Low-magnetic-field NMR relaxometry detects alveolarization in the developing lung

Abstract

Bronchopulmonary dysplasia (BPD) is a major complication of premature birth and a leading cause of morbidity, mortality, and health care utilization. Susceptibility to BPD is strongly linked to the developmental state of the peripheral lung and decreases sharply with the onset of alveolarization, a postnatal phase characterized by rapid increases in tissue microstructural complexity and extracellular matrix assembly. While these processes are well described biologically, their influence on nuclear spin relaxation behavior—particularly at low magnetic field—has not been established.

Here, we hypothesized that the onset and progression of alveolarization produce distinct and measurable changes in hydrogen spin–lattice (T₁) and spin–spin (T₂) relaxation times reflecting evolving tissue composition, water–macromolecule interactions, and microstructural organization. Using a novel and compact low-field ¹H NMR system, we measured T₁ and T₂ in peripheral lung tissues obtained from mouse pups spanning pre- and post-alveolarization stages, as well as from mature adult lungs.

We observed robust, reproducible, and development-dependent reductions in both T₁ and T₂ that coincided with the emergence and maturation of alveolar structures. Relaxation metrics distinguished pre- from post-alveolarization lung tissue, exhibited stable coupling between T₁ and T₂ across development, and showed no detectable inter-lobe variability, indicating sensitivity to intrinsic developmental remodeling. Together, these findings establish low-field NMR relaxometry as a sensitive probe of lung developmental states and provide a framework for interpreting relaxation contrast in heterogeneous, aerated tissues. Our results support continued development of portable relaxometry systems for noninvasive assessment of lung maturation and early stratification of BPD risk. (250/250 words allowable)