Medical Image Analysis
○ Elsevier BV
Preprints posted in the last 7 days, ranked by how well they match Medical Image Analysis's content profile, based on 35 papers previously published here. The average preprint has a 0.03% match score for this journal, so anything above that is already an above-average fit.
Reiter, T.; Weber, O. M.; Weiss, i.; Kraus, N.; Kress, S.; Bauer, W. R.
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Patients with implantable cardioverter-defibrillators (ICDs) often are excluded from receiving CMR scans at 3.0T due to ICD-induced image artifacts. This work aims to transfer sequence protocols established for CMR imaging in the presence of ICDs at 1.5T to a first human application at 3.0T. All measurements were performed on a clinical 3T MRI scanner. Phantom measurements were used to establish and optimize wideband PSIR LGE imaging at 3.0T. Volunteer measurements with externally placed ICDs were used for optimization of CINE imaging and wideband PSIR imaging. Thirdly, patients with implanted ICD were examined with the optimized protocols. Human measurements showed that SA stacks obtained with spoiled GRE after contrast agent showed a markedly lower artifact burden than the conventional approach. For scar imaging, a wideband PSIR with a bandwidth of 3kHz and a frequency offset of +750Hz allowed a sufficient suppression of relevant artifacts in the majority of scans. No strong correlation between the image quality and the distance between the cardiac silhouette and the device was detected. The presented work shows the feasibility of clinical cardiac MRI at 3.0T including GRE-CINE and wideband PSIR-LGE for patients with ICDs.
Habib, G.; Thakur, S.; Shaban, M.; Ahmad, R.; Malik, I. A.
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The -Bonacci weighted sequence space {ell}(,) is introduced for [≥] 2, 1 [≤] < {infty}, and > 0). It is proved to be a Banach space which is isometrically isomorphic to {ell}, with an unconditional Schauder basis. The space is also reflexive and uniformly convex. Its strict inclusion chain, continuous dual, and asymptotic truncation estimate of order - / are also established. Based on this framework, Scaled 𝑚-BonacciNet is proposed as a lightweight CNN that rescales Fibonacci-Net channels using the dominant 𝑚-Bonacci root and employs depth wise separable convolutions. Tribonacci-Net achieved 96.09% accuracy and a 0.9581 macro F1-score on the 15-class Brain MRI dataset using 0.85 million parameters and 0.366 GFLOPs. Pentanacci-Net attained 95.87% accuracy on the 44-class dataset while reducing parameters and FLOPs by 47.10% and 44.48%, respectively. On the CKD ultrasound dataset, Hexanacci-Net achieved 83.75% accuracy and a 0.7941 macro F1-score, with corresponding reductions of 50.37% and 45.10%. These findings support dominant-root scaling as a structured approach to lightweight CNN design.
Roudbari, A.; Van Hentenryck, P.; Zandehshahvar, R.
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Longitudinal clinical cohorts contain heterogeneous progression patterns that are obscured by coarse diagnostic labels. Discovering these latent progression phenotypes requires models that distinguish patients not only by their outcomes, but also by how their clinical trajectories evolve. This paper proposes TRACE, an interpretable temporal phenotyping method that enables the learning of outcome-informed progression phenotypes from longitudinal trajectories. TRACE combines a trajectory- and outcome-aware contrastive objective with a probabilistic predictive phenotype layer, encouraging phenotypes to capture progression structure while remaining predictive of diagnostic state. A dual-attention mechanism further supports interpretation by identifying the visits and clinical variables most associated with each phenotype assignment. TRACE is evaluated on the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort for cognitive disease modeling, showing improved performance in both diagnostic prediction and phenotype discovery compared with other temporal phenotyping baselines. Finally, by allowing the number of phenotypes to exceed the diagnostic labels, TRACE enables discovering additional progression patterns that are not captured by labels defined a priori.
Karoui, H.; Bouke, N. J.; Cole, J. H.; Yeow, R. W.; Dick, F.; Razin, R.; Thomas, D. L.; Schroder, K. H.; Cash, D.; Bocchetta, M.; Williams, S. C.; Vasa, F.
