Three-dimensional Isotropic Functional Imaging of Cystic Fibrosis Using Oxygen-enhanced MRI: Comparison with Hyperpolarized ³He MRI

Abstract

Purpose

To compare the performance of three-dimensional radial ultrashort echo time (UTE) oxygen-enhanced (OE) MRI with that of hyperpolarized helium 3 (³He) MRI with respect to quantitative ventilation measurements in patients with cystic fibrosis (CF).

Materials and Methods

In this prospective study conducted from June 2013 to May 2015, 25 participants with CF aged 10–55 years (14 male; age range, 13–55 years; 11 female; age range, 10–37 years) successfully underwent pulmonary function tests, hyperpolarized ³He MRI, and OE MRI. OE MRI used two sequential 3.5-minute normoxic and hyperoxic steady-state free-breathing UTE acquisitions. Seven participants underwent imaging at two separate examinations 1–2 weeks apart to assess repeatability. Regional ventilation was quantified as ventilation defect percentage (VDP) individually from OE MRI and hyperpolarized ³He MRI by using the same automated quantification tool. Bland-Altman analysis, intraclass correlation coefficient (ICC), Spearman correlation coefficient, and Wilcoxon signed-rank test were used to evaluate repeatability.

Results

In all 24 participants, the global VDP measurements from either OE MRI (ρ = −0.66, P < .001) or hyperpolarized ³He MRI (ρ = −0.75, P < .001) were significantly correlated with the percentage predicted forced expiratory volume in 1 second. VDP reported at OE MRI was 5.0% smaller than (P = .014) but highly correlated with (ρ = 0.78, P < .001) VDP reported at hyperpolarized ³He MRI. Both OE MRI-based VDP and hyperpolarized ³He MRI-based VDP demonstrated good repeatability (ICC = 0.91 and 0.95, respectively; P ≤ .001).

Conclusion

In lungs with cystic fibrosis, ultrashort echo time oxygen-enhanced MRI showed similar performance compared with hyperpolarized ³He MRI for quantitative measures of ventilation defects and their repeatability.

© RSNA, 2018

Online supplemental material is available for this article.

Summary

In lungs with cystic fibrosis, oxygen-enhanced MRI using three-dimensional radial ultrashort echo time yields nonionizing quantitative measures that are highly correlated with ventilation defect percentage at hyperpolarized ³He MRI, are significantly associated with pulmonary function test results, and show high interexamination repeatability.

Implications for Patient Care

• ■ Quantitative ventilation measurements can be readily obtained in patients with cystic fibrosis by using oxygen-enhanced MRI with a three-dimensional radial ultrashort echo time of 80 µsec, whole-lung coverage, and 1-cm isotropic resolution.

• ■ Oxygen-enhanced MRI with three-dimensional radial ultrashort echo time can feasibly be implemented with clinical MRI systems, yielding repeatable lung ventilation information that is comparable with that obtained with hyperpolarized ³He MRI.

Introduction

The standard clinical tools used to monitor cystic fibrosis (CF) lung disease include pulmonary function testing (PFT) and thin-section CT. Although these tools are important, they are problematic for longitudinal follow-up of pediatric patients because they lack sensitivity (1,2) and expose patients to radiation (3,4). Functional MRI techniques, such as hyperpolarized helium 3 (³He) MRI (5–9) and, more recently, oxygen-enhanced (OE) MRI (10–13), have been used to assess regional ventilation abnormalities of the lungs in patients with CF. Hyperpolarized ³He MRI ventilation defect percentage (VDP) is an emerging biomarker in patients with obstructive lung disease (7,14–16). However, because of the need for specialized equipment and because of the high cost of noble gas isotopes, hyperpolarized ³He MRI is currently limited to research applications at a few centers. In contrast, OE MRI uses widely available oxygen (O₂) and can be performed with commercially available MRI hardware.

The basic principle of OE MRI was initially reported by Edelman et al (17) and is the shortening of T1 relaxation time of 100% O₂ (hyperoxic) relative to 21% O₂ (normoxic) inhalation. This can be seen as an increase in MRI proton signal from the existing lung parenchyma, and it can be used to evaluate regional lung ventilation (17–19). A 2018 study (11) showed that OE MRI with a three-dimensional (3D) radial ultrashort echo time (UTE) sequence enables whole-chest coverage and supports quantitative differentiation of diseased lungs from healthy lungs with VDP. Additionally, other studies (20–22) have shown that 3D radial UTE (echo time ≤0.1 msec) MRI supports depiction and scoring of the structural abnormalities and shows a relationship with lung structure found at CT. OE MRI with UTE potentially supports the simultaneous imaging of lung function and structure, unlike CT, and fulfills a need for regional functional ventilation assessment that is inaccessible via global PFTs.

