The aim of the study was to evaluate the sensitivity of magnetic resonance imaging (MRI) to local lung changes in patients treated with CFTR modulators. Among the patients treated at the Cystic Fibrosis Center of the Lombardy Region, 25 were included in the study. Clinical data and MRI images were collected over a 4-year period, before and during therapy, and a total of 157 MRIs were analyzed. The data were collected in a database and analyzed through the development of dedicated algorithms. The study shows a good correlation between MRI and respiratory function data during therapy, with an improvement in both spirometry test results and MRI quantified ventilation. The results suggest that MRI could represent a more precise technique for monitoring the individual response to treatment, sensitive to local lung alterations, without exposing the patient to ionizing radiation, like those generated by X-rays. Further studies with a larger dataset could lead to an evaluation of the local efficacy of drug treatments.