This work was funded by the National Institutes of Health (grant numbers R01-CA172595-01, R01-HL132177, R01-HL167202, S10-OD018079, and UL1-TR003015) and by Siemens Medical Solutions.

A Standardized Workflow for Hyperpolarized 129Xe MRI to Study Pulmonary Function

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</ol>

Authors J.F.M., J.P.M., and Y.M.S. participate in clinical trials supported by Polarean, Inc. Authors J.F.M., and Y.M.S. provide consulting services to Polarean, Inc. (less than $5000). Author J.P.M. receives research support from Polarean, Inc.

The ventilation and anatomical MRI approaches outlined above are designed to maximize image quality and SNR while maintaining simplicity of implementation - these sequence protocols can in general be adapted from vendor product pulse sequences, provided multinuclear operation is enabled, and images will automatically reconstruct on the scanner computer. One disadvantage of the 2D approaches described here is the use of slice-selective excitation RF pulses, which introduces signal differences between slices collected earl...

Hyperpolarized 129Xe MRI is an exciting tool for non-invasive, spatially-resolved characterization and quantification of specific aspects of pulmonary function1,2,3. Acquisition and reconstruction approaches similar to those used in anatomical proton MRI yield images of inhaled 129Xe in the lungs, permitting visualization of non-ventilated lung regions and region-resolved quantification of ventilation distribution4,5,6,7,8. More advanced pulse sequence and analysis techniques yield further complementary information, including quantification of gas-exchange efficacy between alveoli and pulmonary capillaries via spectroscopic MRI9,10,11,12,13 and characterization of alveolar microstructure integrity via diffusion-weighted MRI14,15,16.
Inhaled 129Xe has been proven safe and tolerable in adult and pediatric subjects, including those with pulmonary disease17,18. Measurements of lung function derived from 129Xe MRI have shown sensitivity to structural and functional alterations in many pulmonary disease contexts, including chronic obstructive pulmonary disease6,10,19, cystic fibrosis20,21,22, idiopathic pulmonary fibrosis23,24,25, and asthma7,10,26. Given the high safety and tolerability of 129Xe MRI, the lack of ionizing radiation in MRI compared with other common imaging approaches, and the high reproducibility of 129Xe MRI results27,28, 129Xe MRI holds significant promise, in particular for precise serial monitoring of individuals receiving a time course of therapy for chronic pulmonary disease.
The safety and clinical promise of 129Xe MRI have led to its FDA approval in December 2022 for lung ventilation imaging in persons aged 12 years and older29. Given this, it is anticipated that the number of research and clinical sites capable of performing 129Xe MRI (currently ~20 worldwide) will increase significantly over the coming years. As 129Xe MRI spreads to new institutions, it is important that robust methodological resources exist to allow sites to build out clinically relevant 129Xe MRI techniques quickly and to perform scans and generate results that are closely comparable with those of existing sites.
In this work, we will outline the current best practices for human hyperpolarized 129Xe MRI of lung ventilation, as agreed upon by member institutions of the 129Xe MRI Clinical Trials Consortium (Xe MRI CTC) and summarized in a recent position paper30. Topics will include the preparation of tailored pulse sequences ideal for a complete 129Xe MRI workflow, preparation, and administration of hyperpolarized 129Xe gas, an optimized workflow for human 129Xe MRI sessions, and best practices for monitoring subject safety and comfort during MRI sessions.

