Inflammatory risk and cardiovascular events in patients without obstructive coronary artery disease: the ORFAN multicentre, longitudinal cohort study.

BACKGROUND: Coronary computed tomography angiography (CCTA) is the first line investigation for chest pain, and it is used to guide revascularisation. However, the widespread adoption of CCTA has revealed a large group of individuals without obstructive coronary artery disease (CAD), with unclear prognosis and management. Measurement of coronary inflammation from CCTA using the perivascular fat attenuation index (FAI) Score could enable cardiovascular risk prediction and guide the management of individuals without obstructive CAD. The Oxford Risk Factors And Non-invasive imaging (ORFAN) study aimed to evaluate the risk profile and event rates among patients undergoing CCTA as part of routine clinical care in the UK National Health Service (NHS); to test the hypothesis that coronary arterial inflammation drives cardiac mortality or major adverse cardiac events (MACE) in patients with or without CAD; and to externally validate the performance of the previously trained artificial intelligence (AI)-Risk prognostic algorithm and the related AI-Risk classification system in a UK population. METHODS: This multicentre, longitudinal cohort study included 40 091 consecutive patients undergoing clinically indicated CCTA in eight UK hospitals, who were followed up for MACE (ie, myocardial infarction, new onset heart failure, or cardiac death) for a median of 2·7 years (IQR 1·4-5·3). The prognostic value of FAI Score in the presence and absence of obstructive CAD was evaluated in 3393 consecutive patients from the two hospitals with the longest follow-up (7·7 years [6·4-9·1]). An AI-enhanced cardiac risk prediction algorithm, which integrates FAI Score, coronary plaque metrics, and clinical risk factors, was then evaluated in this population. FINDINGS: In the 2·7 year median follow-up period, patients without obstructive CAD (32 533 [81·1%] of 40 091) accounted for 2857 (66·3%) of the 4307 total MACE and 1118 (63·7%) of the 1754 total cardiac deaths in the whole of Cohort A. Increased FAI Score in all the three coronary arteries had an additive impact on the risk for cardiac mortality (hazard ratio [HR] 29·8 [95% CI 13·9-63·9], p<0·001) or MACE (12·6 [8·5-18·6], p<0·001) comparing three vessels with an FAI Score in the top versus bottom quartile for each artery. FAI Score in any coronary artery predicted cardiac mortality and MACE independently from cardiovascular risk factors and the presence or extent of CAD. The AI-Risk classification was positively associated with cardiac mortality (6·75 [5·17-8·82], p<0·001, for very high risk vs low or medium risk) and MACE (4·68 [3·93-5·57], p<0·001 for very high risk vs low or medium risk). Finally, the AI-Risk model was well calibrated against true events. INTERPRETATION: The FAI Score captures inflammatory risk beyond the current clinical risk stratification and CCTA interpretation, particularly among patients without obstructive CAD. The AI-Risk integrates this information in a prognostic algorithm, which could be used as an alternative to traditional risk factor-based risk calculators. FUNDING: British Heart Foundation, NHS-AI award, Innovate UK, National Institute for Health and Care Research, and the Oxford Biomedical Research Centre.

Predicting Lipid-Rich Plaque Progression in Coronary Arteries Using Multimodal Imaging and Wall Shear Stress Signatures.

BACKGROUND: Plaque composition and wall shear stress (WSS) magnitude act as well-established players in coronary plaque progression. However, WSS magnitude per se does not completely capture the mechanical stimulus to which the endothelium is subjected, since endothelial cells experience changes in the WSS spatiotemporal configuration on the luminal surface. This study explores WSS profile and lipid content signatures of plaque progression to identify novel biomarkers of coronary atherosclerosis. METHODS: Thirty-seven patients with acute coronary syndrome underwent coronary computed tomography angiography, near-infrared spectroscopy intravascular ultrasound, and optical coherence tomography of at least 1 nonculprit vessel at baseline and 1-year follow-up. Baseline coronary artery geometries were reconstructed from intravascular ultrasound and coronary computed tomography angiography and combined with flow information to perform computational fluid dynamics simulations to assess the time-averaged WSS magnitude (TAWSS) and the variability in the contraction/expansion action exerted by WSS on the endothelium, quantifiable in terms of topological shear variation index (TSVI). Plaque progression was measured as intravascular ultrasound-derived percentage plaque atheroma volume change at 1-year follow-up. Plaque composition information was extracted from near-infrared spectroscopy and optical coherence tomography. RESULTS: Exposure to high TSVI and low TAWSS was associated with higher plaque progression (4.00±0.69% and 3.60±0.62%, respectively). Plaque composition acted synergistically with TSVI or TAWSS, resulting in the highest plaque progression (≥5.90%) at locations where lipid-rich plaque is exposed to high TSVI or low TAWSS. CONCLUSIONS: Luminal exposure to high TSVI, solely or combined with a lipid-rich plaque phenotype, is associated with enhanced plaque progression at 1-year follow-up. Where plaque progression occurred, low TAWSS was also observed. These findings suggest TSVI, in addition to low TAWSS, as a potential biomechanical predictor for plaque progression, showing promise for clinical translation to improve patient prognosis.

MSO-GP: 3-D segmentation of large and complex conjoined tree structures.