The quantitative comparison of OE MRI and hyperpolarized ³He MRI for VDP measurements has not been investigated. The purpose of this study was to compare the performance of OE MRI with that of hyperpolarized ³He MRI. Specifically, VDP measured with the two methods was compared with respect to (a) measurement bias and agreement, (b) correlation with PFT results, and (c) interexamination repeatability. We hypothesized that OE MRI may yield comparable whole-lung VDP relative to hyperpolarized ³He MRI as the reference method.

Materials and Methods

Study Population and Design

Twenty-five study participants with CF aged 10–55 years (14 male; age range, 13–55 years; 11 female; age range, 10–37 years) were prospectively and continuously enrolled from June 19, 2013, to May 4, 2015, in an internal review board –approved and Health Insurance Portability and Accountability Act–compliant study with written informed consent. Breakdown of participant characteristics is summarized in Table 1, and the patient flowchart is shown in Figure 1. Imaging protocol is summarized in Figure 2. All participants underwent PFT, hyperpolarized ³He MRI, and OE MRI sequentially at 1.5 T (Signa HDx; GE Healthcare, Waukesha, Wis). A subset of 10 participants was recruited to return for a second examination 1–2 weeks later. Because of imager-related technical factors and patient compliance, only seven of these participants underwent repeated OE MRI and hyperpolarized ³He MRI acquisitions and had image data available. The whole-lung VDP measured by using OE MRI in the first six participants who underwent repeated examinations was previously reported (11). The inclusion criteria were an existing clinical diagnosis of CF and age of at least 10 years. Exclusion criteria were ventilator or oxygen dependence, history of lung transplantation, any contraindication to MRI, administration of intravenous antibiotics for pulmonary infection in the 4 weeks before a study visit, or pregnancy.

Table 1:

Characteristics and Functional Data for 24 Study Participants with Cystic Fibrosis

Note.—Data are mean ± standard deviation, with 95% confidence intervals in parentheses. Oxygen-enhanced (OE) MRI lung volume was acquired approximately at functional residual capacity. Hyperpolarized helium 3 (³He) MRI lung volume was acquired approximately at functional residual capacity + 1 L. FEV₁ = forced expiratory volume in 1 second, FVC = forced vital capacity, VDP = ventilation defect percentage.

Figure 1:

Flowchart showing study design. * Technical failure includes data entry error at the imager console for both examinations in one participant and MRI hardware malfunction at the first examination in one participant that was not related to gas delivery or acquisition of oxygen-enhanced (OE) or hyperpolarized helium 3 (³He) MR images. Results of one examination were not analyzed because of low OE MRI signal on the percent signal enhancement map.

Figure 2:

Timeline of the imaging protocol. Twenty-five participants with cystic fibrosis were prospectively enrolled in the study at examination 1. Seven of these participants returned for examination 2. At each examination, participants underwent pulmonary function testing (PFT), breath-hold ventilation imaging using hyperpolarized helium 3 (³He) MRI, and free-breathing oxygen-enhanced (OE) MRI using a three-dimensional radial ultrashort echo time (UTE) sequence. At examination 1, one participant could not be analyzed because of low OE signal.

Pulmonary Function Testing

Spirometry was performed according to American Thoracic Society guidelines (23). The spirometric measurements include forced expiratory volume in 1 second (FEV₁) and forced vital capacity (FVC). Percentage predicted values of these measurements were calculated by using Global Lung Function Initiative 2012 equations (24).

Oxygen-enhanced MRI

While in the supine position, all study participants freely breathed either medical-grade room air or 100% O₂ via a nonrebreather facemask at a flow rate of 15 L/min throughout the OE MRI examinations. The participant breathed room air for the first 3.5-minute UTE acquisition; thereafter, the O₂ concentration was switched to 100%. After 2 minutes of tidal breathing at 100% O₂ to avoid the transient effects of gas wash-in, the participant then underwent a second 3.5-minute UTE acquisition while breathing nominal 100% O₂.

