The protocol outlined below adheres to the guidelines and standards established by the University of Missouri Human Research Ethics Committee, ensuring the ethical conduct of the study and the protection of participants&#39; rights, safety, and well-being.
NOTE: To ensure the reliability and accuracy of hyperpolarized xenon MRI studies, it is crucial to perform rigorous characterization of acquired images, follow a comprehensive protocol, and employ effective troubleshooting strategies. The im...

Obtaining High-Quality Hyperpolarized Xenon-129 Magnetic Resonance Images

<ol>
	<li>Pellegrino, R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Interpretative+strategies+for+lung+function+tests.">Interpretative strategies for lung function tests.</a> European Respiratory Journal. 26 (5), 948-968 (2005).</li><li>Ebner, L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Hyperpolarized+129Xenon+MRI+to+quantify+regional+ventilation+differences+in+mild+to+moderate+asthma:+A+prospective+comparison+between+semi-automated+ventilation+defect+percentage+calculation+and+pulmonary+function+tests.">Hyperpolarized 129Xenon MRI to quantify regional ventilation differences in mild to moderate asthma: A prospective comparison between semi-automated ventilation defect percentage calculation and pulmonary function tests.</a> Investigative Radiology. 52 (2), 120-127 (2017).</li><li>Abuelhia, E., Alghamdi, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Evaluation+of+arising+exposure+of+ionizing+radiation+from+computed+tomography+and+the+associated+health+concerns.">Evaluation of arising exposure of ionizing radiation from computed tomography and the associated health concerns.</a> Journal of Radiation Research and Applied Sciences. 13 (1), 295-300 (2020).</li><li>Kern, A. L., Vogel-Claussen, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Hyperpolarized+gas+MRI+in+pulmonology.">Hyperpolarized gas MRI in pulmonology.</a> The British Journal of Radiology. 91 (1084), 20170647 (2018).</li><li>M&#246;ller, H. E., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=MRI+of+the+lungs+using+hyperpolarized+noble+gases.">MRI of the lungs using hyperpolarized noble gases.</a> Magnetic Resonance in Medicine. 47 (6), 1029-1051 (2002).</li><li>Salerno, M., Altes, T. A., Mugler, J. P., Nakatsu, M., Hatabu, H., de Lange, E. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Hyperpolarized+noble+gas+MR+imaging+of+the+lung:+Potential+clinical+applications.">Hyperpolarized noble gas MR imaging of the lung: Potential clinical applications.</a> European Journal of Radiology. 40 (1), 33-44 (2001).</li><li>. New Drug Therapy Approvals at 2022 Available from: <a target="_blank" href="https://www.fda.gov/drugs/new-drugs-fda-cders-new-molecular-entities-and-new-therapeutic-biological-products/new-drug-therapy-approvals-2022">https://www.fda.gov/drugs/new-drugs-fda-cders-new-molecular-entities-and-new-therapeutic-biological-products/new-drug-therapy-approvals-2022</a> (2023)</li><li>Nikolaou, P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Near-unity+nuclear+polarization+with+an+open-source+129Xe+hyperpolarizer+for+NMR+and+MRI.">Near-unity nuclear polarization with an open-source 129Xe hyperpolarizer for NMR and MRI.