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IEEE Transactions on Biomedical Engineering

Institute of Electrical and Electronics Engineers (IEEE)

Preprints posted in the last 7 days, ranked by how well they match IEEE Transactions on Biomedical Engineering's content profile, based on 38 papers previously published here. The average preprint has a 0.04% match score for this journal, so anything above that is already an above-average fit.

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Quantum-Refined Latent Diffusion: A Hybrid Generative Framework for Imbalanced ECG Classification

Kritopoulos, G.; Neofotistos, G.; Barmparis, G. D.; Tsironis, G. P.

2026-04-13 cardiovascular medicine 10.64898/2026.04.09.26350502 medRxiv
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Class imbalance in clinical electrocardiogram (ECG) datasets limits the diagnostic sensitivity of automated arrhythmia classifiers, particularly for rare but clinically significant beat types. We propose a three-stage hybrid generative pipeline that combines a spectral-guided conditional Variational Autoencoder (cVAE), a class-conditional latent Denoising Diffusion Probabilistic Model (DDPM), and a Quantum Latent Refinement (QLR) module built on parameterized quantum circuits to augment minority arrhythmia classes in the MIT-BIH Arrhythmia Database. The QLR module applies a bounded residual correction guided by Maximum Mean Discrepancy minimization to align synthetic latent distributions with real class-specific latent banks. A lightweight 1D MobileNetV2 classifier evaluated over five independent random seeds and four augmentation ratios serves as the downstream benchmark. Our findings establish latent diffusion augmentation as an effective strategy for imbalanced ECG classification and motivate further investigation of quantum-classical hybrid methods in cardiac diagnostics.

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REDDI: A Riemannian Ensemble Learning Framework for Interpretable Differential Diagnosis of Neurodegenerative Diseases

Roca, M.; Messuti, G.; Klepachevskyi, D.; Angiolelli, M.; Bonavita, S.; Trojsi, F.; Demuru, M.; Troisi Lopez, E.; Chevallier, S.; Yger, F.; Saudargiene, A.; Sorrentino, P.; Corsi, M.-C.

2026-04-12 neurology 10.64898/2026.04.10.26350617 medRxiv
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Neurodegenerative diseases such as Mild Cognitive Impairment (MCI), Multiple Sclerosis (MS), Parkinson s Disease (PD), and Amyotrophic Lateral Sclerosis (ALS) are becoming more prevalent. Each of these diseases, despite its specific pathophysiological mechanisms, leads to widespread reorganization of brain activity. However, the corresponding neurophysiological signatures of these changes have been elusive. As a consequence, to date, it is not possible to effectively distinguish these diseases from neurophysiological data alone. This work uses Magnetoencephalography (MEG) resting-state data, combined with interpretable machine learning techniques, to support differential diagnosis. We expand on previous work and design a Riemannian geometry-based classification pipeline. The pipeline is fed with typical connectivity metrics, such as covariance or correlation matrices. To maintain interpretability while reducing feature dimensionality, we introduce a classifier-independent feature selection procedure that uses effect sizes derived from the Kruskal-Wallis test. The ensemble classification pipeline, called REDDI, achieved a mean balanced accuracy of 0.81 (+/-0.04) across five folds, representing a 13% improvement over the state-of-the-art, while remaining clinically transparent. As such, our approach achieves reliable, interpretable, data-driven, operator-independent decision-support tools in Neurology.

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Individualised evoked response detection based on the spectral noise colour

Undurraga Lucero, J. A.; Chesnaye, M.; Simpson, D.; Laugesen, S.

2026-04-13 health informatics 10.64898/2026.04.11.26350685 medRxiv
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Objective detection of evoked potentials (EPs) is central to digital diagnostics in hearing assessment and clinical neurophysiology, yet current approaches remain time-intensive and sensitive to inter-individual noise variability. Many existing detection methods rely on population-based assumptions or computationally demanding procedures, limiting robustness and efficiency in real-world clinical settings. We present Fmpi, a digital EP detection framework enabling individualised, real-time response detection through analytical modelling of the spectral colour and temporal dynamics of background noise within each recording. Using extensive simulations and large-scale human electroencephalography datasets spanning brainstem, steady-state, and cortical EPs recorded in adults and infants, we demonstrate performance comparable or superior to state-of-the-art bootstrapped methods while operating at a fraction of the computational cost and maintaining well-controlled sensitivity with improved specificity. Importantly, Fmpi incorporates a futility detection mechanism enabling early termination of uninformative recordings, reducing testing time without compromising diagnostic reliability.

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Hidden risk in normal myocardial perfusion scans: AI-detected proximal coronary calcium on CT attenuation maps improves prognosis

Zhou, J.; Miller, R. J.; Shanbhag, A.; Killekar, A.; Han, D.; Patel, K. K.; Pieszko, K.; Yi, J.; Urs, M. K.; Ramirez, G.; Lemley, M.; Kavanagh, P. B.; Liang, J. X.; Kamagate, A.; Builoff, V.; Einstein, A. J.; Feher, A.; Miller, E. J.; Sinusas, A. J.; Ruddy, T. D.; Knight, S.; Le, V. T.; Mason, S.; Chareonthaitawee, P.; Wopperer, S.; Alexanderson, E.; Carvajal-Juarez, I.; Rosamond, T. L.; Slipczuk, L.; Travin, M. I.; Packard, R. R.; Acampa, W.; Al-Mallah, M.; deKemp, R. A.; Buechel, R. R.; Berman, D. S.; Dey, D.; Di Carli, M. F.; Slomka, P. J.

