Neurol Sci (2015) 36:547–551 DOI 10.1007/s10072-014-1994-z
ORIGINAL ARTICLE
Arterial remodeling of basilar atherosclerosis in isolated pontine infarction Chao Feng • Ting Hua • Yu Xu • Xue-Yuan Liu Jing Huang
•
Received: 23 June 2014 / Accepted: 28 October 2014 / Published online: 4 November 2014 Ó Springer-Verlag Italia 2014
Abstract Isolated pontine infarctions are usually classified as paramedian pontine infarction (PPI) and lacunar pontine infarction (LPI). Although they have different shapes and locations, some recent studies proved that they might both be associated with basilar artery atherosclerosis in pathogenesis. This study aimed to explore the difference of basilar artery remodeling between two subtypes of pontine infarctions. Patients with PPI or LPI were scanned by High-resolution MRI (HR-MRI). The MR images of patients with basilar artery atherosclerosis were further analyzed to measure the vessel, lumen and wall areas at different segments of basilar arteries. Stenosis rate and remodeling index were calculated according to which arterial remodeling was divided into positive, intermediate and negative remodeling. Vascular risk factors and remodeling-related features were compared between PPI
and LPI, and also between patients with and without positive remodeling. 34 patients with PPI and 21 patients with LPI had basilar artery atherosclerosis identified by HR-MRI. Positive remodeling was dominant in LPI group while in PPI group, three subtypes of remodeling were equal. Patients with positive remodeling had higher levels of low-density lipoprotein and homocysteine. Positive remodeling of basilar artery might reflect the low stability of basilar atherosclerotic plaques, which was more closely associated with LPI than PPI. Keywords Paramedian pontine infarction Lacunar pontine infarction Basilar artery atherosclerosis Arterial remodeling High-resolution MRI
Introduction This study was supported by grants from the National Natural Science Foundation of China (No. 81000492,No. 30971029,No. 81171163), Young Excellent Talents Award of Shanghai 10th People’s Hospital (No.10rq110) and the grants for Back-up Tutors of Shanghai 10th People’s Hospital. C. Feng X.-Y. Liu J. Huang (&) Department of Neurology, Shanghai Tenth People’s Hospital of Tongji University, Middle Yanchang Rd. 301#, Zhabei District, Shanghai, China e-mail: [email protected] X.-Y. Liu e-mail: [email protected] C. Feng The Fourth Affiliated Hospital of Zhejiang University School of Medicine, Yiwu, Zhejiang, China T. Hua Y. Xu Department of Radiology, Shanghai Tenth People’s Hospital of Tongji University, Shanghai, China
Isolated pontine infarction is a common type of posterior circulation infarction. According to the lesion shape and location, isolated pontine infarctions are usually classified as either paramedian pontine infarction (PPI) or lacunar pontine infarction (LPI) [10, 20]. PPI was defined as an infarction with large size in the paramedian region and extending to the ventral surface of the pons, while LPI is small deep in the pons [20]. Recently, with high-resolution magnetic resonance imaging (HR-MRI), some studies showed that patients with PPI and LPI both had relatively high prevalence of basilar artery atherosclerosis [3, 8], and suggested that PPI and LPI might be both associated with atherosclerosis. Atherosclerosis is accompanied with different types of arterial remodeling. Usually the dilation and restriction of vessel wall after atherosclerosis are named as positive and negative remodeling, respectively, with vessel wall without
123
548
Neurol Sci (2015) 36:547–551
obvious dilation or restriction being regarded to have intermediate remodeling [1, 11, 19]. For atherosclerosis, arterial remodeling not only results in the dilation or constriction of vessels [15, 19], but also is associated with the compositions of atherosclerotic plaques and subsequent ischemic events [14, 16]. However, arterial remodeling in pontine infarctions was barely studied. In this study, based on the HR-MRI images of basilar arteries, we aimed to analyze the association between basilar artery remodeling and two subtypes of isolated pontine infarctions.