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Background: Ultra-low field (ULF) magnetic resonance imaging (MRI) offers accessible point-of-care neuroimaging, yet its capability to support multivariate network analyses remains understudied. Methods: We systematically evaluated the feasibility and reliability of Morphometric Similarity Networks (MSN) and Morphometric Inverse Divergence (MIND) networks derived from paired high-field (HF, 3T/1.5T) and ULF (64mT) scans in a primary cohort(N=23) and an independent replication cohort (N=19). We tested the impact of super-resolution processing, cortical parcellation granularity (Desikan-Killiany vs. Destrieux), and mesh resolution (fsnative vs. fsaverage5) on edge-level cross-scanner agreement (Lin's concordance correlation coefficient, CCC) and subject-level identifiability. Results: MIND networks demonstrated higher edge-level HF-ULF agreement (mean CCC = 0.95) and ULF reproducibility (mean CCC = 0.98) compared to MSNs (mean CCC = 0.86-0.87 and 0.91-0.94, respectively). In contrast, MSNs yielded higher subject-level differential identifiability across field strengths due to a broader distinction between within- and between-subject similarity. Reconstructing MIND networks on native high-resolution meshes (fsnative) maximised cross-scanner agreement, whereas coarser meshes and finer cortical parcellations enhanced individual network identifiability. Conclusions: Structural similarity networks can be reliably constructed from ULF MRI data. Optimal analytic choices depend on study objectives: MIND on native meshes maximises cross-scanner stability, whereas MSNs excel at preserving individual uniqueness, paving the way for globally scalable connectomic research.
Hew, C. K. W.; Leserri, S.; Aydogan, D. B.; Bastin, M. E.; Bonthrone, A. F.; Paterson, K.; Barclay, G.; Jardine, C.; Smith, K. M.; Thrippleton, M. J.; Marioni, R. P.; Boardman, J. P.; Blesa Cabez, M.
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Structural connectomics provides a means of characterising white matter (WM) network organisation using diffusion MRI (dMRI), but reconstructing neonatal structural connectomes remains challenging due to the immature and heterogeneous nature of the developing brain. Although recent neonatal studies have increasingly adopted approaches beyond conventional diffusion tensor imaging (DTI), there remains scope to incorporate more advanced tractography and streamline post-processing approaches within neonatal pipelines. Here, we propose a neonatal structural connectome pipeline integrating surface-based anatomical constraints, ensemble tractography, hierarchical anatomical refinement of pathways (HARP) filtering, and spherical-deconvolution informed filtering (SIFT2) reweighting. We acquired 3T MRI data from 300 neonates (185 preterm, 115 term-born) to assess the impact of pipeline configuration on network organisation. Mean gestational age (GA) at birth was 29.31 (23.43-32.86) weeks in preterm infants and 39.52 (37.00-42.43) weeks in term infants. At scan, mean GA was 40.85 (36.29-49.00) weeks in preterm infants and 42.06 (38.29-48.00) weeks in term infants. Four connectome variants were generated: raw surfaced-based tractograms, HARP-filtered, SIFT2-weighted, and combined HARP+SIFT2. Pipeline performance was primarily evaluated using an existing brain age prediction model: connectome-based predictive model (CPM) and our derived connectomes to estimate GA at scan in term and preterm infants. In addition, global graph theoretical metric analyses were conducted to provide a complementary assessment of pipeline configuration differences in network organisation. In total, seven graph theoretical metrics were calculated and evaluated: global efficiency, local efficiency, transitivity, modularity, assortativity, degree variance and statistical complexity. Across all configurations, connectomes supported accurate brain age prediction, with mean absolute errors (MAE) of 0.76-0.79 weeks in term infants and 1.00-1.06 weeks in preterm infants. Prediction error and brain age gap variability were greater in preterm than term infants across configurations, with HARP+SIFT2 achieving the lowest preterm MAE (1.00 weeks) and brain age gap (BAG) variability (SD = 1.38 weeks). However, differences in prediction performance across configurations were minimal, suggesting limited influence of pipeline choice on brain age prediction. However, analysis of global network metrics demonstrated that pipeline choice significantly influenced downstream measures of network organisation, with HARP+SIFT2 being the only configuration to identify significant preterm vs. term differences across all seven metrics examined. These findings demonstrate the importance of considering tractography and streamline-processing choices when constructing neonatal structural connectomes and provide a framework for more anatomically informed investigation of early brain development.
