Research Papers

Biochemomechanics of Intraluminal Thrombus in Abdominal Aortic Aneurysms

[+] Author and Article Information
J. S. Wilson

Department of Biomedical Engineering,
Yale University,
New Haven, CT 06520

L. Virag, I. Karšaj

Faculty of Mechanical Engineering and Naval Architecture,
University of Zagreb,
10000 Zagreb, Croatia

P. Di Achille

Department of Biomedical Engineering,
Yale University,
New Haven, CT 06520

J. D. Humphrey

Fellow ASME
Department of Biomedical Engineering,
Yale University,
New Haven, CT 06520;
Vascular Biology and Therapeutics Program,
Yale School of Medicine,
New Haven, CT 06520
e-mail: jay.humphrey@yale.edu

1Corresponding author. Present address: Department of Biomedical Engineering, Malone Engineering Center, Yale University, New Haven, CT 06520.

Contributed by the Bioengineering Division of ASME for publication in the JOURNAL OF BIOMECHANICAL ENGINEERING. Manuscript received November 13, 2012; final manuscript received January 14, 2013; accepted manuscript posted January 18, 2013; published online February 7, 2013. Editor: Victor H. Barocas.

J Biomech Eng 135(2), 021011 (Feb 07, 2013) (14 pages) Paper No: BIO-12-1552; doi: 10.1115/1.4023437 History: Received November 13, 2012; Revised January 14, 2013; Accepted January 18, 2013

Most computational models of abdominal aortic aneurysms address either the hemodynamics within the lesion or the mechanics of the wall. More recently, however, some models have appropriately begun to account for the evolving mechanics of the wall in response to the changing hemodynamic loads. Collectively, this large body of work has provided tremendous insight into this life-threatening condition and has provided important guidance for current research. Nevertheless, there has yet to be a comprehensive model that addresses the mechanobiology, biochemistry, and biomechanics of thrombus-laden abdominal aortic aneurysms. That is, there is a pressing need to include effects of the hemodynamics on both the development of the nearly ubiquitous intraluminal thrombus and the evolving mechanics of the wall, which depends in part on biochemical effects of the adjacent thrombus. Indeed, there is increasing evidence that intraluminal thrombus in abdominal aortic aneurysms is biologically active and should not be treated as homogeneous inert material. In this review paper, we bring together diverse findings from the literature to encourage next generation models that account for the biochemomechanics of growth and remodeling in patient-specific, thrombus-laden abdominal aortic aneurysms.

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Grahic Jump Location
Fig. 1

Patient's AAA volume history. Note the changes in volume of the lumen, ILT (thrombus), and aneurysmal sac over time, with a possible discrete deposition of thrombus between Jun. 2005 and Mar. 2006. From Basciano et al. [31], with kind permission from Springer Science and Business Media.

Grahic Jump Location
Fig. 2

Gross and ultrastructural appearance of a layered intraluminal thrombus from a human AAA. Note the entrapped cells in the luminal thrombus. From Wang et al. [36], with permission.

Grahic Jump Location
Fig. 3

Maximum tangential moduli of ILT from human AAAs separated by luminal (L), medial (M), and adventitial (A) layers and phase (a proposed indicator of age; see Fig. 4). From Tong et al. [12], with permission.

Grahic Jump Location
Fig. 4

Proposed histological phases of ILT maturation. From Tong et al. [12], with permission.

Grahic Jump Location
Fig. 5

Note the “crescent sign” on a contrast-enhanced CT study of a 59 year-old male with an AAA. (Left—axial image; Right—maximum-intensity projection reconstruction on an oblique sagittal projection). From Labruto et al. [124], with permission.

Grahic Jump Location
Fig. 6

Top: Simplified schema of the possible formation of a layered “space filling” ILT by multiple cycles of AAA sac enlargement and ILT deposition secondary to disturbed flow. Note that the specific initiation site in 3 is merely schematic. Bottom: Cross-sectional view at two different axial locations at one instant, when the luminal ILT layer (black) may remain in contact with the wall at the shoulder region while being distant from the anterior wall at the apex of the lesion. (Diagram by Carolyn Valentín).

Grahic Jump Location
Fig. 7

Comparison of a contrast-enhanced CT image (left) and a T2-weighted MR image (right) of an AAA in a 49 year-old male. Note the clear layers of the ILT evident in the MRI that are not delineated by CT. From Labruto et al. [124], with permission.

Grahic Jump Location
Fig. 8

Schema of some of the primary effectors governing the evolution of the mechanics of both the ILT and aneurysmal wall. Solid black arrow – “increases the amount/activity,” dotted black line—“degrades,” dashed gray line—“modulates the effect.” (ILT: intraluminal thrombus, SMC: smooth muscle cell, FB: fibroblast, WBC: white blood cell, RBC: red blood cell).



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