MRI of Lungs Using Partial Liquid Ventilation With Water-in-Perfluorocarbon Emulsions Ming Qiang Huang, Qing Ye, Donald S. Williams, and Chien Ho * A novel 1 H-MRI contrast modality for rat lungs has been devel- oped using water-in-perfluorocarbon (PFC) emulsions for par- tial liquid ventilation ™ (PLV). The feasibility of the new ventila- tion protocol for 1 H-MRI studies of lungs has been demon- strated. 1 H-MR images of lungs have been obtained with sensitivity and spatial resolution higher than those of the 19 F- MRI of lungs previously reported. Diffusion-weighted MRI mea- surements of lungs showed that the results obtained are related to the pulmonary architecture and functional properties of lungs. Although the methodology needs further improvement and evaluation, it appears to have great potential in a wide range of new applications in the field of lung MRI, such as in vivo detection of lung cancer, emphysema, and allograft rejec- tion following lung transplantation. The ability of this technique to achieve high-quality MR images of lungs, together with its technical simplicity, stability, and low cost, makes this method a promising imaging technique for the lungs. Magn Reson Med 48:487– 492, 2002. © 2002 Wiley-Liss, Inc. Key words: lung MRI; water-in-perfluorocarbon emulsions; par- tial liquid ventilation; diffusion-weighted MRI; apparent diffu- sion coefficient The early detection of cancer and emphysema, and of graft rejection following lung transplantation is important for successful clinical treatment of patients with lung disease. Many techniques are available for monitoring various clin- ical conditions, but few of them possess sufficient sensi- tivity to noninvasively detect early signs of illness. Some of these procedures expose patients to high risks. Thus, it is of great importance to develop sensitive and noninva- sive methods for detecting these lung-related diseases. MRI of lungs lags behind the advancements hitherto achieved for MRI of other organs and tissues. Lungs are difficult to image with MRI because of two major factors. First, there is not much water in the lungs, which results in a low spin density of hydrogen nuclei for imaging. Thus, 1 H-MRI sensitivity in lungs is much lower than that in other organs. Second, the diamagnetic lung tissue-air boundaries create inhomogeneity of magnetic field via strong susceptibility differences between lung tissue and lung air space. This causes severe signal loss in MR im- ages. The field inhomogeneity varies as the lung moves during respiration and cardiac pulsation, which causes loss of spin phase coherence within several milliseconds, and, as a result, can cause further signal loss. Many strategies have been developed for MRI of lungs. A recent exciting development is the use of hyperpolarized 129 Xe (1) or 3 He (2–5). However, the expense of the re- quired laser optical pumping facility, and the limited availability of 129 Xe and 3 He limit its potential applica- tions. Furthermore, the inefficiency of 129 Xe and 3 He de- livery through the respiratory system can also hinder their practical use (6). Oxygen ventilation MRI has been suc- cessfully employed to detect regional ventilation defects (7,8). MRI of lungs using inert fluorinated gases has also been reported (9 –11). The short T 1 relaxation time of a few milliseconds for fluorinated gases can permit multiple sig- nal averages within a short period. Although there are potential applications for this method, the rapid pulse and gradient sequence used in 19 F MRI of fluorinated gases imposes some limitations on the gradient hardware and achievable minimal field of view (FOV). Because of its low sensitivity, it still suffers from the limitation of long ex- amination times and residual signal from fat or muscle. Many attempts have been made to develop 19 F MRI of lungs (12–14) and other organs (15–18) using a variety of perfluorocarbon (PFC) emulsions. However, this method- ology still suffers from low sensitivity and low spatial resolution due to low concentrations and the presence of multiple fluorine peaks in the 19 F spectra of many fluoro- carbons. The concept of liquid ventilation (LV) with neat (un- emulsified) liquid PFCs originated from the demonstration that lungs are able to tolerate the introduction of large volumes of saline solution without adverse side effects or ensuing damage (19). LV was first performed in mice in the 1960s using salt solution under hyperbaric conditions (20). Since then, PFCs have been successfully used in partial liquid ventilation™ (PLV) in animals and humans (21,22). Water is an excellent imaging agent for 1 H MRI of lungs, but water is seldom used in LV because due to its low oxygen solubility it can not carry and deliver enough ox- ygen into biological systems to support life. However, this limitation can be overcome by using water-in-PFC emul- sions in PLV. The O 2 - and CO 2 -dissolving capacities of the fluorocarbon emulsions are up to 50 and 210 vol% at 37°C, respectively (23). Thus, the two above-mentioned prob- lems of 1 H MRI of the lungs can be overcome if water-in- PFC emulsions are used in PLV. On the one hand, a water aerosol in the emulsions is used for contrast enhancement, and on the other hand, the higher O 2 - and CO 2 -dissolving capacity of PFCs enable the delivery of sufficient O 2 into the lungs and the efficient removal of CO 2 from the lungs. Compared with 19 F MRI of lungs using PFC emulsions, 1 H MRI of water-in-PFC emulsions offers a higher signal- to-noise ratio (SNR). We believe that the water-in-PFC emulsions in the lungs reduce the lung tissue-air suscep- Pittsburgh NMR Center for Biomedical Research, Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, Pennsylvania. Grant sponsor: National Institutes of Health; Grant number: R01RR/AI-15187. *Correspondence to: Dr. Chien Ho, Department of Biological Sciences, Car- negie Mellon University, 4400 Fifth Ave., Pittsburgh, PA 15213-2683. E-mail address: chienho@andrew.cmu.edu. Received 3 January 2002; revised 15 April 2002; accepted 19 April 2002. DOI 10.1002/mrm.10231 Published online in Wiley InterScience (www.interscience.wiley.com). Magnetic Resonance in Medicine 48:487– 492 (2002) © 2002 Wiley-Liss, Inc. 487