Noh, S. A.; Park, J.; Yoon, Y. E.; Jeon, J.; Jang, Y.; Lee, S.-A.; Bak, M.; Choi, H.-M.; Hwang, I.-C.; Cho, G.-Y.
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Aims: Myocardial strain enables sensitive assessment of cardiac function, but its clinical application has largely focused on individual chambers or selected patient populations. We evaluated the feasibility and clinical relevance of fully automated multi-chamber strain assessment in consecutive patients undergoing routine transthoracic echocardiography (TTE). Methods and results: This retrospective study included 8,350 consecutive adults undergoing TTE. A hospital-wide artificial intelligence (AI)-based system automatically measured left ventricular (LV) global longitudinal strain (LVGLS), left atrial (LA) reservoir strain (LASr), and right ventricular (RV) free-wall strain (RVFWS). AI-derived LVGLS was available from at least one apical view in 97.1% of patients and from all three views in 94.8%; LASr and RVFWS were available in 94.1% and 94.5%, respectively, resulting in complete multi-chamber strain assessment in 90.3%. Strain measures showed modest correlations with conventional chamber-specific echocardiographic parameters and differential associations with clinical outcomes. Gaussian mixture modeling identified three distinct clusters characterized by preserved multi-chamber function, RV-dominant dysfunction, and pan-chamber dysfunction. Compared with the preserved cluster, pan-chamber dysfunction was associated with the highest risk of all-cause death or heart failure hospitalization (adjusted hazard ratio, 3.44; 95% CI, 2.43-4.88; P<0.001). Prognostic associations remained evident in patients with LV ejection fraction (LVEF) [≥]50%, and cluster assignment provided incremental prognostic information beyond clinical factors, LVEF, and RV fractional area change. Conclusions: Fully automated multi-chamber strain assessment was feasible in a large consecutive TTE cohort. Integrating strain across cardiac chambers may provide complementary functional characterization and identify clinically relevant clusters with prognostic information beyond conventional assessment.
Sandor, D.; Nemeth, A.; Daroczy, B.; Sztanek, F.; Harangi, M.; Antal, P.
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Personalized medicine aims to tailor treatments to individual patients, but its implementation is limited by scarce clinical resources and heterogeneous treatment effects. Electronic health records now offer longitudinal data that can support data-driven therapy selection. We focus on SGLT2 inhibitors, medications with broad metabolic and cardiovascular benefits, whose clinical impact varies significantly based on individual patient profiles. We propose a counterfactual Structural Causal Model (SCM) to estimate individual treatment effects (ITE) of SGLT2 inhibitors from observational data. The model assumes counterfactual stability and uses a Gumbel-Max sampling mechanism to capture stochastic treatment assignment while enabling differentiable inference. Optimal treatments are defined by maximizing the counterfactual value of future diagnostic outcomes. We evaluate the Counterfactual Gumbel-Max SCM using a doubly robust value estimator and show that, across diagnostic categories, it outperforms real-world prescriptions in predicted treatment value, highlighting subpopulations where SGLT2 inhibitors yield superior outcomes. By integrating causal inference with electronic health data, this framework provides individualized counterfactual reasoning about SGLT2 treatment effects and can support clinicians in identifying optimal therapies for type 2 diabetes and comorbid conditions.
BOU ALI, M. N.; Mahmoud, M.
