Developing Hyperpolarized Butane Gas for Ventilation Lung Imaging

NMR hyperpolarization dramatically
improves the detection
sensitivity
of magnetic resonance through the increase in nuclear spin polarization.
Because of the sensitivity increase by several orders of magnitude,
additional applications have been unlocked, including imaging of gases
in physiologically relevant conditions. Hyperpolarized 129Xe gas recently received FDA approval as the first inhalable gaseous
MRI contrast agent for clinical functional lung imaging of a wide
range of pulmonary diseases. However, production and utilization of
hyperpolarized 129Xe gas faces a number of translational
challenges including the high cost and complexity of contrast agent
production and imaging using proton-only (i.e., conventional) clinical
MRI scanners, which are typically not suited to scan 129Xe nuclei. As a solution to circumvent the translational challenges
of hyperpolarized 129Xe, we have recently demonstrated
the feasibility of a simple and cheap process for production of proton-hyperpolarized
propane gas contrast agent using ultralow-cost disposable production
equipment and demonstrated the feasibility of lung ventilation imaging
using hyperpolarized propane gas in excised pig lungs. However, previous
pilot studies have concluded that the hyperpolarized state of propane
gas decays very fast with an exponential decay T1 constant of ∼0.8 s at 1 bar (physiologically relevant
pressure); moreover, the previously reported production rates were
too slow for potential clinical utilization. Here, we investigate
the feasibility of high-capacity production of hyperpolarized butane
gas via heterogeneous parahydrogen-induced polarization using Rh nanoparticle-based
catalyst utilizing butene gas as a precursor for parahydrogen pairwise
addition. We demonstrate a remarkable result: the lifetime of the
hyperpolarized state can be nearly doubled compared to that of propane
(T1 of ∼1.6 s and long-lived spin-state TS of ∼3.8 s at clinically relevant 1
bar pressure). Moreover, we demonstrate a production speed of up to
0.7 standard liters of hyperpolarized gas per second. These two synergistic
developments pave the way to biomedical utilization of proton-hyperpolarized gas media for ventilation imaging. Indeed, here we
demonstrate the feasibility of phantom imaging of hyperpolarized butane
gas in Tedlar bags and also the feasibility of subsecond 2D ventilation
gas imaging in excised rabbit lungs with 1.6 × 1.6 mm2 in-plane resolution using a clinical MRI scanner. The demonstrated
results have the potential to revolutionize functional pulmonary imaging
with a simple and inexpensive on-demand production of proton-hyperpolarized gas contrast media, followed by visualization on
virtually any MRI scanner, including emerging bedside low-field MRI
scanner technology.

核磁共振（Nuclear Magnetic Resonance, NMR）超极化技术通过提升核自旋极化水平，可显著改善磁共振检测灵敏度。由于灵敏度可提升数个数量级，该技术解锁了诸多新应用场景，其中包括生理相关条件下的气体成像。超极化氙-129（¹²⁹Xe）气体近日获美国食品药品监督管理局（Food and Drug Administration, FDA）批准，成为首款可吸入气态磁共振成像（Magnetic Resonance Imaging, MRI）对比剂，用于多种肺部疾病的临床功能性肺成像。然而，超极化¹²⁹Xe气体的生产与应用面临诸多转化难题：包括对比剂生产成本高昂、流程复杂，以及常规临床磁共振扫描仪仅支持质子成像（即传统型扫描仪），通常无法对¹²⁹Xe原子核进行扫描。为解决超极化¹²⁹Xe的转化应用难题，我们团队近期证实了一种简便低成本的生产工艺可行性：使用超低成本的一次性生产设备制备质子超极化丙烷气体对比剂，并在离体猪肺中验证了使用超极化丙烷气体进行肺通气成像的可行性。不过，此前的先导研究表明，丙烷气体的超极化态衰减极快，在1巴（生理相关压力）下的指数衰减T₁常数约为0.8秒；且此前报道的生产速率过慢，无法满足潜在临床应用需求。本研究旨在探索通过非均相仲氢诱导极化（parahydrogen-induced polarization）工艺，以丁烯气体为前驱体开展仲氢成对加成反应，利用铑（Rhodium, Rh）纳米颗粒基催化剂实现高产能超极化丁烷气体生产的可行性。我们取得了突破性进展：与丙烷相比，超极化态的寿命可提升近一倍——在临床相关的1巴压力下，其T₁常数约为1.6秒，长寿命自旋态TS约为3.8秒。此外，我们实现的生产速率可达每秒0.7标准升超极化气体。这两项协同进展为质子超极化气体介质用于通气成像的生物医学应用铺平了道路。实际上，本研究验证了超极化丁烷气体在泰德拉（Tedlar）袋中的体模成像可行性，并利用临床磁共振扫描仪在离体兔肺中实现了面内分辨率达1.6×1.6 mm²的亚秒级二维通气气体成像。本次研究成果有望通过简便低成本的按需式质子超极化气体对比剂生产，结合几乎所有类型磁共振扫描仪（包括新兴的床边低场磁共振扫描仪技术）实现可视化，从而彻底革新功能性肺部成像技术。