Preliminary Study On Brain Alterations In Asymptomatic Carotid Vulnerable Plaque Group Using Multi-modality MRIs

Objective:Atherosclerosis is the potential and main cause of most cardiovascular diseases.It has a high risk of death and disability at the first onset.The vulnerability of atherosclerotic plaques is one of the key characteristics to evaluate the severity of the disease and the risk of rupture.At the same time,atherosclerosis is associated with cognitive dysfunction or dementia.However,there are still many difficulties in the regulation mechanism of atherosclerosis,the influence mechanism of vulnerability of plaques and the early warning of central nervous system diseases(including stroke and vascular cognitive impairment)raleted to atherosclerosis.Cerebral neural activity may be involved in the formation of atherosclerotic plaque.The reactivity of blood oxygen level dependent(BOLD)signals in the central nervous system and changes in brain topological properties can be used as imaging markers to predict prognosis and monitor the response to clinical treatment and intervention.In this study,basing on multi-modality MRIs including resting state functional MRI(rs-fMRI),diffusion tensor imaging(DTI)and intravoxel incoherent motion imaging(IVIM),we preliminarily explored the potential brain functional and stuctural alterations in patients with asymptomatic carotid vulnerable plaques but with carotid stenosis<50%,indicating the early stage of atherosclerosis,the possible brain changes caused by different types of carotid plaques(vulnerable plaques and hard plaques),the related underlying neural mechanisms of early atherosclerosis,and try to provide a new perspective for the prevention and treatment of atherosclerosis and the early warning of central nervous system diseases related to carotid plaques.Materials and Methods:This study prospectively obtained multi-modality brain MRIs of volnunteers meeting the inclusion criteria of a carotid stenosis rate less than 50%and other inclusion criteria,and compared parameters of rs-fMRI,topological properties based on DTI and IVIM according to the types of carotid plaque defined by carotid ultrasound.1.Among 96 volunteers who performed rs-fMRI,regional homogeneity(ReHo)and degree centrality(DC)were compared beween vulnerable-plaque group(58 volunteers)and control group(38 volunteers)in a voxel-wise manner using a two-sample t-test.Regions on where ReHo and DC altered were seperately set as the seed points to apply a connectivity analysis and see if there were differences between the vulnerable-plaque group and control group by two-sample t-test.At the same time,Pearson correlation was used to evaluate the relationship between rs-fMRI parameters in altered brain regions and neuropsychiatric inventory questionaire including Mini Mental State Examination,Hamilton anxiety rating scale,Hamilton depression rating scale.2.Among 119 volunteers who performed DTI,the differences of both global and local topological metrics based on DTI networks among carotid vulnerable-plaque group(58 volnuteers),carotid hard-plaque group(23 volnuteers)and control group(38 volnuteers)were explored using One-way ANOVA and post hoc test(p<0.05,Bonfferoni test).And network-based statistic(NBS)method was employed to assess the alterations of the interregional connections among three groups.3.Among 49 volunteers who performed IVIM,IVIM parameters(Ds and f value)were compared beween vulnerable-plaque group(24 volunteers)and control group(25 volunteers)in a voxel-wise manner using a two-sample t-test.Then Pearson correlation was used to evaluate the relationship between IVIM parameters in altered brain regions and systolic blood pressure,diastolic blood pressure,blood glucose,total cholesterol,triglycerides,HDL-C,LDL-C and homocysteine,seperately.Results:1.Basing on rs-fMRI,ReHo value(clusters=72,P<0.05,FWEcorrection)and DC value(clusters=70,P<0.05,FWE correction)were both changed in left superior occipital gyrus in asymptomatic carotid plaque group,and caused a functional connectivity decrease in motor cortex(precentral gyrus,supplementary motor area),visual cortex(occipital lobe),somatosensory cortex(postcentral gyrus,paracentral lobule),dault mode network(medial prefrontal cortex,precuneus).At the same time,values of where the ReHo altered were positively releted with Hamilton depression rating scale(r=0.37,P=0.022).2.Basing on DTI,compared with control group and vulnerable plaque group,hard plaque group demonstrated significantly increased betweenness centrality in the left supramarginal gyrus(P<0.001)after multiple comparison.Compared with control group and hard plaque group,vulnerable plaque group demonstrated significantly decreased nodal clustering coefficiency in the left putamen(P<0.001)after multiple comparison.Compared with control group,both vulnerable-plaque group and hard-plaque group presented significantly differences in 7 edges and 10 nodes(NBS corrected,P<0.001 at voxel level,P<0.05 at cluster level,non-parametric permutation test for 5,000 times).After post hoc test,the fiber number between left superior frontal gyrus(SFG.L)and left supplementary motor area(SMA.L)in vulnerable-plaque group was significantly lower than control group,the fiber number between SFG.L and median cingulate and paracingulate gyrus(DCG.L)invulnerable-plaque group was significantly lower than both hard-plaque group and control group.The fiber number between left precentral gyrus(PreCG.L)and postcentral gyrus(PoCG.L),PoCG.L and left inferior parietal lobule(IPL.L),right calcarine fissure and surrounding cortex(CAL.R)and right precuneus(PCUN.R),right cuneus(CUN.R)and PCUN.R,P CUN.R and right paracentral lobule(PCL.R)in vulnerable-plaque group were significantly higher than both hard-plaque group and control group.The vulnerable-plaque group exhibited decreased structural connectivity in the left superior frontal gyrus-centered component and increased connectivity in the left postcentral gyrus-centered component and right precuneus-centered component.3.For the asymptomatic vulnerabl-plque group,the Z-normalized Ds values were significantly higher in the DCG.L,posterior cingulate gyrus(PCG.L)/PCUN.L(clusters=156,P<0.05,FWE correction)and in the left middle frontal gyrus(MFG.L),orbital middle frontal gyrus(ORBmid.L),and superior frontal gyrus(SFG.L)(clusters=165,P<0.05,FWE correction);the Z-normalized Ds values were significantly lower in the right middle temporal gyrus(MTG.R)and inferior temporal gyrus(ITG.R)(clusters=116,P<0.05,FWE correction);and the Z-normalized f-values were significantly lower in the MTG.R and ITG.R(clusters=85,P<0.05,FWE correction).LDL-C was negatively correlated with the Z-normalized Ds values in the DCG.L,PCG.L,and PCUN.L(r=0.601,P=0.002).LDL-C was positively correlated with the Z-normalized f-value in the MTG.R and ITG.R(r=0.405,P=0.05).Systolic blood pressure was positively correlated with the Z-normalized Ds values in the MFG.L,ORBmidL,and SFG.L(r=0.433,P=0.035).Conclusion:1.In the early stage of atherosclerosis with stenosis rate less than 50%,carotid vulnerable plaque is related to brain function and structure alterations when it has not caused obvious clinical symptoms.2.Multi-modality MRIs might reflect early spontaneous brain activity changes,microvascular and microstructural brain changes,and brain network alterations of asymptomatic carotid vulnerable plaque group.3.Furthermore,this research provides new insights into the structural disruptions to distinguish carotid vulnerable plaque group and hard plaque group.