Diffusion magnetic resonance imaging techniques for microscopic tissue characterization

用于显微组织表征的扩散磁共振成像技术

• 批准号: RGPIN-2020-04765
• 负责人: Bailey, Colleen
• 金额: $ 1.75万
• 依托单位: Ryerson University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=762403
• 关键词: Diffusion; magnetic; resonance; imaging; techniques

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.

组织学图像提供微观信息，但限于来自小组织体积的静态图片。磁共振成像（MRI）可以以更大的视野检查活组织，但分辨率太粗，无法看到单个细胞。然而，MRI信号强度对显微特征敏感。例如，扩散MRI对水运动敏感，包括其与周围结构的相互作用。将信号与特定特征相关联是困难的，因为许多因素影响信号。这项工作提出了两种先进的扩散MRI技术和新的分析方法，以提取相关的水交换率，细胞大小分布和纤维图案的参数。第一种扩散MRI方法探索较长的扩散时间，因此较慢的过程，如水穿过细胞膜。由于被称为T2弛豫的过程，长时间在传统扩散中具有较低的信号。所提出的方法存储磁化沿着纵向轴保存信号。此外，没有简单的方程来分析水交换，所以我们建议使用数值方法。这些将首先应用于急性髓性白血病细胞，其中先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。然后将估计乳腺细胞中的水交换。 第二种扩散方法检查体素内的纤维图案。当纤维结构高度对齐（高各向异性）时，常规扩散对水运动方向的差异敏感。低各向异性很难解释;它可能是由于缺乏纤维或纤维在不同方向上展开。我们将使用一种新兴的MRI序列，其中扩散梯度随时间在不同方向上变化，以揭示微观水平上各向异性的新信息。这种方法识别大脑中的交叉纤维，但其他组织需要新的协议和分析方法。例如，目前没有分析该序列的方法包括水限制，这将研究限制在小结构和有限的扩散权重。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。这将在具有不同纤维密度和排列的胶原支架中生长的乳腺细胞上进行测试，并与组织学进行比较。该计划将提供一个有效的工具，用于乳腺组织中微观特征的非侵入性表征，可以复制以检查其他组织类型。它是一种体内方法，覆盖大视场，以产生目前无法从组织学获得的信息。它有可能提供新的见解凋亡细胞死亡，在伤口愈合过程中的胶原纤维重新定向和其他过程中的细胞及其周围环境的结构变化。