Resting-state functional connectivity mapping using Magnetic Particle Imaging (MPI)

使用磁粒子成像 (MPI) 绘制静息态功能连接图

• 批准号: 10464544
• 负责人: John Michael Drago
• 金额: $ 5.18万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10464544
• 关键词: Alzheimer' s Disease; Amplifiers; Anatomy; BRAIN initiative; Biomedical Engineering; Blood; Brain; Brain Mapping; Brain imaging; Clinical; Clinical Treatment; Cognition; Data; Detection; Development; Devices; Diagnosis; Dose; Economics; Exhibits; Functional Magnetic Resonance Imaging; Goals; Head; Human; Image; Imaging Device; Imaging Phantoms; Imaging Techniques; Individual; Injections; Investigation; Knowledge; Macaca; Macaca mulatta; Magnetic Resonance Imaging; Magnetism; Maps; Measurement; Measures; Mental Depression; Mental disorders; Methods; Modality; Modeling; Neurons; Noise; Nuclear Magnetic Resonance; Phenotype; Physiological; Protons; Research; Research Personnel; Resolution; Rest; Rodent; Rodent Model; Role; Running; Safety; Schizophrenia; Series; Signal Transduction; Stimulus; Testing; Time; Tracer; Translating; United States National Institutes of Health; Update; Work; analog; base; blood oxygen level dependent; cerebral blood volume; clinical application; design; disease phenotype; experimental study; ferumoxytol; hemodynamics; image reconstruction; imaging modality; imaging system; improved; individual patient; iron deficiency; iron oxide nanoparticle; magnetic field; nervous system disorder; neuroimaging; neuropsychiatric disorder; novel; novel strategies; particle; prototype; relating to nervous system; response; superparamagnetism; theories; tomography; tool

PROJECT SUMMARY/ABSTRACT: Since the development of functional MRI (fMRI)-based neuroimaging studies thirty years ago, extensive work has been undertaken to describe the intrinsic connectivity of the human brain, both in response to external stimulus and in resting-state. There have been only modest improvements in the contrast-to-noise ratio (CNR) of fMRI, and resultingly, there have been limited clinical applications of fMRI, as the CNR of fMRI limits its ability for individual-based functional neuroimaging. Magnetic particle imaging (MPI) is a novel imaging modality that capitalizes on the large magnetic moment of injected super-paramagnetic iron oxide nanoparticles (SPIONs) for an improved CNR. By harnessing the increased CNR of MPI, this proposal aims to validate the ability of fMPI to detect resting-state CBV fluctuations and use these signals to map functional connectivity networks in analogy to resting-state fMRI (rs- fMRI) correlation-based connectivity mapping. Recent work in our group has demonstrated the ability to detect MPI-based physiological noise signals in a rodent model that scale with the dose of the injected magnetic SPION. Building off this work and an on-going effort to construct a human MPI scanner, this proposal will characterize the signal fluctuations in resting-state MPI tomographic time-series data and test the ability to generate functional connectivity mappings from these signals. My central hypothesis is that armed with these prototype scanners and an increased focus on signal sensitivity, the ratio of the physiological component of the signal leveraged in correlational mapping to other, non-neuronally-generated fluctuations will be higher in MPI than in conventional blood-oxygen-level-dependent (BOLD) fMRI and more robust network maps will result. I plan to generate the first MPI-based resting-state functional brain connectivity maps, compare to rs-fMRI, and potentially demonstrate improved sensitivity to uncover subtle network alterations, thus potentially advancing our ability to understand and phenotype individual patients with neuropsychiatric disease. In this proposal, I will first demonstrate the ability to characterize cortical association networks in rodents using a small-bore MPI scanner, after improving existing image reconstruction methods. The second aim of the proposal will focus first on updating the hardware of the human MPI scanner to harness the sensitivity of SPIONs necessary to perform resting-state fMPI experiments and then on validating a stable and sensitive phantom image time-series to detect hemodynamic fluctuations that dominate the physiologic “noise”. I will then validate the ability to perform fMPI cortical association network characterization in a macaque model where a wide choice of SPION tracer is available. The third aim is focused on performing rs-fMPI characterization studies in humans. The successful completion of the proposal will determine the potential of MPI as a novel and highly sensitive functional connectivity mapping modality advancing our ability to uncover altered brain networks in individual patients with mental illness.

项目总结/摘要：自从基于功能性MRI（fMRI）的神经影像学发展以来 30年前的研究中，已经进行了大量的工作来描述人类的内在连接性。 大脑，无论是在响应外部刺激和休息状态。在这方面， fMRI的对比噪声比（CNR），因此，fMRI的临床应用有限， 因为功能磁共振成像的CNR限制了其基于个体的功能性神经成像的能力。 磁粒子成像（MPI）是一种新型的成像模式，利用大的磁共振成像技术， 注射超顺磁性氧化铁纳米颗粒（SPION）的时刻，以改善CNR。通过利用 增加MPI的CNR，该提议旨在验证fMPI检测静息态CBV的能力 波动，并使用这些信号来映射功能连接网络，类似于静息态功能磁共振成像（rs- fMRI）相关性为基础的连接映射。我们小组最近的工作已经证明了检测 啮齿动物模型中基于MPI的生理噪声信号，其与注射的磁性SPION的剂量成比例。 在这项工作的基础上，以及正在进行的构建人类MPI扫描仪的努力，该提案将描述 静息态MPI层析成像时间序列数据的信号波动和测试生成功能的能力 这些信号的连接映射。我的核心假设是有了这些原型 扫描仪和增加对信号灵敏度的关注， 在与其他非神经元产生的波动的相关映射中利用的信号将更高 在MPI中比在传统的血氧水平依赖（BOLD）fMRI和更强大的网络地图 将会产生。我计划生成第一个基于MPI的静息状态功能性大脑连接图，与之相比 rs-fMRI，并可能表现出更高的敏感性，以发现微妙的网络改变，因此可能 提高我们对神经精神疾病个体患者的理解和表型的能力。 在这个提议中，我将首先证明在啮齿动物中描述皮层关联网络的能力 使用小口径MPI扫描仪，在改进现有的图像重建方法后。第二个目标 该提案将首先集中在更新人体MPI扫描仪的硬件，以利用SPION的灵敏度 需要进行静息状态fMPI实验，然后验证稳定和灵敏的体模 图像时间序列，以检测主导生理“噪声”的血液动力学波动。然后我将验证 在猕猴模型中进行fMPI皮层关联网络表征的能力， SPION跟踪器可用。第三个目标是专注于在人类中进行rs-fMPI表征研究。 该提案的成功完成将决定MPI作为一种新型和高度敏感的 功能连接映射模式提高了我们发现个体大脑网络改变的能力 精神病患者。