VEGF-A plasma levels are associated with impaired DLCO and radiological sequelae in long COVID patients.

BACKGROUND: Long COVID, also known as post-acute sequelae of COVID-19 (PASC), is characterized by persistent clinical symptoms following COVID-19. OBJECTIVE: To correlate biomarkers of endothelial dysfunction with persistent clinical symptoms and pulmonary function defects at distance from COVID-19. METHODS: Consecutive patients with long COVID-19 suspicion were enrolled. A panel of endothelial biomarkers was measured in each patient during clinical evaluation and pulmonary function test (PFT). RESULTS: The study included 137 PASC patients, mostly male (68%), with a median age of 55 years. A total of 194 PFTs were performed between months 3 and 24 after an episode of SARS-CoV-2 infection. We compared biomarkers evaluated in PASC patients with 20 healthy volunteers (HVs) and acute hospitalized COVID-19 patients (n = 88). The study found that angiogenesis-related biomarkers and von Willebrand factor (VWF) levels were increased in PASC patients compared to HVs without increased inflammatory or platelet activation markers. Moreover, VEGF-A and VWF were associated with persistent lung CT scan lesions and impaired diffusing capacity of the lungs for carbon monoxide (DLCO) measurement. By employing a Cox proportional hazards model adjusted for age, sex, and body mass index, we further confirmed the accuracy of VEGF-A and VWF. Following adjustment, VEGF-A emerged as the most significant predictive factor associated with persistent lung CT scan lesions and impaired DLCO measurement. CONCLUSION: VEGF-A is a relevant predictive factor for DLCO impairment and radiological sequelae in PASC. Beyond being a biomarker, we hypothesize that the persistence of angiogenic disorders may contribute to long COVID symptoms.

Deep Learning-Based Analysis of Aortic Morphology From Three-Dimensional MRI.

BACKGROUND: Quantification of aortic morphology plays an important role in the evaluation and follow-up assessment of patients with aortic diseases, but often requires labor-intensive and operator-dependent measurements. Automatic solutions would help enhance their quality and reproducibility. PURPOSE: To design a deep learning (DL)-based automated approach for aortic landmarks and lumen detection derived from three-dimensional (3D) MRI. STUDY TYPE: Retrospective. POPULATION: Three hundred ninety-one individuals (female: 47%, age = 51.9 ± 18.4) from three sites, including healthy subjects and patients (hypertension, aortic dilation, Turner syndrome), randomly divided into training/validation/test datasets (N = 236/77/78). Twenty-five subjects were randomly selected and analyzed by three operators with different levels of expertise. FIELD STRENGTH/SEQUENCE: 1.5-T and 3-T, 3D spoiled gradient-recalled or steady-state free precession sequences. ASSESSMENT: Reinforcement learning and a two-stage network trained using reference landmarks and segmentation from an existing semi-automatic software were used for aortic landmark detection and segmentation from sinotubular junction to coeliac trunk. Aortic segments were defined using the detected landmarks while the aortic centerline was extracted from the segmentation and morphological indices (length, aortic diameter, and volume) were computed for both the reference and the proposed segmentations. STATISTICAL TESTS: Segmentation: Dice similarity coefficient (DSC), Hausdorff distance (HD), average symmetrical surface distance (ASSD); landmark detection: Euclidian distance (ED); model robustness: Spearman correlation, Bland-Altman analysis, Kruskal-Wallis test for comparisons between reference and DL-derived aortic indices; inter-observer study: Williams index (WI). A WI 95% confidence interval (CI) lower bound >1 indicates that the method is within the inter-observer variability. A P-value <0.05 was considered statistically significant. RESULTS: DSC was 0.90 ± 0.05, HD was 12.11 ± 7.79 mm, and ASSD was 1.07 ± 0.63 mm. ED was 5.0 ± 6.1 mm. A good agreement was found between all DL-derived and reference aortic indices (r >0.95, mean bias <7%). Our segmentation and landmark detection performances were within the inter-observer variability except the sinotubular junction landmark (CI = 0.96;1.04). DATA CONCLUSION: A DL-based aortic segmentation and anatomical landmark detection approach was developed and applied to 3D MRI data for achieve aortic morphology evaluation. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

Four-dimensional flow cardiovascular magnetic resonance aortic cross-sectional pressure changes and their associations with flow patterns in health and ascending thoracic aortic aneurysm.

