Characterization of Atherosclerotic Plaque Components by AFM

Characterization of Atherosclerotic Plaque Components by AFM

Jacques Ohayon, PhD and Philippe Tracqui, PhD

Laboratory TIMC-IMAG/DyCTiM, UJF, CNRS UMR 5525, In³S
Faculty of Medicine of Grenoble - 38706 La Tronche Cedex, France
Email: Jacques.Ohayon@imag.fr

Mapping elasticity moduli of atherosclerotic plaque in situ via atomic force microscopy - Journal of structural Biology, 174(1):115-23, 2011 - Several studies have suggested that evolving mechanical stresses and strains drive atherosclerotic plaque development and vulnerability. Especially, stress distribution in the plaque fibrous capsule is an important determinant for the risk of vulnerable plaque rupture. Knowledge of the stiffness of atherosclerotic plaque components is therefore of critical importance. In this work, force mapping experiments using atomic force microscopy (AFM) were conducted in apolipoprotein E-deficient (ApoE^−/−) mouse, which represents the most widely used experimental model for studying mechanisms underlying the development of atherosclerotic lesions. To obtain the elastic material properties of fibrous caps and lipidic cores of atherosclerotic plaques, serial cross-sections of aortic arch lesions were probed at different sites. Atherosclerotic plaque sub-structures were subdivided into cellular fibrotic, hypocellular fibrotic and lipidic rich areas according to histological staining. Hertz’s contact mechanics were used to determine elasticity (Young’s) moduli that were related to the underlying histological plaque structure. Cellular fibrotic regions exhibit a mean Young modulus of 10.4 ± 5.7 kPa. Hypocellular fibrous caps were almost six-times stiffer, with average modulus value of 59.4 ± 47.4 kPa, locally rising up to ~ 250 kPa. Lipid rich areas exhibit a rather large range of Young’s moduli, with average value of 5.5 ± 3.5 kPa. Such precise quantification of plaque stiffness heterogeneity will allow investigators to have prospectively a better monitoring of atherosclerotic disease evolution, including arterial wall remodeling and plaque rupture, in response to mechanical constraints imposed by vascular shear stress and blood pressure.

Fig. 1 : Mechanical properties of arterial wall. A. Ultrastructure of arterial wall revealed by HES staining, exhibiting the regular organization of elastin sheets (scale bar 15 mm). B. Probing the stiffness of elastic lamina by AFM force spectroscopy (scale bar 50 mm).

Selected Publications

• Ohayon J, Mesnier N, Broisat A, Toczek J, Riou L, Tracqui P. Elucidating atherosclertic vulnerable plaque rupture by modeling cross substitution of ApoE-/- mouse and human plaque component stiffnesses. Biomechanics and Modeling in Mechanobiology. (in press), 2011.

• Ohayon J, Gharib AM, GarciaA, Heroux J, YazdaniSK, Malvè M, Tracqui P, MartinezMA, Doblare M, FinetG, Pettigrew RI. Is arterial wall-strain stiffening and additional process responsible for atherosclerosis in coronary bifurcations? in vivo Study Based on Dynamic CT and MRI. Am J Physiol Heart Circ Physiol. 301(3):H1097-106, 2011.

• Broisat A, Toczek J, Mesnier N, Tracqui P, Ghezzi C, Ohayon J, Riou L. Assessing the low levels of mechanical stress in aortic atherosclerosis lesions from ApoE-/-mouse . Arterioscler Thromb Vasc Biol. 31(5):1007-10, 2011.

• Tracqui P, Broisat A, Toczek J, Mesnier N, Ohayon J, Riou L. Mapping elasticity moduli of atherosclerotic plaque in situ via atomic force microscopy . Journal of structural Biology 174(1):115-23, 2011.

• Heroux J, Gharib AM, Danthi NS, Cecchini S, Ohayon J, Pettigrew RI. High Affinity avb3 Integrin Targeted Optical Probe as a New Imaging Biomarker for Early Atherosclerosis: Initial Studies in Watanabe Rabbits. Mol Imaging Biol., 12(1):2-8, 2010.

• Soloperto G, Keenan NG, Sheppard MN, Ohayon J, Wood N, Pennell DJ, Mohiaddin RH, Xu XY. A combined imaging, computational and histological analysis of a ruptured carotid plaque. Artery Research, 4(2):59-65, 2010.

• Le Floc'h S, Cloutier G, FinetG, TracquiP, PettigrewRI, Ohayon J. On the potential of a new IVUS elasticity modulus imaging approach for detecting vulnerable atherosclerotic coronary plaques: in vitro vessel phantom study. Phys. Med. Biol., 55:5701-5721, 2010.

• Finet G., Huo Y, Riouffol G, Ohayon J, Guerin P, Kassab GS. Structure-function relation in the coronary artery tree: from fluid dynamics to arterial bifurcations. EuroIntervention, 6:J10-J15, 2010.

• Le Floc'h S, Ohayon J, Tracqui P, Finet G, Gharib AM, Maurice R, Cloutier G, Pettigrew RI. Vulnerable Atherosclerotic Plaque Elasticity Reconstruction Based on a Segmentation-Driven Optimization Procedure Using Strain Measurements: Theoretical Framework. IEEE Trans Med Imaging, 28(7):1126-37, 2009.

• Kotys MS, Herzka DA, Vonken EJ, Ohayon J, Heroux J, Gharib AM, Stuber M, Pettigrew RI. Profile order and time-dependent artifacts in contrast-enhanced coronary MR angiography at 3T: origin and prevention. Magn Reson Med., 62(2):292-9, 2009.

• Eskandari H, Salcudean SE, Rohling R, Ohayon J. Viscoelastic characterization of soft tissue from dynamic finite element models. Physics in Medicine and Biology, 53(22):6569-90, 2008.

• Ohayon J, Finet G, Gharib AM, Herzka DA, Tracqui P, Heroux J, Rioufol G, Kotys MS, Elagha A, Pettigrew RI. Necrotic core thickness asnd positive arterial remodeling index: emergent biomechanical factors for evaluating the risk of plaque rupture. Am J Physiol Heart Circ Physiol., 295(2):H717-27, 2008.

• Ohayon J, Dubreuil O, Tracqui P, Le Floc'h S, Rioufol G, Chalabreysse L, Thivolet F, Pettigrew RI, Finet G. Influence of residual stress/strain on the biomechanical stability of vulnerable coronary plaques: potential impact for evaluating the risk of plaque rupture. Am J Physiol Heart Circ Physiol., 293(3):H1987-96, 2007.

• Boudou T., Ohayon J., Arntz Y., Finet G., Picart C., Tracqui P. An extended modeling of the micropipette aspiration experiment for the characterization of the Young’s modulus and Poisson’s ratio of adherent thin biological samples: Numerical and experimental studies. Journal of Biomechanics, 39:1677-85, 2006.

• Boudou T., Ohayon J., Picart C., Tracqui P. Characterization of the Young’s modulus and Poisson’s ratio of polyacrylamide gels using micropipette aspiration technique. Biorheology, 43(6): 721-8, 2006.