Each UTE acquisition used a 3D radial UTE pulse sequence (25) with the following parameters: repetition time msec/echo time msec, 2.9–4.2/0.08–0.12; 32-cm field of view; 8° flip angle, approximately 38 000 projections; 3.2-mm native isotropic spatial resolution interpolated to 1.25-mm isotropic reconstructed voxel size; and prospective gating with a real-time adaptive 50% acceptance window at end expiration. To improve the signal-to-noise ratio for OE images of percent signal enhancement, k-space data were low-pass filtered to 1-cm isotropic resolution (19). Additional details regarding the acquisition, reconstruction, and optimization of this UTE sequence have been previously published (19,25).

Hyperpolarized ³He MRI

Each participant performed a breath hold of 16–20 seconds after inhaling an equivalent volume (approximately 1 L) of room air or a hyperpolarized ³He and N₂ mixture through a plastic tube attached to the bag for proton and hyperpolarized ³He MRI, respectively. Helium was polarized to 30%–40% by using a Heli-Spin prototype commercial polarizer (Polarean, Durham, NC).

The proton scan used a two-dimensional multisection single-shot fast spin-echo sequence (474/31; 40 × 40 cm field of view; acquisition matrix, 128 × 128; 10-mm section thickness; 18–28 axial sections reconstructed at 1.56 × 1.56 × 10 mm). The hyperpolarized ³He MRI examination used a fast two-dimensional multisection gradient-echo sequence (6.5/2.9; 7° flip angle), and the acquisition matrix, field of view, section thickness, and section position were matched to those used in the proton examination. During the examination, blood oxygen saturation, heart rate, and respiratory rate were monitored with pulse oximetry and respiratory bellows, respectively.

Image Analysis

For OE MRI, lungs were automatically segmented from UTE image volumes by using deep convolutional neural networks (26) and were reviewed by an imaging scientist (W.Z.) with 11 years of experience in cardiothoracic MRI. The previously developed semiautomated workflow (11), which included deformable registration and retrospective lung density correction, was used to compute 3D isotropic percent signal enhancement maps and is presented in Appendix E1 (online). Regional ventilation was quantified automatically from the percent signal enhancement map as VDP by using adaptive K-means clustering (11,27).

For hyperpolarized ³He MRI, the semiautomated defect quantification pipeline previously used in 68 patients with asthma (28) was used in this cohort of participants with CF. Proton images were first registered to the hyperpolarized ³He MRI images and were then segmented jointly for a lung mask. The intensity corrected hyperpolarized ³He images were classified by using adaptive K-means clustering to determine whole-lung VDP. Detailed descriptions of defect quantification were discussed in a previously reported repeatability study (27).

Ventilation defect quantification of hyperpolarized ³He MRI in all study participants was performed individually from the quantification of OE MRI by an imaging scientist (W.Z.) who was blinded to clinical information. For interexamination comparison of regional defects, the proton images were aligned by using 3D rigid registration across examinations for hyperpolarized ³He MRI and OE MRI individually. For intermethod comparison, the anatomic proton UTE images were downsampled and deformed to match single-shot fast spin-echo images by using the rigid and B-spline deformable registration (29). The corresponding parametric maps were transformed accordingly by applying the deformation.

Statistical Analysis

For participants who underwent two examinations, measurements at the first visit were used to calculate participant statistics. The association between PFTs and VDP was evaluated by using Spearman rank correlation, with the 95% confidence interval computed with the bootstrapping technique (30). For global VDP agreement, Bland-Altman plots with 95% limits of agreement, intraclass correlation coefficient (ICC), and the Wilcoxon signed-rank test were used for intermethod comparison and interexamination repeatability. For regional VDP agreement, the Dice coefficient was used to assess interexamination and intermethod spatial overlap of the segmented defects, respectively. P < .05 was considered to indicate a significant difference. All statistical analyses were performed by using SAS, version 9.4 (SAS Institute, Cary, NC).

Results

Demographic and functional data from the CF cohort are summarized in Table 1. Of the 25 participants who underwent both hyperpolarized ³He MRI and OE MRI during the same session, 10 participants (four male, six female) were 18 years old or younger. Of the 32 hyperpolarized ³He MRI and OE MRI examinations (25 single and seven repeated examinations), 31 were completed successfully. The results from one participant who underwent a single examination were omitted from analysis because of nonphysical whole-lung median percent signal enhancement of 0.04% at OE MRI, leading to a technical failure rate of one in 32 (approximately 3%) for OE MRI. No adverse effects were observed.