BACKGROUND: Ascending thoracic aortic aneurysm (ATAA) is a silent and threatening dilation of the ascending aorta (AscAo). Maximal aortic diameter which is currently used for ATAA patients management and surgery planning has been shown to inadequately characterize risk of dissection in a large proportion of patients. Our aim was to propose a comprehensive quantitative evaluation of aortic morphology and pressure-flow-wall associations from four-dimensional (4D) flow cardiovascular magnetic resonance (CMR) data in healthy aging and in patients with ATAA. METHODS: We studied 17 ATAA patients (64.7 ± 14.3 years, 5 females) along with 17 age- and sex-matched healthy controls (59.7 ± 13.3 years, 5 females) and 13 younger healthy subjects (33.5 ± 11.1 years, 4 females). All subjects underwent a CMR exam, including 4D flow and three-dimensional anatomical images of the aorta. This latter dataset was used for aortic morphology measurements, including AscAo maximal diameter (iDMAX) and volume, indexed to body surface area. 4D flow MRI data were used to estimate 1) cross-sectional local AscAo spatial (∆PS) and temporal (∆PT) pressure changes as well as the distance (∆DPS) and time duration (∆TPT) between local pressure peaks, 2) AscAo maximal wall shear stress (WSSMAX) at peak systole, and 3) AscAo flow vorticity amplitude (VMAX), duration (VFWHM), and eccentricity (VECC). RESULTS: Consistency of flow and pressure indices was demonstrated through their significant associations with AscAo iDMAX (WSSMAX:r = -0.49, p < 0.001; VECC:r = -0.29, p = 0.045; VFWHM:r = 0.48, p < 0.001; ∆DPS:r = 0.37, p = 0.010; ∆TPT:r = -0.52, p < 0.001) and indexed volume (WSSMAX:r = -0.63, VECC:r = -0.51, VFWHM:r = 0.53, ∆DPS:r = 0.54, ∆TPT:r = -0.63, p < 0.001 for all). Intra-AscAo cross-sectional pressure difference, ∆PS, was significantly and positively associated with both VMAX (r = 0.55, p = 0.002) and WSSMAX (r = 0.59, p < 0.001) in the 30 healthy subjects (48.3 ± 18.0 years). Associations remained significant after adjustment for iDMAX, age, and systolic blood pressure. Superimposition of ATAA patients to normal aging trends between ∆PS and WSSMAX as well as VMAX allowed identifying patients with substantially high pressure differences concomitant with AscAo dilation. CONCLUSION: Local variations in pressures within ascending aortic cross-sections derived from 4D flow MRI were associated with flow changes, as quantified by vorticity, and with stress exerted by blood on the aortic wall, as quantified by wall shear stress. Such flow-wall and pressure interactions might help for the identification of at-risk patients.

The PACIFIC ontology for heterogeneous data management in cardiology.

With the emergence of health data warehouses and major initiatives to collect and analyze multi-modal and multisource data, data organization becomes central. In the PACIFIC-PRESERVED (PhenomApping, ClassIFication, and Innovation for Cardiac Dysfunction - Heart Failure with PRESERVED LVEF Study, NCT04189029) study, a data driven research project aiming at redefining and profiling the Heart Failure with preserved Ejection Fraction (HFpEF), an ontology was developed by different data experts in cardiology to enable better data management in a complex study context (multisource, multiformat, multimodality, multipartners). The PACIFIC ontology provides a cardiac data management framework for the phenomapping of patients. It was built upon the BMS-LM (Biomedical Study -Lifecycle Management) core ontology and framework, proposed in a previous work to ensure data organization and provenance throughout the study lifecycle (specification, acquisition, analysis, publication). The BMS-LM design pattern was applied to the PACIFIC multisource variables. In addition, data was structured using a subset of MeSH headings for diseases, technical procedures, or biological processes, and using the Uberon ontology anatomical entities. A total of 1372 variables were organized and enriched with annotations and description from existing ontologies and taxonomies such as LOINC to enable later semantic interoperability. Both, data structuring using the BMS-LM framework, and its mapping with published standards, foster interoperability of multimodal cardiac phenomapping datasets.

Rationale and design of the direct oral anticoagulants for prevention of left ventricular thrombus after anterior acute myocardial infarction (APERITIF) trial.

BACKGROUND: Anterior acute myocardial infarction (AMI) is associated with an increased risk of left ventricular (LV) thrombus formation. We hypothesized that adding low-dose oral rivaroxaban to the usual antiplatelet regimen would reduce the risk of LV thrombus in patients with large AMI. STUDY DESIGN: APERITIF is an investigator-initiated, multicenter randomized open-label, blinded end-point (PROBE) trial, nested in the ongoing "FRENCHIE" registry, a French multicenter prospective observational study, in which all consecutive patients admitted within 48 hours of symptom onset in a cardiac Intensive Care Unit (ICU) for AMI are included (NCT04050956). Among them, patients with anterior ST-elevation-myocardial infarction (STEMI) or very high-risk non- ST-elevation-myocardial infarction (NSTEMI) patients with involvement of the left anterior descending artery are randomized into 2 groups: Dual Antiplatelet Therapy (DAPT) alone or DAPT plus rivaroxaban 2.5mg twice daily for 4 weeks, started as soon as possible after completion of the initial percutaneous coronary intervention/angiography procedure. The primary endpoint is the presence of LV thrombus at 1 month, as detected by contrast enhanced CMR (CE-CMR). Secondary endpoints include LV thrombus dimension (greatest diameter), the rate of major bleedings and major cardiovascular events at 1 month. Based on estimated event rates, a sample size of 560 patients is needed to show superiority of DAPT plus rivaroxaban therapy versus DAPT alone, with 80% power. CONCLUSION: The APERITIF trial will determine whether, in patients with large AMIs, the use of rivaroxaban 2.5mg twice daily in addition to DAPT reduces LV thrombus formation, compared with DAPT alone. CLINICALTRIALS: gov Identifier: NCT05077683.

