Early 3D Growth in Uncomplicated Type B Aortic Dissection is Associated with Long-Term Outcomes.

OBJECTIVE: Late adverse events (LAE) are common among initially uncomplicated type B aortic dissection (uTBAD), however, identifying those patients at highest risk of LAE remains a significant challenge. Early false lumen (FL) growth has been suggested to increase risk, but confident determination of growth is often hampered by error in 2D clinical measurements. Semi-automated 3D mapping of aortic growth, such as by vascular deformation mapping (VDM), can potentially overcome this limitation using CT angiograms (CTA). We hypothesized that FL growth in the early pre-dissection phase by VDM can accurately predict LAEs. METHODS: We performed a two-centre retrospective study of uTBAD patients, with paired CTAs in the acute (1-14 days) and subacute/early chronic (1-6 months) periods. VDM analysis was used to map 3D growth. Standard clinical CT measures (i.e., aortic diameters, tear characteristics) were also collected. Multivariate analysis was conducted using a decision tree and Cox proportional hazards model. LAEs were defined as aneurysmal FL (>55mm); rapid growth (>5mm within 6 months); aorta-specific mortality, rupture, or re-dissection. RESULTS: 107 (69% male) initially uTBAD patients met inclusion criteria with a median follow-up of 7.3 (IQR 4.7-9.9) years. LAEs occurred in 72 patients (67%) at 2.5 (IQR 0.7-4.8) years after the initial event. A multivariate decision tree model identified VDM growth (>2.1 mm) and baseline diameter (>42.7 mm) as optimal predictors of LAEs (AUC-ROC = 0.94), achieving an 87% accuracy (sensitivity of 93%, specificity of 76%) after leave-one-out validation. Guideline reported high-risk features were not significantly different between groups. CONCLUSION: Early growth of the FL in uTBAD was the best tested indicator for LAEs and improves upon the current gold-standard of baseline diameter in selecting patients for early prophylactic TEVAR.

Inter-observer variability of expert-derived morphologic risk predictors in aortic dissection.

OBJECTIVES: Establishing the reproducibility of expert-derived measurements on CTA exams of aortic dissection is clinically important and paramount for ground-truth determination for machine learning. METHODS: Four independent observers retrospectively evaluated CTA exams of 72 patients with uncomplicated Stanford type B aortic dissection and assessed the reproducibility of a recently proposed combination of four morphologic risk predictors (maximum aortic diameter, false lumen circumferential angle, false lumen outflow, and intercostal arteries). For the first inter-observer variability assessment, 47 CTA scans from one aortic center were evaluated by expert-observer 1 in an unconstrained clinical assessment without a standardized workflow and compared to a composite of three expert-observers (observers 2-4) using a standardized workflow. A second inter-observer variability assessment on 30 out of the 47 CTA scans compared observers 3 and 4 with a constrained, standardized workflow. A third inter-observer variability assessment was done after specialized training and tested between observers 3 and 4 in an external population of 25 CTA scans. Inter-observer agreement was assessed with intraclass correlation coefficients (ICCs) and Bland-Altman plots. RESULTS: Pre-training ICCs of the four morphologic features ranged from 0.04 (-0.05 to 0.13) to 0.68 (0.49-0.81) between observer 1 and observers 2-4 and from 0.50 (0.32-0.69) to 0.89 (0.78-0.95) between observers 3 and 4. ICCs improved after training ranging from 0.69 (0.52-0.87) to 0.97 (0.94-0.99), and Bland-Altman analysis showed decreased bias and limits of agreement. CONCLUSIONS: Manual morphologic feature measurements on CTA images can be optimized resulting in improved inter-observer reliability. This is essential for robust ground-truth determination for machine learning models. KEY POINTS: • Clinical fashion manual measurements of aortic CTA imaging features showed poor inter-observer reproducibility. • A standardized workflow with standardized training resulted in substantial improvements with excellent inter-observer reproducibility. • Robust ground truth labels obtained manually with excellent inter-observer reproducibility are key to develop reliable machine learning models.

4D Flow cardiovascular magnetic resonance consensus statement: 2023 update.

Hemodynamic assessment is an integral part of the diagnosis and management of cardiovascular disease. Four-dimensional cardiovascular magnetic resonance flow imaging (4D Flow CMR) allows comprehensive and accurate assessment of flow in a single acquisition. This consensus paper is an update from the 2015 '4D Flow CMR Consensus Statement'. We elaborate on 4D Flow CMR sequence options and imaging considerations. The document aims to assist centers starting out with 4D Flow CMR of the heart and great vessels with advice on acquisition parameters, post-processing workflows and integration into clinical practice. Furthermore, we define minimum quality assurance and validation standards for clinical centers. We also address the challenges faced in quality assurance and validation in the research setting. We also include a checklist for recommended publication standards, specifically for 4D Flow CMR. Finally, we discuss the current limitations and the future of 4D Flow CMR. This updated consensus paper will further facilitate widespread adoption of 4D Flow CMR in the clinical workflow across the globe and aid consistently high-quality publication standards.