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Background. Real-world 12-lead electrocardiograms (ECGs) often have missing or corrupted leads. A deep-learning classifier can be prepared for this by random lead masking during training, or by injecting clinical knowledge, for example by pulling its attention towards the leads that guidelines use for each diagnosis. Whether this knowledge adds robustness beyond masking is unknown. Methods. Pre-registered comparison of three arms sharing one network (per-lead 1D-ResNet encoder and per-diagnosis attention over the 12 leads): standard training (M0); random whole-lead masking (M1); masking plus a Kullback-Leibler penalty pulling attention towards a fixed guideline-derived key-lead map (M2, guideline-based attention guidance). Six diagnoses; five seeds per arm. Development on PTB-XL (21,799 ECGs); single sealed evaluation on PTB-XL fold 10 (2,198 ECGs) and on CODE-15% (233,204 exams, external validation). Primary endpoint: AUROC difference M2 - M1, averaged over first-degree AV block, right and left bundle branch block and atrial fibrillation and over 1 to 6 lost (zeroed) leads, with a patient-level paired BCa bootstrap 95% confidence interval. Results. The guidance did not change robustness: {Delta}AUROC -0.0010 (95% CI -0.0033 to +0.0006), an interval entirely within the pre-specified +-0.02 margin; the result was unchanged with another bootstrap seed, other interval methods and leave-one-diagnosis-out analyses. Masking improved AUROC: M1 - M0 = +0.0134 (95% CI +0.0102 to +0.0172) when one key lead was lost, and the number of lost leads tolerated before AUROC fell by more than 0.02 rose from 7 (M0) to 10 (M1). M2 attention matched the map and M2 was non-inferior on intact ECGs, but its calibration slope was lower for all six diagnoses in both datasets. M2 lost slightly more when all key leads were lost together (-0.0067) and gained only when one to three leads remained (exploratory; AUROC 0.9408 vs 0.9210 with 11 leads lost). CODE-15% reproduced every pattern (primary -0.0007, 95% CI -0.0011 to -0.0003). Conclusions. Random lead masking suffices to make an ECG classifier robust to missing leads; adding guideline knowledge aligns attention with clinical criteria but adds no robustness and worsens calibration. Guideline-aligned attention should not be taken as evidence of robustness.
Azamat, S.; Singh, A.; Midya, A.; Zhang, Z.; Gilkey, M.; Hajibonabi, F.; Sompalle, P.; Rastinehad, A.; Verma, S.; Kikano, E. G.; Sanda, M.; Hajiha, M. N.; Shiradkar, R.; Viswanath, S. E.; Madabhushi, A.
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Purpose: To evaluate whether visually assessed high-quality prostate MRI, as defined by the Prostate Imaging Quality (PI-QUAL) scoring system, is sufficient to ensure consistent AI model performance, or whether hidden acquisition-related technical effects introduce variability that cannot be detected through visual inspection. Methods: This retrospective study included 568 bpMRI scans from seven institutions, classified using PI-QUAL v2 into high-quality (scores 2-3) and low-quality (score 1) groups. Quantitative image quality features were extracted using MRQy from T2w and ADC sequences. Three experiments were conducted on high-quality scans: (1) unsupervised clustering to identify hidden technical batch effects; (2) V-Net models (M) for prostate capsule segmentation on T2w using single-cluster and balanced multi-cluster training strategies; and (3) VoxelMorph-based deformable registration (M2) to align ADC maps to T2w images. Performance metrics included DSC, precision, recall, volume ratio, HD95, ASSD, and TRE. Kruskal-Wallis tests assessed cross-cluster variability, Two One-Sided Tests (TOST) evaluated performance equivalence, and bootstrap resampling quantified training efficiency. Results: Clustering identified four clusters among 277 high-quality bpMRI scans. Single-cluster models showed variable performance (DSC=0.41-0.85) with significant batch effects (p<0.001), even with 140 training samples. The balanced multi-cluster model (n=60) eliminated batch effects (p=0.075), achieved equivalent performance (p<0.001), and demonstrated 2.23-fold greater training efficiency despite using 2.3-fold fewer samples. Registration performance also varied significantly across clusters (TRE=0.86-5.47 mm, p<0.001). Conclusion: Acquisition-related batch effects significantly impact AI generalizability in prostate MRI, even among high-quality scans. Quantitative clustering enables detection of technical variations and supports diversity-aware training strategies that achieve equivalent performance with 2.3-fold fewer samples while eliminating batch effects.
Dörfel, R. P.; Ozenne, B.
