A Rabbit Model Of Vulnerable Carotid Atherosclerosis Plaque: Noninvasive Detection With PET

Objective:(1)Establishment of a rabbit model of the vulnerable plaque at the right common carotid artery(RCCA).(2)PET imaging of the rabbit model was performed in order to study the feasibility of noninvasive detection of vulnerable plaque with ¹⁸F-FDG.Methods:(1)Atherosclerosis at the RCCA was induced in 15 rabbits by balloon catheter injury to the endothelium via a right common femoral artery approach.3 rabbits were subjected to sham-operation for control.All rabbits were fed with high-cholesterol diet in the following 16 weeks until sacrifice.(2)Digital subtraction angiography(DSA) was performed in order to observe the degree of the carotid artery stenosis.Degree of vascular stenosis＞30%and length＞1.0cm were the necessary condition of this model.(3)The rabbits were injected in vivo with ¹⁸F-FDG(1.0mCi/kg).Then the uptake of ¹⁸F-FDG was assessed with PET(180 minutes after injection).So we had the highest maximal standardized uptake value(SUVmax).(4)Cholesterol was examined 1 week before injuried,instant and 16 weeks after the injury in the experimental group animals.At the same time,the control group animals were also detected.(5)Bilateral common carotid arteries of each rabbit were explanted.Consecutive 5-μm-thick slices were prepared every 2.5mm in the target vessel.The intima cross-sectional area in each segment was obtained by digital camera.Data were analyzed using SPSS for windows version 13.0.Measured data were reported as mean±SD. Multiple groups were compared using analysis of variance,with Dunnett's T3-test for pairwise.Statistical analysis was performed for comparing the segments of the experimental and control group.Correlations between the intima cross-sectional area and SUVmax were performed using Pearson test.Statistical significance was established at P＜0.05.Results:(1)The success rate of vulnerable plaque in experimental group was 66.7%(10/15). One rabbit died from infections and no significant vulnerable plaque was showed in four rabbits(vascular stenosis＜30%and length＜1.0cm).The average stenosis rates of RCCA in experimental group was(59.57±17.51)%.No significant vascular stenosis in left common carotid artery and bilateral common carotid arteries in control group.(2)In vulnerable plaque segments,there were 60 sites whose average SUV max was 0.82±0.42,in the left common carotid artery there were also 60 sites whose average SUVmax was 0.66±0.38.The SUVmax showed significant difference among the both sides(t=2.927,v=59,P＜0.05,T/NT=1.62:1).In control group there were 18 sites whose average SUVmax were RCCA:0.59±0.13 and LCCA:0.62±0.20.(3)Quantitative ¹⁸F-FDG uptake was higher in lesion versus nonlesion segments in experimental group.But there were no significant difference between bilateral common carotid arteries in control group.(4)There was no significant differenet between the content of cholesterol in the experimental group and the control group.(5)The results were confirmed in digital photo of the explanted carotid artery.Injured segments had significantly higher intima cross-sectional area and macrophage density compared with uninjured segments.On histomorphology,the atherosclerotic plaques at this stage were mainly characterized as vulnerable plaque by infilted macrophages.We found a positive correlation between intima cross-sectional area in vulnerable plaques and ¹⁸F-FDG uptakes evaluated by PET(r=0.443,P＜0.05). Conclusion:(1)Injuring the intima of common carotid artery by interventional balloon with concomitant dietary hyperlipidemia is an appropriate experimental technique to develop vulnerable atherosclerotic plaque in rabbit with little technical complications.(2)This study demonstrates the feasibility of detecting inflammation in vulnerable atherosclerosis plaque using ¹⁸F-FDG PET.With the currently available technology and nuclear tracers,these noninvasive imaging modalities could be proposed as clinical tools in the evaluation of lesion prognosis and monitoring of therapies.