Enhanced neonatal brain development MRI at ultra-high field

MRI在研究新生儿正常和异常脑发育方面具有重要价值。由King's和Imperial共同领导的人类连接组计划（Human Connectome Project，dHCP）旨在通过获取胎儿和新生儿的MRI解剖和功能数据来绘制早期生命发育图。正在进行的dHCP数据分析，希望提供新的见解结构和功能的发展。然而，关于早产儿和围产期创伤对大脑发育的影响，现有的MRI方法不太可能解决关键的未知数。新生儿成像的一个挑战是实现足够的空间分辨率来可视化小的大脑结构，保持合理的采集时间和可接受的噪声水平。dHCP使用主要设计用于成人成像的临床3 T MRI扫描仪技术，结合定制的新生儿大脑接收器线圈和专门设计的患者处理1。然而，即使是提供0.8mm各向同性解剖分辨率的专用采集协议仍然仅能够解析关键结构，并且例如不能区分皮质层。随着相关技术挑战的克服，UHF-MRI最近才开始应用于临床和生物医学研究。例如，7 T MRI可以提供癫痫受试者和多发性硬化症患者在低场不可见的局灶性脑病变的信息2，3;超高分辨率脑成像还揭示了惊人的解剖学细节，特别是具有增强的T2* 对比度，这使得UHF特别适合于研究以高铁含量为特征的深核4，5.本项目的目的是探讨UHF-MRI对提高新生儿受试者可用图像数据质量的益处。这将提供一个更近距离的观察大脑在一个旺盛的发展时期，当它既不同于成人大脑（具有不同的MRI特性），并正在快速变化。我们的目标是产生一种在灵敏度和分辨率上超过dHCP新生儿方案的7 T方案，并使用该方案来探索脑发育和损伤的关键方面，例如缺氧缺血性损伤中的深灰色核损伤模式和与早产相关的细微血管变化。我们知道最小的受试者是5岁7.新生儿被扫描的最高场是4.7T8，9.由于新生儿成像从未尝试过7 T，我们的首要任务将是证明可以确保安全操作。据目前所知，没有已知的与暴露于强静磁场相关的固有健康风险10。任何新型MRI应用必须解决的关键风险是成像期间的受试者发热，通过射频能量的比吸收率（SAR）进行量化，在较高频率下固有较高。通过对射频发射器线圈进行建模并与幻影的详细实验进行比较，可以确保安全性-幻影是一种用于对所有其他人群进行成像的方法。应该注意的是，没有与较小受试者相关的固有额外风险。相反，对于许多射频线圈设计11，较小的受试者不太容易受到射频加热效应的影响，并且其较高的表面积与体积比使新生儿比成人更不容易受到射频场的全身加热。此外，RF不均匀性效应，在UHF下成像更大的视场的问题，将在新生儿中不太明显。

MRI is extremely valuable in studying normal and abnormal brain development in neonates. The developing Human Connectome Project (dHCP), led jointly by King's and Imperial, aims to map early life development by acquiring MRI anatomical and functional data from fetuses and neonates. Ongoing analysis of dHCP data is hoped to provide new insights into structural and functional development. However there remain key unknowns relating to the effects of prematurity and perinatal trauma on brain development that existing MRI approaches are unlikely to resolve.One challenge of imaging neonates, is achieving sufficient spatial resolution to visualise small brain structures, maintaining reasonable acquisition times and acceptable noise levels. The dHCP uses a clinical 3T MRI scanner technology primarily designed for imaging adults combined with bespoke neonatal brain receiver coils and purpose designed patient handling1. However, even the dedicated acquisition protocol providing anatomical resolution of 0.8mm isotropic is still only just able to resolve key structures and for example is not able to differentiate cortical layers.MR sensitivity increases approximately with field strength. As the associated technical challenges are overcome, UHF-MRI is only recently starting to be applied to clinical and biomedical research. For instance 7T MRI can provide information on focal brain lesions in epileptic subjects and in multiple sclerosis not visible at lower fields2,3; ultra high resolution brain imaging is also revealing astonishing anatomical details particularly with enhanced T2* contrast that makes UHF particularly well suited for studying deep nuclei characterised by high iron content4,5.The objective of this project is to explore the benefits of UHF-MRI for enhancing the available image data quality for neonatal subjects. This will provide a closer look at the brain during a period of exuberant development, when it is both different from adult brain (with different MRI properties) and is changing fast. We aim to produce a 7T protocol that exceeds the dHCP neonatal protocol in sensitivity and resolution, and use this to explore critical facets of brain development and damage, such as patters of deep grey nuclei damage in hypoxic ischemic injury and subtle vascular changes associated with prematurity6.Few studies scanned children at 7T, with the youngest subjects we are aware of being 5 years old7.The highest field at which neonates have been scanned is 4.7T8,9.Since neonatal imaging has never been attempted at 7T our first task will be to demonstrate that safe operation can be assured. To the best of current knowledge there are no known inherent health risks associated with exposure to strong static magnetic fields10.The key risk that must be addressed for any novel MRI application is subject heating during imaging, quantified by the specific absorption rate (SAR) of radiofrequency energy, intrinsically higher at higher frequencies. Safety can be assured by modelling of RF transmitter coils and comparing with detailed experiments on phantoms - an approach taken for imaging all other populations. It should be noted that there are no inherent additional risks associated with smaller subjects. On the contrary, smaller subjects are less prone to RF heating effects for many RF coil designs11 and their higher surface-to-volume ratios make neonates far less prone to systemic heating from RF fields than adults. Further, RF inhomogeneity effects, problematic for imaging larger fields of view at UHF, will be much less pronounced in neonates.