Abstract 2144: Molecular Imaging of Inflammation in Limb Ischemia
Background: Microvascular inflammation plays a pathophysiologic and adaptive role in chronic ischemic peripheral artery disease (PAD). Inflammatory markers have also been associated with prognosis. We hypothesized that the inflammatory response to severe peripheral vascular disease could be assessed with ultrasound molecular imaging of endothelial activation and leukocyte recruitment.
Methods: Unilateral hindlimb ischemia was produced by arterial occlusion in 15 mice. Perfusion imaging of proximal hindlimb skeletal muscle with non-targeted microbubbles in the ischemic and control limb was performed at day 2, 4, or 7. Molecular imaging was performed with microbubbles targeted to VCAM-1, α5-integrin, or leukocytes (by shell phosphatidylserine [PS]). Immunohistology of muscle samples was performed.
Results: Muscle perfusion in the ischemic limb relative to the normal limb was 13%, 25% and 28% at day 2, 4 and 7 respectively. Targeted signal from activated leukocytes (PS), alpha-5, and VCAM-1 was elevated in the ischemic limb and decreased with time after occlusion (Graph). However, signal from alpha-5 and VCAM-1 remained persistently elevated late after occlusion. Histology demonstrated expression of alpha-5 integrin on monocytic cells, and VCAM-1 on activated endothelial cells.
Conclusions: Molecular imaging with contrast ultrasound can assess microvascular inflammatory responses in PAD. Targeted pan-leukocyte imaging with PS microbubbles reflects primarily the acute response whereas molecular imaging of VCAM-1 or monocyte markers provides information on more chronic activation of the inflammatory response.