Probing Tissue Structures Using Short Diffusion Times

我建议开发和优化一种重要的新方法，用于使用扩散磁共振成像（MRI）区分非常小（~ 1 μm）的组织结构的大小，例如小轴突直径。该方法依赖于探测尽可能短的扩散时间尺度，以便可以检测到最小结构内从受限扩散到受阻扩散的过渡。目前的最先进的方法不能区分这些小结构，因为目前的方法使用脉冲序列，这限制了探测最短扩散时间的能力。我的方法通过使用振荡梯度代替脉冲梯度来规避这些限制。我是使用振荡梯度进行扩散测量的世界级专家。新方法将具有重要的生物学和神经科学应用。 我将扩展OGSE的测量，从研究ADC随扩散时间或频率的变化，到创建一种方法，该方法使用这种变化来推断限制大小，使用尽可能短的扩散时间。该方法克服了当前MR扩散方法（PGSE和q空间）中所需的高梯度强度的问题，并允许区分更小的限制尺寸。我将开发这种方法来推动MRI区分最小可能尺寸的能力。一旦该方法在轴突直径分布测量上得到证实，具有微米级结构灵敏度的MRI新时代将开始。然后，该方法将适用于其他系统，生物系统或其他系统。OGSE和PGSE方法可以一起使用，以区分从非常小（OGSE）到相当大（PGSE）的大范围限制大小。结合这两种方法将允许更完整地理解样品的几何形状。

I propose to develop and optimize an important new method for distinguishing the size of very small (~ 1 µm) tissue structures, such as small axon diameters, using diffusion magnetic resonance imaging (MRI). The method relies on probing the shortest possible diffusion time scales so that the transition from restricted to hindered diffusion within the smallest structures can be detected. Current state-of-the-art methods cannot distinguish these small structures because current methods use pulse sequences which limit the ability to probe the shortest diffusion times. My method circumvents those limitations by using oscillating gradients in place of pulsed gradients. I am a world expert in the use of oscillating gradients for diffusion measurements. The new method will have important biological and neuroscience applications. I will extend the measurements made with OGSE from studying the variation of ADC with diffusion time or frequency to creating a method which uses this variation to infer restriction sizes using the shortest possible diffusion times. This method overcomes problems with high gradient strengths necessary in current MR diffusion methods (PGSE and q-space) and allows smaller restriction sizes to be distinguished. I will develop this method to push the ability of MRI to distinguish the smallest possible sizes. Once the method has been demonstrated on axon diameter distribution measurements, a new era of MRI with sensitivity of micron scale structures will begin. The method will then be adapted to other systems, biological or otherwise. The OGSE and PGSE methods can be used together to distinguish a large range of restriction sizes from very small (OGSE) to fairly large (PGSE). Combining the two methods will allow for a more complete understanding of the geometry of the sample.