarios poses a relevant challenge for machine learning applications. Given the apparent power of machine learning, this study examines how synthetically-generated data can help to reduce the amount of clinical data needed for robust liver surface segmentation in laparoscopic images. Here, we report the results of three experiments, using 525 annotated clinical images from 5 patients alongside 20,000 synthetic photo-realistic images from 10 patient models. The effectiveness of the use of synthetic data is compared to the use of data augmentation, a traditional performance-enhancing technique. For training, a supervised approach employing the U-Net architecture was chosen. The results of these experiments show a progressive increase in accuracy. Our base experiment on clinical data yielded an F1 score of 0.72. Applying data augmentation to this model increased the F1 score to 0.76. Our model pre-trained on synthetic data and fine-tuned with augmented data achieved an F1 score of 0.80, a 4% increase. Additionally, a model evaluation involving k-fold cross validation highlighted the dependency of the result on the test set. These results demonstrate that leveraging synthetic data has the ability of limiting the need for more patient data to increase the segmentation performance.

Abstract:

We investigate the force-frequency relationship (FFR) representation of human ventricular cardiomyocyte models and point out shortcomings, motivated by discrepancies in whole-heart simulations at increased pacing rates. Utilizing the openCARP simulator, simulations across frequencies ranging from 1 Hz to 3 Hz were conducted. Experimental data on healthy human ventricular cardiomyocytes were collected and compared against simulated results. Results show deviations for all models, with Tomek et al. modeling time sensitive biomarkers the best. For example, the ratio of time to peak tension at 2 Hz and 1 Hz is around 85% for experiments, 82% for hybrid data, 95% for Tomek et al., 98% for O’Hara et al. and 138% for ten Tusscher et al. These discrepancies, highlight not only the need for careful selection of ionic models, but also the importance of refining ventricular cardiomyocyte models for advancing in-silico cardiac research.

Abstract:

Background: Extraction of mandibular third molars (M3Ms) is a routine procedure in oral and maxillofacial surgery, often associated with postoperative symptoms like pain, facial swelling, and trismus. This study aimed to introduce a standardized and automated protocol for swelling analysis following M3M surgery, presenting results regarding clinical conditions immediately and one-week after surgery.Methods: In a prospective study, 35 patients were enrolled (mean age: 24.4 ± 5.8 years) for removal of 54 M3Ms. Facial swelling was evaluated through 3D facial scans before surgery (T0), at three days (T1), and seven days (T2) post-surgery. The open-source software 3DSlicer facilitated automated analysis, including data anonymization, orientation, surface registration, qualitative comparisons, linear measurements, and volumetric quantification. Pairwise superimposition of facial models enabled qualitative, vectorial, and quantitative assessments, comparing initial conditions with swelling development at T1 and T2. Additionally, changes between T1 and T2 were also evaluated. Secondary outcomes encompassed clinical evaluations of pain, trismus (maximum mouth opening), and surgery time. Statistical analysis involved the paired Student t-test to assess longitudinal changes and analysis of variance to evaluate outcome variables concerning difficulty scores. Linear regression models correlated primary outcome variables with secondary study variables (α < 0.05).Results: Longitudinal analysis demonstrated significant but variable facial swelling, pain, and trismus at T1, followed by improvement at T2 (p < 0.001). Linear and volumetric differences correlated positively with surgery time (p < 0.05). A direct proportionality between linear and volume differences was observed, higher values at T1 correlated with higher values at T2 (p < 0.05).Conclusions: An innovative digital workflow for precise quantification of postoperative facial changes was implemented, incorporating volumetric measurements that surpass linear assessments. Clinical conditions demonstrated a direct correlation with surgery time, deteriorating immediately and improving one-week after surgery.

Abstract:

