RATIONALE AND OBJECTIVES:Previous studies suggest that "drilling" (eyes fixated at one location within a slice while scrolling rapidly between computed tomography (CT) slices) may be more effective than "scanning" (eyes move rapidly to search within each slice while scrolling slowly between slices) for detecting lesions, but evidence has been limited. The purpose of this study is to examine the association between sensitivity and either drilling or scanning for liver metastasis detection. MATERIALS AND METHODS:Twenty-five radiologists blinded to clinical and previous imaging information marked all suspected hepatic metastases in 40 contrast-enhanced liver CT exams while being monitored by eye-tracking technology. Eye movements were registered to the corresponding liver segment and slice. All livers and proven metastases were demarcated into Couinaud segments. Outcome measures included metastasis detection (sensitivity), interpretation time, average rate of scrolling, and average rate of segment change. RESULTS:There were 91 metastases, and mean sensitivity was 83%. In univariate analysis, higher reader sensitivity was associated with longer interpretation time (adjusted R2 = 0.35, regression coefficient = 5.25, p = 0.002) and smaller segment change rate (i.e., drilling) (adjusted R2 = 0.23, regression coefficient = -4.54, p = 0.009). Scrolling rate was not associated with sensitivity (p=0.37). A regression model predicting sensitivity from both interpretation time and segment change rate yielded an adjusted R2 of 0.43. CONCLUSION:Drilling may outperform scanning in sensitivity for detection of liver metastases when measured as segment change rate, but not as scrolling rate. Longer interpretation time is independently associated with higher sensitivity.

INTRODUCTION:Acute hypoxia can impair cognitive performance, yet the underlying systemic and cerebral physiological mechanisms remain unclear. The objective of this study was to elucidate the systemic and cerebral physiological responses associated with changes in cognitive performance during acute hypoxia. METHODS:There were 11 healthy subjects (5 females) who completed a cognitive test during baseline normoxia (21% fraction of inspired oxygen, FIO2) followed by 2 randomized hypoxia trials: 11.8% FIO2 (moderate hypoxia) and 7.7% FIO2 (severe hypoxia). Subjects were instrumented with an arterial catheter, transcranial doppler ultrasound, and near-infrared spectroscopy to measure systemic (arterial O2 saturation) and cerebral oxygenation (cerebrovascular conductance and cerebral tissue saturation). RESULTS:Moderate hypoxia reduced arterial O2 saturation and cerebral tissue saturation, with no change in cerebrovascular conductance. Severe hypoxia decreased arterial O2 saturation, cerebrovascular conductance, and cerebral tissue saturation. Cognitive performance did not differ from baseline during either hypoxia condition (omission rate, errors/min: baseline 0 ± 1 vs. moderate hypoxia 1 ± 1; baseline 1 ± 1 vs. severe hypoxia 1 ± 1). No associations were observed between physiological changes and cognitive performance during moderate hypoxia. During severe hypoxia, smaller declines in arterial O2 saturation (r = 0.643) and greater declines in cerebrovascular conductance (r = -0.651) were associated with increased omission rates. DISCUSSION:Cognitive performance during acute severe hypoxia correlated with cerebral oxygenation and blood flow. Associations differed between moderate and severe hypoxia, suggesting that both duration and severity of hypoxia influence the relationship between physiological responses and cognitive performance.

Since its introduction in 2002, left atrial appendage closure (LAAC) has rapidly expanded as an alternative to anticoagulation in patients with atrial fibrillation at high risk of stroke. Harmonized processes for data collection, analysis, and reporting in LAAC trials are essential to enhance research quality and improve clinical practice. The Left Atrial Appendage Academic Research Consortium (LAARC) initiative is an independent collaboration of academic research organizations, cardiology and neurology experts, clinical trialists, and regulatory authorities from the USA, Europe, and Asia. The consortium engaged clinical experts, regulators-including the US Food and Drug Administration (FDA), European Notified Bodies, and Japan's Pharmaceuticals and Medical Devices Agency (PMDA)-and industry leaders to define standardized study elements and endpoints for LAAC trials. Key considerations included alignment with prior Academic Research Consortium initiatives, procedural and mechanistic insights, and clinical relevance. Consensus definitions were proposed for mortality, stroke, bleeding, and device performance, along with composite endpoints for safety and effectiveness. The proposed LAARC consensus definitions aim to standardize endpoint reporting, improve comparability across studies, and support regulatory and clinical trial applications for this evolving therapy through broad dissemination in the peer-reviewed literature.