Robust segmentation of large and complex conjoined tree structures in 3-D is a major challenge in computer vision. This is particularly true in computational biology, where we often encounter large data structures in size, but few in number, which poses a hard problem for learning algorithms. We show that merging multiscale opening with geodesic path propagation, can shed new light on this classic machine vision challenge, while circumventing the learning issue by developing an unsupervised visual geometry approach (digital topology/morphometry). The novelty of the proposed MSO-GP method comes from the geodesic path propagation being guided by a skeletonization of the conjoined structure that helps to achieve robust segmentation results in a particularly challenging task in this area, that of artery-vein separation from non-contrast pulmonary computed tomography angiograms. This is an important first step in measuring vascular geometry to then diagnose pulmonary diseases and to develop image-based phenotypes. We first present proof-of-concept results on synthetic data, and then verify the performance on pig lung and human lung data with less segmentation time and user intervention needs than those of the competing methods.

Coronary bypass surgery guided by computed tomography in a low-risk population.

BACKGROUND AND AIMS: In patients with three-vessel disease and/or left main disease, selecting revascularization strategy based on coronary computed tomography angiography (CCTA) has a high level of virtual agreement with treatment decisions based on invasive coronary angiography (ICA). METHODS: In this study, coronary artery bypass grafting (CABG) procedures were planned based on CCTA without knowledge of ICA. The CABG strategy was recommended by a central core laboratory assessing the anatomy and functionality of the coronary circulation. The primary feasibility endpoint was the percentage of operations performed without access to the ICA. The primary safety endpoint was graft patency on 30-day follow-up CCTA. Secondary endpoints included topographical adequacy of grafting, major adverse cardiac and cerebrovascular (MACCE), and major bleeding events at 30 days. The study was considered positive if the lower boundary of confidence intervals (CI) for feasibility was ≥75% (NCT04142021). RESULTS: The study enrolled 114 patients with a mean (standard deviation) anatomical SYNTAX score and Society of Thoracic Surgery score of 43.6 (15.3) and 0.81 (0.63), respectively. Unblinding ICA was required in one case yielding a feasibility of 99.1% (95% CI 95.2%-100%). The concordance and agreement in revascularization planning between the ICA- and CCTA-Heart Teams was 82.9% with a moderate kappa of 0.58 (95% CI 0.50-0.66) and between the CCTA-Heart Team and actual treatment was 83.7% with a substantial kappa of 0.61 (95% CI 0.53-0.68). The 30-day follow-up CCTA in 102 patients (91.9%) showed an anastomosis patency rate of 92.6%, whilst MACCE was 7.2% and major bleeding 2.7%. CONCLUSIONS: CABG guided by CCTA is feasible and has an acceptable safety profile in a selected population of complex coronary artery disease.

Atherosclerosis evaluation and cardiovascular risk estimation using coronary computed tomography angiography.

Clinical risk scores based on traditional risk factors of atherosclerosis correlate imprecisely to an individual's complex pathophysiological predisposition to atherosclerosis and provide limited accuracy for predicting major adverse cardiovascular events (MACE). Over the past two decades, computed tomography scanners and techniques for coronary computed tomography angiography (CCTA) analysis have substantially improved, enabling more precise atherosclerotic plaque quantification and characterization. The accuracy of CCTA for quantifying stenosis and atherosclerosis has been validated in numerous multicentre studies and has shown consistent incremental prognostic value for MACE over the clinical risk spectrum in different populations. Serial CCTA studies have advanced our understanding of vascular biology and atherosclerotic disease progression. The direct disease visualization of CCTA has the potential to be used synergistically with indirect markers of risk to significantly improve prevention of MACE, pending large-scale randomized evaluation.

Atherosclerosis quantification and cardiovascular risk: the ISCHEMIA trial.

BACKGROUND AND AIMS: The aim of this study was to determine the prognostic value of coronary computed tomography angiography (CCTA)-derived atherosclerotic plaque analysis in ISCHEMIA. METHODS: Atherosclerosis imaging quantitative computed tomography (AI-QCT) was performed on all available baseline CCTAs to quantify plaque volume, composition, and distribution. Multivariable Cox regression was used to examine the association between baseline risk factors (age, sex, smoking, diabetes, hypertension, ejection fraction, prior coronary disease, estimated glomerular filtration rate, and statin use), number of diseased vessels, atherosclerotic plaque characteristics determined by AI-QCT, and a composite primary outcome of cardiovascular death or myocardial infarction over a median follow-up of 3.3 (interquartile range 2.2-4.4) years. The predictive value of plaque quantification over risk factors was compared in an area under the curve (AUC) analysis. RESULTS: Analysable CCTA data were available from 3711 participants (mean age 64 years, 21% female, 79% multivessel coronary artery disease). Amongst the AI-QCT variables, total plaque volume was most strongly associated with the primary outcome (adjusted hazard ratio 1.56, 95% confidence interval 1.25-1.97 per interquartile range increase [559 mm3]; P = .001). The addition of AI-QCT plaque quantification and characterization to baseline risk factors improved the model's predictive value for the primary outcome at 6 months (AUC 0.688 vs. 0.637; P = .006), at 2 years (AUC 0.660 vs. 0.617; P = .003), and at 4 years of follow-up (AUC 0.654 vs. 0.608; P = .002). The findings were similar for the other reported outcomes. CONCLUSIONS: In ISCHEMIA, total plaque volume was associated with cardiovascular death or myocardial infarction. In this highly diseased, high-risk population, enhanced assessment of atherosclerotic burden using AI-QCT-derived measures of plaque volume and composition modestly improved event prediction.

On-Site Computed Tomography-Derived Fractional Flow Reserve to Guide Management of Patients With Stable Coronary Artery Disease: The TARGET Randomized Trial.

