MRI T2 and T2* relaxometry to visualize neuromelanin in the dorsal substantia nigra pars compacta
MRI T2 and T2* relaxometry to visualize neuromelanin in the dorsal substantia nigra pars compacta
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DOI：
10.1016/j.neuroimage.2020.116625
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发表时间：
2020-05-01
期刊：
影响因子：
5.7
通讯作者：
Cho, HyungJoon
中科院分区：
文献类型：
--
作者：
Lee, Hansol;Baek, Sun-Yong;Cho, HyungJoon
可视化黑质内神经黑色素分布的逐渐变化是用于监测帕金森病进展的重要指标。本研究旨在确定黑质中磁共振横向弛豫时间（T-2 和 T-2*）之间不匹配区域的起源，并研究其对体内检测神经黑色素作为临床生物标志物的可行性和影响。在死后收集的两块正常黑质和一块脱色黑质中，直接比较通过组织学染色评估的神经黑色素分布与通过 7T 高分辨率和低分辨率磁共振弛豫测量确定的 T-2 和 T-2* 不匹配面积之间的关系。使用 3T 磁共振成像研究了临床上评估 T-2 和 T-2* 不匹配的体内可行性。在正常死后黑质组织中，表现出线性模式的 T-2 和 T-2* 错配区域与沿黑质致密部的神经黑色素分布强烈共定位，但在脱色的大脑中观察到可忽略不计的背侧错配。对于正常死后大脑，MRI 中的 T-2 和 T-2* 不匹配区域、组织学中的神经黑色素色素以及质谱中铁信号升高的区域在空间上重叠。在初步体内研究中，在八名正常受试者的黑质背侧区域观察到类似的线性 T-2 和 T-2* 错配区域；这种不匹配在八名帕金森病患者中被显着掩盖。与正常对照相比，帕金森病患者基于 T-2*-T-2 模板的背侧线性错配线的长度明显较短；通过正电子发射断层扫描评估的[F-18] FP-CIT多巴胺转运蛋白纹状体摄取减少证实了这一结果。总之，T-2 和 T-2* 不匹配的测量可以作为补充成像生物标志物，以可视化含有大量神经黑色素的黑质致密部背部区域。
Visualizing gradual changes in neuromelanin distribution within the substantia nigra is an important metric used to monitor the progression of Parkinsonism. This study aimed to identify the origin of the mismatch region between magnetic resonance transverse relaxation times (T-2 and T-2*) in the substantia nigra and investigate its feasibility and implications for in vivo detection of neuromelanin as a clinical biomarker. The relationships between neuromelanin distribution assessed by histological staining and the area of T-2 and T-2* mismatch determined by high- and low-resolution magnetic resonance relaxometry at 7T were directly compared in two normal and one depigmented substantia nigra collected at postmortem. In vivo feasibility of assessing T-2 and T-2* mismatch, clinically, was investigated using 3T magnetic resonance imaging. In the normal postmortem substantia nigra tissue, the T-2 and T-2* mismatch region exhibiting a linear pattern was strongly colocalized with neuromelanin distribution along the dorsal substantia nigra pars compacta, but a negligible amount of dorsal mismatch was observed in the depigmented brain. The regions of T-2 and T-2* mismatch from MRI, neuromelanin pigments from histology, and elevated iron signals from mass spectrometry were spatially overlapped for a normal postmortem brain. In preliminary in vivo studies, a similar, linear T-2 and T-2* mismatch region was observed in the dorsal area of the substantia nigra in eight normal subjects; this mismatch was significantly obscured in eight Parkinson's disease patients. The length of the dorsal linear mismatch line based on the T-2*-T-2 mask was significantly shorter in the Parkinson's disease patients compared to normal controls; this result was corroborated by reduced striatal uptake of [F-18] FP-CIT dopamine transporters assessed by positron emission tomography scans. In conclusion, the measurement of T-2 and T-2* mismatch could serve as a complementary imaging biomarker to visualize the dorsal region of the substantia nigra pars compacta, which contains large amounts of neuromelanin.