Ultrasensitive Molecular Imaging of Mucosal Inflammation Using Leucocyte-Mimicking Particles Targeted to MAdCAM-1

Abstract

One Sentence Summary: Molecular magnetic resonance imaging allows non-invasive evaluation of mucosal inflammation in clinically relevant experimental models. ABSTRACTMucosal tissues line the digestive, respiratory, urinary, mammary and reproductive tracts and play critical roles in health and disease as the primary barrier between the external world and the inner body. Clinical evaluation of mucosal tissues is currently performed using endoscopy, such as ileocolonoscopy for the intestinal mucosa, that causes significant patient discomfort and can lead to organ damage. Here, we developed a new contrast agent for molecular magnetic resonance imaging (MRI) that is targeted to mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1), an adhesion molecule overexpressed by inflamed mucosal tissues. We investigated the diagnostic performance of molecular MRI of MAdCAM-1 to detect mucosal inflammation in several models of acute and chronic intestinal inflammation in mice. We demonstrated that molecular MRI of MAdCAM-1 reveals disease activity and can evaluate the response to inflammatory treatments along the whole intestinal mucosa in clinically relevant models of inflammatory bowel diseases. We also provide evidence that this new technique can detect low, subclinical levels of mucosal inflammation.Molecular MRI of MAdCAM-1 has thus potential applications in early diagnosis, longitudinal follow-up and therapeutic response monitoring in diseases affecting mucosal tissues, such as inflammatory bowel diseases.Recently, we and others reported the use of a new family of contrast agents for molecular MRI based on micro-sized particles of iron oxide (MPIO) that displays a dramatically higher sensitivity than classically used nano-sized particles(9-12). Thanks to an artefact known as the blooming effect, MPIO appear around 50 times larger than their actual size on iron sensitive T2*-weighted images (12). This characteristic of MPIO makes them particularly interesting for imaging mucosal tissues, since these tissues measure only a few hundred micrometers of thickness in physiological conditions and are thus hardly visible on unenhanced MRI. In the present study in mice, we developed a new MPIO-based contrast agent for MRI targeted to MAdCAM-1 (thereafter named MPIO-αMAdCAM-1). In three different models of intestinal inflammation, including lipopolysaccharides (LPS) induced endothelial activation, dextran sodium sulfate (DSS) induced colitis and trinitrobenzene sulfonic acid (TNBS) induced colitis(13), we demonstrated that this contrast agent allows detection of mucosal inflammation, quantification of disease activity and assessment of the mucosal response to anti-inflammatory treatments.

Adaptive Cylindrical Wireless Metasurfaces in Clinical Magnetic Resonance Imaging

“…[35] Meanwhile, the ACWM enhances the CNR between different tissues without altering their natural contrast, that is, the T 1 /T 2 values. [36,37] The ACWM is also applicable to all common sequences with no additional modifications to the scan parameters. In addition, as the ACWM is wireless, no interface communication protocol is required.…”