Verma Ajay, Hesterman Jacob Y, Chazen J Levi, Holt Robert, Connolly Patrick, Horky Laura, Vallabhajosula Shankar, Mozley P David
Codiak Biosciences Cambridge Massachusetts.
inviCRO Boston Massachusetts.
Alzheimers Dement (Amst). 2020 Apr 29;12(1):e12030. doi: 10.1002/dad2.12030. eCollection 2020.
Cerebrospinal fluid (CSF) molecular exchange with brain interstitial fluid (ISF) and periphery is implicated in neurological disorders but needs better quantitative clinical assessment approaches.
Following intrathecal (ITH) dosing via lumbar puncture, Technetium-99 m (Tc-) diethylenetriaminepentaacetic acid (DTPA) imaging was used to quantify neuraxial spread, CSF-brain molecular exchange, and CSF-peripheral clearance in 15 normal human volunteers. The effect of experimental convection manipulation on these processes was also assessed.
Rostral cranial Tc-DTPA exposures were influenced by the volume of artificial CSF in the formulation. Signal translocation to the cranial cisterns and the brain parenchyma was observable by 3 hours. Tc-DTPA penetrated cortical ISF but showed lower signal in deeper structures. Urinary Tc-DTPA signal elimination was accelerated by higher formulation volumes and mechanical convection.
Widely used for detecting CSF leaks, ITH Tc-DTPA imaging can also become a useful clinical biomarker for measuring molecular exchange physiology between the CSF, brain, and periphery.
脑脊液(CSF)与脑间质液(ISF)及外周之间的分子交换与神经系统疾病有关,但需要更好的定量临床评估方法。
通过腰椎穿刺进行鞘内(ITH)给药后,利用锝-99m(Tc-)二乙三胺五乙酸(DTPA)成像对15名正常人类志愿者的神经轴扩散、脑脊液-脑分子交换和脑脊液-外周清除进行定量分析。还评估了实验性对流操作对这些过程的影响。
头侧颅骨的Tc-DTPA暴露受制剂中人工脑脊液体积的影响。3小时时可观察到信号转移至脑池和脑实质。Tc-DTPA穿透皮质ISF,但在深部结构中信号较低。较高的制剂体积和机械对流加速了尿中Tc-DTPA信号的消除。
ITH Tc-DTPA成像广泛用于检测脑脊液漏,也可成为测量脑脊液、脑和外周之间分子交换生理学的有用临床生物标志物。