Next-generation ultrafast functional 3D pulmonary imaging

下一代超快功能 3D 肺部成像

• 批准号: 10314284
• 负责人: Nuwandi M Ariyasingha U W
• 金额: $ 6.81万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-07 至 2024-09-06
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10314284
• 关键词: Next; generation; ultrafast; functional; 3D

PROJECT SUMMARY Deadly diseases such as COPD, asthma, lung injury, constrictive bronchiolitis, and pulmonary fibrosis affect >300 million people worldwide and cause ~3 million annual deaths. There is currently no widespread clinical imaging modality to perform high-resolution functional lung imaging: CT, conventional MRI, and X-ray can only provide structural images of dense tissues—informing about pathologies like tumors and pneumonia—but yielding little or no information about lung ventilation, perfusion, alveoli size, etc. This state of affairs contrasts with cancer imaging, which includes MRI, CT, ultrasound, mammography, PET and others, which collectively enable early detection (via population screening), diagnoses, and monitoring response to treatment. Furthermore, CT scans expose the body to ionizing radiation, and thus cannot be performed frequently due to increased risk associated with cancer-inducing radiation. MRI of hyperpolarized noble gases (e.g. 129Xe) reports on lung function: ventilation and diffusion. Despite remarkable research breakthroughs in this field demonstrating the effectiveness and safety of hyperpolarized noble gas MRI to detect a wide range of lung diseases and monitor response to treatment, the prospects for widespread clinical adaptation of this imaging modality face major challenges, including (i) the high cost and complexity of the equipment for production of hyperpolarized 129Xe gas, and (ii) the requirement for a customized MRI scanner capable of 129Xe – note, all FDA-approved MRI scanners can image only protons. We have developed clinical-scale production of proton-hyperpolarized propane gas. The process of hyperpolarized propane gas production is remarkably simple, highly efficient and low-cost. A dose of contrast agents can be prepared in 2 seconds using disposable hyperpolarizer. Moreover, propane is already FDA-approved for unlimited safe use in foods. Therefore, hyperpolarized propane lung MRI can obviate the challenges of hyperpolarized 129Xe gas. Under this training award, I will be trained to develop next-generation 3D ultra-fast lung imaging capability using three spin isomers of hyperpolarized propane gas. I hypothesize that it may be possible to create highly symmetric hyperpolarized propane spin isomer capable of retaining hyperpolarized state for ~1 minute in the gas phase at clinically relevant conditions. Sub-second 3D MRI of these spin isomers can produce background-free functional lung images of gas diffusion and ventilation. In this project, I will develop clinical-scale production of these spin isomers and their ultrafast MRI in excised sheep lungs with the goal of systematic relaxation mapping for future in vivo studies. The clinical translation of this new fast and low-cost imaging modality will revolutionize pulmonary imaging and pulmonary care of a wide range of lung diseases—this is my long-term career goal.

项目概要 慢性阻塞性肺病、哮喘、肺损伤、缩窄性细支气管炎和肺纤维化等致命疾病影响 全球超过 3 亿人，每年造成约 300 万人死亡。目前临床尚无广泛应用 进行高分辨率功能性肺部成像的成像方式：CT、常规 MRI 和 X 射线只能 提供致密组织的结构图像——了解肿瘤和肺炎等病理情况——但是 产生很少或没有关于肺通气、灌注、肺泡大小等的信息。这种情况形成对比 癌症成像，包括 MRI、CT、超声波、乳房 X 线摄影、PET 等，这些统称为 实现早期检测（通过人群筛查）、诊断和监测治疗反应。 此外，CT扫描使身体暴露在电离辐射下，因此不能频繁进行，因为 与致癌辐射相关的风险增加。超极化惰性气体（例如 129Xe）的 MRI 报告 对肺功能的影响：通气和弥散。尽管该领域取得了显着的研究突破 超极化惰性气体 MRI 检测和监测多种肺部疾病的有效性和安全性 对治疗的反应，这种成像方式广泛临床适应的前景面临重大挑战 挑战，包括（i）超极化129Xe生产设备的高成本和复杂性 气体，以及 (ii) 对能够达到 129Xe 的定制 MRI 扫描仪的要求 – 请注意，所有 FDA 批准的 MRI 扫描仪只能对质子成像。我们已经开发出质子超极化的临床规模生产 丙烷气。超极化丙烷气生产过程非常简单、高效且 低成本。使用一次性超极化器可在 2 秒内制备一剂造影剂。而且， 丙烷已获得 FDA 批准，可在食品中无限安全使用。因此，超极化丙烷肺 MRI 可以消除超极化 129Xe 气体的挑战。在这个培训奖下，我将接受培训以发展 使用超极化丙烷气体的三种自旋异构体的下一代 3D 超快速肺部成像功能。我 假设有可能产生高度对称的超极化丙烷自旋异构体 在临床相关条件下，在气相中保持超极化状态约 1 分钟。亚秒级 3D 这些自旋异构体的 MRI 可以生成气体扩散和通气的无背景功能性肺部图像。 在这个项目中，我将开发这些自旋异构体的临床规模生产及其在切除中的超快 MRI 羊肺的目标是为未来的体内研究提供系统的松弛图谱。临床翻译 这种新的快速且低成本的成像方式将彻底改变广泛的肺部成像和肺部护理 一系列肺部疾病——这是我的长期职业目标。