Effect of inhaled oxygen concentration on 129 Xe chemical shift of red blood cells in rat lungs.

PURPOSE: To investigate the dependence of dissolved 129 Xe chemical shift on the fraction of inhaled oxygen, Fi O2 , in the lungs of healthy rats. METHODS: The chemical shifts of 129 Xe dissolved in red blood cells, δRBC , and blood plasma and/or tissue, δPlasma , were measured using MRS in 12 Sprague Dawley rats mechanically ventilated at Fi O2 values of 0.14, 0.19, and 0.22. Regional effects on the chemical shifts were controlled using a chemical shift saturation recovery sequence with a fixed delay time. MRS was also performed at an Fi CO2 value of 0.085 to investigate the potential effect of the vascular response on δRBC and δPlasma . RESULTS: δRBC increased with decreasing Fi O2 (P = .0002), and δPlasma showed no dependence on Fi O2 (P = .23). δRBC at Fi CO2 = 0 (210.7 ppm ± 0.1) and at Fi CO2 = 0.085 (210.6 ppm ± 0.2) were not significantly different (P = .67). δPlasma at Fi CO2 = 0 (196.9 ppm ± 0.3) and at Fi CO2 = 0.085 (197.0 ppm ± 0.1) were also not significantly different (P = .81). CONCLUSION: Rat lung δRBC showed an inverse relationship to Fi O2 , opposite to the relationship previously demonstrated for in vitro human blood. Rat lung δRBC did not depend on Fi CO2 .

Enabling Clinical Technologies for Hyperpolarized 129 Xenon Magnetic Resonance Imaging and Spectroscopy.

Hyperpolarization is a technique that can increase nuclear spin polarization with the corresponding gains in nuclear magnetic resonance (NMR) signals by 4-8 orders of magnitude. When this process is applied to biologically relevant samples, the hyperpolarized molecules can be used as exogenous magnetic resonance imaging (MRI) contrast agents. A technique called spin-exchange optical pumping (SEOP) can be applied to hyperpolarize noble gases such as 129 Xe. Techniques based on hyperpolarized 129 Xe are poised to revolutionize clinical lung imaging, offering a non-ionizing, high-contrast alternative to computed tomography (CT) imaging and conventional proton MRI. Moreover, CT and conventional proton MRI report on lung tissue structure but provide little functional information. On the other hand, when a subject breathes hyperpolarized 129 Xe gas, functional lung images reporting on lung ventilation, perfusion and diffusion with 3D readout can be obtained in seconds. In this Review, the physics of SEOP is discussed and the different production modalities are explained in the context of their clinical application. We also briefly compare SEOP to other hyperpolarization methods and conclude this paper with the outlook for biomedical applications of hyperpolarized 129 Xe to lung imaging and beyond.

Hyperpolarized gas diffusion MRI of biphasic lung inflation in short- and long-term emphysema models.

During lung inflation, airspace dimensions are affected nonlinearly by both alveolar expansion and recruitment, potentially confounding the identification of emphysematous lung by hyperpolarized helium-3 diffusion magnetic resonance imaging (HP MRI). This study aimed to characterize lung inflation over a broad range of inflation volume and pressure values in two different models of emphysema, as well as in normal lungs. Elastase-treated rats (n = 7) and healthy controls (n = 7) were imaged with HP MRI. Gradual inflation was achieved by incremental changes to both inflation volume and airway pressure. The apparent diffusion coefficient (ADC) was measured at each level of inflation and fitted to the corresponding airway pressures as the second-order response equation, with minimizing residue (χ2 < 0.001). A biphasic ADC response was detected, with an initial ADC increase followed by a decrease at airway pressures >18 cmH2O. Discrimination between treated and control rats was optimal when airway pressure was intermediate (between 10 and 11 cmH2O). Similar findings were confirmed in mice following long-term exposure to cigarette smoke, where optimal discrimination between treated and healthy mice occurred at a similar airway pressure as in the rats. We subsequently explored the evolution of ADC measured at the intermediate inflation level in mice after prolonged smoke exposure and found a significant increase (P < 0.01) in ADC over time. Our results demonstrate that measuring ADC at intermediate inflation enhances the distinction between healthy and diseased lungs, thereby establishing a model that may improve the diagnostic accuracy of future HP gas diffusion studies.

Regional Fractional Ventilation by Using Multibreath Wash-in (3)He MR Imaging.

