129Xe Magnetic Resonance Imaging Research Articles

Cluster Analysis to Identify Long COVID Phenotypes Using 129Xe Magnetic Resonance Imaging: A Multi-centre Evaluation.

Long COVID impacts ∼10% of people diagnosed with COVID-19, yet the pathophysiology driving ongoing symptoms is poorly understood. We hypothesised that 129Xe magnetic resonance imaging (MRI) could identify unique pulmonary phenotypic subgroups of long COVID, therefore we evaluated ventilation and gas exchange measurements with cluster analysis to generate imaging-based phenotypes. COVID-negative controls and participants who previously tested positive for COVID-19 underwent 129XeMRI ∼14-months post-acute infection across three centres. Long COVID was defined as persistent dyspnea, chest tightness, cough, fatigue, nausea and/or loss of taste/smell at MRI; participants reporting no symptoms were considered fully-recovered. 129XeMRI ventilation defect percent (VDP) and membrane (Mem)/Gas, red blood cell (RBC)/Mem and RBC/Gas ratios were used in k-means clustering for long COVID, and measurements were compared using ANOVA with post-hoc Bonferroni correction. We evaluated 135 participants across three centres: 28 COVID-negative (40±16yrs), 34 fully-recovered (42±14yrs) and 73 long COVID (49±13yrs). RBC/Mem (p=0.03) and FEV1 (p=0.04) were different between long- and COVID-negative; FEV1 and all other pulmonary function tests (PFTs) were within normal ranges. Four unique long COVID clusters were identified compared with recovered and COVID-negative. Cluster1 was the youngest with normal MRI and mild gas-trapping; Cluster2 was the oldest, characterised by reduced RBC/Mem but normal PFTs; Cluster3 had mildly increased Mem/Gas with normal PFTs; and Cluster4 had markedly increased Mem/Gas with concomitant reduction in RBC/Mem and restrictive PFT pattern. We identified four 129XeMRI long COVID phenotypes with distinct characteristics. 129XeMRI can dissect pathophysiologic heterogeneity of long COVID to enable personalised patient care.

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.

Hyperpolarised xenon-129 diffusion-weighted magnetic resonance imaging for assessing lung microstructure in idiopathic pulmonary fibrosis.

Hyperpolarised 129-xenon (129Xe) magnetic resonance imaging (MRI) shows promise in monitoring the progression of idiopathic pulmonary fibrosis (IPF) due to the lack of ionising radiation and the ability to quantify functional impairment. Diffusion-weighted (DW)-MRI with hyperpolarised gases can provide information about lung microstructure. The aims were to compare 129Xe DW-MRI measurements with pulmonary function tests (PFTs), and to assess whether they can detect early signs of disease progression in patients with newly diagnosed IPF. This is a prospective, single-centre, observational imaging study of patients presenting with IPF to Northern General Hospital (Sheffield, UK). Hyperpolarised 129Xe DW-MRI was performed at 1.5 T on a whole-body General Electric HDx scanner and PFTs were performed on the same day as the MRI scan. There was an increase in global 129Xe apparent diffusion coefficient (ADC) between the baseline and 12-month visits (mean 0.043 cm2·s-1, 95% CI 0.040-0.047 cm2·s-1 versus mean 0.045 cm2·s-1, 95% CI 0.040-0.049 cm2·s-1; p=0.044; n=20), with no significant change in PFTs over the same time period. There was also an increase in 129Xe ADC in the lower zone (p=0.027), and an increase in 129Xe mean acinar dimension in the lower zone (p=0.033) between the baseline and 12-month visits. 129Xe DW-MRI measurements correlated strongly with diffusing capacity of the lung for carbon monoxide (% predicted), transfer coefficient of the lung for carbon monoxide (KCO) and KCO (% predicted). 129Xe DW-MRI measurements appear to be sensitive to early changes of microstructural disease that are consistent with progression in IPF at 12 months. As new drug treatments are developed, the ability to quantify subtle changes using 129Xe DW-MRI could be particularly valuable.

Longitudinal Lung Function Assessment of Patients Hospitalized With COVID-19 Using 1H and 129Xe Lung MRI

