Abstract

PurposeA magnetic resonance imaging method is presented that allows for the simultaneous assessment of oxygen delivery, oxygen uptake, and parenchymal density. The technique is applied to a mouse model of porcine pancreatic elastase (PPE) induced lung emphysema in order to investigate how structural changes affect lung function.MethodNine-week-old female C57BL6 mice were instilled with saline or PPE at days 0 and 7. At day 19, oxygen delivery, oxygen uptake, and lung density were quantified from T1 and proton-density measurements obtained via oxygen-enhanced magnetic resonance imaging (OE-MRI) using an ultrashort echo-time imaging sequence. Subsequently, the lungs were sectioned for histological observation. Blood-gas analyses and pulmonary functional tests via FlexiVent were performed in separate cohorts.Principal FindingsPPE-challenged mice had reduced density when assessed via MRI, consistent with the parenchyma loss observed in the histology sections, and an increased lung compliance was detected via FlexiVent. The oxygenation levels, as assessed via the blood-gas analysis, showed no difference between PPE-challenged animals and control. This finding was mirrored in the global MRI assessments of oxygen delivery and uptake, where the changes in relaxation time indices were matched between the groups. The heterogeneity of the same parameters however, were increased in PPE-challenged animals. When the oxygenation status was investigated in regions of varying density, a reduced oxygen-uptake was found in low-density regions of PPE-challenged mice. In high-density regions the uptake was higher than that of regions of corresponding density in control animals. The oxygen delivery was proportional to the oxygen uptake in both groups.ConclusionsThe proposed method allowed for the regional assessment of the relationship between lung density and two aspects of lung function, the oxygen delivery and uptake. When compared to global indices of lung function, an increased sensitivity for detecting heterogeneous lung disorders was found. This indicated that the technique has potential for early detection of lung dysfunction–before global changes occur.

Highlights

  • The proposed method allowed for the regional assessment of the relationship between lung density and two aspects of lung function, the oxygen delivery and uptake

  • Emphysema arising from the destruction of alveolar walls is one of the main conditions of chronic obstructive pulmonary disease (COPD)–presently the third leading cause of death in the world [1]

  • The S0 of the air measurement (S0air), R1, ΔR1, and ΔR2Ã maps for porcine pancreatic elastase (PPE)-challenged animals appeared more heterogeneous than maps for control animals, indicating a less uniform lung density, alveolar oxygen delivery, and oxygen uptake respectively (Fig 1A and 1B)

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Summary

Introduction

Emphysema arising from the destruction of alveolar walls is one of the main conditions of chronic obstructive pulmonary disease (COPD)–presently the third leading cause of death in the world [1]. The lung-tissue breakdown leads to a loss of elastic recoil and to the enlargement of air spaces, causing airflow obstruction, impaired gas exchange, and lung hyperinflation [2] In clinical trials, these conditions can be assessed using pulmonary function tests such as FEV1 (forced expiratory volume in 1 second), arterial blood gas analysis, and lung volume measurements at rest or during exercise [3]. The loss of parenchymal tissue (density) can be detected by magnetic resonance imaging (MRI), being manifested as a reduction in proton density [6,7,8,9] This technique has been applied for portraying the emphysema extent in COPD patients, where an agreement between MRI density mapping and CT densitometry was reported [8]

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