Abstract:

Large-scale electrophysiological simulations to obtain electrocardiograms (ECG) carry the potential to produce extensive datasets for training of machine learning classifiers to, e.g., discriminate between different cardiac pathologies. The adoption of simulations for these purposes is limited due to a lack of ready-to-use models covering atrial anatomical variability. We built a bi-atrial statistical shape model (SSM) of the endocardial wall based on 47 segmented human CT and MRI datasets using Gaussian process morphable models. Generalization, specificity, and compactness metrics were evaluated. The SSM was applied to simulate atrial ECGs in 100 random volumetric instances. The first eigenmode of our SSM reflects a change of the total volume of both atria, the second the asymmetry between left vs. right atrial volume, the third a change in the prominence of the atrial appendages. The SSM is capable of generalizing well to unseen geometries and 95% of the total shape variance is covered by its first 23 eigenvectors. The P waves in the 12-lead ECG of 100 random instances showed a duration of 104ms in accordance with large cohort studies. The novel bi-atrial SSM itself as well as 100 exemplary instances with rule-based augmentation of atrial wall thickness, fiber orientation, inter-atrial bridges and tags for anatomical structures have been made publicly available. The novel, openly available bi-atrial SSM can in future be employed to generate large sets of realistic atrial geometries as a basis for in silico big data approaches.

Abstract:

Ventricular coordinates are widely used as a versatile tool for various applications that benefit from a description of local position within the heart. However, the practical usefulness of ventricular coordinates is determined by their ability to meet application-specific requirements. For regression-based estimation of biventricular position, for example, a consistent definition of coordinate directions in both ventricles is important. For the transfer of data between different hearts as another use case, the coordinate values are required to be consistent across different geometries. Existing ventricular coordinate systems do not meet these requirements. We first compare different approaches to compute coordinates and then present Cobiveco, a consistent and intuitive biventricular coordinate system to overcome these drawbacks. A novel one-way mapping error is introduced to assess the consistency of the coordinates. Evaluation of mapping and linearity errors on 36 patient geometries showed a more than 4-fold improvement compared to a state-of-the-art method. Finally, we show two application examples underlining the relevance for cardiac data processing. Cobiveco MATLAB code is available under a permissive open-source license.

Abstract:

OBJECTIVE: Atrial flutter (AFl) is a common arrhythmia that can be categorized according to different self-sustained electrophysiological mechanisms. The non-invasive discrimination of such mechanisms would greatly benefit ablative methods for AFl therapy as the driving mechanisms would be described prior to the invasive procedure, helping to guide ablation. In the present work, we sought to implement recurrence quantification analysis (RQA) on 12-lead ECG signals from a computational framework to discriminate different electrophysiological mechanisms sustaining AFl. METHODS: 20 different AFl mechanisms were generated in 8 atrial models and were propagated into 8 torso models via forward solution, resulting in 1,256 sets of 12-lead ECG signals. Principal component analysis was applied on the 12-lead ECGs, and six RQA-based features were extracted from the most significant principal component scores in two different approaches: individual component RQA and spatial reduced RQA. RESULTS: In both approaches, RQA-based features were significantly sensitive to the dynamic structures underlying different AFl mechanisms. Hit rate as high as 67.7% was achieved when discriminating the 20 AFl mechanisms. RQA-based features estimated for a clinical sample suggested high agreement with the results found in the computational framework. CONCLUSION: RQA has been shown an effective method to distinguish different AFl electrophysiological mechanisms in a non-invasive computational framework. A clinical 12-lead ECG used as proof of concept showed the value of both the simulations and the methods. SIGNIFICANCE: The non-invasive discrimination of AFl mechanisms helps to delineate the ablation strategy, reducing time and resources required to conduct invasive cardiac mapping and ablation procedures.

