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中华脑血管病杂志(电子版)

中华脑血管病杂志(电子版) ›› 2024, Vol. 18 ›› Issue (04) : 301 -308. doi: 10.11817/j.issn.1673-9248.2024.04.002

论著

脑淀粉样血管病β淀粉样蛋白沉积特征及其与影像学标志物的关系
沙宇惠1, 梁梦琳2, 贾琛皓2, 吴娟娟1, 张天昊3, 朱以诚1, 崔瑞雪2,†(), 倪俊1,†()   
  1. 1. 100730　中国医学科学院　北京协和医学院　北京协和医院神经科　疑难重症及罕见病国家重点实验室
    2. 100730　中国医学科学院　北京协和医学院　北京协和医院核医学科　核医学分子靶向诊疗北京市重点实验室
    3. 100049　中国科学院高能物理研究所北京市射线成像技术与装备工程技术研究中心;100049　北京，中国科学院大学核科学与技术学院
  • 收稿日期:2024-06-07 出版日期:2024-08-01
  • 通信作者: 崔瑞雪, 倪俊
  • 基金资助:
    科技创新2030重大项目(2021ZD0201100 任务5 2021ZD0201105); 国家自然科学基金项目(12175268); 中央高水平医院临床科研专项基金(2022-PUMCH-B-070); 中国科学院高能物理研究所创新基金（2024）(E4545AU210)

Characteristics of amyloid-β deposition in cerebral amyloid angiopathy and its relationship with neuroimaging markers

Yuhui Sha1, Menglin Liang2, Chenhao Jia2, Juanjuan Wu1, Tianhao Zhang3, Yicheng Zhu1, Ruixue Cui2,†(), Jun Ni1,†()   

  1. 1. Department of Neurology, State Key laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
    2. Department of Nuclear Medicine, Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
    3. Beijing Engineering Research Center of Radiographic Techniques and Equipment, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China;School of Nuclear Science and Technology, University of Chinese Academy of Sciences, Beijing 100049, China
  • Received:2024-06-07 Published:2024-08-01
  • Corresponding author: Ruixue Cui, Jun Ni
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引用本文：

沙宇惠, 梁梦琳, 贾琛皓, 吴娟娟, 张天昊, 朱以诚, 崔瑞雪, 倪俊. 脑淀粉样血管病β淀粉样蛋白沉积特征及其与影像学标志物的关系[J]. 中华脑血管病杂志(电子版), 2024, 18(04): 301-308.

Yuhui Sha, Menglin Liang, Chenhao Jia, Juanjuan Wu, Tianhao Zhang, Yicheng Zhu, Ruixue Cui, Jun Ni. Characteristics of amyloid-β deposition in cerebral amyloid angiopathy and its relationship with neuroimaging markers[J]. Chinese Journal of Cerebrovascular Diseases(Electronic Edition), 2024, 18(04): 301-308.

目的

定量分析脑淀粉样血管病（CAA）患者脑内β淀粉样蛋白（Aβ）示踪剂18F-florbetapir的摄取水平及其与脑小血管病影像学标志物的相关性，探究Aβ沉积与小血管病变严重程度的关系。

方法

纳入2021年1月至2024年3月登记于北京协和医院前瞻性脑小血管病研究队列，根据Boston 1.5版诊断标准诊断“很可能CAA”的患者，2例患者符合CAA相关炎症（CAA-ri）的诊断。所有患者在1个月内完成3.0T头颅MRI和18F-florbetapir正电子发射体层摄影（PET）/CT检查，并对PET图像进行视觉分析和定量分析，以大脑白质为参考区计算感兴趣脑区的标准化摄取值比（SUVr）。收集所有患者的人口统计学信息、临床和实验室检查、影像资料和PET图像数据，并分析18F-florbetapir与影像学标志物的关系，包括局限脑叶微出血（CMB）、皮质表面铁沉积（cSS）/凸面蛛网膜下腔出血（cSAH）等出血型标志物和白质高信号（WMH）等非出血型标志物。根据临床和影像学特征将CAA患者分为出血型、认知障碍型和CAA-ri型3组。采用单因素方差分析比较3组患者大脑皮层SUVr、小脑皮层SUVr的差异；采用t检验分别比较按照局限脑叶CMB、WMH Fazekas分级、有无小脑CMB分组的大脑或小脑皮层SUVr；采用Mann-Whitney U检验比较按照有无cSS/cSAH分组的大脑皮层SUVr。

