Search

ObjectivesDiameter-based risk stratification for elective repair of ascending aortic aneurysm fails to prevent type A dissection in many patients. Aneurysm wall stresses may contribute to risk prediction; however, rates of wall stress change over time are poorly understood. Our objective was to examine aneurysm wall stress changes over 3-5 years and subsequent all-cause mortality.MethodsMale veterans with

ObjectivesCurrent diameter-based guidelines for ascending thoracic aortic aneurysms (aTAA) do not consistently predict risk of dissection/rupture. ATAA wall stresses may enhance risk stratification independent of diameter. The relation of wall stresses and diameter indexed to height and body surface area (BSA) is unknown. Our objective was to compare aTAA wall stresses with indexed diameters in relation to all-cause mortality at 3.75 years follow-up.MethodsFinite element analyses were performed in a veteran population with aortas ≥ 4.0 cm. Three-dimensional geometries were reconstructed from computed tomography with models accounting for pre-stress geometries. A fiber-embedded hyperelastic material model was applied to obtain wall stress distributions under systolic pressure. Peak wall stresses were compared across guideline thresholds for diameter/BSA and diameter/height. Hazard ratios for all-cause mortality and surgical aneurysm repair were estimated using cause-specific Cox proportional hazards models.ResultsOf 253 veterans, 54 (21 %) had aneurysm repair at 3.75 years. Indexed diameter alone would have prompted repair at baseline in 17/253 (6.7 %) patients, including only 4/230 (1.7 %) with diameter

ObjectivesRapid diameter growth is a criterion for ascending thoracic aortic aneurysm repair; however, there are sparse data on aneurysm elongation rate. The purpose of this study was to assess aortic elongation rates in nonsyndromic, nonsurgical aneurysms to understand length dynamics and correlate with aortic diameter over time.MethodsPatients with

Background Abdominal aortic aneurysm (AAA) screening programs have been active in the United States since 2005, but are not the only way AAAs are detected. AAA management and outcomes have not been investigated broadly in the context of "implicit AAA screening," whereby radiologic examinations not intended for focused screening can identify AAAs. Methods and Results We examined the association between imaging-based AAA screening, both explicit and implicit, and various outcomes for ≈1.6 million veterans in the Veterans Affairs health care system from 2005 to 2015. Screened-positive, screened-negative, and unscreened veterans were identified in the overall cohort and within a subgroup of veterans aged 65 years in 2005. The yearly composite screening rate increased over 10 years, from 11.7% to 18.3%, whereas the screened-positive rate decreased from 7.3% to 4.9%. Only 12.9% of screening examinations were explicit AAA screening ultrasounds. The subgroup's composite screening rate was 74% within its 10-year eligibility window, with implicit screening accounting for 91.8% of examinations. In the 2005 subgroup, all-cause mortality and Charlson comorbidity scores were higher for veterans who underwent screening compared with those unscreened (31.2% versus 23.1% and 0.47 versus 0.25, respectively; P

BackgroundHistoric studies of nonsyndromic ascending thoracic aortic aneurysms (aTAAs) reported that the typical aTAA growth rate was approximately 0.6 mm/year, but data were limited due to relatively few studies using computed tomography (CT) imaging. Our purpose was to reevaluate the annual growth rate of nonsyndromic aTAAs that do not meet criteria for surgical repair in veterans in the contemporary era, using modern CT imaging suitable for highly accurate and reproducible aneurysm measurement.MethodsNonsurgical patients (diameter 45 mm. Only 3 patients experienced clinically significant changes in diameter with magnitude greater than 5% of baseline.ConclusionsIn this veteran population, most patients did not experience significant annual aneurysm growth over up to 5 years of follow-up, regardless of initial diameter. Thus, in the modern era, aTAAs may not grow as quickly as previously described, which will be important in determining appropriate intervals for aneurysm surveillance based upon risk-benefit ratio.