Abstract:

Acute ischemic stroke is a major health problem with a high mortality rate and a high risk for permanent disabilities. Selective brain hypothermia has the neuroprotective potential to possibly lower cerebral harm. A recently developed catheter system enables to combine endovascular blood cooling and thrombectomy using the same endovascular access. By using the penumbral perfusion via leptomeningeal collaterals, the catheter aims at enabling a cold reperfusion, which mitigates the risk of a reperfusion injury. However, cerebral circulation is highly patient-specific and can vary greatly. Since direct measurement of remaining perfusion and temperature decrease induced by the catheter is not possible without additional harm to the patient, computational modeling provides an alternative to gain knowledge about resulting cerebral temperature decrease. In this work, we present a brain temperature model with a realistic division into gray and white matter and consideration of spatially resolved perfusion. Furthermore, it includes detailed anatomy of cerebral circulation with possibility of personalizing on base of real patient anatomy. For evaluation of catheter performance in terms of cold reperfusion and to analyze its general performance, we calculated the decrease in brain temperature in case of a large vessel occlusion in the middle cerebral artery (MCA) for different scenarios of cerebral arterial anatomy. Congenital arterial variations in the circle of Willis had a distinct influence on the cooling effect and the resulting spatial temperature distribution before vessel recanalization. Independent of the branching configurations, the model predicted a cold reperfusion due to a strong temperature decrease after recanalization (1.4-2.2  C after 25 min of cooling, recanalization after 20 min of cooling). Our model illustrates the effectiveness of endovascular cooling in combination with mechanical thrombectomy and its results serve as an adequate substitute for temperature measurement in a clinical setting in the absence of direct intraparenchymal temperature probes.

Abstract:

Electrical impedance tomography is clinically used to trace ventilation related changes in electrical conductivity of lung tissue. Estimating regional pulmonary perfusion using electrical impedance tomography is still a matter of research. To support clinical decision making, reliable bedside information of pulmonary perfusion is needed. We introduce a method to robustly detect pulmonary perfusion based on indicator-enhanced electrical impedance tomography and validate it by dynamic multidetector computed tomography in two experimental models of acute respiratory distress syndrome. The acute injury was induced in a sublobar segment of the right lung by saline lavage or endotoxin instillation in eight anesthetized mechanically ventilated pigs. For electrical impedance tomography measurements, a conductive bolus (10% saline solution) was injected into the right ventricle during breath hold. Electrical impedance tomography perfusion images were reconstructed by linear and normalized Gauss-Newton reconstruction on a finite element mesh with subsequent element-wise signal and feature analysis. An iodinated contrast agent was used to compute pulmonary blood flow via dynamic multidetector computed tomography. Spatial perfusion was estimated based on first-pass indicator dilution for both electrical impedance and multidetector computed tomography and compared by Pearson correlation and Bland-Altman analysis. Strong correlation was found in dorsoventral (r = 0.92) and in right-to-left directions (r = 0.85) with good limits of agreement of 8.74% in eight lung segments. With a robust electrical impedance tomography perfusion estimation method, we found strong agreement between multidetector computed and electrical impedance tomography perfusion in healthy and regionally injured lungs and demonstrated feasibility of electrical impedance tomography perfusion imaging.

Abstract:

