Chemical Shift Saturation Recovery Research Articles

Hyperpolarized 129 Xe MRI of the rat brain with chemical shift saturation recovery and spiral-IDEAL readout.

To demonstrate the feasibility of 129 Xe chemical shift saturation recovery (CSSR) combined with spiral-IDEAL imaging for simultaneous measurement of the time-course of red blood cell (RBC) and brain tissue signals in the rat brain. Images of both the RBC and brain tissue 129 Xe signals from the brains of five rats were obtained using interleaved spiral-IDEAL imaging following chemical shift saturation pulses applied at multiple CSSR delay times, τ. A linear fit of the signals to τ was used to calculate the slope of the signal for both RBC and brain tissue compartments on a voxel-by-voxel basis. Gas transfer was evaluated by measuring the ratio of the whole brain tissue-to-RBC signal intensities as a function of τ. To investigate the relationship between the CSSR images and gas transfer in the brain, the experiments were repeated during hypercapnic ventilation. Hypercapnia, affected the ratio of the tissue-to-RBC signal intensity (p = 0.026), consistent with an increase in gas transfer. CSSR with spiral-IDEAL imaging is feasible for acquisition of 129 Xe RBC and brain tissue time-course images in the rat brain. Differences in the time-course of the signal intensity ratios are consistent with gas transfer changes expected under hypercapnic conditions.

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

To investigate the dependence of dissolved 129 Xe chemical shift on the fraction of inhaled oxygen, Fi O2 , in the lungs of healthy rats. 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 . 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). 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 .

Investigating biases in the measurement of apparent alveolar septal wall thickness with hyperpolarized 129Xe MRI.

To investigate biases in the measurement of apparent alveolar septal wall thickness (SWT) with hyperpolarized xenon-129 (HXe) as a function of acquisition parameters. The HXe MRI scans with simultaneous gas-phase and dissolved-phase excitation were performed using 1-dimensional projection scans in mechanically ventilated rabbits. The dissolved-phase magnetization was periodically saturated, and the dissolved-phase xenon uptake dynamics were measured at end inspiration and end expiration with temporal resolutions up to 10 ms using a Look-Locker-type acquisition. The apparent alveolar septal wall thickness was extracted by fitting the signal to a theoretical model, and the findings were compared with those from the more commonly use chemical shift saturation recovery MRI spectroscopy technique with several different delay time arrangements. It was found that repeated application of RF saturation pulses in chemical shift saturation recovery acquisitions caused exchange-dependent gas-phase saturation that heavily biased the derived SWT value. When this bias was reduced by our proposed method, the SWT dependence on lung inflation disappeared due to an inherent insensitivity of HXe dissolved-phase MRI to thin alveolar structures with very short . Furthermore, perfusion-based macroscopic gas transport processes were demonstrated to cause increasing apparent SWTs with TE (2.5 μm/ms at end expiration) and a lung periphery-to-center SWT gradient. The apparent SWT measured with HXe MRI was found to be heavily dependent on the acquisition parameters. A method is proposed that can minimize this measurement bias, add limited spatial resolution, and reduce measurement time to a degree that free-breathing studies are feasible.

Investigating short-time diffusion of hyperpolarized 129 Xe in lung air spaces and tissue: A feasibility study in chronic obstructive pulmonary disease patients.

To investigate the diffusion of hyperpolarized 129 Xe in air spaces at short-time scales for determination of lung surface-to-gas-volume ratio in comparison to results from chemical shift saturation recovery, CT, and established clinical measures. A pulse sequence for measurement of time-dependent diffusion of 129 Xe in air spaces at short diffusion times was developed. Gas uptake into lung tissue was measured in the same breathhold using chemical shift saturation recovery spectroscopy in the short-time regime. The potential to obtain thesurface-to-gas-volume ratiousing a first-order and second-order approximation of the short-time expansion of time-dependent diffusion according to Mitra et al11 and its diagnostic relevance were tested in a study with 9 chronic obstructive pulmonary diseases patients. Surface-to-gas-volume ratios obtained from time-dependent diffusion were correlated with results from chemical shift saturation recovery, r=0.840, P=.005 (first-order fits), and r=0.923, P<.001 (second-order fits), and from CT results for second-order fits, r=0.729, P=.026. Group means ± SD were 75.0±15.5cm-1 (first-order fits) and 122.3± 32.8cm-1 (second-order fits) for time-dependent diffusion, 125.9±43.3cm-1 for chemical shift saturation recovery, and 159.5 ±50.9cm-1 for CT. Surface-to-gas-volume ratiosfrom time-dependent diffusion with first-order fits correlated significantly with carbon monoxide diffusing capacity as percent of prediction, r=0.724, P=.028. Time-dependent diffusion measurements of 129 Xe at short-time scales down to ~1ms are feasible in chronic obstructive pulmonary patients and provide clinically relevant information on lung microstructure.