2026-04-15 cardiovascular medicine 10.64898/2026.04.14.26350808 medRxiv
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Purpose: Spatial distribution of coronary artery calcium (CAC) may provide additional prognostic value in patients undergoing SPECT and PET myocardial perfusion imaging (MPI). We aimed to automatically identify CAC in proximal segments from attenuation correction CT (CTAC) scans using artificial intelligence (AI) and to evaluate prognostic significance in two large international multicenter registries. Methods: From hybrid MPI/CT imaging (N=43,099) across 15 sites, we included 4,552 most relevant patients with 1) no prior coronary artery disease; 2) AI-derived mild CAC scores (1-99); and 3) normal perfusion (stress total perfusion deficit <5%). The independent associations between AI-identified proximal CAC and major adverse cardiovascular events (MACE) and all-cause mortality (ACM) were evaluated using multivariable Cox regression, likelihood ratio test (LRT), and continuous net reclassification index (NRI). Results: Among the patients with mild CAC and normal perfusion (mean age 65{+/-}12 years, 51% male), 1,730 (38%) had proximal CAC. Over 3.6 (inter-quartile interval 2.1, 5.2) years follow up, 599 (13%) and 444 (10%) patients had MACE or ACM, respectively. Proximal CAC was associated with an increased risk of MACE (adjusted hazard ratio [HR] 1.24, 95% CI 1.03-1.48, P=0.02) and ACM (adjusted HR 1.25, 95% CI 1.01-1.53, P=0.04) after the adjustment of CAC score and density, clinical risk factors, and perfusion deficit. Proximal CAC improved the risk stratification of MACE (LRT P=0.02; NRI 12%) and ACM (LRT P=0.04; NRI 12%). Conclusion: In patients with mild CAC and normal perfusion, AI detection of proximal CAC identified a higher-risk group for adverse outcomes, highlighting its prognostic utility.

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Wearable-derived physiological features for trans-diagnostic disease comparison and classification in the All of Us longitudinal real-world dataset

Huang, X.; Hsieh, C.; Nguyen, Q.; Renteria, M. E.; Gharahkhani, P.

2026-04-13 epidemiology 10.64898/2026.04.07.26350352 medRxiv
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Wearable-derived physiological features have been associated with disease risk, but most current studies focus on single conditions, limiting understanding of cross-disease patterns. This study adopts a trans-diagnostic approach to examine whether wearable data capture shared and condition-specific physiological signatures across multiple chronic conditions spanning physical and mental health, and then evaluates the utility of these features for disease classification. A total of 9,301 patients with at least 21 days of consecutive FitBit data from the All of Us Controlled Tier Dataset version 8 were analyzed. Disease subcohorts included cardiovascular disease (CVD), diabetes, obstructive sleep apnea (OSA), major depressive disorder (MDD), anxiety, bipolar disorder, and attention-deficit/ hyperactivity disorder (ADHD), chosen based on prevalence and relevance. Logistic regression and XGBoost models were fitted for each disease subcohort versus the control cohort. We found that compared to using just baseline demographic and lifestyle features, incorporating wearable-derived features enabled improved classification performance in all subcohorts for both models, except for ADHD where improvement was mainly observed for ROC-AUC in logistic regression model likely due to the smaller sample size in ADHD subcohort. The largest performance gains were observed in MDD (increase in ROC-AUC of 0.077 for Logistic regression, 0.071 for XGBoost; p < 0.001) and anxiety (increase in ROC-AUC of 0.077 for logistic regression, 0.108 for XGBoost; p < 0.001). This study provides one of the first comprehensive transdiagnostic evaluations of wearable-derived features for disease classification, highlighting their potential to enhance risk stratification in the real-world setting as a practical complement to clinical assessments and providing a foundation to explore more fine-grained wearable data. Author summaryWearable devices such as fitness trackers and smartwatches are becoming increasingly popular and affordable, providing continuous measurements of heart rate, physical activity, and sleep. Alongside the growing digitization of health records, this creates new opportunities for large-scale, real-world health studies. In this study, we analyzed wearable-derived physiological patterns across a range of chronic conditions spanning both physical and mental health to better understand how these signals relate to disease risk. We found that incorporating wearable-derived heart rate, activity and sleep features improved disease risk classification across several conditions, with particularly strong gains for major depressive disorder and anxiety. By examining how individual features contributed to model predictions, we also identified meaningful associations between physiological signals and disease risk. For example, both duration and day-to-day variation of deep and rapid eye movement (REM) sleep were associated with increased risk in certain conditions. Our study supports the development of real-time, automated tools to assess disease risk alongside clinical care.

