Magnetic Resonance Tools for Fetal Developmental and Metabolic Assessment

磁共振的物理原理可以获得软组织的高分辨率、高对比度的三维图像，同样也可以用来获取组织的功能信息，比如其代谢物的浓度和运输。其中一种方法是磁共振光谱学（MRS）。当应用于羊水（AF）样本时，MRS已被证明可以揭示胎儿器官发育标志物的信息，主要是肺和肾。然而，获取房颤样本仍然需要侵入性手术（通过羊膜穿刺术）来提取房颤，这无意中增加了感染和早产的风险。在本研究中，我们将开发一种允许对羊水（AF）进行无创体内检查的MRS方案，从而创建一种更安全的替代技术来评估胎儿肺和肾脏的成熟度，从而允许早期识别胎儿发育迟缓。另一种利用光谱评估的方法是化学交换饱和转移（CEST） MRI，它依赖于从低浓度代谢物到丰富水分子的自然磁化转移。在选定的代谢物和水之间的连续磁饱和和转移允许对代谢物进行放大，使其更容易通过光谱检测，并可用于跟踪其运输和代谢。将这种技术应用于葡萄糖，一种被称为glucoCEST的方法，已被证明可以提供有关成人大脑代谢率的信息。在拟议的研究中，我们将开发葡萄糖测试作为评估胎儿器官代谢率的无创工具。glucoCEST和AF-MRS将共同补充传统的胎儿MR成像，为评估胎儿器官成熟度和代谢功能提供安全和创新的手段。我们将在健康人类妊娠的动物模型上验证它们的使用，并使用临床级MRI扫描仪，从而提供它们潜在转化为临床应用的第一个原理证明。这些技术将彻底改变医学成像领域，通过在产前发育过程中增加新的技术来探测各种物种的生理。这些技术通过促进产前发育和功能缺陷的早期检测，也将有助于医学领域。

The same physics principles of magnetic resonance, which allow acquiring high-resolution, high-contrast, 3-dimensional images of soft tissue, could also be harnessed to acquire functional information about the tissue, such as its metabolite concentrations and transport. One such approach is MR Spectroscopy (MRS). When applied to samples of amniotic fluid (AF), MRS has been shown to reveal information about markers of fetal organ development, primarily the lungs and kidneys. However, acquiring an AF sample still requires an invasive procedure to extract AF (via amniocentesis), which inadvertently increases the risk of an infection and preterm delivery. In the proposed research we will develop an MRS protocol that allows for non-invasive in-vivo interrogations of amniotic fluid (AF), thereby creating a safer alternative technique for assessing fetal lung and kidney maturity, allowing for early identification of developmental delays in the fetus. Another approach that utilizes spectral assessment is Chemical Exchange Saturation Transfer (CEST) MRI, which relies on natural transfer of magnetization from low-concentration metabolites to the abundant water molecules. Continuous magnetic saturation and transfer between a chosen metabolite and water allows for amplification of the metabolite such that it is more easily detected through spectroscopy and can be used to trace its transport and metabolism. Applying this technique to glucose, a method termed glucoCEST, has been shown to provide information about brain metabolic rate in adults. In the proposed research we will develop glucoCEST as a non-invasive tool for evaluating fetal organ metabolic rate. Together, glucoCEST and AF-MRS will supplement classical fetal MR imaging, providing safe and innovative means of assessing fetal organ maturity and metabolic function. We will validate their use on animal models of healthy human gestation and using a clinical-grade MRI scanner, thereby providing the first proof of principle of their potential translation to clinical utility. These techniques will revolutionize the medical imaging field through the addition of novel techniques for probing physiology in a variety of species during prenatal development. These techniques will also contribute to the medical field by facilitating early detection of developmental and functional deficits prenatally.