A low-rank deep image prior reconstruction for free-breathing ungated spiral functional CMR at 0.55 T and 1.5 T.

OBJECTIVE: This study combines a deep image prior with low-rank subspace modeling to enable real-time (free-breathing and ungated) functional cardiac imaging on a commercial 0.55 T scanner. MATERIALS AND METHODS: The proposed low-rank deep image prior (LR-DIP) uses two u-nets to generate spatial and temporal basis functions that are combined to yield dynamic images, with no need for additional training data. Simulations and scans in 13 healthy subjects were performed at 0.55 T and 1.5 T using a golden angle spiral bSSFP sequence with images reconstructed using [Formula: see text]-ESPIRiT, low-rank plus sparse (L + S) matrix completion, and LR-DIP. Cartesian breath-held ECG-gated cine images were acquired for reference at 1.5 T. Two cardiothoracic radiologists rated images on a 1-5 scale for various categories, and LV function measurements were compared. RESULTS: LR-DIP yielded the lowest errors in simulations, especially at high acceleration factors (R [Formula: see text] 8). LR-DIP ejection fraction measurements agreed with 1.5 T reference values (mean bias - 0.3% at 0.55 T and - 0.2% at 1.5 T). Compared to reference images, LR-DIP images received similar ratings at 1.5 T (all categories above 3.9) and slightly lower at 0.55 T (above 3.4). CONCLUSION: Feasibility of real-time functional cardiac imaging using a low-rank deep image prior reconstruction was demonstrated in healthy subjects on a commercial 0.55 T scanner.

Vascular Deformation Mapping for CT Surveillance of Thoracic Aortic Aneurysm Growth.

Background Aortic diameter measurements in patients with a thoracic aortic aneurysm (TAA) show wide variation. There is no technique to quantify aortic growth in a three-dimensional (3D) manner. Purpose To validate a CT-based technique for quantification of 3D growth based on deformable registration in patients with TAA. Materials and Methods Patients with ascending and descending TAA with two or more CT angiography studies between 2006 and 2020 were retrospectively identified. The 3D aortic growth was quantified using vascular deformation mapping (VDM), a technique that uses deformable registration to warp a mesh constructed from baseline aortic anatomy. Growth assessments between VDM and clinical CT diameter measurements were compared. Aortic growth was quantified as the ratio of change in surface area at each mesh element (area ratio). Manual segmentations were performed by independent raters to assess interrater reproducibility. Registration error was assessed using manually placed landmarks. Agreement between VDM and clinical diameter measurements was assessed using Pearson correlation and Cohen κ coefficients. Results A total of 38 patients (68 surveillance intervals) were evaluated (mean age, 69 years ± 9 [standard deviation]; 21 women), with TAA involving the ascending aorta (n = 26), descending aorta (n = 10), or both (n = 2). VDM was technically successful in 35 of 38 (92%) patients and 58 of 68 intervals (85%). Median registration error was 0.77 mm (interquartile range, 0.54-1.10 mm). Interrater agreement was high for aortic segmentation (Dice similarity coefficient = 0.97 ± 0.02) and VDM-derived area ratio (bias = 0.0, limits of agreement: -0.03 to 0.03). There was strong agreement (r = 0.85, P < .001) between peak area ratio values and diameter change. VDM detected growth in 14 of 58 (24%) intervals. VDM revealed growth outside the maximally dilated segment in six of 14 (36%) growth intervals, none of which were detected with diameter measurements. Conclusion Vascular deformation mapping provided reliable and comprehensive quantitative assessment of three-dimensional aortic growth and growth patterns in patients with thoracic aortic aneurysms undergoing CT surveillance. Published under a CC BY 4.0 license Online supplemental material is available for this article. See also the editorial by Wieben in this issue.

False lumen pressure estimation in type B aortic dissection using 4D flow cardiovascular magnetic resonance: comparisons with aortic growth.