Discordance between 2D and 4D flow in the assessment of pulmonary regurgitation severity: a right ventricular remodeling follow-up study.

OBJECTIVES: Pulmonary regurgitation (PR) is common in adult congenital heart disease (ACHD). 2D phase contrast MRI is the reference method for the quantification of PR and helps in the decision of pulmonary valve replacement (PVR). 4D flow MRI can be an alternative method to estimate PR but more validation is still needed. Our purpose was to compare 2D and 4D flow in PR quantification using the degree of right ventricular remodeling after PVR as the reference standard. METHODS: In 30 adult patients with a pulmonary valve disease recruited between 2015 and 2018, PR was assessed using both 2D and 4D flow. Based on the clinical standard of care, 22 underwent PVR. The pre PVR estimate of PR was compared using the post-operative decrease in right ventricle end-diastolic volume on follow-up exam as reference. RESULTS: In the overall cohort, regurgitant volume (Rvol) and regurgitant fraction (RF) of PR measured by 2D and 4D flow were well correlated but with moderate agreement in the overall cohort (r = 0.90, mean diff. -14 ± 12.5 mL; and r = 0.72, mean diff. -15 ± 13%; all p < 0.0001). Correlations between Rvol estimates and right ventricle end-diastolic volume decrease after PVR was higher with 4D flow (r = 0.80, p < 0.0001) than with 2D flow (r = 0.72, p < 0.0001). CONCLUSIONS: In ACHD, PR quantification from 4D flow better predicts post-PVR right ventricle remodeling than that from 2D flow. Further studies are needed to evaluate the added value of this 4D flow quantification for guiding replacement decision. KEY POINTS: • Using 4D flow MRI allows a better quantification of pulmonary regurgitation in adult congenital heart disease than 2D flow when taking right ventricle remodeling after pulmonary valve replacement as a reference. • A plane positioned perpendicular to the ejected flow volume as allowed by 4D flow provides better results to estimate pulmonary regurgitation.

Diastolic Function Assessment of Left and Right Ventricles by MRI in Systemic Sclerosis Patients.

BACKGROUND: Heart involvement is frequent although often clinically silent in systemic sclerosis (SSc) patients. Early identification of cardiac involvement can be improved by noninvasive methods such as MRI, in addition to transthoracic echocardiography (TTE). PURPOSE: To assess the ability of phase-contrast (PC)-MRI to detect subclinical left (LV) and right (RV) ventricular diastolic dysfunction in SSc patients. STUDY TYPE: Prospective. POPULATION: Thirty-five consecutive SSc patients (49 ± 14 years) and 35 sex- and age-matched healthy controls (48.6 ± 13.5 years) who underwent TTE and MRI in the same week. FIELD STRENGTH/SEQUENCE: 5 T/PC-MRI using a breath-hold velocity-encoded gradient echo sequence. ASSESSMENT: LV TTE (E/E') and LV and RV PC-MRI indices of diastolic function (LV early and late transmitral [EM , EfM , AM , AfM ] and RV transtricuspid [ET , EfT , AT , AfT ] peak filling flow velocities and flow rates, as well as LV [ E M ' ] and RV [ E T ' ] peak longitudinal myocardial velocities during diastole) were measured. STATISTICAL TESTS: Two-tailed t-test, Wilcoxon test, or Fischer test for comparison of variables between SSc and healthy control groups; sensitivity, specificity, receiver-operating-characteristic (ROC) area under the curve (AUC) to assess discriminative ability of variables. A P-value <0.05 was considered statistically significant. RESULTS: TTE LV E/E' and MRI EM / E M ' and ET / E T ' were significantly higher in SSc patients than in controls (8.27 ± 1.25 vs. 6.70 ± 1.66; 9.43 ± 2.7 vs. 6.51 ± 1.50; 6.51 [4.70-10.40] vs. 4.13 [3.22-5.75], respectively) and separated SSc patients and healthy controls with good sensitivity (68%, 71%, and 80%), specificity (85%, 94%, and 62%), and AUC (0.787, 0.807, and 0.765). LV EfM was significantly higher in SSc patients than in controls (347.1 ± 113.7 vs. 284.7 ± 94.6) as RVAfT (277 [231-355] vs. 220 [154-253] mL/sec) with impaired relaxation pattern (EfT /AfT , 0.95 [0.87-1.21] vs. 1.12 [0.93-1.47]). DATA CONCLUSION: MRI was able to detect LV and RV diastolic dysfunction in SSc patients with good accuracy in the absence of LV systolic dysfunction at echocardiography. Use of MRI can allow to better assess the early impact of myocardial fibrosis related to SSc. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 2.

