Imaging the lungs in asthmatic patients by using hyperpolarized helium-3 magnetic resonance: Assessment of response to methacholine and exercise challenge

doi:10.1067/mai.2003.1544

Journal of Allergy and Clinical Immunology

Volume 111, Issue 6, June 2003, Pages 1205-1211

https://doi.org/10.1067/mai.2003.1544 Get rights and content

Abstract

Background: Imaging of gas distribution in the lungs of patients with asthma has been restricted because of the lack of a suitable gaseous contrast agent. Hyperpolarized helium-3 (HHe3) provides a new technique for magnetic resonance imaging of lung diseases. Objective: We sought to investigate the use of HHe3 gas to image the lungs of patients with moderate or severe asthma and to assess changes in gas distribution after methacholine and exercise challenge. Methods: Magnetic resonance imaging was performed in asthmatic patients immediately after inhalation of HHe3 gas. In addition, images were obtained before and after methacholine challenge and a standard exercise test. Results: Areas of the lung with no signal or sharply reduced HHe3 signal (ventilation defects) are common in patients with asthma, and the number of defects was inversely related to the percent predicted FEV₁ (r = 0.71, P < .002). After methacholine challenge (n = 3), the number of defects increased. Similarly, imaging of the lungs after exercise (n = 6) showed increased ventilation defects in parallel with decreases in FEV₁. The increase in defects after challenge in these 9 asthmatic patients was significant both for the number (P < .02) and extent (P < .02) of the defects. The variability and speed of changes in ventilation and the complete lack of signal in many areas is in keeping with a model in which the defects result from airway closure. Conclusion: HHe3 magnetic resonance provides a new technique for imaging the distribution of inhaled air in the lungs. The technique is suitable for following responses to treatment of asthma and changes after methacholine or exercise challenge. (J Allergy Clin Immunol 2003;111:1205-11.)

Section snippets

Subjects

Subjects 18 to 40 years of age were recruited through the Asthma and Allergic Diseases Center at the University of Virginia and through local advertisement. The use of HHe3 in human subjects was performed under a Food and Drug Administration-approved physician's Investigational New Drug application (no. 57,866). All studies were performed under a protocol approved by the institutional review board. In total, 39 subjects, 19 asthmatic patients (age, 20-40 years; mean age, 27 years) and 20

Imaging the lungs of patients with mild, moderate, and severe obstruction

We have previously reported the presence of ventilation defects in the HHe3 images of patients with asthma. Imaging patients with more severe disease, we found a more consistent presence of defects and more extensive defects (Fig 1).

. Coronal MR images obtained immediately after inhalation of HHe3 gas in a healthy normal volunteer (A) and in patients with mild (FEV₁ of 132% of predicted value; B ), moderate (FEV₁ of 83% of predicted value; C ), and severe (FEV₁ of 34% of predicted value; D )

Discussion

The diagnosis and management of asthma is largely dependent on measurements of expiratory airflow.10, 11 Transient decreases in peak expiratory flow or FEV₁ are normally interpreted as diffuse narrowing of the bronchi. Indeed, the presence of wheezing or expiratory rales clearly indicates that some tubes are narrowed sufficiently to cause turbulent airflow. On the other hand, it has been clear for many years that some bronchi must close, giving rise to air trapping and decreases in forced vital

References (19)

KB Newman et al.
Quantitative computed tomography detects air trapping due to asthma
Chest
(1994)
J Hunt
Exhaled breath condensate: an evolving tool for noninvasive evaluation of lung disease
J Allergy Clin Immunol
(2002)
National Asthma Education and Prevention Program National Heart Lung and Blood Institute
Practical guide for the diagnosis and management of asthma
(1997)
GG King et al.
Evaluation of airways in obstructive pulmonary disease using high-resolution computed tomography
Am J Respir Crit Care Med
(1999)
H Middleton et al.
MR imaging with hyperpolarized 3He gas
Magn Reson Med
(1995)
JR McFall et al.
Human lung air spaces: potential for MR imaging with hyperpolarized He-3
Radiology
(1996)
EE de Lange et al.
Lung air spaces: MR imaging evaluation with hyperpolarized 3He gas
Radiology
(1999)
HU Kauczor et al.
Imaging of the lungs using 3He MRI: preliminary clinical experience in 18 patients with and without lung disease
J Magn Reson Imaging
(1997)
TA Altes et al.
Hyperpolarized 3 He MR lung ventilation imaging in asthmatics: preliminary findings
J Magn Reson Imaging
(2001)

There are more references available in the full text version of this article.