</a> Proceedings of the National Academy of Sciences. 110 (35), 14150-14155 (2013).</li><li>Birchall, J. R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=XeUS:+A+second-generation+automated+open-source+batch-mode+clinical-scale+hyperpolarizer.">XeUS: A second-generation automated open-source batch-mode clinical-scale hyperpolarizer.</a> Journal of Magnetic Resonance. 319, 106813 (2020).</li><li>He, M., Zha, W., Tan, F., Rankine, L., Fain, S., Driehuys, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+comparison+of+two+hyperpolarized+129Xe+MRI+ventilation+quantification+pipelines:+The+effect+of+signal+to+noise+ratio.">A comparison of two hyperpolarized 129Xe MRI ventilation quantification pipelines: The effect of signal to noise ratio.</a> Academic Radiology. 26 (7), 949-959 (2019).</li><li>Niedbalski, P. J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Protocols+for+multi-site+trials+using+hyperpolarized+129+Xe+MRI+for+imaging+of+ventilation,+alveolar-airspace+size,+and+gas+exchange:+A+position+paper+from+the+129+Xe+MRI+clinical+trials+consortium.">Protocols for multi-site trials using hyperpolarized 129 Xe MRI for imaging of ventilation, alveolar-airspace size, and gas exchange: A position paper from the 129 Xe MRI clinical trials consortium.</a> Magnetic Resonance in Medicine. 86 (6), 2966-2986 (2021).</li><li>M&#246;ller, H. E., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=MRI+of+the+lungs+using+hyperpolarized+noble+gases.">MRI of the lungs using hyperpolarized noble gases.</a> Magnetic Resonance in Medicine. 47 (6), 1029-1051 (2002).</li><li>Bier, E. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+thermally+polarized+129Xe+phantom+for+quality+assurance+in+multi-center+hyperpolarized+gas+MRI+studies.">A thermally polarized 129Xe phantom for quality assurance in multi-center hyperpolarized gas MRI studies.</a> Magnetic Resonance in Medicine. 82 (5), 1961-1968 (2019).</li><li>Wild, J. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Comparison+between+2D+and+3D+gradient-echo+sequences+for+MRI+of+human+lung+ventilation+with+hyperpolarized+3He.">Comparison between 2D and 3D gradient-echo sequences for MRI of human lung ventilation with hyperpolarized 3He.</a> Magnetic Resonance in Medicine. 52 (3), 673-678 (2004).</li><li>Garrison, W. J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Lung+volume+dependence+and+repeatability+of+hyperpolarized+129Xe+MRI+gas+uptake+metrics+in+healthy+volunteers+and+participants+with+COPD.">Lung volume dependence and repeatability of hyperpolarized 129Xe MRI gas uptake metrics in healthy volunteers and participants with COPD.</a> Radiology: Cardiothoracic Imaging. 5 (3), e220096 (2023).</li><li>Ni, W., Qi, J., Liu, L., Li, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+pulse+signal+preprocessing+method+based+on+the+Chauvenet+criterion.">A pulse signal preprocessing method based on the Chauvenet criterion.</a> Computational and Mathematical Methods in Medicine. 2019, 2067196 (2019).</li><li>. Available from: <a target="_blank" href="https://www.129xectc.org">https://www.129xectc.org</a> (2023)</li></ol>

