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Hyperpolarized3 He Magnetic Resonance Imaging of Ventilation Defects in Healthy Elderly Volunteers

Posted May 31, 2008 Updated Apr 7, 2023
By Grace Parraga PhD , Lindsay Mathew BMSc , Roya Etemad-Rezai MD , David G. McCormack MD , Giles E. Santyr PhD
10 min read

Rationale and Objectives

Hyperpolarized 3 He magnetic resonance imaging ventilation defects have been observed in subjects with respiratory disorders. We quantified 3 He ventilation defects in elderly and middle-aged subjects who had no history of smoking, respiratory, or cardiovascular disorders.

Materials and Methods

Hyperpolarized 3 He magnetic resonance imaging ventilation defect volume (VDV) and ventilation defect score (VDS) were assessed in eight elderly healthy volunteers (mean 67 ± 6 years) scanned twice within 7 ± 2 minutes and again 7 ± 2 days later. A younger cohort of 24 subjects (mean 44 ± 10 years) was also scanned for direct comparison. Four observers blinded to scan timepoint and subject identity scored VDS and manually segmented VDV in all center coronal slices.

Results

Center coronal slice ventilation defects were observed in six of eight elderly subjects (ages 63–74 years, 5 males) in all scans acquired and in no middle-aged subjects. At the scan timepoint, mean VDS was 2.7 (mean VDV 52 ± 34 cm 3 ), whereas for same-day rescan, mean VDS was 2.5 (mean VDV 53 ± 35 cm 3 ) and at 7-day rescan, mean VDS was 3.6 (mean VDV 48 ± 39 cm 3 ). Interscan coefficients of variation (COV) for mean VDV was 1.8% (same-day rescan) and 5.3% (7-day rescan) and interobserver COV ranged from 10–12%.

Conclusion

Elderly subjects have ventilation defects that are reproducible in same-day scanning and 7-day scanning visits. The observation of reproducible pulmonary ventilation defects in otherwise healthy elderly volunteers suggests caution must be used in interpreting results from 3 He studies of elderly subjects.

New methods of pulmonary magnetic resonance imaging (MRI) with inhaled hyperpolarized helium-3 ( 3 He) have been shown to provide regional pulmonary 3 He ventilation maps and the location and size of ventilation changes within the lung in asthma ( ), cystic fibrosis ( ) and chronic obstructive pulmonary disease (COPD) ( ). In patients with respiratory disease, areas of decreased ventilation from airflow changes are observed as “ventilation defects” that are visualized as decreased (and/or absence of) 3 He intensity in 3 He MRI spin density images.

Previously, both the size and number of these ventilation defects have been shown to correlate with severity in asthma ( ), and in addition, exercise and methacholine challenge has been shown to alter the size, location, and number of defects that occur in asthma ( ). We have also previously described a preliminary analysis of ventilation defect score (VDS) and ventilation defect volume (VDV) in 3 subjects: one with mild-moderate COPD, one with severe COPD, and a single healthy age-matched control ( ). We noted in this study that significant ventilation defects were observed even in the healthy elderly subject. The finding of numerous center slice ventilation defects in an older healthy individual who was not a smoker, did not have asthma, or cardiovascular disease, and who had normal pulmonary function tests ( ) was surprising and had not been reported previously in other studies of younger healthy volunteers. This result challenged us to explain the physiologic mechanisms related to ventilation defects in healthy lungs as well as the prevalence of ventilation defects in older and middle-aged individuals. To try to address some of these issues, the goal of this study was to examine and compare, using 3 He MRI, ventilation defects in elderly and middle-aged subjects who had no history of smoking, respiratory, or cardiovascular disease.

Materials and methods

Study Population

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Spirometry

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Magnetic Resonance Imaging

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Image Analysis

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Figure 1, Hyperpolarized 3 He magnetic resonance imaging ventilation defect volume segmentation approach. (a) 1 H thoracic cavity: (i) Subject 7-1003, (ii) Subject 7-1008, (iii) Subject 6-007, (iv) Subject 6-001. (b) Hyperpolarized 3 He ventilation image: (i) Subject 7-1003, (ii) Subject 7-1008, (iii) Subject 6-007, (iv) Subject 6-001. (c) Overlay of 3 He ventilation image (yellow) on 1 H thoracic cavity (grey): (i) Subject 7-1003, (ii) Subject 7-1008, (iii) Subject 6-007, (iv) Subject 6-001. (d) Segmentation of 3 He ventilation defects (red): (i) Subject 7-1003, (ii) Subject 7-1008, (iii) Subject 6-007, (iv) Subject 6-001.