Microvascular abnormalities and impaired gas transfer have been observed in patients with COVID-19. The progression of pulmonary changes in these patients remains unclear. Do patients hospitalized with COVID-19 without evidence of architectural distortion on structural imaging exhibit longitudinal improvements in lung function measured by using 1H and 129Xe MRI between 6 and 52weeks following hospitalization? Patients who were hospitalized with COVID-19 pneumonia underwent a pulmonary 1H and 129Xe MRI protocol at 6, 12, 25, and 51weeks following hospital admission in a prospective cohort study between November 2020 and February 2022. The imaging protocol was as follows: 1H ultra-short echo time, contrast-enhanced lung perfusion, 129Xe ventilation, 129Xe diffusion-weighted, and 129Xe spectroscopic imaging of gas exchange. Nine patients were recruited (age 57 ± 14 [median ± interquartile range] years; six of nine patients were male). Patients underwent MRI at 6 (n= 9), 12 (n= 9), 25 (n= 6), and 51 (n= 8) weeks following hospital admission. Patients with signs of interstitial lung damage were excluded. At 6weeks, patients exhibited impaired 129Xe gas transfer (RBC to membrane fraction), but lung microstructure was not increased (apparent diffusion coefficient and mean acinar airway dimensions). Minor ventilation abnormalities present in four patients were largely resolved in the 6- to 25-week period. At 12weeks, all patients with lung perfusion data (n= 6) showed an increase in both pulmonary blood volume and flow compared with 6weeks, although this was not statistically significant. At 12weeks, significant improvements in 129Xe gas transfer were observed compared with 6-week examinations; however, 129Xe gas transfer remained abnormally low at weeks 12, 25, and51. 129Xe gas transfer was impaired up to 1 year following hospitalization in patients who were hospitalized with COVID-19 pneumonia, without evidence of architectural distortion on structural imaging, whereas lung ventilation was normal at 52weeks.

A thermally polarized 129Xenon phantom for MR elastography studies in a ultra-high field MRI system

Being second only to cardiovascular problems, respiratory diseases account for five of the 30 most common causes of death worldwide. One way to address this problem is by improving early diagnostic methods. Due to the complex heterogeneous structure of the lung, conventional imaging and elastography techniques based on ultrasound and magnetic resonance (MR) imaging have been limited in their ability to provide regional detail of morphology and mechanical properties, both of which can be altered by respiratory diseases. Hyperpolarized 129Xe(non) MR imaging has shown promise as a means of regionally quantifying ventilation, microstructure, and gas exchange efficiency in the lung parenchymae. MR elastography of the lungs using hyperpolarized gases is also being explored. To advance development, a stable phantom for MR imaging and elastography calibration using 129Xe is needed. The design, fabrication, and experimental testing of a stable thermally polarized 129Xe MR imaging and elastography phantom for a 9.4 T preclinical MR imaging system are presented.

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.

Synthesis and Physicochemical Properties of Cryptophazane—A Soluble and Functionalizable C1‐Symmetrical Cryptophane

AbstractThe first example of a cryptophazane, a cryptophane functionalized with a nitrogen atom replacing one of the methylene bridges, is obtained with a 28 % overall yield over 8 steps, through the preparation of a C1‐symmetrical aza‐cyclotriveratrylene (aza‐CTV). Herein, we demonstrate that the introduction of a nitrogen atom on this part of the cryptophane core enhances the solubility in organic media of both the cryptophane and the synthetic intermediates, while presenting the same conformation as known cryptophanes. Cryptophazane was prepared on a multigram scale and easily functionalized. We also investigated its ability to encapsulate xenon atoms using hyperpolarized 129Xe (HP 129Xe) NMR spectroscopy. We found that both its affinity and exchange kinetics were in the appropriate range for applications in 129Xe magnetic resonance imaging (MRI). Combined with the wide range of possible functionalization, this makes cryptophazane an excellent candidate for targeted HP 129Xe MRI.

Synthesis and Physicochemical Properties of Cryptophazane-A Soluble and Functionalizable C1 -Symmetrical Cryptophane.

The first example of a cryptophazane, a cryptophane functionalized with a nitrogen atom replacing one of the methylene bridges, is obtained with a 28 % overall yield over 8 steps, through the preparation of a C1 -symmetrical aza-cyclotriveratrylene (aza-CTV). Herein, we demonstrate that the introduction of a nitrogen atom on this part of the cryptophane core enhances the solubility in organic media of both the cryptophane and the synthetic intermediates, while presenting the same conformation as known cryptophanes. Cryptophazane was prepared on a multigram scale and easily functionalized. We also investigated its ability to encapsulate xenon atoms using hyperpolarized 129 Xe (HP 129 Xe) NMR spectroscopy. We found that both its affinity and exchange kinetics were in the appropriate range for applications in 129 Xe magnetic resonance imaging (MRI). Combined with the wide range of possible functionalization, this makes cryptophazane an excellent candidate for targeted HP 129 Xe MRI.

Recent Advances in Metal-Organic Frameworks for Applications in Magnetic Resonance Imaging.

