Magnetic Resonance Imaging ( MRI ) of the lung as a tool for the non-invasive evaluation of drugs in rat models of airways diseases

ALTEX 22, Special Issue 2005 318 The inflammatory status of the lungs in rat models of airways diseases is traditionally inferred from Bronchoalveolar Lavage Fluid (BALF) analysis and/or histology. For lung function analysis rats are usually tracheotomised and artificially ventilated. To suppress spontaneous respiration animals receive a muscle relaxant. From measurements of airflow and transpulmonary pressure, airway resistance is calculated after each respiratory cycle. Clearly, the invasive character of these procedures precludes repeated assessments in the same animal. We have developed MRI approaches in which acquisitions are performed on spontaneously breathing, anaesthetised animals. Neither artificial ventilation nor tracheotomy is necessary. Therefore, interference with the pathophysiology and discomfort for the animals should be minimal. In addition, repetitive measurements are feasible. We estimate that this leads to a reduction in the number of animals used for this sort of experiments by at least 70%. Two illustrative examples are allergen (ovalbumin, OVA) and lipopolysaccharide (LPS) inducing distinct inflammatory responses in rats. For OVA, MRI signals correlate with eosinophilia and increased protein content in BALF. Following LPS, MRI signals reflect secreted mucus as revealed in BALF. Histology confirms these results. The effects of airways remodelling and hyporesponsiveness induced by respectively OVA or LPS can also be monitored by detecting modulations of the parenchymal signal caused by changes in oxygenation levels. This opens the avenue for noninvasive assessments of lung function. Overall, these approaches provide the basis for non-invasive testing of anti-inflammatory compounds for respiratory diseases.