结果

共纳入36例CAA患者，年龄为（67.94±8.10）岁，男性占69.4%，出血型9例（25.0%），认知障碍型21例（58.3%），CAA-ri型6例（16.7%）。认知障碍型和出血型CAA患者大脑皮层18F-florbetapir SUVr分别为0.89±0.13和0.84±0.16，组间差异无统计学意义（P>0.05）；合并cSS/cSAH的患者大脑皮层18F-florbetapir摄取水平比未合并者更低[0.78（0.74，0.86） vs 0.90（0.84，0.99）]，差异具有统计学意义（U=-2.322，P=0.02）。局限脑叶CMB数量≥5个和0~4个的CAA患者，大脑皮层SUVr分别为0.88±0.13和0.83±0.12；WMH Fazekas分级较高（5~6级）和较低（1~4级）的患者，大脑皮层SUVr分别为0.90±0.14和0.83±0.11，差异均无统计学意义（P均>0.05）。合并小脑CMB与不合并小脑CMB的患者，小脑皮层SUVr分别为0.79±0.11和0.74±0.14，差异无统计学意义（P>0.05）。

结论

表现脑叶出血或cSS/cSAH的CAA患者大脑皮层18F-florbetapir摄取水平更低，而脑叶CMB数量多、WMH严重的患者大脑皮层18F-florbetapir摄取水平有更高的趋势，表明18F-florbetapir摄取水平高低可能与不同的临床和影像学表型有关，或提示不同发病机制。

关键词: 脑淀粉样血管病, 淀粉样蛋白, 正电子发射体层摄影, 脑小血管病, 影像学标志物
Objective

To quantify the level of brain 18F-florbetapir uptake in patients with cerebral amyloid angiopathy (CAA), and investigate its relationship with neuroimaging markers of cerebral small vessel disease.

Methods

This study enrolled patients from a prospective cerebral small vessel disease cohort study at Peking Union Medical College Hospital between January 2021 and March 2024. The patients met the diagnosis criteria for ''probable CAA'' according to the Boston criteria version 1.5. Additionally, two patients diagnosed with CAA-related inflammation (CAA-ri) were also included. All participants underwent 3.0T MRI and 18F-florbetapir PET/CT within 1 month of their diagnosis. PET images were analyzed both visually and quantitatively. The standardized uptake value ratio (SUVr) of regions of interest was calculated using white matter as the reference region. Demographic characteristics, clinical, laboratory, MRI, and PET imaging data were collected from all patients. The relationship between 18F-florbetapir uptake and MRI markers was analyzed, including hemorrhagic markers such as strict lobar cerebral microbleeds (CMBs), cortical superficial siderosis (cSS), convexal subarachnoid hemorrhage (cSAH), and non-hemorrhagic markers white matter hyperintensity (WMH). Patients with CAA were classified into three groups according to clinical and neuroimaging characteristics: CAA-related intracranial hemorrhage (ICH), CAA with cognitive impairment, and CAA-ri. We used one-way ANOVA to compare the differences in global cerebral cortex SUVr and cerebellar cortex SUVr among the three groups. Student's t-test was used to compare the global cerebral or cerebellar cortex SUVr between patients grouped by the count of strict lobar CMBs, WMH Fazekas, and cerebellar CMBs. The Mann-Whitney U test was used to compare global cortical SUVr between patients with and without cSS/cSAH.

Results

Thirty-six patients with CAA were included in this study, with a mean age of (67.94±8.10) years, and 69.4% were male. Patients were classified into three subtypes: CAA-related ICH (n=9, 25.0%), CAA with cognitive impairment (n=21, 58.3%), and CAA-ri (n=6, 16.7%). The 18F-florbetapir SUVr for CAA with cognitive impairment and CAA-related ICH were 0.89±0.13 and 0.84±0.16, respectively (P>0.05). The 18F-florbetapir SUVr of CAA with cSS/cSAH was significantly lower than those without cSS/cSAH [0.78(0.74, 0.86) vs 0.90(0.84, 0.99), U=-2.322, P=0.02]. The 18F-florbetapir SUVr in CAA with amount of strict lobar CMBs ≥5 and 0~4 were 0.88±0.13 and 0.83±0.12, respectively (P>0.05), and that in CAA with severe WMH and mild WMH were 0.90±0.14 and 0.83±0.11, respectively (P>0.05). The cerebellar cortex SUVr in patients with and without cerebellar CMBs were 0.79±0.11 and 0.74±0.14, respectively (P>0.05).

