Background/Introduction

Inflammation is a hallmark during initiation and progression of atherosclerosis. Monocytes/Macrophages play a central role in propagation of inflammatory stimuli. For clinical purposes, only Positron-emission-tomography might be sensitive and specific enough to localize and quantify cellular inflammation. However, this is cost intensive and uses radioactive tracers. Alternatively, Fluorine-19 magnetic resonance imaging (19F MRI) with intravenously applied perfluorooctyl bromide-nanoemulsion (PFOB) has proven its feasibility to visualize monocyte-inflammation in various experimental disease models. This approach is based on the properties of monocytes/macrophages to ingest PFOB particles enabling specific cell tracking in vivo. Due to the inherent advantages of 19F-MRI like having a negligible natural 19F-background in the mammalian body and a NMR sensitivity close to 1H, molecular imaging with 19F-MRI is a highly specific technique.

Purpose

      To evaluate the feasibility of vascular monocyte/macrophage imaging with 19F MRI in a vascular injury model in pigs at clinical field strength.

Methods

In 5 Aachen Minipigs, vascular injury was performed in the left carotid artery by Fogarty balloon denudation followed by balloon angioplasty according to published models. At day 3 after Injury, pigs received a body weight adjusted dose of PFOB. At day 6, early vascular inflammation and remodeling was evaluated in vivo by angiography, intravascular ultrasound and 1H/19F MRI as well as ex vivo by histology and 1H/19F MRI.  MR images were acquired in vivo and ex vivo  using a whole-body 3.0 T Achieva X-series MR scanner (Philips Healthcare, Best, the Netherlands) and at 9,4 Tesla using a Bruker AVANCE III Wide Bore nuclear magnetic resonance spectrometer (Bruker, Rheinstetten, Germany).

Results

      Vascular injury was successfully induced in 5 of 5 pigs. In angiographic examination, vascular flow was maintained immediately after the procedure and on day 6. IVUS imaging revealed a lumen narrowing in the treated arteries (4,4±0,3 cm vs. 5,3±0,2 cm) accompanied by only mild impairment of the vascular wall. Injury was followed by a significant infiltration of mainly monocytes/macrophages into the vessel wall of the treated compared to the non-treated artery. 19F MRI showed a reliable signal in the treated artery with a signal-to-noise ratio of 14 for in vivo and 29,1 for ex vivo acquisition. No signal could be detected in the non-treated artery. In ex vivo analysis 19F signals correlated well with the location of macrophage infiltration and signal intensity was proportional to macrophage density.

Conclusion(s)

      19F MRI at clinical field strength is feasible to visualize monocyte/macrophage infiltration into the vascular wall after balloon injury in pigs.