Accurate and reproducible measurement of abdominal aortic aneurysm (AAA) size is an essential component of patient management, and most reliably performed at CT using a multiplanar reformat (MPR) strategy. This approach is not universal, however. This study aims to characterize the measurement error present in routine clinical assessment of AAAs and the potential clinical ramifications. Patients were included if they had AAA assessed by CT and/or MRI at two time points at least 6 months apart. Clinical maximal AAA diameter, assessed by non-standardized methods, was abstracted from the radiology report at each time point and compared to the reference aneurysm diameter measured using a MPR strategy. Discrepancies between clinical and reference diameters, and associated aneurysm enlargement rates were analyzed. Two hundred thirty patients were included, with average follow-up 3.3±2.5 years. When compared to MPR-derived diameters, clinical aneurysm measurement inaccuracy was, on average, 3.3 mm. Broad limits of agreement were found for both clinical diameters [-6.7 to +6.5 mm] and aneurysm enlargement rates [-4.6 to +4.2 mm/year] when compared to MPR-based measures. Of 78 AAAs measuring 5-6 cm by the MPR method, 21 (26.9%) were misclassified by the clinical measurement with respect to a common repair threshold (5.5 cm), of which 5 were misclassified as below, and 16 were misclassified as above the threshold. The clinical use of non-standardized AAA measurement strategies can lead to incorrect classification of AAAs as larger or smaller than the commonly accepted repair threshold of 5.5 cm and can induce large errors in quantification of aneurysm enlargement rate.

Background Intraluminal thrombus (ILT) within abdominal aortic aneurysms (AAAs) may be a potential marker for subsequent aneurysm growth. Purpose To investigate the role of ILT in AAA progression as assessed with CT and MRI. Materials and Methods This was a retrospective study, with patient data included from January 2004 to December 2018 at a Veteran Affairs medical center. Male patients with AAA who underwent contrast material-enhanced CT at baseline and CT or black-blood MRI at follow-up (minimal follow-up duration of 6 months) were included. The maximal AAA diameter was measured with multiplanar reconstruction, and the annual growth rate of aneurysms was calculated. Uni- and multivariable linear regression analyses were used to determine the relationship between demographic and imaging factors and aneurysm growth. Results A total of 225 patients (mean age, 72 years ± 9 [standard deviation]) were followed for a mean of 3.3 years ± 2.5. A total of 207 patients were followed up with CT, and 18 were followed up with MRI. At baseline, the median size of the AAA was 3.8 cm (interquartile range [IQR], 3.3-4.3 cm); 127 of 225 patients (54.7%) had ILT. When compared with AAAs without ILT, AAAs with ILT had larger baseline diameters (median, 4.1 cm [IQR, 3.6-4.8 cm] vs 3.4 cm [IQR, 3.2-3.9 cm]; P < .001) and faster growth rates (median, 2.0 mm/y [IQR, 1.3-3.2 mm/y] vs 1.0 mm/y [IQR, 0.4-1.8 mm/y]; P < .001). Small AAAs (size range, 3-4 cm) with ILT grew 1.9-fold faster than did those without ILT (median, 1.5 mm/y [IQR, 0.9-2.7 mm/y] vs 0.8 mm/y [IQR, 0.3-1.5 mm/y]; P < .001). Medium AAAs (size range, 4-5 cm) with ILT had 1.2-fold faster growth than did those without ILT (median growth, 2.1 mm/y [IQR, 1.4, 3.7 mm/y] vs 1.8 mm/y [IQR, 0.9, 2.0 mm/y]; P = .06). In multivariable analysis, baseline diameter and ILT were independently positively related to aneurysm growth rate (standardized regression coefficient, 0.43 [P < .001] and 0.15 [P = .02], respectively). Conclusion Both maximal cross-sectional aneurysm diameter and the presence of intraluminal thrombus are independent predictors of abdominal aortic aneurysm growth. © RSNA, 2020 Online supplemental material is available for this article.

