Multibreath Hyperpolarized3 He Imaging Scheme to Measure Alveolar Oxygen Tension and Apparent Diffusion Coefficient

Rationale and Objectives

In this study, we compared a newly developed multibreath simultaneous alveolar oxygen tension and apparent diffusion coefficient ( P A O 2 -ADC) imaging sequence to a single-breath acquisition, with the aim of mitigating the compromising effects of intervoxel flow and slow-filling regions on single-breath measurements, especially in chronic obstructive pulmonary disease (COPD) subjects.

Materials and Methods

Both single-breath and multibreath simultaneous P A O 2 -ADC imaging schemes were performed on a total of 10 human subjects (five asymptomatic smokers and five COPD subjects). Estimated P A O 2 and ADC values derived from the different sequences were compared both globally and regionally. The distribution of voxels with nonphysiological values was also compared between the two schemes.

Results

The multibreath protocol decreased the ventilation defect volumes by an average of 12.9 ± 6.6%. The multibreath sequence generated nonphysiological P A O 2 values in 11.0 ± 8.5% fewer voxels than the single-breath sequence. Single-breath P A O 2 maps also showed more regions with gas-flow artifacts and general signal heterogeneity. On average, the standard deviation of the P A O 2 distribution was 16.5 ± 7.0% lower using multibreath P A O 2 -ADC imaging, suggesting a more homogeneous gas distribution. Both mean and standard deviation of the ADC increased significantly from single- to multibreath imaging ( p = 0.048 and p = 0.070, respectively), suggesting more emphysematous regions in the slow-filling lung.

Conclusion

Multibreath P A O 2 -ADC imaging provides superior accuracy and efficiency compared to previous imaging protocols. P A O 2 and ADC maps generated by multibreath imaging allowed for the qualification of various regions as emphysematous or obstructed, which single-breath P A O 2 maps can only identify as defects. The simultaneous P A O 2 and ADC measurements generated by the presented multibreath method were also more physiologically realistic, and allowed for more detailed analysis of the slow-filling regions characteristic of COPD subjects.

Introduction

Hyperpolarized (HP) gas magnetic resonance imaging (MRI) has recently emerged as a technique capable of safely detecting a variety of changes in the lungs such as air flow restriction, airspace enlargement, decreased tissue perfusion, alveolar membrane thickening, and air trapping ( ), thereby expanding upon the parameters available from conventional modalities like computed tomography and x-ray imaging, and enabling the accurate, regional evaluation of gas flow and uptake ( ).

Two parameters that HP gas MRI is uniquely capable of assessing are regional alveolar oxygen tension ( P A O 2 ), which reflects oxygen delivery to the parenchyma and uptake into the blood, and apparent diffusion coefficient (ADC), which describes the diffusion of gas within various regions of the lung. Because P A O 2 reflects the balance between gas replacement through ventilation and uptake into the blood, it is sensitive to early manifestations of chronic obstructive pulmonary disease (COPD), an inflammatory lung condition causing chronic obstruction of airflow. ADC, on the other hand, is primarily indicative of structural changes in alveolar size and connectivity that are expected later in disease progression ( ). Often acquired simultaneously and coregistered, P A O 2 and ADC can serve as important indicators of pathophysiological changes in the lungs ( ), and together provide a more comprehensive portrait of lung function and structure than is available with other methods—increasing sensitivity to early subclinical alterations and, thereby, diagnostic power ( ).

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Materials and Methods

Demographics

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Table 1

Demographics and a Subset of Clinical Test Results

Subject Demographics PFTs Age (Years) TLC (L) Height (in) Weight (lb) BMI (kg/m 2 ) FEV 1 (L) FEV 1 /FVC (%) RV/TLC (%) DL CO (mL/min/mmHg) Pred. FEV 1 (%) Pred. DL CO (%) Life Impact SGRQ Overall (%) AS 1 58 6.01 64.5 141.7 23.9 2.97 78 34 19.29 117 91 15.9 AS 2 64 5.95 70.5 167 23.6 2.88 71 32 19.75 93 88 6.51 AS 3 67 6.91 66.5 198 31.5 2.81 72 46 23.73 110 93 29 AS 4 62 6.55 71.5 176 23.9 3.01 77 36 33.46 80 127 10.39 AS 5 31 7.87 75 207 25.9 5.19 80 16 34.2 101 92 2.64 Mean ± SD 56.4 ± 13.03 6.66 ± 0.79 69.6 ± 3.72 177.9 ± 23.2 25.76 ± 2.98 3.37 ± 0.91 75.6 ± 3.50 32.8 ± 9.68 26.09 ± 6.51 100.2 ± 12.95 98.2 ± 14.50 12.89 ± 9.17 COPD 1 70 6.57 69 184 27.2 0.88 35 59 8.7 28 37 51.5 COPD 2 68 5.04 63.5 158.5 27.2 1.54 58 46 12.44 83 73 18.88 COPD 3 60 9.24 67 178 27.9 1.26 40 62 14.66 39 59 29.79 COPD 4 55 5.14 67 180 28.2 2.29 71 41 16.07 92 68 57.16 COPD 5 61 3.71 63 134 23.7 0.67 49 62 8.95 27 51 7.727 Mean ± SD 62.8 ± 6.14 5.94 ± 2.10 65.9 ± 2.56 166.9 ± 20.9 26.84 ± 1.81 1.33 ± 0.63 51.8 ± 16.6 54.0 ± 9.82 12.16 ± 3.31 53.8 ± 31.28 57.6 ± 14.28 33.01 ± 21.06 P (T ≤ t) 0.406 0.542 0.268 0.587 0.548 0.036 0.036 0.038 0.014 0.080 0.006 0.088

BMI, body mass index; COPD, chronic obstructive pulmonary disease; SD, standard deviation; SGRQ, St. George’s Respiratory Questionnaire.

