Visualizing the 3D collagen structure of human atherosclerotic plaques using Diffusion Tensor Imaging

Introduction Ischemic strokes and heart attacks are mainly caused by rupture of the fibrous cap of an atherosclerotic plaque. Reliable prediction of the fibrous cap rupture is, therefore, crucial to prevent these potentially lethal cardiovascular events. Since cap rupture occurs when the stresses in the cap exceed the strength of the cap, biomechanical modeling may help to improve cap rupture prediction. Biomechanical models depend strongly on the material parameters used as input. Previous studies focused on the anisotropic mechanical behaviour of atherosclerotic plaques and produced stiffness values for the collagen fibers in plaques [1]. However, for a more complete characterization knowledge of the global 3D collagen architecture in atherosclerotic plaques is required. Therefore, for the first time diffusion tensor imaging (DTI) was used to investigate the 3D collagen structure of human atherosclerotic plaques. Methods Until now five human carotid atherosclerotic plaques were obtained from endarterectomy patients and embedded in 4 % type VII agarose. The samples were placed in a 9.4 T horizontal-bore MRI scanner to conduct DTI. DTI enabled the tracking of the fiber directions and visualisation of the collagen fibers [2]. Results The consistent results of five different plaques suggest that collagen fibers are deposited in a new layer in a different direction during the development of atherosclerosis (see figure for one representative result). Two distinct layers of collagen fibers were found; an outer layer, where the collagen is aligned in the circumferential direction (14.5°±28.0°), similar to healthy arteries [2], and an inner layer where the collagen follows a longitudinal direction (77.4°±22.4°). Conclusions DTI allowed the visualization of the global 3D collagen architecture of atherosclerotic plaques. The inner collagen layer showed a surprising result and implies a change of strain distribution in the artery during the later stage of atherosclerosis, possibly due to the thickening and stiffening of the diseased intimal tissue. These data, combined with collagen stiffness data found in previous studies [1], will be used as input for biomechanical models including the anisotropic mechanical behaviour of plaque tissue. Models using general over-simplified assumptions like isotropic behaviour can be replaced by models including the anisotopic behavior and thereby improve the stress analysis of plaques. Improved models might help in the diagnosis and treatment of plaque rupture preventing heart attacks and ischemic strokes. References [1] Chai C-K, Akyildiz AC, Speelman L, Gijsen FJH, Oomens CWJ, Sambeek MRHM, van der Lugt A, Baaijens FTP, Anisotropic mechanical behaviour of carotid atherosclerotic plaques at large strain, The 8th international symposium on Biomechanics in Vascular Biology and Cardiovascular Disease, Rotterdam, 2013. [2] Ghazanfari S, Driessen-Mol A, Strijkers GJ, Kanters FMW, Baaijens FPT, Bouten CVC, A comparative analysis of the collagen architecture in the carotid artery: Second harmonic generation versus diffusion tensor imaging, Biochemical and Biophysical Research Communications, 426(1): 54-58, 2012.