Background:The ability to quantify uncertainty is a desirable feature of explainable artificial intelligence systems. In the case of segmentation models, however, practical clinical applications for uncertainty estimates have been under-explored and most studies are limited to simple single-class problems. The goal of this work is to expand uncertainty analysis to more complex segmentation problems and to evaluate the feasibility of using uncertainty information as a marker of potential pathology. Methods:Using the publicly available TotalSegmentator model, and a custom Multi-Organ Test-Time Augmentation (TTA) pipeline, abdominal segmentation uncertainty was characterized across 14 total organs and 8 total augmentations. Uncertainty was defined as the average entropy across the predicted probabilities for the augmented versions of the provided input image and quantified at an organ and augmentation level by averaging the entropy values within a dilated mask of the target structure. Uncertainty performance was characterized in 872 total abdominal computed tomography cases, and an additional 489 cases were used to evaluate the sensitivity of uncertainty estimates to pathology in the pancreas, liver, colon and kidneys where ground truth was available. Results:Uncertainty estimates were found to be significantly higher in pathologic tissue versus healthy tissue regardless of the organ considered (pancreas: P=1.79e-05; liver: P=8.83e-23; colon: P=1.36e-26; right kidney: P=2.49e-57; left kidney: P=1.43e-50). Receiver operating characteristic analysis of the uncertainty maps highlighted fair voxel-level pathology detection performance in the pancreas [area under the curve (AUC): 0.7097], colon (AUC: 0.7316), and left kidney (AUC: 0.7605), good performance in the right kidney (AUC: 0.8134) and excellent performance in the liver (AUC: 0.8885). Conclusions:TTA-derived uncertainty estimates have been proved useful as a tool for detecting pathology across multiple organ systems. With future development, a tool such as this could prove useful in early screening for pathology, or in an active learning scheme to identify regions in need of manual intervention.

Four-dimensional computed tomography (4DCT) can be used to quantify joint mechanics during dynamic tasks. Post-processing of 3D anatomical renderings permits calculation of joint surface arthrokinematics. Given the complexity and high dimensionality of arthrokinematic data, as well as variations in interparticipant morphology, sophisticated analytical techniques permitting comparisons between participants and throughout motion cycles are needed. Statistical parametric mapping (SPM) has been applied to biomechanical and imaging datasets to overcome this challenge; however, applications to 4DCT remain under-explored. The proposed pipeline is demonstrated at the distal radioulnar joint (DRUJ). This application explores relationships between wrist position (a continuous variable) and arthrokinematic interosseous proximities (a surface-based measure) in two contexts. Static-neutral CT data from 30 normative participants are used in the first application. Bilateral 4DCT pronosupination arcs from two participants with unilateral injury are included in the second application. A canonical joint was created using a multi-level, multi-object statistical shape model, on which the articular surface of interest was defined. Participant-specific joint surfaces were predicted from the canonical template via non-linear morphing. SPM regression and generalized linear models were used to explore relationships between wrist position, injury status, and interosseous proximities. The analysis captured position-related differences in interosseous proximities, demonstrating the application of this pipeline to 3DCT-and 4DCT-derived arthrokinematics. As hypothesized, increased pronation was associated with increased proximities at the sigmoid notch volar margin. The proposed pipeline can be applied to other joints, functional tasks, experimental conditions, or injury states to quantify how arthrokinematics are related to both continuous and categorical variables.