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Estimating the correlation between subject-specific rates of change is a common objective in longitudinal studies. A natural approach is to fit ordinary least squares regressions per subject and correlate the resulting slope estimates directly. Under complete data, this slopes-first estimator is algebraically equivalent to a contrast-based plug-in estimator derived from the joint variance-covariance matrix of the two signals across time. Under independent dropout, however, the slopes-first approach implicitly applies heterogeneous weights across missing-data patterns, introducing bias whenever the cross-covariance between the two signals is not constant over time. We formalise this result and propose an unbiased alternative that estimates the joint covariance matrix before applying the contrast. We further extend our results to include covariates as well. Simulations confirm that the slopes-first estimator is biased under non-constant cross-covariance while the proposed alternative remains unbiased. Further, we show in a real-world example that the two estimators can lead to different scientific conclusions and recommend that researchers working with longitudinal data inspect the missing data pattern to make an informed decision about the estimator of choice.
Pinheiro, A.; Cheng, H.; Karjadi, C.; Gifford, K.; Demissie, S.; Lunetta, K. L.; Liu, C.; Au, R.; Mohammed, S.
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INTRODUCTION: The digital clock drawing test (dCDT) is a cognitive screening tool capturing high-resolution pen-movement data. Existing approaches for classifying cognitive impairment from dCDTs rely on selected features or image-based methods. We propose representing dCDTs as structural networks to classify cognitive impairment and characterize spatial organization in clock drawings. METHODS: Weighted networks were constructed from 3,362 Framingham Heart Study participants, with and without cognitive impairment. Network representations were generated separately for command and copy conditions, with nodes representing pre-defined clock components (digits, hands, clock face) and edges capturing pairwise spatial relationships between components. Random forest models and graph convolutional networks were trained to predict cognitive impairment from the networks. Models were benchmarked against demographics-only and established summary feature baselines. RESULTS: Network-based models achieved AUC values comparable to the established summary feature baseline across command-only and copy-only conditions. Differences in spatial organization between the cognitively intact and impaired groups were greatest in the upper-right clock region, involving digits 1 and 2, the clock hands, and the surrounding clock face. Differences between the command and copy networks were larger among cognitively impaired participants. DISCUSSION: The proposed network representations provide an objective, scalable, and flexible framework for representing clock drawings for use in classification models. dCDT networks matched the predictive performance of established summary feature-based approaches and identified clock regions where spatial organization differed by cognitive status. After external validation, this approach has the potential to be incorporated within a clinical workflow to support automated and interpretable cognitive screening.
Kagawa, E.; Kato, M.; Hidaka, T.; Kunita, E.; Hironobe, N.; Matsui, S.; Kobayashi, Y.; Uotani, Y.; Teramoto, T.; Yoshii, K.; Okumoto, T.; Tani, M.; Dote, K.
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Background: Artificial intelligence (AI) may improve electrocardiographic differentiation of Takotsubo syndrome from acute anterior ST-segment elevation myocardial infarction (STEMI), but its impact on human diagnostic performance, the added value of visual explanations, and differences by reader background and experience remain uncertain. Methods: Using 12-lead electrocardiogram (ECG) images from two hospitals, we developed and externally validated an ensemble of three deep learning models after self-supervised pretraining and fine-tuning. The diagnostic task used ECGs recorded within 14 days after symptom onset, regardless of reperfusion status. We conducted a four-phase reader study. Phases 1-3 compared unaided interpretation, a reference sheet, and additional AI assistance. In Phase 4, readers evaluated a new ECG set after randomization to reference-sheet support alone, with AI predictions, or with AI predictions plus gradient-weighted class activation mapping (Grad-CAM) heatmaps. Diagnostic correctness was analyzed using generalized linear mixed-effects models. Exploratory analyses examined differences by cardiologist status and experience. Results: Development and external-validation cohorts, including healthy controls, comprised 832 and 95 participants, respectively. For Takotsubo-STEMI discrimination, external-validation accuracy was 0.914, with areas under the receiver operating characteristic and precision-recall curves of 0.970 and 0.984. Seventy healthcare providers completed the reader study. The estimated probability of correct diagnosis increased from 0.632 without assistance to 0.864 with AI assistance (odds ratio [OR], 3.71; P<0.001). In randomized Phase 4, AI assistance improved accuracy vs reference-sheet support alone (OR, 4.28; 95% CI, 3.08-5.95; P<0.001), and Grad-CAM provided additional benefit (OR, 1.53; 95% CI, 1.04-2.25; P=0.033). Exploratory analyses showed greater improvement among less experienced readers; with AI assistance, non-cardiologists outperformed cardiologists. AI-assisted readers remained less accurate overall than the model alone. Conclusions: An ECG image-based ensemble differentiated Takotsubo syndrome from anterior STEMI and improved reader accuracy. Visual explanations provided additional benefit, while experience-related differences highlight the importance of effective human-AI interaction.
