Development of the Connectome II MRI Scanner

我们正在开发一种新的基于扩散MRI的脉冲序列，采集和信号建模框架，使我们能够“看到”或检测活体人脑中的精细尺度结构，这些结构比底层体素大小小三个数量级，并且目前使用临床MRI技术是不可见的。具体地说，我们获取具有每侧约1.5mm的各向同性体素的图像，但试图观察微观物体的特征，例如轴突直径和轴突直径分布等，其需要大约2微米的空间分辨率。我们完成这一壮举的一种方法是开发先进的数学/物理模型，描述所观察到的MR信号和各种微结构参数之间的关系进行调查。同样重要的是要纠正各种可能模糊或破坏这些图像的伪影，从而导致成像量的不正确估计。然后，我们试图推断这些信号的生物物理基础。一种转换到Connectome 2.0的方法是AxCaliber MRI，这是我们在NIH发明和开发的一种方法，但在传统MRI扫描仪上的分辨率有限。新的Connectome 2.0扫描仪允许检测具有更细轴突直径的轴突。我们正在迁移的另一种方法是平均表观传播因子（MAP）MRI，这是一种测量组织中扩散水分子的净位移分布或平均传播因子的方法。这提供了关于水在活脑组织内发现自己的不同微环境的信息。我们将其转化为Connectome扫描仪的另一种方法是时间缩放MRI，这需要在不同的扩散时间获得平均表观扩散因子（MAP）MRI数据。这种方法使我们能够推断出某些功能的分层组织组织，如可能的分形维数的组织，我们可以利用提供介观和微观尺度的信息。我们还在研究用于临床翻译的各种多脉冲场梯度（mPFG）MRI方法，其中一些我们以前在实验室中开发过，我们正在广泛审查，并致力于迁移到这个强大的新临床扫描平台。我们开创的一种新的mPFG方法是一种估计每个体素内扩散张量分布（DTD）的方法，可用于研究水传输过程的异质性。这在实验设计、处理的计算速度和支撑其数学基础方面都有了很大的提高。我们也一直在开发NHP图谱，允许组织学图像数据与MRI数据合并和比较，使我们能够测试和审查我们开发的各种MRI方法。在未来几年中，将需要进行更多的审查和测试，以确保我们的采集和建模管道的准确性和精度，以便在该补助金的“淘汰期”为临床实施和测试做好准备，届时原型Connectome 2.0扫描仪将完成并准备用于正常志愿者和临床受试者的扫描。

We are developing a novel diffusion MRI-based pulse sequence, acquisition, and signal modeling framework to enable us to "see" or detect fine-scale structures in the living human brain that are three orders of magnitude smaller than the underlying voxel size, and which are currently invisible using clinical MRI techniques. To be concrete, we acquire images with isotropic voxels that are about 1.5 mm on each side, but attempt to observe features of microscopic objects, such as axon diameters and axon diameter distributions, etc., which require a spatial resolution of about 2 microns. One way we accomplish this feat is to develop advanced mathematical/physical models describing the relationship between the observed MR signal and the various microstructural parameters under investigation. It is also important to correct for various artifacts that can blur or corrupt these images, leading to incorrect estimates of imaging quantities. Then, we attempt to infer the biophysical basis of these signals. One method to translate to the Connectome 2.0 is AxCaliber MRI, an approach we invented and developed at the NIH, but which was limited in its resolution on conventional MRI scanners. The new Connectome 2.0 scanner allows one to detect axons with finer axon diameters. Another approach we are migrating is mean apparent propagator (MAP) MRI, a method that measures the net displacement distribution or average propagator of diffusing water molecules in tissue. This provides information about the different microenvironments water finds itself in within living brain tissue. Another approach we translating to the Connectome scanner is Time-Scaling MRI, which entails obtaining Mean Apparent Propagator (MAP) MRI data at different diffusion times. This approach allows us to infer certain features of hierarchical tissue organizations, such as the possible fractal dimension of tissues, that we can exploit to provide mesoscopic and microscale information. We also are investigating various multiple-pulsed field gradient (mPFG) MRI methods for clinical translation, some of which we have previously developed in our lab, which we are extensively vetting, and working to migrate to this powerful new clinical scanning platform. A new mPFG methodology we have been pioneering is a way to estimate the diffusion tensor distribution (DTD) within each voxel, which can be used to study the heterogeneity of water transport processes. This has been greatly enhanced in terms of experimental design, computational speed of processing, and shoring up its mathematical underpinnings. We have also been developing NHP atlases that allow histological image data to be merged and compared with MRI data to enable us to test and vet various MRI methods we develop. In the coming years, much additional vetting and testing will be required to ensure the accuracy and precision of our acquisition and modeling pipelines so that they are ready for clinical implementation and testing in the "out years" of this grant, when the prototype Connectome 2.0 scanner will be completed and ready for scanning of normal volunteers and clinical subjects.