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Hyperpolarized Helium-3 MRI of Cystic Fibrosis

Sarah Svenningsen University of Western Ontario Medical Biophysics April. 6, 2010. Hyperpolarized Helium-3 MRI of Cystic Fibrosis. Cystic Fibrosis. CF is a lethal, autosomal recessive, disease resulting from mutations in the cystic fibrosis transmembrane regulator (CFTR) gene (1)

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Hyperpolarized Helium-3 MRI of Cystic Fibrosis

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  1. Sarah Svenningsen University of Western Ontario Medical Biophysics April. 6, 2010 Hyperpolarized Helium-3 MRI of Cystic Fibrosis

  2. Cystic Fibrosis • CF is a lethal, autosomal recessive, disease resulting from mutations in the cystic fibrosis transmembrane regulator (CFTR) gene (1) • Mutations in the CFTR gene interfere with epithelial ion transport • Primarily affecting organs of epithelial origin; lungs, pancreas, intestines, and reproductive tract (1) • Children and young adults are predominantly affected • Death is mainly the result of respiratory failure, a consequence of progressive lung damage resulting from lung inflammation and infection (1)

  3. CF: Pathophysiology of Lung Disease

  4. CF: Lung Disease • Multiple Inter-related Clinical Symptoms including: • Bronchiectasis • Pulmonary Hyperinflation • Air Trapping • Ventilation Abnormalities

  5. Cystic Fibrosis: Median Survival Age • Canadian Cystic Fibrosis Patient Data Registry, 2002.

  6. Study Motivation

  7. Current Measurement Tools • Pulmonary function tests (PFT): Global measurement of disease  Limitation: 1)PFT provide no regional information about lung function and/or structure (4) 2) insensitive to small changes in severity (4) • X-ray & X-ray CT: high resolution CT is the current ‘gold standard’ for depicting lung changes in CF (2) Limitation: 1) radiation exposure

  8. Hyperpolarized 3He magnetic resonance imaging: anew imaging modality that allows for the visualization of lung structure and function at high resolution • With a low physical density of protons there is low signal intensity naturally generated in the lungs (3) 3He hyperpolarized ventilation contrast agent generation of high signal intensity in airspaces

  9. Hyperpolarized 3He Magnetic Resonance Imaging (MRI) 3He MR image linked with the proton MR image 3He MR image

  10. Study Objective • Evaluate 3He MRI measurements as possible intermediate endpoints in adult CF patients. This objective will be met by: 1) Assessment of the short term (7-day) reproducibility of 3He MRI measurements 2) Through examination of the relationship between 3He MRI derived measurements and standard measurements of lung function

  11. Standard Measurements of Lung Function • FEV1: forced expiratory volume in 1 second The volume of air exhaled in the 1st second of forced expiration (3) • FVC: forced vital capacity The volume of air that can be forcibly blown out after full inspiration (3) • RV: residual volume The volume of air present in the lungs at the end of exhalation (3)

  12. Study Design: 8 Adult CF Subjects • Between 21 and 41 years of age • FEV1 > 50% predicted • MRI was performed on a whole body 3.0 Tesla Excite 12.0 MRI system

  13. Image Analysis: Ventilation Measurements • Image analysis was performed slice by slice • Ventilation volumes (VV), ventilation defect volumes (VDV), and thoracic cavity volumes (TCV) were manually segmented TCV VDV VV

  14. Patient 001 Baseline Follow Up FEV1= 58% PVV= 45% VDP= 51% FEV1= 61% PVV=34% VDP= 55%

  15. Patient 003 Baseline Follow Up FEV1=82% PVV= 96% VDP= 16% FEV1=79% PVV= 95% VDP= 18%

  16. Patient 007 Baseline Follow Up FEV1=75% PVV= 73% VDP= 25% FEV1=79% PVV= 91% VDP= 12%

  17. Measurement Reproducibility *difference between scan and rescan values are significant (p < 0.05) †(n=6)

  18. Discussion: Measurement Reproducibility • Scan and 7 ± 2 day rescan 3He MRI measurements (VDP, PVV) were highly reproducible • Spirometry measures at scan and 7 ± 2 rescan : • FEV1(%pred) measurements were reproducible • FVC (%pred) measurements were not reproducible • RV measurements were reproducible

  19. Linear Correlation:Relationship between FEV1 and VDP Baseline Follow Up Strong negative correlation for both baseline and follow up data %FEV1 = VDP %

  20. Linear Correlation:Relationship between FVC and VDP Baseline Follow Up weak negative correlation moderately strong negative correlation FVC % = VDP %

  21. Linear Correlation:Relationship between RV and VDP Baseline Follow Up Strong positive correlation Moderate positive correlation RV α VDP %

  22. Discussion: Ventilation Measurements • VDP was associated with FEV1, FVC and RV suggesting that VDP is sensitive to the level of bronchial obstruction, pulmonary hyperinflation and gas trapping • VDP was negatively correlated with FEV1%pred signifying that in CF, an increase in ventilation defects is accompanied by decreased FEV1%pred • Thus there are noteworthy associations between the 3He MRI and lung function measurements

  23. Conclusion • This study demonstrates the potential for 3He MRI phenotypes as clinical endpoints in adult cystic fibrosis patients • Providing an accurate evaluation of disease progression and/or the effect of longitudinal treatment while providing regional information of the lung

  24. Acknowledgements • Grace Parraga, PhD Scientist Imaging Research Laboratories • Hassaan AhmedBSc

  25. References (1) Hodson, Margaret E., Duncan M. Geddes, and Andrew Bush. Cystic Fibrosis. 3rd ed. London: Hodder Arnold, 2007. Print. (2) "Hyperpolarized 3helium Magnetic Resonance Ventilation Imaging of the Lung in Cystic Fibrosis: Comparison with High Resolution CT and Spirometry." EurRadiol 16 (2006): 2483-490. Print. (3) "Lung Function Testing." All about Spirometry. Web. 20 Mar. 2010. <http://www.spirxpert.com/indices7.htm>. (4) "Magnetic Resonance Imaging of the Lung in Cystic Fibrosis." Proc Am Thorac Soc 4 (2007): 321-27. Print.

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