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.

项目摘要/摘要：自功能MRI（fMRI）基于基于功能的神经影像 研究三十年前，已经开展了广泛的工作来描述人类的内在连通性 大脑，无论是响应外部刺激还是在静止状态下。只有适度的改进 fMRI的对比度比（CNR），因此，fMRI的临床应用有限， 作为fMRI的CNR，其基于​​个体的功能神经影像的能力限制了其能力。 磁性粒子成像（MPI）是一种新型的成像方式，可利用大型磁性 用于改进的CNR的注射超顺磁铁氧化铁纳米颗粒（SPION）的力矩。通过利用 MPI的CNR增加，该建议旨在验证FMPI检测静止状态CBV的能力 波动并使用这些信号以类似于静止状态fMRI的功能连接网络（RS-） fMRI）基于相关的连接映射。我们小组的最新工作证明了检测能力 在啮齿动物模型中基于MPI的物理噪声信号，该信号以注入的磁性SPION的剂量扩展。 该提案将建立这项工作，并持续构建人类MPI扫描仪的努力，将表征 静止状态MPI层析成像时间序列数据中的信号波动，并测试产生功能的能力 这些信号的连接映射。我的中心假设是配备了这些原型 扫描仪和对信号灵敏度的关注越来越大，该物理成分的比率 信号在相关映射到其他非神经生成的波动中的信号将更高 在MPI中，比传统的血氧级依赖性（BOLD）fMRI和更强大的网络图 会结果。我计划生成第一个基于MPI的静止状态功能性脑连接图，相比之下 RS-FMRI，并有可能证明对发现微妙的网络改变的敏感性，因此有潜在地 推进我们了解和表型患有神经精神疾病的个体患者的能力。 在此提案中，我将首先证明能够表征啮齿动物中皮质关联网络的能力 改进现有图像重建方法后，使用小孔MPI扫描仪。第二个目标 提案将首先着重于更新人类MPI扫描仪的硬件，以利用SPIONS的敏感性 进行静止状态FMPI实验，然后验证稳定和敏感的幻影所必需 图像时间序列可检测主导生理“噪声”的血流动力学波动。然后我会验证 在猕猴模型中执行FMPI皮质关联网络表征的能力，其中一个广泛的选择 可以使用SPION TRACER。第三个目的是在人类中进行RS-FMPI表征研究。 该提案的成功完成将确定MPI作为新颖且高度敏感的潜力 功能连通性映射方式推进了我们发现单个大脑网络改变的能力 精神病患者。