Intraluminal Thrombus Deposition Research Articles

Intraluminal Thrombus Characteristics in AAA Patients: Non-Invasive Diagnosis Using CFD.

Abdominal aortic aneurysms (AAA) continue to pose a high mortality risk despite advances in medical imaging and surgery. Intraluminal thrombus (ILT) is detected in most AAAs and may critically impact their development. Therefore, understanding ILT deposition and growth is of practical importance. To assist in managing these patients, the scientific community has been researching the relationship between intraluminal thrombus (ILT) and hemodynamic parameters wall shear stress (WSS) derivatives. This study analyzed three patient-specific AAA models reconstructed from CT scans using computational fluid dynamics (CFD) simulations and a pulsatile non-Newtonian blood flow model. The co-localization and relationship between WSS-based hemodynamic parameters and ILT deposition were examined. The results show that ILT tends to occur in regions of low velocity and time-averaged WSS (TAWSS) and high oscillation shear index (OSI), endothelial cell activation potential (ECAP), and relative residence time (RRT) values. ILT deposition areas were found in regions of low TAWSS and high OSI independently of the nature of flow near the wall characterized by transversal WSS (TransWSS). A new approach is suggested which is based on the estimation of CFD-based WSS indices specifically in the thinnest and thickest ILT areas of AAA patients; this approach is promising and supports the effectiveness of CFD as a decision-making tool for clinicians. Further research with a larger patient cohort and follow-up data are needed to confirm these findings.

Influence of the flow field and vortex structure of patient-specific abdominal aortic aneurysm with intraluminal thrombus on the arterial wall

ABSTRACT In this study, numerical simulations and experiments were conducted on patient-specific normal abdominal aorta and abdominal aortic aneurysm (AAA) with intraluminal thrombus (ILT) models, which were reconstructed from computed tomography angiography (CTA) images published online. A scale-adaptive simulation (SAS) of the abdominal aortic aneurysm with a posterior eccentric thrombus was performed and the reliability of the numerical simulation was verified by 2D particle image velocimetry (PIV) experimental results. The distribution of wall shear stress (WSS), oscillatory shear index (OSI), and relative residence time (RRT) of the normal abdominal aorta and AAA were compared and discussed systematically according to the numerical simulation results under rest and exercise conditions. Numerical results indicated that ILT deposition positions were accompanied by low WSS, high OSI, and high RRT regions and were characterized by small vortex groups, which was due to the fragmentation of large vortex structures. The distribution law of the AAA wall parameters has an obvious correlation with the nearby vortex structure formation, development, fragmentation and dissipation. It was also found that high TAWSS, low OSI, and low RRT regions present in the middle and lower aneurysm walls under exercise condition reduce the risk of ILT formation and development.

Mechanical role of intraluminal thrombus in aneurysm growth: A computational study.

Models that seek to improve our current understanding of biochemical processes and predict disease progression have been increasingly in use over the last decades. Recently, we proposed a finite element implementation of arterial wall growth and remodeling with application to abdominal aortic aneurysms (AAAs). The study focused on changes within the aortic wall and did not include the complex role of intraluminal thrombus (ILT) during the AAA evolution. Thus, in this work, we extend the model with a gradual deposition of ILT and its mechanical influence on AAA growth. Despite neglecting the increased biochemical activity due to the presence of a proteolytically active luminal layer of ILT, and thus underestimating rupture risk potential, we show that ILT helps to slow down the growth of the aneurysm in the axial direction by redirecting blood pressure loading from the axial-radial plane to predominately radial direction. This very likely lowers rupture potential. We also show that the ratio of ILT volume to volume sac is an important factor in AAA stabilization and that fully thrombosed aneurysms could stabilize quicker and at smaller maximum diameters compared to partially thrombosed ones. Furthermore, we show that ILT formation and the associated mural stress decrease negatively impact the wall constituent production and thickness. Although further studies that include increased biochemical degradation of the wall after the formation of ILT and ILT deposition based on hemodynamics are needed, the present findings highlight the dual role an ILT plays during AAA progression.