Purpose To assess the feasibility and optimize the accuracy of the multibreath wash-in hyperpolarized helium 3 ((3)He) approach to ventilation measurement by using magnetic resonance (MR) imaging as well as to examine the physiologic differences that this approach reveals among nonsmokers, asymptomatic smokers, and patients with chronic obstructive pulmonary disease (COPD). Materials and Methods All experiments were approved by the local institutional review board and compliant with HIPAA. Informed consent was obtained from all subjects. To measure fractional ventilation, the authors administered a series of identical normoxic hyperpolarized gas breaths to the subject; after each inspiration, an image was acquired during a short breath hold. Signal intensity buildup was fit to a recursive model that regionally solves for fractional ventilation. This measurement was successfully performed in nine subjects: three healthy nonsmokers (one man, two women; mean age, 45 years ± 4), three asymptomatic smokers (three men; mean age, 51 years ± 5), and three patients with COPD (three men; mean age, 59 years ± 5). Repeated measures analysis of variance was performed, followed by post hoc tests with Bonferroni correction, to assess the differences among the three cohorts. Results Whole-lung fractional ventilation as measured with hyperpolarized (3)He in all subjects (mean, 0.24 ± 0.06) showed a strong correlation with global fractional ventilation as measured with a gas delivery device (R(2) = 0.96, P < .001). Significant differences between the means of whole-lung fractional ventilation (F2,10 = 7.144, P = .012) and fractional ventilation heterogeneity (F2,10 = 7.639, P = .010) were detected among cohorts. In patients with COPD, the protocol revealed regions wherein fractional ventilation varied substantially over multiple breaths. Conclusion Multibreath wash-in hyperpolarized (3)He MR imaging of fractional ventilation is feasible in human subjects and demonstrates very good global (whole-lung) precision. Fractional ventilation measurement with this physiologically realistic approach reveals significant differences between patients with COPD and healthy subjects. To minimize error, several sources of potential bias must be corrected when calculating fractional ventilation. (©) RSNA, 2016 Online supplemental material is available for this article.

Alterations of regional alveolar oxygen tension in asymptomatic current smokers: assessment with hyperpolarized (3)He MR imaging.

PURPOSE: To assess the ability of helium 3 ((3)He) magnetic resonance (MR) imaging of regional alveolar partial pressure of oxygen (Pao2) to depict smoking-induced functional alterations and to compare its efficacy to that of current diagnostic techniques. MATERIALS AND METHODS: This study was approved by the local institutional review board and was compliant with HIPAA. All subjects provided informed consent. A total of 43 subjects were separated into three groups: nonsmokers, asymptomatic smokers, and symptomatic smokers. All subjects underwent a Pao2 imaging session followed by clinically standard pulmonary function tests (PFTs), the 6-minute walk test, and St George Respiratory Questionnaire (SGRQ). The whole-lung mean and standard deviation of Pao2 were compared with metrics derived from PFTs, the 6-minute walk test, and the SGRQ. A logistic regression model was developed to identify the predictors of alterations to the lungs of asymptomatic smokers. RESULTS: The whole-lung standard deviation of Pao2 correlated with PFT metrics (forced expiratory volume in 1 second [FEV1]/forced vital capacity [FVC], Pearson r = -0.69, P < .001; percentage predicted FEV1, Pearson r = -0.67, P < .001; diffusing capacity of lung for carbon monoxide [Dlco], Pearson r = -0.45, P = .003), SGRQ score (Pearson r = 0.67, P < .001), and distance walked in 6 minutes (Pearson r = -0.47, P = .002). The standard deviation of Pao2 was significantly higher in asymptomatic smokers than in nonsmokers (change in the standard deviation of Pao2 = 7.59 mm Hg, P = .041) and lower when compared with symptomatic smokers (change in the standard deviation of Pao2 = 10.72 mm Hg, P = .001). A multivariate prediction model containing FEV1/FVC and the standard deviation of Pao2 (as significant predictors of subclinical changes in smokers) and Dlco (as a confounding variable) was formulated. This model resulted in an area under the receiver operating characteristic curve with a significant increase of 29.2% when compared with a prediction model based solely on nonimaging clinical tests. CONCLUSION: The (3)He MR imaging heterogeneity metric (standard deviation of Pao2) enabled the differentiation of all three study cohorts, which indicates that it can depict smoking-related functional alterations in asymptomatic current smokers.