<table><tbody><tr><td>1.5T or 3T human MRI scanner</td><td>Siemens</td><td></td><td>MAGNETOM Symphony (1.5T) or Vida (3T); older models fine, as long as multinuclear option is/can be installed; scanners also available from GE and Philips</td></tr><tr><td>129Xe hyperpolarizer</td><td>Polarean</td><td>9820</td><td></td></tr><tr><td>129Xe MRI phantom</td><td></td><td></td><td></td></tr><tr><td>129Xe MRI vest coil</td><td>Clinical MR Solutions</td><td></td><td>Also available from other vendors</td></tr><tr><td>129Xe polarization measurement station</td><td>Polarean</td><td>2881</td><td></td></tr><tr><td>1H MRI phantom</td><td></td><td></td><td></td></tr><tr><td>Coil file for 129Xe MRI vest coil</td><td></td><td></td><td>Also available from other vendors for their respective coils</td></tr><tr><td>ECG machine</td><td></td><td></td><td></td></tr><tr><td>Helium buffer gas</td><td></td><td></td><td></td></tr><tr><td>Interface box from coil to scanner</td><td></td><td></td><td>May be built into coil, but needs to be included separately if not</td></tr><tr><td>Liquid nitrogen</td><td></td><td></td><td></td></tr><tr><td>MRI-safe pulse oximeter</td><td>Philips</td><td>Expression MR200</td><td></td></tr><tr><td>Nitrogen buffer gas</td><td></td><td></td><td></td></tr><tr><td>PFT machine</td><td></td><td></td><td></td></tr><tr><td>Programming/image analysis software</td><td>MATLAB</td><td>R2023a</td><td>Various other options available</td></tr><tr><td>Pulse sequence design software</td><td>Siemens</td><td></td><td>IDEA software package; also available from GE and Philips for their respective scanners</td></tr><tr><td>Scanner multinuclear option</td><td>Siemens</td><td></td><td>Scanner integrated hardware/software package; also available from GE and Philips for their respective scanners</td></tr><tr><td>Tedlar gas sampling bags (500, 750, 1000, 1250, 1500 mL)</td><td></td><td></td><td></td></tr><tr><td>Xenon gas (129Xe isotopically enriched)</td><td></td><td></td><td></td></tr></tbody></table>

acquiring hyperpolarized 129xe magnetic resonance images of lung ventilation

Hyperpolarized 129Xe MRI comprises a unique array of structural and functional lung imaging techniques. Technique standardization across sites is increasingly important given the recent FDA approval of 129Xe as an MR contrast agent and as interest in 129Xe MRI increases among research and clinical institutions. Members of the 129Xe MRI Clinical Trials Consortium (Xe MRI CTC) have agreed upon best practices for each of the key aspects of the 129Xe MRI workflow, and these recommendations are summarized in a recent publication. This work provides practical information to develop an end-to-end workflow for collecting 129Xe MR images of lung ventilation according to the Xe MRI CTC recommendations. Preparation and administration of 129Xe for MR studies will be discussed and demonstrated, with specific topics including choice of appropriate gas volumes for entire studies and for individual MR scans, preparation&#160;and delivery of individual 129Xe doses, and best practices for monitoring subject safety and 129Xe tolerability during studies. Key MR technical considerations will also be covered, including pulse sequence types and optimized parameters, calibration of 129Xe flip angle and center frequency, and 129Xe MRI ventilation image analysis.

Figure 1 shows representative ventilation and three-plane localizer images from a healthy individual. High 129Xe signal can be observed throughout the lungs in the ventilation images, and no ventilation impairment is evident in this individual.
Figure 2, Figure 3, and Figure 4 show representative ventilation and anatomical images from diseased individuals. <strong ...

Watch this Scientific Journal Video about Acquiring Hyperpolarized 129Xe Magnetic Resonance Images of Lung Ventilation at JoVE.com

Author Spotlight: Standardization and Best Practices for Advancing Lung Imaging Using 129Xe MRI

Hyperpolarized 129Xe magnetic resonance imaging (MRI) is a method for studying regionally resolved aspects of pulmonary function. This work presents an end-to-end standardized workflow for hyperpolarized 129Xe MRI of lung ventilation, with specific attention to pulse sequence design, 129Xe dose preparation, scan workflow, and best practices for subject safety monitoring.

Acquiring Hyperpolarized 129Xe Magnetic Resonance Images of Lung Ventilation

Hyperpolarized 129Xe MRI comprises a unique array of structural and functional lung imaging techniques. Technique standardization across sites is ...

acquiring-hyperpolarized-129xe-magnetic-resonance-images-lung

Research

JoVE Journal

Medicine

787 Views.  University of Virginia. Ons onderzoek is erop gericht om Xenon MRI vast te stellen als een klinisch hulpmiddel voor het karakteriseren van de longfunctie. Xenon MRI stelt ons in staat om beademingsdefecten direct te visualiseren bij patiënten met obstructieve longziekten zoals COPD, astma en cystische fibrose. Het biedt informatie die niet kan worden verkregen uit standaard MRI en longfunctietest.Xenon MRI is onlangs goedgekeurd door de FDA voor klinische evaluatie van longventilatie. Dit is een hoogtepunt v...