Edelman, S.; Elias, U.; Arzy, S.
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Lesion network mapping (LNM) has provided a compelling framework in clinical neuroscience, linking focal brain damage at heterogeneous anatomical locations to shared functional networks across behavioural syndromes. Recently, the methodological specificity of LNM has come under discussion following observations that derived network maps tend to converge onto the normative connectome's generic degree distribution. While current efforts largely treat this convergence as a statistical inference challenge addressable via post-hoc spatial null models or individual-level analyses, we identify a foundational upstream measurement artifact operating within individual patients: the lesion "bystander effect". Because pathological lesions follow biological constraints rather than functional brain parcellations, a typical lesion encapsulates both a symptom-driving critical node and surrounding asymptomatic bystander tissue. By averaging connectivity profiles across the entire lesion mask, LNM mechanically dilutes focal clinical signals. Across empirical clinical cohorts, individual-level machine learning classifiers, synthetic within-cohort lesion unions, and whole-brain spherical simulations, we demonstrate that increasing lesion extent deterministically drives network maps toward the connectome degree vector following a mathematical power law. Fulfilling the clinical promise of LNM will therefore require computational strategies that isolate the causal functional core from surrounding bystander tissue prior to network projection.
Stipechi, L. V.; Craiem, D.; Gencer, U.; Casciaro, M. E.; Hulot, J.-S.; Hagege, A.; Soulat, G.; Mousseaux, E.
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Background: Transthoracic echocardiography (TTE) remains the gold standard for assessing left ventricular (LV) diastolic dysfunction (DD), but noninvasive alternatives are needed to overcome geometric and acoustic limitations. 4D-Flow MRI enables comprehensive assessment of intraventricular pressure differences (IVPDs) and flow propagation velocity (VP). We aimed to evaluate 4D-Flow-derived IVPDs and VP in patients with hypertrophic cardiomyopathy (HCM). Methods: Thirty-eight HCM patients and 38 age- and sex-matched healthy controls underwent TTE and 4D-Flow MRI. Spatiotemporal maps of velocity and IVPDs, decomposed into inertial and convective components, were derived along the main inflow streamline from the mitral valve to the apex. Peak early filling rate (PEFR) was used to normalize IVPDs and VP. Results: While absolute peak flow rates were comparable, HCM patients exhibited significantly faster VP (100.4 vs. 60.2 cm/s, p < 0.01) and higher positive early E IVPD (1.40 vs. 0.92 mmHg, p < 0.01) compared to controls. Normalizing IVPDs by PEFR amplified group differences, revealing a markedly increased flow-normalized E-IVPD (5.13 vs. 2.94 x 103 mmHg.ml1.s, p < 0.001) and deeper reverse ER IVPD (-6.06 vs. -4.61 x 103 mmHg.ml1.s, p < 0.01) in HCM. These differences were primarily driven by the inertial components. Multivariable analysis demonstrated that ER IVPD is independently determined by PEFR and the TTE E/E' ratio (r = 0.65, p < 0.001). Conclusions: 4D-Flow MRI-derived, flow-normalized IVPDs and propagation velocity provide robust, noninvasive markers of altered LV chamber stiffness and impaired diastolic filling in HCM, offering deeper 3D hemodynamic insights into diastolic dysfunction.
Buser, M.; Szczepanowski, M.; Laqua, A.; Chitadze, G.; Baldus, C.; Brueggemann, M.; Marr, C.
