Noninvasive Mapping Research Articles

Investigating Transport through Membranes in Non-Aqueous Redox Flow Batteries with Neutron Radiography

Electrochemical technologies offer a strong platform to decarbonize and electrify our energy economy and thus are poised to play an increasingly important role. Nevertheless, all electrochemical technologies suffer from thermodynamic, kinetic, and other operational losses that can drastically limit the performance of the device. Current macroscopic characterization techniques used to assess those losses (i.e., polarization, electrochemical impedance spectroscopy) fail to assess local inefficiencies challenging complete understanding of the system being investigated. Operando imaging of electrochemical systems, in tandem with electrochemical diagnostics offers a viable option to resolve local information and correlate it with macroscopic electrochemical performance. This dual characterization strategy has been successfully applied for the development of other electrochemical technologies (i.e., polymer electrolyte fuel cells[1,2], lithium-ion batteries[3,4]). In the past years, several groups developed and investigated imaging and spectroscopic techniques for operando characterization of redox flow batteries (RFBs) such as fluorescence microscopy[5], nuclear magnetic resonance spectroscopy[6,7] and infrared thermography[8]. Only recently, Clement et al. reported for the first time the use of neutron radiography to perform through-plane imaging of the gas evolution during operation of an all-vanadium RFB[9]. However, an approach enabling non-invasive operando concentration mapping of the species of interest within the reactor area has remained elusive.In this work, we develop two novel neutron radiography operando methodologies to quantify concentration distributions in RFBs. We first perform cuvette experiments to calibrate the neutron attenuation response of the redox active materials (i.e., TEMPO and TEMPO+) and supporting salts (i.e., BF4 -) used in this study. We find a linear response between the neutron absorption and the concentrations of the species of interest in the electrolyte in the studied range (0.0 to 0.5 M). Next, we performed experiments with redox flow cells under operation and use the ex-situ calibrations together with subtractive neutron imaging to quantify species concentration in the electrolyte. By employing an in-plane optical imaging setup[10], we can resolve species concentration across the porous electrodes (Figure 1). We observe strong variations in the concentration profiles within the reactor area upon changes in the operating conditions and link those differences to material properties (i.e., membrane electrostatic charge). Finally, I will discuss our latest results obtained using time-of-flight neutron imaging to deconvolute concentration maps for TEMPO/TEMPO+ and BF4 - species. Using this methodology, we study mass transport across a porous separator and a dense anion exchange membrane. We find that, while TEMPO/TEMPO+ and BF4 - show almost symmetrical concentration changes in the case of a porous separator, asymmetric transport occurs when a charge selective membrane is used where only BF4 - is allowed to crossover the anion exchange polymer. The developed methodology offers a non-invasive diagnostic tool to image concentration distributions in electrochemical cells and can be applied to support theoretical and experimental efforts aiming to understand the role of materials and reactor designs on complex mass transport phenomena.[1] P. Boillat, E. H. Lehmann, P. Trtik, M. Cochet, Current Opinion in Electrochemistry 2017, 5, 3.[2] J. Eller, T. Rosén, F. Marone, M. Stampanoni, A. Wokaun, F. N. Büchi, J. Electrochem. Soc. 2011, 158, B963.[3] B. Michalak, H. Sommer, D. Mannes, A. Kaestner, T. Brezesinski, J. Janek, Sci Rep 2015, 5, 15627.[4] D. P. Finegan, M. Scheel, J. B. Robinson, B. Tjaden, I. Hunt, T. J. Mason, J. Millichamp, M. Di Michiel, G. J. Offer, G. Hinds, D. J. L. Brett, P. R. Shearing, Nat Commun 2015, 6, 6924.[5] A. A. Wong, M. J. Aziz, S. Rubinstein, ECS Trans. 2017, 77, 153.[6] E. W. Zhao, T. Liu, E. Jónsson, J. Lee, I. Temprano, R. B. Jethwa, A. Wang, H. Smith, J. Carretero-González, Q. Song, C. P. Grey, Nature 2020, 579, 224.[7] E. W. Zhao, E. Jónsson, R. B. Jethwa, D. Hey, D. Lyu, A. Brookfield, P. A. A. Klusener, D. Collison, C. P. Grey, J. Am. Chem. Soc. 2021, 143, 1885.[8] H. Tanaka, Y. Miyafuji, J. Fukushima, T. Tayama, T. Sugita, M. Takezawa, T. Muta, Journal of Energy Storage 2018, 19, 67.[9] J. T. Clement, Investigation of Localized Performance and Gas Evolution in All-Vanadium Redox Flow Batteries via in-Situ Distributed Diagnostic Techniques, Ph.D. thesis, University of Tennessee, 2016.[10] P. Boillat, G. Frei, E. H. Lehmann, G. G. Scherer, A. Wokaun, Electrochem. Solid-State Lett. 2010, 13, B25. Figure 1

Left ventricular endocardial activation maps during right ventricular pacing in pediatric patients.

