Development of the Connectome II MRI Scanner

我们正在继续开发基于扩散磁共振成像的新型脉冲序列、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细微结构，这些结构比潜在的磁共振体素大小小三个数量级，目前使用临床磁共振扫描仪是不可见的。具体地说，我们获取的图像的各向同性体素每边约1.5 mm，但试图观察微观物体的特征，如轴突直径和轴突直径分布等，这需要大约1-2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，描述观察到的磁共振信号与各种微结构参数之间的关系。同样重要的是要纠正可能使这些图像模糊或损坏的各种伪像，从而导致对成像量的错误估计。然后，我们试图推断这些信号的生物物理基础。转换到Connectome 2.0的一种方法是AxCaliber MRI，这是我们在NIH发明和开发的一种方法，但它在传统MRI扫描仪上的分辨率有限。新的Connectome 2.0扫描仪允许人们以更高的精确度和精确度检测轴突直径分布。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。这提供了有关水在活体脑组织中所处的不同微环境的信息。我们转换到Connectome扫描仪的另一种方法是时间缩放MRI，它需要获得不同扩散时间的平均表观传播因子(MAP)MRI数据。这种方法允许我们推断分级组织的某些特征，例如我们可以利用来提供介观和微观信息的分维。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，其中一些方法是我们之前在实验室开发的，我们正在进行广泛的审查，并努力移植到这个强大的新临床扫描平台。我们开创的一种新的mPFG方法是扩散张量分布(DTD)磁共振成像，我们用它来研究体素内水扩散的非均质性。这一努力在实验设计、处理的计算速度以及通过支撑数学基础方面都得到了极大的加强。我们还一直在开发猕猴和绒猴脑图谱，这使得组织图像数据可以合并，并与相同区域的MRI数据进行比较，使我们能够测试和审查我们开发的各种MRI方法。在接下来的几年里，将需要更多的审查和测试，以确保我们的采集和建模管道的准确性和精确度，以便它们准备好在这笔赠款的未来几年用于临床实施和测试，因为原型Connectome 2.0扫描仪已经交付，并准备好扫描正常志愿者和临床受试者。

We are continuing to develop novel diffusion MRI-based pulse sequence, acquisition, and signal modeling frameworks 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 MRI voxel size, and which are currently invisible using clinical MRI scanners. 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 1-2 microns. One way we accomplish this feat is to develop advanced mathematical/physical models describing the relationship between the observed MR signal and various microstructural parameters. 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 axon diameter distributions with greater precision and accuracy. 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 organization, such as the fractal dimension 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 pioneered is diffusion tensor distribution (DTD) MRI, which we use to study the heterogeneity of water diffusion within a voxel. This effort has been greatly enhanced in terms of experimental design, computational speed of processing, and by shoring up mathematical underpinnings. We have also been developing macaque and marmoset brain atlases, which allow histological image data to be merged and compared with MRI data of the same areas 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, now that the prototype Connectome 2.0 scanner has been delivered and is ready for scanning normal volunteers and clinical subjects.