IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING, VOL. 59, NO. 3, MARCH 2012 777 Dynamic Ventilation 3 He MRI for the Quantification of Disease in the Rat Lung Angelos. Kyriazis*, I. Rodriguez, N. Nin, J. L. Izquierdo-Garcia, J. A. Lorente, J. M. Perez-Sanchez, J. Pesic, L. E. Olsson, and J. Ruiz-Cabello Abstract—Pulmonary diseases are known to be largely inhomo- geneous. To evaluate such inhomogeneities, we are testing an image- based method to measure gas flow in the lung regionally. Dynamic, spin-density-weighted hyperpolarized 3 He MR images performed during slow inhalation of this gas were analyzed to quantify re- gional inflation rate. This parameter was measured in regions of interest (ROIs) that were defined by a rectangular grid that covered the entire rat lung and grew dynamically with it during its infla- tion. We used regional inflation rate to quantify elastase-induced emphysema and to differentiate healthy (n = 8) from elastase- treated (n = 9) rat lungs as well as healthy from elastase-treated areas of one rat unilaterally treated with elastase in the left lung. Emphysema was also assessed by gold standard morphological and well-established hyperpolarized 3 He MRI diffusion measure- ments. Mean values of regional inflation rates were significantly different for healthy and elastase-treated animals and correlated well with the apparent diffusion coefficient of 3 He and morpholog- ical measurements. The image-based biomarker inflation rate may be useful for the assessment of regional lung ventilation. Index Terms—Elastase-treated rats, hyperpolarized 3 He MRI, inflation rate, pulmonary ventilation, regional flow. Manuscript received September 19, 2011; revised November 7, 2011 and November 29, 2011; accepted December 5, 2011. Date of publication December 9, 2011; date of current version February 17, 2012. This work was supported by T ¨ UB ˙ ITAK under Project 110E232, by the Marie-Curie Train- ing Networks under Grant MRTN-CT-2006-03602, PHeLINet and ITN-FP7- 264864, π -net, and by the Spanish Ministry of Science and Technology under Grant SAF2008-05412. Asterisk indicates corresponding author. *A. Kyriazis is with the Department of Chemistry-Physics II, Faculty of Pharmacy, Complutense University of Madrid, Madrid 28040, Spain, with the Centro de Investigacion Biomedica en Red Enfermedades Respiratorias (CIBERES), Recinte Hospital Joan March, Illes Balears 07110, Spain, and also with the Politecnica University, Madrid 28040, Spain (e-mail: angelos. kyriazis@yahoo.com). I. Rodriguez, J. L. Izquierdo-Garcia, J. M. Perez-Sanchez, and J. Ruiz- Cabello are with the Department of Chemistry-Physics II, Faculty of Phar- macy, Complutense University of Madrid, Madrid 28040, Spain, and also with the Centro de Investigacion Biomedica en Red Enfermedades Respira- torias (CIBERES), Recinte Hospital Joan March, Illes Balears 07110, Spain (e-mail: ignacio@ieb.ucm.es; izquierdo@ieb.ucm.es; iosephus@ieb.ucm.es; ruizcabe@farm.ucm.es). N. Nin and J. A. Lorente are with the University Hospital of Getafe, 28905 Getafe, Spain, and also with the Centro de Investigacion Biomed- ica en Red Enfermedades Respiratorias (CIBERES), Recinte Hospital Joan March, Illes Balears 07110, Spain (e-mail: niconin@hotmail.com; jose_angel_ lorente@hotmail.com). J. Pesic is with AstraZeneca R&D, DECS Imaging, M¨ olndal SE-431 83, Sweden (e-mail: jelena.pesic@astrazeneca.com). L. E. Olsson is with AstraZeneca R&D, DECS Imaging, M¨ olndal SE- 431 83, Sweden and also with the Department of Radiation Physics, University of Gothenburg, G¨ oteborg SE-413 45, Sweden (e-mail: lars.e. olsson@astrazeneca.com). Color versions of one or more of the figures in this paper are available online at http://ieeexplore.ieee.org. Digital Object Identifier 10.1109/TBME.2011.2179299 I. INTRODUCTION E VEN though MRI has recently developed as a research and diagnostic tool, MRI in the lungs remains a challenge. First, because the density of parenchyma, the lung tissue, is low. This means that protons in the lung parenchyma are sparse, a fact that causes low signal. Moreover, the static magnetic fields in the chest cavity vary because of magnetic susceptibility dif- ferences between paramagnetic oxygen in air and diamagnetic tissue. These magnetic field inhomogeneities cause quick sig- nal dephasing, which means that T ∗ 2 in the lung is short. Lung MRI is further hampered by the complicated structure of this organ, the constant movement of the lung and heart and the flow of blood. The combination of factors makes lung parenchyma visualization with proton MRI particularly challenging [1]. Hyperpolarized 3 He MRI has been introduced as an alter- native to proton MRI with extremely encouraging results. This gas can be laser-hyperpolarized and thus its signal increases up to 5 orders of magnitude [2]. There are many clinical studies that demonstrate the merits of 3 He MRI, mainly fo- cused on diffusion-weighted and static spin-density-weighted MRI [3]–[5]. In this study, we are seeking to validate dynamic, spin- density-weighted 3 He MRI as a technique that can assess lung ventilation. Dynamic, spin-density-weighted 3 He MRI is also termed ventilation 3 He MRI, because the gas that is inhaled and subsequently exhaled from the lungs is indeed visualized. It consists of acquiring a sequence of images over part or the entire respiratory cycle. In the case of experimentation with small rodents, a device is necessary to guarantee control and reproducibility of the experiment. In the field of ventilation, 3 He MRI studies were conducted on motion correction and subsequent measurement of flow dis- tribution [6]–[8]. Other researchers developed optimized pulse sequences to minimize motion artifacts [9], [10]. Chen et al. [11] studied the effect of flip angle on signal intensity in the major and peripheral airways during dynamic 3 He MRI. A technique to quantify ventilation 3 He MRI has been pro- posed and used to measure methacholine-induced bronchocon- striction in rats [12], [13]. These researchers [12], [13] used a contrast media injector to control the experimental conditions. After image postprocessing, they estimated gas arrival time, volume, and flow in different regions of the lung, and found significant differences in those parameters before and after ad- ministration of methacholine. In this study, we used a similar technique to that used previously [12], [13] to quantify lung injury in an elastase- induced model of panacinar emphysema [14], [15] by estimating 0018-9294/$26.00 © 2011 IEEE