Evaluation Of The Efficacy Of Atorvastatin In The Treatment Of Atherosclerotic Lesions In Middle Cerebral Artery And Rabbit Abdominal Aorta By Magnetic Resonance Vessel Wall Imaging

Objective: Intracranial atherosclerosis is one of the main causes of ischemic stroke.Accurate diagnosis and effective prevention of atherosclerotic lesions,reduce the incidence and recurrence rate of ischemic stroke,has important clinical and social significance.Magnetic resonance vessel wall imaging(VWMRI)is regarded as a reliable method for analyzing intracranial artery wall in vivo.We hypothesize that VWMRI can accurately assess the characteristics of plaque changes during atorvastatin treatment in patients with symptomatic middle cerebral artery atherosclerotic stenosis(SMAS)and provide more information to evaluate atorvastatin efficacy.However,VWMRI does not reflect the pathophysiological changes of intracranial atherosclerotic lesions at the cellular and tissue levels,and it is not possible to obtain plaque tissue in vivo.Therefore,to remedy this deficiency,we established an experimental animal model similar to human atherosclerotic lesions and evaluated the consistency of VWMRI of arterial plaques with their pathological findings.Methods: We designed and conducted a prospective,single-arm,single-center,12-month follow-up observational study(Chi CTR2000034235)of VWMRI to evaluate standard-dose atorvastatin in SMAS.Subjects were recruited to accept VWMRI and associated blood biochemistry before treatment(at baseline level)and 1,3,6,and 12 months after receiving treatment.Clinically relevant information was collected from subjects at a baseline level.We analyzed the VWMRI characteristics and blood biochemical examination results at each follow-up time point to investigate the correlation between VWMRI changes and blood biochemical examination results.A model of abdominal aortic atherosclerosis in New Zealand rabbits was established using abdominal aortic balloon dilatation with the high-fat diet.We analyzed blood biochemical examination results and changes in VWMRI of the abdominal aorta during the modeling process.The pathological results were used as the reference standard for successful modeling.After successful modeling,the rabbits were randomly divided into a drug treatment group and standard diet group for six months of lipid-lowering treatment.The correlation between VWMRI and blood biochemical examination was analyzed at the 1st,3rd,and 6th months after receiving lipid-lowering treatment to establish the imaging-pathology control.Results: A total of 46 subjects were recruited in this study,and 24 subjects completed follow-up.Serum non-high-density lipoprotein cholesterol(NHDL)decreased gradually during the 12-month follow-up.There was no significant change in the plaques of the MCA in all subjects at 1 and 3 months of follow-up compared to baseline.A total of 14 subjects(58.3%)had plaque reversal at the end of follow-up,and the median time to plaque reversal was 9.85 months.In 10 subjects(41.67%),the MCA plaques remained stable throughout the follow-up period without significant changes.Continued 12 months of lipid-lowering therapy could reverse plaques but could not reverse vascular remodeling,change the shape and distribution of plaques,and change the characteristics of plaque signals.The serum low-density lipoprotein(LDL)concentration changes were closely related to plaque reversal.After balloon dilation,a rabbit model of atherosclerosis of the abdominal aorta was successfully established on a high-fat diet for two months.The qualitative evaluation of plaques and vascular changes by VWMRI was in good agreement with pathological results.The serum lipoprotein concentration in the drug treatment group showed a significant decreasing trend during the treatment time,while the changes of serum lipoprotein in the normal diet group were significantly lower than the drug treatment group.In the rabbit abdominal aortic appendage plaques,there were no significant abnormal changes in the appendage plaques at one month of treatment,reducing the size of the appendage plaques at three,and no further significant changes in the appendage plaques at six months of treatment.There was no significant change in the plaque of the abdominal aorta in the normal diet group.The morphological manifestations of the abdominal aorta in the drug treatment group were basically the same in the pathological section and magnetic resonance angiography.Conclusions: VWMRI can accurately assess the characteristics of changes in MCA and rabbit abdominal aortic plaques after lipid-lowering therapy and can indirectly reflect the pathophysiological characteristics of plaque changes;it is in good agreement with the pathological results in qualitative and quantitative evaluation of plaques in animal models.In SMAS in northern China,sustained treatment with standard doses of atorvastatin for more than ten months effectively stabilized and reversed plaques.Changes in LDL concentrations were an independent factor affecting plaque stabilization and retraction.Atherosclerotic New Zealand rabbits treated with atorvastatin(4.8 mg/day)for three months showed reversal of abdominal aortic plaques,but were unable to change plaque distribution,plaque shape,or reverse vascular remodeling.The pathological results suggested that the reversal of plaque was mainly reflected in the reduction of lipid core.The stabilization of plaque was reflected primarily in the decrease of macrophage infiltration and the increase of fibrous cap thickness.