Magnetic Resonance Imaging of Atherosclerotic Plaque at Clinically Relevant Field Strengths (1T) by Targeting the Integrin α4β1.
Darren G WoodsideEric A TanifumKetan B GhaghadaRonald J BiedigerAmy R CaivanoZbigniew A StarosolskiSayadeth KhounloSaakshi BhayanaShahrzad AbbasiJohn W CraftDavid S MaxwellChandreshkumar PatelIgor V StupinDeenadayalan BakthavatsalamRobert V MarketJames T WillersonRichard A F DixonPeter VandersliceAnanth V AnnapragadaPublished in: Scientific reports (2018)
Inflammation drives the degradation of atherosclerotic plaque, yet there are no non-invasive techniques available for imaging overall inflammation in atherosclerotic plaques, especially in the coronary arteries. To address this, we have developed a clinically relevant system to image overall inflammatory cell burden in plaque. Here, we describe a targeted contrast agent (THI0567-targeted liposomal-Gd) that is suitable for magnetic resonance (MR) imaging and binds with high affinity and selectivity to the integrin α4β1(very late antigen-4, VLA-4), a key integrin involved in recruiting inflammatory cells to atherosclerotic plaques. This liposomal contrast agent has a high T1 relaxivity (~2 × 105 mM-1s-1 on a particle basis) resulting in the ability to image liposomes at a clinically relevant MR field strength. We were able to visualize atherosclerotic plaques in various regions of the aorta in atherosclerosis-prone ApoE-/- mice on a 1 Tesla small animal MRI scanner. These enhanced signals corresponded to the accumulation of monocyte/macrophages in the subendothelial layer of atherosclerotic plaques in vivo, whereas non-targeted liposomal nanoparticles did not demonstrate comparable signal enhancement. An inflammatory cell-targeted method that has the specificity and sensitivity to measure the inflammatory burden of a plaque could be used to noninvasively identify patients at risk of an acute ischemic event.
Keyphrases
- magnetic resonance
- contrast enhanced
- oxidative stress
- magnetic resonance imaging
- coronary artery disease
- cancer therapy
- induced apoptosis
- single cell
- deep learning
- cell therapy
- coronary artery
- high resolution
- cell migration
- diffusion weighted imaging
- mesenchymal stem cells
- dendritic cells
- pulmonary artery
- stem cells
- liver failure
- heart failure
- pulmonary hypertension
- cognitive decline
- hepatitis b virus
- atrial fibrillation
- drug induced
- pulmonary arterial hypertension
- brain injury
- drug release
- mechanical ventilation
- blood flow