Eleni Metaxa

A Comparative Review of the Hemodynamics and Pathogenesis of Cerebral and Abdominal Aortic Aneurysms: Lessons to Learn From Each Other

Objective Cerebral aneurysms (CAs) and abdominal aortic aneurysms (AAAs) are degenerative vascular pathologies that manifest as abnormal dilations of the arterial wall. They arise with different morphologies in different types of blood vessels under different hemodynamic conditions. Although treated as different pathologies, we examine common pathways in their hemodynamic pathogenesis in order to elucidate mechanisms of formation. Materials and Methods A systematic review of the literature was performed. Current concepts on pathogenesis and hemodynamics were collected and compared. Results CAs arise as saccular dilations on the cerebral arteries of the circle of Willis under high blood flow, high wall shear stress (WSS), and high wall shear stress gradient (WSSG) conditions. AAAs arise as fusiform dilations on the infrarenal aorta under low blood flow, low, oscillating WSS, and high WSSG conditions. While at opposite ends of the WSS spectrum, they share high WSSG, a critical factor in arterial remodeling. This alone may not be enough to initiate aneurysm formation, but may ignite a cascade of downstream events that leads to aneurysm development. Despite differences in morphology and the structure, CAs and AAAs share many histopathological and biomechanical characteristics. Endothelial cell damage, loss of elastin, and smooth muscle cell loss are universal findings in CAs and AAAs. Increased matrix metalloproteinases and other proteinases, reactive oxygen species, and inflammation also contribute to the pathogenesis of both aneurysms. Conclusion Our review revealed similar pathways in seemingly different pathologies. We also highlight the need for cross-disciplinary studies to aid in finding similarities between pathologies.

Value of volume measurements in evaluating abdominal aortic aneurysms growth rate and need for surgical treatment

PURPOSE To examine whether indices other than the traditionally used abdominal aortic aneurysm (AAA) maximum diameter, such as AAA volume, intraluminal thrombus (ILT) thickness and ILT volume, may be superior to evaluate aneurismal enlargement. MATERIALS AND METHODS Thirty-four small AAAs (initially presenting a maximum diameter <5.5cm which is the threshold for surgical repair) with an initial and a follow-up CT were examined. Median increase and percentile annual change of these variables was calculated. Correlation between growth rates as determined by the new indices under evaluation and those of maximum diameter were assessed. AAAs were divided according to outcome (surveillance vs. elective repair after follow-up which is based on the maximum diameter criterion) and according to growth rate (high vs. low) based on four indices. Contingency between groups of high/low growth rate regarding each of the four indices on one hand and those regarding need for surgical repair on the other was assessed. RESULTS A strong correlation between growth rates of maximum diameter and those of AAA and ILT volumes could be established. Evaluation of contingency between groups of outcome and those of growth rate revealed significant associations only for AAA and ILT volumes. Subsequently AAAs with a rapid volumetric increase over time had a likelihood ratio of 10 to be operated compared to those with a slower enlargement. Regarding increase of maximum diameter, likelihood ratio between AAAs with rapid and those with slow expansion was only 3. CONCLUSION Growth rate of aneurysms regarding 3Dimensional indices of AAA and ILT volumes is significantly associated with the need for surgical intervention while the same does not hold for growth rates determined by 2Dimensional indices of maximum diameter and ILT thickness.

Discrepancies in determination of abdominal aortic aneurysms maximum diameter and growth rate, using axial and orhtogonal computed tomography measurements