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Mechanistic Insights into Skin Sympathetic Nerve Activity Dynamics in Healthy Subjects Through a Two-Layer Signal-Analytical and Closed-Loop Physiological Modeling Framework

Lin, R.; Halfwerk, F. R.; Donker, D. W.; Tertoolen, J.; van der Pas, V. R.; Laverman, G. D.; Wang, Y.

2026-04-13 health informatics 10.64898/2026.04.11.26350680 medRxiv
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Objective: Skin sympathetic nerve activity (SKNA) has emerged as a promising non-invasive surrogate measure of sympathetic drive, but its relevant physiological characteristics remain ill-defined. This observational study aims to investigate its regulatory patterns during rest and Valsalva maneuver (VM) in healthy participants. Method: Using a two-layer strategy integrating signal analysis and physiological modelling, we analyzed data recorded from 41 subjects performing repeated VMs. The observational layer includes time-domain feature comparisons using linear mixed-effect models, and time-varying spectral coherence analysis. The mechanistic layer proposes a mathematical model to investigate whether baroreflex and respiratory modulation are sufficient to reproduce the observed HR and average SKNA (aSKNA) dynamics. Main Results: Mean integrated SKNA (iSKNA) showed more significant change than HRV for VM induced effects. We also found mean iSKNA increase during VM varies with BMI and sex. The coherence analysis indicated that iSKNA strongly synchronized with EDR under resting conditions. The proposed model successfully reproduced main characteristics of aSKNA dynamics, yielding a high median Pearson correlation coefficient of 0.80 ([Q1, Q3] = [0.60, 0.91]). In contrast, HR dynamics were only partially captured, with a median PCC of 0.37 ([Q1, Q3] = [0.16, 0.55]). These results likely suggest SKNA provides a more direct representation of sympathetic burst dynamics during VM in healthy subjects. Significance: This study provides convergent evidence that SKNA reflects known autonomic regulatory influences in healthy subjects. These findings strengthen the physiological interpretability of SKNA while clarifying its appropriate use as a practical biomarker of sympathetic function.

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Feasibility of Volumetric Analysis using Bedside Ultra-Low-Field Portable Magnetic Resonance Imaging in Patients receiving Extracorporeal Membrane Oxygenation

Stockbridge, M. D.; Faria, A. V.; Neal, V.; Diaz-Carr, I.; Soule, Z.; Ahmad, Y. B.; Khanduja, S.; Whitman, G.; Hillis, A. E.; Cho, S.-M.

2026-04-13 neurology 10.64898/2026.04.09.26350481 medRxiv
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The SAFE MRI ECMO (NCT05469139) study established the safety of ultra-low-field 64mT MRI in patients receiving extracorporeal membrane oxygenation (ECMO) in the setting of intensive care and demonstrated that these images were highly sensitive in detecting acquired brain injuries. This retrospective analysis of prospectively collected observational data sought to expand on these findings in light of the crucial need for neurological monitoring while patients receive ECMO by evaluating the feasibility of volumetric analyses derived from ultra-low-field MR images. T2-weighted scans from thirty patients who received ultra-low-field MRI while undergoing ECMO at Johns Hopkins Hospital were analyzed using a volumetric pipeline to determine whole brain volume and volumes of total grey matter, total white matter, subcortical grey matter, ventricles, left hemisphere, right hemisphere, telencephalon, left and right lateral ventricles, the total intracranial volume, and the cerebellum. Segmented brain volumes in patients undergoing ECMO were comparable to measurements obtained using conventional field and ultra-low-field MRI in the absence of ECMO instrumentation. The subgroup analysis demonstrated subtle volumetric differences between patients supported with venoarterial ECMO and those receiving venovenous ECMO. These data provide the first evidence that ultra-low-field MRI provides volumetric measurements comparable to conventional field-strength MRI, even in the presence of ECMO circuitry, supporting its feasibility for neuroimaging in critically ill patients.

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Novel Therapeutic Strategy for Orthostatic Hypotension Using Deep Brain Stimulation

Yamasaki, F.; Seike, M.; Hirota, T.; Sato, T.

2026-04-16 cardiovascular medicine 10.64898/2026.04.14.26350914 medRxiv
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Background: Deep brain stimulation (DBS) is a treatment option for Parkinson disease (PD). However, the effect of DBS on the arterial pressure (AP) remains unexplored. We aimed to develop an artificial baroreflex system for treating orthostatic hypotension (OH) due to central baroreflex failure in patients with PD. To achieve this, we developed an appropriate algorithm after estimating the dynamic responses of the AP to DBS using a white noise system identification method. Methods: We randomly performed DBS while measuring the AP tonometrically in 3 trials involving 3 patients with PD treated with DBS. We calculated the frequency response of the AP to the DBS using a fast Fourier transform algorithm. Finally, the feedback correction factors were determined via numerical simulation. Results: The frequency responses of the systolic AP to random DBS were identifiable in all 3 trials, and the steady state gain was 8.24 mmHg/STM. Based on these results, the proportional correction factor was set to 0.12, and the integral correction factor was set to 0.018. The computer simulation revealed that the system could quickly and effectively attenuate a sudden AP drop induced by external disturbances such as head-up tilting. Conclusion: An artificial baroreflex system with DBS may be a novel therapeutic approach for OH caused by central baroreflex failure.

