Upgrading our view of Growing Older: Mapping Brain Changes across the Lifespan with Ultra High Field Multi-Spectral MRI

詹姆斯·韦伯太空望远镜传回的初步数据最近戏剧性地提醒世人，科学认识可以通过提高图像空间分辨率而改变。自1973年磁共振成像（MRI）发明以来，在空间和时间分辨率方面的类似突破一直是其在发现科学中应用的关键。在我们获得任何过程的精细细节之前，我们不知道其建模所需的粒度级别，以提供令人满意的解释和可测试的预测。最近已经认识到，人类大脑的轴突在出生后和成年后继续形成髓鞘；这种髓鞘形成在很大程度上是由每个神经元的经验驱动的自举过程；每个皮质区域的髓鞘形成模式决定了该区域最重要的微回路，在那里水平髓鞘纤维可能携带抑制信号；大脑MRI对比几乎完全依赖于每个图像体素内髓磷脂的数量。因此，生成具有足够空间分辨率以区分和量化骨髓结构的活体磁共振脑图像已成为人类大脑功能研究中一个独特的重要目标。发育过程中骨髓发生的一般人群趋势和个体差异可能成为认知心理学的关键解释性观察结果和精神疾病经验生物标志物的基础。同时，我们已经开始了解大脑能量供应和消耗的机制随年龄的变化而变化，它们可能与突触发生和髓鞘形成在整个生命周期中的变化密切相关。核磁共振成像的分辨率取决于三个主要因素：应用磁场的强度，射频接收器线圈及其电子设备的效率，以及用于捕获磁共振信号的射频和梯度场脉冲序列的独创性。目前，工程要求可处理的最高MRI场强是7特斯拉，大约在2000年引入了人体大小的扫描仪，全球安装的此类扫描仪的数量接近100台。与许多其他医疗技术一样，在摩尔定律、光电子学、成熟的硬件设计技术和激烈的市场竞争的推动下，MRI也在不断快速发展。因此，第一代7T扫描仪，包括2015年在CUBRIC安装的开创性西门子Magnetom扫描仪，现在在技术上远远落后于最近上市的系统，如西门子Terra扫描仪和新的GE 7T Signa。虽然CUBRIC 7T扫描仪在许多方面继续优于同类3T扫描仪，但其辅助硬件、计算机设备和软件环境使其无法实现获取大脑定量微观结构和功能活动的各向同性0.5 mm分辨率图像的可行目标。这使得它不适合前沿研究（例如）：学习新技能的成人受试者的皮质变化，有行为问题的学童大脑的骨髓结构异常，以及新视觉技能发展过程中皮质区域成熟的顺序，以及将所有这些变化与脑代谢的变化和随年龄增长维持健康灌注的变化联系起来。拟议的升级将使CUBRIC能够研究大脑如何在整个生命周期中发展和保持健康功能，这是一个至关重要的研究问题，因为世界人口的寿命比以往任何时候都要长。

The initial data transmitted from the James Webb Space Telescope have recently dramatically reminded the world that scientific understanding can be transformed by the improvement of image spatial resolution. Since the invention of magnetic resonance imaging (MRI) in 1973, similar breakthroughs in its spatial and temporal resolution have been key to its use in discovery science. Until we have access to the fine details of any process, we have no idea of the level of granularity that will be required in its modelling to provide satisfactory explanations and testable predictions.It has recently been recognized that the human brain's axons continue to become myelinated after birth and into adulthood; that this myelination is largely driven in a bootstrapping process by each neuron's experience; that the pattern of myelination in each cortical area defines the most important microcircuits in that area, where horizontal myelinated fibres are likely to carry inhibitory signals; and that brain MRI contrast is conveniently almost entirely dependent on the amount of myelin within each image voxel. In consequence, the generation of in-vivo MR brain images with a spatial resolution sufficient to distinguish and quantify myeloarchitecture has become a uniquely important goal in the study of human brain function. General population-wide trends in myelogenesis during development, and individual differences, may become key explanatory observations for cognitive psychology and the basis of empirical biomarkers in psychiatric disorders. At the same time, we have started to understand that the mechanisms of brain energy supply and consumption vary with age, and they may be closely related with changes in synaptogenesis and myelination across the lifespan.The attainable resolution in MRI depends on three main factors: the strength of the applied magnetic field, the efficiency of the radiofrequency receiver coil and its electronics, and the ingenuity of the sequences of RF and gradient field pulses employed in capturing the magnetic resonance signal. Currently the highest MRI field strength for which the engineering requirements are tractable is 7 Tesla, introduced for human-size scanners in about 2000, and the number of such scanners installed globally is approaching 100. Like many other medical technologies, MRI continues to undergo rapid development driven by Moore's Law, optoelectronics, maturing hardware design techniques, and strong market competition. Thus the first generation of 7T scanners, including the pioneering Siemens Magnetom scanner installed at CUBRIC in 2015, is now technologically far behind more recently marketed systems, such as the Siemens Terra scanner and the new GE 7T Signa. While the CUBRIC 7T scanner continues to outperform comparable 3T scanners in many respects, its ancillary hardware, computer equipment, and software environment leave it unable to deliver the feasible goal of acquiring isotropic 0.5 mm resolution images of brain quantitative microstructure and functional activity. This makes it unsuitable for cutting-edge studies (for example) of cortical changes in adult subjects learning new skills, of myeloarchitectural abnormalities in the brains of schoolchildren with behavioural problems, and of the sequence of cortical area maturation in the development of new visual skills, and to relate all of these changes to the changes in brain metabolism and the maintenance of healthy perfusion with age. The proposed upgrade will enable CUBRIC to investigate how the brain develops and maintains healthy function across the lifespan, a crucial research question as the world population live longer than ever.