Imaging the interaction of atelectasis and overdistension in surfactant-depleted lungs.

OBJECTIVE: Atelectasis and surfactant depletion may contribute to greater distension-and thereby injury-of aerated lung regions; recruitment of atelectatic lung may protect these regions by attenuating such overdistension. However, the effects of atelectasis (and recruitment) on aerated airspaces remain elusive. We tested the hypothesis that during mechanical ventilation, surfactant depletion increases the dimensions of aerated airspaces and that lung recruitment reverses these changes. DESIGN: Prospective imaging study in an animal model. SETTING: Research imaging facility. SUBJECTS: Twenty-seven healthy Sprague Dawley rats. INTERVENTIONS: Surfactant depletion was obtained by saline lavage in anesthetized, ventilated rats. Alveolar recruitment was accomplished using positive end-expiratory pressure and exogenous surfactant administration. MEASUREMENTS AND MAIN RESULTS: Airspace dimensions were estimated by measuring the apparent diffusion coefficient of He, using diffusion-weighted hyperpolarized gas magnetic resonance imaging. Atelectasis was demonstrated using computerized tomography and by measuring oxygenation. Saline lavage increased atelectasis (increase in nonaerated tissue from 1.2% to 13.8% of imaged area, p < 0.001), and produced a concomitant increase in mean apparent diffusion coefficient (~33%, p < 0.001) vs. baseline; the heterogeneity of the computerized tomography signal and the variance of apparent diffusion coefficient were also increased. Application of positive end-expiratory pressure and surfactant reduced the mean apparent diffusion coefficient (~23%, p < 0.001), and its variance, in parallel to alveolar recruitment (i.e., less computerized tomography densities and heterogeneity, increased oxygenation). CONCLUSIONS: Overdistension of aerated lung occurs during atelectasis is detectable using clinically relevant magnetic resonance imaging technology, and could be a key factor in the generation of lung injury during mechanical ventilation. Lung recruitment by higher positive end-expiratory pressure and surfactant administration reduces airspace distension.

Accelerated fractional ventilation imaging with hyperpolarized Gas MRI.

PURPOSE: To investigate the utility of accelerated imaging to enhance multibreath fractional ventilation (r) measurement accuracy using hyperpolarized gas MRI. Undersampling shortens the breath-hold time, thereby reducing the O2 -induced signal decay and allows subjects to maintain a more physiologically relevant breathing pattern. Additionally, it may improve r estimation accuracy by reducing radiofrequency destruction of hyperpolarized gas. METHODS: Image acceleration was achieved using an eight-channel phased array coil. Undersampled image acquisition was simulated in a series of ventilation images and data was reconstructed for various matrix sizes (48-128) using generalized auto-calibrating partially parallel acquisition. Parallel accelerated r imaging was also performed on five mechanically ventilated pigs. RESULTS: Optimal acceleration factor was fairly invariable (2.0-2.2×) over the range of simulated resolutions. Estimation accuracy progressively improved with higher resolutions (39-51% error reduction). In vivo r values were not significantly different between the two methods: 0.27 ± 0.09, 0.35 ± 0.06, 0.40 ± 0.04 (standard) versus 0.23 ± 0.05, 0.34 ± 0.03, 0.37 ± 0.02 (accelerated); for anterior, medial, and posterior slices, respectively, whereas the corresponding vertical r gradients were significant (P < 0.001): 0.021 ± 0.007 (standard) versus 0.019 ± 0.005 (accelerated) (cm(-1) ). CONCLUSION: Quadruple phased array coil simulations resulted in an optimal acceleration factor of ∼2× independent of imaging resolution. Results advocate undersampled image acceleration to improve accuracy of fractional ventilation measurement with hyperpolarized gas MRI.

A variability study of regional alveolar oxygen tension measurement in humans using hyperpolarized (3) He MRI.