Methods General information This study was a cross-sectional study based on the patients of Shanghai Tenth People’s Hospital. Patients were consecutively enrolled from June 2011 to May 2012 if they were diagnosed as acute isolated pontine infarction, and attributed to either PPI or LPI group according to the shape and location of the infarct. Patients were excluded if they had multiple acute infarctions in posterior circulation region, histories of posterior circulation strokes, severe stenosis of occlusion of vertebral arteries identified by color Doppler ultrasound, histories of heart failure with a New York Heart Association degree 3 or 4, myocardial infarction, atrial fibrillation, rheumatic valvular heart disease, arteritis or confirmed diagnosis of such diseases. Venous blood of every patient was tested to identify the levels of blood sugar including Hemoglobin A1c, blood lipid and homocysteine. Besides, all the patients were examined by HR-MRI of basilar artery. Among them, patients with basilar artery atherosclerosis identified by HR-MRI were selected for further study about arterial remodeling, while patients with basilar artery dolichoectasia were excluded. After admitted into hospital, patients were prescribed with aspirin and statins according to the Chinese Guideline for the Diagnosis and Management of Patients with Acute Ischemic Stroke (2010). MR protocols Patients were scanned with a 3.0 T MR scanner (Siemens 3.0T Magnetom Verio, Erlangen, Germany). The whole brain was scanned with a slice thickness of 5.5 mm in the axial plane with protocol consisting of T1- and T2weighted image, FLAIR and DWI. Black-blood HR-MRI sequences including proton-density TSE (TR/TE = 3,290/ 16, FOV = 150 9 150 mm, matrix = 272 9 320, number of excitations = 2) and T2-dark-fluid-spair sequences (TR/ TE = 3,000/26, FOV = 150 9 150 mm, matrix = 251 9
123
Fig. 1 The examples of basilar artery atherosclerosis. The white arrow points to the atherosclerotic plaque the signal of which is relatively low, attached on the vessel wall with high signal on PDTSE. The lumen is surrounded by the atherosclerotic plaque and vessel wall, with lowest signal or flowing void on PD-TSE. The lumen, vessel wall and atherosclerotic plaque could be distinguished clearly from this image
256, number of excitations = 1) were obtained in the axial plane with a slice thickness of 2 mm. Arterial remodeling The evaluation of arterial remodeling was performed on the work station (Advantage Workstation AW4.3_08) of the Department of Radiology. The images of PD-TSE on which the images of vessel walls were clearest were chosen for measurement. Before the measurement, three special sites, i.e., the maximal-lumen-narrowing site where the stenosis of basilar artery was severest, and two reference sites where the vessel walls of basilar artery were normal or had minimal atherosclerosis proximal and distal to the maximal-lumennarrowing site, respectively, were selected after visual comparison. All the measurements were carried out on these sites. Lumen area and vessel area were traced manually by the vessel-blood interface and vessel-CSF interface, respectively. Wall area was defined as vessel area–lumen area. Reference vessel area and reference lumen area were defined as the means of those measured at the distal and proximal reference sites. Plaque area was estimated as wall area at the maximal-lumen-narrowing site–reference wall area. To evaluate the severity of atherosclerosis more objectively, percentage plaque burden was calculated as (plaque area/vessel area at the maximal-lumen narrowing site) 9 100 %. Lumen stenosis rate was calculated as plaque area/(plaque area ? lumen area) at the maximal-
Neurol Sci (2015) 36:547–551
549 Table 1 The comparisons of basic characteristics between PPI and LPI
Fig. 2 The examples of arterial remodeling-related measurement. This image was obtained from the same section with Fig. 1. Area A is lumen area; B is plaque area; B ? C = wall area; A ? B ? C = vessel area
lumen-narrowing site 9 100 %. At last, remodeling index was defined as (vessel area at the maximal-lumen-narrowing site/reference vessel area) 9 100 %. Remodeling index C1.05 was defined as positive remodeling, remodeling index B0.95 as negative remodeling, and 0.95 \ remodeling index \ 1.05 as intermediate remodeling of basilar artery [6, 11]. Negative remodeling and intermediate remodeling were both regarded as non-positive remodeling. The examples of above parameters are illustrated in Figs. 1 and 2. All the measurements were performed by two radiologists blind to clinical data. The final data used for statistical analysis were the means of those measured by two radiologists. Statistical analysis All data were analyzed with SPSS (version 18.0). Categorical data were listed as percentage (numbers) and compared between different groups by v2 test and Fisher’s exact test. Measurement data were listed as mean ± standard deviation and compared by Student’s t test. Intra-class correlation coefficient (ICC) was used to evaluate the interobserver variability for lumen area and vessel area at the maximal-lumen-narrowing site and at reference site. P \ 0.05 was considered to indicate statistical difference.
Results Basic characteristics 81 patients were enrolled and scanned by HR-MRI. 55 of them including 34 patients with PPI and 21 patients with LPI were identified to have basilar artery atherosclerosis.
