| Objective:Perforating artery infarct in the lenticulostriate artery(LSA)territory with a non-stenotic middle cerebral artery is a heterogeneous entity.It can be caused by underlying branch atheromatous disease(BAD)or cerebral small vessel disease(CSVD).However,the differentiation of pathogenesis of PAI has been much debated because of the difficulties of imaging LSA characteristics in vivo by current imaging modalities.Recently,several studies have demonstrated that novel whole-brain vessel-wall imaging(WB-VWI)is capable of imaging both middle cerebral artery(MCA)wall and the LSA lumen in one image setting,which provide a powerful tool for exploring the mechanism of SSI and potential guiding therapeutic intervention.Our study aims to use WB-VWI to quantitatively evaluate the associations between distribution and characteristics of MCA plaque and morphological changes of LSA in the symptomatic and asymptomatic sides of PAI patients.Then,we aimed to investigate the role of clinical features,infarct dimensions,neuroimaging markers of CSVD combined with LSA characteristics in differentiating the pathogenic subtypes of PAI by WB-HRMRI.Methods:Part Ⅰ: 40 PAI patients with no relevant MCA disease on MRA were prospectively enrolled.Plaque location in the MCA was dichotomized as proximal(located adjacent to the LSA origin)or distal(located distal to the LSA origin)on WB-HRMRI.The MCAs with proximal plaques were divided into the symptomatic and asymptomatic side,and asymptomatic side MCAs without proximal plaques were the control group.The morphological characteristics of the LSAs(the number of stems and branches,length,distance,tortuosity)and features of proximal plaques(presence,wall area index,plaque burden,remodeling index and distribution)were analyzed.Part Ⅱ: 92 PAI patients without relevant middle cerebral artery(MCA)stenosis on magnetic resonance angiography(MRA)were prospectively enrolled.SSI was dichotomized as branch atheromatous disease(BAD;a culprit plaque located adjacent to the LSA origin)and cerebral small vessel disease(CSVD;without plaque or plaque located distal to the LSA origin).We compared risk factors,radiologic features of infarct,morphology of LSAs,and neuroimaging markers of cerebral small vessel disease between the two groups.Results:Part Ⅰ: A total of 71 MCAs in 40 patients were analyzed(31 on the symptomatic side,22 on the asymptomatic side,and 18 in the control group).Of the 40 patients(totally 80 MCAs),WB-HRMRI detected 53(66.3%)plaques located adjacent to LSA origin(proximal plaques)of MCAs that did not have stenosis on MRA.Proximal plaques were more frequently located on the symptomatic side 31(77.5%)MCAs than on the asymptomatic side 22(55.0%)MCAs(P = 0.033).Superior-wall plaques of MCAs were observed more frequently on the symptomatic side than the asymptomatic side(45.2% vs.9.1%,P = 0.005).The vessel area,lumen area,wall area,plaque area,wall area index,plaque burden,and remodeling index did not differ significantly between the symptomatic and asymptomatic side.The number of LSA branches was smaller(P = 0.011)in the symptomatic side(5.48 ± 1.88)compared with the control group(6.83 ± 1.92).The symptomatic side had a shorter average length and distance of LSAs than both the asymptomatic side(23.23±3.44 mm vs.25.75±3.76 mm,P=0.025;16.47±3.11 mm vs.21.53±4.76 mm,P<0.001,respectively)and the control group(23.23±3.44 mm vs.26.71±4.86 mm,P=0.004;16.47±3.11 mm vs.21.84±3.61 mm,P < 0.001,respectively).However,no statistically significant differences were found between the asymptomatic side and control group.Part Ⅱ: Of the 92 PAI patients with no relevant MCA disease,62(67.4%)and30(32.6%)were classified as BAD and CSVD,respectively,according to WB-HRMRI.There were comparable baseline NIHSS scores and functional outcomes between the groups.The number of lesion slices was larger in the patients with BAD compared to those with CSVD,with significance(3 [2-4] vs 3 [2-3];P = 0.032),as well as the number of patients with lesion slices ≥ 4(37.1% vs 16.7%;P = 0.046).The average axial lesion diameter was also larger in the BAD group(1.80±0.71cm)than in the CSVD group(1.46±0.58 cm,P = 0.191).However,the proportion of proximal lesions in the BAD(72.6%)was similar to the CSVD(73.3%)groups(P = 0.939).Of the four CSVD MRI markers,patients with BAD 38(61.3%)had significantly more lacunes compared to those with CSVD 11(36.7%)(P = 0.026),whereas severe DWMH(Fazekas ≥ 2)were more common in patients with CSVD10(33.3%)than in those with BAD 5(8.1%)(P = 0.002).However,there were no differences with respect to CMBs,moderate-severe EPVS in the basal ganglia(>20),and total burden score of CSVD between groups.The number of LSA branches was larger in patients with CSVD 7(5.75-8)than those with BAD 6(4-7;P = 0.001),whereas the number of stems did not differ in CSVD 4(4-5.25)and BAD 4(3-5)groups(P = 0.123).The total length and distance of LSA tended to be shorter in the patients with BAD compared to those with CSVD,with borderline significance(104.26±35.07 mm vs.118.73±38.27 mm,P = 0.075;85.96±29.17 mm vs.97.61±31.46 mm,P = 0.083).In a logistic regression model,the presence of lacunes(odds ratio [OR] 3.50,95%confidence interval [CI] 1.19-10.29;P = 0.023)and smaller number of LSA branches(OR 0.73,95% CI 0.56-0.95;P = 0.018)were significantly associated with BAD,whereas severe DWMH(OR 0.20,95% CI 0.05-0.73;P = 0.015)was independently associated with CSVD;there were no associations of average axial lesion diameter and number of lesion slices ≥ 4 with subtypes of PAI.Conclusion:WB-HRMRI is capable of investigating the spatial relationship between LSA origin and atherosclerotic MCA plaques in one image acquisition.In our study using a novel WB-HRMRI modality for direct in vivo visualization of the spatial relationship between MCA plaques and LSA origin we were successful in distinguishing BAD and CSVD within the heterogeneous entity of PAI in the LSA territory.Superiorly distributed MCA plaques at the LSA origin are closely associated with morphological changes of the LSA in symptomatic MCAs,suggesting that the distribution,rather than the inherent features of plaques,determines the occurrence of SSIs.To the best of our knowledge,this is the first study using WB-HRMRI to visualize the spatial relationship between MCA plaques and LSA origin,thus providing insight into the etiologic mechanism of BAD in PAI.The LSA branches combined with lacunes and severe DWMH may delineate subtypes of PAI.The WB-HRMRI technique could be a credible tool for delineating the heterogeneous entity of SSI in the LSA territory.As well as having a useful role for stroke subtype classification,the approach has potential for risk stratification of PAI for prevention and therapeutic treatments. |
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