Diffusion magnetic resonance imaging techniques for microscopic tissue characterization

组织学图像提供微观信息，但仅限于小组织体积的静态图像。磁共振成像(MRI)以更大的视野检查活组织，但分辨率太低，无法看到单个细胞。然而，MRI的信号强度对显微特征很敏感。例如，扩散磁共振成像对水的运动很敏感，包括它与周围结构的相互作用。很难将信号与特定的特征联系起来，因为许多因素都会影响信号。这项工作提出了两种先进的扩散磁共振技术和新的分析方法来提取与水交换率、细胞大小分布和纤维模式相关的参数。第一种扩散磁共振方法探索更长的扩散时间，从而减缓扩散过程，例如水穿过细胞膜。由于T2弛豫过程，长时间在常规扩散中的信号较低。该方法沿纵轴方向存储磁化强度，以保存信号。此外，没有简单的方程来分析水交换，因此我们建议使用数值方法。这些将首先应用于急性髓系白血病细胞，此前已使用基于造影剂的方法表征了水交换，因此该系统可用于验证扩散测量。然后，将评估乳房细胞中的水交换。第二种扩散方法检查体素内的纤维模式。当纤维结构高度排列(高各向异性)时，常规扩散对水的运动方向的差异很敏感。低各向异性很难解释；它可能是由于缺少纤维或在不同方向展开的纤维造成的。我们将使用一个新出现的磁共振序列，其中扩散梯度在不同方向随时间变化，以揭示微观水平上关于各向异性的新信息。这种方法识别大脑中的交叉纤维，但需要一种新的方案和分析方法来识别其他组织。例如，目前还没有分析这一序列的方法包含限制水，这将研究限制在小结构和有限的扩散权重上。我们的分析方法结合了限制，因此适用于更广泛的组织和扩散参数。这将在生长在不同纤维密度和排列的胶原支架中的乳房细胞上进行测试，并与组织学进行比较。该计划将为乳腺组织的显微特征的非侵入性表征提供一个经过验证的工具，可以复制到检查其他组织类型。这是一种体内方法，覆盖了大范围的视野，以产生目前组织学无法获得的信息。它有可能为研究细胞凋亡、伤口愈合过程中的胶原纤维重新定位以及其他与细胞及其周围环境的结构变化有关的过程提供新的见解。

Histological images provide microscopic information but are limited to static pictures from small tissue volumes. Magnetic resonance imaging (MRI) examines living tissues with larger fields-of-view but resolution is too coarse to see individual cells. However, MRI signal intensity is sensitive to microscopic features. For example, diffusion MRI is sensitive to water motion, including its interaction with surrounding structures. Relating the signal to specific features is difficult because many factors influence signal. This work proposes two advanced diffusion MRI techniques and new analysis methods to extract parameters related to the water exchange rate, cell size distributions and fibre patterns. The first diffusion MRI method explores longer diffusion times and therefore slower processes, such as water crossing the cell membrane. Long times have lower signal in conventional diffusion due to a process known as T2 relaxation. The proposed method stores magnetization along the longitudinal axis to preserve signal. In addition, there are no simple equations for analyzing water exchange so we propose to use numerical methods. These will first be applied in acute myeloid leukemia cells where water exchange has been previously characterized using a contrast agent-based method, so this system can be used to validate the diffusion measurement. Water exchange will then be estimated in breast cells. The second diffusion method examines fibre patterns within voxels. Conventional diffusion is sensitive to differences in water motion with direction when fibrous structures are highly aligned (high anisotropy). Low anisotropy is difficult to interpret; it can result from an absence of fibres or fibres that spread out in different directions. We will use an emerging MRI sequence where the diffusion gradient varies over time in different directions to reveal new information about anisotropy at the microscopic level. This method identifies crossing fibres in the brain but a new protocol and analysis method are needed for other tissues. For example, no current methods to analyze this sequence incorporate water restriction, which limits studies to small structures and limited diffusion weightings. Our analysis method incorporates restriction and is therefore suitable for a broader range of tissues and diffusion parameters. This will be tested on breast cells grown in collagen scaffolds with different fibre densities and alignments and compared to histology. This program will provide a validated tool for non-invasive characterization of microscopic features in breast tissue, which can be replicated to examine other tissue types. It is an in vivo method that covers large fields-of-view to yield information that is not currently available from histology. It has the potential to provide new insights into apoptotic cell death, collagen fibre reorientation during wound healing and other processes with structural changes in cells and their surrounding environment.