1. © 2005. The Children’s Hospital of Philadelphia. Proprietary and confidential. Do not copy. The Effects of Secondhand Smoke in the Lung - Hyperpolarized Helium Diffusion MRI Chengbo Wang, PhD 1, T. A. Altes, MD 1,2, G. W. Miller, PhD 2, E. E. de Lange, MD 2, K. Ruppert, PhD 1,2, J. F. Mata, PhD 2, G. D. Cates, Jr, PhD 3, J. P. Mugler, III, PhD 2,4 1 Radiology, The Children’s Hospital of Philadelphia, Philadelphia, PA 2 Radiology, 3 Physics, 4 Biomedical Engineering, University of Virginia, Charlottesville, VA

2. Active Cigarette Smoking 15-30% of smokers develop chronic obstructive pulmonary disease (COPD) High morbidity & mortality  4 th leading cause of death  30 Million (10%) Americans have COPD (estimated) Total estimated cost: $32 Billion for the US in 2002

3. Secondhand cigarette smoking Causes coronary heart disease and lung cancer Evidence suggests but not sufficient to prove secondhand smoke causes COPD before our study The 2006 U.S. Surgeon General's Report on The Health Consequences of Involuntary Exposure to Tobacco Smoke

4. Methods to diagnose COPD Patient shortness of breath × not sensitive Pulmonary function test × not sensitive CT × radiation exposure Helium MRI (New Technique) √ none radiation exposure

5. Hyperpolarized Helium MRI Conventional MRI Helium MRI

6. Helium Diffusion MRI Measures apparent diffusion coefficient (ADC) ADC reflects the alveolar size Emphysema Normal alveoli Normal ADC Healthy Enlarged alveoli Elevated ADC COPD

7. ADC maps Healthy 55 yrs COPD (Gold stage 0) 70 yrs 0.06 0.04 0.02 0 Normal ADC Normal alveoli Elevated ADC Enlarged Alveoli Red - > small ADC values -> good Yellow -> large ADC values -> bad 0.06 0

8. Purpose Determine whether Helium diffusion MRI detects the effects of secondhand smoke in the lungs

9. Subjects 60 total subjects 23 low exposure to secondhand smoke  Negative control group  10 M, 13 F; age: 46 - 71 yrs 22 high exposure to secondhand smoke  3 M, 19 F; age: 41 - 79 yrs 15 past or active smokers  Positive control group  4 M, 11 F; age: 45 - 73 yrs

10. Results: ADC 67% 33%73% 27% 96% 4% P=0.047 P<0.001 (n=23)(n=22)(n=15) Elevated Normal

11. Results: ADC Normal ADC Normal alveoli Highly elevated ADC Enlarged Alveoli Elevated ADC Enlarged Alveoli?? Early emphysema?? cm 2 /s 0.06 0.00 Red - > small ADC values -> good Yellow -> large ADC values -> bad

12. Summary An increased ADC has been found in:  67% of the smokers  27% of the subjects with high exposure  4% of subjects with low exposure This finding may reflect a response to smoking

13. Conclusions Helium diffusion MRI detects elevated ADC in subjects with high exposure to secondhand smoke Elevated ADC may reflect lung structural damage or subclinical emphysema Helium diffusion MRI may be more sensitive than other methods to detect mild emphysematous changes

14. Acknowledgments CHOP Talissa A Altes, MD Kai Ruppert, PhD Yulin Chang, PhD UVA John P Mugler, III, PhD Eduard E de Lange, MD James R Brookeman, PhD G Wilson Miller, PhD Jaime Mata, PhD Gordon D Cates, Jr, PhD Mike Salerno, MD, PhD Jing Cai, PhD John M Christopher, RT Doris A Harding, RN Joanne Gersbach, RN Funding NHLBI: RO1- HL079077 Flight Attendant Medical Research Institute Commonwealth of Virginia Technology Research Fund Siemens Medical Solutions

15. Quit Smoking Quit smoking, for you and for your loved ones!