Diagnostics is an important part of medical practice. The information required for diagnosis is typically collected by performing diagnostic tests, some of which include imaging. Magnetic resonance imaging (MRI) is one of the most widely used and effective imaging techniques. To improve the sensitivity and specificity of MRI, contrast agents are used. In this review, the usage of metal-organic frameworks (MOFs) and composite materials based on them as contrast agents for MRI is discussed. MOFs are crystalline porous coordination polymers. Due to their huge design variety and high density of metal ions, they have been studied as a highly promising class of materials for developing MRI contrast agents. This review highlights the most important studies and focuses on the progress of the field over the last five years. The materials are classified based on their design and structural properties into three groups: MRI-active MOFs, composite materials based on MOFs, and MRI-active compounds loaded in MOFs. Moreover, an overview of MOF-based materials for heteronuclear MRI including 129Xe and 19F MRI is given.

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.

Ultrasensitive molecular building block for biothiol NMR detection at picomolar concentrations

Magnetic resonance imaging (MRI) provides structural and functional information, but it did not probe chemistry. Chemical information could help improve specificity of detection. Herein, we introduce a general method based on a modular design to construct a molecular building block Xe probe to help image intracellular biothiols (glutathione (GSH), cysteine (Cys) and homocysteine (Hcy)), the abnormal content of which is related to various diseases. This molecular building block possesses a high signal-to-noise ratio and no background signal effects. Its detection threshold was 100 pM, which enabled detection of intracellular biothiols in live cells. The construction strategy can be easily extended to the detection of any other biomolecule or biomarker. This modular design strategy promotes efficiency of development of low-cost multifunctional probes that can be combined with other readout parameters, such as optical readouts, to complement 129Xe MRI to usher in new capabilities for molecular imaging.

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.

Xenon ventilation MRI in difficult asthma: initial experience in a clinical setting.

BackgroundHyperpolarised gas magnetic resonance imaging (MRI) can be used to assess ventilation patterns. Previous studies have shown the image-derived metric of ventilation defect per cent (VDP) to correlate with forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) and FEV1 in asthma.ObjectivesThe aim of this study was to explore the utility of hyperpolarised xenon-129 (129Xe) ventilation MRI in clinical care and examine its relationship with spirometry and other clinical metrics in people seen in a severe asthma service.Methods26 people referred from a severe asthma clinic for MRI scanning were assessed by contemporaneous 129Xe MRI and spirometry. A subgroup of 18 patients also underwent reversibility testing with spirometry and MRI. Quantitative MRI measures of ventilation were calculated, VDP and the ventilation heterogeneity index (VHI), and compared to spirometry, Asthma Control Questionnaire 7 (ACQ7) and blood eosinophil count. Images were reviewed by a multidisciplinary team.ResultsVDP and VHI correlated with FEV1, FEV1/FVC and forced expiratory flow between 25% and 75% of FVC but not with ACQ7 or blood eosinophil count. Discordance of MRI imaging and symptoms and/or pulmonary function tests also occurred, prompting diagnostic re-evaluation in some cases.ConclusionHyperpolarised gas MRI provides a complementary method of assessment in people with difficult to manage asthma in a clinical setting. When used as a tool supporting clinical care in a severe asthma service, occurrences of discordance between symptoms, spirometry and MRI scanning indicate how MRI scanning may add to a management pathway.

Regional Gas Exchange Measured by 129 Xe Magnetic Resonance Imaging Before and After Combination Bronchodilators Treatment in Chronic Obstructive Pulmonary Disease.

BackgroundHyperpolarized 129Xe magnetic resonance imaging (MRI) provides a non‐invasive assessment of regional pulmonary gas exchange function. This technique has demonstrated that chronic obstructive pulmonary disease (COPD) patients exhibit ventilation defects, reduced interstitial barrier tissue uptake, and poor transfer to capillary red blood cells (RBCs). However, the behavior of these measurements following therapeutic intervention is unknown.PurposeTo characterize changes in 129Xe gas transfer function following administration of an inhaled long‐acting beta‐agonist/long‐acting muscarinic receptor antagonist (LABA/LAMA) bronchodilator.Study TypeProspective.PopulationSeventeen COPD subjects (GOLD II/III classification per Global Initiative for Chronic Obstructive Lung Disease criteria) were imaged before and after 2 weeks of LABA/LAMA therapy.Field Strength/SequencesDedicated ventilation imaging used a multi‐slice 2D gradient echo sequence. Three‐dimensional images of ventilation, barrier uptake, and RBC transfer used an interleaved, radial, 1‐point Dixon sequence. Imaging was acquired at 3 T.Assessment129Xe measurements were quantified before and after LABA/LAMA treatment by ventilation defect + low percent (vendef + low) and by barrier uptake and RBC transfer relative to a healthy reference population (bar%ref and RBC%ref). Pulmonary function tests, including diffusing capacity of the lung for carbon monoxide (DLCO), were also performed before and after treatment.Statistical TestsPaired t‐test, Pearson correlation coefficient (r).ResultsBaseline vendef + low was 57.8 ± 8.4%, bar%ref was 73.2 ± 19.6%, and RBC%ref was 36.5 ± 13.6%. Following treatment, vendef + low decreased to 52.5 ± 10.6% (P < 0.05), and improved in 14/17 (82.4%) of subjects. However, RBC%ref decreased in 10/17 (58.8%) of subjects. Baseline measurements of bar%ref and DLCO were correlated with the degree of post‐treatment change in vendef + low (r = −0.49, P < 0.05 and r = −0.52, P < 0.05, respectively).ConclusionLABA/LAMA therapy tended to preferentially improve ventilation in subjects whose 129Xe barrier uptake and DLCO were relatively preserved. However, newly ventilated regions often revealed RBC transfer defects, an aspect of lung function opaque to spirometry. These microvasculature abnormalities must be accounted for when assessing the effects of LABA/LAMA therapy.Level of Evidence1Technical Efficacy Stage4