Quantitative evaluation of lung injury caused by PM2.5 using hyperpolarized gas magnetic resonance.

To demonstrate the feasibility of 129 Xe MR in evaluating the pulmonary physiological changes caused by PM2.5 in animal models. Six rats were treated with PM2.5 solution (16.2 mg/kg) by intratracheal instillation twice a week for 4 weeks, and another six rats treated with normal saline served as the control cohort. Pulmonary function tests, hyperpolarized 129 Xe multi-b diffusion-weighted imaging, and chemical shift saturation recovery MR spectroscopywere performed on all rats, and the pulmonary structure and functional parameters were obtained from hyperpolarized 129 Xe MR data. Additionally, histological analysis was performed on all rats to evaluate alveolar septal thickness. Statistical analysis of all the obtained parameters was performed using unpaired 2-tailed t tests. Compared with the control group, the measured exchange time constant increased from 11.74 ± 2.39 to 14.00 ± 2.84 ms (P < .05), and the septal wall thickness increased from 6.17 ± 0.48 to 6.74 ± 0.52 μm (P < .05) in the PM2.5 cohort by 129 Xe MR spectroscopy, which correlated well with that obtained using quantitative histology (increased from 5.52 ± 0.32 to 6.20 ± 0.36 μm). Additionally, the mean TP/GAS ratio increased from 0.828 ± 0.115 to 1.019 ± 0.140 in the PM2.5 cohort (P = .021). Hyperpolarized 129 Xe MR could quantify the changes in gas exchange physiology caused by PM2.5 , indicating that the technique has the potential to be a useful tool for evaluation of pulmonary injury caused by air pollution in the future.

Chemical shift of 129 Xe dissolved in red blood cells: Application to a rat model of bronchopulmonary dysplasia.

To measure the chemical shift of hyperpolarized 129 Xe dissolved in the red blood cells(δRBC )of a cohort of rats exposed to hyperoxia and intermittent hypoxia (IH) to mimic human bronchopulmonary dysplasia, and to investigate the effect of xenon-blood distribution time on δRBC . δRBC was measured from spectra acquired using a chemical shift saturation recovery sequence from 15 Sprague-Dawley rats exposed to hyperoxia-IHand 10 age-matched control rats. Sensitization to the xenon-blood distribution time was achieved by varying the time between saturation pulses, τ. δRBC was compared with blood fraction measured by histology of the cohort and blood oxygenation measured directly using pulse oximetry following a hypoxic challenge in an identically exposed cohort. The mean δRBC in the hyperoxia-IH exposed rats was 0.55 ± 0.04 ppm lower than that of the healthy cohort (P = .0038), and this difference did not depend on τ (P = .996). The blood fraction of the exposed cohort was lower than that of the healthy cohort (P = .0397). Oximetry measurements showed that the baseline arterial oxygen saturation (Sa O2 ) of each cohort was not different (P = .72), but after a hypoxic challenge, the Sa O2 of the exposed cohort was lower than that of the healthy cohort (P = .003). δRBC is reduced in rats exposed to hyperoxia-IH compared with control rats. The change in δRBC is consistent with enhanced blood oxygen desaturation of the exposed cohort measured by pulse oximetry during a hypoxic challenge. This suggests that the observed change in δRBC reflects enhanced desaturation in the hyperoxia-IH exposed cohort compared with the healthy cohort.

Noninvasive Monitoring of the Response of Human Lungs to Low-Dose Lipopolysaccharide Inhalation Challenge Using MRI: A Feasibility Study.

