MRI of atherosclerose

This thesis is aimed at visualization of atherosclerotic plaques with MRI. Noninvasive screening for subclinical atherosclerosis as well as detection of high-risk atherosclerotic plaque in an established population of cardiovascular patients is important for patient management. Anatomical MRI utilizing intrinsic contrast based on different MR relaxation properties of plaque components, contrast-enhanced MRI using non-targeted ultra-small particles of iron oxide (USPIOs) and contrast enhanced MRI using micelles targeting novel targets of advanced atherosclerosis disease in plaque, were investigated. An overview of literature on the subject of MRI of atherosclerosis is provided (chapter 2 and 3). We succeeded in ex vivo discrimination between lipid core and foam cells and better discrimination between lipid core and stable plaque components in human carotid plaque using FLASH with fat suppression (FS) when compared to FLASH without FS (Chapter 4). Addition of Inversion Recovery Spin Echo (IRSE) to a panel of standard techniques (T1w/T2w/PDw) allowed for better identification of intra-plaque hemorrhage. Some research groups have targeted the macrophages in atherosclerotic plaques with USPIOs. The tremendous T2* contrast observed in these studies was also seen in our mouse study, however we were only able to relate the negative contrast caused by USPIOs to uptake in peri-aortic lymph nodes (Chapter 5). Blooming, the effect of spreading of negative contrast beyond the location of uptake of iron oxides, may account for mistaking uptake of USPIOs by peri-aortic lymph node macrophages for uptake by plaque macrophages. Molecular MRI of atherosclerotic plaque has been performed with contrast agents directed against a variety of targets. Some of these targets are macrophage membrane-bound receptors, like the CB2 receptor (Chapter 6 and 8). Other targets are intracellular proteins stored in macrophage granules and released from macrophages to the extracellular matrix, like NGAL (Chapter 6 and 7). We showed increased enhancement at 72 hours after injection of NGAL/24p3 targeted micelles when compared to isotype antibody conjugated micelles (Chapter 7). Just from a practical point of view, in most studies post-injection MRI was planned at 24, 48 and 72 hours after injection. However, accurate definition of the timing window for visualization of specific uptake would be more appropriate in order to increase sensitivity and specificity of the test outcome. Therefore, we performed continuous T1 weighted imaging of the aorta after injection of both CB2-R targeted and control micelles (Chapter 8). Moreover the relation between aortic normalized enhancement ratios (NER) and gadolinium content was calculated from standard T1 weighted images and from inversion-recovery prepared T1 weighted images. The relation was stronger when the NER was calculated from the inversion-recovery prepared T1 weighted image, however we advise averaging of several NER values calculated from sequential images, because of a substantial inter-scan variability. As a separate subject, performance of a self-gated cardiac MRI method has been shown comparable to a prospectively gated cardiac MRI method for evaluation of cardiac function parameters in mice after permanent occlusion of the left anterior descending artery (Chapter 9).