Imaging Collateral Ventilation in Patients With Advanced Chronic Obstructive Pulmonary Disease: Relative Sensitivity of 3 He and 129 Xe MRI.

To the editor:

Endoscopic lung volume reduction (ELVR) can improve lung function, exercise capacity, and quality of life of patients with severe chronic obstructive pulmonary disease (COPD). The assessment of collateral ventilation is key to the success of ELVR, as collateral ventilation from adjacent lung regions prevents collapse of the target lung segment.1

The gold standard assessment of collateral ventilation is gas catheter bronchoscopy, but this is an invasive procedure requiring sedation.1 Assessment of lobar fissure integrity with anatomical computed tomography (CT) can assist in patient selection,1, 2 but functional measurements of gas movement within the lungs have direct relevance.

Long‐range diffusion measurements using hyperpolarized 3He magnetic resonance imaging (MRI) are sensitive to the effects of collateral ventilation.3 Direct imaging of collateral and delayed ventilation has been demonstrated with time‐resolved hyperpolarized 3He MRI during breath‐hold.4 However, 3He has become increasingly scarce and expensive,5 motivating a shift towards 129Xe MRI for most applications in the lungs.6 The aim of this work was to compare 3He and 129Xe time‐resolved imaging for the detection of delayed and collateral ventilation in patients with severe COPD.

Materials and Methods

Three patients with advanced COPD under consideration for ELVR were scanned using a 1.5T whole‐body MRI system (GE HDx, Milwaukee, WI) equipped for hyperpolarized gas imaging. This retrospective analysis was conducted with approval of the research governance and ethics board with a waiver of informed consent. Patients 1 and 2 were 64‐year‐old females, patient 3 was a 52‐year‐old male. Patients were positioned supine in a transmit‐receive quadrature vest coil (Clinical MR Solutions, Brookfield, WI) tuned to the appropriate resonance frequency of 3He or 129Xe. Dynamic time‐series ventilation images were acquired during breath‐hold using a 3D coronal balanced steady‐state free‐precession sequence with full lung coverage (field of view [FOV] = 40–48 cm, slice number = 22–24), in‐plane matrix 64 × 32, 10mm slice thickness, and Cartesian centric phase encoding.

100 mL hyperpolarized 3He (∼25% polarization; GE Healthcare, Amersham, UK) and 900 ml N2 was inhaled from functional residual capacity (FRC). MR sequence parameters: θ = 8.5°, echo time (TE) = 0.5 msec, repetition time (TR) = 1.6 msec, bandwidth (BW) = 167 kHz, scan duration = 21 seconds, and six dynamic volumes acquired at 0, 4, 7, 11, 15, and 19 seconds.

350 mL hyperpolarized 129Xe (129‐enriched [86%], ∼30% polarization) and 650 ml N2 was inhaled from FRC. MR sequence parameters: θ = 6.5°, TE = 1.4 msec, TR = 4.5 msec, BW = 16 kHz, scan duration = 23 seconds, and six dynamic volumes acquired at 0, 4, 8, 12, 16, and 20 seconds.

To quantify dynamic changes in global lung ventilation, whole lung ventilated volume (VV) was calculated for each timepoint using automated spatial fuzzy C‐means segmentation, a methodology which is robust to noise.7

The free diffusion coefficient (D) and 1D mean free diffusion path length (zrms = √(2DΔt)) after time Δt8 were estimated for 3He and 129Xe within the lungs. A volume of 6.6 L of air, corresponding to the average FRC of the three patients, was used to estimate the experimental in situ gas mixture required for the calculation of D.

Volumetric unenhanced thoracic CT images and pulmonary function test results were also reviewed.

Results

Centrilobular emphysema and hyperinflation were evident on the CT images of all patients. Patients 1, 2, and 3 had forced expiratory volume in 1 second of 28.5, 24.7, and 27.4 percent predicted, and residual volume of 272.1, 291.5, and 223.3 percent predicted, respectively. Patient 1 lost breath‐hold after 13 seconds of 3He data acquisition and after 20 seconds of 129Xe data acquisition; patients 2 and 3 performed both breath‐holds successfully.

The figures show 3He and 129Xe images of gas distribution within the lungs at the first timepoint and a later timepoint during breath‐hold. Arrows highlight initially nonventilated lung regions where signal increased over time in the 3He images, but not in the 129Xe images. Some evidence of delayed ventilation was observed with 129Xe but only within lung regions that were ventilated at t = 0 sec with 3He (Figs. 1, 2, 3).