Robert Thomen has provided consulting to Polarean, LLC.

The ability to troubleshoot 129Xe MRI issues is a necessary skill and may help mitigate problems in real time. Until a hyperpolarized gas infrastructure can be purchased from a single party and garner support from scanner manufacturers, these quality control tasks are the sole responsibility of the individual laboratories. The goal of this manuscript is to provide the reader with helpful practices and suggestions for the inevitable event of poor data acquisition. While we attempt to address as many potential i...

For over a century, lung function assessment has primarily relied on global measurements from spirometry and body plethysmography. However, these traditional pulmonary function tests (PFTs) are limited in their ability to capture early-stage disease&#39;s regional nuances and subtle changes in lung tissue1. Nuclear medicine with inhaled radiotracers has been used widely for the assessment of ventilation/perfusion mismatches commonly associated with pulmonary emboli, but this involves ionizing radiation and yields lower resolution. In contrast, computed tomography (CT) has emerged as the gold standard for lung imaging, offering exceptional spatial and temporal clarity compared to nuclear imaging2. While low-dose CT scans can mitigate radiation exposure, potential radiation risk should still be considered3,4. Proton MRI of the lung is uncommon due to low tissue density of the lung and rapid signal decay from lung tissue, although recent advances offer functional information despite potential low signal. On the other hand, hyperpolarized xenon magnetic resonance imaging (HP 129Xe MRI) is a non-invasive modality that allows for imaging of lung function with regional specificity5,6. It produces a high nonequilibrium nuclear magnetization of the gas in liter quantities. The inert gas is then inhaled by a subject inside the MR scanner for a single breath and is directly imaged by the scanner. Thus, the inhaled gas is directly imaged as opposed to the tissue itself. This technique has been used to assess lung ventilation across many diseases, including asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis, idiopathic pulmonary fibrosis, coronavirus disease 2019 (COVID-19), and many others3. In December 2022, HP 129Xe MRI was approved by the United States FDA as an MRI ventilation contrast agent to be used in the United States of America (USA) in adults and pediatric patients aged 12 years and older7. Physicians can now use 129Xe MRI to better care for patients with improved/personalized treatment plans.
Historically, clinical MRI focuses exclusively on imaging hydrogen nuclei (protons) which are abundant in nearly all human viscera. The MRI scanners, sequences, and quality control are generally maintained by the scanner manufacturer as part of the site license and warranty. However, 129Xe requires a multinuclear capable MR scanner and has required a dedicated research team to operationalize the hyperpolarizer, custom-built radiofrequency (RF) coils, dedicated pulse sequences, and offline reconstruction/analysis software. Each of these components can be supplied by third-party vendors or developed in-house. Thus, the burden of quality control generally rests on the 129Xe research team as opposed to the scanner manufacturer or individual third party. Consistent acquisition of high-quality 129Xe data is therefore uniquely challenging as each component of the 129Xe MRI process introduces the potential for error, which must be closely monitored by the 129Xe team. Not only can these situations be extremely frustrating as researchers have to troubleshoot and investigate possible causes for any challenges that may have arisen, but they can be very costly as this slows down patient imaging and subject recruitment. Some costs associated with troubleshooting involve MRI time costs, the hyperpolarization of 129Xe, which involves the consumption of different gases, and the use of materials. Additionally, with the recent FDA approval and growth in 129Xe imaging, providing a standardized protocol for quality control is necessary to avoid common issues and setbacks in 129Xe operation8,9.
Here, we present some of the more commonly encountered issues in 129Xe MRI, including RF coil failures, the emergence of various noise profiles that lead to low signal-to-noise ratio (SNR), and poor quality images10. We aim to provide some concise quality control (QC) guidelines and protocols to ensure the acquisition of high-quality image data and troubleshoot some of the more common issues that can arise in 129Xe MRI. The insights provided here are also relevant for hyperpolarized helium-3 troubleshooting.

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	<tbody>
		<tr>
			<td>Polarization measurement station&#160;</td>
			<td>Polerean</td>
			<td>42881</td>
			<td>https://polarean.com/</td>
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		<tr>
			<td>Pressure vessele with plunger valve</td>
			<td>Ace glass</td>
			<td>8648-85</td>
			<td>https://www.aceglass.com/html/3dissues/Pressure_Vessels/offline/download.pdf</td>
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		<tr>
			<td>Tedlar bag</td>
			<td>Jensen inert</td>
			<td>GST381S-0707TJO&#160;&#160;</td>
			<td>http://www.jenseninert.com/</td>
		</tr>
		<tr>
			<td>Xenon Hyperpolarizer 9820</td>
			<td>Polerean</td>
			<td>49820</td>
			<td>https://polarean.com/</td>
		</tr>
		<tr>
			<td>Xenon loop coil</td>
			<td>Clinical MR Solutions</td>
			<td>Custom device</td>
			<td>https://www.sbir.gov/sbc/clinical-mr-solutions-llc</td>
		</tr>
		<tr>
			<td>Xenon vest coil</td>
			<td>Clinical MR Solutions</td>
			<td>Custom device</td>
			<td>https://www.sbir.gov/sbc/clinical-mr-solutions-llc</td>
		</tr>
	</tbody>
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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 