AIMS: The effective refractory period (ERP) is one of the main electrophysiological properties governing arrhythmia, yet ERP personalization is rarely performed when creating patient-specific computer models of the atria to inform clinical decision-making. This study evaluates the impact of integrating clinical ERP measurements into personalized in silico models on arrhythmia vulnerability. METHODS AND RESULTS: Clinical ERP measurements were obtained in seven patients from multiple locations in the atria. Atrial geometries from the electroanatomical mapping system were used to generate personalized anatomical atrial models. The Courtemanche M. et al. cellular model was adjusted to reproduce patient-specific ERP. Four modeling approaches were compared: homogeneous (A), heterogeneous (B), regional (C), and continuous (D) ERP distributions. Non-personalized approaches (A and B) were based on literature data, while personalized approaches (C and D) were based on patient measurements. Modeling effects were assessed on arrhythmia vulnerability and tachycardia cycle length, with sensitivity analysis on ERP measurement uncertainty. Mean vulnerability was 3.4 ± 4.0%, 7.7 ± 3.4%, 9.0 ± 5.1%, and 7.0 ± 3.6% for scenarios A-D, respectively. Mean tachycardia cycle length was 167.1 ± 12.6 ms, 158.4 ± 27.5 ms, 265.2 ± 39.9 ms, and 285.9 ± 77.3 ms for scenarios A-D, respectively. Incorporating perturbations to the measured ERP in the range of 2, 5, 10, 20, and 50 ms changed the vulnerability of the model to 5.8 ± 2.7%, 6.1 ± 3.5%, 6.9 ± 3.7%, 5.2 ± 3.5%, and 9.7 ± 10.0%, respectively. CONCLUSION: Increased ERP dispersion had a greater effect on re-entry dynamics than on vulnerability. Inducibility was higher in personalized scenarios compared with scenarios with uniformly reduced ERP; however, this effect was reversed when incorporating fibrosis informed by low-voltage areas. Effective refractory period measurement uncertainty up to 20 ms slightly influenced vulnerability. Electrophysiological personalization of atrial in silico models appears essential and requires confirmation in larger cohorts.

Abstract:

The human heart is subject to highly variable amounts of strain during day-to-day activities and needs to adapt to a wide range of physiological demands. This adaptation is driven by an autoregulatory loop that includes both electrical and the mechanical components. In particular, mechanical forces are known to feed back into the cardiac electrophysiology system, which can result in pro- and anti-arrhythmic effects. Despite the widespread use of computational modelling and simulation for cardiac electrophysiology research, the majority of in silico experiments ignore this mechano-electric feedback entirely due to the high computational cost associated with solving cardiac mechanics. In this study, we therefore use an electromechanically coupled whole-heart model to investigate the differential and combined effects of electromechanical feedback mechanisms with a focus on their physiological relevance during sinus rhythm. In particular, we consider troponin-bound calcium, the effect of deformation on the tissue diffusion tensor, and stretch-activated channels. We found that activation of the myocardium was only significantly affected when including deformation into the diffusion term of the monodomain equation. Repolarization, on the other hand, was influenced by both troponin-bound calcium and stretch-activated channels and resulted in steeper repolarization gradients in the atria. The latter also caused afterdepolarizations in the atria. Due to its central role for tension development, calcium bound to troponin affected stroke volume and pressure. In conclusion, we found that mechano-electric feedback changes activation and repolarization patterns throughout the heart during sinus rhythm and lead to a markedly more heterogeneous electrophysiological substrate. KEY POINTS: The electrophysiological and mechanical function of the heart are tightly interrelated by excitation-contraction coupling (ECC) in the forward direction and mechano-electric feedback (MEF) in the reverse direction. While ECC is considered in many state-of-the-art computational models of cardiac electromechanics, less is known about the effect of different MEF mechanisms. Accounting for calcium bound to troponin increases stroke volume and delays repolarization. Geometry-mediated MEF leads to more heterogeneous activation and repolarization with steeper gradients. Both effects combine in an additive way. Non-selective stretch-activated channels as an additional MEF mechanism lead to heterogeneous diastolic transmembrane voltage, higher developed tension and delayed repolarization or afterdepolarizations in highly stretched parts of the atria. The differential and combined effects of these three MEF mechanisms during sinus rhythm activation in a human four-chamber heart model may have implications for arrhythmogenesis, both in terms of substrate (repolarization gradients) and triggers (ectopy).

Abstract:

Objective. 3D-localization of gamma sources has the potential to improve the outcome of radio-guided surgery. The goal of this paper is to analyze the localization accuracy for point-like sources with a single coded aperture camera. Approach. We both simulated and measured a point-like 241Am source at 17 positions distributed within the field of view of an experimental gamma camera. The setup includes a 0.11mm thick Tungsten sheet with a MURA mask of rank 31 and pinholes of 0.08 mm in diameter and a detector based on the photon counting readout circuit Timepix3. Two methods, namely an iterative search including either a symmetric Gaussian fitting or an exponentially modified Gaussian fitting (EMG) and a center of mass method were compared to estimate the 3D source position. Main results. Considering the decreasing axial resolution with source-to-mask distance, the EMG improved the results by a factor of 4 compared to the Gaussian fitting based on the simulated data. Overall, we obtained a mean localization error of 0.77 mm on the simulated and 2.64 mm on the experimental data in the imaging range of 20−100 mm. Significance. This paper shows that despite the low axial resolution, point-like sources in the nearfield can be localized as well as with more sophisticated imaging devices such as stereo cameras. The influence of the source size and the photon count on the imaging and localization accuracy remains an important issue for further research.