Background The burden and pathophysiologic mechanisms of myocardial infarction (MI) in younger patients remain understudied. Prior studies have been limited by selected cohorts and lack of awareness of nonatherothrombotic causes. Objectives We sought to determine the incidence and outcomes of MI according to a unique pathophysiologic mechanism in a large community cohort aged ≤65 years, and to evaluate sex-differences in etiology Methods We identified all residents of Olmsted County, Minnesota, USA, age ≤65 years who experienced an event associated with a cardiac troponin T >99th percentile of upper reference range (≥0.01 ng/mL) from January 2003 to March 2018. Records and imaging were individually scrutinized. Patients classified as MI were assigned to 1 of 6 adjudicated pathophysiologic mechanisms: atherothrombosis, spontaneous coronary artery dissection (SCAD), embolism, vasospasm, myocardial infarction with nonobstructed coronary arteries not meeting another category (MINOCA-U), and supply/demand mismatch secondary myocardial infarction. We determined incidence and long-term all-cause and cardiovascular mortality for each group. Results There were 4,116 myocardial injury events in 2,780 patients (36% women) over 15 years. Excluding periprocedural MI, 1,474 events were classified as index MI, of which 68% were caused by atherothrombosis. The population incidence of MI was much lower in women, particularly in MI caused by atherothrombosis (48 vs 137 per 100,000 person years and 23 vs 105 per 100,000 person-years). Incidence of SCAD was much higher in women (3.2 vs 0.9 per 100,000 person-years) with 55% of cases misclassified as MINOCA or atherothrombosis at index presentation. Women with atherothrombosis were similar in age to men (55 ± 8 years vs 54 ± 8 years), with similar disease extent at angiography but greater burden of risk factors. Proportionately, nonatherothrombotic causes comprised the majority of MI in women (atherothrombosis 47% vs 75%, secondary myocardial infarction [SSDM] 34% vs 19%, SCAD 11% vs 0.7%, embolism 2% vs 2%, vasospasm 3% vs 1%, MINOCA-U 3% vs 2%). The 5-year all-cause mortality was highest after SSDM (SSDM 33%, atherothrombosis 8%, embolism 8%, SCAD 0%) with low cardiovascular mortality in all groups. Conclusions This community-based study demonstrates nonatherothrombotic causes comprise an important burden of acute MI in persons age ≤65 years, particularly women. These cause-specific findings have implications for individualized management and risk stratification and provide epidemiologic benchmarking for future studies.

Background Percutaneous left atrial appendage occlusion (LAAO) is an alternative to long‐term anticoagulation for preventing ischemic stroke in patients with atrial fibrillation. There are limited long‐term outcomes data for “real‐world” patients undergoing LAAO. Methods We performed a retrospective cohort study using the National Cardiovascular Data Registry LAAO registry from January 1, 2016, through December 31, 2019. We linked LAAO data to inpatient Medicare fee‐for‐service claims data using probabilistic matching to establish a cohort of patients 65 years and older undergoing LAAO with a WATCHMAN device. The primary outcomes were any stroke and all‐cause mortality. Results A total of 34 975 patients with a mean±SD CHA2DS2‐VASc (congestive heart failure, hypertension, age ≥75 years, diabetes, previous stroke or transient ischemic attack, vascular disease, age 65 to 74 years, and sex category) score of 4.7±1.4 were included. The median follow‐up was 2.8 years (interquartile range, 2.2–3.7 years). The cumulative incidence of any stroke was 1.57 per 100 person‐years (95% CI, 1.45–1.70), with a 1‐year and 5‐year any stroke estimate of 1.70% (95% CI, 1.57–1.84%) and 5.70% (95% CI, 5.37–6.05%), respectively. The cumulative incidence of ischemic stroke was 1.36 per 100 person‐years (95% CI, 1.25–1.48), with a 1‐year and 5‐year ischemic stroke estimate of 1.42% (95% CI, 1.30–1.54%) and 5.03% (95% CI, 4.71–5.36%), respectively. The cumulative incidence of death was 10.82 per 100 person‐years (95% CI, 10.49–11.13), with a 5‐year mortality estimate of 44.34% (95% CI, 43.35–45.23%). Conclusions Long‐term stroke rates in a large nationally representative cohort of Medicare patients following LAAO were low and durably consistent during long‐term follow‐up despite a high thromboembolic risk. High mortality rates in this elderly population underscore the importance of incorporating patient values and preferences when considering LAAO.

Growing evidence has demonstrated the clinical benefit of percutaneous left atrial appendage closure (LAAC) in patients with atrial fibrillation. Although procedural complication rates have declined with increasing experience, post-procedural device-related complications persist, impacting prognosis and reducing the long-term benefits of the procedure. Given the potential impact of these complications, surveillance imaging after LAAC is mandatory. Currently, different imaging modalities offer unique advantages to manage these complications which warrant a combined approach to optimize both short- and long-term follow-up. The aims of this review are to explore the distinct characteristics of each imaging modality, highlighting the primary findings to be assessed during follow-up imaging. Additionally, we propose an optimized clinical imaging surveillance roadmap from discharge to long-term follow-up.