BACKGROUND: Chronic type B aortic dissection (TBAD) is associated with poor long-term outcome, and accurate risk stratification tools remain lacking. Pressurization of the false lumen (FL) has been recognized as central in promoting aortic growth. Several surrogate imaging-based metrics have been proposed to assess FL hemodynamics; however, their relationship to enlarging aortic dimensions remains unclear. We investigated the association between aortic growth and three cardiovascular magnetic resonance (CMR)-derived metrics of FL pressurization: false lumen ejection fraction (FLEF), maximum systolic deceleration rate (MSDR), and FL relative pressure (FL ΔPmax). METHODS: CMR/CMR angiography was performed in 12 patients with chronic dissection of the descending thoracoabdominal aorta, including contrast-enhanced CMR angiography and time-resolved three-dimensional phase-contrast CMR (4D Flow CMR). Aortic growth rate was calculated as the change in maximal aortic diameter between baseline and follow-up imaging studies over the time interval, with patients categorized as having either 'stable' (< 3 mm/year) or 'enlarging' (≥ 3 mm/year) growth. Three metrics relating to FL pressurization were defined as: (1) FLEF: the ratio between retrograde and antegrade flow at the TBAD entry tear, (2) MSDR: the absolute difference between maximum and minimum systolic acceleration in the proximal FL, and (3) FL ΔPmax: the difference in absolute pressure between aortic root and distal FL. RESULTS: FLEF was higher in enlarging TBAD (49.0 ± 17.9% vs. 10.0 ± 11.9%, p = 0.002), whereas FL ΔPmax was lower (32.2 ± 10.8 vs. 57.2 ± 12.5 mmHg/m, p = 0.017). MSDR and conventional anatomic variables did not differ significantly between groups. FLEF showed positive (r = 0.78, p = 0.003) correlation with aortic growth rate whereas FL ΔPmax showed negative correlation (r = - 0.64, p = 0.026). FLEF and FL ΔPmax remained as independent predictors of aortic growth rate after adjusting for baseline aortic diameter. CONCLUSION: Comparative analysis of three 4D flow CMR metrics of TBAD FL pressurization demonstrated that those that focusing on retrograde flow (FLEF) and relative pressure (FL ΔPmax) independently correlated with growth and differentiated patients with enlarging and stable descending aortic dissections. These results emphasize the highly variable nature of aortic hemodynamics in TBAD patients, and suggest that 4D Flow CMR derived metrics of FL pressurization may be useful to separate patients at highest and lowest risk for progressive aortic growth and complications.

Endovascular ascending aortic repair in type A dissection: A systematic review.

PURPOSE: Up to 10% of acute type A aortic dissection (TAAD) patients are deemed unfit for open surgical repair, exposing these patients to high mortality rates. In recent years, thoracic endovascular aortic repair has proven to be a promising alternative treatment modality in specific cases. This study presents a comprehensive overview of the current state of catheter-based interventions in the setting of primary TAAD. METHODS: A literature search was conducted, using MEDLINE and PubMed databases according to PRISMA guidelines, updated until January 2020. Articles were selected if they reported on the endovascular repair of DeBakey Type I and II aortic dissections. The exclusion criteria were retrograde type A dissection, hybrid procedures, and combined outcome reporting of mixed aortic pathologies (e.g., pseudoaneurysm and intramural hematoma). RESULTS: A total of 31 articles, out of which 19 were case reports and 12 case series, describing a total of 92 patients, were included. The median follow-up was 6 months for case reports and the average follow-up was 14 months for case series. Overall technical success was 95.6% and 30-day mortality of 9%. Stroke and early endoleak rates were 6% and 18%, respectively. Reintervention was required in 14 patients (15%). CONCLUSION: This review not only demonstrates that endovascular repair in the setting of isolated TAAD is feasible with acceptable outcomes at short-term follow-up, but also underlines a lack of mid-late outcomes and reporting consistency. Studies with longer follow-up and careful consideration of patient selection are required before endovascular interventions can be widely introduced.

Critical appraisal of multidimensional CT measurements following acute open repair of type A aortic dissection.

INTRODUCTION: To identify patients with aneurysmal degeneration of the native aorta following type A aortic dissection (TAAD), reproducible serial measurements of aortic dimensions are critical. We used a systematic workflow for measuring aortic geometry following TAAD, using computed tomography angiography data, and test its reproducibility. METHODS: The workflow for aortic measurements included centerline generation, luminal diameter, and area measurement at six anatomically defined locations along the aorta and luminal volumetric measurements in the descending aorta. Two independent observers measured the aortic geometry in 20 surgically repaired TAAD patients, preoperatively and at 3 months follow-up. To test reproducibility, intraobserver and interobserver agreement scores were analyzed using a concordance correlation coefficient (CCC). RESULTS: The interobserver agreement scores of the diameter, area, and volumetric measurements in the descending aorta were acceptable. The agreement scores of the area measurements were highest, with CCCs ranging from 0.909 to 0.984. Luminal diameter measurements scored lower than luminal area measurements and were least reproducible at the mid aortic arch (CCC < 0.886). Overall, intraobserver agreement scores were better than interobserver agreement scores (SD of mean difference was 1.89 vs 1.94 for intraobserver vs interobserver diameter measurements, and 0.61 vs 0.66 for area measurements). CONCLUSION: Although overall reproducibility was acceptable in descending aortic measurements, our results show that it remains challenging to reliably measure luminal diameters, compared with areas. To aid identification of early adverse remodeling following acute TAAD, novel two- and three-dimensional measurement techniques are needed that capture locoregional changes in the false lumen and true lumen morphology more accurately.

