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 &lt;sup&gt;129&lt;/sup&gt;Xe MRI to Study Pulmonary Function

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 border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<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.

Author Spotlight: Standardization and Best Practices for Advancing Lung Imaging Using &lt;sup&gt;129&lt;/sup&gt;Xe MRI

Acquiring Hyperpolarized 129Xe Magnetic Resonance Images of Lung Ventilation

Our research seeks to establish Xenon MRI as a clinical tool for characterizing lung function. Xenon MRI allows us to directly visualize ventilation defects in patients with obstructive lung diseases like COPD, asthma, and cystic fibrosis. It offers information that can't be obtained from standard MRI and pulmonary function test.Xenon MRI was recently approved by the FDA for clinical evaluation of lung ventilation. This represents a culmination of a huge amount of effort by the people in our field and it's an exciting opportunity to show how Xenon MRI can improve patient care and outcomes in pulmonary disease. Xenon MRI is still a relatively new family of techniques, and standardization is still an ongoing process.This protocol distills the existing standards for Xenon ventilation MRI into a form that we hope will be useful to research in clinical sites who are trying to perform these scans for the first time. Common clinical readouts of lung function, like pulmonary function tests, only give a single number for the entire lung with no spatial information included. Xenon MRI can make regional assessments of several aspects of lung health and function, which we believe will be very useful in the clinic.Only a few institutions are currently performing Xenon MRI, but we expect there will be many more sites soon considering the recent FDA approval. We hope that this Xenon ventilation MRI protocol will serve as a blueprint for new sites and help em to ramp up their Xenon MRI operations more quickly.

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

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.

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

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608 Views.  University of Virginia. Our research seeks to establish Xenon MRI as a clinical tool for characterizing lung function. Xenon MRI allows us to directly visualize ventilation defects in patients with obstructive lung diseases like COPD, asthma, and cystic fibrosis. It offers information that can't be obtained from standard MRI and pulmonary function test.Xenon MRI was recently approved by the FDA for clinical evaluation of lung ventilation. This represents a culmination of a huge amount of effort by the people ...

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

Pre-Scan Preparation and Coaching of Subject for 129Xe MRI of Lung Ventilation

To begin, prepare one or more Tedlar bags, containing air, for the subject to practice outside the scanner. Use an air volume that matches the total volume of xenon and buffer gas to be inhaled from the bag during the actual study. Prepare nose clips for the subject to wear during breath hold scanning, fit the nose clips onto the subject's nose before the start of breath holds.Use one air-filled bag for each attempt to coach the subject. Before producing the bag, ask the subject to breathe in and breathe out regularly several times. During the procedure, monitor the subject's chest to confirm that they are executing the instructions properly.Next, place the tube attached to the Tedlar bag into the subject's mouth. Hold the bag such that the subject can inhale from it and open the valve. Ask the subject to breathe in, then ask the subject to hold their breath by saying, hold your breath.When practicing, wait for a count of 10 to 15 seconds, which is the approximate amount of time required for a typical xenon 129 scan to elapse. After that, ask the subject to exhale at this point and breathe. Coach the subject to take several deep breaths in and out for a quicker clearance of xenon 129 from the lungs and a quicker return to normal oxygen saturation levels.Verify that the subject is able to carry out the instructions reliably and consider excluding subjects who cannot do so during practice runs.

Preparation of MRI Scanner Room and Subject Positioning for 129Xe MRI of Lung Ventilation

To begin, ensure anyone entering the MRI scanner room has removed all metallic and electronic objects from their body or pockets. Prepare the Xenon 129 vest coil by plugging it into the scanner and placing it on the MRI scanner patient table. Instruct the subject to lie on the patient table in a feet first or head first supine position depending on the layout of the scanner room.Place pillows under the subject's head, knees, et cetera, as needed to ensure comfort during the procedure. Secure the Xenon 129 vest coil around the subject's chest while keeping the coil midline in the head-foot direction as close as possible to the expected midline of the subject's lungs when the subject is at a comfortable inflation level. Placing the coil to low on the subject may result in undesirable signal reductions at the periphery of the lungs.Set up an MRI safe pulse oximeter next to the patient table in the MRI scanner room and connect the pulse oximeter probe to the subject. Verify that the pulse oximeter is reading correctly. Place a nasal cannula in the subject's nose and connect it to an oxygen source to be used after dose inhalation if needed.Place the oxygen tank and regulator in an MRI safe manner based on local safety policy within reachable distance. Advance the patient table into the MRI scanner, aligning the midline of the coil or the subject's lungs to the scanner's isocenter. The images shown here represent the ventilation images from a study that was unknowingly performed using a Xenon 129 vest coil with a damaged cable.The right lung displays a lower signal-to-noise ratio than the left lung. The ventilation images from a study that was performed with the Xenon 129 vest coil placed too far toward the subject's feet are shown here. Artificially low Xenon 129 signal is observed in both lung apices due to the lack of receiver sensitivity there.

Performing 129Xe MRI Scan of Lung Ventilation to Assess Pulmonary Function

After making the final xenon-129 pre-scan adjustments and ensuring the subject is ready for the xenon-129 dose, proceed to perform the xenon-129 ventilation scan. First, load the xenon-129 ventilation sequence from the prepared protocol. Ensure all pulse sequence parameters are as desired and set proper scan execution settings.Select the field of view, or FOV size, and center location based on the localizer results. Aim for the center of the FOV to coincide with the center of the lungs in all three dimensions and the FOV to be large enough to comfortably contain the entire chest cavity, including the entirety of both lungs. Bring the xenon-129 dose bag intended for the ventilation scan from the polarization measurement station into the scanner room.Hold or place the dose bag near the subject. Avoid regions near the bore opening where the magnetic field strength changes rapidly. Assist the subject in inhaling the xenon-129 dose from the bag, following the already-coached inhalation procedure.Execute the scan immediately upon hearing the signal go"from the individual assisting the subject. Monitor the subject while the scan proceeds. Following the scan, monitor the subject's heart rate and SPO2 using the pulse oximeter and monitor for transient central nervous system effects via verbal communication with the subject.If no significant deviations from baseline occur, then after waiting for at least two minutes, another xenon-129 dose can be administered. The ventilation images from a healthy individual are shown here. A high xenon-129 signal can be observed throughout the lungs in these images, and no ventilation impairment is evident in this individual.This figure depicts an individual with alpha-1 antitrypsin deficiency in which severe ventilation impairment can be easily detected by observing the patchy appearance of the xenon-129 images. Similarly, severe ventilation impairment can be seen in this figure depicting an individual with severe cystic fibrosis. The images shown here depicts an individual with chronic obstructive pulmonary disease in which more subtle ventilation defects can be noted.