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Thursday, August 16, 2018

Fluorescence Imaging of MMP-2 Activity as a Biomarker of Vascular Remodeling in HD Access


Summary


In a recent article in press, researchers from the Penn Image-Guided Intervention Laboratory at the University of Pennsylvania have presented their findings exploring the capability of near-infrared fluorescence (NIRF) imaging for the detection of matrix metalloproteinase 2 (MMP-2) activity as a biomarker of vascular remodeling (VR) in AVFs in vivo. The manuscript reports that 10 AVFs were created in 10 Wistar rats with sham procedures in the contralateral groins. 4 weeks post creation, a fistulogram was performed in a subset of animals from the left common carotid to confirm stenosis. A MMP-2-activated NIRF probe was given and NIRF imaging performed in vivo and ex vivo on both AVF and sham-treated vessels to measure radiant efficiency (RE) of MMP-2-activated NIRF signal over background. Histologic analysis was also done to assess degree of VR by intimal thickening. When compared with sham-treated vessels, AVFs had a significantly higher percentage of RE over background. There was a significant correlation between MMP-2 activity as measured by relative increase in RE for AVFs and thickness of MMP-2 stained neointima. The authors conclude that NIRF imaging can detect MMP activity in remodeled AVFs compared with sham treatment and MMP-2 may be used as a biomarker of vascular remodeling underlying stenosis.




Figure. Ex vivo near-infrared imaging of MMP-2 activation. (a) Representative near-infrared fluorescence and photographic images of MMPSense activity in explanted fistulae and sham-treated vessels. (b) Bar graph illustrating a higher percent increase in radiant efficiency over background for patent AVFs compared with sham-treated vessels after intravenous injection of MMPSense 750. (c) Bar graph illustrating the higher percentage increase in radiant efficiency over background for AVFs compared with sham-treated vessels after intra-arterial injection of MMPSense 750. (d) Bar graph illustrating the significantly higher percentage increase in radiant efficiency over background for AVFs compared with sham-treated vessels after intra-arterial or intravenous injection of MMPSense 750 (**P = .0078). (e) Bar graph illustrating the fold increase in radiant efficiency over sham-treated vessels for rats injected with MMPSense 750 through intravenous or intra-arterial routes. (f) Bar graph illustrating the significantly higher percent increase in radiant efficiency over background for AVFs after intravenous compared with intra-arterial injection of MMPSense 750 (**P = .00357).


Commentary


Treatment of patients with dysfunctional AVFs and AVGs can be challenging. Primary patency is <70% at one-year and patients return frequently with new stenotic lesions. While AVFs and AVGs have been studied extensively, our ability to accurately predict in which patients a stenosis will occur, why they occur, and how best to prevent/treat them is far less than optimal. Previous research has evaluated the morphologic characteristics of lesions within the AV access circuit and we know in what regions lesions are most likely to occur. While useful, this does not allow us to anticipate a dysfunctional AVF/AVG and prevent the need for endovascular treatment. There are several limitations in the provided manuscript including using animals without CKD, lack of pre-AVF NIRF imaging, and using a single time point for evaluation. However, the study is noteworthy as it advances our understanding of the pathophysiology of dysfunctional AV access and identifies a number of factors that can influence cellular proliferation in neointimal hyperplasia. Identifying access circuits that may be at increased risk of developing access site dynsfunction will be impactful on this patient population.

Click here for abstract

Nadolski GJ, Hunt SJ, Weber CN, et al. Near-infrared fluorescence imaging of matrix metalloproteinase 2 activity as a biomarker of vascular remodeling in hemodialysis access. Article in press. DOI: https://doi.org/10.1016/j.jvir.2018.04.032

Post Author:
Luke R. Wilkins, MD
Assistant Professor
Department of Radiology and Medical Imaging
Section of Vascular and Interventional Radiology
University of Virginia
@LukeWilkins_UVA

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