BackgroundThe factors influencing common iliac artery aneurysm (CIA) growth are not fully known. Intraluminal thrombus (ILT) has been studied as a marker of growth in abdominal aortic aneurysms (AAA), but its role in CIAs is unknown. This study aims to examine the factors associated with growth of CIAs coexistent with AAA using serial cross-sectional imaging (CT and MRI) with multiplanar reconstruction (MPR).MethodsPatients with synchronous AAA and CIA observed at contrast-enhanced CT or MRI were included. The maximal diameters of both CIA and AAA were measured using MPR. Correlation of the baseline aneurysm diameter and growth rate between CIA and AAA was evaluated. Multivariate regression analysis was used to investigate the factors associated with CIA growth.ResultsSeventy-five AAA patients (age 74±9 years; all male) with 100 CIAs were followed for an average of 2.2±1.2 years. CIA and AAA growth were positively correlated (r=0.39, P

HypothesisWe hypothesize patient-specific flow models to be an adequate in vitro surrogate to allow for characterization of pulsatile tinnitus (PT) that affects three to five million Americans.BackgroundPT, rhythmic sounds without an extracorporeal source that patients appreciate, can be caused by aberrant blood flow in large cerebral veins near the cochlea. To investigate the sound production mechanism, we created 3D printed flow models based on patient-specific cerebral venous anatomies.MethodsMagnetic resonance angiography datasets from two patients with PT were used to generate patient-specific 3D printed flow models. A flow circuit connecting the patient-specific models to a pulsatile, continuous flow pump simulating cardiac cycle was created. Sound recordings were made along the surface of the models using an electronic stethoscope. Peak-to-rms amplitude, and area under the power spectral density (PSD) curve values were computed to evaluate the sound measurements. Wilcoxon rank sum test was used to statistically determine the differences in measurements between the patient-specific models.ResultsIn patient-1, the recordings (peak-to-rms) from the internal jugular vein stenosis of baseline model (4.29 ± 1.26 for 146 samples) were significantly louder (p

Intraluminal thrombus (ILT) is present in the majority of abdominal aortic aneurysms (AAA) of a size warranting consideration for surgical or endovascular intervention. The rupture risk of AAAs is thought to be related to the balance of vessel wall strength and the mechanical stress caused by systemic blood pressure. Previous finite element analyses of AAAs have shown that ILT can reduce and homogenize aneurysm wall stress. These works have largely considered ILT to be homogeneous in mechanical character or have idealized a stiffness distribution through the thrombus thickness. In this work, we use magnetic resonance imaging (MRI) to delineate the heterogeneous composition of ILT in 7 AAAs and perform patient-specific finite element analysis under multiple conditions of ILT layer stiffness disparity. We find that explicit incorporation of ILT heterogeneity in the finite element analysis is unlikely to substantially alter major stress analysis predictions regarding aneurysm rupture risk in comparison to models assuming a homogenous thrombus, provided that the maximal ILT stiffness is the same between models. Our results also show that under a homogeneous ILT assumption, the choice of ILT stiffness from values common in the literature can result in significantly larger variations in stress predictions compared to the effects of thrombus heterogeneity.

BACKGROUND:Intraluminal thrombus (ILT) signal intensity on MRI has been studied as a potential marker of abdominal aortic aneurysm (AAA) progression. PURPOSE:1) To characterize the relationship between ILT signal intensity and AAA diameter; 2) to evaluate ILT change over time; and 3) to assess the relationship between ILT features and AAA growth. STUDY TYPE:Prospective. SUBJECTS:Eighty AAA patients were imaged, and a subset (n = 41) were followed with repeated MRI for 16 ± 9 months. FIELD STRENGTH/SEQUENCE:3D black-blood fast-spin-echo sequence at 3 T. ASSESSMENT:ILT was designated as "bright" if the signal was greater than 1.2 times that of adjacent psoas muscle. AAAs were divided into three groups based on ILT: Type 1: bright ILT; Type 2: isointense ILT; Type 3: no ILT. During follow-up, an active ILT change was defined as new ILT formation or an increase in ILT signal intensity to bright; stable ILT was defined as no change in ILT type or ILT became isointense from bright previously. STATISTICAL TESTS:Shapiro-Wilk test; Mann-Whitney U-test; Fisher's exact test; Kruskal-Wallis test; Spearman's r; intraclass correlation coefficient (ICC), Cohen's kappa. RESULTS:AAAs with Type 1 ILT were larger than those with Types 2 and 3 ILT (5.1 ± 1.1 cm, 4.4 ± 0.9 cm, 4.2 ± 0.8 cm, P = 0.008). The growth rate of AAAs with Type 1 ILT was significantly greater than that of AAAs with Types 2 and 3 ILT (2.6 ± 2.5, 0.6 ± 1.3, 1.5 ± 0.6 mm/year, P = 0.01). During follow-up, AAAs with active ILT changes had a 3-fold increased growth rate compared with AAAs with stable ILT (3.6 ± 3.0 mm/year vs. 1.2 ± 1.5 mm/year, P = 0.008). DATA CONCLUSION:AAAs with bright ILT are larger in diameter and grow faster. Active ILT change is associated with faster AAA growth. Black-blood MRI can characterize ILT features and monitor their change over time, which may provide new insights into AAA risk assessment. LEVEL OF EVIDENCE:2 Technical Efficacy Stage: 5 J. Magn. Reson. Imaging 2019;50:994-1001.

