Hyperpolarized 129Xe Magnetic Resonance Imaging Research Articles

Three-Dimensional Phase Resolved Functional Lung Magnetic Resonance Imaging.

Pulmonary magnetic resonance imaging (MRI) offers a variety of radiation-free techniques tailored to assess regional lung ventilation or its surrogates. These techniques encompass direct measurements, exemplified by hyperpolarized gas MRI and fluorinated gas MRI, as well as indirect measurements facilitated by oxygen-enhanced MRI and proton-based Fourier decomposition (FD) MRI. In recent times, there has been substantial progress in the field of FD MRI, which involved improving spatial/temporal resolution, refining sequence design and postprocessing, and developing a comprehensive whole-lung approach. The two-dimensional (2D) phase-resolved functional lung (PREFUL) MRI stands out as an FD-based approach developed for the comprehensive assessment of regional ventilation and perfusion dynamics, all within a single MR acquisition. Recently, a new advancement has been made with the development of 3D PREFUL to assess dynamic ventilation of the entire lung using 8 min exam with a self-gated sequence. The 3D PREFUL acquisition involves employing a stack-of-stars spoiled-gradient-echo sequence with a golden angle increment. Following the compressed sensing image reconstruction of approximately 40 breathing phases, all the reconstructed respiratory-resolved images undergo registration onto a fixed breathing phase. Subsequently, the ventilation parameters are extracted from the registered images. In a study cohort comprising healthy volunteers and patients with chronic obstructive pulmonary disease, the 3D PREFUL ventilation parameters demonstrated strong correlations with measurements obtained from pulmonary function tests. Additionally, the interscan repeatability of the 3D PREFUL technique was deemed to be acceptable, indicating its reliability for repeated assessments of the same individuals. In summary, 3D PREFUL ventilation MRI provides a whole lung coverage and captures ventilation dynamics with enhanced spatial resolution compared to 2D PREFUL. 3D PREFUL technique offers a cost-effective alternative to hyperpolarized 129Xe MRI, making it an attractive option for patient-friendly evaluation of pulmonary ventilation.

Hyperpolarized 129Xe Atoms Sense the Presence of Drug Molecules in Nanohosts Revealed by Magnetic Resonance Imaging.

Assessing the effectiveness of nanomedicines involves evaluating the drug content at the target site. Currently, most research focuses on monitoring the signal responses from loaded drugs, neglecting the changes caused by the nanohosts. Here, we propose a strategy to quantitatively evaluate the content of loaded drugs by detecting the signal variations resulting from the alterations in the microenvironment of the nanohosts. Specifically, hyperpolarized (HP) 129Xe atoms are employed as probes to sense the nanohosts' environment and generate a specific magnetic resonance (MR) signal that indicates their accessibility. The introduction of drugs reduces the available space in the nanohosts, leading to a crowded microenvironment that hinders the access of the 129Xe atoms. By employing 129Xe atoms as a signal source to detect the alterations in the microenvironment, we constructed a three-dimensional (3D) map that indicated the concentration of the nanohosts and established a linear relationship to quantitatively measure the drug content within the nanohosts based on the corresponding MR signals. Using the developed strategy, we successfully quantified the uptake of the nanohosts and drugs in living cells through HP 129Xe MR imaging. Overall, the proposed HP 129Xe atom-sensing approach can be used to monitor alterations in the microenvironment of nanohosts induced by loaded drugs and provides a new perspective for the quantitative evaluation of drug presence in various nanomedicines.

R3-Noria-methanesulfonate: A Molecular Cage with Superior Hyperpolarized Xenon-129 MRI Contrast.