PURPOSE: A systematic study of the short-term and long-term variability of regional alveolar partial pressure of oxygen tension (pA O2 ) measurements using (3) He magnetic resonance imaging was presented. Additionally, the repeatability of the average evaluated pA O2 was compared with that of the standard pulmonary function tests. METHODS: Pulmonary function test and pA O2 imaging were performed on 4 nonsmokers (1 M, 3 F, 56 ± 1.7 years) and 4 smokers (3 M, 1 F, 52 ± 7.5 years) during three visits over the course of 2 weeks. Two measurements were performed per visit. Variability of pA O2 was assessed using a mixed-effect model, with an intraclass correlation coefficient calculated for each group. The coefficient of variation of pA O2 over the 3-day period was also compared with the coefficient of variation of pulmonary function test results. RESULTS: Short-term regional variability based on intraclass correlation coefficient was 0.71 for nonsmokers, and 0.63 for smokers, with long-term variability significantly lower at 0.59 and 0.47, respectively. While the coefficient of variation of the average pA O2 was similar to the repeatability of the diffusing capacity of CO, it was significantly higher than that of Forced Vital Capacity (P = 0.02). CONCLUSION: Short-term and long-term pA O2 variability differences were used as an indication of true physiological changes in order to measure technical reproducibility. Smokers show higher physiologic variability and less technical reproducibility. The suggested pA O2 -imaging technique showed a reasonable regional repeatability in nonsmokers as well as the ability to detect differences between the two groups with similar reproducibility and superior discriminatory ability when compared with pulmonary function tests.

Positive end-expiratory pressure increments during anesthesia in normal lung result in hysteresis and greater numbers of smaller aerated airspaces.

BACKGROUND: Although it is recognized that pulmonary hysteresis can influence the effects of positive end-expiratory pressure (PEEP), the extent to which expansion of previously opened (vs. newly opening) peripheral airspaces contribute to increased lung volume is unknown. METHODS: Following a recruitment maneuver, rats were ventilated with constant tidal volumes and imaged during ascending and descending ramps of PEEP. RESULTS: The authors estimated peripheral airspace dimensions by measuring the apparent diffusion coefficient of He in 10 rats. In a separate group (n = 5) undergoing a similar protocol, the authors used computerized tomography to quantify lung volume. Hysteresis was confirmed by larger end-inspiratory lung volume (mean ± SD; all PEEP levels included): 8.4 ± 2.8 versus 6.8 ± 2.0 ml (P < 0.001) and dynamic compliance: 0.52 ± 0.12 versus 0.42 ± 0.09 ml/cm H2O (P < 0.001) during descending versus ascending PEEP ramps. Apparent diffusion coefficient increased with PEEP, but it was smaller during the descending versus ascending ramps for corresponding levels of PEEP: 0.168 ± 0.019 versus 0.183 ± 0.019 cm/s (P < 0.001). Apparent diffusion coefficient was smaller in the posterior versus anterior lung regions, but the effect of PEEP and hysteresis on apparent diffusion coefficient was greater in the posterior regions. CONCLUSIONS: The authors' study results suggest that in healthy lungs, larger lung volumes due to hysteresis are associated with smaller individual airspaces. This may be explained by opening of previously nonaerated peripheral airspaces rather than expansion of those already aerated. Setting PEEP on a descending ramp may minimize distension of individual airspaces.

A multislice single breath-hold scheme for imaging alveolar oxygen tension in humans.

Reliable, noninvasive, and high-resolution imaging of alveolar partial pressure of oxygen (p(A)O(2)) is a potentially valuable tool in the early diagnosis of pulmonary diseases. Several techniques have been proposed for regional measurement of p(A)O(2) based on the increased depolarization rate of hyperpolarized (3) He. In this study, we explore one such technique by applying a multislice p(A)O(2) -imaging scheme that uses interleaved-slice ordering to utilize interslice time-delays more efficiently. This approach addresses the low spatial resolution and long breath-hold requirements of earlier techniques, allowing p(A)O(2) measurements to be made over the entire human lung in 10-15 s with a typical resolution of 8.3 × 8.3 × 15.6 mm(3). PO(2) measurements in a glass syringe phantom were in agreement with independent gas analysis within 4.7 ± 4.1% (R = 0.9993). The technique is demonstrated in four human subjects (healthy nonsmoker, healthy former smoker, healthy smoker, and patient with COPD), each imaged six times on 3 different days during a 2-week span. Two independent measurements were performed in each session, consisting of 12 coronal slices. The overall p(A)O(2) mean across all subjects was 95.9 ± 12.2 Torr and correlated well with end-tidal O(2) (R = 0.805, P < 0.0001). The alveolar O(2) uptake rate was consistent with the expected range of 1-2 Torr/s. Repeatable visual features were observed in p(A)O(2) maps over different days, as were characteristic differences among the subjects and gravity-dependent effects.

Multislice fractional ventilation imaging in large animals with hyperpolarized gas MRI.

