129Xe Magnetic Resonance Research Articles

Quantitative 129Xe MRI detects early impairment of gas-exchange in a rat model of pulmonary hypertension

Hyperpolarized 129Xe magnetic resonance imaging (MRI) is capable of regional mapping of pulmonary gas-exchange and has found application in a wide range of pulmonary disorders in humans and animal model analogs. This study is the first application of 129Xe MRI to the monocrotaline rat model of pulmonary hypertension. Such models of preclinical pulmonary hypertension, a disease of the pulmonary vasculature that results in right heart failure and death, are usually assessed with invasive procedures such as right heart catheterization and histopathology. The work here adapted from protocols from clinical 129Xe MRI to enable preclinical imaging of rat models of pulmonary hypertension on a Bruker 7 T scanner. 129Xe spectroscopy and gas-exchange imaging showed reduced 129Xe uptake by red blood cells early in the progression of the disease, and at a later time point was accompanied by increased uptake by barrier tissues, edema, and ventilation defects—all of which are salient characteristics of the monocrotaline model. Imaging results were validated by H&E histology, which showed evidence of remodeling of arterioles. This proof-of-concept study has demonstrated that hyperpolarized 129Xe MRI has strong potential to be used to non-invasively monitor the progression of pulmonary hypertension in preclinical models and potentially to also assess response to therapy.

Diverse cardiopulmonary diseases are associated with distinct xenon magnetic resonance imaging signatures.

As an increasing number of patients exhibit concomitant cardiac and pulmonary disease, limitations of standard diagnostic criteria are more frequently encountered. Here, we apply noninvasive 129Xe magnetic resonance imaging (MRI) and spectroscopy to identify patterns of regional gas transfer impairment and haemodynamics that are uniquely associated with chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), left heart failure (LHF) and pulmonary arterial hypertension (PAH). Healthy volunteers (n=23) and patients with COPD (n=8), IPF (n=12), LHF (n=6) and PAH (n=10) underwent 129Xe gas transfer imaging and dynamic spectroscopy. For each patient, three-dimensional maps were generated to depict ventilation, barrier uptake (129Xe dissolved in interstitial tissue) and red blood cell (RBC) transfer (129Xe dissolved in RBCs). Dynamic 129Xe spectroscopy was used to quantify cardiogenic oscillations in the RBC signal amplitude and frequency shift. Compared with healthy volunteers, all patient groups exhibited decreased ventilation and RBC transfer (both p≤0.01). Patients with COPD demonstrated more ventilation and barrier defects compared with all other groups (both p≤0.02). In contrast, IPF patients demonstrated elevated barrier uptake compared with all other groups (p≤0.007), and increased RBC amplitude and shift oscillations compared with healthy volunteers (p=0.007 and p≤0.01, respectively). Patients with COPD and PAH both exhibited decreased RBC amplitude oscillations (p=0.02 and p=0.005, respectively) compared with healthy volunteers. LHF was distinguishable from PAH by enhanced RBC amplitude oscillations (p=0.01). COPD, IPF, LHF and PAH each exhibit unique 129Xe MRI and dynamic spectroscopy signatures. These metrics may help with diagnostic challenges in cardiopulmonary disease and increase understanding of regional lung function and haemodynamics at the alveolar-capillary level.

Quantification of Ventilation and Gas Uptake in Free-Breathing Mice With Hyperpolarized 129Xe MRI.

Hyperpolarized 129Xe magnetic resonance imaging is a powerful modality capable of assessing lung structure and function. While it has shown promise as a clinical tool for the longitudinal assessment of lung function, its utility as an investigative tool for animal models of pulmonary diseases is limited by the necessity of invasive intubation and mechanical ventilation procedures. In this paper, we overcame this limitation by developing a gas delivery system and implementing a set of imaging schemes to acquire high-resolution gas- and dissolved-phase images in free-breathing mice. Gradient echo pulse sequences were used to acquire both high- and low-resolution gas-phase images, and regional fractional ventilation was quantified by comparing signal buildup among low-resolution gas-phase images acquired at two flip-angles. Dissolved-phase images were acquired using both ultra-short echo time and chemical shift imaging sequences with discrete sets of flip-angle/repetition time combinations to visualize gas uptake and distribution throughout the body. Spectral features distinct to various anatomical regions were identified in images acquired using the latter sequence and were used for the quantification of gas arrival times for respective compartments.