Development of antiinflammatory drugs for lung diseases demands novel methods for noninvasive assessment of inflammatory processes in the lung. To investigate the feasibility of hyperpolarized 129 Xe MRI, 1 H T1 time mapping, and dynamic contrast-enhanced (DCE) perfusion MRI for monitoring the response of human lungs to low-dose inhaled lipopolysaccharide (LPS) challenge compared to inflammatory cell counts from induced-sputum analysis. Prospective feasibility study. Ten healthy volunteers underwent MRI before and 6 hours after inhaled LPS challenge with subsequent induced-sputum collection. 1.5T/hyperpolarized 129 Xe MRI: Interleaved multiecho imaging of dissolved and gas phase, ventilation imaging, dissolved-phase spectroscopy, and chemical shift saturation recovery spectroscopy. 1 H MRI: Inversion recovery fast low-angle shot imaging for T1 mapping, time-resolved angiography with stochastic trajectories for DCE MRI. Dissolved-phase ratios of 129 Xe in red blood cells (RBC), tissue/plasma (TP) and gas phase (GP), ventilation defect percentage, septal wall thickness, surface-to-volume ratio, capillary transit time, lineshape parameters in dissolved-phase spectroscopy, 1 H T1 time, blood volume, flow, and mean transit time were determined and compared to cell counts. Wilcoxon signed-rank test, Pearson correlation. The percentage of neutrophils in sputum was markedly increased after LPS inhalation compared to baseline, P = 0.002. The group median RBC-TP ratio was significantly reduced from 0.40 to 0.31, P = 0.004, and 1 H T1 was significantly elevated from 1157.6 msec to 1187.8 msec after LPS challenge, P = 0.027. DCE MRI exhibited no significant changes in blood volume, P = 0.64, flow, P = 0.17, and mean transit time, P = 0.11. Hyperpolarized 129 Xe dissolved-phase MRI and 1 H T1 mapping may provide biomarkers for noninvasive assessment of the response of human lungs to LPS inhalation. By its specificity to the alveolar region, hyperpolarized 129 Xe MRI together with 1 H T1 mapping adds value to sputum analysis. 1 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020;51:1669-1676.

Single breath-hold measurement of pulmonary gas exchange and diffusion in humans with hyperpolarized 129 Xe MR.

Pulmonary diseases usually result in changes of the blood-gas exchange function in the early stages. Gas exchange across the respiratory membrane and gas diffusion in the alveoli can be quantified using hyperpolarized 129 Xe MR via chemical shift saturation recovery (CSSR) and diffusion-weighted imaging (DWI), respectively. Generally, CSSR and DWI data have been collected in separate breaths in humans. Unfortunately, the lung inflation level cannot be the exactly same in different breaths, which causes fluctuations in blood-gas exchange and pulmonary microstructure. Here we combine CSSR and DWI obtained with compressed sensing, to evaluate the gas diffusion and exchange function within a single breath-hold in humans. A new parameter, namely the perfusion factor of the respiratory membrane (SVRd/g ), is proposed to evaluate the gas exchange function. Hyperpolarized 129 Xe MR data are compared with pulmonary function tests and computed tomography examinations in healthy young, age-matched control, and chronic obstructive pulmonary disease human cohorts. SVRd/g decreases as the ventilation impairment and emphysema index increase. Our results indicate that the proposed method has the potential to detect the extent of lung parenchyma destruction caused by age and pulmonary diseases, and it would be useful in the early diagnosis of pulmonary diseases in clinical practice.

Mapping of regional lung microstructural parameters using hyperpolarized 129Xe dissolved‐phase MRI in healthy volunteers and patients with chronic obstructive pulmonary disease

