Ventilation-synchronous magnetic resonance microscopy of pulmonary structure and ventilation in mice

Increasing use of transgenic animal models for pulmonary disease has raised the need for methods to assess pulmonary structure and function in a physiologically stable mouse. We report here an integrated protocol using magnetic resonance microscopy with gadolinium (Gd)-labeled starburst dendrimer (G6-1B4M-Gd, MW = 192 +/- 1 kDa, R(h) = 5.50 +/- 0.04 nm) and hyperpolarized (3)helium ((3)He) gas to acquire images that demonstrate pulmonary vasculature and ventilated airways in live mice (n = 9). Registered three-dimensional images of (1)H and (3)He were acquired during breath-hold at 2.0 T using radial acquisition (total acquisition time of 38 and 25 min, respectively). The macromolecular Gd-labeled dendrimer (a half-life of approximately 80 min) increased the signal-to-noise by 81 +/- 30% in the left ventricle, 43 +/- 22% in the lung periphery, and -4 +/- 5% in the chest wall, thus increasing the contrast of these structures relative to the less vascular surrounding tissues. A constant-flow ventilator was developed for the mouse to deliver varied gas mixtures of O(2) and N(2) (or (3)He) during imaging. To avoid hypoxemia, instrumental dead space was minimized and corrections were made to tidal volume lost due to gas compression. The stability of the physiologic support was assessed by the lack of spontaneous breathing and maintenance of a constant heart rate. We were able to stabilize the mouse for >8 hr using ventilation of 105 breath/min and approximately 0.2 mL/breath. The feasibility of acquiring both pulmonary vasculature and ventilated airways was demonstrated in the mouse lung with in-plane spatial resolution of 70 x 70 microm(2) and slice thickness of 800 microm.