PURPOSE Maximum diameter and growth rate of abdominal aortic aneurysms (AAAs) which are currently used as the only variables to set the indication for elective repair are recorded through computed tomography (CT) measurements on an axial plane or on an orthogonal plane that is perpendicular to vessel centerline, interchangeably. We will attempt to record possible discrepancies between the two methods, identify whether such differences could influence therapeutic decisions and determine in which cases this should be expected. MATERIALS AND METHODS We retrospectively reviewed sixty CT-scans performed in thirty-nine patients. Three-dimensional reconstruction of AAAs has been performed and differences in maximum diameter measured on axial and orthogonal planes were recorded. A measure for asymmetry was introduced termed ShapeIndex defined as the value of section minor over major axis and was related with differences in maximum diameter recordings. Growth rates were also determined using both axial and orthogonal measurements. RESULTS Axial measurements overestimate maximum diameter by 2 ± 2.7 mm (P<0.001) with a range of 0-12.3mm. Overall, 20% of the CTs had an axial maximum diameter >5.5 cm indicating the need for intervention whereas, orthogonal diameter was below that threshold. Asymmetry of the axial sections with ShapeIndex≤0.8 was found to be related to an overestimation of maximum diameter by >5mm. There were no significant differences in growth rates when determined using orthogonal or axial measurements in both examinations (median growth rate: 2.3mm and 3.3mm respectively P=0.2). However there were significant differences when orthogonal measurements were used at initial and axial measurements used at follow-up examination or vice versa (median growth rate: 4.9 mm and 0.9 mm respectively P<0.001). CONCLUSIONS Although the mean difference between measurements is low there is a wide range among cases, mainly observed in asymmetrical AAAs. ShapeIndex may identify those which are more likely to be misestimated. CT measurements performed to establish AAA growth rates should consistently use either the axial or orthogonal technique to avoid inaccuracies from occurring.

Effect of Intraluminal Thrombus Asymmetrical Deposition on Abdominal Aortic Aneurysm Growth Rate

Purpose: To determine the relationship between asymmetrical intraluminal thrombus (ILT) deposition in abdominal aortic aneurysm (AAA) and growth rate and to explore its biomechanical perspective. Methods: Thirty-four patients with AAA underwent at least 2 computed tomography scans during surveillance. The volumes of the AAA (VAAA) and thrombus (VILT) and the maximum thrombus thickness (ILTthick) were computed. Thrombus distribution was evaluated by introducing the asymmetrical thrombus deposition index (ATDI), with positive and negative values (–1<ATDI<1) associated with anterior and posterior ILT deposition, respectively. Finite element analysis was applied to estimate wall stress. Aneurysms were divided into high and low growth rate groups based on the cohort’s median growth rate, and the abovementioned parameters were compared between groups. Results: Most AAAs had asymmetrical anterior thrombus deposition. The high and low growth rate groups did not present significant differences in maximum diameter, VAAA, VILT, or maximum ILTthick. However, the high growth rate group had significantly higher ATDI (p=0.02). The ATDI<0 group (posterior ILT distribution) presented a significantly lower median growth rate compared to that of ATDI≥0 group (anterior or symmetrical ILT deposition; p=0.029). The specificity of an ATDI<0 criterion for identifying AAAs with a growth rate below the cohort median was 89%. The ATDI<0 group had a significantly lower posterior maximum wall stress compared with that of the ATDI≥0 group (p=0.03). Overall peak wall stress did not differ between groups. Conclusion: Posterior thrombus deposition in AAAs is associated with significantly lower growth rate and lower posterior maximum wall stress compared with that of AAAs with anterior thrombus deposition and could potentially indicate a lower rupture risk.

Graft inflow stenosis induced by the inflatable ring fixation mechanism of the Ovation stent-graft system: hemodynamic and clinical implications.