Deep Learning-based Automated Aortic Area and Distensibility Assessment: the Multi-Ethnic Study of Atherosclerosis (MESA).

This study details application of deep learning for automatic segmentation of the ascending and descending aorta from 2D phase-contrast cine magnetic resonance imaging for automatic aortic analysis on the large MESA cohort with assessment on an external cohort of thoracic aortic aneurysm (TAA) patients. This study includes images and corresponding analysis of the ascending and descending aorta at the pulmonary artery bifurcation from the MESA study. Train, validation, and internal test sets consisted of 1123 studies (24,282 images), 374 studies (8067 images), and 375 studies (8069 images), respectively. The external test set of TAAs consisted of 37 studies (3224 images). CNN performance was evaluated utilizing a dice coefficient and concordance correlation coefficients (CCC) of geometric parameters. Dice coefficients were as high as 97.55% (CI: 97.47-97.62%) and 93.56% (CI: 84.63-96.68%) on the internal and external test of TAAs, respectively. CCC for maximum and minimum and ascending aortic area were 0.969 and 0.950, respectively, on the internal test set and 0.997 and 0.995, respectively, for the external test. The absolute differences between manual and deep learning segmentations for ascending and descending aortic distensibility were 0.0194 × 10-4 ± 9.67 × 10-4 and 0.002 ± 0.001 mmHg-1, respectively, on the internal test set and 0.44 × 10-4 ± 20.4 × 10-4 and 0.002 ± 0.001 mmHg-1, respectively, on the external test set. We successfully developed a U-Net-based aortic segmentation and analysis algorithm in both MESA and in external cases of TAA.

Quantitative magnetic resonance imaging measures of three-dimensional aortic morphology in healthy aging and hypertension.

Automated segmentation of three-dimensional (3D) aortic magnetic resonance imaging (MRI) renders a possible retrospective selection of any location to perform quantification of aortic caliber perpendicular to its centerline and provides regional and global 3D biomarkers such as length, diameter, or volume. However, normative age-related values of such measures are still lacking. The aim of this study was to provide normal values for 3D aortic morphological measures and investigate their changes in aging and hypertension. This was a retrospective study, in which 119 healthy controls (HC: 48 ± 14 years, 61 men) and 82 hypertensive patients (HT: 60 ± 14 years, 43 men) were enrolled. 1.5 and 3 T/3D steady state free precession or spoiled gradient echo were used. Automated 3D aortic segmentation provided aortic length, diameter, volume for the ascending (AAo), and descending aorta (DAo), along with cross-sectional diameters at three aortic landmarks. Age, sex, body surface area (BSA), smoking, and blood pressures were recorded. Both groups were divided into two subgroups (≤50 years, >50 years). Statistical tests performed were linear regression for age-related normal values and confidence intervals, Wilcoxon rank sum test for differences between groups (HC or HT), and multivariate analysis to identify main determinants of aortic morphological changes. In HC, linear regression revealed an increase in the AAo (respectively DAo) length by 2.84 mm (7.78 mm), maximal diameter by 1.36 mm (1.29 mm), and volume by 4.28 ml (8.71 ml) per decade. AAo morphological measures were higher in HT patients than in HC both ≤50 years but did not reach statistical significance (length: +2 mm, p = 0.531; diameter: +1.4 mm, p = 0.2936; volume:+6.8 ml, p = 0.1857). However, length (+6 mm, p = 0.003), maximal diameter (+4 mm, p < 0.001) and volume (+12 ml, p < 0.001) were significantly higher in HT patients than in HC, both >50 years. In a multivariate analysis, age, sex, and BSA were the major determinants of aortic morphology, irrespective of the presence of hypertension. Global and segmental aortic length, volume, and diameters at specific landmarks were automatically measured from 3D MRI to serve as normative measures of 3D aortic morphology. Such indices increased significantly with age and hypertension among the elderly subjects. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 3.

Visual lung damage CT score at hospital admission of COVID-19 patients and 30-day mortality.

