Probing Cell Sizes Using Short Diffusion Times

使用短扩散时间探测细胞大小

• 批准号: RGPIN-2018-05422
• 负责人: Martin, Melanie
• 金额: $ 2.99万
• 依托单位: University of Winnipeg
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=658898
• 关键词: Probing; Cell; Sizes; Using; Short

A new magnetic resonance imaging (MRI) technique will be developed with the capability to infer micron-scale restrictions to water diffusion in samples with complicated geometries.******Over the next five years the method will be developed to work on live subjects and extended to use more accurate geometric models of white matter which include orientation dispersion, exchange between compartments and cerebrospinal fluid. In short, the current method uses a simplified model of the geometry of the sample; in our case we model axons in fibres as a distribution of parallel impermeable cylinders of varying diameters. An analytical expression is found for the diffusion of water measured perpendicular to the cylinders as a function of frequency. Data from experiments or Monte Carlo simulations are fitted to this analytical model to obtain the fraction of axons with different diameters.******We will improve the model to include permeable membranes for more accurate results in white matter. With permeable membranes, water molecules can diffuse distances longer than an axon diameter. The failure of the current model to take this into account could skew the results making axons seem larger than they actually are.******We will also surround the axons with myelin bilayers. Myelin lipid bilayers will add more diffusion barriers, the effect of which has not been fully studied. In addition, water within the myelin lipid bilayers has a very short relaxation time compared to water in other parts of the central nervous system. While the myelin will cause more restriction to the signal, the magnetization of the water within the myelin bilayers will relax much quicker possibly to the point that that water does not contribute to the signal. We will find analytical formulae for the model and test the geometries and assumptions with Monte Carlo simulations and corpus callosum and spinal cord samples.******We will also optimize the new method so it will be a key in solving the problem with kissing or crossing fibres in MR tractography. MR tractography uses sophisticated methods collecting images using many gradient directions to determine geometrically whether fibres kiss or cross at junctions. Measuring the axon diameter distributions of fibres on either side of the junction will allow a simple determination of whether the fibres kiss or cross if the two fibres contain axons of different diameters. This is of extreme importance to neuroscience because tractography is being used to understand which regions of the brain are connected to each other. The new method will be optimized in terms of the selection of gradient frequencies, amplitudes, and directions to work at junctions with the goal of making a more accurate and faster method for tractography at junctions.******The method will be verified using white matter, vegetables, and other micron-scale porous samples such as cement and lung airspaces.

将开发一种新的磁共振成像 (MRI) 技术，能够推断出复杂几何形状样品中水扩散的微米级限制。********在未来五年内，该方法将开发用于现场工作受试者并扩展到使用更准确的白质几何模型，其中包括方向分散、隔室和脑脊液之间的交换。简而言之，当前的方法使用样品几何形状的简化模型；在我们的例子中，我们将纤维中的轴突建模为不同直径的平行不渗透圆柱体的分布。找到了垂直于圆柱体测量的水扩散作为频率函数的解析表达式。来自实验或蒙特卡罗模拟的数据适合该分析模型，以获得不同直径的轴突的分数。******我们将改进模型以包括渗透膜，以获得更准确的白质结果。通过渗透膜，水分子可以扩散比轴突直径更长的距离。当前模型未能考虑到这一点可能会扭曲结果，使轴突看起来比实际更大。******我们还将用髓磷脂双层包围轴突。髓磷脂脂质双层会增加更多的扩散屏障，其效果尚未得到充分研究。此外，与中枢神经系统其他部分的水相比，髓磷脂脂质双层内的水的弛豫时间非常短。虽然髓磷脂会对信号造成更多限制，但髓磷脂双层内水的磁化强度会更快地松弛，可能达到水对信号不起作用的程度。我们将找到模型的解析公式，并通过蒙特卡罗模拟和胼胝体和脊髓样本来测试几何形状和假设。******我们还将优化新方法，因此它将成为解决问题的关键MR 纤维束成像中的接吻或交叉纤维。 MR纤维束成像采用复杂的方法收集图像，使用许多梯度方向来从几何角度确定纤维在连接处是否亲吻或交叉。如果两条纤维包含不同直径的轴突，测量连接处两侧纤维的轴突直径分布将允许简单地确定纤维是否接吻或交叉。这对于神经科学极其重要，因为纤维束成像技术被用来了解大脑的哪些区域相互连接。新方法将在交叉口工作的梯度频率、幅度和方向的选择方面进行优化，目标是为交叉口的纤维束成像提供更准确、更快速的方法。******该方法将得到验证使用白质、蔬菜和其他微米级多孔样品（例如水泥和肺空间）。