Development of the Connectome II MRI Scanner

Connectome II MRI 扫描仪的开发

• 批准号: 10915333
• 负责人: PETER J. BASSER
• 金额: $ 47.02万
• 依托单位: EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10915333
• 关键词: Architecture; Area; Atlases; Axon; BRAIN initiative; Biophysics; Brain; Brain imaging; Callithrix; Clinical; Data; Development; Diameter; Diffusion; Diffusion Magnetic Resonance Imaging; Dimensions; Ensure; Experimental Designs; Family; Fractals; Funding; Goals; Grant; Heterogeneity; Human; Image; Imaging Device; Infrastructure; Intramural Research Program; Laboratories; Macaca; Magnetic Resonance Imaging; Mathematics; Measures; Methodology; Methods; Microscopic; Modeling; Morphologic artifacts; National Institute of Child Health and Human Development; Noise; Performance; Physiologic pulse; Research Personnel; Resolution; Role; Scanning; Side; Signal Transduction; Structure; Testing; Time; Tissues; Translating; United States National Institutes of Health; Water; brain tissue; clinical implementation; clinical translation; connectome; histological image; image processing; in vivo; invention; magnetic field; mathematical model; migration; novel; physical model; processing speed; prototype; research clinical testing; volunteer; water diffusion

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.

我们正在继续开发新的基于扩散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MRI体素尺寸小三个数量级，并且目前使用临床MRI扫描仪不可见。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1 - 2微米的空间分辨率。我们实现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。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扫描仪允许以更高的精度和准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层次组织组织的某些特征，例如我们可以用来提供介观和微观信息的分形维数。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方法是扩散张量分布（DTD）MRI，我们使用它来研究体素内水扩散的异质性。这一努力在实验设计、处理的计算速度和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的大脑图谱，它允许将组织学图像数据与相同区域的MRI数据进行合并和比较，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，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，以便它们在该资助的“淘汰期”准备好进行临床实施和测试，现在原型Connectome 2.0扫描仪已经交付，并准备用于扫描正常志愿者和临床受试者。