Hyperpolarized (HP) xenon-129 (129Xe) magnetic resonance imaging (MRI) has the potential to be used as a molecular imaging modality. For this purpose, numerous supramolecular cages have been developed and evaluated in the past. Herein, we report a novel and unique macrocycle that can be successfully utilized for xenon MRI, the resorcinarene trimer methanesulfonate (R3-Noria-MeSO3H). This molecule is capable of two different contrast mechanisms for xenon-MRI, resulting from an increase in the effective spin-spin relaxation and hyperpolarized chemical exchange saturation transfer (HyperCEST). We have demonstrated a superior negative contrast caused by R3-Noria-MeSO3H on HP 129Xe MRI at 3.0 T as well as HyperCEST imaging of the studied macrocycle. Additionally, we have found that the complex aggregation behaviors of R3-Noria-methanesulfonate and its impact on xenon-129 relaxivity are an area for future study.

Hyperpolarized 129Xe MRI at low field: Current status and future directions

Magnetic Resonance Imaging (MRI) is dictated by the magnetization of the sample, and is thus a low-sensitivity imaging method. Inhalation of hyperpolarized (HP) noble gases, such as helium–3 and xenon-129, is a non-invasive, radiation-risk free imaging technique permitting high resolution imaging of the lungs and pulmonary functions, such as the lung microstructure, diffusion, perfusion, gas exchange, and dynamic ventilation. Instead of increasing the magnetic field strength, the higher spin polarization achievable from this method results in significantly higher net MR signal independent of tissue/water concentration. Moreover, the significantly longer apparent transverse relaxation time T2* of these HP gases at low magnetic field strengths results in fewer necessary radiofrequency (RF) pulses, permitting larger flip angles; this allows for high-sensitivity imaging of in vivo animal and human lungs at conventionally low (<0.5 T) field strengths and suggests that the low field regime is optimal for pulmonary MRI using hyperpolarized gases.In this review, theory on the common spin-exchange optical-pumping method of hyperpolarization and the field dependence of the MR signal of HP gases are presented, in the context of human lung imaging. The current state-of-the-art is explored, with emphasis on both MRI hardware (low field scanners, RF coils, and polarizers) and image acquisition techniques (pulse sequences) advancements. Common challenges surrounding imaging of HP gases and possible solutions are discussed, and the future of low field hyperpolarized gas MRI is posed as being a clinically-accessible and versatile imaging method, circumventing the siting restrictions of conventional high field scanners and bringing point-of-care pulmonary imaging to global facilities.

Novel Approaches to Imaging the Pulmonary Vasculature and Right Heart.

There is an increased appreciation for the importance of the right heart and pulmonary circulation in several disease states across the spectrum of pulmonary hypertension and left heart failure. However, assessment of the structure and function of the right heart and pulmonary circulation can be challenging, due to the complex geometry of the right ventricle, comorbid pulmonary airways and parenchymal disease, and the overlap of hemodynamic abnormalities with left heart failure. Several new and evolving imaging modalities interrogate the right heart and pulmonary circulation with greater diagnostic precision. Echocardiographic approaches such as speckle-tracking and 3-dimensional imaging provide detailed assessments of regional systolic and diastolic function and volumetric assessments. Magnetic resonance approaches can provide high-resolution views of cardiac structure/function, tissue characterization, and perfusion through the pulmonary vasculature. Molecular imaging with positron emission tomography allows an assessment of specific pathobiologically relevant targets in the right heart and pulmonary circulation. Machine learning analysis of high-resolution computed tomographic lung scans permits quantitative morphometry of the lung circulation without intravenous contrast. Inhaled magnetic resonance imaging probes, such as hyperpolarized 129Xe magnetic resonance imaging, report on pulmonary gas exchange and pulmonary capillary hemodynamics. These approaches provide important information on right ventricular structure and function along with perfusion through the pulmonary circulation. At this time, the majority of these developing technologies have yet to be clinically validated, with few studies demonstrating the utility of these imaging biomarkers for diagnosis or monitoring disease. These technologies hold promise for earlier diagnosis and noninvasive monitoring of right heart failure and pulmonary hypertension that will aid in preclinical studies, enhance patient selection and provide surrogate end points in clinical trials, and ultimately improve bedside care.