Cardiac pacing from right ventricular (RV) sites may cause electromechanical ventricular dyssynchrony. Invasive and noninvasive mapping studies showed left ventricular (LV) activation sequence in adults. Aim of this study was to seek out the LV endocardial activation (LVEA) in pediatric patients who underwent RV pacing. Single-center, prospective study conducted on pediatric patients who underwent left sided catheter ablation of accessory pathways with the Carto Univu mapping system. After successful ablation procedures, LVEA was recorded by the ablation catheter during sinus rhythm (SR) and during para-hisian (PHP), midseptum (MSP), and apical (RVAP) pacing. Seventeen patients, 13 males, aged 12 (10-15) years, registered LV activation maps and times (LVAT). SR showed significantly shorter LVAT than during pacing. LVAT of PHP was shorter than MSP, while there were not significant differences among PHP and MSP versus RVAP. In SR initial LV endocardial activation occurred in two midseptum sites, inferior-posterior and superior-anterior. During PHP, initial activation occurred at parahisian basal septum, rapidly followed by midseptum as in SR. During MSP and RVAP initial activation occurred at midseptum and apex, respectively. From all initial sites, the excitation spreads toward the base of the lateral LV free wall. A mild linear correlation was found between QRS duration and LVAT for MSP and for PHP. In pediatric patients LVEA maps during RV pacing showed that the shortest LVAT was obtained with PHP. The LV activation pattern seemed similar in sinus rhythm, PHP and MSP, from midseptum to LV lateral base.

Functional Network of Neurocognitive Development in Correlations of BOLD Signals

Blood Oxygen Level Dependent (BOLD) fMRI is widely used for non-invasive brain mapping and neuroimaging. Despite the challenges, significant advancements have been made in empirically explaining several (BOLD) signal features. Before applying functional connectivity measures to assess the (BOLD) signal, preprocessing is required. Different stimuli produced by a regular periodic oscillation pulse and propagation loops were applied to generate the (BOLD) signal. The fundamentals of the brain and cognitive development are being highlighted through functional connectivity in a unique approach. In this work, we present an approach that analyzes variations in (BOLD) connectivity over time. Our approach emphasizes the temporal or spatial aspects however, simultaneous co-activation events may trigger (BOLD). Our findings show the measures to assess Functional Connectivity (FC) through Pearson’s correlation to describe FC. (BOLD) responses are used in a voxel-wise linear model with an estimation of the maximum likelihood to get the regressors’ correlated components.

Cerebrovascular super-resolution 4D Flow MRI - Sequential combination of resolution enhancement by deep learning and physics-informed image processing to non-invasively quantify intracranial velocity, flow, and relative pressure.

The development of cerebrovascular disease is tightly coupled to regional changes in intracranial flow and relative pressure. Image-based assessment using phase contrast magnetic resonance imaging has particular promise for non-invasive full-field mapping of cerebrovascular hemodynamics. However, estimations are complicated by the narrow and tortuous intracranial vasculature, with accurate image-based quantification directly dependent on sufficient spatial resolution. Further, extended scan times are required for high-resolution acquisitions, and most clinical acquisitions are performed at comparably low resolution (>1mm) where biases have been observed with regard to the quantification of both flow and relative pressure. The aim of our study was to develop an approach for quantitative intracranial super-resolution 4D Flow MRI, with effective resolution enhancement achieved by a dedicated deep residual network, and with accurate quantification of functional relative pressures achieved by subsequent physics-informed image processing. To achieve this, our two-step approach was trained and validated in a patient-specific in-silico cohort, showing good accuracy in estimating velocity (relative error: 15.0±0.1%, mean absolute error (MAE): 0.07±0.06m/s, and cosine similarity: 0.99±0.06 at peak velocity) and flow (relative error: 6.6±4.7%, root mean square error (RMSE): 0.56mL/s at peak flow), and with the coupled physics-informed image analysis allowing for maintained recovery of functional relative pressure throughout the circle of Willis (relative error: 11.0±7.3%, RMSE: 0.3±0.2mmHg). Furthermore, the quantitative super-resolution approach is applied to an in-vivo volunteer cohort, effectively generating intracranial flow images at <0.5mm resolution and showing reduced low-resolution bias in relative pressure estimation. Our work thus presents a promising two-step approach to non-invasively quantify cerebrovascular hemodynamics, being applicable to dedicated clinical cohorts in the future.

Noninvasive ECG imaging of the intrinsic atrial pacemaker and atrial activation in surgically repaired or palliated congenital heart disease.