BackgroundAvelumab, a human Ig-G1 monoclonal antibody targeting PD-L1 and approved in the USA for the treatment of metastatic Merkel cell carcinoma, has shown antitumour activity and an acceptable safety profile in patients with advanced solid tumours in a dose-escalation phase 1a trial. In this dose-expansion cohort of that trial, we assess avelumab treatment in a cohort of patients with advanced, platinum-treated non-small-cell lung cancer (NSCLC).MethodsIn this dose-expansion cohort of a multicentre, open-label, phase 1 study, patients with progressive or platinum-resistant metastatic or recurrent NSCLC were enrolled at 58 cancer treatment centres and academic hospitals in the USA. Eligible patients had confirmed stage IIIB or IV NSCLC with squamous or non-squamous histology, measurable disease by Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST v1.1), tumour biopsy or archival sample for biomarker assessment, and Eastern Cooperative Oncology Group performance status 0 or 1, among other criteria. Patient selection was not based on PD-L1 expression or expression of other biomarkers, including EGFR or KRAS mutation or ALK translocation status. Patients received infusional avelumab monotherapy 10 mg/kg every 2 weeks until disease progression or toxicity. The primary objective was to assess safety and tolerability. This trial is registered with ClinicalTrials.gov, number NCT01772004; enrolment in this cohort is closed and the trial is ongoing.FindingsBetween Sept 10, 2013, and June 24, 2014, 184 patients were enrolled and initiated treatment with avelumab. Median follow-up duration was 8·8 months (IQR 7·2-11·9). The most common treatment-related adverse events of any grade were fatigue (46 [25%] of 184 patients), infusion-related reaction (38 [21%]), and nausea (23 [13%]). Grade 3 or worse treatment-related adverse events occurred in 23 (13%) of 184 patients; the most common (occurring in more than two patients) were infusion-related reaction (four [2%] patients) and increased lipase level (three [2%]). 16 (9%) of 184 patients had a serious adverse event related to treatment with avelumab, with infusion-related reaction (in four [2%] patients) and dyspnoea (in two [1%]) occurring in more than one patient. Serious adverse events irrespective of cause occurred in 80 (44%) of 184 patients. Those occurring in more than five patients (≥3%) were dyspnoea (ten patients [5%]), pneumonia (nine [5%]), and chronic obstructive pulmonary disease (six [3%]). Immune-related treatment-related events occurred in 22 patients (12%). Of 184 patients, 22 (12% [95% CI 8-18]) achieved a confirmed objective response, including one complete response and 21 partial responses. 70 (38%) had stable disease. Overall, 92 (50%) of 184 patients achieved disease control (they had a confirmed response or stable disease as their best overall response). One patient was initially thought to have died from grade 5 radiation pneumonitis during the study; however, this adverse event was subsequently regraded to grade 3 and the death was attributed to disease progression.InterpretationAvelumab showed an acceptable safety profile and antitumour activity in patients with progressive or treatment-resistant NSCLC, providing a rationale for further studies of avelumab in this disease setting.FundingMerck KGaA and Pfizer.

