Crohn's Disease
Contrast Ultrasound for Imaging Inflammatory Bowel Disease
Inflammatory bowel disease, including Crohn’s disease and ulcerative colitis, is a chronic inflammation of the bowel of varied etiology. In human patients, inflammation may be progressive or cyclical, and non-invasive methods of assessing disease severity are desired. It is valuable to know whether a diseased area contains active inflammation or old fibrotic tissue. This need extends to the preclinical research environment, where imaging tools for quantitative response to therapy and disease assessment are required. Ultrasound is attractive due to its real-time nature, and the use of microbubble contrast agents can extend the information content of ultrasound scans to the functional and molecular levels.
Perfusion Imaging
The use of vascular perfusion imaging for assessment of Crohn’s disease has been evaluated in several clinical studies. In general, qualitative metrices derived from time-intensity curves have demonstrated sensitivity for monitoring response to therapy. In the context of small animal models of disease, contrast agents enable not only quantitative characterization of microvascular blood flow, but also identification of bowel anatomy, which can be difficult with non-contrasted ultrasound alone.
Figure 1. Representative ultrasound images in SAMP/Yit.Fc mouse model of Crohn’s disease. Left: B-mode scan and (Right) same scan with a perfusion contrast agent, Targestar® P. Targestar P enables delineation of structural components of mouse bowel with good sensitivity.
Molecular Imaging
Several molecular markers of relevance to inflammatory bowel disease are known. In particular, MAdCAM-1 and VCAM-1 are structurally related cell surface receptors involved in the leukocyte adhesion cascade. The expression of both receptors is known to correlate with inflammation in bowel disease, which makes them excellent molecular imaging targets. Targeson’s targetable contrast agent, Targestar SA, is a streptavidin-coated microbubble to which biotinylated antibodies can be conjugated. This affords the researcher a significant degree of flexibility in choosing molecular targets, especially in the context of inflammatory bowel disease.
Figure 2. Molecular imaging of inflammation in SAMP/Yit.Fc mouse model of Crohn’s disease. Left: Representative image of cross-section of lower mouse abdomen after administration of Targestar SA conjugated to an anti-MAdCAM-1 antibody. Significant contrast enhancement (blue) is shown throughout the bowel. Right: Quantified contrast enhancement following administration of Targestar SA conjugated to antibodies against MAdCAM-1, VCAM-1, or an isotype control (n=3).