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Measurement of P A O 2

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1T1=0.45(299T)0.42[O2] 1

0.45

(

299

)

0.42

[

]

where T 1 , the longitudinal relaxation time, T , body temperature, and [O 2 ], oxygen concentration, are measured in s, K, and Amagat, respectively. At body temperature, Equation 1 yields:

T1=EPAO2 T

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Mn=M0cosn*NPE(α)×exp[−PAO2*tn(k)ξ] M

(

)

exp

[

−

(

)

]

where M 0 is the initial magnetization level of 3 He, N PE is the number of phase-encode gradients for each imaged slice, and α represents the flip angle. t n ( k ) is the start time of the n th acquisition for the k th slice.

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MA(j)=FV*MS+(1−FV).MA(j−1).exp(DA),MA(0)=0 M

(

)

(

−

)

(

−

)

exp

(

)

(

)

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Simultaneous Measurement of P A O 2 and ADC

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ADC=1b0(logS0S1) ADC

(

log

)

in which S 0 / S 1 corresponds to the measured signal intensity without/with diffusion encoding. The parameter b 0 combines the strength and duration of the gradients, as is standard for liquid and gas diffusion measurements by MRI. Although the numerical value of ADC can vary with gradient duration even as b 0 is held constant, we utilize the commonly chosen standard diffusion pulse timing parameters with no interpulse delay ( ).

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Imaging Parameters

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Imaging Studies

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Gas Delivery Device/System

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HP 3 He Production

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Data Analysis

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Homogeneity=∑i,jp(i,j)1+|i−j| Homogeneity

∑

(

)

−

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Statistical Analyses

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Results/Discussion

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Table 2

Imaging Markers

P A O 2 ADC Single-breath Multibreath Single-breath Multibreath Subject Global (Torr) Heterogeneity \* (Torr) <40 or >160 Nonphysiol. † Global (Torr) Heterogeneity \* (Torr) <40 or >160 Nonphysiol. † Global (cm 2 /s) Heterogeneity \* (cm 2 /s) Global (cm 2 /s) Heterogeneity \* (cm 2 /s) AS 1 116 43 61 69 35 52 0.356 0.118 0.391 0.097 AS 2 ‡ - - - - - - 0.315 0.106 0.317 0.124 AS 3 73 42 102 85 36 89 0.320 0.109 0.328 0.108 AS 4 101 35 48 74 34 48 0.263 0.072 0.272 0.070 AS 5 ‡ - - - - - - 0.204 0.099 0.205 0.111 Mean ± SD 97 ± 22 40 ± 4 70 ± 28 76 ± 8 35 ± 1 63 ± 23 0.292 ± 0.059 0.101 ± 0.017 0.303 ± 0.069 0.102 ± 0.02 COPD 1 106 49 117 73 36 103 0.547 0.143 0.598 0.157 COPD 2 105 42 69 86 34 44 0.396 0.109 0.414 0.119 COPD 3 114 39 33 90 33 33 0.328 0.107 0.329 0.124 COPD 4 85 38 50 76 30 32 0.396 0.111 0.402 0.135 COPD 5 145 48 101 106 42 92 0.269 0.072 0.264 0.119 Mean ± SD 111 ± 22 43 ± 5 67 ± 44 86 ± 13 35 ± 4 56 ± 41 0.387 ± 0.104 0.108 ± 0.025 0.401 ± 0.125 0.131 ± 0.016 P (T ≤ t) 0.416 0.367 0.877 0.225 0.384 0.916 0.122 0.609 0.1720.037

ADC, apparent diffusion coefficient; COPD, chronic obstructive pulmonary disease; SD, standard deviation.

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Table 3

Imaging Markers

Slow-Filling Voxels ADC_P_ A O 2 Subject VDV Decrease (%) Mean (Torr) SD (Torr) Mean (cm 2 /s) SD (cm 2 /s) AS 1 15.8 0.372 0.267 59.8 22.0 AS 2 5.7 0.323 0.054 - - AS 3 13.6 0.274 0.093 73.6 26.4 AS 4 11.2 0.296 0.083 66.4 19.2 AS 5 3.5 0.206 0.033 - - Mean ± SD 10 ± 6.2 0.314 ± 0.052 0.147 ± 0.103 66.6 ± 6.9 22.5 ± 3.6 COPD 1 24.7 0.610 0.237 88.0 30.8 COPD 2 8.2 0.426 0.163 59.7 29.2 COPD 3 14.5 0.337 0.076 109.6 28.6 COPD 4 10.3 0.419 0.047 86.1 21.5 Mean ± SD 15.7 ± 7 0.455 ± 0.14 0.12 ± 0.103 88.4 ± 18.6 27 ± 4.9p ( T ≤ t ) 0.180 0.144 0.922 0.060 0.144

COPD, chronic obstructive pulmonary disease; SD, standard deviation; VDV, ventilation defect volume.

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Limitations

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Conclusion

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Multibreath Hyperpolarized3 He Imaging Scheme to Measure Alveolar Oxygen Tension and Apparent Diffusion Coefficient

Rationale and Objectives

Materials and Methods

Results

Conclusion

Introduction

Materials and Methods

Demographics

Measurement of P A O 2

Simultaneous Measurement of P A O 2 and ADC

Imaging Parameters

Imaging Studies

Gas Delivery Device/System

HP 3 He Production

Data Analysis

Statistical Analyses

Results/Discussion

Limitations

Conclusion

References

Further Reading

Convolutional Neural Networks with Template-Based Data Augmentation for Functional Lung Image Quantification

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