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Flow cytometry is central to clinical hematology, generating extensive archives comprising billions of single-cell profiles linked to expert-derived diagnostic summaries. While these records represent a largely untapped repository of collective expert knowledge, the underlying single-cell annotations required for supervised machine learning are typically not recorded in a standardized, accessible format. We present IMPGAT (implicit gating), a weakly supervised multiple-instance learning framework that reconstructs single-cell gating strategies directly from existing sample-level cell-type frequency distributions. The model utilizes an induced set attention mechanism to map single-cell marker profiles to specific cell populations, requiring neither explicit cell-level labels nor unsupervised clustering during training. We evaluate the framework on acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) cohorts, totaling 711 measurements from 268 individuals and 240 million single cells. In ALL, the model's quantification of cell-type abundances shows no statistically significant difference from human inter-expert variability. In AML, the framework achieves blast quantification on par with a recently established supervised state-of-the-art model that relies on explicit single-cell annotations for training. Error analysis shows that mismatches between model predictions and expert gating primarily involve expert-labeled non-cellular events, reflecting the non-incorporation of any explicit physical prior knowledge (such as the geometric relationships traditionally used to identify doublets and debris in scatter cytograms) in model training. Conversely, model certainty correlates with phenotypic borderline cases where manual bisection is inherently difficult. Our approach enables the systematic utilization of retrospective clinical records for the development of automated, standardized gating logic and is applicable to broader high-throughput contexts, such as large-scale immune monitoring or phenotypic drug screening.
Merritt, S.; Kindrachuk, J.; Nkamba, D.; Hoff, N. A.; Kalengi, H.; Halbrook, M.; Kamba, L.; Beya, M.; Petrichko, S.; Wallace, H. L.; Luhata, C.; Kaba, D.; Rimoin, A. W.
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We report general acceptance (79.0%) of Ebola vaccination in the Democratic Republic of the Congo (DRC) between 2023-2024 (n=5,062). Acceptance varied significantly by province with acceptance ranging from 47.6% in Kongo Central to 92.1% in Tshuapa province and was highest among healthcare workers. While Ebola vaccine acceptance and disease knowledge are relatively strong nationally in the DRC, regional differences do exist and may impact future vaccine rollout.
Simhal, A. K.; Lee, J.; Tan, K. S.; McCormick, P. J.; Fischer, G. W.; Scarpa, J. R.; Sapiro, G.; Mincer, J. S.
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PhenoAge, a blood-based biological aging clock, is associated with cancer outcomes, a finding taken as evidence that biological aging shapes prognosis. In 3,067 patients undergoing primary tumor resection, PhenoAge acceleration rose with tumor stage. One or two of its eight blood components, differing by cancer type, carried the prognostic signal, and replacing its general-population weights with equal weights did not weaken it. In cancer, PhenoAge may reflect disease burden rather than biological aging.
Mao, S.; McMillan, H.; Leone, J. D.; Barbon, C. E. A.; Buoy, S. N.; Brock, K. K.; Lai, S.; Naser, M. A.; Fuller, C. D.; Hutcheson, K. A.; InHANCE Research Program Working Group,
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Purpose: Posterior pharyngeal wall (PPW) thickening is a common structural manifestation of treatment-related internal lymphedema in patients with head and neck cancer and can be evaluated using lateral videofluoroscopic images acquired during modified barium swallow (MBS) studies. However, no standardized method currently exists for quantitative measurement. Methods: This two-phase methodological study first conducted a scoping review to characterize existing approaches to PPW thickness measurement and identify the principal factors contributing to variation in PPW thickness measurement. Eight studies were identified with variation observed across these measurement factors. An empirical reliability study was then performed using 107 MBS studies from 93 Head and Neck Cancer patients. Two independent raters annotated 10 anatomical landmarks on pre-swallow and post-swallow resting frames, and a computer-assisted algorithm quantitatively generated seven candidate PPW thickness measurements based on different vertebral reference points and measurement directions. Reliability was assessed intraclass correlation coefficients (ICCs). Results: Inter-rater reliability was highest for the measurement originating from the midpoint of C3 and extending perpendicular to the anterior C3 surface (ICC, 0.78; 95% CI, 0.72-0.83). Among the normalization references, C2-C4 vertebral length demonstrated greater reliability than C3 vertebral length, with an ICC of 0.88 (95% CI, 0.85-0.91). No significant differences were observed between pre-swallow and post-swallow PPW thickness measurements across the evaluated approaches. Conclusions: These findings provide a methodological foundation for more standardized and reliable quantification of PPW thickness, with potential to expand the role of MBS from the functional evaluation of swallowing to include quantitative characterization of pharyngeal structural abnormalities.