Increased matrix metalloproteinase 9 activity correlates with flow-mediated intraluminal thrombus deposition and wall degeneration in human abdominal aortic aneurysm

ObjectiveWe have previously demonstrated that human abdominal aortic aneurysm (AAA) rupture occurs in zones of low wall shear stress where flow recirculation and intraluminal thrombus (ILT) deposition are increased. Matrix metalloproteinase-9 (MMP-9) is involved in the pathogenesis of AAA via its lytic effect on collagen and elastin. We hypothesize that flow-mediated ILT deposition promotes increased local inflammatory and MMP-9 activity that leads to AAA wall degeneration. The purpose of this study was to examine the correlation between predicted pulsatile flow dynamics and regional differences in MMP-9, elastin, collagen, and ILT deposition in human AAA. MethodsFull-thickness aortic tissue samples were collected from 24 patients undergoing open AAA repair. Control infrarenal aortic tissue was obtained from 6 patients undergoing aortobifemoral bypass. Full-thickness aortic tissue and ILT were assessed for MMP-9 levels using a cytokine array assay. Histologic and immunohistochemical assessment of inflammation, collagen and elastin content, and MMP-9 levels were also measured. Three-dimensional AAA geometry was generated from computed tomography angiogram (CTA) images using Mimics software and computational fluid dynamics was used to predict pulsatile aortic blood flow. ResultsThe majority of AAA showed eccentric ILT deposition which was correlated with predicted recirculation blood flow (R2 = –0.17; P < .05). The regions of high ILT were associated with significant increases in inflammation and loss of elastin and collagen compared with regions of low ILT, or with control tissue. MMP-9 was significantly higher in areas of high ILT deposition compared with areas devoid of ILT. Tissue MMP-9 was correlated with the thickness of ILT deposition (R2 = 0.46; P < .05), and was also present in high levels in thick compared with thin ILT. ConclusionsWe have shown a correlation between flow-mediated ILT deposition with increased tissue levels of MMP-9 activity, increased inflammatory infiltrate, and decreased elastin and collagen content in stereotactically sampled human AAA, suggesting that ILT deposition is associated with local increases in proteolytic activity that may preferentially weaken and promote rupture at selected regions.

Increased Interleukin-8 Expression in Regions of High Intraluminal Thrombus Deposition in Human Abdominal Aortic Aneurysms

Increased Interleukin-8 Expression in Regions of High Intraluminal Thrombus Deposition in Human Abdominal Aortic Aneurysms

Analysis of morphological and hemodynamical indexes in abdominal aortic aneurysms as preliminary indicators of intraluminal thrombus deposition.

In this paper, we study the correlation between the wall shear stress, a hemodynamical index derived from numerical simulations, and an new index MFA-ILT for the characterization of intraluminal thrombus (ILT) in the presence of abdominal aortic aneurysms. Based on the processing of medical images, we define our index MFA-ILT by projecting onto lumen surface a measure of the ILT thickness. From the physical point of view, hemodynamical indexes describe the mechanical stimuli at which the luminal surface of the vessel wall is subject to, due to blood flow. Specifically, we consider the time-averaged wall shear stress and the oscillatory shear index. The first index provides a measurement of the averaged magnitude of the shear stress; the second index measures the rate of change of shear stress. To reconstruct the hemodynamical indexes, we build in silico three-dimensional models. We use the same physical parameters and boundary conditions for all the aneurysms in the sample. The computer simulations do not require any additional invasive patient examination. We consider eleven cases of abdominal aortic aneurysms spanning a wide range of different morphological features. All the cases are characterized by a thin intraluminal thrombus. We can, therefore, assume that the lumen we currently observe does not significantly differ from the one before the thrombus deposition. Our results suggest that the value of wall shear stresses and intraluminal thrombus deposition are correlated. Moreover, we conclude that in six cases time-averaged wall shear stress provides a preliminary indication of the area at risk of thrombus deposition.