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Analytical Choices Impact the Estimation of Rhythmic and Arrhythmic Components of Brain Activity

da Silva Castanheira, J.; Landry, M.; Fleming, S. M.

2026-04-11 neuroscience 10.1101/2025.09.24.678322 medRxiv
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Brain activity comprises both rhythmic (periodic) and arrhythmic (aperiodic) components. These signal elements vary across healthy aging, and disease, and may make distinct contributions to conscious perception. Despite pioneering techniques to parameterize rhythmic and arrhythmic neural components based on power spectra, the methodology for quantifying rhythmic activity remains in its infancy. Previous work has relied on parametric estimates of rhythmic power extracted from specparam, or estimates of rhythmic power obtained after detrending neural spectra. Variation in analytical choices for isolating brain rhythms from background arrhythmic activity makes interpreting findings across studies difficult. Whether these current approaches can accurately recover the independent contribution of these neural signal elements remains to be established. Here, using simulation and parameter recovery approaches, we show that power estimates obtained from detrended spectra conflate these two neurophysiological components, yielding spurious correlations between spectral model parameters. In contrast, modelled rhythmic power obtained from specparam, which detrends the power spectra and parametrizes brain rhythms, independently recovers the rhythmic and arrhythmic components in simulated neural time series, minimising spurious relationships. We validate these methods using resting-state recordings from a large cohort. Based on our findings, we recommend modelled rhythmic power estimates from specparam for the robust independent quantification of rhythmic and arrhythmic signal components for cognitive neuroscience.

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From Chaos to Care: Personalized AI for Early Cardiac Arrhythmia Warning

Halder, S.; Kim, C. M.; Periwal, V.

2026-04-10 cardiovascular medicine 10.64898/2026.04.08.26350403 medRxiv
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Cardiac arrhythmias are abnormal heart rhythms characterized by disordered electrical dynamics that impair cardiac function and pose a major global burden of morbidity and mortality. Early and accurate prediction of arrhythmic anomalies from physiological time series is crucial for effective intervention, yet remains challenging due to the nonlinear, nonstationary, and individualized nature of cardiac dynamics. Despite significant advances in machine learning-based arrhythmia detection, most existing methods operate as static classifiers on electrocardiographic signals and lack online prediction, patient-specific adaptation, and mechanistic interpretability. From a dynamical-systems perspective, arrhythmias represent qualitative regime transitions, often preceded by subtle, temporally extended deviations that are difficult to detect in real time. Here we introduce CASCADE (Chaotic Attractor Sensitivity for Cardiac Anomaly Detection), an online and personalized anomaly forecasting framework built on a special type of reservoir computing called Dynamical Systems Machine Learning (DynML). DynML employs ensembles of continuous-time nonlinear dynamical systems as chaotic reservoirs to reconstruct and forecast short-term cardiac dynamics on a beat-to-beat basis, training only a linear readout. This design enables efficient online adaptation without retraining the underlying dynamical model. Rather than relying on static beat-level classification, CASCADE identifies arrhythmic events as failures of short-term predictability, manifested as statistically significant deviations between predicted and observed dynamics relative to subject-specific baselines. Detection performance is governed by the intrinsic dynamical complexity of the reservoir, quantified by topological entropy. Reservoirs operating near critical entropy regimes optimally amplify subtle, temporally extended irregularities in heartbeat dynamics, rendering incipient arrhythmic signatures linearly separable at the readout level. Topological entropy thus serves both as a predictor of model performance and a principled control parameter for reservoir design. When evaluated on the MIT-BIH Arrhythmia dataset, CASCADE achieved consistently high F1 scores, precision, recall, and overall accuracy across diverse patient populations, demonstrating strong generalizability across clinical and real-world settings. By integrating chaotic reservoir computing, entropy-guided tuning, and online personalized forecasting, CASCADE reframes arrhythmia detection as a problem of dynamical regime transition rather than static classification. This perspective provides a scalable, interpretable, and computationally efficient framework for real-time cardiac monitoring and early-warning clinical decision support.

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Apnea-hypopnea index estimation with wrist-worn photoplethysmography

Fonseca, P.; Ross, M.; van Meulen, F.; Asin, J.; van Gilst, M. M.; Overeem, S.