Abstract:

Background and Aims Patients with persistent atrial fibrillation (AF) experience 50% recurrence despite pulmonary vein isolation (PVI), and no consensus is established for second treatments. The aim of our i-STRATIFICATION study is to provide evidence for stratifying patients with AF recurrence after PVI to optimal pharmacological and ablation therapies, through in-silico trials.Methods A cohort of 800 virtual patients, with variability in atrial anatomy, electrophysiology, and tissue structure (low voltage areas, LVA), was developed and validated against clinical data from ionic currents to ECG. Virtual patients presenting AF post-PVI underwent 13 secondary treatments.Results Sustained AF developed in 522 virtual patients after PVI. Second ablation procedures involving left atrial ablation alone showed 55% efficacy, only succeeding in small right atria (<60mL). When additional cavo-tricuspid isthmus ablation was considered, Marshall-Plan sufficed (66% efficacy) for small left atria (<90mL). For bigger left atria, a more aggressive ablation approach was required, such as anterior mitral line (75% efficacy) or posterior wall isolation plus mitral isthmus ablation (77% efficacy). Virtual patients with LVA greatly benefited from LVA ablation in the left and right atria (100% efficacy). Conversely, in the absence of LVA, synergistic ablation and pharmacotherapy could terminate AF. In the absence of ablation, the patient’s ionic current substrate modulated the response to antiarrhythmic drugs, being the inward currents critical for optimal stratification to amiodarone or vernakalant.Conclusion In-silico trials identify optimal strategies for AF treatment based on virtual patient characteristics, evidencing the power of human modelling and simulation as a clinical assisting tool.

Abstract:

Simulation models and artificial intelligence (AI) are largely used to address healthcare and biomedical engineering problems. Both approaches showed promising results in the analysis and optimization of healthcare processes. Therefore, the combination of simulation models and AI could provide a strategy to further boost the quality of health services. In this work, a systematic review of studies applying a hybrid simulation models and AI approach to address healthcare management challenges was carried out. Scopus, Web of Science, and PubMed databases were screened by independent reviewers. The main strategies to combine simulation and AI as well as the major healthcare application scenarios were identified and discussed. Moreover, tools and algorithms to implement the proposed approaches were described. Results showed that machine learning appears to be the most employed AI strategy in combination with simulation models, which mainly rely on agent-based and discrete-event systems. The scarcity and heterogeneity of the included studies suggested that a standardized framework to implement hybrid machine learning-simulation approaches in healthcare management is yet to be defined. Future efforts should aim to use these approaches to design novel intelligent in-silico models of healthcare processes and to provide effective translation to the clinics.

Abstract:

Purpose: Handheld gamma cameras with coded aperture collimators are under inves- tigation for intraoperative imaging in nuclear medicine. Coded apertures are a promis- ing collimation technique for applications such as lymph node localization due to their high sensitivity and the possibility of 3D imaging. We evaluated the axial resolutionand computational performance of two reconstruction methods.Methods: An experimental gamma camera was set up consisting of the pixelated semiconductor detector Timepix3 and MURA mask of rank 31 with round holesof 0.08 mm in diameter in a 0.11 mm thick Tungsten sheet. A set of measurements was taken where a point-like gamma source was placed centrally at 21 different positions within the range of 12–100 mm. For each source position, the detector image was reconstructed in 0.5 mm steps around the true source position, resulting in an image stack. The axial resolution was assessed by the full width at half maximum (FWHM) of the contrast-to-noise ratio (CNR) profile along the z-axis of the stack. Two reconstruction methods were compared: MURA Decoding and a 3D maximum likeli- hood expectation maximization algorithm (3D-MLEM).Results: While taking 4400 times longer in computation, 3D-MLEM yielded a smaller axial FWHM and a higher CNR. The axial resolution degraded from 5.3 mm and 1.8 mm at 12 mm to 42.2 mm and 13.5 mm at 100 mm for MURA Decoding and 3D-MLEM respectively.Conclusion: Our results show that the coded aperture enables the depth estimation of single point-like sources in the near field. Here, 3D-MLEM offered a better axial reso- lution but was computationally much slower than MURA Decoding, whose reconstruc- tion time is compatible with real-time imaging.