Sinus node location, function, and atrial activation are often abnormal in patients with congenital heart disease (CHD),due to anatomical, surgical, and acquired factors. We aimed to perform noninvasive electrocardiographic imaging (ECGI)of the intrinsic atrial pacemaker and atrial activation in patients with surgically repaired or palliated CHD, compared with control patients with structurally normal hearts. Atrial ECGI was performed in eightCHD patients with prespecified diagnoses (Fontan circulation, dextro transposition of the great arteries post Mustard/Senning, tetralogy of Fallot), and three controls. Activation and propagation maps were constructed in presenting rhythm. Wavefront propagation was analyzed to identify (1) intrinsic atrial pacemaker breakout site, (2) morphological right atrial (RA) activation pattern, (3) morphological left atrial (LA) breakout sites (i.e., interatrial connections), (4) LA activation pattern, and (5) putative lines of block. Physiologically appropriate atrial activation and propagation maps were able to be constructed. In the majority of patients, atrial breakouts were in keeping with the sinus node, observed in a crescent-shaped distribution from the anterior superior vena cava to the posterior RA. Ectopic atrial pacemaker sites were demonstrated in the atriopulmonary (AP) Fontan patient (very diffuse posterolateral RA) and Mustard patient (very posterior RA competing with a low RA focus). RA propagation was laminar in controls, but suggested either a line of block or conduction slowing consistent with an atriotomy scar in the tetralogy of Fallot (TOF) patients. Putative lines of block were more complex and RA propagation more abnormal in the atrial switch and AP Fontan patients, compared with the TOF patients. RA activation in the extracardiac Fontan patients was relatively laminar. Earliest LA breakout was most commonly observed in the region of Bachmann's Bundle in both controls and CHD patients, except for posterior LA breakouts in two patients. LA activation was typically more homogeneous than RA activation in CHD patients. ECGI can be utilized to create a noninvasive mapping model of atrial activation in postsurgical CHD, demonstrating atrial pacemaker location, putative lines of block and interatrial connections. Once validated invasively, this may have clinical implications in predicting risk of sinus node dysfunction and atrial arrhythmias, or in guiding catheter ablation.

A Hardware Non-Invasive Mapping Method for Condition Bits in Binary Translation

Binary translation, as an important bridge for application compatibility between different instruction set architectures (ISAs), has attracted much attention in the industry. However, due to hardware resource limitations of the target ISA, the translation efficiency and the practicability are poor. Recently, Apple has made it possible to run x86 programs on ARM through a translation technology called Rosetta based on software-hardware collaboration. In this paper, we proposed a hardware non-invasive mapping method for condition bits (HNIMCB) in binary translation, which innovatively implements the setting and referencing operations of the condition bits without changing the original instruction encoding and function of the target processor. This method is applicable for binary translation from source architectures with condition bit operations to target architectures without condition bit operations. It eliminates the difference of conditional bit resources between the source and target ISAs, reduces the computational instructions and memory access operations after translation from the source to the target ISA, and dramatically improves the translation efficiency. We conducted this experiment on a functional simulation level using the QEMU binary translator from ARM to RISC-V. A series of benchmark tests revealed that the total number of instructions decreased by 41%, while the number of memory access instructions decreased by 37% after the translation applying with the HNIMCB.

Diffeomorphic Surface Modeling for MRI-Based Characterization of Gastric Anatomy and Motility.

Gastrointestinal magnetic resonance imaging (MRI) provides rich spatiotemporal data about the movement of the food inside the stomach, but does not directly report muscular activity on the stomach wall. Here we describe a novel approach to characterize the motility of the stomach wall that drives the volumetric changes of the ingesta. A neural ordinary differential equation was optimized to model a diffeomorphic flow that ascribed the deformation of the stomach wall to a continuous biomechanical process. Driven by this diffeomorphic flow, the surface of the stomach progressively changes its shape over time, while preserving its topology and manifoldness. We tested this approach with MRI data collected from 10 rats under a lightly anesthetized condition, and demonstrated accurate characterization of gastric motor events with an error in the order of sub-millimeters. Uniquely, we characterized gastric anatomy and motility with a surface coordinate system common at both individual and group levels. Functional maps were generated to reveal the spatial, temporal, and spectral characteristics of muscle activity and its coordination across different regions. The peristalsis at the distal antrum had a dominant frequency and peak-to-peak amplitude of [Formula: see text] cycles per minute and [Formula: see text] mm, respectively. The relationship between muscle thickness and gastric motility was found to be distinct between two functional regions in the proximal and distal stomach. These results demonstrate the efficacy of using MRI to model gastric anatomy and function. The proposed approach is expected to enable non-invasive and accurate mapping of gastric motility for preclinical and clinical studies.