A two-center analysis of hyperpolarized 129Xe lung MRI in stable pediatric cystic fibrosis: Potential as a biomarker for multi-site trials

BackgroundThe ventilation defect percent (VDP), measured from hyperpolarized (HP) 129Xe magnetic resonance imaging (MRI), is sensitive to functional changes in cystic fibrosis (CF) lung disease. The purpose of this study was to measure and compare VDP from HP 129Xe MRI acquired at two institutions in stable pediatric CF subjects with preserved lung function. MethodsThis retrospective analysis included 26 participants from two institutions (18 CF, 8 healthy, age range 10–17). Pulmonary function tests, N2 multiple breath washout (to measure lung clearance index, LCI), and HP 129Xe MRI were performed. VDP measurements were compared between two trained analysts using mean-anchored linear binning. Correlations were investigated for VDP compared to the forced expiratory volume in one second (FEV1) and LCI. ResultsVDP measurements agreed for the two analysts with an intraclass correlation coefficient of 0.99. In the combined dataset, VDP measured by Analyst 1 was 5.96 ± 1.82% and 15.96 ± 6.76% for the healthy and CF groups, respectively (p = .0004). Analyst 2 showed similar differences between healthy and CF (p = .0003). VDP measured by either analyst was shown to correlate with FEV1 (R2 = 0.33, p = .003; and R2 = 0.26, p = .009 for Analysts 1 and 2, respectively) and LCI (R2 = 0.76, p < .0001; and R2 = 0.77, p < .0001 for Analysts 1 and 2, respectively). ConclusionHP 129Xe MRI provides a robust measurement of ventilation heterogeneity in stable pediatric CF subjects at two sites. Since measurements performed at two sites yielded similar VDP values with near-identical values between different analysts, implementation of the technique in multi-center trials in CF appears feasible.

Xenon-129 MRI detects ventilation deficits in paediatric stem cell transplant patients unable to perform spirometry.

Early detection of pulmonary morbidity following haematopoietic stem cell transplantation (HSCT) remains an important challenge for intervention, primarily due to the insensitivity of spirometry to early change, and in paediatrics, patient compliance provides additional challenges. Regional lung ventilation abnormalities in paediatric HSCT patients were quantified using hyperpolarised xenon-129 (129Xe) magnetic resonance imaging (MRI) and compared to spirometry. Medically stable, paediatric allogeneic HSCT patients (n=23, ages 6-16 years) underwent an outpatient MRI scan where regional ventilation was quantified with a breath-hold of hyperpolarised 129Xe gas. Ventilation deficits, regions of the lung that ventilate poorly due to obstruction, were quantified as a ventilation defect percentage (VDP) and compared to forced expiratory volume in 1 s (FEV1), FEV1/forced vital capacity (FVC) ratio, and forced expiratory flow at 25-75% of FVC (FEF25-75%) from spirometry using linear regression. The mean±sd 129Xe VDP was 10.5±9.4% (range 2.6-41.4%). 129Xe VDP correlated with FEV1, FEV1/FVC ratio and FEF25-75% (p≤0.02 for all comparisons). Ventilation deficits were detected in patients with normal spirometry (i.e. FEV1 >80%), supporting the sensitivity of 129Xe MRI to early obstruction reported in other pulmonary conditions. Seven (30%) patients could not perform spirometry, yet ventilation deficits were observed in five of these patients, detecting abnormalities that otherwise may have gone undetected and untreated until advanced. Lung ventilation deficits were detected using hyperpolarised 129Xe gas MRI in asymptomatic paediatric HSCT patients and in a subgroup who were unable to perform reliable spirometry. 129Xe MRI provides a reliable imaging-based assessment of pulmonary involvement in this potentially difficult to diagnose paediatric population.

New Developments in Imaging Idiopathic Pulmonary Fibrosis With Hyperpolarized Xenon Magnetic Resonance Imaging.

