Longitudinal and noninvasive assessment of emphysema evolution in a murine model using proton MRI
Magdalena Zurek1, Laurent Boyer, Philippe Caramelle
1Université de Lyon, CREATIS-LRMN, Lyon, France.
Abstract:
Ultrashort echo time (550 μs) MR imaging was implemented to track the emphysema development in mice lung challenged with elastase. Two parameters, namely, signal intensity and T 2, were used to monitor the disease evolution. Nine mice were imaged before and at 24 h as well as at 3 and 8 weeks after elastase instillation. Five mice instilled with saline served as controls. At week 8, the mean normalized signal intensity ± SD was 0.89 ± 0.20 for healthy controls and 0.64 ± 0.10 for animals with emphysema. Similarly, a reduced value of T 2 (1.27 ± 0.35 ms vs 0.96 ± 0.18 ms) was found in the emphysema group. The mean signal intensity drop and the reduction of T 2 were prominent at 3 weeks following elastase instillation and stabilized between 3 and 8 weeks. The results indicated an excellent agreement between MR findings and histological morphometry (signal intensity, r = -0.78, P = 0.004; T 2, r = -0.78, P = 0.001). This result shows that proton MRI allows structural changes at alveolar level to be monitored longitudinally. This technique, applied routinely in preclinical trials will represent a valuable tool for assessment of drug therapy efficacy.
Insights
Ultrashort echo time MRI effectively tracks emphysema progression in mice lungs by monitoring signal intensity and T2 changes. This non-invasive imaging method correlates well with histology, aiding drug therapy assessment.
Area of Science:
- Biomedical Imaging
- Pulmonary Research
- Preclinical Disease Modeling
Background:
- Emphysema is a progressive lung disease characterized by alveolar destruction.
- Accurate longitudinal monitoring of emphysema development is crucial for therapeutic evaluation.
- Current methods may lack the sensitivity or resolution for early-stage detection.
Purpose of the Study:
- To evaluate ultrashort echo time (550 μs) MRI for tracking emphysema progression in a mouse model.
- To assess the utility of signal intensity and T2 relaxation time as quantitative biomarkers.
- To determine the correlation between MRI findings and histological emphysema severity.
Main Methods:
- Elastase was used to induce emphysema in nine mice, with five saline-instilled mice serving as controls.
- Mice were imaged using ultrashort echo time MRI at baseline, 24 hours, 3 weeks, and 8 weeks post-instillation.
- Signal intensity and T2 values were quantified and compared between groups and correlated with histological data.
Main Results:
- Emphysematous mice showed significantly lower normalized signal intensity (0.64 ± 0.10 vs 0.89 ± 0.20) and T2 values (0.96 ± 0.18 ms vs 1.27 ± 0.35 ms) at 8 weeks compared to controls.
- These changes were prominent by 3 weeks and stabilized thereafter.
- MRI parameters demonstrated excellent agreement with histological morphometry (r = -0.78 for both).
Conclusions:
- Ultrashort echo time proton MRI is a valuable tool for longitudinal monitoring of structural changes in emphysema at the alveolar level.
- Signal intensity and T2 relaxation time serve as reliable biomarkers for disease progression.
- This technique holds promise for routine application in preclinical trials to assess the efficacy of emphysema therapies.