Cryptophane-xenon complexes for 129Xe MRI applications.

The use of magnetic resonance imaging (MRI) and spectroscopy (MRS) in the clinical setting enables the acquisition of valuable anatomical information in a rapid, non-invasive fashion. However, MRI applications for identifying disease-related biomarkers are limited due to low sensitivity at clinical magnetic field strengths. The development of hyperpolarized (hp) 129Xe MRI/MRS techniques as complements to traditional 1H-based imaging has been a burgeoning area of research over the past two decades. Pioneering experiments have shown that hp 129Xe can be encapsulated within host molecules to generate ultrasensitive biosensors. In particular, xenon has high affinity for cryptophanes, which are small organic cages that can be functionalized with affinity tags, fluorophores, solubilizing groups, and other moieties to identify biomedically relevant analytes. Cryptophane sensors designed for proteins, metal ions, nucleic acids, pH, and temperature have achieved nanomolar-to-femtomolar limits of detection via a combination of 129Xe hyperpolarization and chemical exchange saturation transfer (CEST) techniques. This review aims to summarize the development of cryptophane biosensors for 129Xe MRI applications, while highlighting innovative biosensor designs and the consequent enhancements in detection sensitivity, which will be invaluable in expanding the scope of 129Xe MRI.

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

Hyperpolarised xenon MRI and time-resolved X-ray computed tomography studies of structure-transport relationships in hierarchical porous media

Catalysed diesel particulate filter (DPF) monoliths are hierarchical porous solids, as demonstrated by mercury porosimetry. Establishing structure-transport relationships, including assessing the general accessibility of the catalyst, is challenging, and, thus, a comprehensive approach is necessary. Contributions, from each porosity level, to transport have been established using hyperpolarised (hp) xenon-129 magnetic resonance imaging (MRI) of gas dispersion within DPF monoliths at variable water saturation, since X-ray Computerised-Tomography, and 1H and 2H NMR methods, have shown that porosity levels dry out progressively. At high saturation, hp 129Xe MRI showed gas transport between the channels of the monolith is predominantly taking place at channel wall intersections with high macroporosity. The walls themselves make a relatively small contribution to through transport due to the distribution of the micro-/meso-porous washcoat layer away from intersections. Only at low saturation, when the smallest pores are opened, do hp 129Xe MR images became strongly affected by relaxation. This observation indicates accessibility of paramagnetic (catalytic) centres for gases arises only once the smallest pores are open.

Single-Session Bronchial Thermoplasty Guided by 129Xe Magnetic Resonance Imaging. A Pilot Randomized Controlled Clinical Trial.

Rationale: Adverse events have limited the use of bronchial thermoplasty (BT) in severe asthma.Objectives: We sought to evaluate the effectiveness and safety of using 129Xe magnetic resonance imaging (129Xe MRI) to prioritize the most involved airways for guided BT.Methods: Thirty subjects with severe asthma were imaged with volumetric computed tomography and 129Xe MRI to quantitate segmental ventilation defects. Subjects were randomized to treatment of the six most involved airways in the first session (guided group) or a standard three-session BT (unguided). The primary outcome was the change in Asthma Quality of Life Questionnaire score from baseline to 12 weeks after the first BT for the guided group compared with after three treatments for the unguided group.Measurements and Main Results: There was no significant difference in quality of life after one guided compared with three unguided BTs (change in Asthma Quality of Life Questionnaire guided = 0.91 [95% confidence interval, 0.28-1.53]; unguided = 1.49 [95% confidence interval, 0.84-2.14]; P = 0.201). After one BT, the guided group had a greater reduction in the percentage of poorly and nonventilated lung from baseline when compared with unguided (-17.2%; P = 0.009). Thirty-three percent experienced asthma exacerbations after one guided BT compared with 73% after three unguided BTs (P = 0.028).Conclusions: Results of this pilot study suggest that similar short-term improvements can be achieved with one BT treatment guided by 129Xe MRI when compared with standard three-treatment-session BT with fewer periprocedure adverse events.