Video: Auteur in de schijnwerpers: standaardisatie en best practices voor het bevorderen van longbeeldvorming met behulp van 129Xe MRI

Magnetic Resonance Derived Myocardial Strain Assessment Using Feature Tracking 

Purpose: An accurate and practical method to measure parameters like strain in myocardial tissue is of great clinical value, since it has been shown, that strain is a more sensitive and earlier marker for contractile dysfunction than the frequently used parameter EF. Current technologies for CMR are time consuming and difficult to implement in clinical practice. Feature tracking is a technology that can lead to more automization and robustness of quantitative analysis of medical images with less time consumption than comparable methods.
Methods: An automatic or manual input in a single phase serves as an initialization from which the system starts to track the displacement of individual patterns representing anatomical structures over time. The specialty of this method is that the images do not need to be manipulated in any way beforehand like e.g. tagging of CMR images.
Results: The method is very well suited for tracking muscular tissue and with this allowing quantitative elaboration of myocardium and also blood flow.
Conclusions: This new method offers a robust and time saving procedure to quantify myocardial tissue and blood with displacement, velocity and deformation parameters on regular sequences of CMR imaging. It therefore can be implemented in clinical practice.

Magnetic Resonance Derived Myocardial Strain Assessment Using Feature Tracking

An accurate and practical method to measure parameters like strain in myocardial tissue is of great clinical value, since it has been shown, that strain is a more sensitive and earlier marker for contractile dysfunction than the frequently used parameter EF.

Purpose: An accurate and practical method to measure parameters like strain in myocardial tissue is of great clinical value, since it has been shown, that ...

Pressure Controlled Ventilation to Induce Acute Lung Injury in Mice

Murine models are extensively used to investigate acute injuries of different organs systems (1-34). Acute lung injury (ALI), which occurs with prolonged mechanical ventilation, contributes to morbidity and mortality of critical illness, and studies on novel genetic or pharmacological targets are areas of intense investigation (1-3, 5, 8, 26, 30, 33-36). ALI is defined by the acute onset of the disease, which leads to non-cardiac pulmonary edema and subsequent impairment of pulmonary gas exchange (36). We have developed a murine model of ALI by using a pressure-controlled ventilation to induce ventilator-induced lung injury (2). For this purpose, C57BL/6 mice are anesthetized and a tracheotomy is performed followed by induction of ALI via mechanical ventilation. Mice are ventilated in a pressure-controlled setting with an inspiratory peak pressure of 45 mbar over 1 - 3 hours. As outcome parameters, pulmonary edema (wet-to-dry ratio), bronchoalveolar fluid albumin content, bronchoalveolar fluid and pulmonary tissue myeloperoxidase content and pulmonary gas exchange are assessed (2). Using this technique we could show that it sufficiently induces acute lung inflammation and can distinguish between different treatment groups or genotypes (1-3, 5). Therefore this technique may be helpful for researchers who pursue molecular mechanisms involved in ALI using a genetic approach in mice with gene-targeted deletion.

A murine model for ventilator induced lung injury is an important tool to study an acute lung injury in vivo. Here, we report an easy applicable in situ model for acute lung injury using high-pressure mechanical ventilation to induce acute failure of the lung.

Murine models are extensively used to investigate acute injuries of different organs systems (1-34). Acute lung injury (ALI), which occurs with prolonged ...

