Figures & data
Figure 1. A potential scheme utilizing magnetic resonance(MR) methodologies in the risk assessment of long‐term risk for atherothrombotic events (non‐symptomatic individuals) and of short‐term risk for recurrent cardiovascular events after an experienced acute coronary syndrome (ACS) (symptomatic patients). At risk assessment point I the molecular constituents of serum, including lipoprotein subclasses, could be assessed by in vitro1H magnetic resonance spectroscopy (MRS) metabonomics for non‐symptomatic individuals. If high long‐term risk for atherothrombotic events is indicated, non‐invasive in vivo magnetic resonance imaging (MRI) could follow for the potential detection of plaque (risk assessment point IIa) and subsequent compositional evaluation of the vulnerability of the detected plaque(s) for rupture or erosion (IIb). Depending on the outcome from the plaque detection and assessment by MRI the individual could accordingly be directed for further actions. If vulnerable plaque at point IIb would be detected, considerations for aggressive drug therapy or invasive therapies such as angiographic stenting or bypass surgery would be needed. In the case of an individual with an experienced ACS (III) in vitro1H MRS metabonomics could be used to complement the clinical protocols when evaluating the risk for recurrent cardiovascular events and the proper individual treatment options. For some symptomatic patients in vivo MRI might also be feasible at point III for direct assessment of plaque composition and vulnerability. This scheme can be seen as one option to elucidate the potential of MR in detecting individual intermediate atherothrombotic end‐points and utilizing their prognostic value before the occurrence of a definite end‐point. The recent MR findings and developments summarized in this review awaken confidence that this kind of scheme might be operational in the near future saving both human suffering and societal health costs.
Figure 2. Illustration of the spatially enhanced iterative cluster analysis for the multi‐contrast ex vivo magnetic resonance (MR) images of human coronary artery specimens. On the left are shown the T1‐, proton density, and T2‐weighted (T1W, PDW and T2W, respectively) axial plane images that were assigned red (R), green (G), and blue (B) colours, respectively, and combined to yield a colour composite and pseudo‐colour cluster image of the coronary artery with colour distributions corresponding to different tissue types. On the right a comparable histopathology image via a combined Masson's elastic (CME) stain is shown. This type Vb‐Vc lesion exhibits eccentric fibrous deposits and a dark area of calcification. The identified areas include dense fibrous tissue (df), calcium deposits (cal), media (med), and fibrous cap (fc). The CME histopathology shows an excellent agreement with the MR images. (With permission from Itskovich et al. 2004 Citation21.)
Figure 3. A T1‐weighted image from a patient with abdominal aortic aneurysm demonstrating bright signal within thrombus and darker signal in lipid core towards vessel wall (on the left). The cap region is faintly seen on the T1‐weighted image. A comparable T1‐weighted image, but several minutes after infusion of Gd‐DTPA, is shown on the right. Note the improved delineation of fibrous cap by bright signal within (arrow). (With permission from Kramer et al. 2004 Citation39.)
Figure 4. A magnetic resonance imaging(MRI) application at 1.5 T using αvβ3‐integrin‐targeted, paramagnetic perfluorocarbon nanoparticles in a hyperlipidaemic rabbits to detect angiogenesis within the aortic wall. Per cent enhancement maps (false‐coloured from blue to red) are illustrated from individual aortic segments at renal artery (A), mid‐aorta (B), and diaphragm (C) 2 hours after infusion of the αvβ3‐integrin‐targeted nanoparticles. (With permission from Winter et al. 2003 Citation45.)
Figure 5. An application of a high‐density lipoprotein (HDL)‐like nanoparticle contrast agent for macrophage‐targeted in vivo magnetic resonance imaging (MRI). Phospholipid‐based contrast agent Gd‐DTPA‐DMPE and NBD‐DPPE‐labelled phospholipid for fluorescence confocal microscopy were used for the reconstruction of HDL. The MR images of an apolipoprotein E knockout mouse at 1.5 T illustrate the pre‐ and 24 h post‐injection of contrast agent at a rHDL dose of 4.36 μmol/kg. White arrows point to the abdominal aorta; the insets denote a magnification of the aorta region. (Modified from Frias et al. 2004 Citation52 with permission.)
Figure 6. Illustration of quantitative‘magnetic resonance immunohistochemistry’ with the fibrin‐targeted perfluorocarbon nanoparticles in the case of an ex vivo human carotid endarterectomy sample: (a) An optical image of a 5‐mm cross‐section of a human carotid endarterectomy sample. This section showed moderate luminal narrowing as well as several atherosclerotic lesions. (b) A 19F projection image acquired at 4.7 T through the entire carotid artery sample shows high signal along the lumen due to nanoparticles bound to fibrin. (c) A concentration map of bound nanoparticles in the carotid sample. (With permission from Morawski et al. 2004 Citation58.)
Figure 7. Demonstration of the magnetic resonance(MR) image‐guided, single‐voxel ex vivo1H magnetic resonance spectroscopy (MRS) to characterize lipid‐rich and lipid‐poor regions of atherosclerotic plaque. Spectra elicited from 1‐mm3 voxels are illustrated with insets showing the parametric map and voxel position for reference. Panels A and C illustrate the intense water signal without water suppression. Weak lipid signals are evident in panel B only after vertical expansion (inset). In contrast, strong lipid signals (consistent with cholesterol esters) are seen in panel D. (With permission from Ruberg et al. 2006 Citation73.)
