Two-Dimensional Intravascular Near-Infrared Fluorescence Molecular Imaging of Inflammation in Atherosclerosis and Stent-Induced Vascular Injury
Key result
Intravascular 2D NIRF imaging with VM110 yields ~10-fold higher plaque SNR versus saline control.
- P=0.02
- n=22
Why the study?
Few high-resolution inflammation imaging approaches exist for in vivo investigation of arterial inflammation in coronary-sized arteries.
Key Points
- To evaluate a two-dimensional intravascular catheter-based near-infrared fluorescence imaging platform for spatial mapping of cysteine protease activity in atherosclerosis and coronary stent-induced arterial injury.
- Tested 2D NIRF catheter sensitivity, angular resolution, and axial resolution in coronary-scale phantoms filled with saline and blood-like solutions.
- Imaged atheroma-bearing rabbits (n=10) injected with Prosense VM110 (n=7) or saline (n=3) using combined x-ray angiography, IVUS, and in vivo intravascular NIRF pullbacks.
- Evaluated vascular injury in New Zealand white rabbits (n=10) following aortic balloon injury and bare metal stent deployment (3.5×12mm), followed by Prosense VM110 (n=8) or saline (n=2) administration.
- In atheroma-bearing rabbits, in vivo plaque SNR was 12.6 [8.1, 20.6] in the VM110 group versus 1.3 [0.9, 2.1] in the saline group (p=0.02), and in vivo plaque TBR was 6.3 [4.3, 9.4] versus 1.1 [0.9, 1.4] (p=0.02).
- Ex vivo plaque SNR was 218.5 [194.3, 348.0] in the VM110 group versus 90.5 [77.9, 90.9] in the saline group (p=0.01), with plaque TBR of 2.4 [2.0, 3.3] versus 1.0 [1.0, 1.1] (p=0.01).
- In stent-injured arteries, in vivo maximal SNR localized to stent edges and reached 23.1 [11.7, 27.0] compared to 1.1 [1.0, 3.7] in uninjured segments (p=0.02), with maximum stent TBR of 18.3 [2.8, 25.7] versus 1.2 [1.0, 1.4] (p=0.056).
Structured PICO
P
Population
22 New Zealand white rabbits with experimental atherosclerosis or aortic stent implantation used to validate an intravascular 2D near-infrared fluorescence (NIRF) catheter.
I
Intervention
Two-dimensional rotational and automated pullback near-infrared fluorescence (NIRF) intravascular catheter imaging with the protease-activatable agent Prosense VM110 (0.5 mg/kg).
C
Comparator
Matching imaging procedures using saline injection instead of VM110, as well as uninjured normal rabbits injected with VM110.
O
Outcome
In vivo plaque signal-to-noise ratio (SNR) and target-to-background ratio (TBR) for sensing arterial wall inflammation.surrogate
Main Result
Absolute Event Rate: 12.6% vs 1.3%
p-value: p=0.02
Limitations
- Surface-weighting of the NIRF signal as a function of fiber-to-wall distance limits depth resolution
- Requires additional strategies employing 3D radiopaque fiducials for accurate angular NIRF and IVUS co-registration
- Surface-weighting of the NIRF signal as a function of fiber-to-wall distance
- Limited depth resolution in light-attenuating blood
- Requires separated catheters requiring 3D radiopaque fiducials for exact angular co-registration
Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“Inflammation increases the risk of plaque instability but intravascular imaging currently has limited ability to detect it. New developments, such as near-infrared fluorescence, may help to select candidates for the use of novel anti-inflammatory drugs.”
“Because of the complementary nature of microstructural and molecular imaging, this combined technology is a powerful investigational and diagnostic tool. It will allow us, for the first time, to investigate the interplay between molecular activity and structure in living arteries. From a clinical standpoint, it will allow us to better characterize the artery wall of patients to identify vulnerable plaque prior to events and determine stents that may be at risk for thrombosis.”
“We need to do a better job of phenotyping the artery beyond structure, plaque burden, and fibrous cap thickness.”
Implication
Intravascular 2D NIRF molecular imaging enables the spatial mapping and quantification of cysteine protease activity associated with in vivo inflammation in atherosclerosis and stented arteries.
Abstract
Objectives To develop a two-dimensional intravascular near-infrared fluorescence (NIRF) imaging strategy for investigation of arterial inflammation in coronary-sized vessels. Background Molecular imaging of arterial inflammation could provide new insights into the pathogenesis of acute myocardial infarction stemming from coronary atheromata and implanted stents. Presently few high-resolution inflammation approaches can image inflammation in coronary-sized arteries in vivo. Methods A new 2.9F rotational, automated pullback two-dimensional imaging catheter was engineered and optimized for 360-degree viewing intravascular NIRF imaging. In conjunction with the cysteine protease-activatable imaging reporter Prosense VM110, intra-arterial 2D NIRF imaging was performed in rabbit aortas with atherosclerosis (n=10) or implanted coronary bare metal stents (n=10, 3.5mm diameter, day 7 post-implantation). Intravascular ultrasound (IVUS) provided co-registered anatomical images of arteries. After sacrifice, specimens underwent ex vivo NIRF imaging, fluorescence microscopy, and histological and immunohistochemical analyses. Results Imaging of coronary artery-scaled phantoms demonstrated 8-sector angular resolution and submillimeter axial resolution, nanomolar sensitivity to NIR fluorochromes, and modest NIRF light attenuation through blood. High-resolution NIRF images of vessel wall inflammation with signal-to-noise ratios > 10 were obtained in real-time through blood, without flushing or occlusion. In atherosclerosis, 2D NIRF, IVUS-NIRF fusion, microscopy, and immunoblotting studies provided insight into the spatial distribution of plaque protease activity. In stent-implanted vessels, real-time imaging illuminated an edge-based pattern of stent-induced arterial inflammation. Conclusions A new 2D intravascular NIRF imaging strategy provides high-resolution in vivo spatial mapping of arterial inflammation in coronary-sized arteries, and reveals increased inflammation-regulated cysteine protease activity in atheromata and stentinduced arterial injury.
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Cite This Study
Jaffer et al. (2011) studied Atherosclerosis and stent-induced vascular injury (rabbit model) (n=22). 2D NIRF intravascular catheter imaging with Prosense VM110 vs. Saline injection / normal rabbits was evaluated on In vivo plaque signal-to-noise ratio (SNR) (p=0.02). The 2D NIRF intravascular catheter successfully detected in vivo plaque inflammation, demonstrating significantly higher plaque SNR in the VM110 imaging group compared to the saline control (12.6 vs 1.3, p=0.02).