OBJECTIVES: Chest CT has been widely used to screen and to evaluate the severity of COVID-19 disease in the early stages of infection without severe acute respiratory syndrome, but no prospective data are available to study the relationship between extent of lung damage and short-term mortality. The objective was to evaluate association between standardized simple visual lung damage CT score (vldCTs) at admission, which does not require any software, and 30-day mortality. METHODS: In a single-center prospective cohort of COVID-19 patients included during 4 weeks, the presence and extent of ground glass opacities(GGO), consolidation opacities, or both of them were visually assessed in each of the 5 lung lobes (score from 0 to 4 per lobe depending on the percentage and out of 20 per patient = vldCTs) after the first chest CT performed to detect COVID-19 pneumonia. RESULTS: Among 210 confirmed COVID-19 patients, the number of survivors and non-survivors was 162 (77%) and 48 (23%), respectively at 30 days. vldCTs was significantly higher in non-survivors, and the AUC of vldCTs to distinguish survivors and non-survivors was 0.72 (95%CI 0.628-0.807, p < 0.001); the best cut-off vldCTs value was 7. During follow-up, significant differences in discharges and 30-day mortality were observed between patients with vldCTs ≥ 7 versus vldCTs < 7: (98 [85.2%] vs 49 [51.6%]; p < 0.001 and 36 [37.9%] vs 12 [12.4%]; p < 0.001, respectively. The 30-day mortality increased if vldCTs ≥ 7 (HR, 3.16 (1.50-6.43); p = 0.001), independent of age, respiratory rate and oxygen saturation levels, and comorbidities at admission. CONCLUSIONS: By using chest CT in COVID-19 patients, extensive lung damage can be visually assessed with a score related to 30-day mortality independent of conventional risk factors of the disease. KEY POINTS: • In non-selected COVID-19 patients included prospectively during 4 weeks, the extent of ground glass opacities(GGO) and consolidation opacities evaluated by a simple visual score was related to 30-day mortality independent of age, respiratory rate, oxygen saturation levels, comorbidities, and hs-troponin I level at admission. • This severity score should be incorporated into risk stratification algorithms and in structured chest CT reports requiring a standardized reading by radiologists in case of COVID-19.

Vascular Ehlers-Danlos syndrome (vEDS): CT and histologic findings of pleural and lung parenchymal damage.

OBJECTIVES: To describe CT features of lung involvement in patients with vascular Ehlers-Danlos syndrome (vEDS), a rare genetic condition caused by pathogenic variants within the COL3A1 gene, characterized by recurrent arterial, digestive, and pulmonary events. MATERIAL AND METHODS: All consecutive vEDS patients referred to the national tertiary referral center for vEDS, between 2004 and 2016, were included. Chest CT scans obtained during the initial vascular work-up were reviewed retrospectively by two chest radiologists for lung involvement. Five surgical samples underwent histologic examination. RESULTS: Among 136 enrolled patients (83 women, 53 men; mean age 37 years) with molecularly confirmed vEDS, 24 (17.6%) had a history of respiratory events: 17 with pneumothorax, 4 with hemothorax, and 3 with hemoptysis that required thoracic surgery in 11. CT scans detected lung parenchymal abnormalities in 78 (57.3%) patients: emphysema (mostly centrilobular and paraseptal) in 44 (32.3%), comparable for smokers and non-smokers; clusters of calcified small pulmonary nodules in 9 (6.6%); and cavitated nodules in 4 (2.9%). Histologic examination of surgical samples found arterial abnormalities, emphysema with alveolar ruptures in 3, accompanied by diffuse hemorrhage and increased hemosiderin resorption. CONCLUSION: In vEDS patients, identification of lung parenchymal abnormalities is common on CT. The most frequently observed CT finding was emphysema suggesting alveolar wall rupture which might facilitate the diagnostic screening of the disease in asymptomatic carriers of a genetic COL3A1 gene mutation. The prognostic value and evolution of these parenchymal abnormalities remain to be evaluated. KEY POINTS: • Patients with vEDS can have lung parenchymal changes on top of or next to thoracal vascular abnormalities and that these changes can be present in asymptomatic cases. • The presence of these parenchymal changes is associated with a slightly higher incidence of respiratory events (although not statistically significant). • Identification of the described CT pattern by radiologists and chest physicians may facilitate diagnostic screening.

Machine learning in cardiovascular radiology: ESCR position statement on design requirements, quality assessment, current applications, opportunities, and challenges.

Machine learning offers great opportunities to streamline and improve clinical care from the perspective of cardiac imagers, patients, and the industry and is a very active scientific research field. In light of these advances, the European Society of Cardiovascular Radiology (ESCR), a non-profit medical society dedicated to advancing cardiovascular radiology, has assembled a position statement regarding the use of machine learning (ML) in cardiovascular imaging. The purpose of this statement is to provide guidance on requirements for successful development and implementation of ML applications in cardiovascular imaging. In particular, recommendations on how to adequately design ML studies and how to report and interpret their results are provided. Finally, we identify opportunities and challenges ahead. While the focus of this position statement is ML development in cardiovascular imaging, most considerations are relevant to ML in radiology in general. KEY POINTS: • Development and clinical implementation of machine learning in cardiovascular imaging is a multidisciplinary pursuit. • Based on existing study quality standard frameworks such as SPIRIT and STARD, we propose a list of quality criteria for ML studies in radiology. • The cardiovascular imaging research community should strive for the compilation of multicenter datasets for the development, evaluation, and benchmarking of ML algorithms.