Idiopathic pulmonary fibrosis (IPF) is a progressive pulmonary disease that is ultimately fatal. Although the diagnosis of IPF has been revolutionized by high-resolution computed tomography, this imaging modality still exhibits significant limitations, particularly in assessing disease progression and therapy response. The need for noninvasive regional assessment has become more acute in light of recently introduced novel therapies and numerous others in the pipeline. Thus, it will likely be valuable to complement 3-dimensional imaging of lung structure with 3-dimensional regional assessment of function. This challenge is well addressed by hyperpolarized (HP) Xe magnetic resonance imaging (MRI), exploiting the unique properties of this inert gas to image its distribution, not only in the airspaces, but also in the interstitial barrier tissues and red blood cells. This single-breath imaging exam could ultimately become the ideal, noninvasive tool to assess pulmonary gas-exchange impairment in IPF. This review article will detail the evolution of HP Xe MRI from its early development to its current state as a clinical research platform. It will detail the key imaging biomarkers that can be generated from the Xe MRI examination, as well as their potential in IPF for diagnosis, prognosis, and assessment of therapeutic response. We conclude by discussing the types of studies that must be performed for HP Xe MRI to be incorporated into the IPF clinical algorithm and begin to positively impact IPF disease diagnosis and management.

Hyperpolarised 129Xe magnetic resonance imaging to monitor treatment response in children with cystic fibrosis.

Pulmonary magnetic resonance imaging using hyperpolarised 129Xe gas (XeMRI) can quantify ventilation inhomogeneity by measuring the percentage of unventilated lung volume (ventilation defect per cent (VDP)). While previous studies have demonstrated its sensitivity for detecting early cystic fibrosis (CF) lung disease, the utility of XeMRI to monitor response to therapy in CF is unknown. The aim of this study was to assess the ability of XeMRI to capture treatment response in paediatric CF patients undergoing inpatient antibiotic treatment for a pulmonary exacerbation.15 CF patients aged 8-18 years underwent XeMRI, spirometry, plethysmography and multiple-breath nitrogen washout at the beginning and end of inpatient treatment of a pulmonary exacerbation. VDP was calculated from XeMRI images obtained during a static breath hold using semi-automated k-means clustering and linear binning approaches.XeMRI was well tolerated. VDP, lung clearance index and the forced expiratory volume in 1 s all improved with treatment; however, response was not uniform in individual patients. Of all outcome measures, VDP showed the largest relative improvement (-42.1%, 95% CI -52.1--31.9%, p<0.0001).These data support further investigation of XeMRI as a tool to capture treatment response in CF lung disease.

Stabilization and Reversibility of Early Lung Abnormalities Post-HSCT Detected with Serial Hyperpolarized 129Xe MRI

Introduction Early detection of lung abnormalities following hematopoietic stem cell transplant (HSCT) remains a challenge primarily due to the insensitivity of spirometry, the current clinical gold standard, to mild changes. This insensitivity carries through to assessing treatment response and personalizing pulmonary interventions for HSCT patients. Hyperpolarized 129Xe magnetic resonance imaging (MRI) has been demonstrated to be sensitive to early regional airway obstruction, and as a modality free of ionizing radiation, we hypothesized that serial 129Xe MRI could gauge treatment response in pediatric HSCT patients. Methods Four pediatric HSCT patients were recruited for serial 129Xe MRI. Xenon gas (86% 129Xe) was hyperpolarized to ∼20% using a commercial device (Polarean, Durham, NC). 129Xe ventilation images were acquired during a breath-hold (≤ 16 seconds) of up to 1 L Xe on a Philips 3T Achieva MR scanner. 129Xe ventilation defects, regions of relatively lower 129Xe MR signal due to airway obstruction, were quantified using a threshold of Results Figure 1 describes the cohort and clinical courses for each subject. Importantly, Subjects 1 & 2 were first imaged at approximately one-year post-HSCT and both had a diagnosis of multi-system GVHD including established lung involvement at the time of the first 129Xe MRI. Subjects 3 & 4 were imaged within the first year post-HSCT and had signs of early lung involvement. Figure 2 plots the trajectories of 129Xe VDP versus days post-HSCT for this cohort, and at the baseline, 129Xe VDP was elevated for all HSCT subjects (median 19.3%) relative to historical values for age-matched control subjects (∼5%). For the subjects with established lung involvement (1 & 2), stabilization of pulmonary function and 129Xe MRI was seen after extensive immunotherapy. For Subjects 3 and 4 with early lung involvement, improvements in 129Xe VDP were seen with relatively mild intervention of FAM therapy with and without steroids. Figure 3 demonstrates this reversibility of focal 129Xe ventilation deficits in Subject 4. Conclusions 129Xe MRI provides a sensitive means of quantifying early regional lung disease and treatment response following HSCT. These results suggest the potential reversibility of ventilation abnormalities and mild lung involvement with early detection and intervention, though larger studies are needed. 129Xe MRI may be repeated serially to individualize treatment strategies, such as the appropriate escalation or tapering of immunosuppression or to assess the effectiveness of new therapies. Furthermore, the spatial resolution of 129Xe MRI may be leveraged to target invasive procedures like bronchoscopy, where regions of persistent ventilation deficit could be identified and targeted for evaluation.

