Hyperpolarized 129Xe for investigation of mild cystic fibrosis lung disease in pediatric patients

Abstract

Background: Cystic fibrosis (CF) is a genetic disease which carries high morbidity and mortality from lung-function decline. Monitoring disease progression and treatment response in young patients is desirable, but serial imaging via CT is often considered prohibitive, and detailed functional information cannot be obtained using conventional imaging techniques. Hyperpolarized ¹²⁹Xe magnetic resonance imaging (MRI) can depict and quantify regional ventilation, but has not been investigated in pediatrics. We hypothesized that ¹²⁹Xe MRI is feasible and would demonstrate ventilation defects in mild CF lung disease with greater sensitivity than FEV₁.

Methods: 11 healthy controls (age 6-16years) and 11 patients with mild CF (age 8-16years, Forced Expiratory Volume (FEV₁) percent predicted >70%) were recruited for this study. Nine CF patients had an FEV₁>85%. Each subject was imaged via hyperpolarized ¹²⁹Xe MRI, and the ventilation defect percentage (VDP) was measured. FEV₁ and VDP were compared between the groups.

Results: FEV₁ for controls was 100.3%±8.5% (mean±sd) and for CF patients was 97.9%±16.0% (p=0.67). VDP was 6.4%±2.8% for controls and 18.3%±8.6% for CF (p<0.001). When considering the 9 CF patients with normal FEV₁ (>85%), the mean FEV₁ was 103.1%±12.3% (p=0.57 compared to controls) and VDP was 15.4%±6.3% (p=0.002).

Conclusions: Hyperpolarized ¹²⁹Xe MRI demonstrated ventilation defects in CF patients with normal FEV₁ and more effectively discriminated CF from controls than FEV₁. Thus ¹²⁹Xe may be a useful outcome measure to detect mild CF lung disease, to investigate regional lung function in pediatric lung diseases, and to follow disease progression.

Keywords: Cystic fibrosis; Hyperpolarized; Mri; Pediatric.

Figure 1

Plot of whole-lung VDP in control (•) and CF (○) cohorts. VDP was plotted as a function of defect threshold (expressed as percentage of whole-lung signal mean) and the difference between CF and control defect percentages (▲), illustrating the greatest difference near a 60% defect threshold. Lines extending from data points are standard-deviation error bars. Control patient #5 was imaged twice, and both image sets were included here (hence n = 12 for controls).

Figure 2

Axial HP ¹²⁹Xe MRI slices of Healthy Control #10, CF patient #9 (highest VDP), and CF patient #7 (high FEV₁ and VDP) both with and without defect voxels identified.

Figure 3

Hyperpolarized ¹²⁹Xe images in healthy volunteer #5, with and without defect voxels colored, using ¹²⁹Xe hyperpolarized in a homebuilt polarizer (top) and commercial polarizer (bottom). Mean VDP for this patient was 8.6% (higher than our mean for controls, detailed in Table 2).

Figure 4

A: Plot of FEV₁ vs VDP for all subjects (healthy, filled symbols; CF, open symbols) demonstrating the wide range of ventilation defects among the near-normal FEV₁ values. Solid lines are control means, dashed lines are CF means. B: Bar plot showing mean for FEV₁ for control and CF populations. C: Bar plot showing mean VDP for control and CF populations. Error bars are standard deviations. Individual numeric data are provided in Table 2.