Hyperpolarized 129Xe Magnetic Resonance Imaging for Functional Avoidance Treatment Planning in Thoracic Radiation Therapy: A Comparison of Ventilation- and Gas Exchange-Guided Treatment Plans

PurposeTo present a methodology to use pulmonary gas exchange maps to guide functional avoidance treatment planning in radiation therapy (RT) and evaluate its efficacy compared with ventilation-guided treatment planning. Methods and MaterialsBefore receiving conventional RT for non-small cell lung cancer, 11 patients underwent hyperpolarized 129Xe gas exchange magnetic resonance imaging to map the distribution of xenon in its gas phase (ventilation) and transiently bound to red blood cells in the alveolar capillaries (gas exchange). Both ventilation and gas exchange maps were independently used to guide development of new functional avoidance treatment plans for every patient, while adhering to institutional dose-volume constraints for normal tissues and target coverage. Furthermore, dose-volume histogram (DVH)–based reoptimizations of the clinical plan, with reductions in mean lung dose (MLD) equal to the functional avoidance plans, were created to serve as the control group. To evaluate each plan (regardless of type), gas exchange maps, representing end-to-end lung function, were used to calculate gas exchange-weighted MLD (fMLD), gas exchange-weighted volume receiving ≥20 Gy (fV20), and mean dose in the highest gas exchanging 33% and 50% volumes of lung (MLD-f33% and MLD-f50%). Using each clinically approved plan as a baseline, the reductions in functional metrics were compared for ventilation-optimization, gas exchange optimization, and DVH-based reoptimization. Statistical significance was determined using the Freidman test, with subsequent subdivision when indicated by P values less than .10 and post hoc testing with Wilcoxon signed rank tests to determine significant differences (P < .05). Toxicity modeling was performed using an established function-based model to estimate clinical significance of the results. ResultsCompared with DVH-based reoptimization of the clinically approved plans, gas exchange-guided functional avoidance planning more effectively reduced the gas exchange-weighted metrics fMLD (average ± SD, –78 ± 79 cGy, compared with –45 ± 34 cGy; P = .03), MLD-f33% (–135 ± 136 cGy, compared with –52 ± 47 cGy; P = .004), and MLD-f50% (–96 ± 95 cGy, compared with –47 ± 40 cGy; P = .01). Comparing the 2 functional planning types, Gas Exchange-Guided planning more effectively reduced MLD-f33% compared with ventilation-guided planning (–64 ± 95; P = .009). For some patients, Gas Exchange-Guided functional avoidance plans demonstrated clinically significant reductions in model-predicted toxicity, more so than the accompanying ventilation-guided plans and DVH-based reoptimizations. ConclusionGas Exchange-Guided planning effectively reduced dose to high gas exchanging regions of lung while maintaining clinically acceptable plan quality. In many patients, ventilation-guided planning incidentally reduced dose to higher gas exchange regions, to a lesser extent. This methodology enables future prospective trials to examine patient outcomes.

Coloring ultrasensitive MRI with tunable metal-organic frameworks.

As one of the most important imaging modalities, magnetic resonance imaging (MRI) still faces relatively low sensitivity to monitor low-abundance molecules. A newly developed technology, hyperpolarized 129Xe magnetic resonance imaging (MRI), can boost the signal sensitivity to over 10 000-fold compared with that under conventional MRI conditions, and this technique is referred to as ultrasensitive MRI. However, there are few methods to visualize complex mixtures in this field due to the difficulty in achieving favorable “cages” to capture the signal source, namely, 129Xe atoms. Here, we proposed metal–organic frameworks (MOFs) as tunable nanoporous hosts to provide suitable cavities for xenon. Due to the widely dispersed spectroscopic signals, 129Xe in different MOFs was easily visualized by assigning each chemical shift to a specific color. The results illustrated that the pore size determined the exchange rate, and the geometric structure and elemental composition influenced the local charge experienced by xenon. We confirmed that a complex mixture was first differentiated by specific colors in ultrasensitive MRI. The introduction of MOFs helps to overcome long-standing obstacles in ultrasensitive, multiplexed MRI.