2026-04-11 health informatics 10.64898/2026.04.08.26350411 medRxiv
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ObjectiveLong term monitoring of obstructive sleep apnea (OSA) severity may be relevant for several clinical applications. We developed a method for estimating the apnea-hypopnea index (AHI) using wrist-worn, reflective photoplethysmography (PPG). ApproachA neural network was developed to detect respiratory events using PPG and PPG-derived sleep stages as input. The development database encompassed retrospective data from three polysomnographic datasets (N=3111), including a dataset with concurrent reflective PPG recordings from a wrist-worn device (N=969). The model was pre-trained with (transmissive) finger-PPG signals from all overnight recordings and then fine-tuned to wrist-PPG characteristics using transfer learning. Validation was performed on the test portion of the development set and on a fourth, external hold-out dataset containing both wrist-PPG and PSG data (N=171). Performance was evaluated in terms of AHI estimation accuracy and OSA severity classification. Main ResultsThe fine-tuned wrist-PPG model demonstrated strong agreement with the PSG-derived gold-standard AHI, achieving intra-class correlation coefficients of 0.87 in the test portion of the development set and 0.91 in the external hold-out validation set. Diagnostic performance was high, with accuracies above 80% for all severity thresholds. SignificanceThe study highlights the potential of reflective PPG-based AHI estimation, achieving high estimation performance in comparison with PSG. These measurements can be performed with relatively comfortable sensors integrated in convenient wrist-worn wearables, enabling long-term assessment of sleep disordered breathing, both in a diagnostic phase, and during therapy follow-up.

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Leveraging State-of-the-Art LLMs for the De-identification of Sensitive Health Information in Clinical Speech

Dai, H.-J.; Mir, T. H.; Fang, L.-C.; Chen, C.-T.; Feng, H.-H.; Lai, J.-R.; Hsu, H.-C.; Nandy, P.; Panchal, O.; Liao, W.-H.; Tien, Y.-Z.; Chen, P.-Z.; Lin, Y.-R.; Jonnagaddala, J.

2026-04-17 health informatics 10.64898/2026.04.13.26349911 medRxiv
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Accurate recognition and deidentification of sensitive health information (SHI) in spoken dialogues requires multimodal algorithms that can understand medical language and contextual nuance. However, the recognition and deidentification risks expose sensitive health information (SHI). Additionally, the variability and complexity of medical terminology, along with the inherent biases in medical datasets, further complicate this task. This study introduces the SREDH/AI-Cup 2025 Medical Speech Sensitive Information Recognition Challenge, which focuses on two tasks: Task-1: Speech transcription systems must accurately transcribe speech into text; and Task-2: Medical speech de-identification to detect and appropriately classify mentions of SHI. The competition attracted 246 teams; top-performing systems achieved a mixed error rate (MER) of 0.1147 and a macro F1-score of 0.7103, with average MER and macro F1-score of 0.3539 and 0.2696, respectively. Results were presented at the IW-DMRN workshop in 2025. Notably, the results reveal that LLMs were prevalent across both tasks: 97.5% of teams adopted LLMs for Task 1 and 100% for Task 2. Highlighting their growing role in healthcare. Furthermore, we finetuned six models, demonstrating strong precision ([~]0.885-0.889) with slightly lower recall ([~]0.830-0.847), resulting in F1-scores of 0.857-0.867.

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Signal-to-noise evaluation of dynamic versus static 18FDG-PET in focal epilepsy via Bayesian regional estimated signal quality analysis

Quigg, M.; Chernyavskiy, P.; Terrell, W.; Smetana, R.; Muttikal, T. E.; Wardius, M.; Kundu, B.

2026-04-14 neurology 10.64898/2026.04.12.26350712 medRxiv
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Background and Purpose: 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography (static PET) has mixed specificity and sensitivity in targeting epileptic zones in the noninvasive stage of epilepsy surgery evaluations. We compared the signal quality of static PET compared to a method of interictal dynamic PET (iD-PET). Materials and Methods: We calculated the signal quality of static PET and iD-PET obtained from a cohort of patients with focal epilepsy. We developed a Bayesian regional estimated signal quality (BRESQ) technique to objectively compare signal-to-noise ratios (SNRs) by region of interest (ROI) within subjects. Results: Adjusted for ROI size and neighboring regions, iDPET was superior to sPET with probability >95% in 8/36 regions; >90% in 21/36 regions; >80% in 29/36 regions. The top five regions with the largest adjusted SNR differences (greatest magnitude of iDPET superiority) were the Temporal Mesial (Left and Right), Occipital Lateral (Left and Right), and the Left Frontal Inferior Base. Conclusions: We found that iDPET yielded a superior SNR in most ROI. BRESQ offers a scalable and generalizable method to quantify signal quality between brain mapping modalities.

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WITHDRAWN: Volitional Fast Inspiration Enhances Upper Limb Sensorimotor Excitability in Subacute Stroke Patients

Yang, Y.; Li, Z.; Sun, J.; Mo, L.; Liu, A.; Ji, L.; Li, C.