Global Measurements and Comparisons

Six participants had severe pulmonary function alteration with percentage predicted FEV₁ of 50% or less (Table 1), reflecting a wide range of ages and obstructive physiology. Qualitatively, the VDP values measured at both OE MRI and hyperpolarized ³He MRI were of comparable magnitude with similarly large variations (Table 1), indicating the wide range of disease severities in this CF cohort. The whole-lung VDP from hyperpolarized ³He MRI was significantly correlated with percentage predicted FEV₁ (ρ = −0.75, P < .001) and percentage predicted FVC (ρ = −0.75, P < .001) (Table 2; Fig 3, A). Similarly, the VDP from OE MRI (Table 2; Fig 3, B) showed significant correlation to percentage predicted FEV₁ (ρ = −0.66, P < .001) and percentage predicted FVC (ρ = −0.66, P < .001). The average lung inflation volume corresponding to functional residual capacity (FRC) measured for OE MRI was significantly smaller (mean, −1.39 L ± 0.54 [standard deviation]; P < .001) than the lung inflation volume measured for hyperpolarized ³He MRI (approximately FRC + 1 L).

Table 2:

Spearman Correlation of PFTs to OE MRI and ³He MRI in 24 Study Participants with Cystic Fibrosis

Note.—Performance of oxygen-enhanced (OE) MRI and hyperpolarized helium 3 (³He) MRI for correlation to pulmonary function test (PFT) results in study participants with cystic fibrosis. Both tests showed excellent correlation with forced expiratory volume in 1 second (FEV₁) and forced vital capacity (FVC). P < .05 indicated a significant difference. CI = confidence interval, VDP = ventilation defect percentage.

Figure 3:

Scatterplots suggest similar associations with respect to, A, percentage predicted forced expiratory volume in 1 second (FEV1_%pred) using hyperpolarized helium 3 (³He) MRI ventilation defect percentage (VDP) and, B, oxygen-enhanced (OE) MRI VDP. Solid red line indicates the predicted linear regression model, and dotted red lines indicate 95% confidence intervals computed from linear regression.

Intermethod Comparisons

The intermethod VDP also showed a strong correlation (ρ = 0.78; 95% confidence interval: 0.53, 0.89; P < .001) (Fig 4, A). Bland-Altman analysis showed the VDP at OE MRI was biased to lower values by −5.0% (P = .014) relative to that from hyperpolarized ³He MRI (95% limits of agreement: −22.8%, 12.8%) (Fig 4, B).

Figure 4:

A, Scatterplot, with dotted line indicating identity. B, Bland-Altman plot for intermethod ventilation defect percentage (VDP). C, D, Bland-Altman plots for within-method interexamination repeatability of VDP at, C, oxygen-enhanced (OE) MRI and, D, hyperpolarized helium 3 (³He) MRI. Dotted lines in B–D indicate bias (closest to the black zero line) and the upper and lower limits of agreement (outer boundary dotted line). In B, there is good agreement between OE MRI and ³He MRI in participants with cystic fibrosis. The interexamination VDP for both methods yielded insignificant biases (bias of −0.62% [P = .81] for OE MRI, bias of 2.3% [P = .30] for ³He MRI).

Regional agreement on VDP between OE MRI and hyperpolarized ³He MRI among all 24 participants showed low to moderate regional overlap of defect locations. The average Dice coefficient between OE MRI and hyperpolarized ³He MRI was 0.26 ± 0.15 for the defected lung region and 0.82 ± 0.10 for the ventilated region. However, the overlap improved for greater disease severity (Table 3). Specific examples of intermethod comparisons are shown for female participants aged 16 years (Fig 5, A and B) and 24 years (Fig 5, C and D), respectively. Qualitatively, defects measured with OE MRI were spatially aligned in locations but were generally smaller than those seen on hyperpolarized ³He MR images. This is likely due to the methodologic differences in gas delivery between OE MRI and hyperpolarized ³He MRI, with the former being a free-breathing technique and the latter being imaged during a single breath-hold performed at FRC + 1 L.