Spatial Distribution of Abdominal Aortic Aneurysm Surface Growth and Correlation with Diameter and Volume Expansion

Introduction - The management of Abdominal Aortic Aneurysms (AAAs) is currently based on maximum size and growth rate criteria. Large or rapidly growing AAAs are thought to be at an increased risk of rupture, thus being suitable for intervention. Size and growth are determined based on the maximum diameter alone. Nevertheless, this variable takes into account a single portion of the vessel, while expansion is non-uniform, characterized by significant spatial variability. We aim to quantify regional surface growth of a cohort of AAAs. Methods - This is a single institution study including 31 lesions. Each AAA should have at least one baseline and one follow-up CT scan. From those, 3-Dimensional AAA models were created by semi-automated segmentation using dedicated software. Maximum orthogonal diameter and total aneurysm volume were recorded and used to calculate annual growth rate. Regional surface growth was quantified using the VascForm algorithm, which is written in Matlab, adapted to aneurysm follow-up studies and has been recently validated.[1] In general it is based on non-rigid point cloud registration and the iterative closest point algorithm. Initially, surfaces are pre-aligned applying principal component analysis and a general deformation of the Source surface is performed in order to best match the Target. Then, the surfaces are finely matched through a non-rigid local deformation model and each point in the Source surface is placed closer to the Target surface. After the registration, the surface growth distribution is the discretized surface element growth distribution. Maximum and average surface growth were calculated and correlated with the diameter and volume growth rate. The Spearman rho correlation coefficients were calculated and the statistical significance was tested using a two-tailed test. In order to identify potential correlation between intraluminal thrombus deposition (ILT) and surface growth, the co-localization of maximum surface growth with initial ILT maximum thickness was examined. Results - Median annual surface growth was 6.7%(0%>68%) and maximum surface growth was 26%(12%>444%). Correlations between surface and diameter/volume growth are summarized in Table 1. In 48% of follow-ups (15/31), maximum surface growth occurred away from the site of maximum diameter and thus could not have been captured by the measurement of maximum diameter growth. Sixteen cases presented maximum surface growth away and fifteen at the region of maximum initial ILT thickness. AAAs in the former group had significantly lower initial ILT thickness (11.3 vs 19.5mm, p<0.001) compared to those in the latter.Tabled 1DmaxVolumeMaxSurfaceCorrelationCoefficient,465,544Sig. (2-tailed),014,009AvgSurfaceCorrelationCoefficient,389,866Sig. (2-tailed),045,000 Open table in a new tab Conclusion - Regional surface growth of AAAs is not uniform. Average and maximum surface growth are related to the diameter growth but the correlation is only moderate. Volume growth presents very strong correlation with average but only moderate correlation with maximum surface growth rate. Almost half of the lesions display maximum surface growth at a site different from that of maximum diameter. Regional growth is related to initial local amount of ILT. Surface growth provides a means to evaluate spatial distribution of AAA expansion which may be of value for rupture risk predictions. References Metaxa E, Iordanov I, Maravelakis E, Papaharilaou Y. A novel approach for local abdominal aortic aneurysm growth quantification. Medical & Biological Engineering. DOI 10.1007/s11517-016-1592-8.

Intraluminal Thrombus Deposition Is Reduced in Ruptured Compared to Diameter-matched Intact Abdominal Aortic Aneurysms

The aim of this study is to compare the pattern of intraluminal thrombus (ILT) deposition in diameter-matched ruptured and nonruptured abdominal aortic aneurysms (AAAs). We performed a single-center, retrospective study. Ruptured AAAs were collected during 24 months. Diameter-matched intact lesions were randomly selected in a 2:1 ratio and served as controls. ILT cross-sectional area, relative area, maximum thickness, and asymmetric distribution were recorded at the site of maximum aneurysm size and compared between groups. Moreover, additional comparisons were performed inside the group of ruptured AAAs, between the site of maximum size and the site of rupture. Fifteen ruptured cases were compared with 30 nonruptured cases. ILT relative area (37.5% vs. 73.5%, P=0.004) and maximum thickness (14.5 vs. 28mm, P=0.0017) were significantly reduced among ruptured compared to intact AAAs. The latter group presented mostly an anterior eccentric ILT deposition, while the former presented a more symmetrical pattern. The site of rupture was located at the site of maximum size in only 2 cases. In general, ILT was reduced at the site of rupture compared to the site of maximum aneurysm size in ruptured cases but differences did not reach statistical significance. In similar sized AAAs, ILT is reduced in ruptured compared to nonruptured cases.