ObjectivesManagement of abdominal aortic aneurysms (AAAs) is based on diameter. CT angiography (CTA) is commonly used, but requires radiation and iodinated contrast. Non-contrast MRI is an appealing alternative that may allow better characterization of intraluminal thrombus (ILT). This study aims to 1) validate non-contrast MRI for measuring AAA diameter, and 2) to assess ILT with CTA and MRI.Method28 patients with AAAs (diameter 50.7 ± 12.3 mm) underwent CTA and non-contrast MRI. MRI was acquired at 3 T using 1) a conventional 3D gradient echo (GRE) sequence and 2) a 3D T1-weighted black blood fast-spin-echo sequence. Two radiologists independently measured the AAA diameter. The ratio of signal of ILT and adjacent psoas muscle (ILTr = signalILT/signalMuscle) was quantified.ResultsStrong agreement between CTA and non-contrast MRI was shown for AAA diameter (intra-class coefficient > 0.99). Both approaches had excellent inter-observer reproducibility (ICC > 0.99). ILT appeared homogenous on CTA, whereas MRI revealed compositional variations. Patients with AAAs ≥5.5 cm and

PurposeCabozantinib is a multi-kinase inhibitor that targets MET, AXL, and VEGFR2, and may synergize with EGFR inhibition in NSCLC. Cabozantinib was assessed alone or in combination with erlotinib in patients with progressive NSCLC and EGFR mutations who had previously received erlotinib.MethodsThis was a phase Ib/II study (NCT00596648). The primary objectives of phase I were to assess the safety, pharmacokinetics, and pharmacodynamics and to determine maximum tolerated dose (MTD) of cabozantinib plus erlotinib in patients who failed prior erlotinib treatment. In phase II, patients with prior response or stable disease with erlotinib who progressed were randomized to single-agent cabozantinib 100 mg qd vs cabozantinib 100 mg qd and erlotinib 50 mg qd (phase I MTD), with a primary objective of estimating objective response rate (ORR).ResultsSixty-four patients were treated in phase I. Doses of 100 mg cabozantinib plus 50 mg erlotinib, or 40 mg cabozantinib plus 150 mg erlotinib were determined to be MTDs. Diarrhea was the most frequent dose-limiting toxicity and the most frequent AE (87.5% of patients). The ORR for phase I was 8.2% (90% CI 3.3-16.5). In phase II, one patient in the cabozantinib arm (N = 15) experienced a partial response, for an ORR of 6.7% (90% CI 0.3-27.9), with no responses for cabozantinib plus erlotinib (N = 13). There was no evidence that co-administration of cabozantinib markedly altered erlotinib pharmacokinetics or vice versa.ConclusionsDespite responses with cabozantinib/erlotinib in phase I, there were no responses in the combination arm of phase II in patients with acquired resistance to erlotinib. Cabozantinib did not appear to re-sensitize these patients to erlotinib.