Neopulmonary Outflow Tract Obstruction Assessment by 4D Flow MRI in Adults With Transposition of the Great Arteries After Arterial Switch Operation.

BACKGROUND: The main complication in adult patients with transposition of the great arteries (TGA) treated by an arterial switch operation (ASO) is neopulmonary outflow tract stenosis (NPOTS). However, pulmonary flow velocity measurements cannot always be performed with transthoracic echocardiography (TTE) due to complex anatomical features. 4D flow MRI allows detection, quantification, and location of the obstruction site along the NPOTS. PURPOSE AND HYPOTHESIS: To investigate the accuracy of 4D flow for the diagnosis of NPOTS in adults with TGA corrected by ASO. STUDY TYPE: Prospective. POPULATION: Thirty-three adult patients with TGA treated by ASO (19 men, mean age 25.5 years old). FIELD STRENGTH/SEQUENCE: Accelerated 4D flow research sequence at 3T. ASSESSMENT: Maximum NPOTS velocities on TTE and 4D flow MRI done the same day. STATISTICAL TESTS: Pearson correlation coefficient, paired t-test, and Bland-Altman analysis were used to investigate the relationship between TTE and MRI data. RESULTS: In 16 patients (48.5%), evaluation of NPOTS anatomy was not obtained by TTE, while it was always possible by 4D flow. Peak flow velocity (PV) measurements in Doppler and 4D flow were highly correlated (r = 0.78; P < 0.001). PV >350 cm.s-1 was detected in only one patient (3%) by TTE vs. five patients (15%) by 4D flow. Moreover, a high correlation was found between PV and the right ventricle (RV) mass index to body surface area when using 4D flow (r = 0.63; P < 0.001). The location of NPOTS was determined in all patients using 4D flow and concerned the main pulmonary artery in 42%. DATA CONCLUSION: Compared to TTE, 4D flow MRI provides better sensitivity to detect and locate NPOTS in patients with TGA treated by ASO. 4D flow PV measurements in NPOTS were well correlated with TTE PV and RV mass. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2020;51:1699-1705.

Association of calcium density in the thoracic aorta with risk factors and clinical events.

OBJECTIVES: In the ascending aorta, calcification density was independently and inversely associated with cardiovascular disease (CVD) risk prediction. Until now, the density of thoracic aorta calcium (TAC) was estimated as the Agatston score divided by the calcium area (DAG). We thought to analyze TAC density in a full Hounsfield unit (HU) range and to study its association with TAC volume, traditional risk factors, and CVD events. METHODS: Non-enhanced CT images of 1426 patients at intermediate risk were retrospectively reviewed. A calcium density score was estimated as the average of the maximum HU attenuation in all calcified plaques of the entire thoracic aorta (DAV). RESULTS: During a mean 4.0 years follow-up, there were 26 events for a total of 674 patients with TAC > 0. TAC volume and DAV were positively correlated (R = 0.72). The median DAV value was 457 HU (IQ 323-603 HU) and was exponentially related to DAG (R = 0.86). DAV was inversely associated with systolic pressure (p < 0.05), pulse pressure (p < 0.01), hypertension (p < 0.05), and 10-year FRS (p < 0.001) after adjusting for TAC volume. When TAC volume and DAV were included in a logistic model, a significant improvement was shown in CVD risk estimation beyond coronary artery calcium (CAC) (AUC = 0.768 vs 0.814, p < 0.05). In multivariable Cox models, TAC volume and DAV showed an independent association with CVD. CONCLUSIONS: In intermediate risk patients, TAC density was inversely associated with several risk factors after adjustment for TAC volume. A significant improvement was observed over CAC when TAC volume and density were added into the risk prediction model. KEY POINTS: • Calcifications in the aorta can be non-invasively assessed using CT images • A higher calcium score is associated with a higher cardiovascular risk • Measuring the calcifications size and the density separately can improve the risk prediction.

Temporal registration: a new approach to manage the incomplete recovery of the longitudinal magnetization in the Modified Look-Locker Inversion Recovery sequence (MOLLI) for T1 mapping of the heart.

