## 2 Materials and Methods  
### Design of the Breath Cycle Control and Hyperpolarized \({}^{3}\)He Dosing System  
The schematic diagram of the ventilator is presented in Figure 1 and Figure 3a shows its photograph. The components located both inside and outside the Faraday cage are indicated. Initially, the high field MEOP \({}^{3}\)He polarizer is placed in the magnet bore to produce the hyperpolarized gas. After the polarization is complete, the gas is transferred to the plastic Tedlar bag (B), which is inside the rigid, hermetic pressure chamber located in the high and homogeneous field of the magnet. The access to the Tedlar bag is controlled by a nonmetallic pneumatic valve. After the bag is filled with hyperpolarized gas, the polarizer is removed from the magnet to let the patient in. The procedure is described in detail in [20]. The delivery of hyperpolarized gas is accomplished by applying a small, 10 mbar above the atmospheric pressure to the pressure chamber. The dead volume of the \({}^{3}\)He delivery system is less than 1 mL. A set of sterile breathing tubes with the mouthpiece (A) connect the system to the patient, who is able to manipulate them by himself, to achieve the most comfortable position in the scanner. We found it more convenient than the direct application of the Tedlar bag filled with the noble gas. It is required to replace the setup for a new patient to ensure sterility. Inhaling, exhaling and the noble gas delivery processes are controlled by pneumatic one-way valves (C). However, the actual timing is adjusted for each patient by recording his spontaneous breathing. The valves are driven with the 3 bar compressed air delivered by the electronic control module (F), which contains electrical valves and pressure meters. The pneumatic valves are mounted on a lightweight aluminum rack, where the oxygen free nitrogen reservoir for initial lung flushing (E), and the metalized helium-tight bag for exhaled gas collecting (D) are also located. Flexible tubes are connected to the control module to measure the pressure inside the chamber containing the Tedlar bag, as well as the pressures at the inhaling and exhaling tubes. The flow during inhaling and exhaling is measured by the D6F-PH MEMS Differential Pressure Sensor (OMRON Corporation) mounted on a bypass. The control module also monitors the pressure delivered by the air compressor (not shown), and by the nitrogen bottle (H). A dedicated LabView program with a user-friendly graphical user interface (GUI) is installed on the computer (G) and controls the operation of the system. For convenience the computer is located in the MRI control room. All parts of the ventilator located inside the Faraday cage are made of non-magnetic materials, and there is not any electronics. Moreover, all components that have contact with hyperpolarized \({}^{3}\)He (Masterflex tubes, pyrex glass, sterile breathing tubes and mouthpieces) have been carefully chosen to reduce relaxation effects. The ventilator can be quickly removed from the Faraday cage, when the return to a standard proton MRI operation is required. After completing the polarization of 300 mL of \({}^{3}\)He, it is supplemented by 700 mL of pure nitrogen and transferred to the Tedlar bag (B) by the peristaltic compressor. Typically, it is kept there for about 15 min. In spite of having contact with several components of the polarizer and ventilator, the gas mixture maintains its high chemical and biological purity. It takes typically about 15 min to remove the polarizer from the magnet, put the patient in, and start the imaging procedure. In the presence of pure nitrogen, which acts as the buffer gas, the T\({}_{1}\) relaxation time of \({}^{3}\)He is about 3 h. Therefore, the polarization losses are of the order of 8%. Figure 1: Ventilator setup.