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Clinical Trial
. 2021 Jun;56(6):1440-1448.
doi: 10.1002/ppul.25303. Epub 2021 Feb 23.

Measures of ventilation heterogeneity mapped with hyperpolarized helium-3 MRI demonstrate a T2-high phenotype in asthma

W Gerald Teague  1 , Jaime Mata  2 , Kun Qing  2 , Nicholas J Tustison  2 , John P Mugler  2   3 , Craig H Meyer  2   3 , Eduard E de Lange  2 , Yun M Shim  4 , Kristin Wavell  1 , Talissa A Altes  5
Affiliations
Clinical Trial

Measures of ventilation heterogeneity mapped with hyperpolarized helium-3 MRI demonstrate a T2-high phenotype in asthma

W Gerald Teague et al. Pediatr Pulmonol. 2021 Jun.

Abstract

Background: Hyperpolarized gas with helium (HHe-3) MR (magnetic resonance) is a noninvasive imaging method which maps and quantifies regions of ventilation heterogeneity (VH) in the lung. VH is an important feature of asthma, but little is known as to how VH informs patient phenotypes.

Purpose: To determine if VH indicators quantified by HHe-3 MR imaging (MRI) predict phenotypic characteristics and map to regions of inflammation in children with problematic wheeze or asthma.

Methods: Sixty children with poorly-controlled wheeze or asthma underwent HHe-3 MRI, including 22 with bronchoalveolar lavage (BAL). The HHe-3 signal intensity defined four ventilation compartments. The non-ventilated and hypoventilated compartments divided by the total lung volume defined a VH index (VHI %).

Results: Children with VHI % in the upper quartile had significantly greater airflow limitation, bronchodilator responsiveness, blood eosinophils, expired nitric oxide (FeNO), and BAL eosinophilic or neutrophilic granulocyte patterns compared to children with VHI % in the lower quartile. Lavage return from hypoventilated bronchial segments had greater eosinophil % than from ventilated segments.

Conclusion: In children with asthma, greater VHI % as measured by HHe-3 MRI identifies a severe phenotype with higher type 2 inflammatory markers, and maps to regions of lung eosinophilia. Listed on ClinicalTrials. gov (NCT02577497).

Keywords: helium-3 lung MRI; hyperpolarized lung MRI; maldistribution of ventilation; severe asthma; ventilation heterogeneity.

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Conflict of interest statement

Conflict of interest statement: W. Gerald Teague MD received faculty salary support from TEVA Respiratory during the completion of this study.

Figures

Figure 1.
Figure 1.
Violin plots showing the probability distribution of lung volume compartments expressed as % of total lung volume according to the quartile distribution of the VHI % in children with problematic wheeze/asthma. In A), the non-ventilated compartment precent was significantly greater in children with VHI % in the upper quartile, and in B) the hypoventilated compartment percent likewise was significantly higher. In C) the ventilated compartment volume percent was greater in children in the upper quartile VH percent compared to the lower quartile, however in D) the well-ventilated compartment percent was significantly lower in children with VHI % in the upper quartile compared to children with VHI % in the lower quartile.
Figure 2.
Figure 2.
Representative HHe-3 images from children with mild, moderate, and severe ventilation heterogeneity. The VHI % located below each image was derived from the non-ventilated and hypoventilated volume divided by the total lung volume. Regional maps of the lung volume compartments are indicated by a color labeling algorithm. The table compares phenotypic features that were significantly (p < .05) different in children with VHI % in the upper quartile compared to children in the lower quartile.
Figure 3.
Figure 3.
Within subject analysis of granulocyte counts/hpf in BAL return from ventilated and non-ventilated lung regions in 13 children with asthma. Ventilation status of a lung region was determined according to the presence or absence of visible ventilation defects on HHe-3 lung MRI. The plots are probability density functions and paired counts of A) macrophage, B) lymphocyte, C) eosinophil, and D) neutrophil numbers according to regional ventilation status.
See this image and copyright information in PMC

References

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