磁共振成像（MRI）是我们观察难以用X射线成像的柔软水状组织的方式。但是，虽然MRI提供了足够好的分辨率来发现脑肿瘤，但它需要更加清晰才能可视化大脑内的微观细节，从而揭示其组织。
在杜克大学体内显微镜中心与田纳西大学健康科学中心、宾夕法尼亚大学、匹兹堡大学和印第安纳大学的同事领导的长达数十年的技术巡回赛中，研究人员接受了挑战，提高了MRI的分辨率，从而获得了有史以来最清晰的小鼠大脑图像。
恰逢第一台MRI问世50周年，研究人员对小鼠大脑的扫描结果比人类的典型临床MRI清晰得多，相当于从像素化的8位图形到Chuck Close绘画的超现实细节。
新图像的单个体素（将其视为立方像素）的尺寸仅为5微米。这比临床MRI体素小64万倍。
尽管研究人员将磁铁集中在小鼠而不是人类身上，但改进的MRI提供了一种重要的新方法，以破纪录的分辨率可视化整个大脑的连接。研究人员表示，小鼠成像的新见解将反过来导致更好地了解人类的状况，例如大脑如何随着年龄，饮食甚至阿尔茨海默氏症等神经退行性疾病而变化。
“这是真正令人振奋的事情。我们可以开始以完全不同的方式研究神经退行性疾病，“新论文的主要作者，杜克大学查尔斯·E·普特曼大学放射学，物理学和生物医学工程杰出教授G. Allan Johnson博士说。
约翰逊的兴奋是很久了。该团队的新工作于17月40日发表在《美国国家科学院院刊》上，是杜克体内显微镜中心近<>年研究的高潮。
在过去的四十年里，约翰逊、他的工程研究生以及他在杜克大学和远方的许多合作者改进了许多元素，当所有这些元素结合在一起时，使革命性的MRI分辨率成为可能。
一些关键成分包括令人难以置信的强大磁铁（大多数临床MRI依赖于1.5至3特斯拉磁铁;约翰逊的团队使用9.4特斯拉磁铁），一组特殊的梯度线圈，比临床MRI中的线圈强100倍，有助于生成大脑图像，以及相当于近800台笔记本电脑的高性能计算机，所有这些都启动成像一个大脑。
在约翰逊和他的团队“扫描出日光”后，他们发送组织，使用一种称为光片显微镜的不同技术进行成像。这种互补技术使他们能够标记大脑中的特定细胞组，例如多巴胺释放细胞，以观察帕金森病的进展。
The team then maps the light sheet pictures, which give a highly accurate look at brain cells, onto the original MRI scan, which is much more anatomically accurate and provides a vivid view of cells and circuits throughout the entire brain.
With this combined whole brain data imagery, researchers can now peer into the microscopic mysteries of the brain in ways never possible before.
One set of MRI images shows how brain-wide connectivity changes as mice age, as well as how specific regions, like the memory-involved subiculum, change more than the rest of the mouse's brain.
Another set of images showcases a spool of rainbow-colored brain connections that highlight the remarkable deterioration of neural networks in a mouse model of Alzheimer's disease.
The hope is that by making the MRI an even higher-powered microscope, Johnson and others can better understand mouse models of human diseases, such as Huntington's disease, Alzheimer's, and others. And that should lead to a better understanding of how similar things function or go awry in people.
"Research supported by the National Institute of Aging uncovered that modest dietary and drug interventions can lead to animals living 25% longer," Johnson said. "So, the question is, is their brain still intact during this extended lifespan? Could they still do crossword puzzles? Are they going to be able to do Sudoku even though they're living 25% longer? And we have the capacity now to look at it. And as we do so, we can translate that directly into the human condition."
More information: G. Allan Johnson et al, Merged magnetic resonance and light sheet microscopy of the whole mouse brain, Proceedings of the National Academy of Sciences (2023). DOI: 10.1073/pnas.2218617120
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