Assessing Regional Ventilatory Function in Thoracic Insufficiency Syndrome Patients via Dynamic MRI

Background: Free tidal breathing dynamic MRI (dMRI) is useful for practical clinical application in patients with thoracic insufficiency syndrome (TIS). Methods: Volumetric parameters were derived via 129 dMRI images from 51 normal children and 39 TIS patients for left and right lungs, hemi-diaphragms, and hemi-chest walls during tidal breathing. Pairwise t-testing was performed to compare the parameters from TIS patients before and after surgery. Mahalanobis distances (MDs) utilizing parameters of TIS patients and age-matched normal children were assessed to evaluate the closeness of patient lung function to normality. Linear regression was performed to serve as a reference to estimate volume deviations from normality in TIS patients. Findings: Average MDs for right hemi-diaphragm tidal volume (RDtv) were -1.32+1.04 and -0.05+1.11 pre-operatively and post-operatively, respectively, (p=0.004). Average MDs for the ratio of bilateral hemi-diaphragm tidal volume to bilateral lung tidal volume (BDtv/BLtv) were -1.68+1.21 and -0.04+1.10 pre-operatively and post-operatively, respectively (p = 0.001). MDs decreased after treatment suggesting decreased deviations from normality. Regression results showed that all volumes and tidal volumes significantly increased after treatment (p < 0.001), and that increases were greater than those expected from normal growth for RDtv, RLtv, BDtv, and BLtv. Interpretation: Post-operative tidal volumes of bilateral lungs and bilateral hemi-diaphragms of TIS patients came closer to those of normal children indicating positive treatment effects from surgery. QdMRI facilitates assessment of regional effects of surgery to treat TIS. Funding Statement: This research is supported by a grant 1R01HL150147-01 from the National Institutes of Health. This research is also supported in part by the Institute for Translational Medicine and Therapeutics of the University of Pennsylvania through a grant by the National Center for Advancing Translational Sciences of the National Institutes of Health under award number UL1TR001878. Declaration of Interests: There is no conflict of interest or industry support. Ethics Approval Statement: All normal children’s data were acquired under an ongoing prospective research study protocol and all TIS patient data were retrieved from a retrospective study protocol. Both protocols were approved by the Institutional Review Board at the Children’s Hospital of Philadelphia (CHOP) and University of Pennsylvania, along with Health Insurance Portability and Accountability Act waiver.