To develop a novel technique for voxel-based mapping of lung microstructural parameters using hyperpolarized 129 Xe dissolved-phase MR imaging during saturation recovery. A pulse sequence using a highly undersampled stack-of-stars trajectory was developed, and low-rank plus sparse matrix decomposition was employed for reconstruction of regional 129 Xe uptake dynamics into lung tissue. In 4 healthy volunteers and 9 patients with chronic obstructive pulmonary disease, the technique was tested and compared to chemical shift saturation recovery spectroscopy in patients. Reproducibility of 129 Xe gas uptake imaging was assessed by computing coefficients of variation, and results were compared with other modalities. Numerical simulations and results from in vivo measurements in patients with chronic obstructive pulmonary disease showed that septal wall thickness and surface-to-volume ratio can be measured with an accuracy close to spectroscopic measurements. The average of the microstructural parameters of the total lung volume showed good reproducibility (coefficient of variation wall thickness: 7.4% coefficient of variation surface-to-volume ratio: 7.5%) and correlated strongly with the findings of global chemical shift saturation recovery spectroscopy. Gravitational gradients of microstructural parameters and increased heterogeneity in chronic obstructive pulmonary disease patients were observed. A novel technique for mapping of regional lung microstructural parameters was introduced, and its feasibility was shown in healthy volunteers and chronic obstructive pulmonary disease patients.

Regional investigation of lung function and microstructure parameters by localized 129 Xe chemical shift saturation recovery and dissolved-phase imaging: A reproducibility study.

To evaluate the reproducibility and regional variation of parameters obtained from localized 129 Xe chemical shift saturation recovery (CSSR) MR spectroscopy in healthy volunteers and patients with chronic obstructive pulmonary disease (COPD) and to compare the results to 129 Xe dissolved-phase MR imaging. Thirteen healthy volunteers and 10 COPD patients were scanned twice using 129 Xe dissolved-phase imaging, CSSR, and ventilation imaging sequences. A 16-channel phased-array coil in combination with the regularized spectral localization achieved by sensitivity heterogeneity (SPLASH) method was used to perform a regional analysis of CSSR data. Lung function and microstructural parameters were obtained using Patz model functions and their reproducibility was assessed. The Patz model alveolar wall thickness parameter shows good reproducibility on a regional basis with a median coefficient of variation of 6.5% in healthy volunteers and 12.4% in COPD patients. Significant regional differences of lung function parameters derived from localized CSSR were found in healthy volunteers and correlations with spirometric indices were found. Localized 129 Xe CSSR provides reproducible estimates of alveolar wall thickness and is able to detect regional differences of lung microstructure.

Quantitative evaluation of pulmonary gas-exchange function using hyperpolarized 129 Xe CEST MRS and MRI.

Hyperpolarized 129 Xe gas MR has been a powerful tool for evaluating pulmonary structure and function due to the extremely high enhancement in spin polarization, the good solubility in the pulmonary parenchyma, and the excellent chemical sensitivity to its surrounding environment. Generally, the quantitative structural and functional information of the lung are evaluated using hyperpolarized 129 Xe by employing the techniques of chemical shift saturation recovery (CSSR) and xenon polarization transfer contrast (XTC). Hyperpolarized 129 Xe chemical exchange saturation transfer (Hyper-CEST) is another method for quantifying the exchange information of hyperpolarized 129 Xe by using the exchange of xenon signals according to its different chemical shifts, and it has been widely used in biosensor studies in vitro. However, the feasibility of using hyperpolarized 129 Xe CEST to quantify the pulmonary gas exchange function in vivo is still unclear. In this study, the technique of CEST was used to quantitatively evaluate the gas exchange in the lung globally and regionally via hyperpolarized 129 Xe MRS and MRI, respectively. A new parameter, the pulmonary apparent gas exchange time constant (Tapp ), was defined, and it increased from 0.63s to 0.95s in chronic obstructive pulmonary disease (COPD) rats (induced by cigarette smoke and lipopolysaccharide exposure) versus the controls with a significant difference (P=0.001). Additionally, the spatial distribution maps of Tapp in COPD rats' pulmonary parenchyma showed a regionally obvious increase compared with healthy rats. These results indicated that hyperpolarized 129 Xe CEST MR was an effective method for globally and regionally quantifying the pulmonary gas exchange function, which would be helpful in diagnosing lung diseases that are related to gas exchange, such as COPD.

