Multi-modal brain imaging analysis method for brain modeling

拟议研究计划的主要目标是开发和改进脑成像分析方法。脑成像技术的出现，如正电子发射断层扫描（PET）和功能性磁共振成像（fMRI），极大地拓宽了我们对大脑功能的认识。例如，通过注射[18F]氟脱氧葡萄糖（FDG; PET最广泛使用的放射性示踪剂），我们可以定位葡萄糖快速代谢的位置，这与受试者在特定条件下扫描的神经元活动水平有关。尽管具有启发性，但典型FDG-PET技术的局限性之一是不能对区域到区域的连接性进行建模。换句话说，很难将大脑建模为一个网络，在这个网络中，遥远的大脑区域相互通信。利用FDG-PET图像的功能连接性和图论，我已经确定了人脑中的“信息流中心”。刺激（功能性干扰）中枢大脑区域可能对大脑网络结构产生最大影响，并改变大脑处理信息的方式。在这里，使用功能磁共振成像将使个性化的枢纽识别，这是不可能与单独的FDG-PET。在这里，我提出的研究计划的前半部分将集中在基于大型脑成像数据库的数学脑网络建模，并使用非侵入性脑刺激技术通过“扰动和测量”的实验方法验证所构建的模型。这一提议将促进数学理论与实验伙伴关系的文化，类似于物理科学中普遍存在的文化，而这在大脑成像领域一直缺乏。在基础神经科学研究中，使用PET的最大优势可能是可以监测放射性示踪剂靶向的特定神经化学物质的活动。然而，目前的方法通常需要动脉血液采样来估计实际上有多少放射性示踪剂被递送到大脑区域。这与包括动脉闭塞、出血和感染在内的风险有关。通过使用混合PET-MRI同时获取血流信息，我们将开发在大脑图像中准确描绘动脉的方法，从而用“基于图像的血液采样”取代真实的血液采样。我们还将开发一种方法，澄清PET结果测量的变化来源，这些变化通常被同时变化的血流所掩盖。总之，我的团队将开发克服PET和MR成像相关挑战的方法，包括但不限于上述困难。将招收一名博士生和三名硕士生。在拟议的研究计划中培训的HQP及其研究成果将大大有助于脑成像科学的进步。

The primary goal of the proposed research program is to develop and improve the brain imaging analysis methods. The emergence of brain imaging techniques such as positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) significantly contributed to broadening our knowledge about how the brain functions. For example, with injection of [18F]fluorodeoxyglucose (FDG; the most widely used radiotracer for PET), we can locate where glucose is rapidly metabolized which is related with the level of neuronal activity in particular conditions that the subject is scanned under. Although illuminating, one of the limitations of the typical FDG-PET technique is that one cannot model the region-to-region connectivity. In other words, it is difficult to model the brain as a network where distant brain regions are communicating with each other.*******Utilizing the functional connectivity and graph theory on FDG-PET images, I have identified “hubs of information flow” in human brain. Stimulating (functionally interfering) the hub brain region may have the most influence on the brain network structure and alter how the brain processes information. Here, use of fMRI will enable personalized hub identification that is not possible with FDG-PET alone. Here, the first half of my proposed research program will focus on modelling mathematical brain networks based on large brain imaging database and validate the constructed models by “perturbing-and-measuring” experimental approach using non-invasive brain stimulation technique. This proposal will promote a culture of mathematical theory-experiment partnership similar to that prevailing in the physical sciences which has been lacking in the field of brain imaging.*******In basic neuroscience research, perhaps the biggest advantage of using PET is that one can monitor the activities of specific neurochemicals that the radiotracer is targeting. However, current approaches often require arterial blood sampling to estimate how much radiotracer is actually delivered to the brain region. This is associated with risks including arterial occlusion, bleeding and infection. By simultaneously acquiring blood flow information using hybrid PET-MRI, we will develop methods that accurately delineate arteries in the brain images thereby replacing the real blood sampling with “image-based blood sampling.” We will also develop a method that clarifies the sources of changes in the PET outcome measures which has been often obscured by concurrently changing blood flow.*******In sum, my team will develop methods that overcome the challenges associated with PET and MR imaging, including but not limited to the above-mentioned difficulties. One PhD student and three MSc students will be recruited. HQPs trained in the proposed research program and their research outcome will greatly contribute to the advances of brain imaging science.***