Xenon MRI for Detecting Brown Fat in Obesity

Overseen By Rosa Tamara Branca, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: University of North Carolina, Chapel Hill

Must not be taking: Beta blockers

Disqualifiers: Cardiovascular disease, Pregnancy, Claustrophobia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

32 Participants Needed

Trial Summary

What is the purpose of this trial?

The primary goal of this study is to evaluate the feasibility of detecting Brown Adipose Tissue (BAT) in healthy subjects by using hyperpolarized xenon gas MRI. In this pilot study, MRI of BAT of healthy adult volunteers will be performed at 3 Tesla to assess image quality using a prototype surface coil and pulse sequence following inhalation of hyperpolarized 129Xe (xenon) gas at thermoneutrality and under mild cold condition. The investigators are testing the abilities of xenon MRI to see brown adipose tissue and detect its thermogenic activity.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are taking beta blockers.

What data supports the effectiveness of the treatment Xenon MRI for detecting brown fat in obesity?

Research shows that hyperpolarized xenon gas MRI can noninvasively image brown adipose tissue (BAT) in mice, detecting a significant increase in xenon uptake during BAT activation. This suggests that the treatment could effectively identify and measure BAT in both lean and obese subjects, potentially aiding in obesity studies. ^{1 2 3 4 5}

Is hyperpolarized xenon-129 MRI safe for humans?

Studies have shown that hyperpolarized xenon-129 MRI is generally safe for humans, with protocols ensuring oxygen levels remain stable during imaging. Continuous monitoring and standardized procedures are important to maintain safety during the process. ^{6 7 8 9 10}

How is the treatment Xenon MRI for detecting brown fat in obesity different from other treatments?

Xenon MRI is unique because it uses hyperpolarized xenon gas to enhance MRI imaging, allowing for detailed visualization of tissues like brown fat, which is not possible with standard imaging techniques. This method leverages the special properties of xenon gas to improve contrast and image quality, offering a novel approach to studying obesity-related changes in the body. ^{11 12 13 14 15}

Research Team

Rosa Tamara Branca, PhD

Principal Investigator

University of North Carolina, Chapel Hill

Eligibility Criteria

This study is for healthy adults over 18 who haven't smoked in the last 5 years and have no lung conditions or history of significant smoking. Participants must be able to hold their breath for at least 15 seconds, not be pregnant or breastfeeding, free from severe claustrophobia, and without any metal implants that could interfere with MRI.

Inclusion Criteria

Smoking history, if any, is less than or equal to 5 pack-years

Written informed consent (and assent when applicable) obtained from subject or subject's legal representative and ability for subject to comply with the requirements of the study

I am healthy and may or may not have had a PET scan.

Exclusion Criteria

MRI is contraindicated based on responses to MRI screening questionnaire

Severe claustrophobia

I am under 18 years old.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Imaging

Participants undergo MRI scans using hyperpolarized xenon gas to detect brown adipose tissue and its thermogenic activity

1 day

1 visit (in-person)

Follow-up

Participants are monitored for any immediate effects post-MRI scan

1 week

Treatment Details

Interventions

• Xenon

Trial Overview The trial is testing if a special type of MRI using hyperpolarized xenon gas can effectively visualize brown fat tissue in the body under normal and slightly cold conditions. It aims to assess image quality and detect activity within this fat tissue.

Participant Groups

Group I: Xenon inhalation Experimental Treatment 1 Intervention

Inhalation of 5 doses of 750ml of hyperpolarized 129Xe gas

Who Is Running the Clinical Trial?

University of North Carolina, Chapel Hill

Lead Sponsor

Trials

1,588

Recruited

4,364,000+

North Carolina Translational and Clinical Sciences Institute

Collaborator

Trials

61

Recruited

4,600+

Findings from Research

A modified MRI protocol successfully visualized and quantified brown adipose tissue (BAT) in laboratory mice, revealing significantly reduced BAT volume in a Huntington disease (HD) model compared to controls (n = 5 per group).

This reduction in BAT volume may explain the energy deficit observed in HD, highlighting the potential of this imaging technique to study BAT in various metabolic disorders and track disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two-point magnitude MRI for rapid mapping of brown adipose tissue and its application to the R6/2 mouse model of Huntington disease. Lindenberg, KS., Weydt, P., Müller, HP., et al.[2021]

Xenon-enhanced computed tomography allows for accurate quantification of brown adipose tissue (BAT) mass, even in obese phenotypes where traditional imaging fails.

The method works by using xenon gas to enhance the visibility of BAT during thermogenesis, which is linked to increased blood flow and reduced vascular resistance in the tissue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accurate quantification of brown adipose tissue mass by xenon-enhanced computed tomography. Branca, RT., McCallister, A., Yuan, H., et al.[2018]

A new noninvasive imaging technique using hyperpolarized xenon gas MRI allows for the effective measurement of brown adipose tissue (BAT) and its thermogenic function in living mice, overcoming limitations of previous imaging methods.

This technique revealed a significant increase in xenon uptake by BAT during thermogenesis, providing a way to create detailed maps of BAT activity in both lean and obese mice, and enabling direct measurement of BAT temperature to monitor its activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Detection of brown adipose tissue and thermogenic activity in mice by hyperpolarized xenon MRI. Branca, RT., He, T., Zhang, L., et al.[2018]

In a study of 20 healthy volunteers, the relaxation rate (R2*) of supraclavicular brown adipose tissue (scBAT) measured by MRI was found to positively correlate with cold-induced thermogenesis (CIT), suggesting it can be a useful predictor of metabolic activity.