PPI (n = 34)
LPI (n = 21)
P
Age,years
67.82 ± 4.78
67.19 ± 5.27
0.648 0.768
Male, % (n)
67.6 (23)
71.4 (15)
Hypertension, % (n)
82.4 (28)
76.2 (16)
0.579
Diabetes, % (n)
38.2 (13)
28.6 (6)
0.464
Dyslipidemia, % (n)
73.5 (25)
81.0 (17)
0.529
Current smoking, % (n)
32.4 (11)
42.9 (9)
0.431
Homocysteine, mmol/l Hemoglobin A1c, %
15.75 ± 6.43 6.09 ± 0.94
16.55 ± 6.24 6.20 ± 1.31
0.650 0.719
Total cholesterol, mmol/l
5.73 ± 0.81
5.35 ± 0.65
0.080
Triglyceride, mmol/l
1.84 ± 0.43
2.01 ± 0.43
0.138
Low-density lipoprotein, mmol/l
2.86 ± 0.65
2.91 ± 0.79
0.796
High-density lipoprotein, mmol/l
1.10 ± 0.22
1.03 ± 0.25
0.226
Table 2 Arterial remodeling of basilar atherosclerosis for PPI and LPI PPI (n = 34)
LPI (n = 21)
P
Vessel area, mm2
21.18 ± 2.71
20.33 ± 2.37
0.245
Lumen area, mm2
8.76 ± 0.98
8.68 ± 1.02
0.767
Wall area, mm2
12.42 ± 2.12
11.66 ± 1.49
0.156 0.222
At reference sites
At the maximal-lumen-narrowing site Vessel area, mm2
21.21 ± 3.05
22.35 ± 3.74
Lumen area, mm2
5.54 ± 2.10
8.88 ± 3.41
0.000
Wall area, mm2
15.66 ± 2.63
13.47 ± 1.50
0.000
Plaque area, mm2 Plaque burden, %
3.24 ± 1.69 15.20 ± 7.42
1.81 ± 0.84 8.82 ± 4.28
0.000 0.000
Stenosis rate, %
37.16 ± 17.92
18.99 ± 12.17
0.000
Remodeling index
1.00 ± 0.10
1.10 ± 0.15
0.006
Positive remodeling, % (n)
32.4 (11)
61.9 (13)
0.032
Intermediate remodeling, % (n)
32.4 (11)
28.6 (6)
0.768
Negative remodeling, % (n)
35.3 (12)
9.5 (2)
0.033
Basic characteristics of PPI and LPI including age, sex, the prevalence of various vascular risk factors are listed in Table 1, which showed no significant difference between two subtypes. Arterial remodeling of basilar artery atherosclerosis for PPI and LPI Vessel area, lumen area and wall area at the reference sites of basilar arteries were all similar between PPI and LPI
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Neurol Sci (2015) 36:547–551
Table 3 Characteristics of patients with positive and non-positive remodeling Positive remodeling (n = 24)
Non-positive remodeling (n = 31)
P
Age, years
67.50 ± 5.07
67.65 ± 4.90
0.915
Male, % (n)
58.5 (14)
77.4 (24)
0.129
Hypertension, % (n)
87.5 (21)
74.2 (23)
0.221
Diabetes, % (n)
33.3 (8)
35.5 (11)
0.868
Dyslipidemia, % (n)
79.2 (19)
74.2 (23)
0.667
Current smoking, % (n)
37.5 (9)
35.5 (11)
0.877
Homocysteine ,mmol/l
18.37 ± 7.05
14.27 ± 5.11
0.015
Hemoglobin A1c, %
6.25 ± 1.38
6.03 ± 0.80
0.465
Total cholesterol, mmol/l
5.57 ± 0.64
5.60 ± 0.87
0.909
Triglyceride, mmol/l
1.96 ± 0.40
1.85 ± 0.45
0.331
Low-density lipoprotein, mmol/l
3.11 ± 0.57
2.70 ± 0.74
0.032
High-density lipoprotein, mmol/l
1.02 ± 0.25
1.12 ± 0.21
0.096
Vessel area, mm2
20.42 ± 2.20
21.19 ± 2.85
0.284
Lumen area, mm2
8.69 ± 0.88
8.76 ± 1.08
0.817
Wall area, mm2
11.73 ± 1.58
12.43 ± 2.13
0.184
At reference sites
At the maximal-lumen-narrowing site Plaque area, mm2
2.88 ± 1.74
2.55 ± 1.46
0.460
Plaque burden, %
12.32 ± 6.94
13.11 ± 7.29
0.688
Stenosis rate, %
24.88 ± 14.33
34.36 ± 19.91
0.045
(P [ 0.05). However, the characteristics at the maximallumen-narrowing sites of basilar arteries were quite different between PPI and LPI. Lumen area at the maximallumen-narrowing sites of PPI was much smaller than that of LPI, while the wall area, plaque area, plaque burden and stenosis rate of LPI were all smaller than those of PPI (P \ 0.01). The results of ICC for the measurements of vessel area, lumen area at the maximal-lumen-narrowing site and reference sites were all higher than 0.90 (details not shown) and suggested high consistency between two radiologists. The remodeling index of LPI was higher than that of PPI (P \ 0.01). For PPI, the percentages of three remodeling types were similar, while for LPI, positive remodeling was the majority. The detailed results are listed in Table 2.
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Characteristics of positive remodeling and non-positive remodeling In this part, the data of PPI and LPI were summarized and then re-divided into positive remodeling group and nonpositive remodeling group. 24 of the 55 patients had positive remodeling of basilar arteries; the rest 31 patients had non-positive remodeling. There was no statistical difference of age, sex, the prevalence of hypertension, diabetes and dyslipidemia between two groups (P [ 0.05). However, patients of positive remodeling had higher levels of homocysteine and low-density lipoprotein (P \ 0.05). The parameters of normal basilar arteries were similar between positive- and non-positive remodeling groups. At the maximal-lumen-narrowing sites, there was no difference of plaque area and plaque burden. However, the stenosis rate was lower in positive-remodeling group (P \ 0.05). The detailed results are listed in Table 3.
