Probing Cell Sizes Using Short Diffusion Times

将开发一种新的磁共振成像（MRI）技术，该技术能够推断具有复杂几何形状的样品中对水扩散的微米级限制。在接下来的五年里，该方法将被开发用于活体研究，并扩展到使用更精确的白色物质几何模型，包括方向分散、隔室和脑脊液之间的交换。简而言之，目前的方法使用一个简化的模型的几何形状的样品，在我们的情况下，我们的模型轴突在纤维作为一个分布的平行的不可渗透的圆柱体的直径不同。一个解析表达式被发现作为频率的函数的水的扩散测量垂直于圆柱。将来自实验或蒙特卡罗模拟的数据拟合到该分析模型，以获得具有不同直径的轴突的分数。我们将改进模型，以包括渗透膜，从而在白色物质中获得更准确的结果。通过渗透膜，水分子可以扩散比轴突直径更长的距离。目前的模型没有考虑到这一点，可能会扭曲结果，使轴突看起来比实际更大。我们还将用髓鞘双层包围轴突。髓鞘脂质双层将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中的水相比，髓磷脂脂质双层中的水具有非常短的弛豫时间。虽然髓磷脂会对信号造成更多的限制，但髓磷脂双层内的水的磁化会更快地松弛，可能达到水对信号没有贡献的程度。我们将找到模型的分析公式，并使用Monte Carlo模拟和胼胝体和脊髓样本测试几何形状和假设。我们还将优化新的方法，使其成为解决磁共振纤维束成像中的吻或交叉纤维问题的关键。磁共振纤维束成像使用复杂的方法收集图像，使用许多梯度方向，以确定几何纤维是否亲吻或交叉的交界处。如果两个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触或交叉。这对神经科学来说非常重要，因为纤维束描记术被用来了解大脑的哪些区域是相互连接的。新方法将在选择梯度频率、振幅和方向方面进行优化，以在交叉点处工作，目标是在交叉点处进行纤维束成像更准确、更快速。该方法将使用白色物质、蔬菜和其他微米级多孔样品（如水泥和肺空间）进行验证。

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.