Giampaolo Martufi

Local Quantification of Wall Thickness and Intraluminal Thrombus Offer Insight into the Mechanical Properties of the Aneurysmal Aorta.

Wall stress is a powerful tool to assist clinical decisions in rupture risk assessment of abdominal aortic aneurysms. Key modeling assumptions that influence wall stress magnitude and distribution are the inclusion or exclusion of the intraluminal thrombus in the model and the assumption of a uniform wall thickness. We employed a combined numerical-experimental approach to test the hypothesis that abdominal aortic aneurysm (AAA) wall tissues with different thickness as well as wall tissues covered by different thrombus thickness, exhibit differences in the mechanical behavior. Ultimate tissue strength was measured from in vitro tensile testing of AAA specimens and material properties of the wall were estimated by fitting the results of the tensile tests to a histo-mechanical constitutive model. Results showed a decrease in tissue strength and collagen stiffness with increasing wall thickness, supporting the hypothesis of wall thickening being mediated by accumulation of non load-bearing components. Additionally, an increase in thrombus deposition resulted in a reduction of elastin content, collagen stiffness and tissue strength. Local wall thickness and thrombus coverage may be used as surrogate measures of local mechanical properties of the tissue, and therefore, are possible candidates to improve the specificity of AAA wall stress and rupture risk evaluations.

Mechano-biology in the thoracic aortic aneurysm: a review and case study

An aortic aneurysm is a permanent and localized dilatation of the aorta resulting from an irreversible loss of structural integrity of the aortic wall. The infrarenal segment of the abdominal aorta is the most common site of aneurysms; however, they are also common in the ascending and descending thoracic aorta. Many cases remain undetected because thoracic aortic aneurysms (TAAs) are usually asymptomatic until complications such as aortic dissection or rupture occurs. Clinical estimates of rupture potential and dissection risk, and thus interventional planning for TAAs, are currently based primarily on the maximum diameter and growth rate. The growth rate is calculated from maximum diameter measurements at two subsequent time points; however, this measure cannot reflect the complex changes of vessel wall morphology and local areas of weakening that underline the strong regional heterogeneity of TAA. Due to the high risks associated with both open and endovascular repair, an intervention is only justified if the risk for aortic rupture or dissection exceeds the interventional risks. Consequently, TAAs clinical management remains a challenge, and new methods are needed to better identify patients for elective repair. We reviewed the pathophysiology of TAAs and the role of mechanical stresses and mathematical growth models in TAA management; as a proof of concept, we applied a multiscale biomechanical analysis to a case study of TAA.

Is There a Role for Biomechanical Engineering in Helping to Elucidate the Risk Profile of the Thoracic Aorta

Clinical estimates of rupture and dissection risk of thoracic aortic aneurysms are based on nonsophisticated measurements of maximum diameter and growth rate. The use of aortic size alone may overlook the role that vessel heterogeneity plays in assessing the risk of catastrophic complications. Biomechanics may help provide a more nuanced approach to predict the behavior of thoracic aortic aneurysms. In this report, we review modeling studies with an emphasis on mechanical and fluid dynamics analyses. We identify open problems and highlight the future possibility of a multidisciplinary approach that includes biomechanics and imaging to evaluate the likelihood of rupture or dissection.

In vivo strain assessment of the abdominal aortic aneurysm

The only criteria currently used to inform surgical decision for abdominal aortic aneurysms are maximum diameter (>5.5 cm) and rate of growth, even though several studies have identified the need for more specific indicators of risk. Patient-specific biomechanical variables likely to affect rupture risk would be a valuable addition to the science of understanding rupture risk and prove to be a life saving benefit for patients. Local deformability of the aorta is related to the local mechanical properties of the wall and may provide indication on the state of weakening of the wall tissue. We propose a 3D image-based approach to compute aortic wall strain maps in vivo. The method is applicable to a variety of imaging modalities that provide sequential images at different phases in the cardiac cycle. We applied the method to a series of abdominal aneurysms imaged using cine-MRI obtaining strain maps at different phases in the cardiac cycle. These maps could be used to evaluate the distensibility of an aneurysm at baseline and at different follow-up times and provide an additional index to clinicians to facilitate decisions on the best course of action for a specific patient.

Local Diameter, Wall Stress, and Thrombus Thickness Influence the Local Growth of Abdominal Aortic Aneurysms.