BackgroundAtezolizumab is a humanised antiprogrammed death-ligand 1 (PD-L1) monoclonal antibody that inhibits PD-L1 and programmed death-1 (PD-1) and PD-L1 and B7-1 interactions, reinvigorating anticancer immunity. We assessed its efficacy and safety versus docetaxel in previously treated patients with non-small-cell lung cancer.MethodsWe did a randomised, open-label, phase 3 trial (OAK) in 194 academic or community oncology centres in 31 countries. We enrolled patients who had squamous or non-squamous non-small-cell lung cancer, were 18 years or older, had measurable disease per Response Evaluation Criteria in Solid Tumors, and had an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients had received one to two previous cytotoxic chemotherapy regimens (one or more platinum based combination therapies) for stage IIIB or IV non-small-cell lung cancer. Patients with a history of autoimmune disease and those who had received previous treatments with docetaxel, CD137 agonists, anti-CTLA4, or therapies targeting the PD-L1 and PD-1 pathway were excluded. Patients were randomly assigned (1:1) to intravenously receive either atezolizumab 1200 mg or docetaxel 75 mg/m2 every 3 weeks by permuted block randomisation (block size of eight) via an interactive voice or web response system. Coprimary endpoints were overall survival in the intention-to-treat (ITT) and PD-L1-expression population TC1/2/3 or IC1/2/3 (≥1% PD-L1 on tumour cells or tumour-infiltrating immune cells). The primary efficacy analysis was done in the first 850 of 1225 enrolled patients. This study is registered with ClinicalTrials.gov, number NCT02008227.FindingsBetween March 11, 2014, and April 29, 2015, 1225 patients were recruited. In the primary population, 425 patients were randomly assigned to receive atezolizumab and 425 patients were assigned to receive docetaxel. Overall survival was significantly longer with atezolizumab in the ITT and PD-L1-expression populations. In the ITT population, overall survival was improved with atezolizumab compared with docetaxel (median overall survival was 13·8 months [95% CI 11·8-15·7] vs 9·6 months [8·6-11·2]; hazard ratio [HR] 0·73 [95% CI 0·62-0·87], p=0·0003). Overall survival in the TC1/2/3 or IC1/2/3 population was improved with atezolizumab (n=241) compared with docetaxel (n=222; median overall survival was 15·7 months [95% CI 12·6-18·0] with atezolizumab vs 10·3 months [8·8-12·0] with docetaxel; HR 0·74 [95% CI 0·58-0·93]; p=0·0102). Patients in the PD-L1 low or undetectable subgroup (TC0 and IC0) also had improved survival with atezolizumab (median overall survival 12·6 months vs 8·9 months; HR 0·75 [95% CI 0·59-0·96]). Overall survival improvement was similar in patients with squamous (HR 0·73 [95% CI 0·54-0·98]; n=112 in the atezolizumab group and n=110 in the docetaxel group) or non-squamous (0·73 [0·60-0·89]; n=313 and n=315) histology. Fewer patients had treatment-related grade 3 or 4 adverse events with atezolizumab (90 [15%] of 609 patients) versus docetaxel (247 [43%] of 578 patients). One treatment-related death from a respiratory tract infection was reported in the docetaxel group.InterpretationTo our knowledge, OAK is the first randomised phase 3 study to report results of a PD-L1-targeted therapy, with atezolizumab treatment resulting in a clinically relevant improvement of overall survival versus docetaxel in previously treated non-small-cell lung cancer, regardless of PD-L1 expression or histology, with a favourable safety profile.FundingF. Hoffmann-La Roche Ltd, Genentech, Inc.

Ischemic mitral regurgitation is associated with substantial risk of death. We sought to: (1) detail significant recent improvements to the Dassault Systèmes human cardiac function simulator (HCFS); (2) use the HCFS to simulate normal cardiac function as well as pathologic function in the setting of posterior left ventricular (LV) papillary muscle infarction; and (3) debut our novel device for correction of ischemic mitral regurgitation. We synthesized two recent studies of human myocardial mechanics. The first study presented the robust and integrative finite element HCFS. Its primary limitation was its poor diastolic performance with an LV ejection fraction below 20% caused by overly stiff ex vivo porcine tissue parameters. The second study derived improved diastolic myocardial material parameters using in vivo MRI data from five normal human subjects. We combined these models to simulate ischemic mitral regurgitation by computationally infarcting an LV region including the posterior papillary muscle. Contact between our novel device and the mitral valve apparatus was simulated using Dassault Systèmes SIMULIA software. Incorporating improved cardiac geometry and diastolic myocardial material properties in the HCFS resulted in a realistic LV ejection fraction of 55%. Simulating infarction of posterior papillary muscle caused regurgitant mitral valve mechanics. Implementation of our novel device corrected valve dysfunction. Improvements in the current study to the HCFS permit increasingly accurate study of myocardial mechanics. The first application of this simulator to abnormal human cardiac function suggests that our novel annuloplasty ring with a sub-valvular element will correct ischemic mitral regurgitation.