Fundus autofluorescence imaging using red excitation light

Retinal disease accounts significantly for visual impairment and blindness. An important role in the pathophysiology of retinal disease and aging is attributed to lipofuscin, a complex of fluorescent metabolites. Fundus autofluorescence (AF) imaging allows non-invasive mapping of lipofuscin and is a key technology to diagnose and monitor retinal disease. However, currently used short-wavelength (SW) excitation light has several limitations, including glare and discomfort during image acquisition, reduced image quality in case of lens opacities, limited visualization of the central retina, and potential retinal light toxicity. Here, we establish a novel imaging modality which uses red excitation light (R-AF) and overcomes these drawbacks. R-AF images are high-quality, high-contrast fundus images and image interpretation may build on clinical experience due to similar appearance of pathology as on SW-AF images. Additionally, R-AF images may uncover disease features that previously remained undetected. The R-AF signal increases with higher abundance of lipofuscin and does not depend on photopigment bleaching or on the amount of macular pigment. Improved patient comfort, limited effect of cataract on image quality, and lack of safety concerns qualify R-AF for routine clinical monitoring, e.g. for patients with age-related macular degeneration, Stargardt disease, or for quantitative analysis of AF signal intensity.

Non-Invasive Mapping of Cerebral Autoregulation Using Near-Infrared Spectroscopy: A Study Protocol.

The ability of cerebral vessels to maintain a fairly constant cerebral blood flow is referred to as cerebral autoregulation (CA). Using near-infrared spectroscopy (NIRS) paired with arterial blood pressure (ABP) monitoring, continuous CA can be assessed non-invasively. Recent advances in NIRS technology can help improve the understanding of continuously assessed CA in humans with high spatial and temporal resolutions. We describe a study protocol for creating a new wearable and portable imaging system that derives CA maps of the entire brain with high sampling rates at each point. The first objective is to evaluate the CA mapping system's performance during various perturbations using a block-trial design in 50 healthy volunteers. The second objective is to explore the impact of age and sex on regional disparities in CA using static recording and perturbation testing in 200 healthy volunteers. Using entirely non-invasive NIRS and ABP systems, we hope to prove the feasibility of deriving CA maps of the entire brain with high spatial and temporal resolutions. The development of this imaging system could potentially revolutionize the way we monitor brain physiology in humans since it would allow for an entirely non-invasive continuous assessment of regional differences in CA and improve our understanding of the impact of the aging process on cerebral vessel function.

Protocol for mapping of the supplementary motor area using repetitive navigated transcranial magnetic stimulation.

Damage to the supplementary motor area (SMA) can lead to impairments of motor and language function. A detailed preoperative mapping of functional boarders of the SMA could therefore aid preoperative diagnostics in these patients. The aim of this study was the development of a repetitive nTMS protocol for non-invasive functional mapping of the SMA while assuring effects are caused by SMA rather than M1 activation. The SMA in the dominant hemisphere of 12 healthy subjects (28.2 ± 7.7 years, 6 females) was mapped using repetitive nTMS at 20 Hz (120% RMT), while subjects performed a finger tapping task. Reductions in finger taps were classified in three error categories (≤15% = no errors, 15-30% = mild, >30% significant). The location and category of induced errors was marked in each subject's individual MRI. Effects of SMA stimulation were then directly compared to effects of M1 stimulation in four different tasks (finger tapping, writing, line tracing, targeting circles). Mapping of the SMA was possible for all subjects, yet effect sizes varied. Stimulation of the SMA led to a significant reduction of finger taps compared to baseline (BL: 45taps, SMA: 35.5taps; p < 0.01). Line tracing, writing and targeting of circles was less accurate during SMA compared to M1 stimulation. Mapping of the SMA using repetitive nTMS is feasible. While errors induced in the SMA are not entirely independent of M1, disruption of the SMA induces functionally distinct errors. These error maps can aid preoperative diagnostics in patients with SMA related lesions.

Detection of Myocardial Ischemia Using Cardiovascular MRI Stress T1 Mapping: A Miniature-Swine Validation Study

Purpose To assess the efficacy of cardiac MRI stress T1 mapping in detecting ischemic and infarcted myocardium in a miniature-swine model, using pathologic findings as the reference standard. Materials and Methods Ten adult male Chinese miniature swine, with coronary artery stenosis induced by an ameroid constrictor, and two healthy control swine were studied. Cardiac 3-T MRI rest and adenosine triphosphate stress T1 mapping and perfusion images, along with resting and late gadolinium enhancement images, were acquired at baseline and weekly up to 4 weeks after surgery or until humanely killed. A receiver operating characteristic analysis was used to analyze the performance of T1 mapping in the detection of myocardial ischemia. Results In the experimental group, both the infarcted myocardium (ΔT1 = 10 msec ± 2 [SD]; ΔT1 percentage = 0.7% ± 0.1) and ischemic myocardium (ΔT1 = 10 msec ± 2; ΔT1 percentage = 0.9% ± 0.2) exhibited reduced T1 reactivity compared with the remote myocardium (ΔT1 = 53 msec ± 7; ΔT1 percentage = 4.7% ± 0.6) and normal myocardium (ΔT1 = 56 msec ± 11; ΔT1 percentage = 4.9% ± 1.1). Receiver operating characteristic analysis demonstrated high diagnostic performance of ΔT1 in detecting ischemic myocardium, with an area under the curve (AUC) of 0.84 (P < .001). Rest T1 displayed high diagnostic performance in detecting infarcted myocardium (AUC = 0.95; P < .001). When rest T1 and ΔT1 were combined, the diagnostic performance for both ischemic and infarcted myocardium were improved (AUCs, 0.89 and 0.97, respectively; all P < .001). The collagen volume fraction correlated with ΔT1, ΔT1 percentage, and Δ extracellular volume percentage (r = −0.70, −0.70, and −0.50, respectively; P = .001, .001, and .03, respectively). Conclusion Using histopathologic validation in a swine model, noninvasive cardiac MRI stress T1 mapping demonstrated high performance in detecting ischemic and infarcted myocardium without the need for contrast agents. Keywords: Coronary Artery Disease, MRI, Myocardial Ischemia, Rest T1 Mapping, Stress T1 Mapping, Swine Model Supplemental material is available for this article. © RSNA, 2023 See also commentary by Burrage and Ferreira in this issue.