Figure 1

3He images (top) and 129Xe images (bottom) acquired from patient 1 during breath‐hold; (a,d) at the start of the imaging sequence, t = 0 sec, and (b,e) after 11 seconds, both shown with the same signal range. (c,f) Maps of signal increase from t = 0 sec to t = 11 sec. White arrows highlight a region of lung where 3He signal increased over time, but 129Xe signal did not. The coronal unenhanced thoracic CT (g) showed moderate centrilobular emphysema and hyperinflation, and an intact left oblique fissure. Mean signal‐to‐noise ratio (SNR) over the whole lung ventilated volume for that timepoint is displayed for a, b, d, and e.

Figure 2

3He images (top) and 129Xe images (bottom) acquired from patient 2 during breath‐hold; (a,d) at the start of the imaging sequence, t = 0 sec, and (b,e) after 15 seconds, both shown with the same signal range. (c,f) Maps of signal increase from t = 0 sec to t = 15 sec. White arrows highlight regions of lung where 3He signal increased over time, but 129Xe signal did not. (g) CT showed severe centrilobular emphysema and severe hyperinflation, and all fissures appeared intact. Mean SNR over the whole lung ventilated volume for that timepoint is displayed for a, b, d, and e.

Figure 3

3He images (top) and 129Xe images (bottom) acquired from patient 3 during breath‐hold; (a,d) at the start of the imaging sequence, t = 0 sec, and (b,e) after 15 seconds, both shown with the same signal range. (c,f) Maps of signal increase from t = 0 sec to t = 15 sec. White arrows highlight regions of lung where 3He signal increased over time, but 129Xe signal did not. (g) CT showed severe centrilobular emphysema and hyperinflation, and all fissures appeared intact. Mean SNR over the whole lung ventilated volume for that timepoint is displayed for a, b, d, and e.

Whole lung ventilated volume increased over time for both gases, but the ratio VV3He/VV129Xe was greater at the end of the breath‐holds than at t = 0 sec. VV3He/VV129Xe increased from 1.10 to 1.19 for patient 1, from 1.37 to 1.54 for patient 2, and from 1.25 to 1.31 for patient 3.

The ratio of 129Xe diffusivity to 3He diffusivity within the hyperinflated lungs of a patient with an FRC of 6.6 L was 0.15 for the estimated experimental gas mixtures (D(129Xe‐air,lungs) = 0.13 cm2s‐1, D(3He‐air,lungs) = 0.87 cm2s‐1) . This was associated with a mean free diffusion path length of 2.0 cm for 129Xe and 5.1 cm for 3He on the time‐course of the time‐resolved experiment (Δt = 15 sec).

Discussion

The visualization of delayed and collateral ventilation with 3He but not with 129Xe, and the increased VV3He/VV129Xe ratio at the end of the breath‐holds compared to t = 0 sec, are likely due to the large difference in diffusivity between the gas mixtures used. The observation of reduced ventilated volume in 129Xe images when compared to 3He images acquired from the same patients with COPD has been reported before for single timepoint ventilation imaging.9 The diffusion coefficient of 129Xe diluted in air (0.14 cm2s‐1)8 is closer to that of air alone (0.22 cm2s‐1)10 than 3He diluted in air (0.86 cm2s‐1).8 However, the higher diffusivity of 3He highlights delayed ventilation which would take place on a longer time‐scale for pure air rather than the 3He‐air mixture used for imaging; for example, it would take 60 seconds for pure air to travel the same mean free diffusion path length as the 3He‐air mixture within the lungs would travel in 15 seconds. Even if it were feasible to image 3He and 129Xe at the same mean free diffusion path length, other inherent differences between the two gases, such as increased density and viscosity of 129Xe compared to 3He, may affect the relative sensitivity of 3He and 129Xe MRI.

In conclusion, although the number of patients studied was small, all showed instances where delayed and collateral ventilation were detected with 3He MRI but not observed using 129Xe MRI, indicating a limitation of time‐resolved 129Xe MRI for this emergent application.

Grant Support

This work was funded by the Medical Research Council (MR/M008894/1) and the National Institute of Health Research (NIHR‐RP‐R3‐12‐027). The views expressed in this publication are those of the authors and not necessarily those of the National Health Service, the National Institute for Health Research or the Department of Health.

Supporting information Figures

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