Simultaneous assessment of both lung morphometry and gas exchange function within a single breath-hold by hyperpolarized 129 Xe MRI

During the measurement of hyperpolarized 129 Xe magnetic resonance imaging (MRI), the diffusion-weighted imaging (DWI) technique provides valuable information for the assessment of lung morphometry at the alveolar level, whereas the chemical shift saturation recovery (CSSR) technique can evaluate the gas exchange function of the lungs. To date, the two techniques have only been performed during separate breaths. However, the request for multiple breaths increases the cost and scanning time, limiting clinical application. Moreover, acquisition during separate breath-holds will increase the measurement error, because of the inconsistent physiological status of the lungs. Here, we present a new method, referred to as diffusion-weighted chemical shift saturation recovery (DWCSSR), in order to perform both DWI and CSSR within a single breath-hold. Compared with sequential single-breath schemes (namely the 'CSSR + DWI' scheme and the 'DWI+CSSR' scheme), the DWCSSR scheme is able to significantly shorten the breath-hold time, as well as to obtain high signal-to-noise ratio (SNR) signals in both DWI and CSSR data. This scheme enables comprehensive information on lung morphometry and function to be obtained within a single breath-hold. In vivo experimental results demonstrate that DWCSSR has great potential for the evaluation and diagnosis of pulmonary diseases.

Quantitative comparison of lung physiological parameters in single and multiple breathhold with hyperpolarized xenon magnetic resonance

Hyperpolarized (HP) xenon MR has been an important tool for quantifying the pulmonary structure and gaining functional information by measuring the dynamics of xenon in different lung components, e.g., gas exchange between gaseous xenon in the alveoli and dissolved xenon in tissue/plasma and red blood cells. Chemical shift saturation recovery is a commonly used pulse sequence to measure the xenon dynamics in the lung globally. However, the effect of the dissolved xenon signal oscillation caused by the cardiac cycle on the physiological parameters of the lung is still unclear. In this study, both single-breathhold (SB) and multiple-breathhold (MB) measurements were used to evaluate these effects in rats, and the data acquired with the MB measurement, which did not have oscillations, served as a reference. The pulmonary physiological parameters were extracted using the model of xenon exchange. The results showed that the physiological parameters derived from SB and MB measurements were not significantly different. These findings have clarified a previously unknown issue and will further promote the design of faster real-time acquisition sequences to quantify structural and functional information about the lung.

Reproducibility of quantitative indices of lung function and microstructure from 129 Xe chemical shift saturation recovery (CSSR) MR spectroscopy.

PurposeTo evaluate the reproducibility of indices of lung microstructure and function derived from 129Xe chemical shift saturation recovery (CSSR) spectroscopy in healthy volunteers and patients with chronic obstructive pulmonary disease (COPD), and to study the sensitivity of CSSR‐derived parameters to pulse sequence design and lung inflation level.MethodsPreliminary data were collected from five volunteers on three occasions, using two implementations of the CSSR sequence. Separately, three volunteers each underwent CSSR at three different lung inflation levels. After analysis of these preliminary data, five COPD patients were scanned on three separate days, and nine age‐matched volunteers were scanned three times on one day, to assess reproducibility.ResultsCSSR‐derived alveolar septal thickness (ST) and surface‐area‐to‐volume (S/V) ratio values decreased with lung inflation level (P < 0.001; P = 0.057, respectively). Intra‐subject standard deviations of ST were lower than the previously measured differences between volunteers and subjects with interstitial lung disease. The mean coefficient of variation (CV) values of ST were 3.9 ± 1.9% and 6.0 ± 4.5% in volunteers and COPD patients, respectively, similar to CV values for whole‐lung carbon monoxide diffusing capacity. The mean CV of S/V in volunteers and patients was 14.1 ± 8.0% and 18.0 ± 19.3%, respectively.Conclusion 129Xe CSSR presents a reproducible method for estimation of alveolar septal thickness. Magn Reson Med 77:2107–2113, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Quantitative evaluation of radiation-induced lung injury with hyperpolarized xenon magnetic resonance.

