In-vivo synchrotron imaging of regional ventilation and blood volume after methacholine provocation in rabbit

Update in biomedical applications of synchrotron radiation & lung imagingLiisa PorraHelsingin yliopisto / HUS

Liisa Porra

1www.helsinki.fi/yliopistowww.helsinki.fi/yliopisto1The 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 exchangeLung functionwww.helsinki.fi/yliopistoBreathing and Lung Physiology

Lungs contain about 700 million alveoli, producing 70m2 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 micrometreswww.helsinki.fi/yliopistoGas compartment volumeGas flow -> ventilation

Tissue compartment volume

Blood compartmemt volumeBlood flow -> perfusion

Relationship between these parametersLung tissue structure in phycisist point of view4Gas spaceTissue space containing blood vesselsLung tissue consists ofwww.helsinki.fi/yliopistoDensity distributionX-raysImaging with absorption contrast

Contrast agentInside an objectX-rays

Direct imaging of contrast agent distributionX-rays

www.helsinki.fi/yliopisto5Ek = 34.56 keV103

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10-130 35 40 45 Energy (keV)Mass attenuation/ (cm2/g)Bayat et al, Phys Med Biol 2001Principles of the K-edge subtraction (KES) imaging using xenon gasNegligible absorption for xenon

Subtraction image

Marked absorption for xenon

XenonBone Tissue

www.helsinki.fi/yliopisto6The imaging method used in this study was K-edge subtraction imaging. In K edge subtraction imaging it is possible to quantify the quantity of a contrast agent. In the lung studies, stable Xe gas is used as contrast agent. 2 images are taken at the same time using 2 nearly monochromatic beams with slightly different energies, that bracet the K-energy of the contrast agent. The difference in the resultant imaages is only in the xenon filled areas.Subtraction of these 2 images shows the distribution of xenon while bone and tissue is subtracted away.Because the 2 images are taken at the same time, there is no movement artifacts in the subtraction figure.Moreover, with this method we obtain a normal absorption image showing the structure and a subtracted xenon image showing the lung function simultaneouslyEk = 33.17 keV103

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10-130 35 40 45 Energy (keV)Mass attenuation/ (cm2/g)Suhonen et al, Phys Med Biol 2008Principles of the K-edge subtraction (KES) imaging using iodine infusionNegligible absorption for iodineSubtraction imageMarked absorption for iodineIodineBone Tissue

www.helsinki.fi/yliopisto7The imaging method used in this study was K-edge subtraction imaging. In K edge subtraction imaging it is possible to quantify the quantity of a contrast agent. In the lung studies, stable Xe gas is used as contrast agent. 2 images are taken at the same time using 2 nearly monochromatic beams with slightly different energies, that bracet the K-energy of the contrast agent. The difference in the resultant imaages is only in the xenon filled areas.Subtraction of these 2 images shows the distribution of xenon while bone and tissue is subtracted away.Because the 2 images are taken at the same time, there is no movement artifacts in the subtraction figure.Moreover, with this method we obtain a normal absorption image showing the structure and a subtracted xenon image showing the lung function simultaneouslyWhat 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 irritantsReversible limitation of airflow, due to airway narrowing It is impossible to study the function of small airways with existing imaging methodNon-specific provocation vs. specific provocation

www.helsinki.fi/yliopisto8Experimental asthma studies in sensitized rabbitsThe 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;180:296303, 2009 Reactions in the airwaysChanges in the uniformity of ventilationwww.helsinki.fi/yliopisto9Regional aerosol deposition using aerosolized iodine

www.helsinki.fi/yliopisto10In the same animal these images show a 3D rendering of ; in blue: the central bronchi; in red; a segmentation of the iodine hotspots, based on the regional iodine concentration; and in green: the lung parenchyma. As you can see, the areas with maximal iodine concentration are very heterogeneously distributed, with a significant autocorrelation. In other words the areas with higher Iodine concentration keep getting more iodine. Distribution of iodine aerosol in the lungs

www.helsinki.fi/yliopistoMotivation of the study:It is an experimental model of respiratory distress in premature babiesBroncho-alveolar lavege removes surfactant from the alveoli and causes collapsePositive end-expiratory pressure (PEEP) is used to open collapsed lung zonesExperiment protocol

Baseline images normal pressure (PEEP=9cmH2O)

Lavage injury

Images after injuryNormal pressurePEEP (9cmH2O)Normal pressure

Respiratory distress syndromewww.helsinki.fi/yliopisto12Images before and after the lavage

www.helsinki.fi/yliopistoIt consists of an in-line arrangement of an X-ray source, the sample and an X-ray detector and no other optical elements are requiredPBI 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 intensityPropagation based imagingLiisa Porra 14

www.helsinki.fi/yliopisto

PBI images of lungsLiisa Porra 15

www.helsinki.fi/yliopisto

Short-term recruitment / derecruitment of collapsed lungLiisa Porra 16www.helsinki.fi/yliopistoOther intresting SR studies: Phase contrast imaging, SPring8, JapanLiisa Porra 17

Sera T, et al: J Appl Physiol. 2013 Jul 15;115(2):219-28. www.helsinki.fi/yliopistoPhase contrast imaging, Australia / Spring8 JapanLiisa Porra 18

Hooper S et al: PLoS One. 2013 Aug12;8(8):e70895.www.helsinki.fi/yliopistoPhase contrast imaging, Australia / Spring8Liisa Porra 19

Dubsky S et al: J R Soc Interface. 2012 Sep 7;9(74):2213-24.www.helsinki.fi/yliopistoAcknowledgementsBronchography team in HelsinkiProf. Pekka Suortti, Dr. Liisa Porra, Dr. Satu StrengellProf. Anssi Sovijrvi HUS

University of Amiens, FranceGeneva University Central Hospital, SwitzerlandUniversity of Szeged, HungaryUniversity of Bari, ItalyUppsala Academiska Sjukhuset, Sweden

Liisa Porra 20www.helsinki.fi/yliopisto20Thanks to everybody, and thanks for your attentionThank you for your attention!Liisa Porra 21www.helsinki.fi/yliopistowww.helsinki.fi/yliopisto21