Table 3:

Intermethod Dice Coefficient Results between OE MRI and ³He MRI in Study Participants with Cystic Fibrosis

Note.—The Dice coefficient results between oxygen-enhanced (OE) MRI and hyperpolarized helium 3 (³He) MRI suggested low to modest spatial agreement in the defected lung volumes and high spatial agreement in the ventilated lung volumes, with varying ventilation defect percentage (VDP) values. In more severely obstructed lungs, the intermethod agreement on the defect locations was better.

Figure 5:

Regional ventilation defects (contoured in green) measured at breath-hold hyperpolarized helium 3 (³He) MRI and spatially registered free-breathing oxygen-enhanced (OE) MRI in, A, B, a 16-year-old girl with percentage predicted forced expiratory volume in 1 second (FEV1_%pred) of 26.9% and percentage predicted forced vital capacity (FVC) of 40.6% and, C, D, a 24-year-old woman with percentage predicted FEV₁ of 75.3% and percentage predicted FVC of 76.2%. Differences in the whole-lung ventilation defect percentage (VDP) between OE MRI and ³He MRI were −7.1% (A and B) and 4.5% (C and D). Dice coefficients in the sections displayed from left to right were 0.66, 0.57, 0.53, 0.48, and 0.06, respectively, in A and B and 0.43, 0.57, 0.28, 0.52, and 0.21, respectively, in C and D. Average Dice coefficient of regional defects between the two methods was 0.53 (A and B) and 0.47 (C and D). Note that the percent signal enhancement images in B and D reflect long-term exposure to free breathing of oxygen for the participant rather than a single breath hold.

Interexamination Comparisons

In the seven participants who underwent two examinations, Bland-Altman analysis (Fig 4, C and D) suggests similarly high repeatability for VDP with OE MRI (bias, −0.6%; 95% limits of agreement: −12.9%, 11.7%) and hyperpolarized ³He MRI (bias, 2.3%; 95% limits of agreement: −6.0%, 10.5%). The ICC of VDP was 0.91 (P = .001) for OE MRI and 0.95 (P < .001) for hyperpolarized ³He MRI, showing good repeatability of whole-lung VDP with either method (Table 4). The Dice coefficient for regional repeatability of defects across examinations was 0.37 for OE MRI and 0.55 for hyperpolarized ³He MRI, suggesting only moderate repeatability of defect locations observed by using both methods.

Table 4:

Bland-Altman Repeatability and ICC of Interexamination VDP from OE MRI and ³He MRI in Seven Study Participants with Cystic Fibrosis

Note.—Interexamination repeatability of oxygen-enhanced (OE) MRI and hyperpolarized helium 3 (³He) MRI for finding ventilation defect percentage (VDP) in study participants with cystic fibrosis. OE MRI did not have as high a Dice coefficient as ³He MRI for VDP. Data in parentheses are P values. P < .05 indicated a significant difference. ICC = intraclass correlation coefficient.

*Data are mean ± standard deviation.

A specific example of interexamination comparison is shown in Figure 6. In a 37-year-old participant with impaired global lung function (percentage predicted FEV₁ of approximately 55%), large focal defects were observed at both examinations with either method. Both methods yielded similar interexamination global VDPs (range, 36%–39% for OE MRI [Fig 6, A] and 54%–55% for hyperpolarized ³He MRI [Fig 6, B]). In addition to differences in magnitude of VDP, the spatial overlap of defects between examinations was better with breath-hold hyperpolarized ³He MRI than with free-breathing OE MRI (Dice coefficient, 0.72 vs 0.48, respectively).

Figure 6:

Repeatability of ventilation defect percentage (VDP) measured with, A, oxygen-enhanced (OE) MRI and, B, hyperpolarized helium 3 (³He) MRI in a 37-year-old woman with cystic fibrosis. Percentage predicted forced expiratory lung volume in 1 second (FEV1_%pred) was 65.1% and 64.3% in the two examinations, which were separated by 1 week. Regional ventilation defects are outlined in green. Both imaging methods reported similar VDP measurements for the two examinations. The large focal defects were observed at both examinations, with some variation in the spatial locations. Section-specific Dice coefficients were 0.60 (axial), 0.55 (sagittal), and 0.64 (coronal) in A and 0.73 (axial), 0.72 (sagittal), and 0.72 (coronal) in B. The average Dice coefficient of regional defects between examinations was 0.48 for OE MRI and 0.72 for ³He MRI.

