Next-generation ultrafast functional 3D pulmonary imaging

项目总结 COPD、哮喘、肺损伤、缩窄性毛细支气管炎和肺纤维化等致命疾病会影响 &gt；全球有3亿人，每年造成约300万人死亡。目前还没有广泛的临床应用 进行高分辨率功能肺成像的成像方式：CT、常规MRI和X光只能 提供致密组织的结构图像-告知肿瘤和肺炎等病理-但 很少或根本没有关于肺通气量、血流灌注量、肺泡大小等的信息。 癌症成像，包括MRI、CT、超声波、乳房X光检查、PET和其他，这些共同 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，因此不能经常进行，因为 与致癌辐射相关的风险增加。超极化惰性气体(如129Xe)的磁共振成像报告 肺功能：换气和弥散。尽管在这一领域取得了显著的研究突破 超极化稀有气体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，这种成像方式在临床上广泛适应的前景面临主要 挑战，包括：(1)生产超极化129Xe的设备成本高且复杂 GAS，以及(Ii)要求定制能够支持129Xe-note的MRI扫描仪，均为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质子超极化生产 丙烷气体。超极化丙烷气的生产工艺非常简单、高效和 低成本。使用一次性超偏振器可以在2秒内制备出一定剂量的造影剂。此外， 丙烷已经被FDA批准在食品中无限制安全使用。因此，超极化丙烷肺磁共振成像 可以避免超极化129Xe气体的挑战。在这个培训奖项下，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超快速肺部成像能力。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~1分钟。亚秒级3D 这些自旋异构体的磁共振成像可以产生气体扩散和通风的无背景功能肺图像。 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的超快mri。 绵羊的肺，目标是为未来的活体研究系统地松弛作图。《红楼梦》的临床翻译 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广泛的肺部护理 一系列肺部疾病--这是我长期的职业目标。

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.