Abstract 16918: Non-Invasive Diagnosis of Pulmonary Vascular Disease Using Inhaled 129-XenonMRI

Introduction: Pulmonary arterial hypertension (PAH) carries significant morbidity and mortality. Its diagnosis requires meeting specific hemodynamic and clinical criteria and can be particularly challenging in patients with concomitant heart or lung disease. Hyperpolarized 129 Xenon ( 129 Xe) magnetic resonance imaging and dynamic spectroscopy may overcome these challenges, providing a non-invasive new tool to diagnose and monitor PAH. This is based on its unique cardiogenic oscillations reflected in the 129 Xe spectrum as it transfers to red blood cells (RBCs, Figure). Hypothesis: We hypothesized that changes in the RBC 129 Xe spectroscopic parameters will discriminate PAH from healthy volunteers, patients with left heart failure, idiopathic pulmonary fibrosis (IPF) or chronic obstructive pulmonary disease (COPD). Methods: 129 Xe spectra were dynamically acquired every 20 milliseconds in all subjects. At each time point, the amplitude, chemical shift, linewidth, and phase of the 129 Xe-RBC resonance was calculated. Cardiogenic oscillations in these spectral parameters were compared using the Kruskal-Wallis test, followed by pairwise comparisons with the Wilcoxon rank sum test. Results: A total of 14 healthy volunteers, 10 subjects with PAH, 5 subjects with left heart failure, 9 subjects with IPF, and 7 subjects with COPD underwent 129 Xe spectroscopy. In patients with PAH, RBC amplitude oscillations were significantly reduced compared to those with IPF (p &lt; 0.001) or healthy subjects (p = 0.0064, Figure). Oscillations in chemical shift and phase were only observed in IPF patients. Conclusions: 129 Xenon dynamic spectroscopy produces different RBC signatures in patients with PAH, IPF, and healthy volunteers. 129 Xe uniquely probes the alveolar-capillary interface and can thus detect the effect of arterial lesions on capillary blood volume oscillations.

Protein Nanostructures Produce Self-Adjusting Hyperpolarized Magnetic Resonance Imaging Contrast through Physical Gas Partitioning

Signal amplification strategies are critical for overcoming the intrinsically poor sensitivity of nuclear magnetic resonance (NMR) reporters in noninvasive molecular detection. A mechanism widely used for signal enhancement is chemical exchange saturation transfer (CEST) of nuclei between a dilute sensing pool and an abundant detection pool. However, the dependence of CEST amplification on the relative size of these spin pools confounds quantitative molecular detection with a larger detection pool typically making saturation transfer less efficient. Here we show that a recently discovered class of genetically encoded nanoscale reporters for 129Xe magnetic resonance overcomes this fundamental limitation through an elastic binding capacity for NMR-active nuclei. This approach pairs high signal amplification from hyperpolarized spins with ideal, self-adjusting saturation transfer behavior as the overall spin ensemble changes in size. These reporters are based on gas vesicles, i.e., microbe-derived, gas-filled protein nanostructures. We show that the xenon fraction that partitions into gas vesicles follows the ideal gas law, allowing the signal transfer under hyperpolarized xenon chemical exchange saturation transfer (Hyper-CEST) imaging to scale linearly with the total xenon ensemble. This conceptually distinct elastic response allows the production of quantitative signal contrast that is robust to variability in the concentration of xenon, enabling virtually unlimited improvement in absolute contrast with increased xenon delivery, and establishing a unique principle of operation for contrast agent development in emerging biochemical and in vivo applications of hyperpolarized NMR and magnetic resonance imaging.

