Progression of Emphysema in a 12-month Hyperpolarized3 He-MRI Study

Rationale and Objectives

Inhaled hyperpolarized 3 He magnetic resonance (MR) imaging has been used to measure alveolar size in patients with emphysema. The aim of this study was to test the hypothesis that 3 He MR images could be used to develop a biomarker of emphysema progression.

Materials and Methods

Twelve healthy controls and 18 patients with emphysema (eight current smokers, 10 ex-smokers) were imaged at baseline and 6 and 12 months. An additional nine subjects with α-1 antitrypsin deficiency (four with emphysema, six without symptoms) were also imaged at baseline and at 6 months. Each subject was imaged at two lung volumes: functional residual capacity (FRC) and FRC plus 15% of total lung capacity. Means and standard deviations of apparent diffusion coefficients (ADCs) were calculated from coronal images of the entire lung and correlated with pulmonary function test results. The lacunarity hypothesis was tested and calculated from the data using a range of 2 × 2 × 2 to 6 × 6 × 6 voxels, and the average was calculated.

Results

There was no change in the mean ADC at either lung volume in any subject over the 6- or 12-month period. FRC and residual volume increased over the 12 months, suggesting air trapping. The lacunarity of images collected at FRC increased at 6 and 12 months in smokers only ( P = .063 and P = .023, respectively).

Conclusions

The mean ADC calculated from MR images of the lungs with helium was not sufficiently sensitive to detect changes over a 12-month period. However, lacunarity captured more of the spatial information in the images and detected emphysema progress in the smokers.

Chronic obstructive lung disease (COPD) is a combination of airway inflammation (bronchitis) and lung tissue destruction (emphysema) . COPD is detected primarily by a fall in forced expiratory volume in 1 second (FEV 1 ) relative to forced vital capacity, and this measure, along with symptoms, is the basis for the Global Initiative for Chronic Obstructive Lung Disease classification of the severity of COPD . FEV 1 is a low-cost and effective method for assessing airway obstruction, but it does not discriminate bronchitis from emphysema, and it is relatively insensitive to the progression of the disease over 6 to 12 months . A noninvasive measure of lung tissue structure is needed to detect and quantify emphysema in patients with COPD. The method also needs to be sufficiently sensitive to measure the progression of the disease so that the effects of therapies on disease progression can be determined in cost-effective studies. Computed tomographic (CT) imaging provides a measure of lung structure, but it involves ionizing radiation. Mishima et al and Uppaluri et al applied more sophisticated analytic techniques to CT data to improve the sensitivity and specificity of CT imaging for detecting emphysema, but to our knowledge, none of these techniques have been used to demonstrate an ability of CT imaging to detect the progression of emphysema in individual patients with COPD within a 12-month period.

Magnetic resonance (MR) imaging of the lungs after inhaling a gas mixture of nitrogen and hyperpolarized 3 He (HeliSpin; GE Healthcare, Little Chalfont, UK) provides a measure of the apparent diffusion coefficient (ADC) of the helium within the airways . The mean value of the ADC measured in each of the approximately 10 to 20,000 voxels of a lung image provides a measure of airspace dimensions that has been shown to correlate with histologic measures and lung structure as assessed on CT imaging . Fain et al also demonstrated a natural increase in mean ADC with age. The use of hyperpolarized 3 He for MR lung airspace imaging is attractive because it does not require ionizing radiation, and it has been shown to be effective in detecting emphysema in humans . However, it is not known whether MR imaging of the lungs with HeliSpin is sufficiently sensitive to detect the changes in lung structure that occur within 6 to 12 months because of emphysema progression in patients with COPD.

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Materials and methods

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Subjects

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Post Hoc Lacunarity Analysis

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Statistical Analysis

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Results

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Table 1

Demographics and Smoking History

Group_n_ Age (y) Women Body Mass Index (kg/m 2 ) Pack-Years Control 12 52 ± 13 42% 24.6 ± 4.7 0.2 ± 0.5 COPD s 8 54 ± 7 88% 22.3 ± 3.4 39 ± 19 COPD x 10 62 ± 8 50% 22.7 ± 4.0 35 ± 12 COPD a 4 58 ± 5 50% 25.1 ± 6.2 14 ± 8 Control a 5 39 ± 12 80% 27.6 ± 2.9 4 ± 9

Data are expressed as mean ± standard deviation.