Discussion Arterial remodeling has been studied for years involving both coronary and carotid artery diseases [13, 14, 18, 19]. Although coronary and carotid arteries have different structures and are classified as muscular and elastic arteries, respectively, their remodeling might have similar significance. Most studies proved that positive remodeling was associated with unstable plaques which tend to bleed, corrupt and fall off, with inflammation and proliferation as the main pathological change [2, 7, 9, 14], while negative remodeling is the process of vessel constriction caused by the calcification and sclerosis of plaques at relatively late stage of atherosclerosis [18]. Considering that most conclusions about arterial remodeling were from studies about coronary and carotid arteries, but not basilar arteries, we further analyzed the characteristics of basilar artery remodeling. Structurally, basilar arteries with positive remodeling seemed to be mildly stenotic compared with those of non-positive remodeling, with no obvious difference in the normal segments between them. It indicated that positive remodeling of basilar arteries leads to lumen dilation compared with non-positive remodeling. In vascular risk factors, the comparison showed that patients with positive remodeling had higher levels of low-density lipoprotein and homocysteine, both of which were associated with advanced atherosclerosis and unstable plaques, and also proven to be related to positive remodeling of coronary and carotid arteries [4, 5, 12, 17, 21]. Anyway, basilar artery remodeling seemed to be similar to the remodeling of coronary and carotid arteries in various respects, thus it is reasonable
Neurol Sci (2015) 36:547–551
to speculate that they also have similar clinical significance, such as the association with unstable plaques and acute ischemic events. This study showed that most patients with LPI and part of patients with PPI had positive remodeling without obvious lumen stenosis. This explained why most of them had no basilar artery atherosclerosis identified by conventional MRA [3, 8], and also suggested that most LPI and part of PPI might be related to unstable plaques, which lead to local thrombosis and occlusion of perforating arteries at distal or proximal segments. On the other hand, most patients with PPI had non-positive remodeling of basilar arteries, with more stable plaques and severe lumen stenosis. Some patients even had lumen stenosis more than 50 %. Differently to those with positive remodeling and unstable plaques, it is more reasonable to attribute these infarctions to the large stable plaques which progressed in situ and then covered the perforating orifices. In conclusion, this study showed that most LPI and part of PPI might be related to unstable plaques accompanied with positive remodeling of basilar arteries identified by HR-MRI. It is suggested that for patients with basilar artery atherosclerosis, evaluation of arterial remodeling and identification of unstable plaques are necessary to make a proper treatment plan of plaque stabilization. However, the sample of this study was small, with no control group of non-symptomatic basilar artery atherosclerosis. We could not analyze the ingredient of atherosclerotic plaques which would supply more direct information about the plaque stability without contrast-enhanced HR-MRI. Thus the significance of this study was limited. Further studies were still required and should avoid the above-mentioned limitations to explore more about the pathological mechanism of arterial remodeling and its clinical significance.
551
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
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in coronary arteries in asymptomatic patients with type 2 diabetes mellitus. J Atheroscler Thromb 20:452–464 Hong MK, Park SW, Lee CW et al (2002) Elevated homocysteine levels might be associated with coronary artery remodeling in patients with stable angina: an intravascular ultrasound study. Clin Cardiol 25:225–229 Hong YJ, Jeong MH, Choi YH et al (2012) Positive remodeling is associated with vulnerable coronary plaque components regardless of clinical presentation: virtual histology-intravascular ultrasound analysis. Int J Cardiol 167(3):871–876 Kashiwagi M, Tanaka A, Kitabata H et al (2009) Relationship between coronary arterial remodeling, fibrous cap thickness and high-sensitivity C-reactive protein levels in patients with acute coronary syndrome. Circ J 73:1291–1295 Klein IF, Lavallee PC, Mazighi M et al (2010) Basilar artery atherosclerotic plaques in paramedian and lacunar pontine infarctions: a high-resolution MRI study. Stroke 41:1405–1409 Lee CW, Park CS, Hwang I et al (2011) Comparison of ruptured coronary plaques in patients with unstable and stable clinical presentation. J Thromb Thrombolysis 32:150–157 Erro ME, Ga´llego J, Herrera M, Bermejo B (2005) Isolated pontine infarcts: etiopathogenic mechanisms. Eur J Neurol 12:984–988 Ma N, Jiang WJ, Lou X et al (2010) Arterial remodeling of advanced basilar atherosclerosis: a 3-tesla MRI study. Neurology 75:253–258 Marti-Carvajal AJ, Sola I, Lathyris D et al (2013) Homocysteinelowering interventions for preventing cardiovascular events. Cochrane Database Syst Rev 1:CD006612 Matsuo Y, Takumi T, Mathew V et al (2012) Plaque characteristics and arterial remodeling in coronary and peripheral arterial systems. Atherosclerosis 223:365–371 Miura T, Matsukawa N, Sakurai K et al (2011) Plaque vulnerability in