Schaeffer David J, Adam Ramina, Gilbert Kyle M, Gati Joseph S, Li Alex X, Menon Ravi S, Everling Stefan
Robarts Research Institute, University of Western Ontario, London, Ontario, Canada; and.
Graduate Program in Neuroscience, University of Western Ontario, London, Ontario, Canada.
J Neurophysiol. 2017 Aug 1;118(2):1344-1354. doi: 10.1152/jn.00259.2017. Epub 2017 Jun 14.
The common marmoset () is a small New World primate that is becoming increasingly popular in the neurosciences as an animal model of preclinical human disease. With several major disorders characterized by alterations in neural white matter (e.g., multiple sclerosis, Alzheimer's disease, schizophrenia), proposed to be transgenically modeled using marmosets, the ability to isolate and characterize reliably major white matter fiber tracts with MRI will be of use for evaluating structural brain changes related to disease processes and symptomatology. Here, we propose protocols for isolating major white matter fiber tracts in the common marmoset using in vivo ultrahigh-field MRI (9.4T) diffusion-weighted imaging (DWI) data. With the use of a high angular-resolution DWI (256 diffusion-encoding directions) sequence, collected on four anesthetized marmosets, we provide guidelines for manually drawing fiber-tracking regions of interest, based on easily identified anatomical landmarks in DWI native space. These fiber-tract isolation protocols are expected to be experimentally useful for visualization and quantification of individual white matter fiber tracts in both control and experimental groups of marmosets (e.g., transgenic models). As disease models in the marmoset advance, the determination of how macroscopic white matter anatomy is altered as a function of disease state will be relevant in bridging the existing translational gap between preclinical rodent models and human patients. Although significant progress has been made in mapping white matter connections in the marmoset brain using ex vivo tracing techniques, the application of in vivo virtual dissection of major white matter fiber tracts has been established by few studies in the marmoset literature. Here, we demonstrate the feasibility of whole-brain diffusion-weighted tractography in anesthetized marmosets at ultrahigh-field MRI (9.4T) and propose protocols for isolating nine major white matter fiber tracts in the marmoset brain.
普通狨猴()是一种小型新大陆灵长类动物,在神经科学领域作为临床前人类疾病的动物模型正变得越来越受欢迎。有几种以神经白质改变为特征的主要疾病(如多发性硬化症、阿尔茨海默病、精神分裂症),提议使用狨猴进行转基因建模,利用磁共振成像(MRI)可靠地分离和表征主要白质纤维束的能力将有助于评估与疾病进程和症状学相关的脑结构变化。在此,我们提出了使用体内超高场MRI(9.4T)扩散加权成像(DWI)数据在普通狨猴中分离主要白质纤维束的方案。通过在四只麻醉的狨猴身上采集的高角分辨率DWI(256个扩散编码方向)序列,我们基于DWI原始空间中易于识别的解剖标志,提供了手动绘制纤维追踪感兴趣区域的指南。这些纤维束分离方案预计在实验上对狨猴对照组和实验组(如转基因模型)中单个白质纤维束的可视化和定量有用。随着狨猴疾病模型的发展,确定宏观白质解剖结构如何随疾病状态而改变,将有助于弥合现有的临床前啮齿动物模型与人类患者之间的转化差距。尽管使用离体追踪技术在狨猴脑中绘制白质连接方面已经取得了重大进展,但在狨猴文献中,很少有研究建立主要白质纤维束的体内虚拟解剖应用。在此,我们展示了在超高场MRI(9.4T)下对麻醉的狨猴进行全脑扩散加权纤维束成像的可行性,并提出了在狨猴脑中分离九条主要白质纤维束的方案。