BACKGROUND: Computed tomography-derived fractional flow reserve (CT-FFR) using on-site machine learning enables identification of both the presence of coronary artery disease and vessel-specific ischemia. However, it is unclear whether on-site CT-FFR improves clinical or economic outcomes when compared with the standard of care in patients with stable coronary artery disease. METHODS: In total, 1216 patients with stable coronary artery disease and an intermediate stenosis of 30% to 90% on coronary computed tomographic angiography were randomized to an on-site CT-FFR care pathway using machine learning or to standard care in 6 Chinese medical centers. The primary end point was the proportion of patients undergoing invasive coronary angiography without obstructive coronary artery disease or with obstructive disease who did not undergo intervention within 90 days. Secondary end points included major adverse cardiovascular events, quality of life, symptoms of angina, and medical expenditure at 1 year. RESULTS: Baseline characteristics were similar in both groups, with 72.4% (881/1216) having either typical or atypical anginal symptoms. A total of 421 of 608 patients (69.2%) in the CT-FFR care group and 483 of 608 patients (79.4%) in the standard care group underwent invasive coronary angiography. Compared with standard care, the proportion of patients undergoing invasive coronary angiography without obstructive coronary artery disease or with obstructive disease not undergoing intervention was significantly reduced in the CT-FFR care group (28.3% [119/421] versus 46.2% [223/483]; P<0.001). Overall, more patients underwent revascularization in the CT-FFR care group than in the standard care group (49.7% [302/608] versus 42.8% [260/608]; P=0.02), but major adverse cardiovascular events at 1 year did not differ (hazard ratio, 0.88 [95% CI, 0.59-1.30]). Quality of life and symptoms improved similarly during follow-up in both groups, and there was a trend towards lower costs in the CT-FFR care group (difference, -¥4233 [95% CI, -¥8165 to ¥973]; P=0.07). CONCLUSIONS: On-site CT-FFR using machine learning reduced the proportion of patients with stable coronary artery disease undergoing invasive coronary angiography without obstructive disease or requiring intervention within 90 days, but increased revascularization overall without improving symptoms or quality of life, or reducing major adverse cardiovascular events. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03901326.

Computed Tomography Cardiac Angiography Before Invasive Coronary Angiography in Patients With Previous Bypass Surgery: The BYPASS-CTCA Trial.

BACKGROUND: Patients with previous coronary artery bypass grafting often require invasive coronary angiography (ICA). However, for these patients, the procedure is technically more challenging and has a higher risk of complications. Observational studies suggest that computed tomography cardiac angiography (CTCA) may facilitate ICA in this group, but this has not been tested in a randomized controlled trial. METHODS: This study was a single-center, open-label randomized controlled trial assessing the benefit of adjunctive CTCA in patients with previous coronary artery bypass grafting referred for ICA. Patients were randomized 1:1 to undergo CTCA before ICA or ICA alone. The co-primary end points were procedural duration of the ICA (defined as the interval between local anesthesia administration for obtaining vascular access and removal of the last catheter), patient satisfaction after ICA using a validated questionnaire, and the incidence of contrast-induced nephropathy. Linear regression was used for procedural duration and patient satisfaction score; contrast-induced nephropathy was analyzed using logistic regression. We applied the Bonferroni correction, with P<0.017 considered significant and 98.33% CIs presented. Secondary end points included incidence of procedural complications and 1-year major adverse cardiac events. RESULTS: Over 3 years, 688 patients were randomized with a median follow-up of 1.0 years. The mean age was 69.8±10.4 years, 108 (15.7%) were women, 402 (58.4%) were White, and there was a high burden of comorbidity (85.3% hypertension and 53.8% diabetes). The median time from coronary artery bypass grafting to angiography was 12.0 years, and there were a median of 3 (interquartile range, 2 to 3) grafts per participant. Procedure duration of the ICA was significantly shorter in the CTCA+ICA group (CTCA+ICA, 18.6±9.5 minutes versus ICA alone, 39.5±16.9 minutes [98.33% CI, -23.5 to -18.4]; P<0.001), alongside improved mean ICA satisfaction scores (1=very good to 5=very poor; -1.1 difference [98.33% CI, -1.2 to -0.9]; P<0.001), and reduced incidence of contrast-induced nephropathy (3.4% versus 27.9%; odds ratio, 0.09 [98.33% CI, 0.04-0.2]; P<0.001). Procedural complications (2.3% versus 10.8%; odds ratio, 0.2 [95% CI, 0.1-0.4]; P<0.001) and 1-year major adverse cardiac events (16.0% versus 29.4%; hazard ratio, 0.4 [95% CI, 0.3-0.6]; P<0.001) were also lower in the CTCA+ICA group. CONCLUSIONS: For patients with previous coronary artery bypass grafting, CTCA before ICA leads to reductions in procedure time and contrast-induced nephropathy, with improved patient satisfaction. CTCA before ICA should be considered in this group of patients. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03736018.

Automated Prediction of Proximal Middle Cerebral Artery Occlusions in Noncontrast Brain Computed Tomography.