internal carotid arteries with positive remodeling. Cerebrovasc Dis Extra 1:54–65 Reddy HK, Koshy SK, Wasson S et al (2006) Adaptive-outward and maladaptive-inward arterial remodeling measured by intravascular ultrasound in hyperhomocysteinemia and diabetes. J Cardiovasc Pharmacol Ther 11:65–76 Samady H, Eshtehardi P, McDaniel MC et al (2011) Coronary artery wall shear stress is associated with progression and transformation of atherosclerotic plaque and arterial remodeling in patients with coronary artery disease. Circulation 124:779–788 Schartl M, Bocksch W, Fateh-Moghadam S (2004) Effects of lipid-lowering therapy on coronary artery remodeling. Coron Artery Dis 15:45–51 Schoenhagen P, Nissen SE, Tuzcu EM (2003) Coronary arterial remodeling: from bench to bedside. Curr Atheroscler Rep 5:150–154 Schoenhagen P, Ziada KM, Vince DG et al (2001) Arterial remodeling and coronary artery disease: the concept of ‘‘dilated’’ versus ‘‘obstructive’’ coronary atherosclerosis. J Am Coll Cardiol 38:297–306 Toyoda K, Saku Y, Ibayashi S et al (1994) Pontine infarction extending to the basal surface. Stroke 25:2171–2178 Xu H, Liu C, Wang Q (2013) Plaque image characteristics, hyperhomocysteinemia, and gene polymorphism of homocysteine metabolism-related enzyme (MTHFR C677T) in acute coronary syndrome. Cell Biochem Biophys 66:403–407
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ORIGINAL ARTICLE
Arterial remodeling of basilar atherosclerosis in isolated pontine infarction Chao Feng • Ting Hua • Yu Xu • Xue-Yuan Liu Jing Huang
•
Received: 23 June 2014 / Accepted: 28 October 2014 / Published online: 4 November 2014 Ó Springer-Verlag Italia 2014
Abstract Isolated pontine infarctions are usually classified as paramedian pontine infarction (PPI) and lacunar pontine infarction (LPI). Although they have different shapes and locations, some recent studies proved that they might both be associated with basilar artery atherosclerosis in pathogenesis. This study aimed to explore the difference of basilar artery remodeling between two subtypes of pontine infarctions. Patients with PPI or LPI were scanned by High-resolution MRI (HR-MRI). The MR images of patients with basilar artery atherosclerosis were further analyzed to measure the vessel, lumen and wall areas at different segments of basilar arteries. Stenosis rate and remodeling index were calculated according to which arterial remodeling was divided into positive, intermediate and negative remodeling. Vascular risk factors and remodeling-related features were compared between PPI
and LPI, and also between patients with and without positive remodeling. 34 patients with PPI and 21 patients with LPI had basilar artery atherosclerosis identified by HR-MRI. Positive remodeling was dominant in LPI group while in PPI group, three subtypes of remodeling were equal. Patients with positive remodeling had higher levels of low-density lipoprotein and homocysteine. Positive remodeling of basilar artery might reflect the low stability of basilar atherosclerotic plaques, which was more closely associated with LPI than PPI. Keywords Paramedian pontine infarction Lacunar pontine infarction Basilar artery atherosclerosis Arterial remodeling High-resolution MRI
Introduction This study was supported by grants from the National Natural Science Foundation of China (No. 81000492,No. 30971029,No. 81171163), Young Excellent Talents Award of Shanghai 10th People’s Hospital (No.10rq110) and the grants for Back-up Tutors of Shanghai 10th People’s Hospital. C. Feng X.-Y. Liu J. Huang (&) Department of Neurology, Shanghai Tenth People’s Hospital of Tongji University, Middle Yanchang Rd. 301#, Zhabei District, Shanghai, China e-mail: [email protected] X.-Y. Liu e-mail: [email protected] C. Feng The Fourth Affiliated Hospital of Zhejiang University School of Medicine, Yiwu, Zhejiang, China T. Hua Y. Xu Department of Radiology, Shanghai Tenth People’s Hospital of Tongji University, Shanghai, China
Isolated pontine infarction is a common type of posterior circulation infarction. According to the lesion shape and location, isolated pontine infarctions are usually classified as either paramedian pontine infarction (PPI) or lacunar pontine infarction (LPI) [10, 20]. PPI was defined as an infarction with large size in the paramedian region and extending to the ventral surface of the pons, while LPI is small deep in the pons [20]. Recently, with high-resolution magnetic resonance imaging (HR-MRI), some studies showed that patients with PPI and LPI both had relatively high prevalence of basilar artery atherosclerosis [3, 8], and suggested that PPI and LPI might be both associated with atherosclerosis. Atherosclerosis is accompanied with different types of arterial remodeling. Usually the dilation and restriction of vessel wall after atherosclerosis are named as positive and negative remodeling, respectively, with vessel wall without
123
548
Neurol Sci (2015) 36:547–551
obvious dilation or restriction being regarded to have intermediate remodeling [1, 11, 19]. For atherosclerosis, arterial remodeling not only results in the dilation or constriction of vessels [15, 19], but also is associated with the compositions of atherosclerotic plaques and subsequent ischemic events [14, 16]. However, arterial remodeling in pontine infarctions was barely studied. In this study, based on the HR-MRI images of basilar arteries, we aimed to analyze the association between basilar artery remodeling and two subtypes of isolated pontine infarctions.
