IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING, VOL. 57, NO. 7, JULY 2010 1745 A MRI and Polarized Gases Compatible Respirator and Gas Administrator for the Study of the Small Animal Lung: Volume Measurement and Control Angelos Kyriazis * , Rigoberto Perez de Alejo, Ignacio Rodriguez, Lars E. Olsson, and Jesus Ruiz-Cabello Abstract—We have developed over the past years an experimen- tal magnetic resonance imaging (MRI) and polarized gases compat- ible mechanical respirator for the study of the small experimental animal. The respirator has been successfully used for experiments both in the MRI setting for polarized 3 He, 19 F, and proton imaging as well as for functional measurements of the lungs. The new main pneumatic valve with the two integrated sensors for simultane- ous lung pressure and volume measurements and the proportional valve to set the tidal volume of the respiration are described. It is shown how the device measures and controls the tidal volume of the lungs. Index Terms—Animal studies, magnetic resonance imag- ing (MRI), mechanical respiration, polarized gases, pulmonary studies. I. INTRODUCTION S MALL animal respirators are useful tools for the study of the lung. Especially in the context of polarized gases mag- netic resonance imaging (MRI), they are designed to guarantee not only ventilation with precise pressure, volume, and inspira- tion to expiration ratio but also triggering over the respiration for image acquisition and gas mixing ratio. Moreover, apneas of controlled duration may be imposed at any moment during image acquisition. Most importantly, polarized gases compati- ble respirators and administrators ensure that gas depolarization will be minimal. Nowadays there are some animal respirators for pulmonary studies, each of them focused in a different kind of research. The SAR-830 series small animal ventilator (CWE, Ardmore) is a volume-controlled, MR-compatible but not polarized gases Manuscript received October 26, 2009; revised December 17, 2009; accepted January 23, 2010. Date of publication February 18, 2010; date of current version June 16, 2010. This work was supported by the Marie–Curie training net- work under Grant MRTN-CT-2006-03602, the Polarized Helium Lung Imaging Network, and the Spanish Ministry of Science and Technology under Grant SAF2008-05412. Asterisk indicates corresponding author. * A. Kyriazis is with the Instituto de Estudios Biofuncionales, Universidad Complutense de Madrid, Madrid 28040, Spain, and also with the Centro de In- vestigacion Biomedica en Red, Recinte Hospital Joan March, 07110 Bunyola, Palma de Mallorca, Illes Balears, Spain (e-mail: angelos@ieb.ucm.es). R. P. de Alejo is with the Global Product Management Group, Air Product Sud Europa, Madrid 28703, Spain (e-mail: perezdr3@airproducts.com). I. Rodriguez and J. Ruiz-Cabello are with the Instituto de Estudios Bio- funcionales, Universidad Complutense de Madrid, Madrid 28040, Spain, and also with the Centro de Investigacion Biomedica en Red, Recinte Hospital Joan March, 07110 Bunyola, Palma de Mallorca, Illes Balears, Spain (e-mail: ignacio@ieb.ucm.es; ruizcabe@farm.ucm.es). L. E. Olsson is with AstraZeneca R&D, DECS Imaging, M¨ olndal, Sweden and also with the Department of Radiation Physics, University of Gothenburg, SE-413 45 G ¨ oteborg Sweden (e-mail: Lars.E.Olsson@astrazeneca.com). Digital Object Identifier 10.1109/TBME.2010.2042596 compatible device. The flexiVent (SCIREQ, Scientific Respi- ratory Equipment, Inc., Montreal, Canada) [1] is an MRI and polarized gases compatible ventilator that controls the tidal vol- ume by the displacement of a piston. In [2], a negative pres- sure piston actuated mechanical respirator is described that was used for functional measurements of newborn mice. A ven- tilator for neonates, the Babylog 8000 (Draeger Medical Inc, Telford), and a ventilator for adults and infants, the Siemens 900C (Soma Technology Inc, Bloomfield) are reported to be used in preclinical tests to ventilate mechanically small ani- mals by [3] and [4], respectively. However, these devices have restricted possibilities concerning the possible breathing pat- terns, such as imposing apneas at any point of the respiratory cycle, and are not MRI-compatible. In [5] and [6], a polarized gases and MRI-compatible ventilator with possibility of differ- ent breathing patterns is described. The same ventilator is used for diffusion experiments in [7]. The latter model was proven capable of handling very small volumes in the mouse lung. Chen et al. [8] used a custom-designed system to perform dynamic 3 He MRI in rats and in [9], the same ventilator was modified for mice to perform MR microscopy of the pulmonary tree. The respirator described in [10] has been employed at dif- ferent stages of its development in a number of experiments. Ruiz-Cabello et al. [11] and Perez-Sanchez et al. [12] measured diffusion in rat lungs by 19 F MRI whereas Olsson et al. [13] monitored the spread of chronic obstructive pulmonary disease in the mouse lung by proton and polarized 3 He MRI. The res- pirator has been also used as a spirometry tool to perform func- tional measurements of the lungs of elastase-treated rats [14] and tobacco-induced mice [15]. This device has been constantly updated to catch up with the demands of the rapidly growing MRI with gases field of research. The improvements are intended to guarantee the ac- quisition of reliable, useful, repeatable data and the robustness of the system during the ongoing experiments. In comparison with the version published in [10], there is a new pneumatic valve more compact and easier to fit in an MRI scanner than the previous one; it incorporates two sensors, which make it possible to monitor and register lung pressure and volume si- multaneously. This feature is particularly useful because the pressure over volume data are known to characterize the dis- ease state of the lungs [16]. Moreover, the respiration is now volume-controlled by a proportional valve. We are examining more closely the volume measurement and the flow controlled ventilation. We are presenting experimental results and observations that arose by the use of the device in 0018-9294/$26.00 © 2010 IEEE