Frontiers in Research Clinical and Experimental Pharmacology and Physiology (2009) 36, 95–106 Correspondence: Dr Jean-François Adam, Unité INSERM 836, Equipe 6, ESRF Medical Beamline 6, rue Jules Horrowitz, BP220, 38043 Grenoble cedex, France. Email: adam@esrf.fr This paper has been peer reviewed. Received 3 December 2007; revision 24 June 2008; accepted 25 June 2008. © 2008 Université Joseph Fourier Journal compilation © 2008 Blackwell Publishing Asia Pty Ltd doi: 10.1111/j.1440-1681.2008.05043.x Blackwell Publishing Asia SRCT for quantitative functional imaging JF Adam et al. Frontiers in Research Review: Synchrotron Radiation for Dynamic Imaging of Living Systems QUANTITATIVE FUNCTIONAL IMAGING AND KINETIC STUDIES WITH HIGH-Z CONTRAST AGENTS USING SYNCHROTRON RADIATION COMPUTED TOMOGRAPHY JF Adam,* †‡ S Bayat, ‡§ L Porra, ‡¶ H Elleaume,* ‡ F Estève,* †‡∫ and P Suortti ‡¶ *INSERM U836, Grenoble-Neurosciences Institute, Team 6: Synchrotron Radiation and Medical Research, † Joseph Fourier University, ‡ Biomedical Beamline ID17, European Synchrotron Radiation Facility, ∫ MRI Department, Grenoble University Hospital, Grenoble, § Jules Verne University Medical School, Department of Physiology – PériTox, and Amiens University Hospital, Amiens, France and ¶ Department of Physics, University of Helsinki, Helsinki, Finland SUMMARY 1. There is an increasing demand in diagnostic radiology for extracting additional morphological and functional quantitative parameters from three-dimensional computed tomography (CT) images. Synchrotron radiation computed tomography (SRCT) is the state-of-the-art method in preclinical X-ray CT, because its performance is close to the theoretical limits in terms of accuracy and precision. 2. The SRCT method with monochromatic X-ray beams yields absolute high-Z element contrast agent concentrations, without errors arising from beam hardening or scatter artefacts, by using digital subtraction techniques of the sinograms. Each pixel of the reconstructed difference images provides a quantitative concen- tration versus time curve of inhaled or injected high-Z contrast agents (xenon or iodine) with a high sensitivity. This is the key point of two functional imaging techniques that were developed at the European Synchrotron Radiation Facility: brain perfusion and lung function (ventilation and perfusion). 3. These two imaging techniques provide parametric images expressed in absolute perfusion parameters (blood volume, blood flow, mean transit time and capillary permeability) or ventilation parameters (lung volume, regional lung ventilation, bronchial lumen size, regional airway and lung compliance) with a high accuracy and precision. 4. The aim of the present brief review is to give a snapshot of the status and perspectives of these two imaging techniques, with emphasis on the performances and interests for functional imaging. Two separate sections will then describe the results obtained so far using SRCT as an in vivo functional imaging tool for measuring changes in haemodynamics and ventilation, in the investigation of experimental pathophysiology and in the effects of therapeutic intervention. Key words: airway hyperreactivity, brain perfusion, brain tum- ours, computed tomography, contrast agent kinetics, lung disease, lung pathologies, lung volume measurements, synchrotron radiation. INTRODUCTION The methods of nuclear medicine, magnetic resonance imaging, ultra- sound and conventional X-ray computed tomography (CT) are con- tinuously developed to meet the ever-increasing requirements for diagnosis, staging of surgical procedures, follow-up of treatments and basic research in physiology. These methods provide essential and complementary information of the morphology and function of inner organs, but none of these present methods fulfils simultaneously all the requirements of quantitative functional imaging with high spatial and temporal resolution. Syn- chrotron radiation computed tomography (SRCT) was devel- oped to meet these requirements and it is the state-of-the-art method in preclinical X-ray CT because its performance is close to the theoretical limits in terms of accuracy and precision. This tech- nique is now available in many synchrotron facilities worldwide. Among these facilities, the European Synchrotron Radiation Facility (ESRF) medical beamline was designed to allow for intravenous coronary angiography clinical trials, which have now been completed successfully, from the first patient in 2000 1 until the publication of the final sensitivity study (60 patients with right and left coronary disease). 2 “state-of-the-art method in preclinical X-ray CT”