Detection of Small Pulmonary Nodules with Ultrashort Echo Time Sequences in Oncology Patients by Using a PET/MR System.

PURPOSE: To investigate the utility of a free-breathing ultrashort echo time (UTE) sequence for the evaluation of small pulmonary nodules in oncology patients by using a hybrid positron emission tomography (PET)/magnetic resonance (MR) imaging system and to compare the nodule detection rate between UTE and a conventional three-dimensional gradient-recalled-echo (GRE) technique. MATERIALS AND METHODS: In this HIPAA-compliant, institutional review board-approved prospective study, 82 pulmonary nodules were identified in eight patients with extrathoracic malignancies. Patients underwent free-breathing UTE and dual-echo three-dimensional GRE imaging of the lungs in a hybrid PET/MR imaging unit immediately after clinical PET/computed tomography (CT). CT was considered the reference standard for nodule detection. Two reviewers identified nodules and obtained measurements on MR images. The McNemar test was used to evaluate differences in nodule detection rate between MR techniques, and interrater agreement was assessed by using Bland-Altman plots. RESULTS: Mean nodule diameter ± standard deviation was 6.2 mm ± 2.7 (range, 3-17 mm). The detection rate was higher for UTE imaging than for dual-echo GRE imaging for nodules of at least 4 mm (82% vs 34%, respectively; P < .001), with the largest difference in detection noted in the 4-8-mm nodule group (79% vs 21%, P < .001). UTE imaging displayed a higher detection rate than dual-echo GRE imaging for nodules without fluorodeoxyglucose avidity (68% vs 22%, respectively; P < .001). Interrater reliability of nodule detection with MR imaging was high (κ = 0.90 for UTE imaging and κ = 0.92 for dual-echo GRE imaging). CONCLUSION: A free-breathing UTE sequence has high sensitivity for the detection of small pulmonary nodules (4-8 mm) and outperformed a three-dimensional dual-echo GRE technique for the detection of small, non-fluorodeoxyglucose-avid nodules.

Ascending Aortic Stiffness with Bicuspid Aortic Valve is Variable and Not Predicted by Conventional Parameters in Young Patients.

BACKGROUND: Bicuspid aortic valve (BAV)-related aortopathy is characterized by histological abnormalities that result in aortic wall stiffening and aortic dilation. The study aim was to determine the range of ascending aortic stiffness seen in a clinical cohort of patients with BAV, and to identify the association of aortic stiffness with standard clinical and imaging parameters. METHODS: Patients with BAV (n = 65) and normal subjects (n = 10) were studied using conventional phase-contrast magnetic resonance imaging through the ascending aorta. Local aortic stiffness was estimated by measuring pulse wave velocity (PWV) using the flow-area (QA) method. Correlations between PWV and other imaging and clinical variables were assessed, and multiple linear regression models were used to examine independent predictors of PWV. RESULTS: BAV patients demonstrated a significantly higher mean PWV compared to normal subjects (6.53 ± 5.88 versus 3.51 ± 0.92 m/s; p <0.01) with a considerably wider range of values noted in the BAV group. Significant associations were found between PWV and age (r = 0.4, p <0.001) and history of hypertension (r = 0.36, p = 0.005) in the overall BAV cohort. The correlation between age and PWV was significantly strengthened above 40 years of age. In a subgroup of BAV patients aged <40 years (n = 37) there were no significant predictors of PWV identified by multiple linear regression models. CONCLUSIONS: BAV patients demonstrated an increased average ascending aortic stiffness and a dramatically higher range of stiffness values compared to normal subjects. Increased stiffness is not predicted by standard clinical or imaging parameters in patients aged <40 years. Ascending aortic stiffness may be a unique marker of early aortic dysfunction in young BAV patients.

Pulmonary Metastatic Follicular Thyroid Carcinoma Without Intrathyroidal Primary Thyroid Cancer.