Magnetic Resonance Imaging Quantification of Pulmonary Perfusion using Calibrated Arterial Spin Labeling

This demonstrates a MR imaging method to measure the spatial distribution of pulmonary blood flow in healthy subjects 
during normoxia (inspired O2, fraction (FIO2) = 0.21) hypoxia (FIO2 = 0.125), and hyperoxia 
(FIO2 = 1.00). In addition, the physiological responses of the subject are monitored in the MR scan environment. MR images 
were obtained on a 1.5 T GE MRI scanner during a breath hold from a sagittal slice in the right lung at functional residual capacity. An arterial 
spin labeling sequence (ASL-FAIRER) was used to measure the spatial distribution of pulmonary blood flow 1,2 and a multi-echo fast 
gradient echo (mGRE) sequence 3 was used to quantify the regional proton (i.e. H2O) density, allowing the quantification 
of density-normalized perfusion for each voxel (milliliters blood per minute per gram lung tissue). 
With a pneumatic switching valve and facemask equipped with a 2-way non-rebreathing valve, different oxygen concentrations 
were introduced to the subject in the MR scanner through the inspired gas tubing. A metabolic cart collected expiratory gas via expiratory tubing. Mixed expiratory O2 and CO2 concentrations, oxygen consumption, carbon dioxide production, respiratory exchange ratio, 
respiratory frequency and tidal volume were measured. Heart rate and oxygen saturation were monitored using pulse-oximetry. 
Data obtained from a normal subject showed that, as expected, heart rate was higher in hypoxia (60 bpm) than during normoxia (51) or hyperoxia (50) and the arterial oxygen saturation (SpO2) was reduced during hypoxia to 86%. Mean ventilation was 8.31 L/min BTPS during hypoxia, 7.04 L/min during normoxia, and 6.64 L/min during hyperoxia. Tidal volume was 0.76 L during hypoxia, 0.69 L during normoxia, and 0.67 L during hyperoxia. 
Representative quantified ASL data showed that the mean density normalized perfusion was 8.86 ml/min/g during hypoxia, 8.26 ml/min/g during normoxia and 8.46 ml/min/g during hyperoxia, respectively. In this subject, the relative dispersion4, an index of global heterogeneity, was increased in hypoxia (1.07 during hypoxia, 0.85 during normoxia, and 0.87 during hyperoxia) while the fractal dimension (Ds), another index of heterogeneity reflecting vascular branching structure, was unchanged (1.24 during hypoxia, 1.26 during normoxia, and 1.26 during hyperoxia). 
Overview. This protocol will demonstrate the acquisition of data to measure the distribution of pulmonary perfusion noninvasively under conditions of normoxia, hypoxia, and hyperoxia using a magnetic resonance imaging technique known as arterial spin labeling (ASL). 
Rationale: Measurement of pulmonary blood flow and lung proton density using MR technique offers high spatial resolution images which can be quantified and the ability to perform repeated measurements under several different physiological conditions. In human studies, PET, SPECT, and CT are commonly used as the alternative techniques. However, these techniques involve exposure to ionizing radiation, and thus are not suitable for repeated measurements in human subjects.

A MR imaging method to study the distribution of pulmonary blood flow under a variety of physiological conditions, in this case exposure to three different inspired oxygen concentrations: hypoxia, normoxia, and hyperoxia, is described. This technique utilizes human pulmonary physiology research techniques in an MR scanning environment.

This demonstrates a MR imaging method to measure the spatial distribution of pulmonary blood flow in healthy subjects 
during normoxia (inspired O2, ...

Quantitative Magnetic Resonance Imaging of Skeletal Muscle Disease

Quantitative magnetic resonance imaging (qMRI) describes the development and use of MRI to quantify physical, chemical, and/or biological properties of living systems. Neuromuscular diseases often exhibit a temporally varying, spatially heterogeneous, and multi-faceted pathology. The goal of this protocol is to characterize this pathology using qMRI methods. The MRI acquisition protocol begins with localizer images (used to locate the position of the body and tissue of interest within the MRI system), quality control measurements of relevant magnetic field distributions, and structural imaging for general anatomical characterization. The qMRI portion of the protocol includes measurements of the longitudinal and transverse relaxation time constants (T1 and T2, respectively). Also acquired are diffusion-tensor MRI data, in which water diffusivity is measured and used to infer pathological processes such as edema. Quantitative magnetization transfer imaging is used to characterize the relative tissue content of macromolecular and free water protons. Lastly, fat-water MRI methods are used to characterize fibro-adipose tissue replacement of muscle. In addition to describing the data acquisition and analysis procedures, this paper also discusses the potential problems associated with these methods, the analysis and interpretation of the data, MRI safety, and strategies for artifact reduction and protocol optimization.