Purpose: To investigate the observed inflow stenosis at the O-rings of the Ovation stent-graft and evaluate its hemodynamic and clinical impact. Methods: The study involved 49 consecutive patients (48 men; mean age 71.2±7.7 years) treated successfully with the Ovation abdominal aortic stent-graft between June 2011 and January 2014 at a single center. Cross-sectional area and radius measurements of the infrarenal aorta just proximal to the sealing mechanism, as well at the site of stenosis, were measured from 3D reconstructions of the 1-month postoperative computed tomographic angiograms. Based on Poiseuilles law, the predicted pressure drop was calculated for each patient based on the length of the stenosis. Invasive blood pressure measurements at 3 levels (proximal to the inflatable rings, halfway inside the stenosis, and distal to the stenosis) were obtained in 10 patients intraoperatively. Ankle-brachial index (ABI) values preoperatively were compared to those after the procedure for all patients to assess the clinical impact of this phenomenon. Results: Median internal cross-sectional area at the site of the stenosis was significantly reduced compared to the area just proximal to the O-rings [57% reduction: 123 mm2 (range 28–254) vs. 283 mm2 (range 177–531), respectively; p<0.001]. The same was observed for the radius [6.5 mm (range 3–9) vs. 9.5 mm (range 7.5–13), respectively; p<0.001]. Based on the median 15 mm length of the stenosis (range 13–17) observed in the study population, a median pressure drop of 0.13 mmHg (range 0–0.25) along the stenosis was calculated. Invasive blood pressure measurements indicated a non-significant pressure change along the stenosis (e.g., 0.7 mmHg between the proximal level and halfway inside the stenosis). ABI remained practically unchanged postoperatively. Conclusion: The advantages of the Ovation devices unique sealing mechanism come at the expense of a median area inflow stenosis of ∼60%. This stenosis does not cause a hemodynamically significant pressure drop. Future modification of the graft ring design may be needed in order to reduce this stenosis.

Advancements in identifying biomechanical determinants for abdominal aortic aneurysm rupture

Abdominal aortic aneurysms are a common health problem and currently the need for surgical intervention is determined based on maximum diameter and growth rate criteria. Since these universal variables often fail to predict accurately every abdominal aortic aneurysms evolution, there is a considerable effort in the literature for other markers to be identified towards individualized rupture risk estimations and growth rate predictions. To this effort, biomechanical tools have been extensively used since abdominal aortic aneurysm rupture is in fact a material failure of the diseased arterial wall to compensate the stress acting on it. The peak wall stress, the role of the unique geometry of every individual abdominal aortic aneurysm as well as the mechanical properties and the local strength of the degenerated aneurysmal wall, all confer to rupture risk. In this review article, the assessment of these variables through mechanical testing, advanced imaging and computational modeling is reviewed and the clinical perspective is discussed.

A robust approach for exploring hemodynamics and thrombus growth associations in abdominal aortic aneurysms

Longitudinal studies of vascular diseases often need to establish correspondence between follow-up images, as the diseased regions may change shape over time. In addition, spatial data structures should be taken into account in the statistical analyses to avoid inferential errors. This study investigates the association between hemodynamics and thrombus growth in abdominal aortic aneurysms (AAAs) while emphasizing on the abovementioned methodological issues. Six AAA surfaces and their follow-ups were three-dimensionally reconstructed from computed-tomography images. AAA surfaces were mapped onto a rectangular grid which allowed identification of corresponding regions between follow-ups. Local thrombus thickness was measured at initial and follow-up surfaces and computational fluid dynamic simulations provided time-average wall shear stress (TAWSS), oscillatory shear index (OSI), and relative residence time. Six Bayesian regression models, which account for spatially correlated measurements, were employed to explore associations between hemodynamics and thrombus growth. Results suggest that spatial regression models based on TAWSS and OSI offer superior predictive performance for thrombus growth relative to alternative specifications. Ignoring the spatial data structure may lead to improper assessment with regard to predictor significance.

Prognosis of Abdominal Aortic Aneurysms: A Machine Learning-Enabled Approach Merging Clinical, Morphometric, Biomechanical and Texture Information

