Advancing and calibrating anisotropic diffusion MR imaging brain connectome with Taxon brain network diffusion phantoms

各向异性扩散磁共振成像(AdMRI)的可靠性存在很大差距。这一差距可以是 通过使用地面真实测量能力来填充，允许对填充的水进行必要的参数控制 微米级的管的几何形状，它可以产生代表数百万条横跨厘米的轴突的路径 脑部轨迹。弥散张量成像(DTI)出版物报告了临床上显著的系统误差 混淆了不同工具和时间的准确定量评估。提供精确误差的参考模体 度量学将促进MRI生物物理科学和临床定量准确性的提高。使用参考数据的校正算法 可以减少系统测量误差，实现准确的可重复测量，并提供交叉扫描仪规范 做ADMRI病理学检查。该项目将提供第一个可行的admri幻象“地面真相”使用‘Taxons™’(纺织品 轴突状纳米管)，并应用先进的双组分聚合物纳米级生产方法 创造出与人类组织学相匹配的结构。在这样做的过程中，我们将提供800纳米的轴突规模的分类单元 直径，堆积密度为100万个分类单位/mm2，与实际的人类愈伤组织轴突相匹配 测量。在第一阶段，我们提出并交付了12微米内径管的分类群，填充密度为 每平方毫米1241个，可以充满水并产生人体组织范围内的FA测量。我们实际上“结束了- 超过了覆盖人类轴突组织范围的每平方毫米1,000,000的堆积密度。我们现在可以 精确地参数控制直径、堆积密度、受限/受阻和各向同性含水率，以测试和 改进领先的扩散区隔模式。我们创造了一台束状布线机，它可以以可行的成本创建 人类鳞片束路径与人类组织相匹配，例如视觉系统眼到LGN，由2000万个被路由的分类单元组成。 1到1比例分类网络模体量化具有100微米路径的每个分类单元路径的dMRI测量精度 沿着弹道精确定位。我们扫描了十个地点的第一阶段幻影。我们在实证研究中证实， 是否存在相当大的系统、跨仪器和测量误差(例如，5倍于TBI效应大小)，误差是稳定的，以及 可进行校正(消除94%的系统误差)。该项目的第二阶段将：1)提供第一个AdMRI体模 用于地面真实测量，以量化dMRI生物物理、空间均质性和布线精度；2)提供充分的 自动量化测量的准确性和可重复性；3)评估20多个部位的AdMRI精度，量化 1.5、3、7、9.4和14T场强下的测量误差；以及4)开发一组布线模体(Eye&GT；LGN&GT；V1，脊柱 脊髓和皮质束)。这些模体和/或子组件将使用非MRI方法(共焦和 电子显微镜)使用NIST可追溯测量。参与第一阶段扫描的研究人员和中心主任 对结果的评价非常积极，有30多个网站提供免费扫描时间来使用该幻影，并利用 由此产生的质量保证报告。放射学已经取得了基于体模的关键成功(即CT Hounsfield体模 20世纪90年代)。该项目将提供一个量化的AdMRI体模，使MRI指标在 供应商和实施量化质量保证(QQA)的时间。

There is a critical gap in the reliability of anisotropic diffusion magnetic resonance imaging (AdMRI). This gap can be filled by using a ground truth measurement capability that allows for the necessary parametric control of water filled geometries of tubes at the micron scale that can produce paths representative of the millions of axons across centimeters in brain tract trajectories. Diffusion Tensor Imaging (DTI) publications report clinically significant systematic error that confounds accurate quantitative assessments across instruments and time. Reference phantoms that provide exact error metrics will advance MRI biophysics science and clinical quantitative accuracy. Correction algorithms using reference data can reduce systematic measurement error, enabling accurate reproducible measurement and provide cross scanner norms for AdMRI pathology. This project will deliver the first viable AdMRI phantom “ground truth” using ‘Taxons™’ (textile axon shaped nanotubes), invented by this team, and apply advanced bi-component polymer nanoscale production methods to create structures matched to human tissue histology. In doing this we will deliver axon scale taxons at 800 nanometer diameter, with a packing density of one million taxons per mm2, matched to actual human corpus callosum axon measurements. In Phase I we proposed and delivered taxons with 12 micron inner diameter tubes with a packing density of 1241 per mm2 that could be filled with water and produce FA measurement in the human tissue range. We actually “over- delivered”, exceeding a packing density of 1,000,000 per mm2 covering the human axonal tissue range. We can now precisely parametrically control the diameters, packing density, restricted/hindered, and isotropic water fractions to test and improve leading compartmental models of diffusion. We created a fasciculus routing machine that can, at viable cost, create human scale fasciculus routes matched to human tissue, such as the optic system eye to LGN, of 20 million routed taxons. The 1 to 1 scale taxonal network phantoms quantify dMRI measurement accuracy for each taxon path with 100 micron path precision along the trajectory. We scanned the phase I phantoms at ten sites. We established in empirical studies that there is substantial systematic, cross instrument and measurement error (e.g., 5x the TBI effect size), that the error is stable, and can be corrected for (removed 94% of systematic error). Phase II of this project will: 1) provide the first AdMRI phantom for ground truth measurement to quantify dMRI biophysics, spatial homogeneity, and routing precision; 2) provide fully automated quantification of accuracy and repeatability of measurement; 3) assess AdMRI precision of 20+ sites, quantifying measurement error at 1.5, 3, 7, 9.4 and 14T field strength; and4) develop a set of routing phantoms (Eye>LGN> V1, spinal cord and cortical tracts). These phantoms and/or subcomponents will be measured with non-MRI methods (confocal & electron microscope) using NIST traceable measurements. Researchers and center directors involved in Phase I scanning and reviewing of the results were very positive, with 30+ sites offering free scanning time to use the phantom, and to utilize the resulting quality assurance reports. Radiology has had phantom based pivotal successes (i.e., CT Hounsfield phantoms in the 1990s). This project will deliver a quantitative AdMRI phantom, enabling MRI metrics to become accurate across vendors and time implementing quantitative quality assurance (QQA).