Predicting post-Percutaneous Coronary Intervention (PCI) outcomes is crucial for effective patient management and quality improvement in healthcare. However, achieving accurate predictions requires the integration of multimodal clinical data, including physiological signals, demographics, and patient history, to estimate prognosis. The integration of such high-dimensional, multi-modal data presents a significant challenge due to its complexity and the need for sophisticated analytical methods. Our study focuses on comparative performance analysis for state-of-theart vision transformer (ViT) and proposed a novel multi-branch CNN model with block attention for multimodal data analysis in a joint fusion framework. To design a comparative model for ViT, we proposed a new joint fusion architecture that consists of a convolutional neural network (CNN) with a convolutional block attention module (CBAM). We integrate images of electrocardiogram (ECG) data and tabular electronic health records (EHR) of 13,064 subjects, considering 6871 samples for training and 6193 for testing (stratified sampling) in order to predict 3 clinically relevant post-PCI (6 months) clinical endpoints - heart failure, all-cause mortality, and stroke. The learned representations are combined at an intermediate layer, followed by processing these representations using a fully connected layer. The proposed model demonstrates excellent performance with the highest AUROC scores of 0.849, 0.913, and 0.794 for predicting heart failure, all-cause mortality, and stroke, respectively. Surpassing the baseline EHR model and ViT, the proposed CNN + CBAM fusion model showcases superior predictive capabilities for heart failure prediction (DeLong's test p-value = 0.043) which highlights the importance of preserving local spatial features via CNN low-level filters and semi-global dependency using block attention. Without using any laboratory test results and vital data, we obtained state-of-the-art performance using ECG image directly using proposed attention based CNN model and outperformed the ViT baseline. Proposed multimodal integration strategy would lead to the development of more accurate, mutlimodal data-driven models for predicting PCI outcomes. As a result, cardiologists could better tailor treatment plans, optimize patient management strategies, and improve overall clinical outcomes after the complex PCI procedure.

Background Aortic stenosis (AS) is a complex condition with various hemodynamic subtypes, each with distinct clinical profiles and outcomes. This study aimed to assess the characteristics and outcomes of different AS phenotypes based on flow and gradient patterns. Methods In this retrospective cohort study, we included 930 patients who underwent transcatheter aortic valve replacement (TAVR) for severe symptomatic AS at Mayo Clinic sites from 2012-2017. Patients were classified into three groups: high gradient (HG), low-flow low-gradient (LFLG), and normal-flow low-gradient (NFLG). Baseline clinical, echocardiographic, and computed tomography (CT) characteristics, including aortic valve area (AVA), aortic valve calcium score (AVCS), left ventricular ejection fraction (LVEF), and the prevalence of tricuspid regurgitation (TR) and atrial fibrillation were analyzed. One- and five-year all-cause mortality outcomes were compared using Kaplan-Meier analysis and Cox proportional hazards models. Results The final cohort included 273 patients in the NFLG group (29.4%), 563 in the HG group (60.5%), and 94 in the LFLG group (10.1%). After reevaluation and careful review of the echocardiograms, 41 NFLG patients were reclassified into the LFLG group. LFLG patients had the highest prevalence of atrial fibrillation/flutter (60%) and TR (17%). AVCS was significantly lower in NFLG compared to HG and LFLG groups. One-year mortality was highest in the LFLG group (17.4%), followed by HG (13.9%) and NFLG (10.9%), but the difference was not statistically significant (p=0.2). Five-year mortality rate was higher in the LFLG group (55.6%) compared to NFLG (47.2%) and HG (47.9%) but did not reach statistical significance (p=0.2). Conclusions LFLG AS is associated with more comorbidities and higher mortality compared to HG and NFLG groups, though differences in mortality were not statistically significant. The NFLG group, after close review and reclassification, showed the least significant AS. Randomized trials are needed to clarify the prognosis and management of NFLG AS.

