Therapeutic Effects Assessment in Acute Lung Injury Using Hyperpolarized ¹²⁹Xe Magnetic Resonance

Therapeutic effects in acute lung injury (ALI) vary considerably among individuals, presenting a significant clinical challenge in optimizing treatment strategies-particularly with agents such as glucocorticoids. Non-invasive techniques capable of quantifying pulmonary physiological changes in the lung are essential for evaluating treatment efficacy and elucidating underlying mechanisms. Herein, we investigated the feasibility of hyperpolarized ¹²⁹Xe magnetic resonance (MR) for assessing the effects of dexamethasone treatment in a rat model of ALI. Fifteen Wistar rats were randomly assigned to three groups (n = 5 each): a treatment group with lipopolysaccharide (LPS)-induced ALI treated with dexamethasone (DEX), an ALI group subjected to the same LPS induction but treated with normal saline, and a control group receiving only normal saline. All rats underwent ¹²⁹Xe MR, pulmonary function tests (PFTs), computed tomography (CT), and histological analysis. Quantitative results from ¹²⁹Xe MR were analyzed using Kruskal-Wallis tests followed by Conover-Iman multiple comparison tests. Correlations among MRI, PFTs, and CT findings were evaluated. The ratio of ¹²⁹Xe signal in red blood cells to pulmonary Membrane (RBC/Mem) was reduced in the ALI group compared with the control group (median, 0.356 [IQR,0.035] vs. 0.607 [IQR,0.086], p < 0.001) and partially recovered in the treatment group (p < 0.001). Notably, persistent functional impairment in the treatment group was not detected by PFTs or CT imaging. The RBC/Mem correlated well with forced vital capacity (FVC) and mean lung density (MLD) (both p < 0.05). Additionally, hematocrit (Hct) increased in the treatment group compared to the ALI group (Hct: median, 0.242 [IQR, 0.031] vs. 0.216 [IQR, 0.019], p < 0.001). These findings demonstrate the potential of hyperpolarized ¹²⁹Xe MR as a non-invasive and highly sensitive modality for detecting subtle or residual gas-exchange abnormalities, supporting its further application in interventional studies of acute lung injury.