Singlet Assisted Diffusion Tensor Imaging (SAD-TI)

弥散张量成像(DTI)是一种磁共振成像技术，它提供了独特的生物学和临床重要信息，这些信息是其他成像技术所不能提供的，包括显微结构和纤维方向图。例如，DTI用于脑束造影术，以可视化大脑不同部分之间的解剖联系。DTI使用射频和磁场梯度脉冲的组合来确定物质在介质中的扩散张量(在临床上，磁共振是水在组织中的扩散张量)。寻求整个张量，而不仅仅是扩散常数，因为在微结构可以推断约束的介质中，扩散是各向异性的。通过逐个体素绘制扩散张量轨迹的值，就有可能获得以水在不同组织中的扩散作为对比的解剖图像。这些图像可以报告与疾病相关的异常。DTI(和许多其他核磁共振技术一样)依赖于对自旋态的记忆。这些需要足够的时间让分子在介质中扩散并经历限制(没有限制就意味着各向同性的扩散)。通常情况下，自旋记忆会保留几毫秒到几秒。在如此短的时间内，分子只能移动到~100，因此只有这种大小及以下的结构才能推断出足够的限制，因此在DTI实验中扩散表现为各向异性。在我的实验室里，我们最近开发了一种核磁共振方法[1-3]来克服这种限制，因此能够延长自旋记忆许多分钟，从而检测到长达2毫米的结构中的限制[2]，或者探测介质的曲折，因为分子在许多孔中移动了几毫米[3]。我们将这项技术称为单重态辅助扩散核磁共振(SAD-核磁共振)，因为单重态是一种长寿命的自旋态。这位博士生将把这种方法扩展到DTI领域。将SAD-核磁共振方法引入DTI(SAD-TI)后可获得的扩散时间延长，不仅可以比目前可用的方法更准确地表征扩散张量分量，而且更有趣的是，还可以可视化包括生物组织在内的多孔介质中大通道、纤维或孔之间的连接。特别是，我们将应用这项技术来研究营养物质在3D打印脚手架内的扩散(样本由澳大利亚布里斯班昆士兰理工大学的合作者提供)。这些支架正在开发中，用于组织工程目的，但随着细胞沿着支架生长，通道关闭，坏死核形成。这些通道的尺寸(0.5-1 mm)远远高于目前DTI可测量的尺寸。相反，SAD-TI方法将提供前所未有的数据，用于指导下一代脚手架架构的设计。

Diffusion tensor imaging (DTI) is a magnetic resonance modality that provides unique biologically and clinically important information not available via other modalities, including microstructure and fibre orientation mapping. DTI, for example, is used in tractography to visualize anatomic connections between different parts of the brain. DTI uses a combination of radiofrequency and magnetic field gradient pulses to determine the diffusion tensor of a substance in a medium (in clinical MRI is the diffusion tensor of water in tissues). The whole tensor, and not only the diffusion constant, is sought since diffusion is anisotropic in a medium where the microstructure can infer confinement. By plotting the value of the trace of the diffusion tensor voxel-by-voxel it is then possible to obtain anatomical images where the diffusion of water in different tissues is used as contrast. These images can report on anomalies associated with diseases. DTI (as many other NMR technique) relies on the memory of spin states. These need to survive enough time for the molecule to diffuse in the medium and experience the confinement (no confinement would mean isotropic diffusion). Typically, spin memory is preserved for between a few millisecond and a few seconds. In such short time molecules can only travel up to ~100 and thus only structure of this size and below can infer enough confinement so that diffusion appears anisotropic in DTI experiments. In my laboratory, we have recently developed [1-3] an NMR methodology to overcome such limitation and therefore be able to prolong spin memory for many minutes so to detect confinement in structures of up to 2 mm [2] or probe the tortuosity of the medium as experienced by molecules traveling for millimetres across many pores [3]. We dubbed the technique as singlet-assisted diffusion NMR (SAD-NMR) since singlet is the spin state with a long lifetime. The PhD student will to extend this methodology into the field of DTI. The extended diffusion time available after incorporation of the SAD-NMR method into DTI (SAD-TI) will not only allow the characterisation of the diffusion tensor components with greater accuracy than what currently available, but also, and more interesting, will allow the possibility to visualise connections between large channels, fibres or pores in porous media, including biological tissues. In particular we will apply this technique to study the diffusion of nutrients inside 3D printed scaffoldings holding cells (sample provided by collaborators at QUT in Brisbane, AU). These scaffoldings are under development for tissue engineering purposes but as the cells grow along the support the channels close up and a necrotic core develops. The dimension of those channels (0.5-1 mm) are well above what currently measurable with DTI. The SAD-TI method will instead provide unprecedented data to be used to inform the design of next-generation scaffold architecture.