Background/Objective: Follicular thyroid cancer without an intrathyroidal primary cancer is rare. We present a patient with multifocal pulmonary metastatic follicular thyroid cancer without apparent cancer within her thyroid. Case Report: A 44-year-old woman was referred to the thyroid cancer clinic via telemedicine for evaluation of intrapulmonary thyroid tissue. Her past medical history included Roux-en-Y gastric bypass and hysterectomy with bilateral oophorectomy. Six months prior, abdominal computed tomography (CT) showed incidental bilateral lung nodules. Chest CT demonstrated 4 solid left and 1 solid right lung nodules. Lung nodule core biopsy revealed benign thyroid tissue. Thyroid ultrasound showed bilateral subcentimeter anechoic nodules. Chest CT 6 months after initial CT demonstrated stable lung nodules. The levels of thyroid-stimulating hormone, serum thyroglobulin, and thyroglobulin antibody were 1.63 mIU/L (reference range, 0.3-5.5 mIU/L), 40.9 ng/mL (reference range, 0-35 ng/mL), and <1 IU/mL (reference range, <4), respectively. Positron emission tomography/CT showed fluorodeoxyglucose-avid lung lesions measuring 1.5, 1.1, and 2.2 cm and other subcentimeter pulmonary nodules. Repeat lung core biopsy showed thyroid tissue with microfollicular architecture, favoring metastatic follicular carcinoma with neuroblastoma-RAS gene (NRAS) mutation. Total thyroidectomy performed showed multinodular hyperplasia without thyroid cancer. Her postoperative radioiodine scan demonstrated bilateral iodine-avid pulmonary nodules, a serum thyroglobulin level of 179.8 ng/mL, a thyroid-stimulating hormone level of 151.3 mIU/L, and undetectable serum thyroglobulin antibody. She received 261 mCi of radioactive iodine. Fourteen months later, chest CT revealed decreased lung nodules and a serum thyroglobulin level of 0.7 ng/mL. Discussion: Approximately 2 cases of multifocal pulmonary follicular thyroid cancer without a primary source and no other site of metastasis have been reported. Conclusion: Pulmonary follicular thyroid cancer without a primary source and no other site of metastasis is extremely rare.

Changes in aortic root dimensions post aortic root enlargement with Y-incision and modified aortotomy.

Background: Lifetime management in aortic stenosis (AS) can be facilitated by aortic root enlargement (ARE) to improve anatomy for future valve-in-valve (ViV) procedures. A mitral valve-sparing ARE technique ("Y-incision") and sinotubular junction (STJ) enlargement ("roof" patch aortotomy) allow upsizing by 3-4 valve sizes, but quantitative analysis of changes in root anatomy is lacking. Methods: Among 78 patients who underwent ARE by Y-incision technique (± roof aortotomy closure) we identified 45 patients with high-quality pre- and post-operative computed tomography angiography (CTA) scans to allow analysis of change in aortic root dimensions. Detailed measurements of the annulus/basilar ring and sinuses were performed by an expert imager on both pre- and post-operative CTAs. The basal ring was defined as the functional annulus when a bioprosthetic valve was present. Results: Average age was 65±11 years, the majority were female (29, 64%), and 9 (20%) had undergone prior aortic valve replacement (AVR). Valve upsizing was ≥3 sizes in 41 (91%). Post-operative mean basal ring diameter was larger compared to the native annular diameter (26.3 vs. 25.3 mm, P<0.01) and substantially larger than prior prosthetic valve in redo AVR (25.6 vs. 19.3 mm, P<0.001). Diameters of the sinuses at pre-operative computed tomography (CT) increased by +7.7±2.8 [right sinuses of Valsalva (R SVS)], +6.7±3.0 [left sinuses of Valsalva (L SVS)], and +6.6±2.9 mm [non-coronary sinuses of Valsalva (N SVS)]. Mean diameter of the STJ increased to 38.3±3.7 post-operative (+8.1±3.2 mm). Left main (LM) and right coronary artery (RCA) heights decreased by -6.3±3.3 and -3.7±3.4 mm respectively due to the supra-annular position of the valve, however, the post-operative valve-to-coronary (VTC) artery distances were 6.6±2.3 and 4.9±2.0 mm, respectively. Conclusion: The Y-incision root enlargement technique significantly enlarges the sinus and STJ diameters by 6-7 mm while preserving VTC distances despite upsizing by 3-4 valve sizes, resulting in post-operative anatomy that is favorable for future transcatheter aortic valve-in-surgical aortic valve (TAV-in-SAV).

Generalized super-resolution 4D Flow MRI - using ensemble learning to extend across the cardiovascular system.