Hyperpolarized Gas Magnetic Resonance Imaging of Pediatric Cystic Fibrosis Lung Disease

Conventional pulmonary function tests appear normal in early cystic fibrosis (CF) lung disease. Therefore, new diagnostic approaches are required that can detect CF lung disease in children and monitor treatment response. Hyperpolarized (HP) gas (129Xe and 3He) magnetic resonance imaging (MRI) is a powerful, emergent tool for mapping regional lung function and may be well suited for studying pediatric CF. HP gas MRI is well tolerated, reproducible, and it can be performed longitudinally without the need for ionizing radiation. In particular, quantification of the distribution of ventilation, or ventilation defect percent (VDP), has been shown to be a sensitive indicator of CF lung disease and correlates well with pulmonary function tests. This article presents the current state of CF diagnosis and treatment and describes the potential role of HP gas MRI for detection of early CF lung disease and following the effects of interventions. The typical HP gas imaging workflow is described, along with a discussion of image analysis to calculate VDP, dosing considerations, and the reproducibility of VDP. The potential use of VDP as an outcome measure in CF is discussed, by considering the correlation with pulmonary function measures, preliminary interventional studies, and case studies involving longitudinal imaging and pulmonary exacerbations. Finally, emerging HP gas imaging techniques such as multiple breath washout imaging are introduced, followed by a discussion of future directions. Overall, HP gas MRI biomarkers are expected to provide sensitive outcome measures that can be used in disease surveillance as well as interventional studies involving novel CF therapies.

Inhaled Xenon Washout as a Biomarker of Alzheimer's Disease.

Biomarkers have the potential to aid in the study of Alzheimer’s disease (AD); unfortunately, AD biomarker values often have a high degree of overlap between healthy and AD individuals. This study investigates the potential utility of a series of novel AD biomarkers, the sixty second 129Xe retention time, and the xenon washout parameter, based on the washout of hyperpolarized 129Xe from the brain of AD participants following inhalation. The xenon washout parameter is influenced by cerebral perfusion, T1 relaxation of xenon, and the xenon partition coefficient, all factors influenced by AD. Participants with AD (n = 4) and healthy volunteers (n = 4) were imaged using hyperpolarized 129Xe magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) to determine the amount of retained xenon in the brain. At 60 s after the breath hold, AD patients retained significantly higher amounts of 129Xe compared to healthy controls. Data was fit to a pharmacokinetic model and the xenon washout parameter was extracted. Xenon washout in white and grey matter occurs at a slower rate in Alzheimer’s participants (129Xe half-life time of 42 s and 43 s, respectively) relative to controls (20 s and 16 s, respectively). Following larger scale clinical trials for validation, the xenon washout parameter has the potential to become a useful biomarker for the support of AD diagnosis.

Human Pulmonary Hyperpolarized 129Xe MRI: a Preliminary Study**Supported by the National Natural Science Foundation of China under Grant Nos 81227902 and 81625011, the National Key Research and Development Program of China under Grant No 2016YFC1304702, and the Key Research Program of Frontier Sciences of CAS (QYZDY-SSW-SLH018).

We study the feasibility and safety of human lung hyperpolarized (HP) 129Xe magnetic resonance imaging (MRI). There is no significant change in physiological parameters before and after the examinations of all subjects. Compared with computed tomography, HP 129Xe MRI is sensitive to earlier and smaller ventilation defects. The distribution of the HP 129Xe MRI signal reflects the pulmonary compliance with the gravity gradient. This is the first application of HP 129Xe MRI ventilation imaging in China, and this technology is expected to provide more useful information for clinical practice.

Correlation of Regional Lung Ventilation and Gas Transfer to Red Blood Cells: Implications for Functional-Avoidance Radiation Therapy Planning