Non-invasive flow mapping of parasagittal meningeal lymphatics using 2D interslice flow saturation MRI

The clearance pathways of brain waste products in humans are still under debate in part due to the lack of noninvasive imaging techniques for meningeal lymphatic vessels (mLVs). In this study, we propose a new noninvasive mLVs imaging technique based on an inter-slice blood perfusion MRI called alternate ascending/descending directional navigation (ALADDIN). ALADDIN with inversion recovery (IR) at single inversion time of 2300 ms (single-TI IR-ALADDIN) clearly demonstrated parasagittal mLVs around the human superior sagittal sinus (SSS) with better detectability and specificity than the previously suggested noninvasive imaging techniques. While in many studies it has been difficult to detect mLVs and confirm their signal source noninvasively, the detection of mLVs in this study was confirmed by their posterior to anterior flow direction and their velocities and morphological features, which were consistent with those from the literature. In addition, IR-ALADDIN was compared with contrast-enhanced black blood imaging to confirm the detection of mLVs and its similarity. For the quantification of flow velocity of mLVs, IR-ALADDIN was performed at three inversion times of 2000, 2300, and 2600 ms (three-TI IR-ALADDIN) for both a flow phantom and humans. For this preliminary result, the flow velocity of the dorsal mLVs in humans ranged between 2.2 and 2.7 mm/s. Overall, (i) the single-TI IR-ALADDIN can be used as a novel non-invasive method to visualize mLVs in the whole brain with scan time of ~ 17 min and (ii) the multi-TI IR-ALADDIN can be used as a way to quantify the flow velocity of mLVs with a scan time of ~ 10 min (or shorter) in a limited coverage. Accordingly, the suggested approach can be applied to noninvasively studying meningeal lymphatic flows in general and also understanding the clearance pathways of waste production through mLVs in humans, which warrants further investigation.

A Workflow to Quantitatively Determine Age-Related Macular Degeneration Lesion-Specific Variations in Fundus Autofluorescence.

Fundus autofluorescence (FAF) imaging allows the noninvasive mapping of intrinsic fluorophores of the ocular fundus, particularly the retinal pigment epithelium (RPE), now quantifiable with the advent of confocal scanning laser ophthalmoscopy-based quantitative autofluorescence (QAF). QAF has been shown to be generally decreased at the posterior pole in age-related macular degeneration (AMD). The relationship between QAF and various AMD lesions (drusen, subretinal drusenoid deposits) is still unclear. This paper describes a workflow to determine lesion-specific QAF in AMD. A multimodal in vivo imaging approach is used, including but not limited to spectral domain optical coherence tomography (SD-OCT) macular volume scanning and QAF. Using customized FIJI plug-ins, the corresponding QAF image is aligned with the near-infrared image from the SD-OCT scan (characteristic landmarks; i.e., vessel bifurcations). The foveola and the edge of the optic nerve head are marked in the OCT images (and transferred to the registered QAF image) for accurate positioning of the analysis grids. AMD-specific lesions can then be marked on individual OCT BScans or the QAF image itself. Normative QAF maps are created to account for the varying mean and standard deviation of QAF values throughout the fundus (QAF images from a representative AMD group were averaged to build normative standard retinal QAF AMD maps). The plug-ins record the X and Y coordinates, z-score (a numerical measurement that describes the QAF value in relation to the mean of AF maps in terms of standard deviation from the mean), mean intensity value, standard deviation, and number of pixels marked. The tools also determine z-scores from the border zone of marked lesions.This workflow and the analysis tools will improve the understanding of the pathophysiology and clinical AF image interpretation in AMD.

