Significance: Hyperpolarized ¹²⁹ Xe NMR/MRI is a useful method for diagnosis of diseases of the respiratory system. However, the sensitive detection of specific compounds in blood remains a challenge because of the weak ¹²⁹ Xe signal in aqueous solution. We developed a way, Hyper-SAME, to promote the ¹²⁹ Xe signal in aqueous solution. The ¹²⁹ Xe signal intensity is four times beyond that of free ¹²⁹ Xe in water and 200 times better than the benchmark molecular cage, cryptophane-A, in its saturated aqueous solution. Additionally, the hyperpolarized ¹²⁹ Xe signal can be amplified further by combining Hyper-SAME with hyperpolarized ¹²⁹ Xe chemical exchange saturation transfer.

The recovery process of COVID-19 patients is unclear. Some recovered patients complain of continued shortness of breath. Vasculopathy has been reported in COVID-19, stressing the importance of probing microstructure and function of lungs at the alveolar-capillary interface. While CT detects structural abnormalities, little is known about the impact of disease on lung function. ¹²⁹Xe MRI is a technique uniquely capable of assessing ventilation, microstructure and gas exchange. Using ¹²⁹Xe MRI, we found COVID-19 patients have higher ventilation defects percentage (5.9% vs 3.7%), unchanged microstructure, longer gas-blood exchange time (43.5 ms vs 32.5 ms), and reduced RBC/TP (0.279 vs 0.330) compared with healthy subjects. These findings suggest regional ventilation and alveolar airspace dimensions are relatively normal around the time of discharge, while gas-blood exchange function is diminished. This study establishes the feasibility of localized lung function measurement in COVID-19 patients. Such readouts could be useful as a supplement to structural imaging.