Atherosclerosis at the carotid bifurcation is a major risk factor for stroke. As mechanical forces may impact lesion stability, finite element studies have been conducted on models of diseased vessels to elucidate the effects of lesion characteristics on the stresses within plaque materials. It is hoped that patient-specific biomechanical analyses may serve clinically to assess the rupture potential for any particular lesion, allowing better stratification of patients into the most appropriate treatments. Due to a sparsity of in vivo plaque rupture data, the relationship between various mechanical descriptors such as stresses or strains and rupture vulnerability is incompletely known, and the patient-specific utility of biomechanical analyses is unclear. In this article, we present a comparison between carotid atheroma rupture observed in vivo and the plaque stress distribution from fluid–structure interaction analysis based on pre-rupture medical imaging. The effects of image resolution are explored and the calculated stress fields are shown to vary by as much as 50% with sub-pixel geometric uncertainty. Within these bounds, we find a region of pronounced elevation in stress within the fibrous plaque layer of the lesion with a location and extent corresponding to that of the observed site of plaque rupture.

Patient-specific biomechanical modeling of atherosclerotic arteries has the potential to aid clinicians in characterizing lesions and determining optimal treatment plans. To attain high levels of accuracy, recent models use medical imaging data to determine plaque component boundaries in three dimensions, and fluid–structure interaction is used to capture mechanical loading of the diseased vessel. As the plaque components and vessel wall are often highly complex in shape, constructing a suitable structured computational mesh is very challenging and can require a great deal of time. Models based on unstructured computational meshes require relatively less time to construct and are capable of accurately representing plaque components in three dimensions. These models unfortunately require additional computational resources and computing time for accurate and meaningful results. A two-stage modeling strategy based on unstructured computational meshes is proposed to achieve a reasonable balance between meshing difficulty and computational resource and time demand. In this method, a coarsegrained simulation of the full arterial domain is used to guide and constrain a fine-scale simulation of a smaller region of interest within the full domain. Results for a patient-specific carotid bifurcation model demonstrate that the two-stage approach can afford a large savings in both time for mesh generation and time and resources needed for computation. The effects of solid and fluid domain truncation were explored, and were shown to minimally affect accuracy of the stress fields predicted with the two-stage approach.

Background: Abdominal aortic aneurysms (AAAs) may rupture before reaching maximum diameter (Dmax) thresholds for repair. Aortic wall microvasculature has been associated with elastin content and rupture sites in specimens, but its relation to progression is unknown. Purpose: To investigate whether dynamic contrast‐enhanced (DCE) MRI of AAA is associated with Dmax or growth. Study Type: Prospective. Population: A total of 27 male patients with infrarenal AAA (mean age ± standard deviation = 75 ± 5 years) under surveillance with DCE MRI and 2 years of prior follow‐up intervals with computed tomography (CT) or MRI. Field Strength/Sequence: A 3‐T, dynamic three‐dimensional (3D) fast gradient‐echo stack‐of‐stars volumetric interpolated breath‐hold examination (Star‐VIBE). Assessment: Wall voxels were manually segmented in two consecutive slices at the level of Dmax. We measured slope to 1‐minute and area under the curve (AUC) to 1 minute and 4 minutes of the signal intensity change postcontrast relative to that precontrast arrival, and, Ktrans, a measure of microvascular permeability, using the Patlak model. These were averaged over all wall voxels for association to Dmax and growth rate, and, over left/right and anterior/posterior quadrants for testing circumferential homogeneity. Dmax was measured orthogonal to the aortic centerline and growth rate was calculated by linear fit of Dmax measurements. Statistical Tests: Pearson correlation and linear mixed effects models. A P value <0.05 was considered statistically significant. Results: In 44 DCE MRIs, mean Dmax was 45 ± 7 mm and growth rate in 1.5 ± 0.4 years of prior follow‐up was 1.7 ± 1.2 mm per year. DCE measurements correlated with each other (Pearson r = 0.39–0.99) and significantly differed between anterior/posterior versus left/right quadrants. DCE measurements were not significantly associated with Dmax (P = 0.084, 0.289, 0.054 and 0.255 for slope, AUC at 1 minute and 4 minutes, and Ktrans, respectively). Slope and 4 minutes AUC significantly associated with growth rate after controlling for Dmax. Conclusion: Contrast uptake may be increased in lateral aspects of the AAA. Contrast enhancement 1‐minute slope and 4‐minutes AUC may be associated with a period of recent AAA growth that is independent of Dmax. Evidence Level: 3. Technical Efficacy: Stage 2. [ABSTRACT FROM AUTHOR]