Ultrasensitive molecular imaging of intestinal mucosal inflammation using leukocyte-mimicking particles targeted to MAdCAM-1 in mice

Abstract

Mucosal tissues play critical roles in health and disease as the primary barrier between the external world and the inner body, lining the digestive, respiratory, urinary, mammary, and reproductive tracts. Clinical evaluation of mucosal tissues is currently performed using endoscopy, such as ileocolonoscopy for the intestinal mucosa, which causes substantial patient discomfort and can lead to organ damage. Here, we developed a 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 technique can detect low, subclinical mucosal inflammation. Molecular MRI of MAdCAM-1 has potential applications in early diagnosis, longitudinal follow-up, and therapeutic response monitoring in diseases affecting mucosal tissues, such as inflammatory bowel diseases.

Tracking the immune response by MRI using biodegradable and ultrasensitive microprobes

“…Beyond improved sensitivity, this larger size also prevents passive extravasation and accumulation of the contrast carrying particles and, therefore, improves the specificity of the signal. This comes at the cost of a strictly intravascular biodistribution, limiting imaging to vascular targets, and a short half-life due to rapid uptake by the reticuloendothelial system ( 13 , 31 ). Accordingly, the plasmatic half-life of targeted 700-nm M3P is very short, with near-complete plasma clearance achieved a couple of minutes after intravenous injection.…”

“…MPIO display a higher sensitivity than US-PIO thanks to higher iron content (8). We and others demonstrated the applicability of targeted MPIO for molecular MRI in several experimental models, including cardiovascular (9,10) and neurovascular disorders (11), autoimmune diseases (12,13), and cancer (14). Notably, MPIO are rapidly eliminated from the circulation by the reticuloendothelial system, thereby limiting their ability to reach their target (15).…”

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.…”

New Opportunities for Diagnosis and Prognosis of Stroke: The Benefits of Across Border Approaches

“…We demonstrated the applicability of this method to improve the diagnostic performance of MRI in several neurovascular, neurological, cardiovascular, and autoimmune diseases. [6][7][8][9] These methods of molecular MRI has now been widely adopted for preclinical research and warrant further development toward clinical application. Unfortunately, currently available MPIOs are not biodegradable and therefore not usable in humans.…”