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Pulmonary Functional Magnetic Resonance Imaging

Posted Oct 31, 2014 Updated Apr 10, 2023
By Sarah Svenningsen BMSc , Fumin Guo MEng , Mira Kirby PhD , Stephen Choy MD , Andrew Wheatley BSc , David G. McCormack MD FRCPC , Grace Parraga PhD
12 min read

Rationale and Objectives

Hyperpolarized 3 He magnetic resonance imaging (MRI) previously revealed the temporal and spatial heterogeneity of ventilation defects in asthmatics, but these findings have not been used in treatment studies or to guide personalized therapy. Our objective was to exploit the temporal and spatial information inherent to 3 He MRI and develop image processing methods to generate pulmonary ventilation temporal–spatial maps that could be used to measure, optimize, and guide asthma therapy.

Materials and Methods

In this proof-of-concept study, seven asthmatics provided written informed consent to an approved protocol and underwent spirometry and 3 He MRI on three occasions, each 5 ± 2 days apart. A registration and segmentation pipeline was developed to generate three-dimensional, temporal–spatial, pulmonary function maps. Briefly, 3 He ventilation images were segmented to generate ventilation masks that were coregistered and voxels classified according to their temporal behavior. This enabled the regional mapping of temporally persistent and intermittent ventilation defects that were normalized to the 1 H MRI thoracic cavity volume to generate persistent ventilation defect percent (VDP P ) and intermittent ventilation defect percent (VDP I ).

Results

3 He temporal–spatial pulmonary function maps identified temporally persistent and intermittent ventilation defects. VDP I was significantly greater in the posterior ( P = .04) and inferior ( P = .04) lung as compared to the anterior and superior lung. Persistent and intermittent ventilation defect percent were strongly correlated with forced expiratory volume in one second/forced vital capacity (VDP P : r = −0.87, P = .01; VDP I : r = −0.96, P = .0008).

Conclusions

Temporal–spatial pulmonary maps generated from 3 He MRI can be used to quantify temporally persistent and intermittent ventilation defects as asthma intermediate end points and targets for therapy.

Asthma is a chronic pulmonary disease characterized by acute and predominantly reversible episodes of airflow limitation and airway hyper-responsiveness that leads to airway remodeling . Currently used asthma measurements are largely dependent on spirometry measurements of airflow limitation made at the mouth. Such measurements tend to overestimate large airway constriction and underestimate small airways disease , and these measurements cannot regionally identify the airways responsible for airflow limitation, asthma symptoms, or control.

Currently, pulmonary imaging techniques play a minor role in the clinical diagnosis and management of asthma, although quantitative measurements of regional, structural, and functional pulmonary abnormalities can be derived using a number of imaging methods. For example, x-ray computed tomography (CT) has been used to show airway remodeling and evidence of gas trapping in asthmatics . Single-photon emission computed tomography and positron-emission tomography have revealed the spatial distribution and extent of airway remodeling in asthmatics at rest and during exacerbations. Hyperpolarized noble gas magnetic resonance imaging (MRI), using either 3 He or 129 Xe, also provides a way to visualize and quantify lung regions that participate in ventilation and those that do not . Longitudinal and interventional 3 He MRI studies have revealed the regional and temporal nature of ventilation defects in asthma before and after provocation (exercise and methacholine) and therapy . Previous work also showed that in asthma, ventilation defects are related to disease severity , CT measurements of gas trapping , and airway morphological abnormalities . Taken together, these studies suggest that in asthma, ventilation defects are related to airways disease, are regionally heterogeneous, temporally variable, and responsive to therapy and provocation . Asthma ventilation defects may be considered as therapy targets or intermediate end points as they are present in older asthmatics with more advanced or severe disease, increased indices of inflammation, and more severely remodeled airways .

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Materials and methods

Study Design

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Magnetic Resonance Imaging

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Image Analysis

Overview of Pipeline

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Figure 1, Pipeline to generate whole-lung, two-dimensional, hyperpolarized 3 He magnetic resonance imaging (MRI) temporal–spatial pulmonary function maps. The pipeline is divided into four steps: 1) registration, 2) 1 H MRI segmentation, 3) 3 He MRI segmentation and, 4) temporal map generation. The inputs to the pipeline are N N 3 He MR images acquired at visits i∈{1,2...,N} i∈{1,2...,N} , where N ≥ 2, and an associated 1 H MR image acquired at an arbitrary visit j j , j∈{1,2...,N} j∈{1,2...,N} .

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Step 1: Registration

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Step 2: 1 H MRI Segmentation

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Step 3: 3 He MRI Segmentation

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Step 4: Temporal Map Generation

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Registration Performance Evaluation

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Statistical Analysis

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Results

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Table 1

Subject Demographic Characteristics

Parameter Asthma (±SD) [Range]; ( n = 7) Age, years 28 (9) [21–47] Male/female 4/3 BMI kg/m 2 26 (4) [21–33] SaO 2 97 (2) [94–98] FEV 1 % pred 88 (11) [65–99] FVC% pred 104 (10) [89–120] FEV 1 /FVC% 72 (8) [61–81]

BMI, body mass index; FEV 1 , forced expiratory volume in 1 second; FVC, forced vital capacity; SaO 2 , arterial oxygen saturation; SD, standard deviation; % pred , percent predicted.

