Abstract
Molecular imaging of atherosclerosis by Magnetic Resonance Imaging (MRI) has been impaired by a lack of validation of the specific substrate responsible for the molecular imaging signal. We therefore aimed to investigate the additive value of mass spectrometry imaging (MSI) of atherosclerosis-affine Gadofluorine P for molecular MRI of atherosclerotic plaques. Atherosclerotic Ldlr−/− mice were investigated by high-field MRI (7 T) at different time points following injection of atherosclerosis-affine Gadofluorine P as well as at different stages of atherosclerosis formation (4, 8, 16 and 20 weeks of HFD). At each imaging time point mice were immediately sacrificed after imaging and aortas were excised for mass spectrometry imaging: Matrix Assisted Laser Desorption Ionization (MALDI) Imaging and Laser Ablation – Inductively Coupled Plasma – Mass Spectrometry (LA-ICP-MS) imaging. Mass spectrometry imaging allowed to visualize the localization and measure the concentration of the MR imaging probe Gadofluorine P in plaque tissue ex vivo with high spatial resolution and thus adds novel and more target specific information to molecular MR imaging of atherosclerosis.
Highlights
Visualization of atherosclerosis using MR imaging is an emerging tool to gain deeper and more dynamic insights into biological processes of atherosclerosis with a high spatial and temporal resolution as well as high sensitivity
We show that Gadofluorine P, an amphiphilic MR contrast agent, accumulates in atherosclerotic plaques and that Gadofluorine P accumulation increases during progression of atherosclerosis in Ldlr−/− mice on a high-fat diet
We show that this experimental gadolinium-based MR probe can be visualized and quantified in atherosclerotic lesions by mass spectrometry imaging with a high spatial resolution down to 15 μm
Summary
Visualization of atherosclerosis using MR imaging is an emerging tool to gain deeper and more dynamic insights into biological processes of atherosclerosis with a high spatial and temporal resolution as well as high sensitivity. In in vivo MRI it cannot be defined to which degree a certain substrate e.g. a molecular contrast agent contributes to the actual imaging signal Traditional methods such as immunohistochemistry have severe drawbacks as they only can detect biological plaque components but fail to visualize molecular MR agents . Mass spectrometry imaging has been used in the past years to provide comprehensive maps of lipid and protein distribution in experimental and clinical atherosclerosis down to a spatial resolution of 30 μm These approaches allow for detailed analysis of key molecular alterations during atherosclerotic plaque development and potentially to detect therapy induced changes in the future[13,14,15,16,17]. We hypothesize that mass spectrometry imaging is able to visualize and quantify a molecular MR imaging agent within atherosclerotic plaques with high spatial resolution
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