Breuer Heike, Meier Martin, Schneefeld Sophie, Härtig Wolfgang, Wittneben Alexander, Märkel Martin, Ross Tobias L, Bengel Frank M, Bankstahl Marion, Bankstahl Jens P
1 Department of Nuclear Medicine, Hannover Medical School, Hannover, Germany.
2 Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine Hannover and Center for Systems Neuroscience, Hannover, Germany.
J Cereb Blood Flow Metab. 2017 Jun;37(6):2049-2061. doi: 10.1177/0271678X16659672. Epub 2016 Jan 1.
Insult-associated blood-brain barrier leakage is strongly suggested to be a key step during epileptogenesis. In this study, we used three non-invasive translational imaging modalities, i.e. positron emission tomography, single photon emission computed tomography, and magnetic resonance imaging, to evaluate BBB leakage after an epileptogenic brain insult. Sprague-Dawley rats were scanned during early epileptogenesis initiated by status epilepticus. Positron emission tomography and single photon emission computed tomography scans were performed using the novel tracer [Ga]DTPA or [Tc]DTPA, respectively. Magnetic resonance imaging included T2 and post-contrast T1 sequence after infusion of Gd-DTPA, gadobutrol, or Gd-albumin. All modalities revealed increased blood-brain barrier permeability 48 h post status epilepticus, mainly in epileptogenesis-associated brain regions like hippocampus, piriform cortex, thalamus, or amygdala. In hippocampus, Gd-DTPA-enhanced T1 magnetic resonance imaging signal was increased by 199%, [Ga]DTPA positron emission tomography by 37%, and [Tc]DTPA single photon emission computed tomography by 56%. Imaging results were substantiated by histological detection of albumin extravasation. Comparison with quantitative positron emission tomography and single photon emission computed tomography shows that magnetic resonance imaging sequences successfully amplify the signal from a moderate amount of extravasated DTPA molecules, enabling sensitive detection of blood-brain barrier disturbance in epileptogenesis. Imaging of the disturbed blood-brain barrier will give further pathophysiologic insights, will help to stratify anti-epileptogenic treatment targeting blood-brain barrier integrity, and may serve as a prognostic biomarker.
强烈提示，与损伤相关的血脑屏障渗漏是癫痫发生过程中的关键步骤。在本研究中，我们使用了三种非侵入性的转化成像方式，即正电子发射断层扫描、单光子发射计算机断层扫描和磁共振成像，来评估致痫性脑损伤后的血脑屏障渗漏情况。对由癫痫持续状态引发早期癫痫发生过程中的斯普拉格-道利大鼠进行扫描。正电子发射断层扫描和单光子发射计算机断层扫描分别使用新型示踪剂[镓]二乙三胺五乙酸（[Ga]DTPA）或[锝]二乙三胺五乙酸（[Tc]DTPA）进行。磁共振成像包括在注入钆喷酸葡胺、钆布醇或钆白蛋白后进行的T2序列和增强后T1序列。所有成像方式均显示癫痫持续状态后48小时血脑屏障通透性增加，主要发生在与癫痫发生相关的脑区，如海马体、梨状皮质、丘脑或杏仁核。在海马体中，钆喷酸葡胺增强的T1磁共振成像信号增加了199%，[Ga]DTPA正电子发射断层扫描增加了37%，[Tc]DTPA单光子发射计算机断层扫描增加了56%。成像结果通过白蛋白外渗的组织学检测得到证实。与定量正电子发射断层扫描和单光子发射计算机断层扫描的比较表明，磁共振成像序列成功放大了来自适量外渗DTPA分子的信号，从而能够灵敏地检测癫痫发生过程中的血脑屏障紊乱。对受损血脑屏障进行成像将提供进一步的病理生理学见解，有助于对针对血脑屏障完整性的抗癫痫发生治疗进行分层，并且可能作为一种预后生物标志物。