The distal radioulnar joint (DRUJ) is a load-bearing joint that permits pronosupination of the forearm. Pronosupination may provoke instability following injuries to the soft tissue stabilizers of the joint, particularly when loaded against resistance. The objective of this study was to assess osteokinematics between the radius and ulna during pronosupination in 12 participants with suspected unilateral DRUJ injury enrolled in a prospective study using four-dimensional computed tomography (4DCT) at baseline and six months after arthroscopic surgery. We hypothesized that inter-landmark distances between the ulnar styloid and three landmarks on the distal radius—the central reference point, dorsal corner, and volar corner—would be related to relative pronosupination position, wrist injury status (injured versus uninjured), application of load (unresisted versus resisted), and timepoint (preoperative versus postoperative). Generalized linear mixed effects models were created to assess the change in inter-landmark distances with different levels of the predictor variables. Inter-landmark distances at all three radius landmarks were significantly associated with pronosupination angle and application of resistance. The effects of injury and surgery were less consistent and, if present, significant at only the volar corner landmark. The random effect for participant was statistically significant in all models. 4DCT-derived osteokinematics reflect position in the pronosupination arc and the application of resistance. However, the effect of injury or intervention was not statistically significant in the majority of single-landmark models. This suggests that 4DCT detects changes in biomechanical phenomena, although more sophisticated biomarkers may be justified for injury classification.

BACKGROUND:Transcatheter left atrial appendage occlusion (LAAO) is an alternative to lifelong anticoagulation, but optimal patient selection remains challenging. OBJECTIVES:This study sought to apply a novel causal machine learning framework to identify patients who would benefit from LAAO vs a direct oral anticoagulant (DOAC). METHODS:We identified 744,190 adult patients with atrial fibrillation treated with either LAAO or DOAC between March 13, 2015, and December 31, 2019, using data from OptumLabs Data Warehouse. One-to-one propensity score matching was used to create a cohort where patients were similar in 107 baseline characteristics. A causal forest model was used to estimate the heterogeneous treatment effect for a composite outcome of ischemic stroke, systemic embolism, major bleeding, and all-cause mortality. RESULTS:In the matched cohort of 28,930 patients, the mean age was 76.8 ± 6.3 years; 5,818 patients (40%) were female, and the mean CHA2DS2-VASc score was 5.8. LAAO was associated with no difference with the primary composite outcome in comparison to NOAC early on (average treatment effect of -0.68% [-1.4%, 0.06%] at 1 year), but a lower risk at the end of 2 years (average treatment effect of -2.9% [-3.7%, -2.0%]). At the end of 2 years, 30.1% of the overall cohort were classified as potentially benefiting from LAAO, 69.7% were classified as neutral, and 1.4% were potentially harmed by LAAO. CONCLUSIONS:Novel machine learning algorithms were developed to identify patients who are more likely to benefit from LAAO vs DOACs. This information can support clinical decision-making to determine which patients should be referred to subspecialists for further examination and discussion of LAAO.

BACKGROUND:SynthesiZed Improved Resolution and Concurrent nOise reductioN (ZIRCON) is a multi-kernel synthesis method that creates a single series of thin-slice computed tomography (CT) images displaying low noise and high spatial resolution, increasing reader efficiency and minimizing partial volume averaging. PURPOSE:To compare the diagnostic performance of a single set of ZIRCON images to two routine clinical image series using conventional CT head and bone reconstruction kernels for diagnosing intracranial findings and fractures in patients with trauma or suspected acute neurologic deficit. MATERIAL AND METHODS:In total, 50 patients underwent clinically indicated head CT in the ER (15 normal, 35 abnormal cases). A non-reader neuroradiologist established the reference standard. Three neuroradiologists reviewed two routine clinical series (head and bone kernels) and a single ZIRCON series, detecting intracranial findings or fractures and rating confidence (0-100). Sensitivity, specificity, and jackknife free-response receiver operating characteristic (JAFROC) figure of merit (FOM) were compared (limit of non-inferiority: -0.10). RESULTS:ZIRCON and conventional images demonstrated comparable performance for fractures (sensitivity: 51.5% vs. 54.5%; specificity: 40.2% vs. 34.2%) and intracranial findings (sensitivity: 88.2% vs. 91.4%; specificity: 77.2% vs. 73.7%).The estimated difference of JAFROC FOM demonstrated ZIRCON non-inferiority for acute pathologies overall (0.003 [95% CI=-0.051-0.057]) and fractures (0.048 [95% CI=-0.050-0.145]) but not for intracranial findings alone (-0.024 [95% CI=-0.100-0.052]). CONCLUSION:Thin-slice, low noise, and high spatial resolution images can be created to display intracranial findings and fractures replacing multiple images series in head CT with similar performance. Future studies in more patients and further algorithmic development are warranted.