The noninvasive assessment of regional lung ventilation is of critical importance in the quantification of the severity of disease and evaluation of response to therapy in many pulmonary diseases. This work presents, for the first time, the implementation of a hyperpolarized (HP) gas MRI technique to measure whole-lung regional fractional ventilation (r) in Yorkshire pigs (n = 5) through the use of a gas mixing and delivery device in the supine position. The proposed technique utilizes a series of back-to-back HP gas breaths with images acquired during short end-inspiratory breath-holds. In order to decouple the radiofrequency pulse decay effect from the ventilatory signal build-up in the airways, the regional distribution of the flip angle (α) was estimated in the imaged slices by acquiring a series of back-to-back images with no interscan time delay during a breath-hold at the tail end of the ventilation sequence. Analysis was performed to assess the sensitivity of the multislice ventilation model to noise, oxygen and the number of flip angle images. The optimal α value was determined on the basis of the minimization of the error in r estimation: α(opt) = 5-6º for the set of acquisition parameters in pigs. The mean r values for the group of pigs were 0.27 ± 0.09, 0.35 ± 0.06 and 0.40 ± 0.04 for the ventral, middle and dorsal slices, respectively (excluding conductive airways r 0.9). A positive gravitational (ventral-dorsal) ventilation gradient effect was present in all animals. The trachea and major conductive airways showed a uniform near-unity r value, with progressively smaller values corresponding to smaller diameter airways, and ultimately leading to lung parenchyma. The results demonstrate the feasibility of the measurement of the fractional ventilation in large species, and provide a platform to address the technical challenges associated with long breathing time scales through the optimization of acquisition parameters in species with a pulmonary physiology very similar to that of humans.

A simple and low-cost device for generating hyperpolarized contrast agents using parahydrogen.

A detailed description of the construction and use of a device for hyperpolarization of select contrast agents is presented. The device is based on molecular incorporation of the spin-order inherent to parahydrogen, followed by order transfer to a metastable heteronuclear alignment. Design considerations and experimental results relating to catalyst/solvent choice and handling, solvent heating, efficient gas entrainment and spin-order transfer are described. The resulting degree of hyperpolarization is shown to be substantial, ranging from a few to over 50%, depending on the choice of target molecule. Finally, the use of the hyperpolarized agent is demonstrated in a series of in vivo images.

Regional determination of oxygen uptake in rodent lungs using hyperpolarized gas and an analytical treatment of intrapulmonary gas redistribution.

A method is presented which allows for the accurate extraction of regional functional metrics in rodent lungs using hyperpolarized gas. The technique is based on the combination of measured T(1) decay, an independent measure of specific ventilation and mass balance considerations to extract the regional oxygen levels and uptake. In phantom and animal experiments, it is demonstrated that the redistribution of gas during the measurement is a significant confounding factor, and this effect is addressed analytically. The resulting parameterization of gas flow increases the accuracy of oxygen-sensitive MRI, and may also be used independently to assess air trapping and airway constriction. Limitations of the technique with respect to spatial resolution and robustness are also discussed.

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.

A semi-empirical model to optimize continuous-flow hyperpolarized 129Xe production under practical cryogenic-accumulation conditions.

Continuous-flow spin exchange optical pumping (SEOP) with cryogenic accumulation is a powerful technique to generate multiple, large volumes of hyperpolarized (HP) 129Xe in rapid succession. It enables a range of studies, from dark matter tracking to preclinical and clinical MRI. Multiple analytical models based on first principles atomic physics and device-specific design features have been proposed for individual processes within HP 129Xe production. However, the modeling efforts have not yet integrated all the steps involved in practical, large volume HP 129Xe production process (e.g., alkali vapor generation, continuous-flow SEOP, and cryogenic accumulation). Here, we use a simplified analytical model that couples both SEOP and cryogenic accumulation, incorporating only two system-specific empirical parameters: the longitudinal relaxation time of the polycrystalline 129Xe "snow', T1snow, generated during cryogenic accumulation, and 2) the average Rb density during active, continuous-flow polarization. By fitting the model to polarization data collected from >140 L of 129Xe polarized across a range of flow and volume conditions, the estimates for Rb density and T1snow were 1.6 ± 0.1 × 1013 cm-3 and 84 ± 5 min, respectively - each notably less than expected based on previous literature. Together, these findings indicate that 1) earlier polarization predictions were hindered by miscalculated Rb densities, and 2) polarization is not optimized by maximizing SEOP efficiency with a low concentration 129Xe, but rather by using richer 129Xe-buffer gas blends that enable faster accumulation. Accordingly, modeling and experimentation revealed the optimal fraction of 129Xe, f, in the 129Xe-buffer gas blend was ~2%. Further, if coupled with modest increases in laser power, the model predicts liter volumes of HP 129Xe with polarizations exceeding 60% could be generated routinely in only tens of minutes.

