Abstract:
Background and Significance
Abdominal aortic aneurysms (AAAs) are focal dilatations of infrarenal abdominal aorta caused by imbalance in production and degradation of the extracellular matrix. They tend to grow over several decades but rupture abruptly when wall stress exceeds wall strength. Although the pathogenesis is still not well understood, there is a wealth of biological, clinical, histopathological, and mechanical data on AAAs, and there has been significant progress in the biomechanical modeling of these lesions, ( Humphrey & Holzapfel 2012; Humphrey & Taylor 2009). Nevertheless, our ability to predict whether a specific lesion will arrest, continue to enlarge either slowly or rapidly, or ultimately rupture remains wanting. Clinical interventions thus continue to be based primarily on the maximum dimension or expansion rate of the lesion as well as symptoms (e.g., pain) despite the observation that many small lesions rupture whereas larger lesions may remain asymptomatic, (Vorp 2007). One possible reason for this variability in clinical outcomes that has garnered increased attention is the intraluminal thrombus (ILT). The majority of AAAs harbor an ILT, which may vary in thickness from a few millimeters to several centimeters. A large population based study has shown that all AAAs larger than 6 cm contain ILTs, as well as majority of smaller ones, (Behr-Rasmussen et al. 2014). These thrombi have complex natural histories and structures, and their biological and mechanical roles in the progression and potential rupture of AAAs remains controversial. An increased ability to understand and quantify the evolving heterogeneous biochemomechanical properties of ILT and its effects on the natural history of the aneurysmal wall will not only help resolve controversies that have arisen from past consideration of the ILT as a homogeneous and/or inert structure, it will also guide future clinically motivated experimental and computational efforts to understand, predict, and therapeutically address the roles of ILT in this challenging and important vascular pathology.
Up to now we have developed growth model describing thrombus laden aneurysm, which takes into account the overall impact of intraluminal thrombus on the aortic wall. It considers ILT / aortic wall interaction from the mechanical point of view (the effect of thrombus on the stress distribution within the aortic wall, and thus the production and removal of structurally important parts of the wall of the aorta), and biochemical (impact of proteolyticaly active intraluminal thrombus on increased degradation of the extracellular matrix). The model is restricted to axisymmetric cylindrical geometry.
Research Plan
Proper biochemomechanical modeling of the development of an intraluminal thrombus (ILT) has the potential to help us answer the question “Why do certain abdominal aortic aneurysms (AAAs) grow and eventually rupture?’’ The overall goal of this project, therefore, is to quantify the development of ILT from the initial blood clot to a mature formation, with special attention to changes in the clot structure. We hypothesize that AAA growth is influenced by ILT development.
Based on previously mentioned achievements we propose following aims for this project:
1. To implement growth and remodeling model of thrombus-laden fusiform aneurysm from the moment of initiation into the finite element code. Although the majority of abdominal aortic aneurysms are saccular, basilar aneurysms are typically more fusiform. Three layers of aortic wall, i.e. tunica intima, media, and adventitia, as well as heterogenic, layered, biochemomechanically active intraluminal thrombus will be considered. We will employ a rule-of-mixtures relation for the stress response and a constrained mixture theory for the turnover of constituents in a stressed configuration. Finite element method will allow us to address changes in axial direction (from the neck of AAA to the thickest part).
2. To systematically investigate the biomechanical properties of intraluminal thrombus and to develop a method that could effectively reveal the distribution of strains within samples. We collect samples of ILT from the anterior part of the aneurysm during open surgical repair. All samples will be classified upon size, age, gender, preoperative data etc. The samples are stored in Dulbecco’s Modified Eagle’s Medium within the operating room immediately after retrieval. Experiments will be performed within six hours after the surgical treatment. From each thrombus we will cut samples from the luminal, medial and abluminal parts. Each specimen will then be fixed with sutures and fish hooks to the testing machine. All specimens are then tested on a biaxial machine available at Tongji University. Futhermore for each tested sample additional histological and chemical analysis will be performed. All these data (mechanical, chemical, histological) expressed for specific thrombus and adjoining arterial wall will be used to tune numerical model.
We strongly believe that a joint work by the groups from Tongji University, School of Medicine and the Faculty of Mechanical Engineering and Naval Architecture University of Zagreb is essential for the success of this bilateral project. The group from Shanghai has the necessary equipment and knoweledge of experimental testings on ILT samples while the group from Zagreb has developed the numerical code describing aneurysmal growth.
Contact:
Dr.sc. Igor Karšaj, Associate Professor
Faculty of Mechanical Engineering and Naval Architecture
University of Zagreb
Ivana Lučića 5
HR-10000 Zagreb, Croatia
Phone: ++385 1 61 68 125
Fax: ++385 1 61 68 187
e-mail: igor.karsaj@fsb.hr