Methods General information This study was a cross-sectional study based on the patients of Shanghai Tenth People’s Hospital. Patients were consecutively enrolled from June 2011 to May 2012 if they were diagnosed as acute isolated pontine infarction, and attributed to either PPI or LPI group according to the shape and location of the infarct. Patients were excluded if they had multiple acute infarctions in posterior circulation region, histories of posterior circulation strokes, severe stenosis of occlusion of vertebral arteries identified by color Doppler ultrasound, histories of heart failure with a New York Heart Association degree 3 or 4, myocardial infarction, atrial fibrillation, rheumatic valvular heart disease, arteritis or confirmed diagnosis of such diseases. Venous blood of every patient was tested to identify the levels of blood sugar including Hemoglobin A1c, blood lipid and homocysteine. Besides, all the patients were examined by HR-MRI of basilar artery. Among them, patients with basilar artery atherosclerosis identified by HR-MRI were selected for further study about arterial remodeling, while patients with basilar artery dolichoectasia were excluded. After admitted into hospital, patients were prescribed with aspirin and statins according to the Chinese Guideline for the Diagnosis and Management of Patients with Acute Ischemic Stroke (2010). MR protocols Patients were scanned with a 3.0 T MR scanner (Siemens 3.0T Magnetom Verio, Erlangen, Germany). The whole brain was scanned with a slice thickness of 5.5 mm in the axial plane with protocol consisting of T1- and T2weighted image, FLAIR and DWI. Black-blood HR-MRI sequences including proton-density TSE (TR/TE = 3,290/ 16, FOV = 150 9 150 mm, matrix = 272 9 320, number of excitations = 2) and T2-dark-fluid-spair sequences (TR/ TE = 3,000/26, FOV = 150 9 150 mm, matrix = 251 9
123
Fig. 1 The examples of basilar artery atherosclerosis. The white arrow points to the atherosclerotic plaque the signal of which is relatively low, attached on the vessel wall with high signal on PDTSE. The lumen is surrounded by the atherosclerotic plaque and vessel wall, with lowest signal or flowing void on PD-TSE. The lumen, vessel wall and atherosclerotic plaque could be distinguished clearly from this image
256, number of excitations = 1) were obtained in the axial plane with a slice thickness of 2 mm. Arterial remodeling The evaluation of arterial remodeling was performed on the work station (Advantage Workstation AW4.3_08) of the Department of Radiology. The images of PD-TSE on which the images of vessel walls were clearest were chosen for measurement. Before the measurement, three special sites, i.e., the maximal-lumen-narrowing site where the stenosis of basilar artery was severest, and two reference sites where the vessel walls of basilar artery were normal or had minimal atherosclerosis proximal and distal to the maximal-lumennarrowing site, respectively, were selected after visual comparison. All the measurements were carried out on these sites. Lumen area and vessel area were traced manually by the vessel-blood interface and vessel-CSF interface, respectively. Wall area was defined as vessel area–lumen area. Reference vessel area and reference lumen area were defined as the means of those measured at the distal and proximal reference sites. Plaque area was estimated as wall area at the maximal-lumen-narrowing site–reference wall area. To evaluate the severity of atherosclerosis more objectively, percentage plaque burden was calculated as (plaque area/vessel area at the maximal-lumen narrowing site) 9 100 %. Lumen stenosis rate was calculated as plaque area/(plaque area ? lumen area) at the maximal-
Neurol Sci (2015) 36:547–551
549 Table 1 The comparisons of basic characteristics between PPI and LPI
Fig. 2 The examples of arterial remodeling-related measurement. This image was obtained from the same section with Fig. 1. Area A is lumen area; B is plaque area; B ? C = wall area; A ? B ? C = vessel area
lumen-narrowing site 9 100 %. At last, remodeling index was defined as (vessel area at the maximal-lumen-narrowing site/reference vessel area) 9 100 %. Remodeling index C1.05 was defined as positive remodeling, remodeling index B0.95 as negative remodeling, and 0.95 \ remodeling index \ 1.05 as intermediate remodeling of basilar artery [6, 11]. Negative remodeling and intermediate remodeling were both regarded as non-positive remodeling. The examples of above parameters are illustrated in Figs. 1 and 2. All the measurements were performed by two radiologists blind to clinical data. The final data used for statistical analysis were the means of those measured by two radiologists. Statistical analysis All data were analyzed with SPSS (version 18.0). Categorical data were listed as percentage (numbers) and compared between different groups by v2 test and Fisher’s exact test. Measurement data were listed as mean ± standard deviation and compared by Student’s t test. Intra-class correlation coefficient (ICC) was used to evaluate the interobserver variability for lumen area and vessel area at the maximal-lumen-narrowing site and at reference site. P \ 0.05 was considered to indicate statistical difference.
