Lung morphometry with hyperpolarized 129Xe: Theoretical background

The ³He lung morphometry technique, based on MRI measurements of hyperpolarized ³He gas diffusion in lung airspaces, provides unique information on the lung microstructure at the alveolar level. In vivo 3D tomographic images of standard morphological parameters (airspace chord length, lung parenchyma surface‐to‐volume ratio, and number of alveoli per unit volume) can be generated from a rather short (several seconds) MRI scan. The technique is based on a theory of gas diffusion in lung acinar airways and experimental measurements of diffusion‐attenuated MRI signal. The present work aims at developing the theoretical background of a similar technique based on hyperpolarized ¹²⁹Xe gas. As the diffusion coefficient and gyromagnetic ratio of ¹²⁹Xe gas are substantially different from those of ³He gas, the specific details of the theory and experimental measurements with ¹²⁹Xe should be amended. We establish phenomenological relationships between acinar airway geometrical parameters and the diffusion‐attenuated MR signal for human and small animal lungs, both normal lungs and lungs with mild emphysema. Optimal diffusion times are shown to be about 5 ms for human and 1.3 ms for small animals. The expected uncertainties in measuring main morphometrical parameters of the lungs are estimated in the framework of Bayesian probability theory. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc.     

Hyperpolarized Xenon-129 gas-exchange imaging of lung microstructure: first case studies in subjects with obstructive lung disease

Purpose:

To develop and test a method to noninvasively assess the functional lung microstructure.

Materials and Methods:

The Multiple exchange time Xenon polarization Transfer Contrast technique (MXTC) encodes xenon gas‐exchange contrast at multiple delay times permitting two lung‐function parameters to be derived: (i) MXTC‐F, the long exchange‐time depolarization value, which is proportional to the tissue to alveolar‐volume ratio and (ii) MXTC‐S, the square root of the xenon exchange‐time constant, which characterizes thickness and composition of alveolar septa. Three healthy volunteers, one asthmatic, and two chronic obstructive pulmonary disease (COPD) (GOLD stage I and II) subjects were imaged with MXTC MRI. In a subset of subjects, hyperpolarized xenon‐129 ADC MRI and CT imaging were also performed.

Results:

The MXTC‐S parameter was found to be elevated in subjects with lung disease (P‐value = 0.018). In the MXTC‐F parameter map it was feasible to identify regional loss of functional tissue in a COPD patient. MXTC‐F maps showed excellent regional correlation with CT and ADC (P ≥ 0.90) in one COPD subject.

Conclusion:

The functional tissue‐density parameter MXTC‐F showed regional agreement with other imaging techniques. The newly developed parameter MXTC‐S, which characterizes the functional thickness of alveolar septa, has potential as a novel biomarker for regional parenchymal inflammation or thickening. J. Magn. Reson. Imaging 2011;33:1052–1062. © 2011 Wiley‐Liss, Inc.     

Characterization of diffusing capacity and perfusion of the rat lung in a lipopolysaccaride disease model using hyperpolarized 129Xe.

The ability to quantify pulmonary diffusing capacity and perfusion using dynamic hyperpolarized ¹²⁹Xe NMR spectroscopy is demonstrated. A model of alveolar gas exchange was developed, which, in conjunction with ¹²⁹Xe NMR, enables quantification of average alveolar wall thickness, pulmonary perfusion, capillary diffusion length, and mean transit time. The technique was employed to compare a group of naïve rats (n = 10) with a group of rats with acute inflammatory lung injury (n = 10), caused by instillation of lipopolysaccaride (LPS). The measured structural and perfusion‐related parameters were in agreement with reported values from studies using non‐NMR methods. Significant differences between the groups were found in total diffusion length (control 8.5 ± 0.5 μm, LPS 9.9 ± 0.6 μm, P < 0.001), in capillary diffusion length (control 2.9 ± 0.4 μm, LPS 3.9 ± 1.0 μm, P < 0.05), and in pulmonary hematocrit (control 0.55 ± 0.06, LPS 0.43 ± 0.08, P < 0.01), whereas no differences were observed in alveolar wall thickness, pulmonary perfusion, and mean transit time. These results demonstrate the ability of the method to distinguish two main aspects of lung function, namely, diffusing capacity and pulmonary perfusion. Magn Reson Med 50:1170–1179, 2003. © 2003 Wiley‐Liss, Inc.     