Purpose: To investigate the influence of the local diameter, the intraluminal thrombus (ILT) thickness, and wall stress on the local growth rate of abdominal aortic aneurysms. Methods: The infrarenal aortas of 90 asymptomatic abdominal aortic aneurysm (AAA) patients (mean age 70 years; 77 men) were retrospectively reconstructed from at least 2 computed tomography angiography scans (median follow-up of 1 year) and biomechanically analyzed with the finite element method. Each individual AAA model was automatically sliced orthogonally to the lumen centerline and represented by 100 cross sections with corresponding diameters, ILT thicknesses, and wall stresses. The data were grouped according to these parameters for comparison of differences among the variables. Results: Diameter growth was continuously distributed over the entire aneurysm sac, reaching absolute and relative median peaks of 3.06 mm/y and 7.3%/y, respectively. The local growth rate was dependent on the local baseline diameter, the local ILT thickness, and for wall segments not covered by ILT, also on the local wall stress level (all p<0.001). For wall segments that were covered by a thick ILT layer, wall stress did not affect the growth rate (p=0.08). Conclusion: Diameter is not only a strong global predictor but also a local predictor of aneurysm growth. In addition, and independent of the diameter, the ILT thickness and wall stress (for the ILT-free wall) also influence the local growth rate. The high stress sensitivity of nondilated aortic walls suggests that wall stress peaks could initiate AAA formation. In contrast, local diameters and ILT thicknesses determine AAA growth for dilated and ILT-covered aortic walls.

On the Impact of Intraluminal Thrombus Mechanical Behavior in AAA Passive Mechanics

Intraluminal thrombus (ILT) is a pseudo-tissue that develops from coagulated blood, and is found in most abdominal aortic aneurysms (AAAs) of clinically relevant size. A number of studies have suggested that ILT mechanical characteristics may be related to AAA risk of rupture, even though there is still great controversy in this regard. ILT is isotropic and inhomogeneous and may appear as a soft (single-layered) or stiff (multilayered fibrotic) tissue. This paper aims to investigate how ILT constitution and topology influence the magnitude and location of peak wall stress (PWS). In total 21 patient-specific AAAs (diameter 4.2–5.4xa0cm) were reconstructed from computer tomography images and biomechanically analyzed using state-of-the-art modeling assumptions. Results indicated that PWS correlated stronger with ILT volume (ρxa0=xa00.44, pxa0=xa00.05) and minimum thickness of ILT layer (ρxa0=xa00.73, pxa0=xa00.001) than with maximum AAA diameter (ρxa0=xa00.05, pxa0=xa00.82). On average PWS was 20% (SD 12%) higher for FE models that used soft instead of stiff ILT models (pxa0<xa00.001). PWS location strongly correlated with sites of minimum ILT thickness in the section of maximum AAA diameter and was independent from ILT stiffness. In addition, ILT heterogeneity, i.e., the spatial composition of soft and stiff thrombus tissue, can considerably influence stress in the AAA wall. The present study is limited to identification of influential biomechanical factors, and how its findings translate to an AAA rupture risk assessment remains to be explored by clinical studies.

MULTIDIMENSIONAL ANEURYSMAL GROWTH - A NOVEL TECHNIQUE DERIVED FROM BIOMEDICAL ENGINEERING PRINCIPLES TO HELP REFINE ASSESSMENT OF AORTIC GROWTH

rare medial cell senescence that was 4.2-fold more prevalent in dilated aortas (0.83 0.10%) than in non-dilated aortas (0.20 0.10%, p1⁄40.048). Expression of p16 was abundantly detected in medial SMCs within dilated aortas (24.0 1.5%) and 3-fold more abundant than in non-dilated aortas (8.2 1.5%, p<0.0001). Interestingly, medial p16 expression did not correlate with telomere length of medial cells, as determined by quantitative and standardized PCR (p1⁄40.35). Immunostaining for gH2A.X (phosphorylated Ser139) interestingly revealed discrete nuclear DNA double-strand breakage signals in 25.7 3.8% of medial cells in dilated aortas from patients with BAV, which was 2.3-fold higher than that found in non-dilated aortas (11.0 4.9, p1⁄40.03). Medial cell outgrowths from BAV patients showed increased senescenceassociated s-galactosidase activity compared to control patient SMC outgrowths (38.9 2.9 vs. 19.5 1.9, p1⁄40.0005). Furthermore, incubation of early passage SMCs with 50nM of angiotensin II for 3 days caused a 1.4-fold increase in senescence-associated s-galactosidase expressing SMCs from BAV patients (p1⁄40.0006), but elicited no change in senescence-associated s-galactosidase expression in SMCs from control patients (p1⁄40.83). CONCLUSION: These findings identify a previously unrecognized phenomenon of accelerated SMC aging in the aortas of patients with BAV, with cellular senescence and unresolved DNA breaks. Accelerated cell aging could thus be a driver of aortic wall degeneration in these patients and a potential therapeutic target.