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微米)组织结构的大小，例如小轴突直径。该方法依赖于探测可能的最短扩散时间尺度，从而可以检测到在最小结构内从受限扩散到受阻扩散的转变。目前最先进的方法无法区分这些小结构，因为当前方法使用的脉冲序列限制了探测最短扩散时间的能力。我的方法绕过了这些限制，用振荡梯度代替脉冲梯度。我是使用振荡梯度进行扩散测量的世界专家。这种新方法将在生物和神经科学方面有重要的应用。 我将把用OGSE进行的测量从研究ADC随扩散时间或频率的变化扩展到创建一种方法，该方法利用这种变化来推断使用尽可能短的扩散时间的限制大小。这种方法克服了当前MR扩散方法(PGSE和Q空间)所需的高梯度强度的问题，并允许区分较小的限制尺寸。我将开发这一方法，以推动MRI区分最小尺寸的能力。一旦该方法在轴突直径分布测量上被证明，具有微米级结构灵敏度的MRI的新时代将开始。然后，该方法将适用于其他系统，无论是生物系统还是其他系统。OGSE和PGSE方法可以一起用于区分从非常小(OGSE)到相当大(PGSE)的大范围的限制大小。将这两种方法结合起来，可以更全面地了解样品的几何结构。

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.