Next-generation ultrafast functional 3D pulmonary imaging

下一代超快功能 3D 肺部成像

• 批准号: 10534125
• 负责人: Nuwandi M Ariyasingha U W
• 金额: $ 6.97万
• 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/10534125
• 关键词: 3-Dimensional; Address; Affect; Alveolus; Asthma; Attention; Award; Bronchiolitis; Caring; Cause of Death; Cessation of life; Chronic Obstructive Pulmonary Disease; Clinical; Clinical Research; Communities; Contrast Media; Custom; Detection; Devices; Diagnosis; Diffusion; Disease; Disease Progression; Dose; Early Diagnosis; Effectiveness; Epidemic; Equipment; FDA approved; Face; Fatty acid glycerol esters; Food; Functional Imaging; Future; Gases; Goals; Hour; Human; Image; Imaging Techniques; Inhalation; Ionizing radiation; Isomerism; Lung; Lung diseases; MRI Scans; Magnetic Resonance Imaging; Mammary Ultrasonography; Modality; Modeling; Monitor; Noble Gases; Nuclear; Pathology; Patient-Focused Outcomes; Perfusion; Persons; Phase; Physics; Physiologic pulse; Pneumonia; Population; Positron-Emission Tomography; Preparation; Process; Production; Propane; Protons; Pulmonary Fibrosis; Radiation-Induced Cancer; Relaxation; Reporting; Research; Research Proposals; Resolution; Risk; Roentgen Rays; Safety; Scientist; Sheep; Signal Transduction; Techniques; Three-Dimensional Imaging; Time; Tissues; Training; Variant; Viral; Water; Woman; X-Ray Computed Tomography; cancer imaging; career; clinical imaging; clinical translation; clinically relevant; constriction; coronavirus disease; cost; design; effectiveness study; high throughput technology; idiopathic pulmonary fibrosis; imaging capabilities; imaging modality; improved; in vivo; lung imaging; lung injury; magnetic field; men; next generation; novel; pulmonary function; research study; screening; skills; soft tissue; tool; treatment response; tumor; ventilation

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.

项目摘要 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会影响 全世界超过3亿人，每年造成约300万人死亡。目前临床上还没有广泛的 进行高分辨率功能性肺成像的成像方式：CT、常规MRI和X线只能 提供致密组织的结构图像-提供肿瘤和肺炎等病理信息-但 很少或没有关于肺通气、灌注、肺泡大小等的信息。 癌症成像，包括MRI，CT，超声，乳房X光检查，PET和其他， 能够早期发现（通过人群筛查）、诊断和监测对治疗的反应。 此外，CT扫描使身体暴露于电离辐射，并且因此不能频繁地进行，这是由于： 与致癌辐射相关的风险增加。超极化惰性气体（例如129 Xe）的MRI报告 对肺功能的影响：通气和弥散。尽管在这一领域取得了显著的研究突破， 超极化惰性气体MRI检测多种肺部疾病和监测的有效性和安全性 治疗反应，这种成像方式的广泛临床适应的前景面临重大挑战。 挑战，包括（i）用于生产超极化129 π ι的设备的高成本和复杂性 气体，以及（ii）定制的MRI扫描仪的要求，能够129毫米-注意，所有FDA批准的MRI 扫描仪只能对质子成像。我们已经开发了临床规模的生产质子超极化 丙烷气超极化丙烷气体生产的方法非常简单，高效， 低成本。使用一次性超偏振器可在2秒内制备造影剂剂量。此外，委员会认为， 丙烷已经被FDA批准在食品中无限制地安全使用。因此，超极化丙烷肺MRI 可以应对超极化129氪气体的挑战。在这个培训奖下，我将接受培训， 使用超极化丙烷气体的三种自旋异构体的下一代3D超快速肺部成像能力。我 假设有可能产生高度对称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可以产生气体扩散和通气的无背景功能性肺图像。 在这个项目中，我将开发临床规模的生产这些自旋异构体和他们的超快MRI在切除 绵羊肺的目标是系统的松弛映射，为未来的体内研究。临床翻译 这种新的快速和低成本的成像方式将彻底改变肺部成像和肺部护理的广泛 一系列的肺部疾病-这是我的长期职业目标。