Beste, N. C.; Bauer, F.; Lopez, N.; Schoemig, T.; Schoenfeld, M.; Zopfs, D.; Goertz, L.; Persigehl, T.; Kabbasch, C.; Schlamann, M.; Maintz, D.; Gertz, R. J.; Weitzer, N.; Kottlors, J.
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Objectives: To determine how strongly clinical referral text, rather than image content, drives the decisions of multimodal large language models (LLMs) differentiating glioma from brain abscess on MRI. Materials and methods: This retrospective single-center study included 60 contrast-enhanced T1-weighted brain MRI examinations (30 gliomas, 30 abscesses; reference-standard diagnosis). One axial slice per case was paired with five referral texts (explicitly inflammatory to explicitly tumor-suggestive) under three prompt instructions and submitted 20 times each to GPT-4o, Claude Sonnet 5, Gemini 3.5 Flash, and Qwen 3.6 (72,000 answers). The primary outcome was the text-driven span (difference in tumor-call frequency between explicit inflammatory and explicit tumor text). Two blinded radiologists classified the images without text; sensitivity, specificity, and accuracy were compared descriptively. Results: Patients (29 women) had a mean age of 55.8 +/- 16.4 years. With neutral text, models answered tumor in 45-67% of queries (specificity, 0.38-0.78), versus 52% and 60% for radiologists (specificity, 0.77 and 0.63). The text-driven span was 0.79-1.00 (p < 0.001 for all models), whereas confirmed gliomas and abscesses differed by only 0.01-0.10 in three models and 0.25 in Gemini 3.5 Flash. Subtle wording produced at least 83% of the span in three models. An instruction to ignore the text reduced the span to 0.48-0.70 in three models and to 0.04 in Gemini 3.5 Flash, partly through reversion to a tumor default. Model accuracy was 0.52-0.73 versus 0.78 and 0.73 for radiologists. Conclusion: Multimodal LLMs deferred to referral text over imaging evidence in differentiating glioma from brain abscess, and prompt instructions did not reliably correct this.
GODINEZ VAZQUEZ, V. J.
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Background: Commercial spaceflight now carries civilians on short missions, yet their stress-axis physiology is poorly described. Earlier shuttle data suggest that sympathetic responses predominate after short flights and glucocorticoid responses after long ones. The neutrophil-to-lymphocyte ratio (NLR) is a low-cost readout of both. Methods: Preregistered secondary analysis of open clinical laboratory data (NASA Open Science Data Repository OSD-569 and OSD-575) from the four Inspiration4 crew members, each sampled seven times: three draws before launch, one the day after return (R+1) and three during recovery (R+45 to R+194). Log-transformed NLR was modelled with a linear mixed model with a random intercept per crew member and Kenward-Roger inference. Lymphocyte and eosinophil counts and C-reactive protein were secondary outcomes with false discovery rate correction. Results: All 28 draws were analysed. NLR at R+1 did not differ from pre-flight (fold change 1.04; 95% CI 0.81 to 1.34; p = 0.73); two crew members increased (+25% and +46%) and two decreased (-27% and -11%). During recovery NLR was 23% lower than pre-flight (fold change 0.77; 95% CI 0.64 to 0.92; p = 0.005). No secondary outcome changed after correction; lymphocytes were 18% lower at R+1 (95% CI -35% to +4%; q = 0.31). Between-person differences explained 58% of the variance. An ordinary regression ignoring repeated measures missed the recovery effect (p = 0.08). Conclusions: A 3-day orbital flight produced no consistent leukocyte stress signature one day after return. The lower NLR during recovery suggests that pre-flight values, not recovery values, deviate from the resting state, which has implications for how baselines are defined in short-duration spaceflight studies.