2026-04-13 neurology 10.64898/2026.04.08.26350460 medRxiv
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BackgroundRespiration is a key central nervous system rhythm that modulates sensorimotor function in healthy individuals, but the neurophysiological mechanisms of volitional breathing-mediated sensorimotor modulation and its preservation in stroke patients remain unclear. This study aimed to characterize the effects of volitional fast inspiration on sensorimotor pathway excitability in healthy and stroke populations, and provide a mechanistic basis for respiratory-integrated post-stroke rehabilitation. MethodsA multimodal case-control neurophysiology study was conducted in 52 healthy volunteers (26 {+/-} 3 years, 30 males) and 44 first-ever subacute stroke patients (66 {+/-} 10 years, 30 males). Three complementary experiments assessed transcranial magnetic stimulation-induced motor-evoked potentials (MEPs), peripheral nerve stimulation-induced somatosensory-evoked potentials (SEPs), and functional electrical stimulation -evoked muscle force under three breathing conditions: volitional fast inspiration (IN), fast expiration (EX), and spontaneous breathing (CON). Two-way and one-way repeated measures ANOVA with Bonferroni post hoc tests were used for statistical analysis. ResultsVolitional fast inspiration significantly enhanced sensorimotor pathway excitability and muscle force generation in both groups. Volitional fast inspiration increased MEP amplitudes relative to spontaneous breathing and fast expiration (p {inverted exclamation} 0.05), with further amplification during active muscle contraction (p {inverted exclamation} 0.05). It also elevated SEP amplitudes in healthy parietal/frontal cortical regions and the stroke parietal cortex (p {inverted exclamation} 0.05). Synchronizing volitional fast inspiration with voluntary finger contraction increased muscle force evoked by functional electrical stimulation by 16-18% relative to spontaneous breathing (p {inverted exclamation} 0.05), with non-significant force gains at rest. ConclusionsVolitional fast inspiration bidirectionally enhances corticospinal transmission, somatosensory integration, and functional force generation in both healthy individuals and stroke patients, with preserved respiratory modulation in stroke-damaged neuropathways. By demonstrating preserved respiratory modulation in stroke-damaged neuropathways, our results provide mechanistic support for integrating controlled breathing into low-cost, non-invasive post-stroke rehabilitation paradigms.

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The relationship between limb dystonia severity and functional impact in children with cerebral palsy

Lott, E.; Kim, S.; Blackburn, J. S.; Gelineau-Morel, R.; Mingbunjerdsuk, D.; O'Malley, J.; Tochen, L.; Waugh, J.; Wu, S.; Aravamuthan, B. R.

2026-04-13 neurology 10.64898/2026.04.11.26350684 medRxiv
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Dystonia treatment evaluation in cerebral palsy (CP) is limited by the lack of clinician-assessed scales linking dystonia severity to functional impact. We asked 7 pediatric movement disorder specialists to review videos of 27 children with CP while performing an upper extremity task and while walking. Experts rated arm and leg dystonia severity using the Global Dystonia Severity Rating Scale (GDRS) and task-specific functional impact on a five-point scale adapted from the Dyskinetic Cerebral Palsy Functional Impact Scale. Arm GDRS scores correlated with functional impact on the upper extremity task (linear regression R^2=0.48, p=0.0005). Leg GDRS scores correlated with gait impact (R^2=0.43, p=0.001). A four-point increase in total GDRS corresponded to a one-point worsening in combined functional impact. By demonstrating how expert-rated limb dystonia severity correlates with task-specific functional impact in children with CP, these results could help clinically identify functionally-meaningful differences in dystonia severity.

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VIsual STAndardized Quantification of LGE (VISTAQ), a contour-less method for late gadolinium enhancement quantification

Aquaro, G. D.; Licordari, R.; De Gori, C.; Todiere, G.; Ianni, U.; Barison, A.; De Luca, A.; Folgheraiter, a.; Grigoratos, C.; alberti, m.; lombardo, m.; De Caterina, R.; Sinagra, G.; Emdin, M.; Di Bella, G.; fulceri, l.

2026-04-15 cardiovascular medicine 10.64898/2026.04.09.26350552 medRxiv
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Background: Late gadolinium enhancement (LGE) quantification by cardiovascular magnetic resonance is central to risk stratification in hypertrophic cardiomyopathy (HCM), yet conventional techniques require contour tracing and region-of-interest (ROI) placement, which may reduce reproducibility and increase analysis time. We developed a novel visual standardized approach, the Visual Standardized Quantification of LGE (VISTAQ), that does not require myocardial contouring, arbitrary ROI positioning, or dedicated post-processing software. Methods: In this multicenter, multivendor retrospective study, LGE images from 400 patients (100 prior myocardial infarction, 250 HCM, 50 other non-ischemic heart diseases) were analyzed. VISTAQ subdivides each myocardial segment into transmural mini-segments and classifies LGE visually using predefined criteria, expressing global LGE burden as the percentage of positive mini-segments. Reproducibility was assessed in 250 patients across different observer expertise levels using intraclass correlation coefficients (ICC) and Bland?Altman analysis. In 100 HCM patients, VISTAQ was compared with conventional methods (mean+2SD, +5SD, +6SD, FWHM, visual thresholding). Prognostic performance was evaluated in 250 HCM patients over a median 5-year follow-up. Results: VISTAQ demonstrated excellent intra- and inter-observer reproducibility (ICC up to 0.98 and 0.97, respectively), consistent across disease subtypes. Compared with conventional techniques, VISTAQ showed similar ICC to FWHM but significantly lower net and absolute inter-observer differences (median absolute difference 1.3%). Mean+2SD markedly overestimated LGE, whereas mean+6SD slightly underestimated LGE compared with VISTAQ, mean+5SD, FWHM, and visual thresholding. Analysis time was substantially shorter with VISTAQ (median 105 vs. 375 seconds, p<0.0001). During follow-up, 21 hard cardiac events occurred in HCM population. An LGE threshold >10% predicted events with higher accuracy using VISTAQ (AUC 0.90; sensitivity 85%; specificity 94%) compared with mean+6SD (AUC 0.75; sensitivity 57%; specificity 93%). Conclusions: VISTAQ provides highly reproducible, time-efficient LGE quantification without dedicated software and demonstrates non-inferior prognostic discrimination in HCM compared with conventional threshold-based techniques.

