1. www.helsinki.fi/yliopisto Update in biomedical applications of synchrotron radiation & lung imaging Liisa Porra Helsingin yliopisto / HUS Liisa Porra 1

2. www.helsinki.fi/yliopisto The most important function of lungs is the exchange of oxygen and carbon dioxide To fulfill this task effectively the distributions of pulmonary ventilation, blood flow and gas diffusion between alveoli and pulmonary capillaries must all be uniform and matched with each other Most pulmonary disorders disturb lung function through several patho-physiological mechanisms at different stages of gas exchange Lung function

3. www.helsinki.fi/yliopisto Breathing and Lung Physiology Lungs contain about 700 million alveoli, producing 70m 2 of surface area. [ The alveoli stretch during inhalation and spring back during exhalation Each alveolus is wrapped in a fine mesh of capillaries An average alveolus has an diameter of 200 micrometres

4. www.helsinki.fi/yliopisto Gas compartment volume Gas flow -> ventilation Tissue compartment volume Blood compartmemt volume Blood flow -> perfusion Relationship between these parameters Lung tissue structure in phycisist point of view 4 Gas space Tissue space containing blood vessels Lung tissue consists of

5. www.helsinki.fi/yliopisto Density distribution X-rays Imaging with absorption contrast Contrast agent Inside an object X-rays Direct imaging of contrast agent distribution X-rays

6. www.helsinki.fi/yliopisto E k = 34.56 keV 10 3 10 2 10 1 10 0 10 -1 30 35 40 45 Energy (keV) Mass attenuation μ/ρ (cm 2 /g) Bayat et al, Phys Med Biol 2001 Principles of the K-edge subtraction (KES) imaging using xenon gas Negligible absorption for xenon Subtraction image Marked absorption for xenon Xenon Bone Tissue

7. www.helsinki.fi/yliopisto E k = 33.17 keV 10 3 10 2 10 1 10 0 10 -1 30 35 40 45 Energy (keV) Mass attenuation μ/ρ (cm 2 /g) Suhonen et al, Phys Med Biol 2008 Principles of the K-edge subtraction (KES) imaging using iodine infusion Negligible absorption for iodine Subtraction image Marked absorption for iodine Iodine Bone Tissue

8. www.helsinki.fi/yliopisto What is asthma? Asthma is a chronic inflammatory disease of the airways The inflammation makes the airways very sensitive, and they tend to react strongly to allergens and irritants Reversible limitation of airflow, due to airway narrowing It is impossible to study the function of small airways with existing imaging method Non-specific provocation vs. specific provocation

9. www.helsinki.fi/yliopisto Experimental asthma studies in sensitized rabbits The aim was to compare asthmatic reactions in healthy and allergic rabbits caused by: A non-specific challenge (i.v. methacholine) An allergen challenge (i.v. ovalbumine) Results show very different pattern of response in the large airways and the periphery of the lungs Baseline Methacholine Recovery Allergen Bayat et al.AJCCRM;180:296–303, 2009 Reactions in the airways Changes in the uniformity of ventilation

10. www.helsinki.fi/yliopisto Regional aerosol deposition using aerosolized iodine

11. www.helsinki.fi/yliopisto Distribution of iodine aerosol in the lungs

12. www.helsinki.fi/yliopisto Motivation of the study: It is an experimental model of respiratory distress in premature babies Broncho-alveolar lavege removes surfactant from the alveoli and causes collapse Positive end-expiratory pressure (PEEP) is used to open collapsed lung zones Experiment protocol Baseline images normal pressure (PEEP=9cmH2O) Lavage injury Images after injury Normal pressure PEEP (9cmH2O) Normal pressure Respiratory distress syndrome

13. www.helsinki.fi/yliopisto Images before and after the lavage

14. www.helsinki.fi/yliopisto It consists of an in-line arrangement of an X-ray source, the sample and an X-ray detector and no other optical elements are required PBI can be used to enhance the contrast of an absorption image, in this case the phase information in the image plane is lost but contributes to the image intensity Propagation based imaging Liisa Porra14

15. www.helsinki.fi/yliopisto PBI images of lungs Liisa Porra15

16. www.helsinki.fi/yliopisto Short-term recruitment / derecruitment of collapsed lung Liisa Porra16

17. www.helsinki.fi/yliopisto Other intresting SR studies: Phase contrast imaging, SPring8, Japan Liisa Porra17 Sera T, et al: J Appl Physiol. 2013 Jul 15;115(2):219-28.

18. www.helsinki.fi/yliopisto Phase contrast imaging, Australia / Spring8 Japan Liisa Porra18 Hooper S et al: PLoS One. 2013 Aug12;8(8):e70895.

19. www.helsinki.fi/yliopisto Phase contrast imaging, Australia / Spring8 Liisa Porra19 Dubsky S et al: J R Soc Interface. 2012 Sep 7;9(74):2213-24.

20. www.helsinki.fi/yliopisto Acknowledgements Bronchography team in Helsinki Prof. Pekka Suortti, Dr. Liisa Porra, Dr. Satu Strengell Prof. Anssi Sovijärvi HUS University of Amiens, France Geneva University Central Hospital, Switzerland University of Szeged, Hungary University of Bari, Italy Uppsala Academiska Sjukhuset, Sweden Liisa Porra20

21. www.helsinki.fi/yliopisto Thank you for your attention! Liisa Porra21