Generation of cardiac digital twins based on noninvasive cardiac mapping

Abstract Funding Acknowledgements Type of funding sources: Other. Main funding source(s): Generalitat Valenciana Grants Ministerio de Ciencia, Innovación y Universidades Background Personalized cardiac digital twins have been proposed as a clinical tool to plan ablation strategies during cardiac arrhythmias. However, these personalization frameworks normally rely on invasive recordings which limits their clinical applicability. Electrocardiographic Imaging (ECGI) is a mapping technique that allows the reconstruction of global cardiac activity non-invasively. Purpose Evaluate the applicability of ECGI as a non-invasive tool for the planification of ablation strategies based on personalized digital twins. Methods Cardiac digital twins generated from endocardial or ECGI mapping were compared in a patient with Atrial Flutter prescribed for cardiac ablation. Endocardial mapping was obtained in the right atrium by using electroanatomical mappings. ECGI was recorded during the ablation procedure with a mapping system of 128 body surface recordings. For the cardiac digital twin based on endocardial mapping, the reentrant circuit around the tricuspid valve was reproduced based on the activation time maps obtained with the electroanatomical mapping system. Total activation time of both atria was personalized based on the duration of the F-waves on the ECG since the left atrium was not endocardialy mapped. For the cardiac digital twin based on the ECGI, activation times obtained in both left and right atrium were used to set-up the personalized model. From both approaches, computed torso potentials were calculated. The correlation with real body surface recordings was compared. To further evaluate the fidelity of the models, the efficacy of the ablation strategy performed on the real patient was evaluated over the digital twins. Results Both digital twins, the one based on endocardial mapping, and the one based on ECGI were compared. Regarding dynamics of the model, both models reproduced the reentrant circuit around the tricuspid valve. Interestingly, only the ECGI digital twin reproduced a reentrant wave around the right pulmonary veins. When endocardial map was used for the personalization, a median conduction velocity (CV) of 90.5 cm/s was obtained for the right atrium and 174.7 cm/s for the left; whereas when ECGI was used, the median CV were 104.2 cm/s at the right and 129.1 cm/s at the left atrium. The ability to reproduce body surface ECGs of both digital twins demonstrated that the one based on endocardial mapping obtained a low correlation of 0.13, whereas the ECGI digital twin increase the correlation up to 0.66. Regarding the ablation outcome, ablation terminated the arrhythmia only in the cardiac digital twin based on ECGI. Conclusion The possibility to generate cardiac digital twins based on non-invasive ECGI mapping has been demonstrated. This opens the door to obtaining personalized cardiac digital twins before endocardial interventions which can be used to plan ablation procedures.

Clinical evaluation of the new 12-lead ECG noninvasive epi-endocardial mapping technology

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): XSpline S.p.a. Aim Noninvasive electrocardiographic mapping systems may require multichannel (150-250) ECG body surface recordings which is a huge limitation for the adoption into clinical practice. However, most of the currently available noninvasive mapping systems accurately represent epicardial activation. Over the last few years, various technical solutions have been implemented to increase the accuracy of ECG forward-inverse calculations including machine learning algorithms. We developed a novel 12-lead ECG-based, fully automated system for noninvasive full transmural (epi-endocardial) mapping. The aim of this study was to evaluate accuracy of this system in heart failure patients with typical LBBB. Methods Eight consecutive patients (median age: 65; 25-75% range 59-64; 5 male) with typical LBBB QRS morphology (QRS duration 146–224 ms), scheduled for CRT implantation underwent a cardiac CT scan and 12-lead ECG recording, followed by detailed bi-ventricular endocardial electroanatomical contact mapping (EAM). A median of 258 (181-576) local electrograms in LV and 86 (70-139) in RV were collected during EAM. Cardiac CT data were semiautomatically processed using a Unet-like neural network to obtain meshes containing the heart (each chamber with both endocardial and epicardial contour as well as coronary sinus and its branches), lungs and torso using different segmentation module. Noninvasive epi-endocardial activation maps were calculated using state-of-the-art mathematical models including machine learning methods. These data were compared with EAM from the invasive mapping system using Spearman correlation (r), mean absolute error (MAE) and relative distance metrics. Results All early and latest activation patterns were correctly identified (see figure). The average correlation (r) of endocardial activation maps was 0.92 for all cases (min-max: 0.82-0.96). MAE was rather small (9-15 mm) when the non-invasive late activation zone nearly matches the CARTO data (average distance error 14 mm). Overall, the QRS complex was correctly reproduced by our method in all cases (r = 0.96). Conclusions This study shows that new mapping technique can accurately reconstruct endocardial electrical activation maps based on 12-lead ECG and cardiac CT scan. The approach may be very useful in pre-procedural planning of device implantation and catheter ablation. Larger validation studies are however needed for confirming method accuracy at epicardial site.