4D Flow Magnetic Resonance Imaging (4D Flow MRI) is a non-invasive measurement technique capable of quantifying blood flow across the cardiovascular system. While practical use is limited by spatial resolution and image noise, incorporation of trained super-resolution (SR) networks has potential to enhance image quality post-scan. However, these efforts have predominantly been restricted to narrowly defined cardiovascular domains, with limited exploration of how SR performance extends across the cardiovascular system; a task aggravated by contrasting hemodynamic conditions apparent across the cardiovasculature. The aim of our study was therefore to explore the generalizability of SR 4D Flow MRI using a combination of existing super-resolution base models, novel heterogeneous training sets, and dedicated ensemble learning techniques; the latter-most being effectively used for improved domain adaption in other domains or modalities, however, with no previous exploration in the setting of 4D Flow MRI. With synthetic training data generated across three disparate domains (cardiac, aortic, cerebrovascular), varying convolutional base and ensemble learners were evaluated as a function of domain and architecture, quantifying performance on both in-silico and acquired in-vivo data from the same three domains. Results show that both bagging and stacking ensembling enhance SR performance across domains, accurately predicting high-resolution velocities from low-resolution input data in-silico. Likewise, optimized networks successfully recover native resolution velocities from downsampled in-vivo data, as well as show qualitative potential in generating denoised SR-images from clinicallevel input data. In conclusion, our work presents a viable approach for generalized SR 4D Flow MRI, with the novel use of ensemble learning in the setting of advanced fullfield flow imaging extending utility across various clinical areas of interest.

Fully automated pipeline for measurement of the thoracic aorta using joint segmentation and localization neural network.

Purpose: Diagnosis and surveillance of thoracic aortic aneurysm (TAA) involves measuring the aortic diameter at various locations along the length of the aorta, often using computed tomography angiography (CTA). Currently, measurements are performed by human raters using specialized software for three-dimensional analysis, a time-consuming process, requiring 15 to 45 min of focused effort. Thus, we aimed to develop a convolutional neural network (CNN)-based algorithm for fully automated and accurate aortic measurements. Approach: Using 212 CTA scans, we trained a CNN to perform segmentation and localization of key landmarks jointly. Segmentation mask and landmarks are subsequently used to obtain the centerline and cross-sectional diameters of the aorta. Subsequently, a cubic spline is fit to the aortic boundary at the sinuses of Valsalva to avoid errors related inclusions of coronary artery origins. Performance was evaluated on a test set of 60 scans with automated measurements compared against expert manual raters. Result: Compared to training separate networks for each task, joint training yielded higher accuracy for segmentation, especially at the boundary (p<0.001), but a marginally worse (0.2 to 0.5 mm) accuracy for landmark localization (p<0.001). Mean absolute error between human and automated was ≤1 mm at six of nine standard clinical measurement locations. However, higher errors were noted in the aortic root and arch regions, ranging between 1.4 and 2.2 mm, although agreement of manual raters was also lower in these regions. Conclusion: Fully automated aortic diameter measurements in TAA are feasible using a CNN-based algorithm. Automated measurements demonstrated low errors that are comparable in magnitude to those with manual raters; however, measurement error was highest in the aortic root and arch.

Three-Dimensional Characterization of Aortic Root Motion by Vascular Deformation Mapping.

The aorta is in constant motion due to the combination of cyclic loading and unloading with its mechanical coupling to the contractile left ventricle (LV) myocardium. This aortic root motion has been proposed as a marker for aortic disease progression. Aortic root motion extraction techniques have been mostly based on 2D image analysis and have thus lacked a rigorous description of the different components of aortic root motion (e.g., axial versus in-plane). In this study, we utilized a novel technique termed vascular deformation mapping (VDM(D)) to extract 3D aortic root motion from dynamic computed tomography angiography images. Aortic root displacement (axial and in-plane), area ratio and distensibility, axial tilt, aortic rotation, and LV/Ao angles were extracted and compared for four different subject groups: non-aneurysmal, TAA, Marfan, and repair. The repair group showed smaller aortic root displacement, aortic rotation, and distensibility than the other groups. The repair group was also the only group that showed a larger relative in-plane displacement than relative axial displacement. The Marfan group showed the largest heterogeneity in aortic root displacement, distensibility, and age. The non-aneurysmal group showed a negative correlation between age and distensibility, consistent with previous studies. Our results revealed a strong positive correlation between LV/Ao angle and relative axial displacement and a strong negative correlation between LV/Ao angle and relative in-plane displacement. VDM(D)-derived 3D aortic root motion can be used in future studies to define improved boundary conditions for aortic wall stress analysis.

lGeneralized super-resolution 4D Flow MRI-using ensemble learning to extend across the cardiovascular system.

