John M. Woodburn

Improved Technique for Measurement of Regional Fractional Ventilation by Hyperpolarized 3He MRI

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. Magn Reson Med, 2010.

Simultaneous measurement of pulmonary partial pressure of oxygen and apparent diffusion coefficient by hyperpolarized 3He MRI

Hyperpolarized 3He (HP 3He) MRI shows promise to assess structural and functional pulmonary parameters in a sensitive, regional, and noninvasive way. Structural HP 3He MRI has applied the apparent diffusion coefficient (ADC) for the detection of disease‐induced lung microstructure changes at the alveolar level, and HP 3He pulmonary partial pressure of oxygen (pO2) imaging measures the oxygen transfer efficiency between the lung and blood stream. Although both parameters are affected in chronic obstructive pulmonary disease (COPD), a quantitative assessment of the regional correlation of the two parameters has not been reported in the literature. In this work, a single acquisition technique for the simultaneous measurement of ADC and pO2 is presented. This technique is based on the multiple regression method, in which a general linear estimator is used to retrieve the values of ADC and pO2 from a series of measurements. The measurement uncertainties are also analytically derived and used to find an optimal measurement scheme. The technique was first tested on a phantom model, and then on an in vivo normal pig experiment. A case study was performed on a COPD patient, which showed that in a region of interest ADC was 29% higher while oxygen depletion rate was 61% lower than the corresponding global average values. Magn Reson Med, 2009.

Quantitative Assessment of Lung Ventilation and Microstructure in an Animal Model of Idiopathic Pulmonary Fibrosis Using Hyperpolarized Gas MRI

RATIONALE AND OBJECTIVES The use of hyperpolarized (3)He magnetic resonance imaging as a quantitative lung imaging tool has progressed rapidly in the past decade, mostly in the assessment of the airway diseases chronic obstructive pulmonary disease and asthma. This technique has shown potential to assess both structural and functional information in healthy and diseased lungs. In this study, the regional measurements of structure and function were applied to a bleomycin rat model of interstitial lung disease. MATERIALS AND METHODS Male Sprague-Dawley rats (weight, 300-350 g) were administered intratracheal bleomycin. After 3 weeks, apparent diffusion coefficient and fractional ventilation were measured by (3)He magnetic resonance imaging 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 No significant 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-week bleomycin rats, and fractional ventilation was significantly decreased compared to control animals (P < .0004). The apparent diffusion coefficient of (3)He showed a smaller change but still a significant decrease in 3-week bleomycin animals (P < .05). CONCLUSIONS Preliminary results suggest that quantitative (3)He magnetic resonance imaging 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.

Measurement of Pulmonary Partial Pressure of Oxygen and Oxygen Depletion Rate with Hyperpolarized Helium-3 MRI: A Preliminary Reproducibility Study on Pig Model

RATIONAL AND OBJECTIVES Pulmonary partial pressure of oxygen (pO(2)) and oxygen depletion rate (R) are two important parameters of lung function. The dependence of hyperpolarized (3)He (HP (3)He) T(1) on local oxygen concentration provides the basis for high-resolution mapping of the regional distributions of pO(2) and R in the lung. Although the oxygen-sensitive HP (3)He magnetic resonance imaging technique has been applied in human subjects and several animal species, reproducibility studies are rarely reported in the literature. This work presents a preliminary reproducibility study on a pig model. In this study, important scan parameters, such as measurement timing and flip angle, are optimized to minimize the noise-induced measurement uncertainty. MATERIALS AND METHODS In the in vivo study, five normal pigs and one diseased pig with simulated pulmonary emboli were scanned with a small flip angle gradient echo sequence. The pulmonary oxygen measurement was repeated two to four times in each pig. In each measurement, a series of six images were acquired with optimal timing and flip angle. The parametric maps were generated using a bin-based data processing procedure that applied the multiple regression fitting method to extract the pO(2) and R. Variations of global mean, percentiles, and regions of interest were calculated from the maps to analyze reproducibility. RESULTS The global statistical analyses show that average variation of global mean is 10.7% for pO(2) and 23.8% for R, and that the average variation of percentiles (10th, 25th, 50th, 75th, and 90th) and interquartile range is 14.8% for pO(2) and 30.4% for R. The region-of-interest analysis on the manually selected regions shows that the average variation of mean is 12.6% for pO(2) and 21.9% for R. CONCLUSION In this work, a preliminary study on the reproducibility of measuring pO(2) and R with HP (3)He magnetic resonance imaging on a pig model is presented.

Optimization of scan parameters in pulmonary partial pressure oxygen measurement by hyperpolarized 3He MRI

The dependence of hyperpolarized (HP) 3He T1 on local oxygen concentration provides the basis for measuring the partial pressure of oxygen (pO2) 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 single‐acquisition 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 (pO2: 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 pO2 and 12.0% for R, and that the average variation of percentiles (10th, 25th, 50th, 75th, and 90th) is 8.7% for pO2 and 19.0% for R. Magn Reson Med, 2007.