Relationship between Pulmonary Gas Exchange Function and Brain Uptake Dynamics Investigated with Hyperpolarized 129Xe MR Imaging and Spectroscopy in a Murine Model of Chronic Obstructive Pulmonary Disease.

Purpose: Chronic obstructive pulmonary disease (COPD) is a complex multisystem disease associated with comorbidities outside the lungs. The aim of this study was to measure changes in metrics of pulmonary gas exchange function and brain tissue metabolism in a mouse model of COPD using hyperpolarized ¹²⁹Xe (HP ¹²⁹Xe) MRI/MR spectroscopy (MRS) and investigate the relationship between the metrics of lung and brain.

Methods: COPD phenotypes were induced in 15 mice by 6-week administration of cigarette smoke extract (CSE) and lipopolysaccharide (LPS). A separate negative control (NC) group was formed of 6 mice administered with saline for 6 weeks. After these 6-week administrations, the pulmonary gas exchange function parameter f_D (%) and the rate constant, α (s^-1), which are composed of the cerebral blood flow F_i and the longitudinal relaxation rate 1/T_1i in brain tissue, were evaluated by HP ¹²⁹Xe MRI/MRS.

Results: The f_D of CSE-LPS mice was significantly lower than that of NC mice, which was in parallel with an increase in bronchial wall thickness. The α in the CSE-LPS mice decreased with the decrease of f_D in contrast to the trend in the NC mice. To further elucidate the opposed trend, the contribution of T_1i was separately determined by measuring F_i. The T_1i in the CSE-LPS mice was found to correlate negatively with f_D as opposed to the positive trend in the NC mice. The opposite trend in T_1i between CSE-LPS and NC mice suggests hypoxia in the brain, which is induced by the impaired oxygen uptake as indicated by the reduced f_D.

Conclusion: This study demonstrates the feasibility of using HP ¹²⁹Xe MRI/MRS to study pathological mechanisms of brain dysfunction in comorbidities with COPD.