4D Flow Magnetic Resonance Imaging (4D Flow MRI) is a non-invasive measurement technique capable of quantifying blood flow across the cardiovascular system. While practical use is limited by spatial resolution and image noise, incorporation of trained super-resolution (SR) networks has potential to enhance image quality post-scan. However, these efforts have predominantly been restricted to narrowly defined cardiovascular domains, with limited exploration of how SR performance extends across the cardiovascular system; a task aggravated by contrasting hemodynamic conditions apparent across the cardiovasculature. The aim of our study was to explore the generalizability of SR 4D Flow MRI using a combination of heterogeneous training sets and dedicated ensemble learning. With synthetic training data generated across three disparate domains (cardiac, aortic, cerebrovascular), varying convolutional base and ensemble learners were evaluated as a function of domain and architecture, quantifying performance on both in-silico and acquired in-vivo data from the same three domains. Results show that both bagging and stacking ensembling enhance SR performance across domains, accurately predicting high-resolution velocities from low-resolution input data in-silico. Likewise, optimized networks successfully recover native resolution velocities from downsampled in-vivo data, as well as show qualitative potential in generating denoised SR-images from clinicallevel input data. In conclusion, our work presents a viable approach for generalized SR 4D Flow MRI, with ensemble learning extending utility across various clinical areas of interest.

Natural history and clinical significance of aortic focal intimal flaps.

Objective: Focal intimal flaps (FIF) are a variety of defects of the aorta that result in a short, flap-like projection into the lumen, and are often encountered in asymptomatic patients undergoing computed tomography angiography (CTA) surveillance for aortic aneurysm, but the natural history and clinical significance of such lesions has not yet been studied. Methods: We retrospectively identified patients with an asymptomatic FIF and available imaging follow-up (>1 year). FIF was defined as flap-like intimal irregularity < 4 cm in length involving the thoracic aorta (TA), abdominal aorta (AA) or common iliac arteries (CIA). FIF characteristics included length and circumferential extent as well as the presence and size (width and depth) of associated penetrating aortic ulcers (PAUs). Patient characteristics, adverse events and history of surgical repair was determined by chart review. FIFs and associated PAUs were assessed for progression by comparing baseline and follow-up CTA studies. Results: A total of 84 FIFs were identified in 77 patients. Average age was 69.2 ± 10.1 years, and 81% were male (81%). Common co-morbidities included: hypertension (78%), hyperlipidemia (68%), smoking (60%), coronary artery disease (41%), aortic aneurysm (34%), type II diabetes mellitus (27%) and prior cardiovascular surgery (25%). FIFs were most commonly located in the abdominal aorta (n = 50, 60%). Nearly all FIFs were associated with local atherosclerotic plaque (93%). Mean follow-up interval was 3.5 ± 2.6 years (259 cumulative follow-up years). Change in FIF length and local aortic diameter over follow-up were 0.7 ± 2.3 mm and 0.8 ± 1.1 mm, respectively. Nearly half (47%) of FIFs were associated with penetrating aortic ulcers (PAU) with baseline depth of 7.3 mm (IQR: 6.1-10.2) and change in depth of 0.5 ± 1.4 mm. Only 12% of FIFs and 0% of associated PAUs demonstrated growth (≥3 mm) at follow-up. No acute pathology developed in the location of FIFs and no aortic interventions were performed specifically to treat FIFs. Conclusion: Focal intimal flaps identified in asymptomatic patients with aortic disease were co-localized with atherosclerotic plaque and PAUs, and demonstrated indolent behavior, not leading to significant growth or acute aortic events, supporting a conservative management approach.

Validation of a robust method for quantification of three-dimensional growth of the thoracic aorta using deformable image registration.

PURPOSE: Accurate assessment of thoracic aortic aneurysm (TAA) growth is important for appropriate clinical management. Maximal aortic diameter is the primary metric that is used to assess growth, but it suffers from substantial measurement variability. A recently proposed technique, termed vascular deformation mapping (VDM), is able to quantify three-dimensional aortic growth using clinical computed tomography angiography (CTA) data using an approach based on deformable image registration (DIR). However, the accuracy and robustness of VDM remains undefined given the lack of ground truth from clinical CTA data, and, furthermore, the performance of VDM relative to standard manual diameter measurements is unknown. METHODS: To evaluate the performance of the VDM pipeline for quantifying aortic growth, we developed a novel and systematic evaluation process to generate 76 unique synthetic CTA growth phantoms (based on 10 unique cases) with variable degrees and locations of aortic wall deformation. Aortic deformation was quantified using two metrics: area ratio (AR), defined as the ratio of surface area in triangular mesh elements and the magnitude of deformation in the normal direction (DiN) relative to the aortic surface. Using these phantoms, we further investigated the effects on VDM's measurement accuracy resulting from factors that influence the quality of clinical CTA data such as respiratory translations, slice thickness, and image noise. Lastly, we compare the measurement error of VDM TAA growth assessments against two expert raters performing standard diameter measurements of synthetic phantom images. RESULTS: Across our population of 76 synthetic growth phantoms, the median absolute error was 0.063 (IQR: 0.073-0.054) for AR and 0.181 mm (interquartile range [IQR]: 0.214-0.143 mm) for DiN. Median relative error was 1.4% for AR and 3.3 % $3.3\%$ for DiN at the highest tested noise level (contrast-to-noise ratio [CNR] = 2.66). Error in VDM output increased with slice thickness, with the highest median relative error of 1.5% for AR and 4.1% for DiN at a slice thickness of 2.0 mm. Respiratory motion of the aorta resulted in maximal absolute error of 3% AR and 0.6 mm in DiN, but bulk translations in aortic position had a very small effect on measured AR and DiN values (relative errors < 1 % $< 1\%$ ). VDM-derived measurements of magnitude and location of maximal diameter change demonstrated significantly high accuracy and lower variability compared to two expert manual raters ( p < 0.03 $p<0.03$ across all comparisons). CONCLUSIONS: VDM yields an accurate, three-dimensional assessment of aortic growth in TAA patients and is robust to factors such as image noise, respiration-induced translations, and differences in patient position. Further, VDM significantly outperformed two expert manual raters in assessing the magnitude and location of aortic growth despite optimized experimental measurement conditions. These results support validation of the VDM technique for accurate quantification of aortic growth in patients and highlight several important advantages over diameter measurements.

