Improved MRI Contrast Agent Visibility Through Contrast Agent Manipulation

项目总结/摘要 在MR分子成像中依赖于造影剂来提供正或负对比以显示 在体内的生物学特定结构和过程。注射前后对比剂的检测灵敏度 在复杂的图像背景下很难改变。这是临床应用的主要限制因素。 靶向造影剂的部署，因为不敏感的检测转化为需要大剂量，或 高度集中的分子目标。该问题可归因于图像中的生物1/f波动 在图像之间的5-30分钟内发生的注射前和注射后扫描之间的强度。其他 造影剂采集中的基本考虑包括造影剂作为“阳性”或“非阳性”的外观 “否定”背景的对比与习得区分束缚与非束缚的能力 靶向造影剂的结合池。我们将通过开发两个类来解决这些限制 外部调制造影剂如何在每个k空间之前影响图像信号的新方法 采集第一类的目的是使用最近开发的自旋锁定序列，是共振敏感 声波或氧化铁纳米颗粒的非线性响应。效果被调制为“开”或 通过简单地改变外部声波或所施加的驱动场的共振开或关，可以将外部声波或所施加的驱动场的共振频率改变为“关”。自旋锁定 序列具有控制药剂作为“阳性”对比剂的外观的能力， “负”对比。它通过快速调制消除了1/f噪声的影响，并提供了一个统计特性。 框架来表征检测不确定性。第二类调制被设计为添加 目标造影剂的结合池和未结合池之间的区分。我们建议进行野外循环 方法，即施加的场在不同的制备阶段调节药物的弛豫性 绑定和未绑定池的方式。我们将证明磁共振梯度线圈执行这一作用的能力 使用MGH 300 mT/m“Connectome”梯度。因此，这种方法具有巨大的潜力， 靶向造影剂在人体中的结合池，并将使重要的新应用， 生物医学成像，可以立即使用某些FDA批准的造影剂。 马萨诸塞州总医院的马蒂诺斯中心是世界上最大的成像中心之一， 并具有完成拟议研究战略所需的理想环境和基础设施。的 中心拥有广泛的硬件和计算资源，有几个大口径和小口径（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，将促进 我提出的新型造影剂MR采集的发展。此外，劳伦斯·沃尔德博士和 Peter Caravan拥有MR分子成像和脉冲序列开发方面的专业知识， 指导经验，这将有助于指导这个项目和我的培训。

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.