Cited by (288)

Hyperpolarized 129Xe MRI, 99mTc scintigraphy, and SPECT in lung ventilation imaging: a quantitative comparison
2024, Academic Radiology
The current clinical standard for functional imaging of patients with lung ailments is nuclear medicine scintigraphy and Single Photon Emission Computed Tomography (SPECT) which detect the gamma decay of inhaled radioactive tracers. Hyperpolarized (HP) Xenon-129 MRI (XeMRI) of the lungs has recently been FDA approved and provides similar functional images of the lungs with higher spatial resolution than scintigraphy and SPECT. Here we compare Technetium-99m (^99mTc) diethylene-triamine-pentaacetate scintigraphy and SPECT with HP XeMRI in healthy controls, asthma, and chronic obstructive pulmonary disorder (COPD) patients.
59 subjects, healthy, with asthma, and with COPD, underwent ^99mTc scintigraphy/SPECT, standard spirometry, and HP XeMRI. XeMRI and SPECT images were registered for direct voxel-wise signal comparisons. Images were also compared using ventilation defect percentage (VDP), and a standard 6-compartment method. VDP calculated from XeMRI and SPECT images was compared to spirometry.
Median Pearson correlation coefficient for voxel-wise signal comparison was 0.698 (0.613–0.782) between scintigraphy and XeMRI and 0.398 (0.286–0.502) between SPECT and XeMRI. Correlation between VDP measures was r = 0.853, p < 0.05. VDP separated asthma and COPD from the control group and was significantly correlated with FEV1, FEV1/FVC, and FEF 25–75.
HP XeMRI provides equivalent information to ^99mTc SPECT and standard spirometry measures. Additionally, XeMRI is non-invasive, hence it could be used for longitudinal studies for evaluating emerging treatment for lung ailments.
MR Imaging for the Evaluation of Diffuse Lung Disease: Where Are We?
2022, Radiologic Clinics of North America
Hyperpolarized 129Xenon MRI Ventilation Defect Quantification via Thresholding and Linear Binning in Multiple Pulmonary Diseases
2022, Academic Radiology
There is no agreed upon method for quantifying ventilation defect percentage (VDP) with high sensitivity and specificity from hyperpolarized (HP) gas ventilation MR images in multiple pulmonary diseases for both pediatrics and adults, yet identifying such methods will be necessary for future multi-site trials. Most HP gas MRI ventilation research focuses on a specific pulmonary disease and utilizes one quantification scheme for determining VDP. Here we sought to determine the potential of different methods for quantifying VDP from HP ¹²⁹Xe images in multiple pulmonary diseases through comparison of the most utilized quantification schemes: linear binning and thresholding.
HP ¹²⁹Xe MRI was performed in a total of 176 subjects (125 pediatrics and 51 adults, age 20.98±16.48 years) who were either healthy controls (n = 23) or clinically diagnosed with cystic fibrosis (CF) (n = 37), lymphangioleiomyomatosis (LAM) (n = 29), asthma (n = 22), systemic juvenile idiopathic arthritis (sJIA) (n = 11), interstitial lung disease (ILD) (n = 7), or were bone marrow transplant (BMT) recipients (n = 47). HP ¹²⁹Xe ventilation images were acquired during a ≤16 second breath-hold using a 2D multi-slice gradient echo sequence on a 3T Philips scanner (TR/TE 8.0/4.0ms, FA 10-12°, FOV 300 × 300mm, voxel size≈3 × 3 × 15mm). Images were analyzed using 5 different methods to quantify VDPs: linear binning (histogram normalization with binning into 6 clusters) following either linear or a variant of a nonparametric nonuniform intensity normalization algorithm (N4ITK) bias-field correction, thresholding ≤60% of the mean signal intensity with linear bias-field correction, and thresholding ≤60% and ≤75% of the mean signal intensity following N4ITK bias-field correction. Spirometry was successfully obtained in 84% of subjects.
All quantification schemes were able to label visually identifiable ventilation defects in similar regions within all subjects. The VDPs of control subjects were significantly lower (p<0.05) compared to BMT, CF, LAM, and ILD subjects for most of the quantification methods. No one quantification scheme was better able to differentiate individual disease groups from the control group. Advanced statistical modeling of the VDP quantification schemes revealed that in comparing controls to the combined disease group, N4ITK bias-field corrected 60% thresholding had the highest predictive efficacy, sensitivity, and specificity at the VDP cut-point of 2.3%. However, compared to the thresholding quantification schemes, linear binning was able to capture and label subtle low-ventilation regions in subjects with milder obstruction, such as subjects with asthma.
The difference in VDP between healthy controls and patients varied between the different disease states for all quantification methods. Although N4ITK bias-field corrected 60% thresholding was superior in separating the combined diseased group from controls, linear binning is able to better label low-ventilation regions unlike the current, 60% thresholding scheme. For future clinical trials, a consensus will need to be reached on which VDP scheme to utilize, as there are subtle advantages for each for specific disease.
Comparison of Hyperpolarized 3He and 129Xe MR Imaging in Cystic Fibrosis Patients
2022, Academic Radiology
