Enhanced neonatal brain development MRI at ultra-high field

MRI在研究新生儿大脑正常和异常发育方面具有重要的价值。正在发展中的人类连接组项目（dHCP）由国王学院和帝国理工学院联合领导，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。对dHCP数据的持续分析有望为结构和功能发展提供新的见解。然而，关于早产和围产期创伤对大脑发育的影响，现有的MRI方法不太可能解决一些关键的未知问题。新生儿成像的一个挑战是获得足够的空间分辨率来显示小的大脑结构，保持合理的采集时间和可接受的噪音水平。dHCP使用主要为成人成像设计的临床3T MRI扫描仪技术，结合定制的新生儿脑接收器线圈和专门设计的患者处理技术1。然而，即使是提供0.8mm各向同性解剖分辨率的专用采集方案仍然只能解决关键结构，例如无法区分皮质层。磁流变灵敏度随场强近似增加。随着相关技术挑战的克服，超高频磁共振成像最近才开始应用于临床和生物医学研究。例如，7T MRI可以提供癫痫患者和多发性硬化症患者局灶性脑病变的信息，这些病变在低视场中是不可见的2,3；超高分辨率脑成像也揭示了惊人的解剖细节，特别是增强的T2*对比度，这使得超高频特别适合研究以高铁含量为特征的深部核。该项目的目的是探讨超高频磁共振成像的好处，以提高新生儿受试者的可用图像数据质量。这将使我们更近距离地观察旺盛发育时期的大脑，此时的大脑与成人的大脑不同（具有不同的MRI特征），并且变化迅速。我们的目标是建立一个在敏感性和分辨率上超过dHCP新生儿协议的7T协议，并利用它来探索大脑发育和损伤的关键方面，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6。很少有研究在7岁时对儿童进行扫描，我们所知道的最小的受试者只有5岁。新生儿被扫描的最高视场是4.7 t8,9。由于新生儿影像学从未尝试过7T，我们的首要任务将是证明可以确保安全操作。据目前所知，暴露在强静电磁场下没有已知的固有健康风险。任何新型MRI应用必须解决的关键风险是成像过程中的受热，通过射频能量的特定吸收率（SAR）来量化，本质上在更高的频率下更高。通过对射频发射线圈进行建模，并与对幽灵的详细实验进行比较，可以确保安全性——这是对所有其他人群进行成像的一种方法。应该注意的是，较小的受试者没有固有的额外风险。相反，对于许多射频线圈设计来说，较小的受试者不太容易受到射频加热效应的影响，而且它们较高的表面体积比使新生儿比成年人更不容易受到射频场的全身加热。此外，射频不均匀性效应，在超高频成像大视场时存在问题，在新生儿中将不那么明显。

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.