Results Basic characteristics 81 patients were enrolled and scanned by HR-MRI. 55 of them including 34 patients with PPI and 21 patients with LPI were identified to have basilar artery atherosclerosis.
PPI (n = 34)
LPI (n = 21)
P
Age,years
67.82 ± 4.78
67.19 ± 5.27
0.648 0.768
Male, % (n)
67.6 (23)
71.4 (15)
Hypertension, % (n)
82.4 (28)
76.2 (16)
0.579
Diabetes, % (n)
38.2 (13)
28.6 (6)
0.464
Dyslipidemia, % (n)
73.5 (25)
81.0 (17)
0.529
Current smoking, % (n)
32.4 (11)
42.9 (9)
0.431
Homocysteine, mmol/l Hemoglobin A1c, %
15.75 ± 6.43 6.09 ± 0.94
16.55 ± 6.24 6.20 ± 1.31
0.650 0.719
Total cholesterol, mmol/l
5.73 ± 0.81
5.35 ± 0.65
0.080
Triglyceride, mmol/l
1.84 ± 0.43
2.01 ± 0.43
0.138
Low-density lipoprotein, mmol/l
2.86 ± 0.65
2.91 ± 0.79
0.796
High-density lipoprotein, mmol/l
1.10 ± 0.22
1.03 ± 0.25
0.226
Table 2 Arterial remodeling of basilar atherosclerosis for PPI and LPI PPI (n = 34)
LPI (n = 21)
P
Vessel area, mm2
21.18 ± 2.71
20.33 ± 2.37
0.245
Lumen area, mm2
8.76 ± 0.98
8.68 ± 1.02
0.767
Wall area, mm2
12.42 ± 2.12
11.66 ± 1.49
0.156 0.222
At reference sites
At the maximal-lumen-narrowing site Vessel area, mm2
21.21 ± 3.05
22.35 ± 3.74
Lumen area, mm2
5.54 ± 2.10
8.88 ± 3.41
0.000
Wall area, mm2
15.66 ± 2.63
13.47 ± 1.50
0.000
Plaque area, mm2 Plaque burden, %
3.24 ± 1.69 15.20 ± 7.42
1.81 ± 0.84 8.82 ± 4.28
0.000 0.000
Stenosis rate, %
37.16 ± 17.92
18.99 ± 12.17
0.000
Remodeling index
1.00 ± 0.10
1.10 ± 0.15
0.006
Positive remodeling, % (n)
32.4 (11)
61.9 (13)
0.032
Intermediate remodeling, % (n)
32.4 (11)
28.6 (6)
0.768
Negative remodeling, % (n)
35.3 (12)
9.5 (2)
0.033
Basic characteristics of PPI and LPI including age, sex, the prevalence of various vascular risk factors are listed in Table 1, which showed no significant difference between two subtypes. Arterial remodeling of basilar artery atherosclerosis for PPI and LPI Vessel area, lumen area and wall area at the reference sites of basilar arteries were all similar between PPI and LPI
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Table 3 Characteristics of patients with positive and non-positive remodeling Positive remodeling (n = 24)
Non-positive remodeling (n = 31)
P
Age, years
67.50 ± 5.07
67.65 ± 4.90
0.915
Male, % (n)
58.5 (14)
77.4 (24)
0.129
Hypertension, % (n)
87.5 (21)
74.2 (23)
0.221
Diabetes, % (n)
33.3 (8)
35.5 (11)
0.868
Dyslipidemia, % (n)
79.2 (19)
74.2 (23)
0.667
Current smoking, % (n)
37.5 (9)
35.5 (11)
0.877
Homocysteine ,mmol/l
18.37 ± 7.05
14.27 ± 5.11
0.015
Hemoglobin A1c, %
6.25 ± 1.38
6.03 ± 0.80
0.465
Total cholesterol, mmol/l
5.57 ± 0.64
5.60 ± 0.87
0.909
Triglyceride, mmol/l
1.96 ± 0.40
1.85 ± 0.45
0.331
Low-density lipoprotein, mmol/l
3.11 ± 0.57
2.70 ± 0.74
0.032
High-density lipoprotein, mmol/l
1.02 ± 0.25
1.12 ± 0.21
0.096
Vessel area, mm2
20.42 ± 2.20
21.19 ± 2.85
0.284
Lumen area, mm2
8.69 ± 0.88
8.76 ± 1.08
0.817
Wall area, mm2
11.73 ± 1.58
12.43 ± 2.13
0.184
At reference sites
At the maximal-lumen-narrowing site Plaque area, mm2
2.88 ± 1.74
2.55 ± 1.46
0.460
Plaque burden, %
12.32 ± 6.94
13.11 ± 7.29
0.688
Stenosis rate, %
24.88 ± 14.33
34.36 ± 19.91
0.045
(P [ 0.05). However, the characteristics at the maximallumen-narrowing sites of basilar arteries were quite different between PPI and LPI. Lumen area at the maximallumen-narrowing sites of PPI was much smaller than that of LPI, while the wall area, plaque area, plaque burden and stenosis rate of LPI were all smaller than those of PPI (P \ 0.01). The results of ICC for the measurements of vessel area, lumen area at the maximal-lumen-narrowing site and reference sites were all higher than 0.90 (details not shown) and suggested high consistency between two radiologists. The remodeling index of LPI was higher than that of PPI (P \ 0.01). For PPI, the percentages of three remodeling types were similar, while for LPI, positive remodeling was the majority. The detailed results are listed in Table 2.
