The screening and monitoring of intestinal diseases still provides challenges within in vivo and clinical research. For example, patients with Crohns disease will typically have a biannual endoscopic examination this invasive procedure is distressing for patients and hence its frequency is limited at the expense of sufficient monitoring of pathological progression. Modalities such as CT and MRI can image the GI tract, however, they are ionising, which normally precludes them for screening purposes, and limits their frequency for monitoring. Recent advances in post-processing techniques with Contrast Enhanced UltraSound (CEUS) allows functional imaging of the GI tract with resolutions of approximately 60um. Ultrasound is relatively cheap, non-invasive, and non-ionising, thus, supporting its use for regular screening and monitoring. Anaesthetised rats received, via IV, a vehicle control infusion followed by either vehicle control or Teduglutide (a GLP-2 agonist) infusion. During each infusion a bolus of microbubbles (MB) commonly used as ultrasonic contrast agents were injected and high frame-rate, high frequency CEUS sampled the 15 minute bolus response. For the first time, intestinal villi were visualised non-invasively. Furthermore, novel metrics such as blood velocity and perfusion within the villi were quantified and a significant difference was found between control animals and animals receiving Teduglutide. Specifically, Teduglutide was found to increase: the peak intensity response and the area under a time intensity curve, indicating greater perfusion; the blood velocity in duodenal villi; and the diameter of mesenteric arteries. The unprecedented functional resolution achieved with our novel methods are translational to a multitude of applications, for example: rapid quantification of dose response within drug discovery programs; the localised microcirculatory response to food could be quantified during digestion; and longitudinal structural change to the villi or bowel wall thickness could be tracked. Moreover, the non-invasive nature of this method could dramatically reduce animal numbers.
08 Nov 2021 - 10 Nov 2021