Discussion

Our study compared the functional lung biomarker ventilation defect percentage for oxygen-enhanced MRI and hyperpolarized ³He MRI performed on the same day in study participants with a wide age range and a wide range of cystic fibrosis severity. Repeatability of these measurements was also assessed in a subset of the same cohort for both methods across 1–2 weeks. The VDP measured with OE MRI showed strong correlation with VDP measured with hyperpolarized ³He MRI and similarly strong correlation for both methods with PFTs in 24 participants. Good to excellent interexamination repeatability of VDP was observed for both methods in the seven participants who underwent repeat examinations. Taken together, the VDP measurements showed comparable repeatability, high intermethod correlation, and high correlation with PFT results.

Many static and dynamic OE MRI studies have reported the physiologic importance of oxygen enhancement or wash-in and wash-out characteristics in patients with pulmonary diseases, such as lung cancer (31,32), chronic obstructive pulmonary disease (18,33), asthma (11,34), and CF (11,13). These previous studies have advanced OE MRI from feasibility to quantitative measurement of regional lung function. The distinguishing feature of our study is its ability to provide whole-lung coverage and isotropic resolution during free-breathing UTE with direct comparison with VDP measured with hyperpolarized ³He MRI. Use of the same automated defect quantification tool eliminated potential discrepancies in VDP calculation. The strong correlation of whole-lung VDP measured with the two methods implies that the VDP from OE MRI may be an adequate surrogate for VDP measured with hyperpolarized ³He MRI.

The VDP measured with OE MRI was, on average, slightly smaller than that measured with hyperpolarized ³He MRI. There are many possible reasons for this. First, this might be primarily attributed to the underlying physiology being different for the two methods. Hyperpolarized ³He MRI reliably captures static snapshot images of ³He gas flow in the lung during an approximately 15-second breath-hold window. Thus, the regions with delayed gas wash-in might result in signal voids and would be classified as ventilation defects. These regions might appear normally ventilated on the OE MRI parametric map, given the 9-minute acquisition time needed for OE MRI. Thus, defects observed at OE MRI might represent more chronic persistent defects, while hyperpolarized ³He MR images might depict both chronic and transient defects. This implies that hyperpolarized ³He MRI may yield information that is complementary to that obtained with OE MRI with lung ventilation. Second, OE MRI yields not only regional ventilation, but also respiratory-related information, such as oxygen transfer from alveoli to capillary beds. It might reflect the physiologic condition of oxygen delivery and solubility of O₂ (35). Third, the in-plane resolution is dramatically different between the two methods. This may cause the size of a segmented defect to vary when it is seen at the same location on the OE and hyperpolarized ³He MR images. The whole-lung VDP from hyperpolarized ³He MRI may be lower once interpolated to the isotropic resolution of OE MRI. Fourth, the different lung inflation volumes at which the two MRI methods were performed might lead to differences in observed ventilation. These factors also contribute to the low to moderate agreement for the regional overlap of defects between methods using the Dice coefficient, which is known to lead to poor intertest agreement when the regions being compared are small (eg, VDP <5%).

There were several limitations in our study. First, the sample size was small, especially for interexamination repeatability, and it was mixed with pediatric and adult participants with a wide range of severities. Second, the interval between the two repeat examinations varied and was possibly long enough to reflect some underlying disease variability. Third, the time constant for equilibration between normoxic and hyperoxic breathing to reach the steady state may be different in severely diseased populations. Recent dynamic OE MRI studies (13,34) reported the wash-in time constant was significantly longer in subjects with severe asthma (1.6 minutes) than in subjects with mild asthma (0.7 minutes), and the average wash-in time for adult participants with CF was 1.8 minutes. Thus, a future comparative OE MRI study should use a longer waiting period to accommodate varying wash-in time constants and feature a more rigorous repeatability study design. Fourth, the fact that ³He MRI yielded better interexamination agreement on regional defects than OE MRI implies the need for a better gating strategy to compensate for irregular breathing patterns and bulk motion to improve UTE examination quality and reduce test-retest variability. Future work will extend the 3D UTE OE MRI method to a dynamic imaging method to compare the wash-in and wash-out time constants in obstructed versus well-ventilated regions. Time constants will be compared with reported measurements by using a 3D inversion recovery imaging sequence (13) and will be assessed in the context of the structure-function relationships available at UTE MRI.

In conclusion, ultrashort echo time oxygen-enhanced MRI reports ventilation defect percentage measurements with similar correlation to obstructive physiology at spirometry and interexamination repeatability compared with hyperpolarized ³He MRI.