Table 2

Repeated Spirometry and Hyperpolarized 3 He Measurements

Parameter Time Point (±SD) [Range]; ( n = 7) Significance of Difference ( P ) ∗ Visit 1 Visit 2 Visit 3 Spirometry FEV 1 % pred 88 (11) [65–99] 86 (12) [59–96] 84 (12) [62–95] .22 FVC% pred 104 (10) [89–120] 101 (15) [77–127] 99 (14) [83–126] .18 FEV 1 /FVC% 72 (8) [61–81] 71 (7) [60–81] 72 (8) [62–82] .76 Hyperpolarized 3 He Dose, mL 386 (70) [290–490] 380 (76) [250–490] 386 (95) [250–550] .74 Polarization, % 13 (2) [10–15] 12 (2) [8–14] 12 (2) [9–14] .31 MRI VDP, % 4 (2) [1–7] 4 (3) [1–9] 4 (3) [1–8] .93

FEV 1 , forced expiratory volume in 1 second; FVC, forced vital capacity; MRI, magnetic resonance imaging; SD, standard deviation; VDP, ventilation defect percent; % pred , percent predicted.

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Table 3

Subject Listing of Demographic, Spirometry and Hyperpolarized 3 He MRI Measurements

Subject Age Spirometry Hyperpolarized 3 He MRI Sex FEV 1 % pred FVC% pred FEV 1 /FVC, % Dose, mL Polarization, % VDP, % VDP P , % VDP I , % PVP, % V1/V2/V3 V1/V2/V3 V1/V2/V3 V1/V2/V3 V1/V2/V3 V1/V2/V3 1 27 M 89/88/77 108/103/95 69/70/68 390/390/390 13/14/14 3/5/8 0.59 6.45 92.96 2 25 M 85/83/84 94/96/87 76//73/81 420/420/420 13/12/14 1/1/1 0.02 1.49 98.49 3 22 M 88/91/94 120/127/126 62/60/63 390/390/390 15/12/13 7/9/2 0.30 7.23 92.47 4 28 M 95/89/90 106/101/95 75/74/79 490/490/550 11/9/12 2/2/1 0.03 3.13 96.84 5 27 F 94/96/95 102/105/102 81/81/82 290/250/250 10/8/9 4/1/2 0.02 1.97 98.01 6 21 F 99/93/87 108/100/105 77/78/70 420/400/400 14/14/14 2/4/5 0.13 3.35 96.53 7 47 F 65/59/62 89/77/83 61/64/62 300/320/300 14/13/9 6/4/6 0.34 6.68 92.98 Mean 28 — 88/86/84 104/101/99 72/71/72 386/380/386 13/12/12 4/4/4 0.20 4.33 95.47 SD 9 — 11/12/12 10/15/14 8/7/8 70/76/95 2/2/2 2/3/3 0.22 2.40 2.58

FEV 1 , forced expiratory volume in 1 second; FVC, forced vital capacity; PVP, persistent ventilation percent; V1, visit 1; V2, visit 2; V3, visit 3; VDP, ventilation defect percent; VDP P , persistent ventilation defect percent; VDP I , intermittent ventilation defect percent; % pred , percent predicted.

Figure 2, Coronal 3 He magnetic resonance imaging (MRI) coregistered to the corresponding 1 H MRI acquired at visits 1–3, and the corresponding temporal–spatial pulmonary function maps for seven asthmatic subjects. Regional differences in the spatial distribution of 3 He MRI ventilation defects are visually apparent between visits for each subject. This short-term temporal 3 He ventilation defect behavior is shown in the corresponding two-dimensional temporal–spatial map for each subject.

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Temporal–Spatial Pulmonary Function Maps

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Target Registration Error

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Ventilation Defect Temporal Behavior

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Anatomic Differences

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Figure 3, Three-dimensional 3 He magnetic resonance imaging (MRI) temporal–spatial pulmonary function maps for three representative asthmatic subjects. Three-dimensional 3 He MRI in the coronal, axial, and sagittal view to qualitatively evaluate persistent and intermittent ventilation defects. Both persistent and intermittent ventilation defects are prominent in the gravity-dependent posterior and inferior lung regions.

Figure 4, 3 He magnetic resonance imaging (MRI) intermittent ventilation defect percent (VDP I ) and persistent ventilation defect percent (VDP P ) anatomic differences. Plots show anatomic differences in VDP I and VDP P for regions of interest in the anterior-centre-posterior (a,b) and superior-middle-inferior directions (c,d) . Box and whisker plots represent minimum, 25th percentile, median, 75th percentile, and maximum. Statistically significant differences between regions of interest are shown.

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Relationships with Spirometry

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Figure 5, Relationship of 3 He magnetic resonance imaging (MRI) temporal–spatial pulmonary function with airflow obstruction at baseline and following exercise challenge. Baseline FEV 1FVC was significantly correlated with intermittent ventilation defect percent (VDP I ; r = −0.96, P = .0008) (a) , and persistent ventilation defect percent (VDP P ; r = −0.87, P = .01) (b) . Postexercise FEV 1FVC was significantly correlated with VDP I ( r = −0.96, P = .003) (c) , and VDP P ( r = −0.79, P = .04) (d) . Dotted lines indicate the 95% limits of agreement.

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Discussion

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Acknowledgments

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Academic Radiology, Volume 21, Issue 11
Journals General Radiology
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