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Results

Study Subjects

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Table 1

Study Subject Demographic Characteristics

Elderly Healthy Volunteers (n = 8) Middle-aged Healthy Volunteers (n = 24) Male (n) 5 14 Age (± SD) [range] (yrs) 67 (6) 44 (10) [58–74] [23–57] Weight (± SD) kg 76 (17) 76 (13) Body mass index (± SD) [range] 27 (4) 25 (3) [24–35] [20–34] FEV 1 % predicted (± SD) 106 (19) 101 (11) FEV 1 /FVC % (± SD) 77 (5) 80 (8) Subjects with ventilation defects (n) (male) 6 (3) 0 (0) Total ventilation defects (n) Scan 16 0 Same-day rescan 15 0 7-day Rescan 18 0 Mean VDV cm 3 (± SD) Scan 52 (34) 0 Same-day rescan 53 (35) 0 7-day rescan 48 (39) 0

SD, subgroup standard deviation for eight healthy volunteers; FEV, forced expiratory volume in 1 second; FVC, forced vital capacity.

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Ventilation Defects and Ventilation Defect Volume

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Table 2

Ventilation Defects in Elderly Healthy Volunteers

Ventilation Defects in Center Slice Scan Same-day Rescan 7-day Rescan Subject 1001 (n) 0 0 0 Subject 1002 (n) 3 3 ND Subject 1003 (n) 3 3 5 Subject 1004 (n) 2 2 4 Subject 1005 (n) 3 2 3 Subject 1006 (n) 0 0 0 Subject 1007 (n) 2 2 3 Subject 1008 (n) 3 3 3 Total sum defects 16 15 18 Mean defect score 2.7 2.5 3.6

ND, not done (patient withdrew from study due to claustrophobia)

Figure 2, Elderly healthy volunteers 3 He magnetic resonance imaging. (a) Subject 7-1004 70-year-old female, forced expiratory volume in 1 second (FEV 1 ) = 149% predicted, FEV 1 forced vital capacity (FVC) = 75% (i) 3 He image (ii) overlay of 3 He image with 1 H thorax image. (b) Subject 7-1007 73-year-old male, FEV 1 = 104% predicted, FEV 1FVC = 84%. (i) 3 He image (ii) overlay of 3 He image with 1 H thorax image. (c) Subject 7-1008 74-year-old male, FEV 1 = 91% predicted, FEV 1FVC=79% (i) 3 He image (ii) overlay of 3 He image with 1 H thorax image.

Figure 3, Middle-aged healthy volunteers 3 He magnetic resonance imaging. (a) Subject 6-1001 45-year-old female. (b) Subject 6-1003 42-year-old male. (c) Subject 6-1010 39-year-old male.

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Ventilation Defect Volume Interscan and Interobserver Reproducibility

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Figure 4, Reproducibility of 3 He ventilation in elderly and middle-aged healthy volunteers. (a) Subject 7-1005 elderly volunteer: (i) scan, (ii) same-day rescan, (iii) 7-day rescan. (b) Subject 7-1008 elderly volunteer: (i) scan, (ii) same-day rescan, (iii) 7-day rescan. (c) Subject 6-1001 middle-aged volunteer: (i) scan, (ii) rescan 1, (iii) rescan 2. (d) Subject 6-1002 middle-aged volunteer: (i) scan, (ii) rescan 1, (iii) re-scan 2.

Table 3

Elderly Volunteer Ventilation Defect Volume Interobserver Reproduciblity

Mean VDV cm 3 (± SD) Scan Same-day Rescan 7-day Rescan Observer 1 52 (34) 53 (35) 48 (39) Observer 2 72 (55) 67 (47) 60 (48) Observer 3 67 (43) 64 (42) 53 (40) Observer 4 70 (63) 65 (61) 46 (44) Mean Ob1-4 66 (8) ⁎ 62 (6) ⁎ 52 (6) ⁎ COV (%) 12 10 12

SD, subgroup standard deviation for eight healthy volunteers, except for *SD is observer standard deviation; COV,

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Discussion

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Conclusions

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Acknowledgements

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Academic Radiology, Volume 15, Issue 6
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