Correlation of Intraluminal Thrombus Deposition, Biomechanics, and Hemodynamics with Surface Growth and Rupture in Abdominal Aortic Aneurysm—Application in a Clinical Paradigm

The natural history of abdominal aortic aneurysm (AAA) can be investigated through longitudinal evaluation of localized aneurysm characteristics exploiting clinical images. The major challenge is to identify corresponding regions between follow-ups. We have recently developed an algorithm (VascForm) based on nonrigid registration that can obtain surface correspondence and quantify surface growth distribution. A ruptured AAA with an initial computed tomography scan 2years ago was studied. Following 3-dimensional reconstruction of outer wall and luminal surfaces, the wall/thrombus thickness was obtained. Wall stress distribution was computed with finite element analysis, and computational fluid dynamics simulation was performed. VascForm was applied and allowed for the ruptured wall site to be traced back to the initial wall surface and be correlated with local initial intraluminal thrombus thickness, wall stress, and hemodynamic parameters. It also allowed for the quantification of wall surface growth based on surface element growth. Rupture occurred at the posterolateral side. Initial wall surface growth was in most regions 40%. However, a large section of the posterior wall presented 110% growth. Initial thrombus deposition was more prevalent anteriorly, and a posterior thrombus-free isle was present. Peak wall stress (initial and follow-up) occurred at AAA neck. Nonrigid registration revealed that rupture originated from the vicinity of the initial thrombus-free isle. Furthermore, rupture occurred at the wall region with the largest growth (110%). No clear correlation between hemodynamics and rupture site could be identified. High local surface growth correlates with rupture site and could therefore potentially become a marker of rupture risk. The ongoing application of this methodology to a large cohort of AAA patients will focus on identifying characteristic features of AAA regions that present high surface growth in follow-up evaluations, to assist in improved rupture risk estimation.

Correlation Between Matrix Metalloproteinase 9 Activity, Intraluminal Thrombus Deposition, and Computational Pulsatile Hemodynamics in Human Abdominal Aortic Aneurysms

Correlation Between Matrix Metalloproteinase 9 Activity, Intraluminal Thrombus Deposition, and Computational Pulsatile Hemodynamics in Human Abdominal Aortic Aneurysms

The Relationship Between Pulsatile Flow Impingement and Intraluminal Thrombus Deposition in Abdominal Aortic Aneurysms.

Direct numerical simulations were performed on four patient-specific abdominal aortic aneurysm (AAA) geometries and the resulting pulsatile blood flow dynamics were compared to aneurysm shape and correlated with intraluminal thrombus (ILT) deposition. For three of the cases, turbulent vortex structures impinged/sheared along the anterior wall and along the posterior wall a zone of recirculating blood formed. Within the impingement region the AAA wall was devoid of ILT and remote to this region there was an accumulation of ILT. The high wall shear stress (WSS) caused by the impact of vortexes is thought to prevent the attachment of ILT. WSS from impingement is comparable to peak-systolic WSS in a normal-sized aorta and therefore may not damage the wall. Expansion occurred to a greater extent in the direction of jet impingement and the wall-normal force from the continuous impact of vortexes may contribute to expansion. It was shown that the impingement region has low oscillatory shear index (OSI) and recirculation zones can have either low or high OSI. No correlation could be identified between OSI and ILT deposition since different flow dynamics can have similar OSI values.

The - Not So - Solid 5.5 cm Threshold for Abdominal Aortic Aneurysm Repair: Facts, Misinterpretations, and Future Directions.

