Assessment of Pulmonary Disease in Cystic Fibrosis via Computed Tomography Lung Density Mapping

Isabella Y. Liu, MS (medical student)1,2; Goutham Mylavarapu, PhD3; Raouf S. Amin, MD3; Robert J. Fleck, MD (PI)2

1University of Cincinnati College of Medicine, Cincinnati, Ohio

2Department of Radiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio

3Division of Pulmonary Medicine, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio

Introduction: Pulmonary disease in cystic fibrosis (CF) is characterized by chronic airway inflammation and recurrent lung infections causing progressive lung destruction. Structural lung changes can be detected on chest CT scans when infants with CF have not yet presented with any clinical symptoms. Given the early onset of lung changes, more sensitive measures are needed to monitor early CF lung disease. Lung density maps allow for quantitative assessment of lung volume changes and may be a useful method for evaluating disease severity. We hypothesized that CF patients would have greater total lung volume and greater lung volume in the low-density range (< 920 HU) compared to children with normal lungs.

Methods: This study is part of a larger 3-year case-control study of 93 CF patients and 100 age- and gender-matched controls. High-resolution non-contrast chest CT scans from CF patients with a range of disease severity and control subjects were included. CF disease severity was based on FEV1%: normal (FEV 1% > 100), mild (FEV 1% ≥ 90), moderate (60 ≤ FEV1% < 90) and severe (FEV1% < 60). Control studies were obtained through query of the Radiology Information System (RIS) from January 1, 2015 to December 31, 2019 for children with solid tumors who had lung scans before initiation of treatment. Inclusion criteria for control subjects: 1) absence of acute/chronic respiratory disease, 2) absence of congenital disorder or syndrome, 3) absence of prior surgery violating the chest wall, 4) normal findings on impression and secondary vetting by radiologist as normal study. Eligible controls had chest CT scans within 1 year of diagnosis of malignancy. Semi-automatic three-dimensional lung segmentation was performed using Vitrea CT Lung Density Analysis. Lung density maps were generated and measurements of total lung volumes, low density (-1024 to -920 HU), medium density (-920 to -720 HU), and high density (-720 to 0 HU) volumes were performed. Lung density measures in CF and control subjects were compared with a Mann-Whitney U statistical test.

Results: A total of 57 CF patients (14 normal CF, 15 mild, 11 moderate, 17 severe; 14.7 ± 4.1 years of age) and 80 control subjects (14.5 ± 3.1 years of age) were included in this study. CF patients had significantly greater total lung volume normalized by body surface area (p = 0.005), high-density volume (612.4 ± 306.4 ml vs 468.9 ± 211.9 ml, p = 0.002), and low-density volume index (10.7 ± 13.0 vs 6.9 ± 10.6, p = 0.049) compared to controls. CF patients with severe disease had significantly greater total lung volume normalized by body surface area (p = 0.006), low-density volume (748.5 ± 943.6 ml vs 306.7 ± 649.3 ml, p = 0.01), high-density volume (709.8 ml ± 378.6 ml, p = 0.004), and low density volume index (16.9 ± 16.5, p = 0.004) compared to controls.

Conclusions: Total lung volume normalized by body surface area, high-density volume and low density volume index were significantly greater in CF patients compared to controls. Low density volume was significantly greater in CF patients with severe disease compared to controls. Lung density analysis may be useful in assessing disease severity in the pediatric CF population.

Contact information:

Isabella Y. Liu, MS

liuia@mail.uc.edu

Key Words/Tags:

Cystic fibrosis

Pulmonary disease

Computed tomography (CT)

Lung density

Image analysis