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Wearable sleep staging using photoplethysmography and accelerometry across sleep apnea severity: a focus on very severe sleep apnea

Ogaki, S.; Kaneda, M.; Nohara, T.; Fujita, S.; Osako, N.; Yagi, T.; Tomita, Y.; Ogata, T.

2026-04-13 health informatics 10.64898/2026.04.09.26350266 medRxiv
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Study ObjectivesTo evaluate wearable sleep staging across sleep apnea severity, including very severe sleep apnea defined as an apnea-hypopnea index (AHI)[&ge;] 50 events/h, and to assess how training-set composition affects performance in this subgroup. MethodsWe analyzed 552 overnight recordings, 318 from the Sleep Lab Dataset and 234 from the Hospital Dataset. In the Hospital Dataset, 26.5% had very severe sleep apnea. We developed a deep learning model for sleep staging using RR intervals from wrist-worn photoplethysmography and three-axis accelerometry. Baseline performance was assessed by cross-validation under 5-stage and 4-stage staging. We examined night-level associations with AHI severity. We also compared the baseline model with an ablation model trained on the same number of recordings but with more Sleep Lab Dataset and lower-AHI Hospital Dataset recordings, evaluating both models in the very severe subgroup. ResultsIn 5-stage classification, Cohens kappa was 0.586 in the Sleep Lab Dataset and 0.446 in the Hospital Dataset. Under 4-stage staging, the gap narrowed, with kappa values of 0.632 and 0.525, respectively. In the Hospital Dataset, performance declined with increasing AHI severity. Among 62 recordings with very severe sleep apnea, reducing high-AHI representation in training lowered kappa from 0.365 to 0.303. ConclusionsWearable sleep staging performance declined across greater sleep apnea severity in this clinical cohort. Clinical utility may benefit from training data that better represent the target severity spectrum and from selecting staging granularity to match the intended use case. Statement of SignificanceRepeated laboratory polysomnography is impractical for long-term sleep apnea management. Wearable sleep staging could support scalable monitoring, yet its reliability in clinically severe sleep apnea has remained unclear. This study developed and evaluated a wearable sleep staging approach in both sleep-laboratory and hospital cohorts. The hospital cohort included many severe and very severe cases. Performance was lower in the hospital cohort and declined with greater sleep apnea severity. A coarser staging scheme reduced the gap between cohorts, and models trained without representative very severe cases performed worse in this target population. These findings highlight the value of severity-aware model development and motivate future multi-night home validation with reliability cues.

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A Modified Percutaneous Spinal Cord Stimulation Implant Approach to Target the Ventral Spinal Cord

Valestrino, K. J.; Ihediwa, C. V.; Dorius, G. T.; Conger, A. M.; Glinka-Przybysz, A.; McCormick, Z. L.; Fogarty, A. E.; Mahan, M. A.; Hernandez-Bello, J.; Konrad, P. E.; Burnham, T. R.; Dalrymple, A. N.

2026-04-13 surgery 10.64898/2026.04.06.26350176 medRxiv
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ObjectivesEpidural spinal cord stimulation (SCS) is an emerging therapy for motor rehabilitation following spinal cord injury (SCI) and other motor disorders. Conventionally, SCS leads are placed along the dorsal spinal cord (SCSD), where stimulation activates large diameter afferent fibers, which indirectly activate motoneurons through reflex pathways. This leads to broad activation of flexor and extensor muscles and limited fine-tuned control of motor output. Targeting the ventral spinal cord (SCSV) may enable more direct activation of motoneuron pools, potentially improving the specificity of muscle activation; however, there is currently no established method to place leads ventrally. To address this, we evaluated the feasibility of four modified percutaneous implantation techniques to target the ventrolateral thoracolumbar spinal cord. Materials and methodsPercutaneous SCSV implantation was performed in three human cadaver torso specimens under fluoroscopic guidance. The following approaches were evaluated: sacral hiatus, transforaminal, interlaminar contralateral, and interlaminar ipsilateral. The leads in the latter 3 approaches were inserted between L1 and L5. Eighteen implants were attempted, with nine leads retained for analysis. Lead and electrode position were assessed using computed tomography (CT) with three-dimensional reconstruction, along with anatomical dissection to verify lead and electrode placement within the epidural space. ResultsSuccessful ventral epidural lead placement was achieved using all four implantation approaches. The sacral hiatus (16/16 electrodes) and transforaminal (8/8 electrodes) approaches resulted in exclusively ventrolateral placement. The interlaminar contralateral approach led to 27/32 electrodes positioned ventrolaterally and 5/32 dorsally. The interlaminar ipsilateral implantation approach led to 14/32 electrodes positioned ventrolaterally and 18/32 positioned ventromedially. ConclusionsThese findings demonstrate that ventral epidural SCS lead placement can be achieved using modified percutaneous implant techniques. The four approaches outlined here provide a clinically feasible pathway to SCSV and establishes a foundation for future clinical studies investigating SCSV for motor rehabilitation following SCI.