Abdominal aortic aneurysms (AAAs) represent a focal dilation of the aorta exceeding 1.5 times its normal diameter. It is reported that 4–8% of men and 0.5–1% of women above 50 years of age bear an AAA. Rupture represents the most disastrous complication of aneurysmal disease that is accompanied by an overall mortality of 80%. Autopsy data have shown that nearly 13% of AAAs with a maximum diameter ≤5 cm were ruptured and 60% of the AAAs >5 cm in diameter never ruptured. It is therefore obvious that the “maximum diameter criterion,” as a single parameter that fits all patients, is obsolete. Investigators have begun a search for more reliable rupture risk markers for AAA expansion, such as the level and change of peak wall stress or AAA geometry. Furthermore, it is becoming more and more evident that intraluminal thrombus (ILT), which is present in 75% of all AAAs, affects AAA features and promotes their expansion. Though these hemodynamic properties of AAAs are significant and seem to better describe rupture risk, they are in need of specialized equipment and software and demand time for processing making them difficult in use and unattractive to clinicians in everyday practice. In the search for the addition of other risk factors or user-friendly tools, which may predict AAA expansion and rupture, the use of the asymmetrical ILT deposition index seems appealing since it has been reported to identify AAAs that may have an increased or decreased growth rate.

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.

A longitudinal comparison of hemodynamics and intraluminal thrombus deposition in abdominal aortic aneurysms.

Abdominal aortic aneurysm (AAA) is often accompanied by in traluminal thrombus (ILT), which complicates AAA progression and risk of rupture. Patient-specific computational fluid dynamics modeling of 10 small human AAA was performed to investigate relations between hemodynamics and ILT progression. The patients were imaged using magnetic resonance twice in a 2- to 3-yr interval. Wall content data were obtained by a planar T1-weighted fast spin echo black-blood scan, which enabled quantification of thrombus thickness at midaneurysm location during baseline and followup. Computational simulations with patient-specific geometry and boundary conditions were performed to quantify the hemodynamic parameters of time-averaged wall shear stress (TAWSS), oscillatory shear index (OSI), and mean exposure time at baseline. Spatially resolved quantifications of the change in ILT thickness were compared with the different hemodynamic parameters. Regions of low OSI had the strongest correlation with ILT growth and demonstrated a statistically significant correlation coefficient. Prominent regions of high OSI (>0.4) and low TAWSS (<1 dyn/cm(2)) did not appear to coincide with locations of thrombus deposition.

Flow Residence Time and Regions of Intraluminal Thrombus Deposition in Intracranial Aneurysms

Thrombus formation in intracranial aneurysms, while sometimes stabilizing lesion growth, can present additional risk of thrombo-embolism. The role of hemodynamics in the progression of aneurysmal disease can be elucidated by patient-specific computational modeling. In our previous work, patient-specific computational fluid dynamics (CFD) models were constructed from MRI data for three patients who had fusiform basilar aneurysms that were thrombus-free and then proceeded to develop intraluminal thrombus. In this study, we investigated the effect of increased flow residence time (RT) by modeling passive scalar advection in the same aneurysmal geometries. Non-Newtonian pulsatile flow simulations were carried out in base-line geometries and a new postprocessing technique, referred to as “virtual ink” and based on the passive scalar distribution maps, was used to visualize the flow and estimate the flow RT. The virtual ink technique clearly depicted regions of flow separation. The flow RT at different locations adjacent to aneurysmal walls was calculated as the time the virtual ink scalar remained above a threshold value. The RT values obtained in different areas were then correlated with the location of intra-aneurysmal thrombus observed at a follow-up MR study. For each patient, the wall shear stress (WSS) distribution was also obtained from CFD simulations and correlated with thrombus location. The correlation analysis determined a significant relationship between regions where CFD predicted either an increased RT or low WSS and the regions where thrombus deposition was observed to occur in vivo. A model including both low WSS and increased RT predicted thrombus-prone regions significantly better than the models with RT or WSS alone.