Abstract:

Background: The global coronavirus disease 2019 (COVID-19) pandemic has posed substantial challenges for healthcare systems, notably the increased demand for chest computed tomography (CT) scans, which lack automated analysis. Our study addresses this by utilizing artificial intelligence-supported automated computer analysis to investigate lung involvement distribution and extent in COVID-19 patients. Additionally, we explore the association between lung involvement and intensive care unit (ICU) admission, while also comparing computer analysis performance with expert radiologists’ assessments.Methods: A total of 81 patients from an open-source COVID database with confirmed COVID-19 infection were included in the study. Three patients were excluded. Lung involvement was assessed in 78 patients using CT scans, and the extent of infiltration and collapse was quantified across various lung lobes and regions. The associations between lung involvement and ICU admission were analysed. Additionally, the computer analysis of COVID-19 involvement was compared against a human rating provided by radiological experts.Results: The results showed a higher degree of infiltration and collapse in the lower lobes compared to the upper lobes (P<0.05). No significant difference was detected in the COVID-19-related involvement of the left and right lower lobes. The right middle lobe demonstrated lower involvement compared to the right lower lobes (P<0.05). When examining the regions, significantly more COVID-19 involvement was found when comparing the posterior vs. the anterior halves and the lower vs. the upper half of the lungs. Patients, who required ICU admission during their treatment exhibited significantly higher COVID-19 involvement in their lung parenchyma according to computer analysis, compared to patients who remained in general wards. Patients with more than 40% COVID-19 involvement were almost exclusively treated in intensive care. A high correlation was observed between computer detection of COVID-19 affections and the rating by radiological experts.Conclusions: The findings suggest that the extent of lung involvement, particularly in the lower lobes, dorsal lungs, and lower half of the lungs, may be associated with the need for ICU admission in patients with COVID-19. Computer analysis showed a high correlation with expert rating, highlighting its potential utility in clinical settings for assessing lung involvement. This information may help guide clinical decision-making and resource allocation during ongoing or future pandemics. Further studies with larger sample sizes are warranted to validate these findings.

Abstract:

Feature importance methods promise to provide a ranking of features according to importance for a given classification task. A wide range of methods exist but their rankings often disagree and they are inherently difficult to evaluate due to a lack of ground truth beyond synthetic datasets. In this work, we put feature importance methods to the test on real-world data in the domain of cardiology, where we try to distinguish three specific pathologies from healthy subjects based on ECG features comparing to features used in cardiologists' decision rules as ground truth. We found that the SHAP and LIME methods and Chi-squared test all worked well together with the native Random forest and Logistic regression feature rankings. Some methods gave inconsistent results, which included the Maximum Relevance Minimum Redundancy and Neighbourhood Component Analysis methods. The permutation-based methods generally performed quite poorly. A surprising result was found in the case of left bundle branch block, where T-wave morphology features were consistently identified as being important for diagnosis, but are not used by clinicians.

Abstract:

We investigate the properties of static mechanical and dynamic electro-mechanical models for the deformation of the human heart. Numerically this is realized by a staggered scheme for the coupled partial/ordinary differential equation (PDE-ODE) system. First, we consider a static and purely mechanical benchmark configuration on a realistic geometry of the human ventricles. Using a penalty term for quasi-incompressibility, we test different parameters and mesh sizes and observe that this approach is not sufficient for lowest order conforming finite elements. Then, we compare the approaches of active stress and active strain for cardiac muscle contraction. Finally, we compare in a coupled anatomically realistic electro-mechanical model numerical Newmark damping with a visco-elastic model using Rayleigh damping. Nonphysiological oscillations can be better mitigated using viscosity.

Abstract:

ntercellular heterogeneity is fundamental to most biological tissues. For some cell types, heterogeneity is thought to be responsible for distinct cellular phenotypes and functional roles. In the pancreatic islet, subsets of phenotypically distinct beta cells (hub and leader cells) are thought to coordinate electrical activity of the beta cell network. This hypothesis has been addressed by experimental and computational approaches, but none have attempted to reconstruct functional specialization directly from measured heterogeneity. To evaluate if electrophysiologic heterogeneity alone can explain these specialized functional roles, we created a population of human beta cell models (via genetic algorithm optimization) recapitulating the heterogeneity in an extensive patch clamp dataset (1021 pancreatic cells). Then we applied the simplified Kirchhoff network (SKNM) formalism to simulate activity of that population in a connected beta cell network. We could not immediately observe cells with obvious hub or leader phenotypes within the heterogeneous network. However, with this study we built the basis for further ''ground-up'' investigation of relationships between beta cell heterogeneity and human islet function. Moreover, our workflow may be translated to other tissues where large electrophysiologic data sets become available, and heterogeneity is thought to influence tissue function e.g. human atria.