PURPOSE: To correct with post-processing effects of incomplete recovery of the longitudinal magnetization before a new inversion pulse in the Modified Look-Locker Inversion recovery sequence (MOLLI) sequence. THEORY AND METHODS: We model such effects as a temporal shift ([Formula: see text]) of the signal of the Look-Locker block following next inversion pulses. After using the following equation [Formula: see text], a temporal registration of [Formula: see text] is applied to the signal of the affected block to adjust the sampling time of the recovery signal and correct the underlying effect on quantitative T1. To test our approach, simulations, phantoms, and five volunteers' data were used while applying different MOLLI sampling schemes at different heart rates and compared to the reference three-parameter fit. RESULTS: The temporal registration of the affected signals allows to reach higher accuracy on long T1 when compared to the reference three parameters fit (10.15 vs 22.12% for T1 = 1785 ms; 8.22 vs 14.65% for T1 = 1278 ms), and lower average variation in case of rest-period deletion (62 vs 231 ms). CONCLUSION: The proposed approach leads to more accurate T1 in case of incomplete recovery. It is less sensitive to parameters affecting the recovery such as the rest period or the sampling scheme; and, therefore, supports multi-center studies with different MOLLI protocols.

Left ventricular and proximal aorta coupling in magnetic resonance imaging: aging together?

The importance of aorta-ventricular coupling in cardiovascular disease is recognized but underestimated. The contribution of the age-related decline in ascending aortic function compared with characteristic impedance and total peripheral resistance on left ventricular function and remodeling is poorly studied. Our aim was to evaluate the relation of proximal aortic distensibility and impedance with left ventricular geometry and function in asymptomatic individuals. We prospectively studied 100 subjects (47 men, 53 women, age: 20-84 yr). Aortic strain, distensibility, arch pulse wave velocity, characteristic impedance (Zc), total peripheral resistance, left ventricular (LV) volumes and mass, wall stress, and peak global circumferential myocardial strain and strain rates were determined by MRI. Central pressures were measured from tonometry. Ea/Ev, an index of vascular-ventricular coupling, and LV wall stress were preserved across age- or aortic-stiffness-stratified groups. Static and pulsatile components of aortic load were differentially associated with age. Increased total vascular resistance was associated with decreased LV strain and increased concentric remodeling [ratio of LV mass to end-diastolic volume (M/V ratio)] in all individuals. In younger individuals (<45 yr), aortic distensibility was related to LV strain and concentric remodeling (M/V ratio), whereas Zc was related to LV strain and concentric remodeling (M/V ratio) in older individuals (>45 yr). Early age-related stiffening of the ascending aorta is a component of LV afterload subsequently associated with increased aortic impedance and alterations in LV geometry, namely concentric remodeling, decreased myocardial strain, and increased stroke work such that LV wall stress and arterial-ventricular coupling are preserved. NEW & NOTEWORTHY Local flow and deformation can both be assessed with high precision noninvasively in the ascending aorta using MRI. Combined with central pressure measurement, they provide distensibility and impedance and simultaneous reference assessment of left ventricular deformation and geometry, hence a comprehensive evaluation of arterial-ventricular coupling to study physiology and disease.

Analysis of aortic pressure fields from 4D flow MRI in healthy volunteers: Associations with age and left ventricular remodeling.

BACKGROUND: Aging-related arterial stiffness is associated with substantial changes in global and local arterial pressures. The subsequent early return of reflected pressure waves leads to an elevated left ventricular (LV) afterload and ultimately to a deleterious concentric LV remodeling. PURPOSE: To compute aortic time-resolved pressure fields of healthy subjects from 4D flow MRI and to define relevant pressure-based markers while investigating their relationship with age, LV remodeling, as well as tonometric augmentation index (AIx) and pulse wave velocity (PWV). STUDY TYPE: Retrospective. POPULATION: Forty-seven healthy subjects (age: 49.5 ± 18 years, 24 women). FIELD STRENGTH/SEQUENCE: 3 T/4D flow MRI. ASSESSMENT: Spatiotemporal pressure fields were computed by integrating velocity-derived pressure gradients using Navier-Stokes equations, while assuming zero pressure at the sino-tubular junction. To quantify aortic pressure spatiotemporal variations, we defined the following markers: 1) volumetric aortic pressure propagation rates ΔP E1 /ΔV and ΔP E2 /ΔV, representing variations of early and late systolic relative pressure peaks along the aorta, respectively, according to the cumulated aortic volume; 2) ΔA PE1-PE2 defined in four aortic regions as the absolute difference between early and late systolic relative pressure peaks amplitude. STATISTICAL TESTS: Linear regression, Wilcoxon rank sum test, Bland-Altman analysis, and intraclass correlation coefficients (ICC). RESULTS: Spatiotemporal variations of aortic pressure peaks were moderately to highly reproducible (ICC ≥0.50) and decreased significantly with age, in terms of absolute magnitude: ΔP E1 /ΔV (r = 0.70, P < 0.005), ΔP E2 /ΔV (r = -0.45, P < 0.005) and ΔA PE1-PE2 (|r| > 0.39, P < 0.005). ΔP E1 /ΔV was associated with LV remodeling (r = 0.53, P < 0.001) and ascending aorta ΔA PE1-PE2 was associated with AIx (r = -0.59, P < 0.001). Both associations were independent of age and systolic blood pressures. Only weak associations were found between pressure indices and PWV (r ≤ 0.40). DATA CONCLUSION: 4D flow MRI relative aortic pressures were consistent with physiological knowledge as demonstrated by their significant volumetric and temporal variations with age and their independent association with LV remodeling and augmentation index. Level of Evidence 2 Technical Efficacy Stage 3 J. Magn. Reson. Imaging 2019;50:982-993.