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Characteristics of positive remodeling and non-positive remodeling In this part, the data of PPI and LPI were summarized and then re-divided into positive remodeling group and nonpositive remodeling group. 24 of the 55 patients had positive remodeling of basilar arteries; the rest 31 patients had non-positive remodeling. There was no statistical difference of age, sex, the prevalence of hypertension, diabetes and dyslipidemia between two groups (P [ 0.05). However, patients of positive remodeling had higher levels of homocysteine and low-density lipoprotein (P \ 0.05). The parameters of normal basilar arteries were similar between positive- and non-positive remodeling groups. At the maximal-lumen-narrowing sites, there was no difference of plaque area and plaque burden. However, the stenosis rate was lower in positive-remodeling group (P \ 0.05). The detailed results are listed in Table 3.
Discussion Arterial remodeling has been studied for years involving both coronary and carotid artery diseases [13, 14, 18, 19]. Although coronary and carotid arteries have different structures and are classified as muscular and elastic arteries, respectively, their remodeling might have similar significance. Most studies proved that positive remodeling was associated with unstable plaques which tend to bleed, corrupt and fall off, with inflammation and proliferation as the main pathological change [2, 7, 9, 14], while negative remodeling is the process of vessel constriction caused by the calcification and sclerosis of plaques at relatively late stage of atherosclerosis [18]. Considering that most conclusions about arterial remodeling were from studies about coronary and carotid arteries, but not basilar arteries, we further analyzed the characteristics of basilar artery remodeling. Structurally, basilar arteries with positive remodeling seemed to be mildly stenotic compared with those of non-positive remodeling, with no obvious difference in the normal segments between them. It indicated that positive remodeling of basilar arteries leads to lumen dilation compared with non-positive remodeling. In vascular risk factors, the comparison showed that patients with positive remodeling had higher levels of low-density lipoprotein and homocysteine, both of which were associated with advanced atherosclerosis and unstable plaques, and also proven to be related to positive remodeling of coronary and carotid arteries [4, 5, 12, 17, 21]. Anyway, basilar artery remodeling seemed to be similar to the remodeling of coronary and carotid arteries in various respects, thus it is reasonable
Neurol Sci (2015) 36:547–551
to speculate that they also have similar clinical significance, such as the association with unstable plaques and acute ischemic events. This study showed that most patients with LPI and part of patients with PPI had positive remodeling without obvious lumen stenosis. This explained why most of them had no basilar artery atherosclerosis identified by conventional MRA [3, 8], and also suggested that most LPI and part of PPI might be related to unstable plaques, which lead to local thrombosis and occlusion of perforating arteries at distal or proximal segments. On the other hand, most patients with PPI had non-positive remodeling of basilar arteries, with more stable plaques and severe lumen stenosis. Some patients even had lumen stenosis more than 50 %. Differently to those with positive remodeling and unstable plaques, it is more reasonable to attribute these infarctions to the large stable plaques which progressed in situ and then covered the perforating orifices. In conclusion, this study showed that most LPI and part of PPI might be related to unstable plaques accompanied with positive remodeling of basilar arteries identified by HR-MRI. It is suggested that for patients with basilar artery atherosclerosis, evaluation of arterial remodeling and identification of unstable plaques are necessary to make a proper treatment plan of plaque stabilization. However, the sample of this study was small, with no control group of non-symptomatic basilar artery atherosclerosis. We could not analyze the ingredient of atherosclerotic plaques which would supply more direct information about the plaque stability without contrast-enhanced HR-MRI. Thus the significance of this study was limited. Further studies were still required and should avoid the above-mentioned limitations to explore more about the pathological mechanism of arterial remodeling and its clinical significance.
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15.
16.
17.
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