1. Image Functional Modeling: Combining Lung Models with Imaging Modalities and Mechanical Measures Nora T. Tgavalekos, Jose G. Venegas, Mitchell Albert, Allison Bell, and K. R. Lutchen October 14, 2004 BMES Conference

2. Stimuli Cell activation Inflammatory mediators Airway Changes Airway Obstruction (Allergens,outdoor pollutants and viruses) (mast cells, eosinophils, neutrophils) Size and LocationDistribution ? ? (proinflammatory mediators: histamine) (inflammation, remodeling, bronchoconstriction) Asthma http://www.merckfrosst.ca/e/health/asthma/sum_01.html

3. Mechanical Heterogeneity in Asthma Which airways are most responsible for degradation in Which airways are most responsible for degradation in function and hyperresponsiveness? function and hyperresponsiveness?

4. Apnea Time (secs) Washout PET Imaging: Tracer Kinetics

5. Apnea Time (secs) Washout PET Imaging: Tracer Kinetics

6. PET Imaging apex base Images from Mass General Hospital Pre ChallengePost Challenge

7. Hyperpolarized 3 He MRI Imaging Images from Brigham and Women’s Hospital Pre ChallengePost Challenge

8. Image-Functional Modeling (IFM) Goal: To synthesize the imaging and mechanical information in order to identify which airways are responsible for the degradation in the mechanics and ventilation distribution on a patient specific basis. Method: Combine the imaging and mechanical data with 3D anatomically consistent multi-scale lung models.

9. Advancing 3D Models for Computation of Mechanical Function Impedance of a Single Airway Airways Terminate on Alveoli with Viscoelastic Tissue Tawhai et al, 1999

10. IFM: Mapping PET Ventilation Defects into 3D Model Post Washout: Tracer Retention Pre Washout: Baseline

11. d < 2.5 mm Size Range of Allowable Closed Airways: 0.3-2.5 mm. d<.9 mm PET: IFM Application 0 closed 100 open Percent of Baseline Airway Diameter 80 60 40 20 d <.6 mm

12. Hyperpolarized MRI : IFM Application

13. 2 1.6 1.2.8.4 0 Ventilation Spectrum: Fraction of Baseline Ventilation normal over under PET BasedModel Based Image and Model Based Ventilation Images

14. Summary We identified constriction conditions, which are consistent with both the lung mechanics and imaging information for 4 asthmatics: Maximum airway size for closures: 0.9 -2.4 mm Mean airway sizes affected: <1 mm and below Constriction Conditions:  = 60%, SD= 20% The IFM paradigm provides a platform for multi-scale sensitivity analysis regarding how the integrated components of lung structure determined the degradation in function during airway disease.

15. Acknowledgements Anesthesia & Critical Care,MGH Jose G. Venegas R. Scott Harris Marcos Vidal Melo Guido Musch Tilo Winkler Giacomo Bellani BU Respiratory Lab Kenneth R. Lutchen Carissa Bellardine Derek Affonce Brian Szender Allison Bell Mike Hamilton Jen Kenyon Adam LaPrad University of Auckland, New Zealand Merryn Tawhai Brigham and Women’s Hospital Mitchell Albert Yang- Sheng Tzeng Funding Sources AAUW Selected Professions Fellowship NIH BMES

16. PET: IFM Application d < 2.5 mm Size Range of Allowable Closed Airways: 0.3-2.5 mm. d<.9 mm 100 open Percent of Baseline Airway Diameter 80 60 40 20 0 closed d <.6 mm