To demonstrate the feasibility of quantitative and comprehensive global evaluation of pulmonary function and microstructural changes in rats with radiation-induced lung injury (RILI) using hyperpolarized xenon MR. Dissolved xenon spectra were dynamically acquired using a modified chemical shift saturation recovery pulse sequence in five rats with RILI (bilaterally exposed by 6-MV x-ray with a dose of 14 Gy 3 mo. prior to MR experiments) and five healthy rats. The dissolved xenon signals were quantitatively analyzed, and the pulmonary physiological parameters were extracted with the model of xenon exchange. The obtained pulmonary physiological parameters and the ratio of (129) Xe signal in red blood cells (RBCs) versus barrier showed a significant difference between the groups. In RILI rats versus controls, the exchange time increased from 44.5 to 112 ms, the pulmonary capillary transit time increased from 0.51 to 1.48 s, and the ratio of (129) Xe spectroscopic signal in RBCs versus barrier increased from 0.294 to 0.484. Hyperpolarized xenon MR is effective for quantitative and comprehensive global evaluation of pulmonary function and structural changes without the use of radiation. This may open the door for its use in the diagnosis of lung diseases that are related to gas exchange. Magn Reson Med 76:408-416, 2016. © 2015 Wiley Periodicals, Inc.

Detecting pulmonary capillary blood pulsations using hyperpolarized xenon-129 chemical shift saturation recovery (CSSR) MR spectroscopy.

To investigate whether chemical shift saturation recovery (CSSR) MR spectroscopy with hyperpolarized xenon-129 is sensitive to the pulsatile nature of pulmonary blood flow during the cardiac cycle. A CSSR pulse sequence typically uses radiofrequency (RF) pulses to saturate the magnetization of xenon-129 dissolved in lung tissue followed, after a variable delay time, by an RF excitation and subsequent acquisition of a free-induction decay. Thereby it is possible to monitor the uptake of xenon-129 by lung tissue and extract physiological parameters of pulmonary gas exchange. In the current studies, the delay time was instead held at a constant value, which permitted observation of xenon-129 gas uptake as a function of breath-hold time. CSSR studies were performed in 13 subjects (10 healthy, 2 chronic obstructive pulmonary disease [COPD], 1 second-hand smoke exposure), holding their breath at total lung capacity. The areas of the tissue/plasma and the red-blood-cell peaks in healthy subjects varied by an average of 1.7±0.7% and 15.1±3.8%, respectively, during the cardiac cycle. In 2 subjects with COPD these peak pulsations were not detectable during at least part of the measurement period. CSSR spectroscopy is sufficiently sensitive to detect oscillations in the xenon-129 gas-uptake rate associated with the cardiac cycle.

Assessment of lung function in asthma and COPD using hyperpolarized 129Xe chemical shift saturation recovery spectroscopy and dissolved-phase MRI.

Magnetic-resonance spectroscopy and imaging using hyperpolarized xenon-129 show great potential for evaluation of the most important function of the human lung -- gas exchange. In particular, chemical shift saturation recovery (CSSR) xenon-129 spectroscopy provides important physiological information for the lung as a whole by characterizing the dynamic process of gas exchange, while dissolved-phase (DP) xenon-129 imaging captures the time-averaged regional distribution of gas uptake by lung tissue and blood. Herein, we present recent advances in assessing lung function using CSSR spectroscopy and DP imaging in a total of 45 subjects (23 healthy, 13 chronic obstructive pulmonary disease (COPD) and 9 asthma). From CSSR acquisitions, the COPD subjects showed red blood cell to tissue-plasma (RBC-to-TP) ratios below the average for the healthy subjects (p < 0.001), but significantly higher septal wall thicknesses as compared with the healthy subjects (p < 0.005); the RBC-to-TP ratios for the asthmatic subjects fell outside two standard deviations (either higher or lower) from the mean of the healthy subjects, although there was no statistically significant difference for the average ratio of the study group as a whole. Similarly, from the 3D DP imaging acquisitions, we found that all the ratios (TP to gas phase (GP), RBC to GP, RBC to TP) measured in the COPD subjects were lower than those from the healthy subjects (p < 0.05 for all ratios), while these ratios in the asthmatic subjects differed considerably between subjects. Despite having been performed at different lung inflation levels, the RBC-to-TP ratios measured by CSSR and 3D DP imaging were fairly consistent with each other, with a mean difference of 0.037 (ratios from 3D DP imaging larger). In ten subjects the RBC-to-GP ratios obtained from the 3D DP imaging acquisitions were also highly correlated with their diffusing capacity of the lung for carbon monoxide per unit alveolar volume ratios measured by pulmonary function testing (R = 0.91).