Non-invasive electrocardiographic ventricular mapping based on the equivalent double layer model: different workflows, same accuracy

Abstract Funding Acknowledgements Type of funding sources: None. Background and aim Electrocardiographic imaging (ECGI) is capable of performing activation maps with a single premature beat. The endo-epicardial ECGI system based on the equivalent double layer model (EDL), is a portable system that uses a patient-specific heart torso geometry obtained from a CT-scan or cardiac magnetic resonance (CMR), and a conventional 12-lead ECG. The simplicity of the system allows for its use either as a pre-procedural or intra-procedural tool. The aim of this study was to assess the accuracy of the system in centres using different workflows. Methods We studied consecutive patients referred for ablation of ventricular arrhythmias that had an ECGI performed with the endo-epicardial system based on the EDL model to guide mapping and catheter ablation, at four centres. Three centres performed the ECGI pre-procedurally, two with the use of a bedside portable ECG recorder and one on ambulatory basis with a 12-lead Holter recorder, and ablation was performed either manually or with remote magnetic navigation (RMN). The fourth centre performed the ECGI intra-procedurally, recording the ECG directly from the electrophysiology digital multichannel system, and the ablation was performed manually with the use of intracardiac echo (ICE) in all cases. VAs were localised using a segmental model, which included 22 left ventricular segments (classical 17-segment model, plus the aortic cusps and the papillary muscles), and 12 segments on the right ventricle including 4 on the right ventricular outflow tract (RVOT): Anterior, lateral, right septum and left septum. A perfect match (PM) was defined as a predicted location within the same anatomic segment, whereas a near match (NM) was defined as a predicted location within the same segment or a contiguous one. We studied the three different workflows. Results Sixty-three arrhythmias were studied in 58 patients. The ECGI was performed pre-procedurally with a bedside ECG recorder in 26 cases, pre-procedurally with a Holter recorder in 27 cases and intra-procedurally in 10 cases. The results according to each group are presented in the Table. The accuracy of the ECGI was not different between groups. The system correctly identified the SOO of the VAs in the same or a contiguous segment when compared to the invasive mapping in all patients, regardless of the approach used. The percentage of PM was also not significantly different. The group with ICE guidance had lower fluoroscopy and mapping times, but the success and recurrence rates were similar. Conclusions The results of this multicentre experience show that this ECGI system, using a conventional 12 -lead ECG is simple and accurate across different clinical workflows, and presents a useful and versatile tool to facilitate planning the ablation strategy as well as intra-procedural guidance for mapping and ablation of patients with VAs.

Non-invasive electrocardiographic mapping using an endo-epicardial system based on extracellular potentials shows better accuracy for atrial arrhythmias than ventricular arrhythmias

Abstract Funding Acknowledgements Type of funding sources: Private hospital(s). Main funding source(s): Learning Health Background and aim Electrocardiographic imaging (ECGI) is capable of performing an activation map with a single beat. The endo-epicardial system based on extracellular potentials allows for the reconstruction of endo-epicardial potentials both in the ventricles and the atria. The aim of this study was to compare the accuracy of the system to predict the site of origin (SOO) of ventricular focal arrhythmias (VAs) versus atrial focal arrhythmias (AAs). Methods We studied 55 consecutive patients referred for ablation of VAs or AAs that had an ECGI performed before ablation. Ablations were performed with remote magnetic navigation or manually. The localization of the VAs and AAs based on the ECGI and invasive electroanatomic mapping was performed using a segmental model of the atria and the ventricles. A perfect match (PM) was defined as a predicted location within the same anatomic segment, whereas a near match (NM) as a predicted location within the same segment or a contiguous one. The number of leads used for ECGI mapping, the agreement between the ECGI and the invasive map, and the success of the procedure were evaluated. Results Ablation was performed in 49 patients. We mapped 54 arrhythmias, 37 VAs (37 patients) and 17 AAs (12 patients). The results according to the atrial or ventricular origin of the arrhythmia are depicted in the table. Patients with AAs were older, no other differences were significant. The ECGI system correctly identified the SOO of both VAs and AAs in the same segment or a contiguous one in 100% of AAs and 97% of VAs, p=1.000. However, the percentage of a PM (Figure) was higher for AAs than for VAs (100% vs 76%, p=0.044). Conclusions The endo-epicardial ECGI correctly identified the origin of both ventricular and atrial arrhythmias. However, the accuracy was higher for the latter.