Patient-Specific Computational Modeling of Different Cannulation Strategies for Extracorporeal Membrane Oxygenation.

Institution of extracorporeal membrane oxygenation (ECMO) results in unique blood flow characteristics to the end-organ vascular beds. We studied the interplay between cardiac-driven and extracorporeal membrane oxygenation (ECMO)-driven flow to vascular beds in different ECMO configurations using a patient-specific computational fluid dynamics (CFD) analysis. A computational ECMO model (femoral artery cannulation [FAC]) was constructed using patient-specific imaging and hemodynamic data. Following model calibration, we augmented the 3D geometrical model to represent alternative ECMO configurations (ascending aorta cannulation [AAC] and subclavian artery cannulation [SAC]). We performed CFD analyses, including a novel virtual color-dye analysis to compare global and regional blood flow and pressure characteristics as well as contributions of cardiac and ECMO-derived flow to the various vascular beds. Flow waveforms at all the aortic branch vessels were pulsatile, despite low cardiac output and predominant nonpulsatile ECMO-driven hemodynamics. Virtual color-dye analysis revealed differential contribution of cardiac and ECMO-derived flow to the end-organ vascular beds in the FAC model, while this was more evenly distributed in the AAC and SAC models. While global hemodynamics were relatively similar between various ECMO configurations, several distinct hemodynamic indices, in particular wall shear stress and oscillatory shear patterns, as well as differential contribution of ECMO-derived flow to various vascular beds, showed remarkable differences. The clinical impact of this study highlighting the relevance of CFD modeling in assessment of complex hemodynamics in ECMO warrants further evaluation.

Left ventricular remodeling following aortic root and ascending aneurysm repair.

Objective: Adverse left ventricular remodeling due to a mismatch between stiffness of native aortic tissue and current polyester grafts may be under-recognized. This study was conducted to evaluate the impact of proximal aortic replacement on adverse remodeling of the left ventricle. Materials and methods: All aortic root and ascending aortic aneurysm patients were identified (n = 2,001, 2006-2019). The study cohort consisted of a subset of patients (n = 98) with two or more electrocardiogram (ECG)-gated CT angiograms, but without concomitant aortic valve disease or bicuspid aortic valve, connective tissue disease, acute aortic syndrome or prior history of aortic repair or mitral valve surgery. LV myocardial mass was measured from CT data and indexed to body surface area (LVMI). The study cohort was divided into a surgery group (n = 47) and a control group; optimal medical therapy group (OMT, n = 51). Results: The mean age was 60 ± 11 years (80% male). Beta-blocker use was significantly more frequent in the surgery group (89 vs. 57%, p < 0.001), whereas, all other antihypertensive drugs were more frequent in the OMT group. The average follow-up was 9.1 ± 4.0 months for the surgery group and 13.7 ± 6.3 months for the OMT group. Average LVMI at baseline was similar in both groups (p = 0.934). LVMI increased significantly in the surgery group compared to the OMT group (3.7 ± 4.1 vs. 0.6 ± 4.4 g/m2, p = 0.001). Surgery, baseline LVMI, age, and sex were found to be independent predictors of LVMI increased on multivariable analysis. Conclusion: Proximal aortic repair with stiff polyester grafts was associated with increased LV mass in the first-year post-operative and may promote long-term adverse cardiac remodeling. Further studies should be considered to evaluate the competing effects of aortic aneurysm related mortality against risks of long-term graft induced aortic stiffening and the potential implications on current size thresholds for intervention.