In this study, we compared hyperpolarized ³He and ¹²⁹Xe images from patients with cystic fibrosis using two commonly applied magnetic resonance sequences, standard gradient echo (GRE) and balanced steady-state free precession (TrueFISP) to quantify regional similarities and differences in signal distribution and defect analysis.
Ten patients (7M/3F) with cystic fibrosis underwent hyperpolarized gas MR imaging with both ³He and ¹²⁹Xe. Six had MRI with both GRE, and TrueFISP sequences and four patients had only GRE sequence but not TrueFISP. Ventilation defect percentages (VDPs) were calculated as lung voxels with <60% of the whole-lung hyperpolarized gas signal mean and was measured in all datasets. The voxel signal distributions of both ¹²⁹Xe and ³He gases were visualized and compared using violin plots. VDPs of hyperpolarized 3 He and 129 Xe were compared in Bland-Altman plots; Pearson correlation coefficients were used to evaluate the relationships between inter-gas and inter-scan to assess the reproducibility.
A significant correlation was demonstrated between ¹²⁹Xe VDP and ³He VDP for both GRE and TrueFISP sequences (ρ = 0.78, p<0.0004). The correlation between the GRE and TrueFISP VDP for ³He was ρ = 0.98 and was ρ = 0.91 for ¹²⁹Xe. Overall, ¹²⁹Xe (27.2±9.4) VDP was higher than ³He (24.3±6.9) VDP on average on cystic fibrosis patients.
In patients with cystic fibrosis, the selection of hyperpolarized ¹²⁹Xe or ³He gas is most likely inconsequential when it comes to measure the overall lung function by VDP although ¹²⁹Xe may be more sensitive to starker lung defects, particularly when using a TrueFISP sequence.
Peripheral and proximal lung ventilation in asthma: Short-term variation and response to bronchodilator inhalation
2021, Journal of Allergy and Clinical Immunology
The relative involvement of the large and small airways in asthma is not clear. Hyperpolarized gas magnetic resonance imaging (MRI) provides high-resolution 3-dimensional images of ventilation distribution that can be quantified by the ventilated volume percentage (VV%) of the lungs.
Our aims were to (1) quantify the baseline reproducibility of VV%, (2) assess the ventilation distribution between the proximal and peripheral lungs, and (3) investigate regional ventilation response to bronchodilator inhalation in a cohort of patients with asthma.
A total of 33 patients with poorly controlled, moderate-to-severe asthma were scanned with hyperpolarized ³He MRI. Two image data sets were acquired at baseline, and 1 image data set was acquired after bronchodilator inhalation. Images were divided into proximal and peripheral regions for analysis.
Bland-Altman analysis showed strong reproducibility of VV% (bias = 0.12%; LOA = –1.86% to 2.10%). VV% variation at baseline was greater in the periphery than in the proximal lung. The proximal lung was better ventilated than the peripheral lung. Ventilation increased significantly in response to bronchodilator inhalation, globally and regionally, and the ventilation increase in response to bronchodilator inhalation was greater in the peripheral lung than in the proximal lung. Hyperpolarized gas MRI was more sensitive to changes in response to bronchodilator inhalation (58%) than spirometry (33%).
The peripheral lung showed reduced ventilation and a greater response to bronchodilator inhalation than the proximal lung. The high level of baseline reproducibility and sensitivity of hyperpolarized gas MRI to bronchodilator reversibility suggests that it is suitable for low subject number studies of therapy response.
Evaluating post-bronchodilator response in well-controlled paediatric severe asthma using hyperpolarised 129Xe-MRI: A pilot study
2021, Respiratory Medicine
Pulmonary function tests (PFTs) are the main objective measures used to assess asthma in children. However, PFTs provide a global measure of lung function. Hyperpolarised xenon-129 magnetic resonance imaging (129Xe-MRI) can assess lung function spatially. This cross-sectional cohort study aimed to evaluate the use of 129Xe-MRI in detecting ventilation abnormalities in children with well-controlled severe asthma pre- and post-bronchodilator (BD).
Six healthy children (aged 11 ± 3) and six with well-controlled severe asthma (14 ± 1) underwent spirometry, multiple breath washout (MBW), and 129Xe-MRI. These tests were repeated post-BD in the asthma cohort. Image analysis was performed in MATLAB. Wilcoxon signed-rank test, repeated measures analysis of variance (ANOVA), and Spearman's rank correlation coefficient were used for statistical analysis.
A significantly higher number of ventilation defects were found in the asthma cohort pre-BD compared to the healthy participants and post-BD within the asthma cohort (p = 0.02 and 0.01). A greater number of wedge-shaped defects were detected in the asthma cohort pre-BD compared to healthy participants and post-BD within the asthma cohort (p = 0.01 and 0.008, respectively). 129Xe ventilation defect percentage (VDP) and coefficient of variation (CoV) were significantly higher in the asthma cohort pre-BD compared to the healthy cohort (p = 0.006 for both). VDP and CoV were reduced significantly post-BD in the asthma cohort, to a level where there was no longer a significant difference between the two cohorts.
129Xe-MRI is a sensitive marker of ventilation inhomogeneity in paediatric severe asthma and may potentially be used as a biomarker to assess disease progression and therapeutic response.