Experimental validation of the hyperpolarized 129 Xe chemical shift saturation recovery technique in healthy volunteers and subjects with interstitial lung disease.

To assess the sensitivity of the hyperpolarized 129 Xe chemical shift saturation recovery (CSSR) technique for noninvasive quantification of changes to lung microstructure and function in idiopathic pulmonary fibrosis (IPF) and systemic sclerosis (SSc). Ten healthy volunteers, four subjects with SSc and four with IPF were scanned at 1.5 T. A CSSR pulse sequence was implemented using binomial-composite radiofrequency pulses to monitor 129 Xe magnetization in tissues and blood plasma (T/P) and red blood cells (RBCs). The dynamics of 129 Xe uptake into these compartments were fitted with three existing analytical models of gas diffusion to extract parameters of lung physiology. These parameters were quantitatively compared between models. Uptake of xenon into the pulmonary capillaries was impaired in subjects with IPF and SSc. Statistically significant septal thickening was measured by 129 Xe CSSR in IPF patients. Preliminary data suggests age-dependent alterations to septal thickness in healthy volunteers. These findings were reproduced using each of the literature models. CSSR-derived parameters were compared with gold-standard indicators of pulmonary function; diffusing capacity of carbon monoxide and pulmonary transit-time. CSSR with hyperpolarized 129 Xe is sensitive to pathology-induced degradation of lung structure/function and shows promise for quantification of disease severity and monitoring treatment response. Magn Reson Med 74:196-207, 2015. © 2014 Wiley Periodicals, Inc.

Quantification of human lung structure and physiology using hyperpolarized 129Xe

To present in vivo, human validation of a previously proposed method to measure key pulmonary parameters related to lung microstructure and physiology. Some parameters, such as blood-air barrier thickness, cannot be measured readily by any other noninvasive modality. Healthy volunteers (n = 12) were studied in 1.5T and 3T whole body human scanners using hyperpolarized xenon. Xenon uptake by lung parenchyma and blood was measured using a chemical shift saturation recovery sequence. Both dissolved-xenon peaks at 197 ppm and 217-218 ppm were fitted against a model of xenon exchange (MOXE) as functions of exchange time. Parameters related to lung function and structure can be obtained by fitting to this model. The following results were obtained from xenon uptake (averaged over all healthy volunteers): surface-area-to-volume ratio = 210 ± 50 cm(-1) ; total septal wall thickness = 9.2 ± 6.5 μm; blood-air barrier thickness = 1.0 ± 0.3 μm; hematocrit = 27 ± 4%; pulmonary capillary blood transit time = 1.3 ± 0.3 s, in good agreement with literature values from invasive experiments. More detailed fitting results are listed in the text. The initial in vivo human results demonstrate that our proposed methods can be used to noninvasively determine lung physiology by simultaneous quantification of a few important pulmonary parameters. This method is highly promising to become a versatile screening method for lung diseases.

Noninvasive detection of pulmonary tissue destruction in a mouse model of emphysema using hyperpolarized 129Xe MRS under spontaneous respiration

In the present study, a chemical shift saturation recovery method in hyperpolarized (129)Xe MR spectroscopy measurements was applied to two groups of spontaneously breathing mice, an elastase-induced emphysema model and a control group. Parameters detected were those related to lung structures and functions, such as alveolar septal thickness, h, the ratio of the alveolar septal volume relative to gas space volume, V(s)/V(a), and the transit time of blood through the gas exchange region, τ. To investigate the potential of these parameters as biomarkers, an attempt was made to detect physiologic changes in the lungs of elastase-treated mice. Our results showed that V(s)/V(a) was significantly reduced in elastase-treated mice, reflecting emphysema-like destruction of the alveolar wall. Compared with histologic results, this degree of reduction was shown to reflect the severity of wall destruction. On the other hand, significant changes in other parameters, h and τ, were not shown. This study is the first application of hyperpolarized (129)Xe MR spectroscopy to a mouse model of emphysema and shows that the V(s)/V(a) volume ratio is an effective biomarker for emphysema that could become useful in drug research and development through noninvasive detection of pathologic changes in small rodents.