To investigate the degree to which lung ventilation and gas exchange are regionally correlated, using the emerging technology of hyperpolarized (HP)-129Xe magnetic resonance imaging (MRI). Hyperpolarized-129Xe MRI studies were performed on 17 institutional review board-approved human subjects, including 13 healthy volunteers, 1 emphysema patient, and 3 non-small cell lung cancer patients imaged before and approximately 11weeks after radiation therapy (RT). Subjects inhaled 1L of HP-129Xe mixture, followed by the acquisition of interleaved ventilation and gas exchange images, from which maps were obtained of the relative HP-129Xe distribution in three states: (1) gaseous, in lung airspaces; (2) dissolved interstitially, in alveolar barrier tissue; and (3) transferred to red blood cells (RBCs), in the capillary vasculature. The relative spatial distributions of HP-129Xe in airspaces (regional ventilation) and RBCs (regional gas transfer) were compared. Further, we investigated the degree to which ventilation and RBC transfer images identified similar functional regions of interest (ROIs) suitable for functionally guided RT. For the RT patients, both ventilation and RBC functional images were used to calculate differences in the lung dose-function histogram and functional effective uniform dose. The correlation of ventilation and RBC transfer was ρ=0.39±0.15 in healthy volunteers. For the RT patients, this correlation was ρ=0.53±0.02 before treatment and ρ=0.39±0.07 after treatment; for the emphysema patient it was ρ=0.24. Comparing functional ROIs, ventilation and RBC transfer demonstrated poor spatial agreement: Dice similarity coefficient=0.50±0.07 and 0.26±0.12 for the highest-33%- and highest-10%-function ROIs in healthy volunteers, and in RT patients (before treatment) these were 0.58±0.04 and 0.40±0.04. The average magnitude of the differences between RBC- and ventilation-derived functional effective uniform dose, fV20Gy, fV10Gy, and fV5Gy were 1.5±1.4Gy, 4.1%±3.8%, 5.0%±3.8%, and 5.3%±3.9%, respectively. Ventilation may not be an effective surrogate for true regional lung function for all patients.

Cyclodextrin-Based Pseudorotaxanes: Easily Conjugatable Scaffolds for Synthesizing Hyperpolarized Xenon-129 Magnetic Resonance Imaging Agents.

Hyperpolarized (HP) xenon-129 (Xe) magnetic resonance (MR) imaging has the potential to detect biological analytes with high sensitivity and high resolution when coupled with xenon-encapsulating molecular probes. Despite the development of numerous HP Xe probes, one of the challenges that has hampered the translation of these agents from in vitro demonstration to in vivo testing is the difficulty in synthesizing the Xe-encapsulating cage molecule. In this study, we demonstrate that a pseudorotaxane, based on a γ-cyclodextrin macrocycle, is easily synthesized in one step and is detectable using HyperCEST-enhanced 129Xe MR spectroscopy.

Brain Imaging Using Hyperpolarized 129Xe Magnetic Resonance Imaging.

Hyperpolarized (HP) 129Xe magnetic resonance imaging (MRI) is a novel iteration of traditional MRI that relies on detecting the spins of 1H. Since 129Xe is a gaseous signal source, it can be used for lung imaging. Additionally, 129Xe dissolves in the blood stream and can therefore be detectable in the brain parenchyma and vasculature. In this work, we provide detailed information on the protocols that we have developed to image 129Xe within the brains of both rodents and human subjects.

Assessment of pulmonary microstructural changes by hyperpolarized 129Xe diffusion-weighted imaging in an elastase-instilled rat model of emphysema.

The purpose of this study was to explore the feasibility of hyperpolarized 129Xe diffusion-weighted imaging (DWI) for the evaluation of pulmonary microstructural changes in the presence of pancreatic porcine elastase (PPE)-induced pulmonary emphysema rat model. Sixteen male Sprague-Dawley (SD) rats were randomly divided into two groups, the emphysema model group and control group. Experimental emphysematous models were made by instilling elastase into rat lungs of model group, the control group were instilled with isodose saline. Hyperpolarized 129Xe magnetic resonance imaging (MRI) and histology were performed in all 16 rats after 30 days. DWIs were performed on a Bruker 7.0 T micro MRI, and the apparent diffusion coefficients (ADCs) were measured in all rats. Mean linear intercepts (MLIs) of pulmonary alveoli were measured on histology. The statistical analyses were performed about the correlation between the mean ADC of hyperpolarized 129Xe in the whole lung and MLI of pulmonary histology metric. The pulmonary emphysematous model was successfully confirmed by the histology and all scans were also successful. The ADC value of 129Xe in the model group (0.0313±0.0005 cm2/s) was significantly increased compared with that of the control group (0.0288±0.0007 cm2/s, P<0.0001). Morphological differences such as MLI of pulmonary alveoli were observed between the two groups, the MLI of pulmonary alveoli in model group significantly increased (91±5 µm) than that of control group (50±3 µm, P<0.0001). Furthermore, the ADCs was moderately correlated with MLIs (r=0.724, P<0.01). These results indicate that 129Xe ADC value can quantitatively reflect the alveolar space enlargement and it is a promising biomarker for the detection of pulmonary emphysema.