Table 2

Lung Function and Lung Volume

FEV 1 (% Predicted) DLCO (% Predicted) FRC (% Predicted) RV (% Predicted) Group Baseline 6 Months 12 Months Baseline 6 Months 12 Months Baseline 6 Months 12 Months Baseline 6 Months 12 Months Control 104 ± 13 103 ± 15 102 ± 16 95 ± 10 95 ± 9 93 ± 8 108 ± 21 113 ± 23 112 ± 18 110 ± 21 118 ± 14 116 ± 17 COPD s 56 ± 11 55 ± 11 50 ± 17 57 ± 16 58 ± 17 56 ± 16 133 ± 32 148 ± 33 153 ± 39 173 ± 44 195 ± 45 204 ± 59 COPD x 47 ± 10 46 ± 10 46 ± 10 54 ± 16 56 ± 17 54 ± 16 129 ± 26 126 ± 22 127 ± 29 157 ± 57 153 ± 58 157 ± 61 COPD a 52 ± 7 51 ± 8 49 ± 14 51 ± 11 142 ± 45 141 ± 41 175 ± 70 173 ± 69 Control a 84 ± 8 81 ± 11 75 ± 9 76 ± 9 91 ± 24 99 ± 26 94 ± 13 98 ± 15

Control a , controls with α-1 antitrypsin deficiency; COPD, chronic obstructive pulmonary disease; COPD a , patients with COPD and α-1 antitrypsin deficiency; COPD s , smokers with COPD; COPD x , ex-smokers with COPD; DLCO, diffusing capacity of carbon monoxide; FEV 1 , forced expiratory volume in 1 second; FRC, functional residual capacity; RV, residual volume.

Data are expressed as mean ± standard deviation.

Table 3

Mean ADC and Emphysema Index

ADC (cm 2 /s) FRC Plus 15% TLC FRC EI Group Baseline 6 Months 12 Months Baseline 6 Months 12 Months 6 Months Control 0.217 ± 0.040 0.217 ± 0.037 0.220 ± 0.038 0.188 ± 0.038 0.176 ± 0.037 0.191 ± 0.045 † COPD s 0.348 ± 0.127 0.344 ± 0.131 0.350 ± 0.134 0.312 ± 0.140 0.318 ± 0.150 0.279 ± 0.083 0.165 ± 0.125 COPD x 0.389 ± 0.097 0.384 ± 0.094 0.386 ± 0.100 0.363 ± 0.094 0.359 ± 0.095 0.346 ± 0.086 0.106 ± 0.092 COPD a 0.483 ± 0.103 0.499 ± 0.106 ∗ 0.428 ± 0.094 0.446 ± 0.108 ∗ 0.182 ± 0.139 Control a 0.208 ± 0.038 0.216 ± 0.046 ∗ 0.169 ± 0.031 0.178 ± 0.040 ∗ 0.004 ± 0.006

ADC, apparent diffusion coefficient; Control a , controls with α-1 antitrypsin deficiency; COPD, chronic obstructive pulmonary disease; COPD a , patients with COPD and α-1 antitrypsin deficiency; COPD s , smokers with COPD; COPD x , ex-smokers with COPD; EI, emphysema index; FRC, functional residual capacity; TLC, total lung capacity.

Data are expressed as mean ± standard deviation.

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Identifying Emphysema

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Detecting Progression

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Table 4

Lacunarity

FRC Plus 15% TLC FRC Group Baseline 6 Months 12 Months Baseline 6 Months 12 Months Control 1.027 ± 0.007 1.024 ± 0.004 1.027 ± 0.007 1.040 ± 0.011 1.038 ± 0.012 1.037 ± 0.012 COPD s 1.059 ± 0.053 1.062 ± 0.50 1.057 ± 0.040 1.040 ± 0.017 1.056 ∗ ± 0.040 1.060 † ± 0.046 COPD x 1.056 ± 0.032 1.056 ± 0.030 1.055 ± 0.029 1.053 ± 0.023 1.061 ± 0.032 1.054 ± 0.028 COPD a 1.076 ± 0.058 1.083 ± 0.075 1.103 ± 0.120 1.095 ± 0.093 Control a 1.022 ± 0.001 1.021 ± 0.001 1.032 ± 0.005 1.028 ± 0.004

Control a , controls with α-1 antitrypsin deficiency; COPD, chronic obstructive pulmonary disease; COPD a , patients with COPD and α-1 antitrypsin deficiency; COPD s , smokers with COPD; COPD x , ex-smokers with COPD; FRC, functional residual capacity; TLC, total lung capacity.

Data are expressed as mean ± standard deviation.

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Discussion

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Identifying Emphysema

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Detecting Progression

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References

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Progression of Emphysema in a 12-month Hyperpolarized3 He-MRI Study

Rationale and Objectives

Materials and Methods

Results

Conclusions

Materials and methods

Subjects

Post Hoc Lacunarity Analysis

Statistical Analysis

Results

Identifying Emphysema

Detecting Progression

Discussion

Identifying Emphysema

Detecting Progression

References

Further Reading

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