BACKGROUND: Early identification of large vessel occlusion (LVO) in patients with ischemic stroke is crucial for timely interventions. We propose a machine learning-based algorithm (JLK-CTL) that uses handcrafted features from noncontrast computed tomography to predict LVO. METHODS: We included patients with ischemic stroke who underwent concurrent noncontrast computed tomography and computed tomography angiography in seven hospitals. Patients from 5 of these hospitals, admitted between May 2011 and March 2015, were randomly divided into training and internal validation (9:1 ratio). Those from the remaining 2 hospitals, admitted between March 2021 and September 2021, were designated for external validation. From each noncontrast computed tomography scan, we extracted differences in volume, tissue density, and Hounsfield unit distribution between bihemispheric regions (striatocapsular, insula, M1-M3, and M4-M6, modified from the Alberta Stroke Program Early Computed Tomography Score). A deep learning algorithm was used to incorporate clot signs as an additional feature. Machine learning models, including ExtraTrees, random forest, extreme gradient boosting, support vector machine, and multilayer perceptron, as well as a deep learning model, were trained and evaluated. Additionally, we assessed the models' performance after incorporating the National Institutes of Health Stroke Scale scores as an additional feature. RESULTS: Among 2919 patients, 83 were excluded. Across the training (n=2463), internal validation (n=275), and external validation (n=95) datasets, the mean ages were 68.5±12.4, 67.6±13.8, and 67.9±13.6 years, respectively. The proportions of men were 57%, 53%, and 59%, with LVO prevalences of 17.0%, 16.4%, and 26.3%, respectively. In the external validation, the ExtraTrees model achieved a robust area under the curve of 0.888 (95% CI, 0.850-0.925), with a sensitivity of 80.1% (95% CI, 72.0-88.1) and a specificity of 88.6% (95% CI, 84.7-92.5). Adding the National Institutes of Health Stroke Scale score to the ExtraTrees model increased sensitivity (from 80.1% to 92.1%) while maintaining specificity. CONCLUSIONS: Our algorithm provides reliable predictions of LVO using noncontrast computed tomography. By enabling early LVO identification, our algorithm has the potential to expedite the stroke workflow.

Diagnostic Performance of Carotid Ring Sign on CT-Angiography in Internal Carotid True Occlusion.

BACKGROUND: To differentiate between pseudo occlusion (PO) and true occlusion (TO) of internal carotid artery (ICA) is important in thrombectomy treatment planning for patients with acute ischemic stroke. Although delayed contrast filling has been differentiated carotid PO from TO, its application has been limited by the implementations of multiphasic computed tomography angiography. In this study, we hypothesized that carotid ring sign, which is readily acquired from single-phasic CTA, can sufficiently differentiate carotid TO from PO. METHODS: One thousand four hundred and twenty patients with anterior circulation stroke receiving endovascular therapy were consecutively recruited through a hospital- and web-based registry. Two hundred patients with nonvisualization of the proximal ICA were included in the analysis after a retrospective screening. Diagnosis of PO or TO of the cervical segment of ICA was made based on digital subtraction angiography. Diagnostic performances of carotid ring sign on arterial-phasic CTA and delayed contrast filling on multiphasic computed tomography angiography were evaluated and compared. RESULTS: One-hundred twelve patients had ICA PO and 88 had TO. Carotid ring sign was more common in patients with TO (70.5% versus 6.3%; P<0.001), whereas delayed contrast filling was more common in PO (94.9% versus 7.7%; P<0.001). The sensitivity and specificity of carotid ring sign in diagnosing carotid TO were 0.70 and 0.94, respectively, whereas sensitivity and specificity of delayed contrast filling was 0.95 and 0.92 in judging carotid PO. CONCLUSIONS: Carotid ring sign is a potent imaging marker in diagnosing ICA TO. Carotid ring sign could be complementary to delayed contrast filling sign in differentiating TO from PO, in particular in centers with only single-phasic CTA.

Combining Early Ischemic Change and Collateral Extent for Functional Outcomes After Endovascular Therapy: An Analysis From AcT Trial.

BACKGROUND: Early ischemic change and collateral extent are colinear with ischemic core volume (ICV). We investigated the relationship between a combined score using the Alberta Stroke Program Early Computed Tomography Score and multiphase computed tomography angiography (mCTA) collateral extent, named mCTA-ACE score, on functional outcomes in endovascular therapy-treated patients. METHODS: We performed a post hoc analysis of a subset of endovascular therapy-treated patients from the Alteplase Compared to Tenecteplase trial which was conducted between December 2019 and January 2022 at 22 centers across Canada. Ten-point mCTA collateral corresponding to M2 to M6 regions of the Alberta Stroke Program Early Computed Tomography Score grid was evaluated as 0 (poor), 1 (moderate), or 2 (normal) and additively combined with the 10-point Alberta Stroke Program Early Computed Tomography Score to produce a 20-point mCTA-ACE score. We investigated the association of mCTA-ACE score with modified Rankin Scale score ≤2 and return to prestroke level of function at 90 to 120 days using mixed-effects logistic regression. In the subset of patients who underwent baseline computed tomography perfusion imaging, we compared the mCTA-ACE score and ICV for outcome prediction. RESULTS: Among 1577 intention-to-treat population in the trial, 368 (23%; 179 men; median age, 73 years) were included, with Alberta Stroke Program Early Computed Tomography Score, mCTA collateral, and combination of both (mCTA-ACE score: median [interquartile range], 8 [7-10], 9 [8-10], and 17 [16-19], respectively). The probability of modified Rankin Scale score ≤2 and return to prestroke level of function increased for each 1-point increase in mCTA-ACE score (odds ratio, 1.16 [95% CI, 1.06-1.28] and 1.22 [95% CI, 1.06-1.40], respectively). Among 173 patients in whom computed tomography perfusion data was assessable, the mCTA-ACE score was inversely correlated with ICV (ρ=-0.46; P<0.01). The mCTA-ACE score was comparable to ICV to predict a modified Rankin Scale score ≤2 and return to prestroke level of function (C statistics 0.71 versus 0.69 and 0.68 versus 0.64, respectively). CONCLUSIONS: The mCTA-ACE score had a significant positive association with functional outcomes after endovascular therapy and had a similar predictive performance as ICV.