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

Hyperpolarized (3)He (HP (3)He) MRI shows promise to assess structural and functional pulmonary parameters in a sensitive, regional, and noninvasive way. Structural HP (3)He MRI has applied the apparent diffusion coefficient (ADC) for the detection of disease-induced lung microstructure changes at the alveolar level, and HP (3)He pulmonary partial pressure of oxygen (pO(2)) 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 pO(2) 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 pO(2) 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.

Early changes of lung function and structure in an elastase model of emphysema--a hyperpolarized 3He MRI study.

Early changes of lung function and structure were studied in the presence of an elastase-induced model of emphysema in 35 Sprague-Dawley rats at mild (5 U/100 g) and moderate (10 U/100 g) severities. Lung ventilation was measured on a regional basis (at a planar resolution of 3.2 mm) by hyperpolarized 3He MRI at 5 and 10 wk after model induction. Subsequent to imaging, average alveolar diameter was measured from histological slices taken from the centers of each lobe. Changes of mean fractional ventilation, mean linear intercept, and intrasubject heterogeneity of ventilation were studied during disease progression. Mean fractional ventilation was significantly different between healthy controls (0.23 +/- 0.04) and emphysematous animals at both time points in the 10-unit group (0.06 +/- 0.02 and 0.12 +/- 0.05, respectively). Changes in average alveolar diameter were not statistically observable until the 10th wk between healthy (37 +/- 10 microm) and emphysematous rats (73 +/- 25 and 95 +/- 31 microm, for 5 and 10 units, respectively). Assessment of function-structure correlation suggested that the majority of the decline in fractional ventilation occurred in the first 5 wk, while enlargement of alveolar diameters appeared primarily between the 5th and 10th wk. A thresholding metric, based on the 20th percentile of fractional ventilation over the entire lung, was utilized to detect the onset of the disease with confidence, independent of whether the regional ventilation measurements were normalized with respect to the delivered tidal volume and estimated functional residual capacity of each individual rat.

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.

A robust method for estimating regional pulmonary parameters in presence of noise.

RATIONALE AND OBJECTIVES: Estimation of regional lung function parameters from hyperpolarized gas magnetic resonance images can be very sensitive to presence of noise. Clustering pixels and averaging over the resulting groups is an effective method for reducing the effects of noise in these images, commonly performed by grouping proximal pixels together, thus creating large groups called "bins." This method has several drawbacks, primarily that it can group dissimilar pixels together, and it degrades spatial resolution. This study presents an improved approach to simplifying data via principal component analysis (PCA) when noise level prohibits a pixel-by-pixel treatment of data, by clustering them based on similarity to one another rather than spatial proximity. The application to this technique is demonstrated in measurements of regional lung oxygen tension using hyperpolarized (3)He magnetic resonance imaging (MRI). MATERIALS AND METHODS: A synthetic dataset was generated from an experimental set of oxygen tension measurements by treating the experimentally derived parameters as "true" values, and then solving backwards to generate "noiseless" images. Artificial noise was added to the synthetic data, and both traditional binning and PCA-based clustering were performed. For both methods, the root-mean-square (RMS) error between each pixel's "estimated" and "true" parameters was computed and the resulting effects were compared. RESULTS: At high signal-to-noise ratios (SNRs), clustering did not enhance accuracy. Clustering did, however, improve parameter estimations for moderate SNR values (below 100). For SNR values between 100 and 20, the PCA-based K-means clustering analysis yielded greater accuracy than Cartesian binning. In extreme cases (SNR<5), Cartesian binning can be more accurate. CONCLUSIONS: The reliability of parameters estimation in imaging-based regional functional measurements can be improved in the presence of noise by utilizing principal component analysis-based clustering without sacrificing spatial resolution compared to Cartesian binning. Results suggest that this approach has a great potential for robust grouping of pixels in hyperpolarized (3)He MRI maps of lung oxygen tension.