Quantitative analysis of hyperpolarized 129 Xe gas transfer MRI.

Hyperpolarized 129 Xe magnetic resonance imaging (MRI) using Dixon-based decomposition enables single-breath imaging of 129 Xe in the airspaces, interstitial barrier tissues, and red blood cells (RBCs). However, methods to quantitatively visualize information from these images of pulmonary gas transfer are lacking. Here, we introduce a novel method to transform these data into quantitative maps of pulmonary ventilation, and 129 Xe gas transfer to barrier and RBC compartments. A total of 13 healthy subjects and 12 idiopathic pulmonary fibrosis (IPF) subjects underwent thoracic 1 H MRI and hyperpolarized 129 Xe MRI with one-point Dixon decomposition to obtain images of 129 Xe in airspaces, barrier and red blood cells (RBCs). 129 Xe images were processed into quantitative binning maps of all three compartments using thresholds based on the mean and standard deviations of distributions derived from the healthy reference cohort. Binning maps were analyzed to derive quantitative measures of ventilation, barrier uptake, and RBC transfer. This method was also used to illustrate different ventilation and gas transfer patterns in a patient with emphysema and one with pulmonary arterial hypertension (PAH). In the healthy reference cohort, the mean normalized signals were 0.51 ± 0.19 for ventilation, 4.9 ± 1.5 x 10-3 for barrier uptake and 2.6 ± 1.0 × 10-3 for RBC (transfer). In IPF patients, ventilation was similarly homogenous to healthy subjects, although shifted toward slightly lower values (0.43 ± 0.19). However, mean barrier uptake in IPF patients was nearly 2× higher than in healthy subjects, with 47% of voxels classified as high, compared to 3% in healthy controls. Moreover, in IPF, RBC transfer was reduced, mainly in the basal lung with 41% of voxels classified as low. In healthy volunteers, only 15% of RBC transfer was classified as low and these voxels were typically in the anterior, gravitationally nondependent lung. This study demonstrates a straightforward means to generate semiquantitative binning maps depicting 129 Xe ventilation and gas transfer to barrier and RBC compartments. These initial results suggest that the method could be valuable for characterizing both normal physiology and pathophysiology associated with a wide range of pulmonary disorders.

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.

Chronic Obstructive Pulmonary Disease: Lobar Analysis with Hyperpolarized 129Xe MR Imaging.

Purpose To compare lobar ventilation and apparent diffusion coefficient (ADC) values obtained with hyperpolarized xenon 129 (129Xe) magnetic resonance (MR) imaging to quantitative computed tomography (CT) metrics on a lobar basis and pulmonary function test (PFT) results on a whole-lung basis in patients with chronic obstructive pulmonary disease (COPD). Materials and Methods The study was approved by the National Research Ethics Service Committee; written informed consent was obtained from all patients. Twenty-two patients with COPD (Global Initiative for Chronic Obstructive Lung Disease stage II-IV) underwent hyperpolarized 129Xe MR imaging at 1.5 T, quantitative CT, and PFTs. Whole-lung and lobar 129Xe MR imaging parameters were obtained by using automated segmentation of multisection hyperpolarized 129Xe MR ventilation images and hyperpolarized 129Xe MR diffusion-weighted images after coregistration to CT scans. Whole-lung and lobar quantitative CT-derived metrics for emphysema and bronchial wall thickness were calculated. Pearson correlation coefficients were used to evaluate the relationship between imaging measures and PFT results. Results Percentage ventilated volume and average ADC at lobar 129Xe MR imaging showed correlation with percentage emphysema at lobar quantitative CT (r = -0.32, P < .001 and r = 0.75, P < .0001, respectively). The average ADC at whole-lung 129Xe MR imaging showed moderate correlation with PFT results (percentage predicted transfer factor of the lung for carbon monoxide [Tlco]: r = -0.61, P < .005) and percentage predicted functional residual capacity (r = 0.47, P < .05). Whole-lung quantitative CT percentage emphysema also showed statistically significant correlation with percentage predicted Tlco (r = -0.65, P < .005). Conclusion Lobar ventilation and ADC values obtained from hyperpolarized 129Xe MR imaging demonstrated correlation with quantitative CT percentage emphysema on a lobar basis and with PFT results on a whole-lung basis. © RSNA, 2016.