1. ISBE-AstraZeneca Strategic Alliance Project 23 Progress Report Development and assessment of quantitative oxygen-enhanced MRI in patients with obstructive lung disease Ninth meeting of the Strategic Alliance ISBE, University of Manchester 29 September 2003

2. ISBE-AstraZeneca Strategic Alliance Project 23 Progress Report Project objectives To implement methods for measuring oxygen-enhanced MRI (OE- MRI) in the lung. To extend these methods to quantitative parametric mapping of dynamic OE-MRI in the lung To apply these methods in a cohort of normal volunteers and chronic obstructive pulmonary disease (COPD) patients to assess aspects of lung function and technique reproducibility

3. ISBE-AstraZeneca Strategic Alliance Project 23 Progress Report Imaging IR HASTE sequence, 10mm thick coronal slice 6 normal volunteers MR compatible Intersurgical Bain Breathing system with 9.5 m tube volunteers commented that breathing was uncomfortable especially on expiration Protocol (approx 10 minutes per slice) T1T1 T1T1 dynamic airoxygenair time

4. ISBE-AstraZeneca Strategic Alliance Project 23 Progress Report Image registration attempts at registration using clamped plate spline had limited success, partly due to the difficulty in defining corresponding points around lung outline try something simpler as a first approximation: –assume most variation is in vertical direction –resample points along top edge of lung and diaphragm at discrete x-locations and perform simple linear stretch

5. ISBE-AstraZeneca Strategic Alliance Project 23 Progress Report Results: T 1 maps selecting images for which right diaphragm position matches to <2 pixels registering all images by 1D linear

6. ISBE-AstraZeneca Strategic Alliance Project 23 Progress Report T 1 maps breathing air and oxygen airoxygen

7. ISBE-AstraZeneca Strategic Alliance Project 23 Progress Report T 1 maps breathing air and oxygen airoxygen

8. ISBE-AstraZeneca Strategic Alliance Project 23 Progress Report 1/T 1 (O 2 ) – 1/T 1 (air)

9. ISBE-AstraZeneca Strategic Alliance Project 23 Progress Report Results: dynamic sequence ROI top third of right lungROI middle third of right lung blue: raw imagesred: registered images

10. ISBE-AstraZeneca Strategic Alliance Project 23 Progress Report Results: dynamic sequence ROI bottom third of right lung blue: raw imagesred: registered images

11. ISBE-AstraZeneca Strategic Alliance Project 23 Progress Report Results: dynamic sequence ROI top third of right lung blue: raw imagesred: registered images

12. ISBE-AstraZeneca Strategic Alliance Project 23 Progress Report Results: dynamic sequence ROI middle third of right lung blue: raw imagesred: registered images

13. ISBE-AstraZeneca Strategic Alliance Project 23 Progress Report Results: dynamic sequence blue: raw imagesred: registered images

14. ISBE-AstraZeneca Strategic Alliance Project 23 Progress Report sd(raw) – sd(registered)

15. ISBE-AstraZeneca Strategic Alliance Project 23 Progress Report Oxygen uptake time very little literature on dynamic measurements –Hatabu et al (2001) fit to exponential using ROI whole right or left lung, found decay times of 27±10s (9 subjects) –Muller et al (2002) pixel by pixel straight line fit, find mean slope of 10±1% per min and total signal change of 15±6% (4 volunteers) i.e. total uptake time of about 90s fit whole of right lung to exponential function, find decay time 50±12s (for 4 volunteers) fit 8 ROI in right lung to slope plus constant to find average total uptake time of around 100s (1 volunteer)

16. ISBE-AstraZeneca Strategic Alliance Project 23 Progress Report Summary pilot study on volunteers has demonstrated that we can measure oxygen enhancement in the lung average T 1 values while breathing air and O 2 are in agreement with published data using a simple registration we can obtain higher quality regional T 1 maps than have previously been reported and this allows the calculation of (1/T 1(oxygen) -1/T 1(air) ) maps registration allows the calculation of uptake times without the need for temporal smoothing- find longer times then previously reported, possibly due to differences in breathing apparatus publication opportunities: –ISMRM –journal publication (on registration?)

17. ISBE-AstraZeneca Strategic Alliance Project 23 Progress Report Future plans construct and test alternative breathing system –exchange face mask for mouth piece –replace anaesthetic trolley with simple solenoid valve for more rapid switching between air and O 2 –monitor oxygen concentration at the mouth piece –test Bain system vs. non-rebreathing system –test different flow rates COPD patients –ethics application –patient recruitment Wythenshaw MR protocol –optimise inversion time –investigate rapid T1 mapping e.g. Snapshot FLASH, TrueFISP