BackgroundDiffusion weighted (DW) cardiovascular magnetic resonance (CMR) has shown great potential to discriminate between healthy and diseased vessel tissue by evaluating the apparent diffusion coefficient (ADC) along the arterial axis. Recently, ex vivo studies on porcine arteries utilizing diffusion tensor imaging (DTI) revealed a circumferential fiber orientation rather than an organization in axial direction, suggesting dominant diffusion perpendicular to the slice direction. In the present study, we propose a method to access tangential and radial diffusion of carotids in vivo by utilizing a pulse sequence that enables high resolution DW imaging in combination with a two-dimensional (2D) diffusion gradient direction sampling scheme perpendicular to the longitudinal axis of the artery.MethodsHigh resolution DTI of 12 healthy male volunteers (age: 25–60 years) was performed on one selected axial slice using a read-out segmented EPI (rs-EPI) sequence on a 3T MR scanner.ResultsIt was found consistently for all 12 volunteers, that the tangential component as the principle direction of diffusion. Mean vessel wall fractional anisotropy (FA) values ranged from 0.7 for the youngest to 0.56 for the oldest participant. Linear regression analysis between the FA values and volunteers age revealed a highly significant (P < 0.01) linear relationship with an adjusted R2 of 0.52. In addition, a linear trend (P < 0.1) could be observed between radial diffusivity (RD) and age.ConclusionThese results point to FA being a sensitive parameter able to capture changes in the vascular architecture with age. In detail, the data demonstrate a decrease in FA with advancing age indicating possible alterations of tissue microstructural integrity. Moreover, analyzing 2D diffusion tensor directions is sufficient and applicable in a clinical setup concerning the overall scan time.
Background: Magnetic liposomes (MLs) are phospholipid vesicles that encapsulate magnetic and/or paramagnetic nanoparticles. They are applied as contrast agents for magnetic resonance imaging (MRI). MLs have an advantage over free magnetic nanocores, in that various functional groups can be attached to the surface of liposomes for ligand-specific targeting. We have synthesized PEG-coated sterically-stabilized magnetic liposomes (sMLs) containing ultrasmall superparamagnetic iron oxides (USPIOs) with the aim of generating stable liposomal carriers equipped with a high payload of USPIOs for enhanced MRI contrast. Methods: Regarding iron oxide nanoparticles, we have applied two different commercially available surface-coated USPIOs; sMLs synthesized and loaded with USPIOs were compared in terms of magnetization and colloidal stability. The average diameter size, morphology, phospholipid membrane fluidity, and the iron content of the sMLs were determined by dynamic light scattering (DLS), transmission electron microscopy (TEM), fluorescence polarization, and absorption spectroscopy, respectively. A colorimetric assay using potassium thiocyanate (KSCN) was performed to evaluate the encapsulation efficiency (EE%) to express the amount of iron enclosed into a liposome. Subsequently, MRI measurements were carried out in vitro in agarose gel phantoms to evaluate the signal enhancement on T1-and T2-weighted sequences of sMLs. To monitor the biodistribution and the clearance of the particles over time in vivo, sMLs were injected in wild type mice. Results: DLS revealed a mean particle diameter of sMLs in the range between 100 and 200 nm, as confirmed by TEM. An effective iron oxide loading was achieved just for one type of USPIO, with an EE% between 74% and 92%, depending on the initial Fe concentration (being higher for lower amounts of Fe). MRI measurements demonstrated the applicability of these nanostructures as MRI probes. Conclusion: Our results show that the development of sMLs is strictly dependent on the physicochemical characteristics of the nanocores. Once established, sMLs can be further modified to enable noninvasive targeted molecular imaging.
Background: Atherosclerosis, the leading cause of cardiovascular disease responsible for the majority of deaths worldwide, cannot be sufficiently explained by established risk factors including hypercholesterolemia. Elevated plasma homocysteine is an independent risk factor for atherosclerosis and is strongly linked to cardiovascular mortality. However, the role of homocysteine in atherosclerosis is still insufficiently understood. Previous research in this area has been also hampered by the lack of reproducible in-vivo models of atherosclerosis that resemble the human situation.Methods: Aortic specimens obtained from balloon injured rabbits fed either diet deficient in B vitamins, supplemented with 1% cholesterol or combined diet were subjected to ex vivo MRI, myographical, biomechanical, microscopical and histological analysis. Lipoproteins were analyzed by FPLC.Findings: We developed and applied an automated system for vessel wall injury that leads to more homogenous damage and more pronounced atherosclerotic plaque development even at low balloon pressure. Already in the absence of hypercholesterolemia, B vitamin deficiency results in accumulation of macrophages and lipids in the aorta, impairment of its biomechanical properties and disorganization of aortic collagen. Combination of B vitamin deficiency and hypercholesterolemia leads to thickening of the aorta, decreased aortic water diffusion, increased LDL-cholesterol and impaired vascular reactivity of the aorta.Interpretation: Our findings suggest that deficiency of B vitamins leads to atherosclerotic transformation of the aorta already in the absence of hypercholesterolemia and aggravates atherosclerosis development in its presence.Funding: This work was funded by the Austrian Science Fund (FWF) (Projects P31105 and P33672), the EU project NanoAthero and BioTechMed-Graz.
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