Endovascular treatment versus no endovascular treatment after 6-24 h in patients with ischaemic stroke and collateral flow on CT angiography (MR CLEAN-LATE) in the Netherlands: a multicentre, open-label, blinded-endpoint, randomised, controlled, phase 3 trial.

BACKGROUND: Endovascular treatment for anterior circulation ischaemic stroke is effective and safe within a 6 h window. MR CLEAN-LATE aimed to assess efficacy and safety of endovascular treatment for patients treated in the late window (6-24 h from symptom onset or last seen well) selected on the basis of the presence of collateral flow on CT angiography (CTA). METHODS: MR CLEAN-LATE was a multicentre, open-label, blinded-endpoint, randomised, controlled, phase 3 trial done in 18 stroke intervention centres in the Netherlands. Patients aged 18 years or older with ischaemic stroke, presenting in the late window with an anterior circulation large-vessel occlusion and collateral flow on CTA, and a neurological deficit score of at least 2 on the National Institutes of Health Stroke Scale were included. Patients who were eligible for late-window endovascular treatment were treated according to national guidelines (based on clinical and perfusion imaging criteria derived from the DAWN and DEFUSE-3 trials) and excluded from MR CLEAN-LATE enrolment. Patients were randomly assigned (1:1) to receive endovascular treatment or no endovascular treatment (control), in addition to best medical treatment. Randomisation was web based, with block sizes ranging from eight to 20, and stratified by centre. The primary outcome was the modified Rankin Scale (mRS) score at 90 days after randomisation. Safety outcomes included all-cause mortality at 90 days after randomisation and symptomatic intracranial haemorrhage. All randomly assigned patients who provided deferred consent or died before consent could be obtained comprised the modified intention-to-treat population, in which the primary and safety outcomes were assessed. Analyses were adjusted for predefined confounders. Treatment effect was estimated with ordinal logistic regression and reported as an adjusted common odds ratio (OR) with a 95% CI. This trial was registered with the ISRCTN, ISRCTN19922220. FINDINGS: Between Feb 2, 2018, and Jan 27, 2022, 535 patients were randomly assigned, and 502 (94%) patients provided deferred consent or died before consent was obtained (255 in the endovascular treatment group and 247 in the control group; 261 [52%] females). The median mRS score at 90 days was lower in the endovascular treatment group than in the control group (3 [IQR 2-5] vs 4 [2-6]), and we observed a shift towards better outcomes on the mRS for the endovascular treatment group (adjusted common OR 1·67 [95% CI 1·20-2·32]). All-cause mortality did not differ significantly between groups (62 [24%] of 255 patients vs 74 [30%] of 247 patients; adjusted OR 0·72 [95% CI 0·44-1·18]). Symptomatic intracranial haemorrhage occurred more often in the endovascular treatment group than in the control group (17 [7%] vs four [2%]; adjusted OR 4·59 [95% CI 1·49-14·10]). INTERPRETATION: In this study, endovascular treatment was efficacious and safe for patients with ischaemic stroke caused by an anterior circulation large-vessel occlusion who presented 6-24 h from onset or last seen well, and who were selected on the basis of the presence of collateral flow on CTA. Selection of patients for endovascular treatment in the late window could be primarily based on the presence of collateral flow. FUNDING: Collaboration for New Treatments of Acute Stroke consortium, Dutch Heart Foundation, Stryker, Medtronic, Cerenovus, Top Sector Life Sciences & Health, and the Netherlands Brain Foundation.

CT Myocardial Perfusion and CT-FFR versus Invasive FFR for Hemodynamic Relevance of Coronary Artery Disease.

Background CT-derived fractional flow reserve (CT-FFR) and dynamic CT myocardial perfusion imaging enhance the specificity of coronary CT angiography (CCTA) for ruling out coronary artery disease (CAD). However, evidence on comparative diagnostic value remains scarce. Purpose To compare the diagnostic accuracy of CCTA plus CT-FFR, CCTA plus CT perfusion, and sequential CCTA plus CT-FFR and CT perfusion for detecting hemodynamically relevant CAD with that of invasive angiography. Materials and Methods This secondary analysis of a prospective study included patients with chest pain referred for invasive coronary angiography at nine centers from July 2016 to September 2019. CCTA and CT perfusion were performed with third-generation dual-source CT scanners. CT-FFR was assessed on-site. Independent core laboratories analyzed CCTA alone, CCTA plus CT perfusion, CCTA plus CT-FFR, and a sequential approach involving CCTA plus CT-FFR and CT perfusion for the presence of hemodynamically relevant stenosis. Invasive coronary angiography with invasive fractional flow reserve was the reference standard. Diagnostic accuracy metrics and the area under the receiver operating characteristic curve (AUC) were compared with the Sign test and DeLong test. Results Of the 105 participants (mean age, 64 years ± 8 [SD]; 68 male), 49 (47%) had hemodynamically relevant stenoses at invasive coronary angiography. CCTA plus CT-FFR and CCTA plus CT perfusion showed no evidence of a difference for participant-based sensitivities (90% vs 90%, P > .99), specificities (77% vs 79%, P > .99) and vessel-based AUCs (0.84 [95% CI: 0.77, 0.91] vs 0.83 [95% CI: 0.75, 0.91], P = .90). Both had higher participant-based specificity than CCTA alone (54%, both P < .001) without evidence of a difference in sensitivity between CCTA (94%) and CCTA plus CT perfusion (P = .50) or CCTA plus CT-FFR (P = .63). The sequential approach combining CCTA plus CT-FFR with CT perfusion achieved higher participant-based specificity than CCTA plus CT-FFR (88% vs 77%, P = .03) without evidence of a difference in participant-based sensitivity (88% vs 90%, P > .99) and vessel-based AUC (0.85 [95% CI: 0.77, 0.93], P = .78). Compared with CCTA plus CT perfusion, the sequential approach showed no evidence of a difference in participant-based sensitivity (P > .99), specificity (P = .06), or vessel-based AUC (P = .54). Conclusion There was no evidence of a difference in diagnostic accuracy between CCTA plus CT-FFR and CCTA plus CT perfusion for detecting hemodynamically relevant CAD. A sequential approach combining CCTA plus CT-FFR with CT perfusion led to improved participant-based specificity with no evidence of a difference in sensitivity compared with CCTA plus CT-FFR. ClinicalTrials.gov registration no.: NCT02810795 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Sinitsyn in this issue.

