Keogh B P, Cordes D, Stanberry L, Figler B D, Robbins C A, Tempel B L, Green C G, Emmi A, Maravilla K M, Schwartzkroin P A
Department of Radiology, University of Washington, Mail# 357115, RR-218, Seattle, WA 98195, USA.
Epilepsy Res. 2005 Aug-Sep;66(1-3):75-90. doi: 10.1016/j.eplepsyres.2005.07.008.
To develop a non-invasive method for exploring seizure initiation and propagation in the brain of intact experimental animals.
We have developed and applied a model-independent statistical method--Hierarchical Cluster Analysis (HCA)--for analyzing BOLD-fMRI data following administration of pentylenetetrazol (PTZ) to intact rats. HCA clusters voxels into groups that share similar time courses and magnitudes of signal change, without any assumptions about when and/or where the seizure begins.
Epileptiform spiking activity was monitored by EEG (outside the magnet) following intravenous PTZ (IV-PTZ; n=4) or intraperitoneal PTZ administration (IP-PTZ; n=5). Onset of cortical spiking first occurred at 29+/-16 s (IV-PTZ) and 147+/-29 s (IP-PTZ) following drug delivery. HCA of fMRI data following IV-PTZ (n=4) demonstrated a single dominant cluster, involving the majority of the brain and first activating at 27+/-23s. In contrast, IP-PTZ produced multiple, relatively small, clusters with heterogeneous time courses that varied markedly across animals (n=5); activation of the first cluster (involving cortex) occurred at 130+/-59 s. With both routes of PTZ administration, the timing of the fMRI signal increase correlated with onset of EEG spiking.
These experiments demonstrate that fMRI activity associated with seizure activity can be analyzed with a model-independent statistical method. HCA indicated that seizure initiation in the IV- and IP-PTZ models involves multiple regions of sensitivity that vary with route of drug administration and that show significant variability across animal subjects. Even given this heterogeneity, fMRI shows clear differences that are not apparent with typical EEG monitoring procedures, in the activation patterns between IV and IP-PTZ models. These results suggest that fMRI can be used to assess different models and patterns of seizure activation.
开发一种用于探究完整实验动物大脑中癫痫发作起始和传播的非侵入性方法。
我们已开发并应用了一种与模型无关的统计方法——层次聚类分析（HCA），用于分析向完整大鼠注射戊四氮（PTZ）后获得的血氧水平依赖性功能磁共振成像（BOLD-fMRI）数据。HCA将体素聚类为具有相似时间进程和信号变化幅度的组，而无需对癫痫发作的起始时间和/或位置做任何假设。
静脉注射PTZ（IV-PTZ；n = 4）或腹腔注射PTZ（IP-PTZ；n = 5）后，通过脑电图（在磁体外部）监测癫痫样棘波活动。给药后，皮质棘波的起始分别在29±16秒（IV-PTZ）和147±29秒（IP-PTZ）首次出现。IV-PTZ（n = 4）后fMRI数据的HCA显示出一个单一的主要聚类，涉及大脑的大部分区域，且在27±23秒首次激活。相比之下，IP-PTZ产生多个相对较小的聚类，其时间进程各异，在不同动物之间差异显著（n = 5）；第一个聚类（涉及皮质）的激活发生在130±59秒。两种PTZ给药途径下，fMRI信号增加的时间与脑电图棘波的起始时间相关。
这些实验表明，与癫痫发作活动相关的fMRI活动可用与模型无关的统计方法进行分析。HCA表明，IV-PTZ和IP-PTZ模型中的癫痫发作起始涉及多个敏感区域，这些区域随给药途径而异，且在不同动物个体之间存在显著差异。即便存在这种异质性，fMRI在IV-PTZ和IP-PTZ模型的激活模式上仍显示出典型脑电图监测程序中不明显的明显差异。这些结果表明，fMRI可用于评估不同的癫痫发作激活模型和模式。