Neuromuscular diseases often exhibit a temporally varying, spatially heterogeneous, and multi-faceted pathology. The goal of this protocol is to characterize this pathology using non-invasive magnetic resonance imaging methods.

Quantitative magnetic resonance imaging (qMRI) describes the development and use of MRI to quantify physical, chemical, and/or biological properties of ...

Human Brown Adipose Tissue Depots Automatically Segmented by Positron Emission Tomography/Computed Tomography and Registered Magnetic Resonance Images

Reliably differentiating brown adipose tissue (BAT) from other tissues using a non-invasive imaging method is an important step toward studying BAT in humans. Detecting BAT is typically confirmed by the uptake of the injected radioactive tracer 18F-Fluorodeoxyglucose (18F-FDG) into adipose tissue depots, as measured by positron emission tomography/computed tomography (PET-CT) scans after exposing the subject to cold stimulus. Fat-water separated magnetic resonance imaging (MRI) has the ability to distinguish BAT without the use of a radioactive tracer. To date, MRI of BAT in adult humans has not been co-registered with cold-activated PET-CT. Therefore, this protocol uses 18F-FDG PET-CT scans to automatically generate a BAT mask, which is then applied to co-registered MRI scans of the same subject. This approach enables measurement of quantitative MRI properties of BAT without manual segmentation. BAT masks are created from two PET-CT scans: after exposure for 2 hr to either thermoneutral (TN) (24 &#176;C) or cold-activated (CA) (17 &#176;C) conditions. The TN and CA PET-CT scans are registered, and the PET standardized uptake and CT Hounsfield values are used to create a mask containing only BAT. CA and TN MRI scans are also acquired on the same subject and registered to the PET-CT scans in order to establish quantitative MRI properties within the automatically defined BAT mask. An advantage of this approach is that the segmentation is completely automated and is based on widely accepted methods for identification of activated BAT (PET-CT). The quantitative MRI properties of BAT established using this protocol can serve as the basis for an MRI-only BAT examination that avoids the radiation associated with PET-CT.

The method presented here uses 18F-Fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET-CT) and fat-water separated magnetic resonance imaging (MRI), each scanned following 2 hr exposure to thermoneutral (24 &#176;C) and cold conditions (17 &#176;C) in order to map brown adipose tissue (BAT) in adult human subjects.

Reliably differentiating brown adipose tissue (BAT) from other tissues using a non-invasive imaging method is an important step toward studying BAT in ...

Simultaneous PET/MRI Imaging During Mouse Cerebral Hypoxia-ischemia

Dynamic changes in tissue water diffusion and glucose metabolism occur during and after hypoxia in cerebral hypoxia-ischemia reflecting a bioenergetics disturbance in affected cells. Diffusion weighted magnetic resonance imaging (MRI) identifies regions that are damaged, potentially irreversibly, by hypoxia-ischemia. Alterations in glucose utilization in the affected tissue may be detectable by positron emission tomography (PET) imaging of 2-deoxy-2-(18F)fluoro-&#7429;-glucose ([18F]FDG) uptake. Due to the rapid and variable nature of injury in this animal model, acquisition of both modes of data must be performed simultaneously in order to meaningfully correlate PET and MRI data. In addition, inter-animal variability in the hypoxic-ischemic injury due to vascular differences limits the ability to analyze multi-modal data and observe changes to a group-wise approach if data is not acquired simultaneously in individual subjects. The method presented here allows one to acquire both diffusion-weighted MRI and [18F]FDG uptake data in the same animal before, during, and after the hypoxic challenge in order to interrogate immediate physiological changes.

The method presented here uses simultaneous positron emission tomography and magnetic resonance imaging. In the cerebral hypoxia-ischemia model, dynamic changes in diffusion and glucose metabolism occur during and after injury. The evolving and irreproducible damage in this model necessitates simultaneous acquisition if meaningful multi-modal imaging data are to be acquired.