ABSTRACT Phage therapy has not been established in the clinical routine, in part due to uncertainties concerning efficacy and immunogenicity. Here, three rabbits were immunized against staphylococcal phage K to assess viral potency in the presence of immunized serum. Three rabbits received weekly intramuscular injections of ~10 10±1 pfu/mL phage K. Phage K-specific IgG formation was measured by an enzyme-linked immunosorbent assay (ELISA); phage inactivation was assessed by calculating K-rates. Using transmission electron microscopy (TEM) and immunogold labeling, antibody binding to phage K was visualized. This was numerically assessed by objective imaging analysis comparing the relative distances of each gold particle to the nearest phage head and tail structure. Immunization led to a strong IgG response, plateauing 7 days after the last phage injection. There was no significant correlation between K-rate and antibody titer over time. TEM showed IgG binding to the head structure of phage K. Image analysis showed a significant reduction in relative distances between antibodies and phage head structures when comparing samples from day 0 and day 28 ( P < 0.0001). These results suggest that while individual serum analysis for antibodies against therapeutic phage bears consideration prior to and with prolonged therapy, during phage application, the formation of specific antibodies against phage may only partially explain decreased phage potency in the presence of immunized serum. Instead, other factors may contribute to an individual’s “humoral receptiveness” to phage therapy. Future investigations should be directed toward the identification of the humoral factors that have the most significant predictive value on phage potency in vivo .

BACKGROUND AND PURPOSE: Progressive MS is typically heralded by a myelopathic pattern of asymmetric progressive motor weakness. Focal individual ?critical? demyelinating spinal cord lesions anatomically associated with progressive motor impairment may be a compelling explanation for this clinical presentation as described in progressive solitary sclerosis (single CNS demyelinating lesion), progressive demyelination with highly restricted MR imaging lesion burden (2?5 total CNS demyelinating lesions; progressive paucisclerotic MS), and progressive, exclusively unilateral hemi- or monoparetic MS (>5 CNS demyelinating progressive unilateral hemi- or monoparetic MS [PUHMS] lesions). Critical demyelinating lesions appear strikingly similar across these cohorts, and we describe their specific spinal cord MR imaging characteristics. MATERIALS AND METHODS: We performed a retrospective, observational MR imaging study comparing spinal cord critical demyelinating lesions anatomically associated with progressive motor impairment with any additional ?noncritical? (not anatomically associated with progressive motor impairment) spinal cord demyelinating lesions. All spinal cord MR images (302 cervical and 91 thoracic) were reviewed by an experienced neuroradiologist with final radiologic assessment on the most recent MR imaging. Anatomic association with clinical progressive motor impairment was confirmed independently by MS subspecialists. RESULTS: Ninety-one individuals (PUHMS, 37 [41%], progressive paucisclerosis 35 [38%], progressive solitary sclerosis 19 [21%]) with 91 critical and 98 noncritical spinal cord MR imaging demyelinating lesions were evaluated. MR imaging characteristics that favored critical spinal cord demyelinating lesions over noncritical lesions included moderate-to-severe, focal, lesion-associated spinal cord atrophy: 41/91 (45%) versus 0/98 (0%) (OR, 161.91; 9.43 to >999.9); lateral column axial location (OR, 10.43; 3.88?28.07); central region (OR, 3.23; 1.78?5.88); ventral column (OR, 2.98; 1.55?5.72); and larger lesion size of the axial width (OR, 2.01;1.49?2.72), transverse axial size (OR, 1.66; 1.36?2.01), or lesion area (OR, 1.14; 1.08?1.2). Multiple regression analysis revealed focal atrophy and lateral axial location as having the strongest association with critical demyelinating lesions. CONCLUSIONS: Focal, lesion-associated atrophy, lateral column axial location, and larger lesion size are spinal cord MR imaging characteristics of critical demyelinating lesions. The presence of critical demyelinating lesions should be sought as these features may be associated with the development of progressive motor impairment in MS.