129Xe MRI as a measure of clinical disease severity for pediatric asthma

Measurement of regional lung ventilation with hyperpolarized 129Xe magnetic resonance imaging (129Xe MRI) in pediatric asthma is poised to advance our understanding of disease mechanisms and pathophysiology in a disorder with diverse clinical phenotypes. 129Xe MRI has not been investigated in a pediatric asthma cohort. We hypothesized that 129Xe MRI is feasible and can demonstrate ventilation defects that relate to and predict clinical severity in a pediatric asthma cohort. Thirty-seven children (13 with severe asthma, 8 with mild/moderate asthma, 16 age-matched healthy controls) aged 6 to 17 years old were imaged with 129Xe MRI. Ventilation defect percentage (VDP) and image reader score were calculated and compared with clinical measures at baseline and at follow-up. Children with asthma had higher VDP (P= .002) and number of defects per image slice (defects/slice) (P= .0001) than children without asthma. Children with clinically severe asthma had significantly higher VDP and number of defects/slice than healthy controls. Children with asthma who had a higher number of defects/slice had a higher rate of health care utilization (r= 0.48; P= .03) and oral corticosteroid use (r= 0.43; P= .05) at baseline. Receiver-operating characteristic analysis demonstrated that the VDP and number of defects/slice were predictive of increased health care utilization, asthma, and severe asthma. VDP correlated with FEV1 (r= -0.35; P= .04) and FEV1/forced vital capacity ratio (r= -0.41; P= .01). 129Xe MRI correlates with asthma severity, health care utilization, and oral corticosteroid use. Because delineation of clinical severity is often difficult in children, 129Xe MRI may be an important biomarker for severity, with potential to identify children at higher risk for exacerbations and improve outcomes.

Pulmonary Gas Exchange-guided Functional Avoidance Treatment Planning for Thoracic Radiation Therapy Using Hyperpolarized 129Xe Magnetic Resonance Imaging

Pulmonary Gas Exchange-guided Functional Avoidance Treatment Planning for Thoracic Radiation Therapy Using Hyperpolarized 129Xe Magnetic Resonance Imaging

Comparison of Functional Free-Breathing Pulmonary 1H and Hyperpolarized 129Xe Magnetic Resonance Imaging in Pediatric Cystic Fibrosis

Phase resolved functional lung (PREFUL) magnetic resonance imaging (MRI) is a free-breathing 1H-based technique that produces maps of fractional ventilation (FV). This study compared ventilation defect percent (VDP) calculated using PREFUL to hyperpolarized (HP) 129Xe MRI and pulmonary function tests in pediatric cystic fibrosis (CF). 27 pediatric participants were recruited (mean age 13.0 ± 2.7), including 6 with clinically stable CF, 11 CF patients undergoing a pulmonary exacerbation (PEx), and 10 healthy controls. Spirometry was performed to measure forced expiratory volume in 1 second (FEV1), along with nitrogen multiple breath washout to measure lung clearance index (LCI). VDP was calculated from single central coronal slice PREFUL FV maps and the corresponding HP 129Xe slice. The stable CF group had a normal FEV1 (p = 0.41) and elevated LCI (p = 0.007). The CF PEx group had a decreased FEV1 (p < 0.0001) and elevated LCI (p < 0.0001). PREFUL and HP 129Xe VDP were significantly different between the CF PEx and healthy groups (p < 0.05). In the stable CF group, PREFUL and HP 129Xe VDP were not significantly different from the healthy group (p = 0.18 and 0.08, respectively). There was a correlation between PREFUL and HP 129Xe VDP (R2 = 0.31, p = 0.004), and both parameters were significantly correlated with FEV1 and LCI. PREFUL MRI is feasible in pediatric CF, distinguishes patients undergoing pulmonary exacerbations compared to healthy subjects, and correlates with HP 129Xe MRI as well as functional measures of disease severity. PREFUL MRI does not require breath-holds and is straight forward to implement on any MRI scanner.

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.

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.

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.

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.

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.

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.