Knowledge-Augmented Deep Learning for Segmenting and Detecting Cerebral Aneurysms With CT Angiography: A Multicenter Study.

Background Deep learning (DL) could improve the labor-intensive, challenging processes of diagnosing cerebral aneurysms but requires large multicenter data sets. Purpose To construct a DL model using a multicenter data set for accurate cerebral aneurysm segmentation and detection on CT angiography (CTA) images and to compare its performance with radiology reports. Materials and Methods Consecutive head or head and neck CTA images of suspected unruptured cerebral aneurysms were gathered retrospectively from eight hospitals between February 2018 and October 2021 for model development. An external test set with reference standard digital subtraction angiography (DSA) scans was obtained retrospectively from one of the eight hospitals between February 2022 and February 2023. Radiologists (reference standard) assessed aneurysm segmentation, while model performance was evaluated using the Dice similarity coefficient (DSC). The model's aneurysm detection performance was assessed by sensitivity and comparing areas under the receiver operating characteristic curves (AUCs) between the model and radiology reports in the DSA data set with use of the DeLong test. Results Images from 6060 patients (mean age, 56 years ± 12 [SD]; 3375 [55.7%] female) were included for model development (training: 4342; validation: 1086; and internal test set: 632). Another 118 patients (mean age, 59 years ± 14; 79 [66.9%] female) were included in an external test set to evaluate performance based on DSA. The model achieved a DSC of 0.87 for aneurysm segmentation performance in the internal test set. Using DSA, the model achieved 85.7% (108 of 126 aneurysms [95% CI: 78.1, 90.1]) sensitivity in detecting aneurysms on per-vessel analysis, with no evidence of a difference versus radiology reports (AUC, 0.93 [95% CI: 0.90, 0.95] vs 0.91 [95% CI: 0.87, 0.94]; P = .67). Model processing time from reconstruction to detection was 1.76 minutes ± 0.32 per scan. Conclusion The proposed DL model could accurately segment and detect cerebral aneurysms at CTA with no evidence of a significant difference in diagnostic performance compared with radiology reports. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Payabvash in this issue.

Clinical Effectiveness of Automated Coronary CT-derived Fractional Flow Reserve: A Chinese Randomized Controlled Trial.

Background Coronary CT-derived fractional flow reserve (CT-FFR) has been used in patients with suspected coronary artery disease (CAD); however, whether it decreases invasive coronary angiography (ICA) use and affects prognosis remains insufficiently evidenced. Purpose To explore the effectiveness of adding CT-FFR to routine coronary CT angiography (CCTA) on short-term ICA rate and major adverse cardiovascular events (MACE) in a Chinese setting. Materials and Methods A multicenter randomized controlled trial was conducted in 17 Chinese centers, with patient inclusion from May 2021 to September 2021. Eligible individuals with 25%-99% stenosis at CCTA were randomly assigned 1:1 to a strategy of CCTA plus automated CT-FFR or CCTA alone for guiding downstream care. The primary end point was the ICA rate 90 days after enrollment. Secondary end points included 90-day and 1-year MACE rates (comprised of all-cause mortality, nonfatal myocardial infarction, and urgent revascularization) and 1-year cardiac events (comprised of cardiac death, nonfatal myocardial infarction, and urgent revascularization). The Cox proportional hazards model with center effect adjustment was used for survival comparisons. Results A total of 5297 participants (mean age, 63.5 years ± 10.8 [SD]; 3178 male) were included. During the 90-day follow-up, ICA was performed in 263 of 2633 participants (10.0%) in the CCTA plus CT-FFR group and 327 of 2640 participants (12.4%) in the CCTA-alone group (absolute rate difference: -2.40%; 95% CI: -4.10, -0.70; P = .006). The MACE rates at 90 days (0.5% [12 of 2633 participants] vs 0.8% [21 of 2640 participants]; P = .12) and 1 year (2.9% [74 of 2546 participants] vs 2.8% [72 of 2531 participants]; P = .90) were similar for both groups. At 1-year follow-up, fewer cardiac events were observed in the CCTA plus CT-FFR group compared with the CCTA-alone group (0.5% vs 1.1%; adjusted hazard ratio: 0.52; 95% CI: 0.27, 0.99; P = .047). Conclusion CT-FFR added to CCTA led to a lower 90-day ICA rate and similar 1-year MACE rate in a Chinese real-world setting. Further follow-up is warranted to demonstrate the long-term prognostic value of this management approach. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Pundziute-do Prado in this issue.

