Quantitative measurement of regional lung ventilation is of great significance in assessment of lung function in many obstructive and restrictive pulmonary diseases. A new technique for regional measurement of fractional ventilation using hyperpolarized 3He MRI is proposed, addressing the shortcomings of an earlier approach that limited its use to small animals. The new approach allows for the acquisition of similar quantitative maps over a shortened period and requires substantially less 3He gas. This technique is therefore a better platform for implementation in large species, including humans. The measurements using the two approaches were comparable to a great degree, as verified in a healthy rat lung, and are very reproducible. Preliminary validation is performed in a lung phantom system. Volume dependency of measurements was assessed both in vivo and in vitro. A scheme for selecting an optimum flip angle is proposed. In addition, a dead space modeling approach is proposed to yield more accurate measurements of regional fractional ventilation using either method. Finally, sensitivity of the new technique to model parameters, noise, and number of included images were assessed numerically. As a prelude to application in humans, the technique was implemented in a large animal study successfully.

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RATIONALE AND OBJECTIVES-The use of hyperpolarized 3 He MRI as a quantitative lung imaging tool has progressed rapidly in the past decade, mostly in assessment of the airways diseases COPD and asthma. This technique has shown potential to assess both structural and functional information in healthy and diseased lungs. In this study, we apply the regional measurements of structure and function to a bleomycin rat model of interstitial lung disease. MATERIALS AND METHODS-MaleSprague Dawley rats (300-350 g) were administered intratracheal bleomycin. After 3 weeks, apparent diffusion coefficient and fractional ventilation were measured by 3 He MRI and pulmonary function testing using a rodent-specific plethysmography chamber. Sensitized and healthy animals were then compared using threshold analysis to assess the potential sensitivity of these techniques to pulmonary abnormalities. RESULTS-Nosignificant changes were observed in total lung volume and compliance between the two groups. Airway resistance elevated and forced expiratory volume significantly declined in the 3-wk bleomycin rats, and fractional ventilation was significantly decreased compared to control animals (p < 4×10 −4 ). Apparent diffusion coefficient of 3 He showed a smaller change, but still a significant decrease in 3-wk bleomycin animals (p < 0.05). 3 He MRI can be a sensitive and noninvasive tool to assess changes in an animal interstitial lung disease model. This technique may be useful for longitudinal animal studies and also in the investigation of human interstitial lung diseases. CONCLUSION-Preliminary results suggest that quantitative

The dependence of hyperpolarized (HP) 3 He T 1 on local oxygen concentration provides the basis for measuring the partial pressure of oxygen (pO 2 ) and oxygen depletion rate (R) in the lungs. Precise measurements of this type are difficult because the oxygen effect manifests itself through a decay of signal, leading to noisy images at the end of the series. The depolarization caused by RF excitation pulses further complicates the problem. It is therefore important to optimize scan parameters, such as measurement timing and flip angle, to obtain accurate and reproducible measurements. This work presents a new singleacquisition technique in conjunction with the multiple regression fitting method for data evaluation. Analytical expressions for the measurement uncertainties are derived. A total of four types of single-acquisition timing schemes are investigated; simulation shows a large uncertainty variation between these schemes (pO 2 : 7.5-30.2%; R: 47.4 -173.7%). A basic procedure for optimizing scan parameters is then described. A phantom experiment was conducted to verify the simulation results. Repeated in vivo measurements with the optimal scheme in a rabbit experiment showed that average variation of global mean is 6.2% for pO 2 and 12.0% for R, and that the average variation of percentiles (10th, 25th, 50th, 75th, and 90th) is 8. In recent years, hyperpolarized helium-3 magnetic resonance imaging (HP 3 He MRI) has been researched extensively as a promising tool for quantitatively assessing pulmonary parameters (1-6). This technique is sensitive, regional, and noninvasive. It is also capable of providing both structural and functional information on lung tissue. Structural HP 3 He MRI has used the apparent diffusion coefficient (ADC), which is a function of alveolar size and geometry, to characterize the lung's morphology at very small spatial scales (7-17). The pulmonary oxygen measurement, which is an example of functional imaging, yields regional alveolar partial pressure of oxygen (pO 2 ) and oxygen depletion rate (R). These values provide a marker that is sensitive to both ventilation abnormality and impaired oxygen exchange efficiency between the lung and the bloodstream (18 -25).The HP 3 He MRI pulmonary oxygen measurement has not been studied as intensively as the ADC measurement. To the best of our knowledge, only one reproducibility study has been reported, performed only at a few manually-selected regions of interest (23). There are two likely reasons for this relative lack of activity. First, while ADC is a structural parameter that is relatively stable over various pulmonary physiological conditions (e.g., breathing patterns, inhaled gas composition, and ventilation-perfusion ratios), pO2 and R are functional parameters strongly dependent on the state of these conditions. We can therefore expect simpler and more repeatable ADC measurements because the necessity to monitor or control physiological state is not as strong as that in oxygen measurement. Second, the ADC measurement is typically base...