Conclusion

Patients with CAA exhibiting lobar ICH or cSS/cSAH demonstrated lower global cerebral 18F-florbetapir uptake, whereas those with a higher number of strict lobar CMBs and severe WMH might exhibit greater 18F-florbetapir uptake. This suggests that the condition of 18F-florbetapir uptake could be potentially associated with distinct clinical and imaging phenotypes with different pathogenic mechanisms.

Key words: Cerebral amyloid angiopathy, Amyloid, Positron emission tomography, Cerebral small vessel disease, Neuroimaging markers
表1 脑淀粉样血管病患者人口统计学特征和临床资料分析
资料 出血型（n=9） 认知障碍型（n=21） CAA-ri型（n=6） 统计值 P值
年龄（岁，） 67.67±9.94 69.71±7.22 62.17±6.24 F=2.171 0.130
男性[例（%）] 6（66.7） 16（76.2） 3（50.0） χ2=1.552 0.460
高血压[例（%）] 4（44.4） 12（57.1） 5（83.3） χ2=2.269 0.322
糖尿病[例（%）] 2（22.2） 6（28.6） 1（16.7） χ2=0.402 0.818
吸烟[例（%）] 4（44.4） 9（42.9） 2（33.3） χ2=0.212 0.899
MMSE（分，） 26±3 18±7a 22±8 F=4.148 0.026
MoCA（分，） 21±3 12±7a 18±9 F=9.142 0.004
ApoE ε2携带者[例（%）] 6（66.7） 5（23.8） 1（16.7） χ2=6.107 0.047
ApoE ε4携带者[例（%）] 3（33.3） 9（42.9） 6（100） χ2=7.429 0.024
图1 不同亚型脑淀粉样血管病（CAA）患者头MRI和18F-florbetapir正电子发射断层显像/计算机断层成像（PET/CT）显示：出血型CAA患者在出血亚急性期呈T2高-等混杂血肿信号（图a），磁敏感加权成像（SWI）呈高-低混杂血肿信号（图b），PET/CT可见血肿处示踪剂低摄取，大脑皮层可见弥漫摄取增高，但程度稍低于白质（图c，d）。认知障碍型CAA患者T2像可见半卵圆中心血管周围间隙和皮层下多发点状白质高信号（图e），SWI可见皮层多发脑微出血信号，枕叶为著（图f），PET/CT可见双侧大脑半球皮层弥漫性摄取增高，程度同白质（图g，h）。CAA相关炎症型患者T2像可见双侧不对称白质病变，延伸至皮层下，U型纤维保留，半卵圆中心重度血管周围间隙（图i），SWI可见双侧脑叶皮层弥漫的脑微出血信号（图j），PET/CT可见双侧大脑半球皮层弥漫性摄取增高，程度同白质（图k，l）
表2 CAA不同亚型患者18F-florbetapir显像剂摄取水平比较
组别 例数 视觉分析阳性[例（%）] 大脑皮层SUVr（） 小脑皮层SUVr（）
出血型 9 8（88.9） 0.84±0.16 0.77±0.13
认知障碍型 21 21（100） 0.89±0.13 0.77±0.13
CAA-ri型 6 6（100） 0.88±0.08 0.78±0.06
统计值 χ2=3.086 F=0.349 F=0.040
P值 0.214 0.708 0.961
表3 脑影像学标志物和18F-florbetapir摄取的关系
项目 例数 大脑皮层SUVr 统计值 P值
局限脑叶CMB（） t=-0.977 0.336
0~4个 6 0.83±0.12
≥5个 30 0.88±0.13
cSS/cSAH[M（QR）] U=-2.322 0.020
无 23 0.90（0.84，0.99）
有 13 0.78（0.74，0.86）
WMH Fazekas分级（） t=-1.644 0.109
1~4级 14 0.83±0.11
5~6级 22 0.90±0.14
表4 有无小脑CMB的脑淀粉样血管病患者18F-florbetapir摄取的比较（）
组别 例数 大脑皮层SUVr 小脑皮层SUVr
无CMB 13 0.88±0.14 0.74±0.14
有CMB 23 0.87±0.13 0.79±0.11
t值 0.221 -1.100
P值 0.827 0.279
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