Huaijun Wang MD, PhD, Presenter: Nothing to Disclose

Stephen A. Felt DVM, MPH, Abstract Co-Author: Nothing to Disclose

Ismayil Guracar, Abstract Co-Author: Employee, Siemens AG

Steven B. Machtaler PhD, Abstract Co-Author: Nothing to Disclose

Thierry Bettinger, Abstract Co-Author: Employee, Bracco Group

Juergen Karl Willmann MD, Abstract Co-Author: Research Consultant, Bracco Group Research Grant, Siemens AG Research Grant, Bracco Group

To assess reproducibility and optimal dosing for ultrasound molecular imaging (USMI) of inflammation using a clinically translatable dual P- and E-selectin-targeted contrast agent (MBSelectin) in a porcine model of acute terminal ileitis.

An acute terminal ileitis model was established in 17 pigs (ileitis pig). Another 3 pigs without inflammation served as controls. USMI was performed with a clinical system (Acuson Sequoia 512, Siemens; transducer 15L8W). Increasing doses of MBSelectin (0.5, 1, 2.5, 5, 10, and 20×108MB/kg) were injected and a total of 18 different segments of ileitis were imaged in an intra-animal comparison study. To test the reproducibility of USMI, scans of the same anatomical locations were repeated twice following both MBSelectin and non-targeted control microbubble (MBControl) administrations. After imaging, scanned ileal segments were analyzed ex vivo for both inflammation grade on H&E staining and for expression of selectins on immunofluorescence staining.

Signal intensities increased with higher doses of MBSelectin. However, further increase of the contrast agent dose beyond 5×108MB/kg resulted in a relatively lower further signal increase compared to lower doses (P=0.01), suggesting that the signal reached a plateau at a dose of approximately 5×108MB/kg. Using a dose of 5×108MB/kg, USMI was highly reproducible with an intraclass coefficient of 0.88 (95%CI, 0.25-0.99) using MBSelectin and of 0.84 (95%CI, 0.24-0.98) using MBControl. Administration of MBSelectin in ileitis resulted in a significantly higher (P<0.001) imaging signal compared to control ileum. Also, imaging signal using MBSelectin was significantly higher (P<0.001) compared to MBControl in ileitis. In control ileum, imaging signal was not significantly different (P=0.06) with MBSelectin or MBControl. Ex vivo analysis showed significantly higher inflammation scores and expression of selectins in acute ileitis compared to control ileum (P<0.05, Fig 1). 

Quantitative measurements of inflammation obtained by selectin-targeted USMI are highly reproducible in a porcine ileitis model and correlate well with the extent of inflammation on histology. 

USMI of inflammation is reproducible and quantitative and can be further developed for monitoring patients with inflammatory bowel disease.

Wang, H, Felt, S, Guracar, I, Machtaler, S, Bettinger, T, Willmann, J, Molecular Imaging of Inflammation in Inflammatory Bowel Disease with Ultrasound: Reproducibility and Dose Escalation Study in Swine.  Radiological Society of North America 2014 Scientific Assembly and Annual Meeting, - ,Chicago IL. http://archive.rsna.org/2014/14011571.html