Coronary Artery Calcium Scoring Using Virtual Versus True Noncontrast Images From Photon-Counting Coronary CT Angiography.

Background Coronary artery calcium scoring (CACS) for coronary artery disease requires true noncontrast (TNC) CT alongside contrast-enhanced coronary CT angiography (CCTA). Photon-counting CT provides an algorithm (PureCalcium) for reconstructing virtual noncontrast images from CCTA specifically for CACS. Purpose To assess CACS differences based on PureCalcium images derived from contrast-enhanced photon-counting CCTA compared with TNC images and evaluate the impact of these differences on the clinically relevant classification of patients into plaque burden groups. Materials and Methods Photon-counting CCTA images acquired between August 2022 and May 2023 were retrospectively identified. Agatston scores were derived from both TNC and PureCalcium images and tested for differences with use of the Wilcoxon signed-rank test. The agreement was assessed with use of equivalence tests, Bland-Altman analysis, and intraclass correlation coefficient. Plaque burden groups were established based on Agatston scores, and agreement was evaluated using weighted Cohen kappa. The dose-length product was analyzed. Results Among 170 patients (mean age, 63 years ± 13 [SD]; 92 male), 111 had Agatston scores higher than 0. Median Agatston scores did not differ between TNC and PureCalcium images (4.8 [IQR, 0-84.4; range, 0.0-2151.8] vs 2.7 [IQR, 0-90.7; range, 0.0-2377.1]; P = .99), with strong correlation (intraclass correlation coefficient, 0.98 [95% CI: 0.97, 0.99]). The equivalence test was inconclusive, with a 95% CI of 0.90, 1.19. Bland-Altman analysis showed wide repeatability limits, indicating low agreement between the two scores. With use of the PureCalcium algorithm, 125 of 170 patients (74%) were correctly classified into plaque burden groups (excellent agreement, κ = 0.88). Patients without plaque burden were misclassified at higher than normal rates (P < .001). TNC image acquisition contributed a mean of 19.7% ± 8.8 of the radiation dose of the entire examination. Conclusion PureCalcium images show potential to replace TNC images for measuring Agatston scores, thereby reducing radiation dose in CCTA. There was strong correlation in calcium scores between TNC and PureCalcium, but limited agreement. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Sakuma in this issue.

Quantification of Aortic Valve Fibrotic and Calcific Tissue from CTA: Prospective Comparison with Histology.

Background Quantifying the fibrotic and calcific composition of the aortic valve at CT angiography (CTA) can be useful for assessing disease severity and outcomes of patients with aortic stenosis (AS); however, it has not yet been validated against quantitative histologic findings. Purpose To compare quantification of aortic valve fibrotic and calcific tissue composition at CTA versus histologic examination. Materials and Methods This prospective study included patients who underwent CTA before either surgical aortic valve replacement for AS or orthotopic heart transplant (controls) at two centers between January 2022 and April 2023. At CTA, fibrotic and calcific tissue composition were quantified using automated Gaussian mixture modeling applied to the density of aortic valve tissue components, calculated as [(volume/total tissue volume) × 100]. For histologic evaluation, explanted valve cusps were stained with Movat pentachrome as well as hematoxylin and eosin. For each cusp, three 5-µm slices were obtained. Fibrotic and calcific tissue composition were quantified using a validated artificial intelligence tool and averaged across the aortic valve. Correlations were assessed using the Spearman rank correlation coefficient. Intermodality and interobserver variability were measured using the intraclass correlation coefficient (ICC) and Bland-Altman plots. Results Twenty-nine participants (mean age, 63 years ± 10 [SD]; 23 male) were evaluated: 19 with severe AS, five with moderate AS, and five controls. Fibrocalcific tissue composition strongly correlated with histologic findings (r = 0.92; P < .001). The agreement between CTA and histologic findings for fibrocalcific tissue quantification was excellent (ICC, 0.94; P = .001), with underestimation of fibrotic composition at CTA (bias, -4.9%; 95% limits of agreement [LoA]: -18.5%, 8.7%). Finally, there was excellent interobserver repeatability for fibrotic (ICC, 0.99) and calcific (ICC, 0.99) aortic valve tissue volume measurements, with no evidence of a difference in measurements between readers (bias, -0.04 cm3 [95% LoA: -0.27 cm3, 0.19 cm3] and 0.02 cm3 [95% LoA: -0.14 cm3, 0.19 cm3], respectively). Conclusion In a direct comparison, standardized quantitative aortic valve tissue characterization at CTA showed excellent concordance with histologic findings and demonstrated interobserver reproducibility. Clinical trial registration no. NCT06136689 Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Almeida in this issue.

Case 331.