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

In hyperpolarized xenon MRI, the actual inhaled gas is directly imaged. The gas uniformly distributes itself in lungs of healthy individuals, but in those with lung disease, such as asthma, COPD or cystic fibrosis, it does not. We aim to understand these diseases better using this technology.X-ray computed tomography, or CT, provides the current clinical standard in pulmonary structural imaging, but involves ionizing radiation and shows only lung tissue, not the inhaled gas. Nuclear medicine, by inhaled or injected radio tracers can also be used to assess pulmonary ventilation and profusion, but is ionizing and relatively low resolution. Xenon MRI, however, provides a high resolution snapshot of an individual's pulmonary ventilation and gas exchange.Implementing xenon MRI is uniquely challenging, requiring specialized hardware, xenon imaging coils, and sequence development. The journey doesn't end there. The acquired data must undergo meticulous reconstruction and analysis.Without proper expertise, these tasks can be daunting, leading to frustrating and expensive outcomes. This protocol offers insight into quality control, troubleshooting, and tools for xenon MRI sites, We explored the setup of hyperpolarizer labs, xenon MRI coils, data acquisition consideration, and image properties. Our goal is to guide the audience through potential errors, challenges, and occurrences that may impact image quality or outcomes.Troubleshooting xenon MRI issues is necessary to mitigate problems in real life. Given the absence of a dedicated hyperpolarized gas infrastructure and limited support from scanner manufacturers, quality control tasks fall solely on individual labs. This video aims to equip viewers with practical tips for addressing challenges and ensuring successful data acquisition.

Figure 4&#160;depicts the results of the noise characterization analysis performed on the noise scan. The plot demonstrates the impact of both regular and irregular noise on the k-space, where the deviation from the ideal y=x reference line is observed. Regular noise leads to a continuous pattern in the k-space, while irregular noise results in high-value outliers in the QQ plot.
Moving on to Figure 5, a series of lung images acquired...

Watch this Scientific Journal Video about Using Hyperpolarized Xenon-129 MRI to Study Lung Diseases at JoVE.com

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 ...

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Research

JoVE Journal

Bioengineering

129Xe Hyperpolarization and Assessment of Polarization Loss During Transport

129Xe Hyperpolarization and Assessment of Polarization Loss During Transport  

To begin, ensure the XENON 129 hyperpolarizer is set up and operational as per the manufacturer's guidelines. Next, use NMR at the Hyperpolarization or HP Measurement Station to conduct T1 relaxation measurements on a representative HP Xenon 129 gas sample. Ensure a direct and efficient route from the Xenon collection point to the Magnet Room designated for imaging to minimize delays during Xenon transportation.Measure the initial dose equivalent, or DE, of the hyperpolarized Xenon 129 gas before transportation using the displayed equation. Avoid extraneous radio frequency signals along the route as they can contribute to polarization loss. After completing the round trip by transporting the gas from the measurement station into the magnet bore, then back along the same route to the Polarimetry station.Measure DE again to quantify the anticipated signal loss during gas transport.

Performing 129Xe Spectroscopy and Hyperpolarized 129Xe Imaging for Quality Control at 129Xe MRI Sites

Performing 129Xe Spectroscopy and Hyperpolarized 129Xe Imaging for Quality Control at 129Xe MRI Sites  

