背景:脑脊液(CSF)清除率降低已被认为是阿尔茨海默病(AD)的病理特征。由于在非人类哺乳动物中的大量文献和相互矛盾的人类神经影像学数据,鼻粘膜是否是人类的CSF引流部位仍然未知。这里,我们使用动态PET和[1-11C]-丁醇,一种高度可渗透的放射性示踪剂,没有明显的大脑结合,以检验以下假设:来自鼻通路的示踪剂引流反映了来自脑的CSF引流。作为对假设的检验,我们检查了脑和鼻液引流时间是否相关以及是否受脑淀粉样蛋白的影响。
方法:对24名认知正常受试者(≥65岁)进行动态PET成像60分钟。使用[1-11C]-丁醇。用[11C]-PiB或[18F]-FBB成像鉴定8个淀粉样蛋白PET阳性(Aβ+)和16个Aβ-受试者。MRI确定的感兴趣区域(ROI)包括:颈动脉,外侧眶额叶(LOF)大脑,筛板,和一个由上级组成的全鼻甲区域,中间,和下鼻甲。双侧颞肌和颈静脉作为控制区。区域时间活动被用来模拟示踪剂流入,出口,AUC。
结果:LOF和全鼻甲60分钟AUC呈正相关,从而暗示了大脑和鼻子之间的联系。Further,Aβ+亚组示踪剂动力学受损,以示踪剂流入减少和出口变慢为标志。
结论:数据表明,脑和鼻甲的示踪剂动力学彼此相关,并且都反映了脑的淀粉样蛋白状态。因此,这些数据增加了鼻通路是人类潜在的CSF引流部位的证据.这些数据保证了对神经退行性疾病中脑和鼻对蛋白质清除的贡献的进一步研究。
BACKGROUND: Reduced clearance of cerebrospinal fluid (CSF) has been suggested as a pathological feature of Alzheimer\'s disease (AD). With extensive documentation in non-human mammals and contradictory human neuroimaging data it remains unknown whether the nasal mucosa is a CSF drainage site in humans. Here, we used dynamic PET with [1-11C]-Butanol, a highly permeable radiotracer with no appreciable brain binding, to test the hypothesis that tracer drainage from the nasal pathway reflects CSF drainage from brain. As a test of the hypothesis, we examined whether brain and nasal fluid drainage times were correlated and affected by brain amyloid.
METHODS: 24 cognitively normal subjects (≥ 65 years) were dynamically PET imaged for 60 min. using [1-11C]-Butanol. Imaging with either [11C]-PiB or [18F]-FBB identified 8 amyloid PET positive (Aβ+) and 16 Aβ- subjects. MRI-determined regions of interest (ROI) included: the carotid artery, the lateral orbitofrontal (LOF) brain, the cribriform plate, and an All-turbinate region comprised of the superior, middle, and inferior
turbinates. The bilateral temporalis muscle and jugular veins served as control regions. Regional time-activity were used to model tracer influx, egress, and AUC.
RESULTS: LOF and All-turbinate 60 min AUC were positively associated, thus suggesting a connection between the brain and the nose. Further, the Aβ+ subgroup demonstrated impaired tracer kinetics, marked by reduced tracer influx and slower egress.
CONCLUSIONS: The data show that tracer kinetics for brain and nasal
turbinates are related to each other and both reflect the amyloid status of the brain. As such, these data add to evidence that the nasal pathway is a potential CSF drainage site in humans. These data warrant further investigation of brain and nasal contributions to protein clearance in neurodegenerative disease.