View all citing articles on Scopus

^☆: Supported in part by Siemens Medical Solutions; Amersham Health; the Commonwealth Technology Research Fund; National Institutes of Health grants AI20565, PO1-NIEHS/NIAID-50989, R-44-HL59022, and R01HL66479; and the Society of Pediatric Radiology.

^☆☆: Reprint requests: Thomas A. E. Platts-Mills, MD, PhD, University of Virginia Health Systems, Asthma and Allergic Diseases Center, PO Box 801355, Charlottesville, VA 22908-1355.

View full text

Article preview

Journal of Allergy and Clinical Immunology

Abstract

Section snippets

Subjects

Imaging the lungs of patients with mild, moderate, and severe obstruction

Discussion

References (19)

Quantitative computed tomography detects air trapping due to asthma

Chest

Exhaled breath condensate: an evolving tool for noninvasive evaluation of lung disease

J Allergy Clin Immunol

Practical guide for the diagnosis and management of asthma

Evaluation of airways in obstructive pulmonary disease using high-resolution computed tomography

Am J Respir Crit Care Med

MR imaging with hyperpolarized 3He gas

Magn Reson Med

Human lung air spaces: potential for MR imaging with hyperpolarized He-3

Radiology

Lung air spaces: MR imaging evaluation with hyperpolarized 3He gas

Radiology

Imaging of the lungs using 3He MRI: preliminary clinical experience in 18 patients with and without lung disease

J Magn Reson Imaging

Hyperpolarized 3 He MR lung ventilation imaging in asthmatics: preliminary findings

J Magn Reson Imaging

Cited by (288)

Hyperpolarized <sup>129</sup>Xe MRI, <sup>99m</sup>Tc scintigraphy, and SPECT in lung ventilation imaging: a quantitative comparison

MR Imaging for the Evaluation of Diffuse Lung Disease: Where Are We?

Hyperpolarized <sup>129</sup>Xenon MRI Ventilation Defect Quantification via Thresholding and Linear Binning in Multiple Pulmonary Diseases

Comparison of Hyperpolarized <sup>3</sup>He and <sup>129</sup>Xe MR Imaging in Cystic Fibrosis Patients

Peripheral and proximal lung ventilation in asthma: Short-term variation and response to bronchodilator inhalation

Evaluating post-bronchodilator response in well-controlled paediatric severe asthma using hyperpolarised 129Xe-MRI: A pilot study

Asthma, Rhinitis, Other Respiratory Diseases: Rapid PublicationImaging the lungs in asthmatic patients by using hyperpolarized helium-3 magnetic resonance: Assessment of response to methacholine and exercise challenge☆,☆☆

Abstract

Section snippets

Subjects

Imaging the lungs of patients with mild, moderate, and severe obstruction

Discussion

Chest

J Allergy Clin Immunol

Practical guide for the diagnosis and management of asthma

Evaluation of airways in obstructive pulmonary disease using high-resolution computed tomography

Am J Respir Crit Care Med

MR imaging with hyperpolarized 3He gas

Magn Reson Med

Human lung air spaces: potential for MR imaging with hyperpolarized He-3

Radiology

Lung air spaces: MR imaging evaluation with hyperpolarized 3He gas

Radiology

Imaging of the lungs using 3He MRI: preliminary clinical experience in 18 patients with and without lung disease

J Magn Reson Imaging

Hyperpolarized 3 He MR lung ventilation imaging in asthmatics: preliminary findings

J Magn Reson Imaging

Asthma, Rhinitis, Other Respiratory Diseases: Rapid Publication
Imaging the lungs in asthmatic patients by using hyperpolarized helium-3 magnetic resonance: Assessment of response to methacholine and exercise challenge☆,☆☆