Validation of diffusion tensor imaging measures of nigrostriatal neurons in macaques
Validation of diffusion tensor imaging measures of nigrostriatal neurons in macaques
复制标题
DOI：
10.1371/journal.pone.0202201
复制
发表时间：
2018-09-05
期刊：
影响因子：
3.7
通讯作者：
Perlmutter, Joel S.
中科院分区：
文献类型：
--
作者：
Shimony, Joshua S.;Rutlin, Jerrel;Perlmutter, Joel S.
目的对活体脑弥散MRI的解释需要对金标准组织学测量进行验证。我们比较了由MPTP（一种多巴胺能神经元选择性毒素）引起的不同程度单侧黑质纹状体损伤的非人灵长类动物（NHPs）的PET扩散值和组织学结果。方法16例NHPs在单侧颈动脉注射可变剂量MPTP前后对3种不同的突触前放射配体进行MRI和PET扫描，并进行盲法视频运动评分。计算中脑与纹状体连接的扩散量。然后对动物实施安乐死，定量纹状体多巴胺浓度、纹状体酪氨酸羟化酶（TH）免疫染色纤维密度的体视测量以及TH染色的黑质细胞的无偏体视计数。结果弥散测量与MPTP剂量、黑质th阳性细胞体和纹状体th阳性纤维密度相关，但与体外黑质纹状体终端场测量或体内PET测量纹状体突触前标记物摄取无关。一旦黑质TH细胞计数损失超过50%，体视终端场测量接近零底效应，但扩散测量继续与黑质细胞计数相关。结论黑质纹状体束弥散测量与多巴胺神经元和纹状体纤维密度相关，但与突触前神经元纹状体PET测量的终末场测量关系相同。这些扩散测量有可能作为黑质纹状体损伤严重程度的非侵入性指标。黑质纹状体束弥散成像可能对帕金森病或相关疾病有潜在的诊断价值。
ObjectiveInterpretation of diffusion MRI in the living brain requires validation against gold standard histological measures. We compared diffusion values of the nigrostriatal tract to PET and histological results in non-human primates (NHPs) with varying degrees of unilateral nigrostriatal injury induced by MPTP, a toxin selective for dopaminergic neurons.MethodsSixteen NHPs had MRI and PET scans of three different presynaptic radioligands and blinded video-based motor ratings before and after unilateral carotid artery infusion of variable doses of MPTP. Diffusion measures of connections between midbrain and striatum were calculated. Then animals were euthanized to quantify striatal dopamine concentration, stereologic measures of striatal tyrosine hydroxylase (TH) immunostained fiber density and unbiased stereologic counts of TH stained nigral cells.ResultsDiffusion measures correlated with MPTP dose, nigral TH-positive cell bodies and striatal TH-positive fiber density but did not correlate with in vitro nigrostriatal terminal field measures or in vivo PET measures of striatal uptake of presynaptic markers. Once nigral TH cell count loss exceeded 50% the stereologic terminal field measures reached a near zero floor effect but the diffusion measures continued to correlate with nigral cell counts.ConclusionDiffusion measures in the nigrostriatal tract correlate with nigral dopamine neurons and striatal fiber density, but have the same relationship to terminal field measures as a previous report of striatal PET measures of presynaptic neurons. These diffusion measures have the potential to act as non-invasive index of the severity of nigrostriatal injury. Diffusion imaging of the nigrostriatal tract could potentially have diagnostic value in humans with Parkinson disease or related disorders.