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Democratizing Scientific Publishing: A Local, Multi-Agent LLM Framework for Objective Manuscript Editing

Bhansali, R.; Gorenshtein, A.; Westover, B.; Goldenholz, D. M.

2026-04-17 health informatics 10.64898/2026.04.13.26350761 medRxiv
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Manuscript preparation is a critical bottleneck in scientific publishing, yet existing AI writing tools require cloud transmission of sensitive content, creating data-confidentiality barriers for clinical researchers. We introduce the Paper Analysis Tool (PAT), a free, multi-agent framework that deploys 31 specialized agents powered by small language models (SLMs) to audit manuscripts across multiple quality dimensions without external data transmission. Applied to three published clinical neurological papers, PAT generated 540 evaluable suggestions. Validation by two expert reviewers (R.B., A.G.) confirmed 391 actionable, high-value revisions (90% agreement), achieving a 72.4% overall usefulness accuracy spanning methodological, statistical, and visual domains. Furthermore, deterministic re-evaluation of 126 agent-suggested rewrite pairs using Phase 0 metrics confirmed text improvement: total word count decreased by 25%, passive voice prevalence dropped sharply from 35% to 5%, average sentence length decreased by 24%, long-sentence fraction fell by 67%, and the Flesch-Kincaid grade improved by 17% . Our validation confirms that systematic, agent-driven pre-submission review drives measurable improvements, successfully converting manuscript optimization from an opaque, manual endeavor into a transparent and rigorous scientific process. Manuscript preparation is a critical bottleneck in scientific publishing, yet existing AI writing tools require cloud transmission of sensitive content, creating data-confidentiality barriers for clinical researchers. We introduce the Paper Analysis Tool (PAT), a free, multi-agent framework that deploys 31 specialized agents powered by small language models (SLMs) to audit manuscripts across multiple quality dimensions without external data transmission. Applied to three published clinical neurological papers, PAT generated 540 evaluable suggestions. Independent validation by two expert reviewers (R.B., A.G.) confirmed 391 actionable, high-value revisions (90% agreement), achieving a 72.4% overall usefulness accuracy spanning methodological, statistical, and visual domains. Furthermore, deterministic re-evaluation of 126 suggested Phase 0 rewrite pairs confirmed text improvement: total word count decreased by 25%, passive voice prevalence dropped sharply from 35% to 5%, average sentence length decreased by 24%, and long-sentence fraction fell by 67%, and the Flesch-Kincaid grade improved modestly. Our validation confirms that systematic, agent-driven pre-submission review drives measurable improvements, successfully converting manuscript optimization from an opaque, manual endeavor into a transparent and rigorous scientific process.

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CTA versus TOF-MRA for circle of Willis segmentation: Implications for hemodynamic modelling

Vikström, A.; Zarrinkoob, L.; Johannesdottir, M.; Wahlin, A.; Hellström, J.; Appelblad, M.; Holmlund, P.

2026-04-11 cardiovascular medicine 10.64898/2026.04.10.26350583 medRxiv
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Modelling of hemodynamics in the circle of Willis (CoW) depends on vascular segmentation, which may vary based on imaging modality. Computed tomography angiography (CTA) is commonly used in clinic but involves radiation and injection of contrast agents, whereas magnetic resonance angiography (MRA) offers a non-invasive alternative. This study aims to compare CoW morphology and modelled cerebral perfusion pressure of CTA and MRA segmentations, validating if MRA can replace CTA in modelling workflows. CTA and time-of-flight MRA (TOF-MRA) of the CoW was performed in 19 patients undergoing elective aortic arch surgery (67{+/-}7 years, 8 women). The CoW was semi-automatically segmented based on signal intensity thresholding. A TOF-MRA threshold was optimized against the CTA segmentation, using the CTA as reference standard. Computational fluid dynamics (CFD) modelling with boundary conditions based on subject-specific flow rates from 4D flow MRI simulated cerebral perfusion pressure in the segmented geometries. A baseline simulation and a unilateral brain inflow simulation, i.e., occlusion of a carotid, were carried out. Linear mixed models indicated there was no effect of choice of modality on either average arterial lumen area (CTA - TOF-MRA: -0.2{+/-}1.3 mm2; p=0.762) or baseline pressure drops (0.2{+/-}1.9 mmHg; p=0.257). In the unilateral inflow simulation, we found no difference in pressure laterality (-6.6{+/-}18.4 mmHg; p=0.185) or collateral flow rate (10{+/-}46 ml/min; p=0.421). TOF-MRA geometries can with signal intensity thresholding be matched to produce similar morphology and modelled cerebral perfusion pressure to CTA geometries. The modelled pressure drops over the collateral arteries were sensitive to the segmentation regardless of modality.