A magnetic particle imager (MPI) for functional brain imaging in humans

在这个U 01赠款，我们提出了一个5年的工程开发工作，以推进磁 粒子成像（MPI）将取代MRI成为下一代人类功能性脑成像工具 神经科学MPI是一种年轻但极具前景的技术，它使用非线性磁 铁氧化物纳米颗粒的响应，以定位其在体内的存在。MPI直接检测 纳米颗粒的磁化，而不是使用磁共振的二次效应 放松时间因此，虽然MPI和MRI共享许多技术，但MPI方法不使用 磁共振现象。我们的计划是检测激活诱导和静息状态 通过监测局部铁，改变脑毛细血管网中氧化铁浓度 氧化物浓度（以及局部脑血容量，CBV）。这个CBV对比源很好- 在动物和人类功能磁共振成像研究中得到证实，这些研究通过使用相同的铁- 氧化剂，但间接。但是，通过开发MPI作为检测模态，我们表明， 人类神经元激活的对比噪声比（CNR）可能增加10倍。 在计划拨款阶段，我们分析了多种潜在的人类MPI扫描仪设计， 决定采用无场线几何。我们开发了模拟工具来模拟性能 人体大小的仪器。此外，我们通过构建和测试一个小的， 啮齿动物规模的MPI探测器在我们的实验室在MGH。利用这个设备，我们首次展示了 使用啮齿动物高碳酸血症模型的MPI功能成像的演示。在U 01阶段 我们寻求资源来构建和验证人类规模的旋转FFL式MPI设备 在规划中分析。构建完成后，我们将在Phantom中验证其性能 研究，以及我们以前用于功能磁共振成像的清醒行为猕猴模型 问题研究最后，我们将在有限的人体fMPI研究中验证器械的性能。 通过开发一种新的、更灵敏的功能性人体成像检测方法， 我希望为神经科学家的研究工具增加一种强大的新的非侵入性方法， 健康和疾病中的人类大脑。

In this U01 grant we propose a 5 year engineering development effort to advance Magnetic Particle Imaging (MPI) to replace MRI as the next-generation functional brain imaging tool for human neuroscience. MPI is a young but extremely promising technology that uses the non-linear magnetic response of ironoxide nanoparticles to localize their presence in the body. MPI directly detects the nanoparticle's magnetization rather than using secondary effects on the Magnetic Resonance relaxation times. Thus, while MPI and MRI share many technologies, the MPI method does not use the MR phenomena in any way. Our plan is to detect the activation-induced and resting-state changes in the iron-oxide concentration in the cerebral capillary network by monitoring the local iron oxide concentration (and thus local Cerebral Blood Volume, CBV). This CBV-contrast source is well- proven in animal and human fMRI studies which detect CBV changes by MRI using the same iron- oxide agents, but indirectly. But, by developing MPI as the detection modality, we show that there is a potential 10-fold increase in the contrast-to-noise ratio (CNR) of human neuronal activation. In the planning grant stage, we analyzed multiple potential MPI scanner designs for humans and settled on a Field-Free-Line geometry. We developed the simulation tools to model the performance of a human sized instrument. Additionally, we validated our modeling by building and testing a small, rodent-scale MPI detector in our lab at MGH. Using this device, we showed the first ever demonstration of functional imaging with MPI using a rodent hypercapnia model. In this U01 phase we seek the resources to construct and validate the human scale, rotating FFL-style MPI device analyzed in the planning grant. After construction, we will validate its performance in phantom studies, and also in an awake-behaving macaque model that we have previously used for fMRI studies. Finally, we will validate the performance of the device in limited human fMPI studies. By developing a new and more sensitive detection methodology for functional human imaging, we hope to add a powerful new non-invasive methods to the tools available to neuroscientists studying the human brain in health and disease.