HISTORY: A 43-year-old male patient with no known past medical history presented to the emergency department with new-onset bitemporal headache, dizziness, and bilateral lower extremity weakness for 1 day. The patient denied chest pain, shortness of breath, cough, or recent exposure to sick individuals. He was not on any medications and denied alcohol or illicit drug use. Vital signs were unremarkable. Physical examination was notable for a left-sided pronator drift and bilateral dysmetria that was more pronounced on the left. Results of routine laboratory workup, including complete blood count, metabolic panel, and high-sensitivity troponin level, were normal. An electrocardiogram revealed sinus tachycardia with a heart rate of 102 beats per minute, T-wave inversions in the inferior leads, left axis deviation, incomplete right bundle branch block, and frequent premature ventricular contractions. A radiograph of the chest was unremarkable. CT of the head without contrast enhancement demonstrated no acute intracranial abnormities. MRI of the brain without contrast enhancement revealed multiple acute infarcts involving left posterior inferior cerebellar artery distribution, right cerebellar hemisphere, right mesial temporal lobe, and right posterior limb of the internal capsule. CT angiography of the head and neck showed an occlusion of the right posterior cerebral artery near its origin, with a trace of distal flow. Given that these findings were concerning for a cardioembolic etiology of acute ischemic stroke, transesophageal echocardiography was performed. This showed mild left ventricular systolic dysfunction with an ejection fraction of 40%, mild global hypokinesis, and an additional finding also seen at subsequent cardiac CT and MRI that will be disclosed in part 2 of the case. The patient was started on systemic anticoagulation and guideline-directed medical therapy for heart failure with reduced ejection fraction. CT of the chest showed no evidence of lymphadenopathy or abnormalities in the lung parenchyma or interstitium. Coronary CT angiography was performed (Fig 1), followed by cardiac MRI (Fig 2).

Ultrahigh-Spatial-Resolution Photon-counting Detector CT Angiography of Coronary Artery Disease for Stenosis Assessment.

Background Coronary CT angiography is a first-line test in coronary artery disease but is limited by severe calcifications. Photon-counting-detector (PCD) CT improves spatial resolution. Purpose To investigate the effect of improved spatial resolution on coronary stenosis assessment and reclassification. Materials and Methods Coronary stenoses were evaluated prospectively in a vessel phantom (in vitro) containing two stenoses (25%, 50%), and retrospectively in patients (in vivo) who underwent ultrahigh-spatial-resolution cardiac PCD CT (from July 2022 to April 2023). Images were reconstructed at standard resolution (section thickness, 0.6 mm; increment, 0.4 mm; Bv44 kernel), high spatial resolution (section thickness, 0.4 mm; increment, 0.2 mm; Bv44 kernel), and ultrahigh spatial resolution (section thickness, 0.2; increment, 0.1 mm; Bv64 kernel). Percentages of diameter stenosis (DS) were compared between reconstructions. In vitro values were compared with the manufacturer specifications of the phantom and patient results were assessed regarding effects on Coronary Artery Disease Reporting and Data System (CAD-RADS) reclassification. Results The in vivo sample included 114 patients (mean age, 68 years ± 9 [SD]; 71 male patients). In vitro percentage DS measurements were more accurate with increasing spatial resolution for both 25% and 50% stenoses (mean bias for standard resolution, high spatial resolution, and ultrahigh spatial resolution, respectively: 10.1%, 8.0%, and 2.3%; P < .001). In vivo results confirmed decreasing median percentage DS with increasing spatial resolution for calcified stenoses (n = 161) (standard resolution, high spatial resolution, and ultrahigh spatial resolution, respectively: 41.5% [IQR, 27.3%-58.2%], 34.8% [IQR, 23.7%-55.1%], and 26.7% [IQR, 18.6%-44.3%]; P < .001), whereas noncalcified (n = 13) and mixed plaques (n = 19) did not show evidence of a difference (P ≥ .88). Ultrahigh-spatial-resolution reconstructions led to reclassification of 62 of 114 (54.4%) patients to lower CAD-RADS category than that assigned using standard resolution. Conclusion In vivo and in vitro coronary stenosis assessment improved for calcified stenoses by using ultrahigh-spatial-resolution PCD CT reconstructions, leading to lower percentage DS compared with standard resolution and clinically relevant rates of reclassification. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by McCollough in this issue.

Optimisation of detecting chronic thromboembolic pulmonary hypertension in acute pulmonary embolism survivors: the InShape IV study.

INTRODUCTION: Chronic thromboembolic pulmonary hypertension (CTEPH) is often diagnosed late in acute pulmonary embolism survivors: more efficient testing to expedite diagnosis may considerably improve patient outcomes. The InShape II algorithm safely rules out CTEPH (failure rate 0.29%) while requiring echocardiography in only 19% of patients but may be improved by adding detailed reading of the computed tomography pulmonary angiography diagnosing the index pulmonary embolism. METHODS: We evaluated 12 new algorithms, incorporating the CTEPH prediction score, ECG reading, N­terminal pro-brain natriuretic peptide levels and dedicated computed tomography pulmonary angiography reading, in the international InShape II cohort (n=341) and part of the German FOCUS cohort (n=171). Evaluation criteria included failure rate, defined as the incidence of confirmed CTEPH in pulmonary embolism patients in whom echocardiography was deemed unnecessary by the algorithm, and the overall net reclassification index compared to the InShape II algorithm. RESULTS: The algorithm starting with computed tomography pulmonary angiography reading of the index pulmonary embolism for six signs of CTEPH, followed by ECG/N-terminal pro-brain natriuretic peptide level assessment and echocardiography resulted in the most beneficial change compared to InShape II, with a need for echocardiography in 20% (+5%), a failure rate of 0% and a net reclassification index of +3.5%, reflecting improved performance over the InShape II algorithm. In the FOCUS cohort, this approach lowered echocardiography need to 24% (-6%) and missed no CTEPH cases, with a net reclassification index of +6.0%. CONCLUSION: Dedicated computed tomography pulmonary angiography reading of the index pulmonary embolism improved the performance of the InShape II algorithm and may improve the selection of pulmonary embolism survivors who require echocardiography to rule out CTEPH.