Dynamic changes in tissue water diffusion and glucose metabolism occur during and after hypoxia in cerebral hypoxia-ischemia reflecting a bioenergetics ...

Phosphorus-31 Magnetic Resonance Spectroscopy: A Tool for Measuring In Vivo Mitochondrial Oxidative Phosphorylation Capacity in Human Skeletal Muscle

Skeletal muscle mitochondrial oxidative phosphorylation (OXPHOS) capacity, which is critically important in health and disease, can be measured in vivo and noninvasively in humans via phosphorus-31 magnetic resonance spectroscopy (31PMRS). However, the approach has not been widely adopted in translational and clinical research, with variations in methodology and limited guidance from the literature. Increased optimization, standardization, and dissemination of methods for in vivo 31PMRS would facilitate the development of targeted therapies to improve OXPHOS capacity and could ultimately favorably impact cardiovascular health. 31PMRS produces a noninvasive, in vivo measure of OXPHOS capacity in human skeletal muscle, as opposed to alternative measures obtained from explanted and potentially altered mitochondria via muscle biopsy. It relies upon only modest additional instrumentation beyond what is already in place on magnetic resonance scanners available for clinical and translational research at most institutions. In this work, we outline a method to measure in vivo skeletal muscle OXPHOS. The technique is demonstrated using a 1.5 Tesla whole-body MR scanner equipped with the suitable hardware and software for 31PMRS, and we explain a simple and robust protocol for in-magnet resistive exercise to rapidly fatigue the quadriceps muscle. Reproducibility and feasibility are demonstrated in volunteers as well as subjects over a wide range of functional capacities.

Phosphorus-31 Magnetic Resonance Spectroscopy: A Tool for Measuring In Vivo Mitochondrial Oxidative Phosphorylation Capacity in Human Skeletal Muscle

This work demonstrates the feasibility of an in vivo phosphorus-31 magnetic resonance spectroscopy (31PMRS) technique to quantify mitochondrial oxidative phosphorylation (OXPHOS) capacity in human skeletal muscle.

Skeletal muscle mitochondrial oxidative phosphorylation (OXPHOS) capacity, which is critically important in health and disease, can be measured in vivo ...

Obtaining High-Quality Hyperpolarized Xenon-129 Magnetic Resonance Images

Troubleshooting and Quality Assurance in Hyperpolarized Xenon Magnetic Resonance Imaging: Tools for High-Quality Image Acquisition

Hyperpolarized (HP) xenon magnetic resonance imaging (129Xe MRI) is a recently federal drug administration (FDA)-approved imaging modality that produces high-resolution images of an inhaled breath of xenon gas for investigation of lung function. However, implementing 129Xe MRI is uniquely challenging as it requires specialized hardware and equipment for hyperpolarization, procurement of xenon imaging coils and coil software, development and compilation of multinuclear MR imaging sequences, and reconstruction/analysis of acquired data. Without proper expertise, these tasks can be daunting, and failure to acquire high-quality images can be&#160;frustrating, and expensive. Here, we present some quality control (QC) protocols, troubleshooting practices, and helpful tools for129Xe MRI sites, which may aid in the acquisition of optimized, high-quality data and accurate results. The discussion will begin with an overview of the process for implementing HP 129Xe MRI, including requirements for a hyperpolarizer lab, the combination of 129Xe MRI coil hardware/software, data acquisition and sequence considerations, data structures, k-space and image properties, and measured signal and noise characteristics. Within each of these necessary steps lies opportunities for errors, challenges, and unfavorable occurrences leading to poor image quality or failed imaging, and this presentation aims to address some of the more commonly encountered issues. In particular, identification and characterization of anomalous noise patterns in acquired data are necessary to avoid image artifacts and low-quality images; examples will be given, and mitigation strategies will be discussed. We aim to make the 129Xe MRI implementation process easier for new sites while providing some guidelines and strategies for real-time troubleshooting.