Begin by creating a thermally polarized 129 xenon phantom. To do so, connect a glass pressure vessel to a xenon gas filled bag, having an appropriate size and volume aligning with the vessel's capacity. Then submerge the pressure vessel in a small amount of liquid nitrogen to allow xenon diffusion and freezing.Seal the vessel after the xenon has formed frozen snow inside. Allow it to thaw while pressurizing the vessel before calculating the pressure in the vessel. To detect peak frequency, put the phantom inside the xenon 129 coil and place it similar to that of a loaded patient.Perform a scan with proton frequency as some scanners may disallow multinuclear scans without initial proton frequency localizer. Use a broadband transmit pulse if available, high bandwidth and high resolution readout experiment, to accurately detect the xenon frequency peak. Once a well-defined peak is detected, record the frequency to full precision.Repeat the new experiment at the new frequency with a low bandwidth of about 1000 hertz to maximize signal to noise ratio or SNR and peak frequency precision. Once a satisfactory high signal peak is detected, save the protocol for future quality control tests. Use a small amount of hyperpolarized xenon 129, which is well concentrated and free of oxygen for imaging.Measure the xenon 129 dose equivalent or DE accurately immediately prior to imaging. Set the test imaging protocol to reflect desired in vivo parameters as closely as possible. Acquire and save the image of the xenon bag as a baseline measure of scanner performance.Measure and record the SNR of the acquired images alongside all scan parameters and xenon DE.For measuring alpha, the flip angle, perform a full volume spoiled gradient echo scan in which the field of view is imaged twice in succession using identical sequence parameters. Measure the SNR at the DC offset of the two images S0 and S1.Count the number of phase encoding steps n, and calculate the flip angle.

Systemic Noise Detection and Characterization During 129Xe MRI Troubleshooting

Systemic Noise Detection and Characterization During 129Xe MRI Troubleshooting  

Begin by creating a control noise profile for quality control, or QC purposes. Use a specific customized 2D GRE sequence, including a high field of view, to capture the maximum signal from the area, a high bandwidth per pixel to identify nearby noise resonances and the lowest possible repetition time, or TR, and echo time, or TE.Acquire the QC for noise profile using a xenon vest or a loop coil. Obtain an image with no hyperpolarized xenon 129 sample in the coil.This image will characterize the noise profile. Examine the acquired noise data, particularly the K-space for non-Gaussian elements, such as spikes, patterns, or discretized or binned values. Create a quantile-quantile, or QQ plot, by plotting the acquired real or imaginary data against a synthesized Gaussian dataset with identical mean, standard deviation, and vector length, both ordered from the smallest to largest.Deviations from the line Y is equal to X in the QQ plot, indicate the presence of non-Gaussian components within the acquired data, requiring further investigation. Proceed to identify the noise distribution pattern and potential outliers with a suitable plot of choice. To rule out the scanner as a noise source, acquire images using the standard site protocol with various pulse sequence parameters disabled, and electronic components powered off.Refer to the list on the screen for possible noise sources. To eliminate noise sources from the room, use a simple surface loop coil tuned to the xenon 129 frequency to sniff around the magnet room for noise sources. Physically place the xenon coil element near potential problematic devices and run a test sequence to detect amplified noise.Examine K-space and image data to pinpoint the exact source of coherence noise. If a specified source is identified, attempt to disable it or cover it with aluminum foil, flashing or a copper mesh to reduce noise. Rerun the scan after disabling or covering noise sources to see if the noise resolves.Continue this process until all noise sources are eliminated, leaving only low root mean square Gaussian noise. Identify irregular noise as high signal spikes in individual K-space pixels with abnormally high or low signals in the real or imaginary channels. Perform imaging in different phase encoding orientations, including anterior to posterior, head to foot, and left to right.Eliminate potential issues with X-Y-or Z-gradients, by enabling or disabling individual gradients selectively. Systematically examine the resulting images to identify which specific gradient direction is contributing to the noise. The results of the noise characterization analysis performed on the noise scan demonstrated the impact of both regular and irregular noise on the K-space.Regular noise led to a continuous pattern in the K-space, while irregular noise resulted in high value outliers in the QQ plot. A series of lung images acquired using HPG MRI showed that a distinct bright spot centered in the K-space indicated a clear lung signal with low noise. Conversely, the presence of regular noise was spread throughout the images.Irregular noise evidently caused high value spikes in the K-space, and resulted in a striped pattern in image space. A scenario where both regular and irregular noises were present simultaneously also affected the lung image.

768 Views.  University of Missouri.  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.

Obtaining High-Quality Hyperpolarized Xenon-129 Magnetic Resonance Images

Summary