Development of a Frontier Magnetic Resonance (MR) Imaging Technology As a Tool for Visualization and Quantified Vascular-Feature Measurement for Use in Brain and Behavioral Research on Small Animals

开发前沿磁共振 (MR) 成像技术作为可视化和量化血管特征测量的工具，用于小动物的大脑和行为研究

• 批准号: 10384839
• 负责人: Codi Amir Gharagouzloo
• 金额: $ 43.66万
• 依托单位: IMAGINOSTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-01-11 至 2024-01-10
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10384839
• 关键词: 3-Dimensional; Acceleration; Address; Age; Animal Experimentation; Animal Model; Animals; Anxiety; Behavioral Research; Benzodiazepines; Biological Markers; Blood - brain barrier anatomy; Blood Vessels; Brain; Brain Diseases; Calibration; Cerebrum; Citalopram; Clinical; Collaborations; Communities; Complement; Computer software; Cone; Data; Data Set; Development; Diazepam; Disease; Drug Formulations; Engineering; Ensure; Exhibits; Extravasation; Functional Magnetic Resonance Imaging; Goals; Hour; Image; Imaging Device; Imaging Techniques; Imaging technology; Individual; Industry; Industry Standard; Intervention; Intravenous; Investigation; Isoflurane; Journals; Magnetic Resonance; Magnetic Resonance Imaging; Major Depressive Disorder; Maps; Measurement; Medicine; Mental disorders; Methods; Modality; Neurosciences; Neurotransmitters; Noise; Obsessive-Compulsive Disorder; Panic Disorder; Peer Review; Pharmaceutical Preparations; Phase; Physics; Physiologic pulse; Physiological; Physiology; Production; Protocols documentation; Psyche structure; Publishing; Radial; Reproducibility; Research; Research Personnel; Resolution; Sampling; Scanning; Scientist; Selective Serotonin Reuptake Inhibitor; Services; Signal Transduction; Slide; Social Phobia; Sprague-Dawley Rats; Standardization; Structure; Techniques; Technology; Testing; Time; Translating; Translational Research; Translations; Treatment Efficacy; United States; Visualization; Visualization software; analytical tool; animal care; biomarker panel; brain behavior; brain research; cancer therapy; contrast enhanced; contrast imaging; cost; drug development; drug discovery; experimental study; ferumoxytol; flexibility; frontier; gamma-Aminobutyric Acid; image reconstruction; imaging biomarker; imaging modality; improved; in vivo; insight; magnetic field; mouse development; neurovascular; novel; pre-clinical; pre-clinical research; primary endpoint; prototype; reconstruction; research study; response biomarker; temporal measurement; tool

PROJECT SUMMARY The burden of mental illness continues to be a growing challenge in the United States. At the same time, the scientific community continues to study the brain and behavior, revealing relationships between brain structure and function and physiology and illness. The outer scope of brain and behavior research is governed by the imaging and analytical tools available to scientists. Magnetic resonance imaging (MRI) has greatly improved the study of the brain. However, even advanced forms of the technology have significant limitations. Specifically, all MRI techniques rely on a qualitative signal for semi-quantitative measurements. Moreover, standard MRI acquisition exhibit as much as 70% signal amplitude bias change with the orientation of the cerebral cortical (and hence the large pial vessels) relative to magnetic field. Quantitative Ultra-short Time-to-Echo Contrast-Enhanced (QUTE-CE, pronounced “cute-see”) MRI is a novel imaging modality that generates a quantitative signal directly representative of physiological information that can broaden the outer limit of what current technology makes possible. QUTE-CE advantages, thus far, include production of the highest quantitative measurement of CA concentration in mice; development of unprecedent non-invasive in vivo maps of brain vascular structure (CBV); mapping of neurofunctional response; biomarkers for cancer treatment efficacy; and, measurement of blood- brain barrier (BBB) leakage. This project strives to create a robust software suite to overcome current limitations unlocking the potential of phMRI and fMRI measurement with higher sampling time, increasing signal-to-noise by 1.67 compared to radial sampling and enabling sliding-window reconstruction for simultaneous high-spatial and temporal image reconstruction using the same data set. To achieve this, the project aims to develop and optimize a software prototype for use with industry-standard 7T small animal research scanners, implementing Imaginostics’ proprietary 3D UTE Radial Cones Pulse Sequence. Next, the project strives to test software prototypes and analytically characterize biomarkers. The goal of the project is to ultimately improve and standardize measurements to complement or replace existing options for a more precise approach that is uniquely quantitative at both the individual and group levels. This means potentially fewer animals would be needed to arrive at meaningful results. Moreover, structural, functional and BBB leakage metrics can be captured within one imaging session, greatly enriching the study of healthy and disordered brains. Overall, these efforts can help advance pre-clinical and related brain research efforts on small animals, by incorporating a novel MRI imaging technology into the repertoire of researchers.

项目摘要 在美国，精神疾病的负担仍然是一个日益严峻的挑战。同时对 科学界继续研究大脑和行为，揭示大脑结构之间的关系， 功能、生理和疾病。大脑和行为研究的外部范围由 成像和分析工具。磁共振成像（MRI）大大改善了 大脑的研究。然而，即使是先进的技术形式也有很大的局限性。具体而言，所有 MRI技术依赖于半定量测量的定性信号。此外，标准MRI 采集表现出多达70%的信号幅度偏置随着大脑皮层的取向而变化（以及 因此是大的软膜血管）相对于磁场。定量超短回波时间对比度增强 （QUTE-CE，发音为“cute-see”）MRI是一种新的成像方式，可直接生成定量信号 生理信息的代表，可以扩大当前技术的外部限制， 可能迄今为止，QUTE-CE的优势包括生产CA的最高定量测量 开发前所未有的脑血管结构（CBV）的非侵入性体内图; 神经功能反应的映射;癌症治疗功效的生物标志物;以及血液- 脑屏障（BBB）渗漏。该项目致力于创建一个强大的软件套件，以克服当前的限制 通过更高的采样时间释放phMRI和fMRI测量的潜力，提高信噪比 与径向采样相比提高了1.67倍， 和使用相同数据集的时间图像重建。为了实现这一目标，该项目旨在开发和 优化软件原型，用于行业标准的7 T小型动物研究扫描仪， Imaginostics专有的3D UTE径向锥体脉冲序列。接下来，该项目努力测试软件 原型和分析表征生物标志物。该项目的目标是最终改善和 标准化测量，以补充或取代现有的更精确的方法， 在个人和群体层面上都是独一无二的。这意味着可能会减少动物数量 需要达成有意义的结果。此外，可以捕获结构、功能和BBB泄漏指标 这极大地丰富了对健康和紊乱大脑的研究。总的来说，这些努力 通过整合一种新型的MRI， 成像技术进入研究人员的剧目。