Impact of left ventricular scar burden on response to two different modalities of conduction system CRT

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): British Heart Foundation Introduction Cardiac resynchronisation therapy (CRT) in the form of His bundle CRT and left bundle area CRT can be more effective than the gold standard, biventricular pacing (BVP). In BVP scar burden is known to predict response whether this is true for these novel modalities is not known. Purpose The purpose of this study was to determine whether left ventricular scar burden assessed using cardiac MRI can be used to predict the electrical and acute haemodynamic response to two novel CRT modalities. Methods Patients with standard CRT indications were recruited. They underwent a pre-procedure cardiac MRI, with late gadolinium enhancement (LGE) to quantify scar. His bundle CRT (His CRT) and left bundle area CRT (LBA CRT) were attempted. The electrical response was measured using high precision non-invasive mapping ECGi (CardioInsight, Medtronic). The haemodynamic response was measured with a high precision protocol. We investigated the impact of scar and baseline electrical characteristic on ECGi and haemodynamic response. Results 26 patients were recruited (85% male, mean age 69 ± 10, with ischaemic cardiomyopathy in 35%). LGE was observed in 96% of cases and the mean (range 1-39%). We found a significant correlation between scar extent and the electrical response with both modalities. There was a significant correlation between a lower scar burden and better electrical response. For His CRT the reduction in left ventricular activation time was better with lower scar burden (R= 0.77, p &amp;lt; 0.01, Picture 1), for LBA CRT for reduction in left ventricular activation was also better with lower scar burden (R = 0.53, p = 0.05, Picture 2). With His CRT there was also a significant correlation between lower scar extent and better acute haemodynamic response ( R = 0.6, p = 0.002) but this was not observed with LBA CRT (R = 0.07, p = 0.77). Conclusion Left ventricular myocardial scar can be used to predict the electrical response to two different conduction system CRT modalities.

Dynamic-Reversible MRI Nanoprobe for Continuous Imaging Redox Homeostasis in Hepatic Ischemia-Reperfusion Injury.

Hepatic ischemia-reperfusion (I/R) injury accompanied by oxidative stress is responsible for postoperative liver dysfunction and failure of liver surgery. However, the dynamic non-invasive mapping of redox homeostasis in deep-seated liver during hepatic I/R injury remains a great challenge. Herein, inspired by the intrinsic reversibility of disulfide bond in proteins, a kind of reversible redox-responsive magnetic nanoparticles (RRMNs) is designed for reversible imaging of both oxidant and antioxidant levels (ONOO-/GSH), based on sulfhydryl coupling/cleaving reaction. We develop a facile strategy to prepare such reversible MRI nanoprobe via one-step surface modification. Owing to the significant change in size during the reversible response, the imaging sensitivity of RRMNs is greatly improved, which enables RRMNs to monitor the tiny change of oxidative stress in liver injury. Notably, such reversible MRI nanoprobe can non-invasively visualize the deep-seated liver tissue slice by slice in living mice. Moreover, this MRI nanoprobe can not only report molecular information about the degree of liver injury but also provide anatomical information about where the pathology occurred. The reversible MRI probe is promising for accurately and facilely monitoring I/R process, accessing injury degree and developing powerful strategy for precise treatment.

CI-452767-4 NON-INVASIVE 3D ELECTRICAL ACTIVATION MAPPING TO PREDICT CRT RESPONSE: SITE OF LATEST LV ACTIVATION RELATIVE TO PACING SITE

Left ventricular (LV) pacing remote to the latest LV electrically activated site (LEAS) may diminish efficacy of cardiac resynchronization therapy (CRT). However, this has not been evaluated rigorously using global LV mapping. Test whether the distance “dp” between LV pacing site (LVPS) and LEAS influences the rate of CRT response. Consecutive CRT patients in 5 centers underwent noninvasive 3D electrical activation mapping and torso CT 6-24 months post-implant. LVPS, LEAS and dp were assessed. LV end-systolic volume (LVESV) reduction of ≥15% at clinical follow-up defined response. Logistic regression probabilistically modeled Non-Response; variables included demographics, heart failure classification, left bundle branch block (LBBB), ischemic heart disease, atrial fibrillation (AF), baseline QRS duration, baseline ejection fraction (EF), baseline LVESV, comorbidities, use of CRT optimization algorithm, ACE inhibitor/ARB, beta-blocker, diuretics, and dp. Of 111 patients (age 64 ± 11 years, baseline LVEF 28 ± 6%, baseline QRS duration 172 ± 21 ms, baseline LVESV 183 ± 87 mL, implant duration 12 ± 5 months (mean ± SD); 93%/7% had class I/IIa CRT indication, 31%/69% had NYHA Class II/III, 74% were males, 98% had LBBB, 38% had ischemic heart disease and 18% had a history of AF), 67% responded at 10 ±3 months post-implant (55% and 75% for ischemic and non-ischemic patients, respectively). LEAS were outside the mid and basal lateral segments in 35% of the patients. dp was 42 ± 23 mm (range 2-137): 31 ± 14 mm in Responders vs 63 ± 24 mm in Non-Responders. The distance dp, and the use of CRT optimization algorithms, remained the only independent predictors of non-response (area under the curve (AUC) 0.906). dp = 47 mm delineated Responders from Non-Responders (AUC 0.931). The distance between LV pacing site and site of latest electrical activation is a strong independent predictor for CRT response. Non-invasive electrical evaluation to characterize intrinsic activation and guide LV lead deployment may improve CRT efficacy.