Pulmonary 3He Magnetic Resonance Imaging Biomarkers of Regional Airspace Enlargement in Alpha-1 Antitrypsin Deficiency

Eric Lessard; Heather M Young; Anurag Bhalla; Damien Pike; Khadija Sheikh; David G McCormack; Alexei Ouriadov; Grace Parraga

doi:10.1016/j.acra.2017.05.008

Pulmonary ³He Magnetic Resonance Imaging Biomarkers of Regional Airspace Enlargement in Alpha-1 Antitrypsin Deficiency

Acad Radiol. 2017 Nov;24(11):1402-1411. doi: 10.1016/j.acra.2017.05.008. Epub 2017 Jun 20.

Authors

Eric Lessard¹, Heather M Young¹, Anurag Bhalla², Damien Pike¹, Khadija Sheikh¹, David G McCormack³, Alexei Ouriadov¹, Grace Parraga⁴

Affiliations

¹ Robarts Research Institute, 1151 Richmond Street North, London, ON, Canada N6A 5B7; Department of Medical Biophysics, The University of Western Ontario, 1151 Richmond St North, London, ON, Canada N6A 5C1.
² Robarts Research Institute, 1151 Richmond Street North, London, ON, Canada N6A 5B7.
³ Division of Respirology, Department of Medicine, The University of Western Ontario, London, Ontario, Canada.
⁴ Robarts Research Institute, 1151 Richmond Street North, London, ON, Canada N6A 5B7; Department of Medical Biophysics, The University of Western Ontario, 1151 Richmond St North, London, ON, Canada N6A 5C1. Electronic address: gparraga@robarts.ca.

PMID: 28645458
DOI: 10.1016/j.acra.2017.05.008

Abstract

Rationale and objectives: Thoracic x-ray computed tomography (CT) and hyperpolarized ³He magnetic resonance imaging (MRI) provide quantitative measurements of airspace enlargement in patients with emphysema. For patients with panlobular emphysema due to alpha-1 antitrypsin deficiency (AATD), sensitive biomarkers of disease progression and response to therapy have been difficult to develop and exploit, especially those biomarkers that correlate with outcomes like quality of life. Here, our objective was to generate and compare CT and diffusion-weighted inhaled-gas MRI measurements of emphysema including apparent diffusion coefficient (ADC) and MRI-derived mean linear intercept (L_m) in patients with AATD, chronic obstructive pulmonary disease (COPD) ex-smokers, and elderly never-smokers.

Materials and methods: We enrolled patients with AATD (n = 8; 57 ± 7 years), ex-smokers with COPD (n = 8; 77 ± 6 years), and a control group of never-smokers (n = 5; 64 ± 2 years) who underwent thoracic CT, MRI, spirometry, plethysmography, the St. George's Respiratory Questionnaire, and the 6-minute walk test during a single 2-hour visit. MRI-derived ADC, L_m, surface-to-volume ratio, and ventilation defect percent were generated for the apical, basal, and whole lung as was CT lung area ≤-950 Hounsfield units (RA₉₅₀), low attenuating clusters, and airway count.

Results: In patients with AATD, there was a significantly different MRI-derived ADC (P = .03), L_m (P < .0001), and surface-to-volume ratio (P < .0001), but not diffusing capacity of carbon monoxide, residual volume or total lung capacity, or CT RA₉₅₀ (P > .05) compared to COPD ex-smokers with a significantly different St. George's Respiratory Questionnaire.

Conclusions: In this proof-of-concept demonstration, we evaluated CT and MRI lung emphysema measurements and observed significantly worse MRI biomarkers of emphysema in patients with AATD compared to patients with COPD, although CT RA₉₅₀ and diffusing capacity of carbon monoxide were not significantly different, underscoring the sensitivity of MRI measurements of AATD emphysema.

Keywords: Alpha-1 antitrypsin deficiency; augmentation therapy; emphysema; hyperpolarized (3)He magnetic resonance imaging.

Publication types

Comparative Study

MeSH terms

Aged
Aged, 80 and over
Biomarkers
Diffusion Magnetic Resonance Imaging / methods*
Female
Helium
Humans
Isotopes
Magnetic Resonance Imaging / methods*
Male
Middle Aged
Proof of Concept Study
Pulmonary Diffusing Capacity
Pulmonary Disease, Chronic Obstructive / diagnostic imaging
Pulmonary Disease, Chronic Obstructive / physiopathology
Pulmonary Emphysema / diagnostic imaging*
Pulmonary Emphysema / etiology
Pulmonary Emphysema / physiopathology*
Quality of Life
Radiopharmaceuticals
Residual Volume
Smoking Cessation
Tomography, X-Ray Computed*
Total Lung Capacity
alpha 1-Antitrypsin Deficiency / complications*

Substances

Biomarkers
Isotopes
Radiopharmaceuticals
Helium
Helium-3