Author Spotlight: Using Hyperpolarized Xenon-129 MRI to Study Lung Diseases 

Here, we present a protocol for obtaining high-quality hyperpolarized xenon-129 magnetic resonance images, covering hardware, software, data acquisition, sequence selection, data management, k-space utilization, and noise analysis.

Hyperpolarized (HP) xenon magnetic resonance imaging (129Xe MRI) is a recently federal drug administration (FDA)-approved imaging modality that produces ...

Bioengineering

Hyperpolarized 129Xe Lung MRI and Spectroscopy in Mechanically Ventilated Mice

Hyperpolarized (HP) xenon-129 (129Xe) is an inhaled magnetic resonance imaging (MRI) contrast agent with unique spectral and physical properties that can be exploited to quantify pulmonary physiology, including ventilation, restricted diffusion (alveolar-airspace size), and gas exchange. In humans, it has been used to evaluate disease severity and progression in a variety of pulmonary disorders and is approved for clinical use in the United States and United Kingdom. Beyond its clinical applications, the ability of 129Xe MRI to noninvasively assess pulmonary pathophysiology and provide spatially resolved information is valuable for preclinical research. Among animal models, mice are the most widely used due to the accessibility of genetically modified disease models. Here, 129Xe MRI is promising as a minimally invasive, radiation-free, and sensitive technique to longitudinally monitor lung disease progression and therapy response (e.g., in drug discovery). This technique can extend to preclinical applications by incorporating an MRI-triggered, free-breathing apparatus or mechanical ventilator to deliver gas. Here, we describe the steps and provide checklists to ensure robust data collection and analysis, including creating a thermally polarized xenon gas phantom for quality control, optimizing polarization, animal handling (sedation, intubation, ventilation, and care for mice), and protocols for ventilation, restricted diffusion, and gas exchange data. While preclinical 129Xe MRI can be applied in various animal models (e.g., rats, pigs, sheep), this protocol focuses on mice due to the challenges posed by their small anatomy, which are balanced by their affordability and the availability of many disease models.

Hyperpolarized xenon MRI can quantify regional lung microstructure (air-space dimensions) and physiology (ventilation and gas exchange) in translational research and clinical care. Although challenging, it can provide comparable pulmonary insights in preclinical studies. This protocol describes the infrastructure and procedures needed to perform routine xenon lung MRI in mice.

Hyperpolarized (HP) xenon-129 (129Xe) is an inhaled magnetic resonance imaging (MRI) contrast agent with unique spectral and physical properties that can ...

Multi-modal Pulmonary Imaging: Using Complementary Information from CT and Hyperpolarized 129Xe MRI to Evaluate Lung Structure-Function

Hyperpolarized 129Xe gas MRI is an emerging technique to evaluate and measure regional lung function including pulmonary gas distribution and gas exchange. Chest computed tomography (CT) still remains the clinical gold standard for imaging of the lungs, though, in part due to the rapid CT protocols that acquire high-resolution images in seconds and the widespread availability of CT scanners. Quantitative approaches have enabled the extraction of structural lung parenchymal, airway and vascular measurements from chest CT that have been evaluated in many clinical research studies. Together, CT and 129Xe MRI provide complementary information that can be used to evaluate regional lung structure and function, resulting in new insights into lung health and disease. 129Xe MR-CT image registration can be performed to measure regional lung structure-function to better understand lung disease pathophysiology, and to perform image-guided pulmonary interventions. Here, a method for 129Xe MRI-CT registration is outlined to support implementation in research or clinical settings. Registration methods and applications that have been employed to date in the literature are also summarized, and suggestions are provided for future directions that may further overcome technical challenges related to 129Xe MR-CT image registration and facilitate broader implementation of regional lung structure-function evaluation.

Multi-modal Pulmonary Imaging: Using Complementary Information from CT and Hyperpolarized 129Xe MRI to Evaluate Lung Structure-Function

CT and 129Xe MRI provide complementary lung structure-function information that can be exploited for regional analysis using image registration. Here, we provide a protocol that builds from the existing literature for 129Xe MR to CT image registration using open-source platforms.

Acquiring Hyperpolarized ¹²⁹Xe Magnetic Resonance Images of Lung Ventilation

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