Comparison of different methods for the estimation of aortic pulse wave velocity from 4D flow cardiovascular magnetic resonance.

BACKGROUND: Arterial pulse wave velocity (PWV) is associated with increased mortality in aging and disease. Several studies have shown the accuracy of applanation tonometry carotid-femoral PWV (Cf-PWV) and the relevance of evaluating central aorta stiffness using 2D cardiovascular magnetic resonance (CMR) to estimate PWV, and aortic distensibility-derived PWV through the theoretical Bramwell-Hill model (BH-PWV). Our aim was to compare various methods of aortic PWV (aoPWV) estimation from 4D flow CMR, in terms of associations with age, Cf-PWV, BH-PWV and left ventricular (LV) mass-to-volume ratio while evaluating inter-observer reproducibility and robustness to temporal resolution. METHODS: We studied 47 healthy subjects (49.5 ± 18 years) who underwent Cf-PWV and CMR including aortic 4D flow CMR as well as 2D cine SSFP for BH-PWV and LV mass-to-volume ratio estimation. The aorta was semi-automatically segmented from 4D flow data, and mean velocity waveforms were estimated in 25 planes perpendicular to the aortic centerline. 4D flow CMR aoPWV was calculated: using velocity curves at two locations, namely ascending aorta (AAo) and distal descending aorta (DAo) aorta (S1, 2D-like strategy), or using all velocity curves along the entire aortic centreline (3D-like strategies) with iterative transit time (TT) estimates (S2) or a plane fitting of velocity curves systolic upslope (S3). For S1 and S2, TT was calculated using three approaches: cross-correlation (TTc), wavelets (TTw) and Fourier transforms (TTf). Intra-class correlation coefficients (ICC) and Bland-Altman biases (BA) were used to evaluate inter-observer reproducibility and effect of lower temporal resolution. RESULTS: 4D flow CMR aoPWV estimates were significantly (p < 0.05) correlated to the CMR-independent Cf-PWV, BH-PWV, age and LV mass-to-volume ratio, with the strongest correlations for the 3D-like strategy using wavelets TT (S2-TTw) (R = 0.62, 0.65, 0.77 and 0.52, respectively, all p < 0.001). S2-TTw was also highly reproducible (ICC = 0.99, BA = 0.09 m/s) and robust to lower temporal resolution (ICC = 0.97, BA = 0.15 m/s). CONCLUSIONS: Reproducible 4D flow CMR aoPWV estimates can be obtained using full 3D aortic coverage. Such 4D flow CMR stiffness measures were significantly associated with Cf-PWV, BH-PWV, age and LV mass-to-volume ratio, with a slight superiority of the 3D strategy using wavelets transit time (S2-TTw).

Automatic correction of background phase offset in 4D-flow of great vessels and of the heart in MRI using a third-order surface model.

OBJECTIVE: To evaluate an automatic correction method for velocity offset errors in cardiac 4D-flow acquisitions. MATERIALS AND METHODS: Velocity offset correction was done in a plane-by-plane scheme and compared to a volumetric approach. Stationary regions were automatically detected. In vitro experiments were conducted in a phantom using two orientations and two encoding velocities (Venc). First- to third-order models were fit to the time-averaged images of the three velocity components. In vivo experiments included realistic ROIs in a volunteer superimposed to a phantom. In 15 volunteers, blood flow volume of the proximal and distal descending aorta, of the pulmonary artery (Qp) and the ascending aorta (Qs) was compared. RESULTS: Offset errors were reduced after correction with a third-order model, yielding residual phantom velocities below 0.6 cm/s and 0.4% of Venc. The plane-by-plane correction method was more effective than the volumetric approach. Mean velocities through superimposed ROIs of a volunteer vs phantom were highly correlated (r2 = 0.96). The significant difference between proximal and distal descending aortic flows was decreased after correction from 8.1 to - 1.4 ml (p < 0.001) and Qp/Qs reduced from 1.08 ± 0.09 to 1.01 ± 0.05. DISCUSSION: An automatic third-order model corrected velocity offset errors in 4D-flow acquisitions, achieving acceptable levels for clinical applications.