An effective surveillance strategy for the progression of abdominal aortic aneurysms (AAAs) may be achieved by assessing its expected growth rate in a personalized manner. Given the variety of factors with an impact on AAA growth, an integrative approach to the problem could potentially benefit from incorporating clinical and morphometric data, as well as mechanical stress characterizations. In addition, here we investigated the use of texture information on computed tomography angiography images within the AAA sac. A cohort of n=38 patients underwent a baseline examination, plus a follow-up visit to measure AAA growth rates, in terms of its maximum diameter (Dmax) divided by the elapsed time period. Subsequently, each case was labelled as slow, medium or quick growth, compared to the expected rate reported in demographic studies, as a function of gender and baseline Dmax. We computed a total of 102 features (5 clinical, 17 morphometric, 4 biomechanical, and 76 on texture) and used a number of machine learning (ML) algorithms; with the aim of minimizing misclassification costs. The performance of the system was evaluated with a leave-one-out cross-validation scheme. The results achieved by the best performing approach, an ensemble of decision trees (LPBoost) using the entire 102-dimensional feature space, indicated that the combination of different information sources, along with ML algorithms, may have a positive impact on the AAA prognosis assessment.

Commentary: Unraveling the Natural History of Aneurysms by Exploiting Clinical Images: Insightful Follow-up of Localized Aneurysm Characteristics

In addition to abdominal aortic aneurysm (AAA) size, which is the major clinical predictor of rupture risk, growth rate is also being used to support decision making in the clinical management of these lesions. Rapid growth may reflect undesirable remodeling that leads to weakening of the sac wall and may indicate a high rupture potential. Currently in clinical practice, AAA growth is determined by the change in maximum diameter over time, and intervention is indicated when the expansion rate exceeds 10 mm/year. Although maximum diameter progression can be easily recorded through 2-dimensional computed tomography (CT) imaging and simple multiplanar reconstruction, which is readily available in most vascular institutes, such measurements may not be in accord with the pathophysiology and natural history of aneurysmal disease. Specifically, it has been found that aneurysm enlargement is accompanied by high inhomogeneity in the distribution of wall mechanical properties, such as stiffness, thickness, and strength throughout the aneurysmal surface. Subsequently, AAA expansion is expected to be nonuniform, characterized by significant spatial variability. Thus, a metric that quantifies regional growth may be more appropriate to describe this process compared with the maximum diameter, which may fail to highlight regions of rapid growth. Moreover, rupture, which is the target event to be predicted, is by nature a rather localized phenomenon resulting from material failure of the degenerated aortic wall. It is therefore reasonable during the evaluation of AAA rupture risk to consider indices that describe both regional (strength, distensibility, and growth) and global (diameter, sac volume) AAA characteristics. The former are expected to improve rupture risk stratification by complementing maximum diameter measurements. In this context, growth rate should also be evaluated based on local parameters. The major challenge in quantifying local growth comes from the complexity of the aneurysm enlargement process. In fact, each AAA is characterized by a unique, complex geometric configuration that alters continuously during disease progression. In this regard, the aneurysm may elongate, become tortuous, and present significant torsion and/ or bulge toward either side. Therefore, matching corresponding wall regions in serial follow-up scans is not straightforward. To overcome this difficulty, Martufi et al have recently generated a surrogate model that consists of a center line and 100 consecutive cross sections between the lowest renal artery and the aortic bifurcation. By comparing the diameter of each cross section with its follow-up diameter at the same relative centerline position, the authors showed that neither maximum diameter nor volume measurements over time are able to measure the largest diameter growth of the aneurysm sac. They concluded that localized spots of large diameter growth can be detected through multiple centerline-based diameter measurements over the entire aneurysm sac. In this issue of the JEVT, Martufi and colleagues have gone one step further with this technique and searched for local correlations between the initial outer diameter, thrombus thickness, and wall stress. Such an investigation could provide significant insight into a long-debated subject concerning the 654890 JETXXX10.1177/1526602816654890Journal of Endovascular TherapyMetaxa et al research-article2016

Abdominal aortic aneurysm rupture risk assessment exploiting dynamic (4D) CT BASEd wall motion data and finite element analysis

Abdominal aortic aneurysm (AAA) disease is primarily a degenerative process, where rupture occurs when stress exerted on the aortic wall exceeds its failure strength. Therefore, knowledge of both the wall stress distribution and the mechanical properties of the AAA wall is required for patient specific rupture risk estimation.Copyright