In many patients suffering from severely impaired gas exchange of the lungs, regional pulmonary ventilation and perfusion are not aligned. Especially, if patients are suffering from the acute respiratory distress syndrome, very heterogeneous distributions of ventilation and perfusion are observed, and patients need to be artificially ventilated and monitored in an intensive care unit, in order to ensure sufficient gas exchange. In severely injured lungs, it is very challenging to find an optimal trade off between recruiting collapsed regions by applying high pressures and volumes, while protecting the lung from further damage caused by the externally applied pressure. In order to ensure lung protective ventilation and to optimize and to support clinical decision making, a growing need for bedside monitoring of regional lung ventilation, as well as regional perfusion, has been reported. Electrical Impedance Tomography (EIT) is a non-invasive, radiation-free and portable system, which has raised interest especially among physicians treating critically ill patients in ICUs. It provides high temporal sampling and a functional spatial resolution, which allows to visualize and monitor dynamic (patho-) physiological processes. Medical EIT research has mainly focused on estimating spatial ventilation distributions, and commercially available systems have proven that EIT is a valuable extension for clinical decision making during mechanical ventilation. Estimating pulmonary perfusion with EIT nevertheless has not been established yet and might represent the missing link to enable the analysis of pulmonary gas exchange at the bedside. Though some publications have shown the principle feasibility of indicator-enhanced EIT to estimate spatial distributions of pulmonary blood flow, the methods need to be optimized and validated against gold-standards of pulmonary perfusion monitoring. Additionally, further research is needed to understand the underlying physiological information of EIT perfusion estimations. With this thesis, we aim to contribute to the question, whether EIT can be applied clinically to provide spatial information of pulmonary blood flow alongside regional ventilation to potentially assess pulmonary gas exchange at the bedside. Spatial distributions of perfusion were estimated by injecting a conductive saline indicator bolus, to trace the passage of the indicator during its progression through the vascular system of the lungs. We developed and compared different dynamic EIT reconstruction methods as well as perfusion parameter estimations, to be able to robustly assess pulmonary blood flow. The estimated regional EIT perfusion distributions were validated against gold-standard lung perfusion measurement techniques. A first validation has been conducted using data of an experimental animal study, where multidetector Computed Tomography was used as comparative lung perfusionmeasure. On top, a comprehensive preclinical animal study has been conducted to investigate pulmonary perfusion with indicator-enhanced EIT and Positron Emission Tomography during multiple different experimental states. Besides a thorough method comparison, we aimed to investigate the clinical applicability of the indicator-enhanced EIT perfusion measurement by above all analyzing the minimal indicator concentration, which allows robust perfusion estimations and presents no harm to the patient. Besides the experimental validation studies, we conducted two in-silico investigations to firstly evaluate the sensitivity of EIT to the passage of a conductive indicator through the lungs in front of severely heterogeneous pulmonary backgrounds. Secondly, we studied the physiological contributors to the reconstructed EIT perfusion image to find basic limitations of the method. We concluded, that pulmonary perfusion estimation based on indicator-enhanced EIT shows great potential to be applied in clinical practice, since we were able to validate it against two established perfusion measurement techniques and provided valuable information about the physiological contributors to the estimated EIT perfusion distributions.

Abstract:

Classic otoscopes are modern diagnostic instruments that allow users to examine and evaluate human or animal ears, including their tympanic membranes. In the last years and along with new technologies like the development of the laser after 1960, traditional otoscopes were further improved by the introduction of and combination with other optical systems and technologies. One advance in otoscope technology also involved the introduction/functional integration of optical alignments and system components that were initially used in (surgical) endoscopes, and which gave rise to new devices called “otoendoscopes” or (sometimes) “telescope otoendoscopes” (Olympus America, 2012) – a de- vice classification that fuses and unites classic otoscopes with systematic concepts of endoscopic systems. Those otoscope setups offer distinct advantages compared to tra- ditional otoscopes, like a larger Field of View (FOV) and Depth of Field (DOF), tailored (variable) optical magnifications, refocus abilities for an extended focus/object distance range in front of the otoscope (by simple axial shifts of system components like the ocular), or an additional exit pupil stability (i.e., improved lateral tolerances in case of human eye/head movements). This master’s thesis aims to pick up an older, already drafted HEINE visual otoen- doscope design and carry out a feasibility study regarding the realizability of a hybrid otoendoscope: A device which features not only the “classic” visual system part (to be used by the examiner’s eye) and merges in components from endoscopic system concepts, but additionally contains a second, digital beam path for a simultaneously camera-based examination. Based on the already existing (visual-only) otoendoscope design, such a hybridized system offers further possibilities to create, share and archive image data in parallel to the common, visual in-ear examination and generates additional data for, e.g., digital patient recordings during a regular examination scenario. At the end, the thesis’ development project outlines possible design limitations, conceptual tradeoffs, and provides answers to three hypothetic questions: 1. Is the system design to be realized with a simple (optical) fix-focus design approach? 2. Does the system solution appropriately yield the desired simultaneous and synchro- nized observation of the same in-ear plane by the eye and the camera chip? 3. Are exactly all given/applied (optical) design requirements fulfilled and covered by both beam paths simultaneously? To approach the realization of this new and unique hybrid otoendoscope concept, dif- ferent previously unknown design requirements (prospective benchmarks) for the new prototype’s FOV diameter, its resolution and its DOF capabilities are first derived and set according to analyzed reference data of comparable, already existing commercial oto- and otoendoscope solutions. The thesis project then continues with the modification of HEINE’s existing visual otoendoscope layout and the optics design of the new hybridized otoendoscope system, such that, at the project’s end, the assembled prototype can finally be tested, evaluated and validated via the defined (contrast) evaluation methods and with respect to the settled design specifications. The design requirement determination founds on different image characterization methods (pixel data evaluation and histogram/edge contrast criteria) which are accord- ingly developed and introduced to characterize the commercial reference devices with respect to their imaging performance of defined spatial structures in front of the otoscope tips. The FOV size determination is done via a pixel-based evaluation of the image (area) with reference to the overall image size and a given spatial frequency component on the test chart. The contrast criteria, relevant for the benchmarking of the devices’ resolution and DOF performances, found on the assessment of spatially aligned, rectangular struc- tures on a USAF 1951 resolution test chart whose average pixel (area) gray scale values (histogram contrast criterion) or gray scale line profiles of the edges between two adjacent rectangles (edge contrast criterion) yield the respective contrast characteristics. As for the project results, the eventually optimized and assembled system solution could not be realized via a fix-focus design approach since the performance requirements could, during the optical system simulation, not be fulfilled for the given otoendoscope design concept. Instead, a suitable system solution was found via a fixed intermediate image (plane) position buried inside the system, and whose information content changes, depending on the axial shifts (axial positioning) of the otoendoscope’s relay group, thus forwarding the addressed object plane information to the static intermediate image plane. This intermediate image plane is optically accessed by both beam paths, such that a synchronized observation of the same object plane is guaranteed and the hybrid otoendoscope’s functionality is realized. However, the characterization results show that, although the “beam path synchronization” (device hybridization) was achieved, the prototype’s performance only satisfies one of three optic design requirements (the FOV requirement), while the required resolution performances and DOF depths could not entirely be fulfilled. Those device benchmarks result, additionally supported by simulated opto-mechanical tolerances of the designed camera objective, primarily from given (project-related) design and manufacturing constraints, such that, e.g., for the digital beam path, more than 80 % of the 100 simulated, randomly manufactured and assembled optical alignments (Monte Carlo systems) did not yield sufficient resolution and DOF outcomes. Nonetheless, the basic device functionality proved to be feasible/realizable, and was, in principle, implemented, such that – for the project outlook – the hybrid otoendoscope prototype concept needs to be refined via the adjustment of the underlying (optics) design parameters and requirements. Additionally, prospective researchers will also have to address, contact and question the actual users directly to clarify further, central improvement topics which primarily involve the device’s usability, the refined and user- oriented parameter weighting of the device’s (optical) design concept, and the device’s (optical) calibration process (which, so far and as hypothetically proposed, could not sufficiently be achieved with reference to the eye’s retinal image only).

