Image Functional Modeling: Combining Lung Models with Imaging Modalities and Mechanical Measures

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

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

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

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

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

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

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

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 Tawhai et al, 1999 • Airways Terminate on • Alveoli with Viscoelastic Tissue

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

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

12. Hyperpolarized MRI : IFM Application

13. Image and Model Based Ventilation Images Ventilation Spectrum: Fraction of Baseline Ventilation PET Based Model Based 2 over 1.6 1.2 normal .8 .4 0 under

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: m = 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 BU Respiratory Lab Kenneth R. Lutchen Carissa Bellardine Derek Affonce Brian Szender Allison Bell Mike Hamilton Jen Kenyon Adam LaPrad Anesthesia & Critical Care,MGH Jose G. Venegas R. Scott Harris Marcos Vidal Melo Guido Musch Tilo Winkler Giacomo Bellani 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. Percent of Baseline Airway Diameter d< .9 mm 100 open d <.6 mm 80 60 d < 2.5 mm 40 20 0 closed PET: IFM Application Size Range of Allowable Closed Airways: 0.3-2.5 mm.