Diffusion‐weighted hyperpolarized 129Xe MRI in healthy volunteers and subjects with chronic obstructive pulmonary disease

Given its greater availability and lower cost, ¹²⁹Xe apparent diffusion coefficient (ADC) MRI offers an alternative to ³He ADC MRI. To demonstrate the feasibility of hyperpolarized ¹²⁹Xe ADC MRI, we present results from healthy volunteers (HV), chronic obstructive pulmonary disease (COPD) subjects, and age‐matched healthy controls (AMC). The mean parenchymal ADC was 0.036 ± 0.003 cm² sec^?1 for HV, 0.043 ± 0.006 cm² sec^?1 for AMC, and 0.056 ± 0.008 cm² sec^?1 for COPD subjects with emphysema. In healthy individuals, but not the COPD group, ADC decreased significantly in the anterior–posterior direction by ～22% (P = 0.006, AMC; 0.0059, HV), likely because of gravity‐induced tissue compression. The COPD group exhibited a significantly larger superior–inferior ADC reduction (～28%) than the healthy groups (～24%) (P = 0.00018, HV; P = 3.45 × 10^?5, AMC), consistent with smoking‐related tissue destruction in the superior lung. Superior–inferior gradients in healthy subjects may result from regional differences in xenon concentration. ADC was significantly correlated with pulmonary function tests (forced expiratory volume in 1 sec, r = ?0.77, P = 0.0002; forced expiratory volume in 1 sec/forced vital capacity, r = ?0.77, P = 0.0002; diffusing capacity of carbon monoxide in the lung/alveolar volume (V_A), r = ?0.77, P = 0.0002). In healthy groups, ADC increased with age by 0.0002 cm² sec^?1 year^?1 (r = 0.56, P = 0.02). This study shows that ¹²⁹Xe ADC MRI is clinically feasible, sufficiently sensitive to distinguish HV from subjects with emphysema, and detects age‐ and posture‐dependent changes. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

Clinical aspects of the apparent diffusion coefficient in 3He MRI: results in healthy volunteers and patients after lung transplantation

PURPOSE: To measure the apparent diffusion coefficient (ADC) after inhalation of hyperpolarized (3)He in healthy volunteers and lung transplant recipients, and demonstrate the gravity dependence of ADC values. MATERIALS AND METHODS: Six healthy volunteers, 10 patients after single-lung transplantation, and six patients after double-lung transplantation were examined at 1.5T during inspiration and expiration. The inhalation of 300 mL of hyperpolarized (3)He was performed with a computer-controlled delivery device. A two-dimensional fast low-angle shot (FLASH) sequence measured the (3)He diffusive gas movement. From these data the ADC was calculated. RESULTS: The mean ADC was 0.143 cm(2)/second in healthy individuals, 0.162 cm(2)/second in transplanted healthy lungs, and 0.173 cm(2)/second in rejected transplanted lungs, whereas it was 0.216 cm(2)/second in native fibrotic lungs and 0.239 cm(2)/second in emphysematous lungs. The difference in mean ADC values among healthy lungs, healthy transplanted lungs, and native diseased lungs was significant (P < 0.001). In inspiration the healthy volunteers showed higher ADC values in the anterior than in the posterior parts of the lungs. In expiration this gradient doubled. CONCLUSION: An anterior-posterior (A/P) gradient was found in inspiration and expiration in healthy lungs. Healthy, transplanted, and native diseased lungs had significantly different mean ADC values. From our preliminary results, (3)He MRI appears to be sensitive for detecting areas of abnormal ventilation in transplanted lungs.