Abstract:

The availability of wearable medical devices on the market is rapidly increasing, con- firming the trend towards unobtrusive wearable home-care, but bulky and obtrusive cardiorespiratory monitoring is still the gold standard. A possible explanation could be the lack of knowledge regarding the best placement on the body of new multimodal sensor patches. This research project aims to participate in the field of multimodal wearable monitoring devices by targeting this lack of knowledge regarding their optimal placement on the body. Therefore the best position for each measured signal in terms of signal quality is assessed. The studied signals are ECG, IP, and heart and lung sounds. This project proposes a performance mapping of the upper body through a conducted study based on a sensor patch prototype designed by the TU Berlin EMSP team. A study including fifteen subjects and comparing nine upper body patch positions has been done. The influence of movement on all signals measured by the patch device has also been studied. Six minutes of data have been retrieved for each position, meaning a total of 54 minutes raw data per subject. The quality of each signal at each position and for phases with and without movement has then been quantified via defined performance metrics. Their condensation to one metric per signal then enabled a first verdict about the optimal positioning for each assessed biosignal. It has been found that the ECG signal performed best on the lower left sternal border in all cases, while the IP’s maximum quality was reached between the 1st and 2nd ICS near the right midclavicular line without movement and on the least impacted position in the presence of movement. The stethoscope best detected heart sounds in the direct heart proximity, and respiratory sounds were best monitored on the upper right part of the chest. The IMU signals were all best on the lower chest positions in the presence of movement, as these positions are the least affected. Without movement, heart sounds could best be measured on the left side either directly near the heart (AccZ and GyrY) or at a lower point (GyrX), while the respiratory vibrations were best detected on the sternum for the AccZ and on the right and left lower chest for the GyrX and GyrY signals respectively. The found results mean that there is no universal best position for all measured signals, but that the placement of such patch devices should be application-specific by determining the most important signals in each case.