Improved MRI Contrast Agent Visibility Through Contrast Agent Manipulation

通过造影剂操作提高 MRI 造影剂可见度

• 批准号: 9794003
• 负责人: Eugene Milshteyn
• 金额: $ 6.57万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-21 至 2020-12-20
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9794003
• 关键词: Acoustics; Address; Affect; Animals; Appearance; Binding; Biological; Biomedical Engineering; Cardiac; Chemistry; Clinical; Complex; Contrast Media; Contrast Sensitivity; Data; Detection; Development; Discrimination; Disease; Dose; Environment; FDA approved; Fibrin; Frequencies; Functional Magnetic Resonance Imaging; Gadolinium; General Hospitals; Hour; Human; Image; Infrastructure; Injections; Iron; Laboratories; Logistics; Magnetic Resonance Imaging; Masks; Massachusetts; Mentorship; Methods; Molecular; Molecular Target; Motion; Neoplasm Metastasis; Noise; Operative Surgical Procedures; Organ; Output; Phase; Physics; Physiologic pulse; Physiological; Preparation; Process; Relaxation; Research; Rodent; Role; Scanning; Scheme; Signal Transduction; Specificity; Structure; System; Technology; Testing; Tissues; Tracer; Training; Translating; Uncertainty; Validation; base; bioimaging; computing resources; connectome; contrast imaging; design; experience; experimental study; ferumoxytol; imaging agent; imaging detection; improved; in vivo; iron oxide nanoparticle; lymph nodes; metabolic imaging; molecular imaging; nanoparticle; novel; respiratory; response

PROJECT SUMMARY/ABSTRACT Contrast agents are relied upon in MR molecular imaging to provide positive or negative contrast to reveal biologically specific structures and processes in vivo. The detection sensitivity of the pre-post injection contrast changes is difficult against a complex image background. This is a major limiting factor to the clinical deployment of targeted contrast agent, since insensitive detection translates to the need for large doses, or highly concentrated molecular targets. The problem can be attributed to biological 1/f fluctuations in image intensity between the pre and post injection scan that occur in the 5-30 min between the images. Other essential considerations in a contrast agent acquisition includes the appearance of the agent as a “positive” or “negative” contrast against the background and the ability of the acquisition to distinguish the bound and un- bound pools of a targeted contrast agent. We will address each of these limitations by developing two classes of novel methods to externally modulate how the contrast agent affects the image signal prior to each k-space acquisition. The first class aims to use a recently developed spin-locking sequence that is resonantly sensitive to either acoustic waves or the non-linear response of iron-oxide nanoparticles. The effect is modulated “on” or “off” by simply altering the external acoustic wave or applied drive field on or off resonance. The spin-locking sequence has the ability to control the appearance of the agent as either “positive” contrast or “negative” contrast. It defeats the effect of 1/f noise by rapid modulation and provides a statistical framework to characterize the detection uncertainty. The second class of modulation is designed to add discrimination between bound and unbound pools of the targeted contrast agent. We propose a field cycling approach, whereby the applied field modulates the agents' relaxivity during a preparation phase in a different way for bound and unbound pools. We will demonstrate the ability of MR gradient coils to perform this role using the MGH 300 mT/m “Connectome” gradient. This method thus has tremendous potential to quantify the bound pool of targeted contrast agents in humans, and will enable important new applications in biomedical imaging that can be immediately utilized with certain FDA-approved contrast agents. The Martinos Center at the Massachusetts General Hospital is one of the largest imaging centers in the world, and features the ideal environment and infrastructure needed to complete the proposed research strategy. The Center has extensive hardware and computing resources, several large bore and small bore (animal) MR scanners, as well as dedicated molecular imaging, chemistry, and animal surgery laboratories that will facilitate my development of the proposed novel contrast agent MR acquisitions. Furthermore, Drs. Lawrence Wald and Peter Caravan have the expertise in MR molecular imaging and pulse sequence development, as well as experience in mentorship, that will help guide this project and my training.

项目摘要/摘要 MR分子成像中依赖对比剂以提供阳性或负对比以揭示 体内生物学特定的结构和过程。前注射对比的检测灵敏度 在复杂的图像背景下，很难更改。这是临床的主要限制因素 靶向对比剂的部署，因为不敏感的检测转化为大剂量的需求，或 高度浓缩的分子靶标。该问题可以归因于图像中的生物1/f波动 在图像之间5-30分钟内发生的预注射扫描和后注射后的强度。其他 对比代理商中的基本考虑因素包括代理人作为“正”或 与背景的“负”对比以及获取区分约束和不区分的能力 目标对比剂的绑定池。我们将通过开发两个类来解决这些限制 新型方法的外部调节对比剂在每个k空间之前如何影响图像信号 获得。一流的目的是使用最近开发的自旋锁定序列，该序列具有共识敏感的 要么声波或铁氧化物纳米颗粒的非线性响应。效果被调制为“ on”或 通过简单地更改外部声波或施加的驱动场，“关闭”。旋转锁 序列具有控制代理的外观为“正”对比度或 “负”对比。它通过快速调制来打败1/f噪声的效果，并提供统计 表征检测不确定性的框架。第二类调制旨在添加 靶向对比剂的绑定和未结合池之间的区分。我们提出了一个场骑行 方法，因此，应用场在制备阶段调节了药物的放松性 绑定和未结合池的方式。我们将展示MR梯度线圈执行此角色的能力 使用MGH 300 MT/M“ Connectome”梯度。因此，该方法具有量化的巨大潜力 人类目标对比剂的绑定池，并将在 可以立即使用某些FDA批准的对比剂使用的生物医学成像。 马萨诸塞州综合医院的马提尼斯中心是世界上最大的成像中心之一 并具有完成拟议的研究策略所需的理想环境和基础设施。这 中心拥有广泛的硬件和计算资源，几个大孔和小孔（动物）MR 扫描仪以及专用的分子成像，化学和动物手术实验室，这些实验室将有助于 我对拟议的新型对比代理MR采集的发展。此外，博士。劳伦斯·瓦尔德（Lawrence Wald）和 彼得大篷车在MR分子成像和脉冲序列发展方面具有专业知识，以及 具有Mentalship的经验，这将有助于指导该项目和我的培训。