The volume and fat fraction (FF) of scBAT did not show a significant correlation with CIT, indicating that R2* may be a more reliable measure for assessing the metabolic function of brown fat compared to these other metrics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MRI characteristics of supraclavicular brown adipose tissue in relation to cold-induced thermogenesis in healthy human adults. Gashi, G., Madoerin, P., Maushart, CI., et al.[2020]

MRI using the DUAL-SPIR technique was found to reliably visualize and quantify brown adipose tissue (BAT) in rats, showing a strong correlation with histological findings, which suggests it could be a more effective method than the current gold standard, (18)FDG-PET.

Unlike (18)FDG-PET, MRI can detect BAT regardless of its metabolic activation state and is a low-cost, non-radiative alternative for assessing BAT in vivo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Measurement of brown adipose tissue mass using a novel dual-echo magnetic resonance imaging approach: a validation study. Holstila, M., Virtanen, KA., Grönroos, TJ., et al.[2022]

In a study involving 17 rats, alternating breaths of hyperpolarized helium or xenon with oxygen resulted in less than a 5% decrease in blood oxygen saturation, indicating these protocols are safe for MRI experiments.

However, continuous breathing of noble gases led to significant drops in oxygen saturation, particularly with helium and xenon, highlighting the importance of careful monitoring and standardized procedures during such inhalation protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Physiological response of rats to delivery of helium and xenon: implications for hyperpolarized noble gas imaging. Ramirez, MP., Sigaloff, KC., Kubatina, LV., et al.[2019]

A new phantom assembly made from high-density polyethylene and filled with a xenon-oxygen mixture has been developed to standardize quality assurance for hyperpolarized 129 Xe MRI across different imaging centers.

This assembly allows for effective testing and performance tracking of MRI systems, demonstrating consistent signal-to-noise ratios (SNR) and enabling reliable imaging protocols essential for improving the accuracy of hyperpolarized 129 Xe imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A thermally polarized 129 Xe phantom for quality assurance in multi-center hyperpolarized gas MRI studies. Bier, EA., Nouls, JC., Wang, Z., et al.[2020]

A new continuous-flow system for producing hyperpolarized xenon (129Xe) has been developed, achieving production rates of 0.3 liters per hour with 64% polarization, significantly improving the availability of this imaging agent for lung MRI studies.

This technology allows for the production of multiliter quantities of hyperpolarized xenon several times daily, enabling more extensive human lung imaging studies that were previously limited by the availability of hyperpolarized gas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Large production system for hyperpolarized 129Xe for human lung imaging studies. Hersman, FW., Ruset, IC., Ketel, S., et al.[2022]

Inhalation of hyperpolarized xenon-129 (129Xe) was found to be safe and well tolerated among 44 subjects, including healthy individuals and patients with chronic obstructive pulmonary disease (COPD), with no serious adverse events reported.

While 91% of participants experienced mild and transient symptoms such as dizziness and euphoria, these symptoms resolved quickly without the need for clinical intervention, indicating that the procedure is generally safe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic obstructive pulmonary disease: safety and tolerability of hyperpolarized 129Xe MR imaging in healthy volunteers and patients. Driehuys, B., Martinez-Jimenez, S., Cleveland, ZI., et al.[2022]

Hyperpolarized 129Xe MRI (HypX-MRI) shows great promise as a new diagnostic tool, enhancing the detectability of lung structures and potentially allowing for better imaging of lipid-rich tissues, which has been challenging with traditional methods.

This technique could help identify issues like ventilation-perfusion mismatch in pulmonary diseases and may also be used for functional MRI studies of the brain, opening new avenues for understanding lung function and brain perfusion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of hyperpolarized noble gas MRI. Albert, MS., Balamore, D.[2019]

High-quality MRI of lung ventilation can be achieved using naturally abundant xenon (NAXe) gas, demonstrating its potential as a cost-effective imaging agent for pulmonary studies.

The study showed that NAXe MRI provided comparable image quality to enriched xenon and helium-3 (3He) imaging, with the ability to detect minor ventilation defects, particularly in a healthy smoker's lungs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility of human lung ventilation imaging using highly polarized naturally abundant xenon and optimized three-dimensional steady-state free precession. Stewart, NJ., Norquay, G., Griffiths, PD., et al.[2022]

The study measured the polarization lifetime (T1) of hyperpolarized 129-xenon in human blood, finding T1 values of 4.5 seconds for red blood cells and 9.6 seconds for plasma, which are sufficient for potential MRI applications beyond lung imaging.

Despite the T1 values being shorter than expected, they are comparable to blood transport times, suggesting that hyperpolarized 129-xenon could be effectively used for MRI studies in various body tissues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Measurement of 129Xe T1 in blood to explore the feasibility of hyperpolarized 129Xe MRI. Albert, MS., Schepkin, VD., Budinger, TF.[2019]

This study successfully demonstrates the use of laser-polarized 129Xe MRI in a small animal model, specifically Sprague-Dawley rats, showing that polarized xenon can be introduced into the lungs and effectively transported to the brain for imaging.

The research reveals that 129Xe accumulates in brain tissue, allowing for detailed imaging and potential clinical applications in measuring regional cerebral blood flow, which could enhance our understanding of brain function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain MRI with laser-polarized 129Xe. Swanson, SD., Rosen, MS., Agranoff, BW., et al.[2019]

Hyperpolarized noble gases like 3He and 129Xe show unique magnetization properties that can enhance MRI imaging, particularly in air spaces like the lungs and trachea, but require careful optimization of imaging parameters.

Using hyperpolarized 129Xe for functional MRI (fMRI) could provide new insights into blood flow, although its short-lived hyperpolarization presents both opportunities and challenges for its application as a tracer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnetization and diffusion effects in NMR imaging of hyperpolarized substances. Gao, JH., Lemen, L., Xiong, J., et al.[2019]

Laser-polarized xenon NMR can be a powerful tool for probing living tissues due to its sensitivity to the local environment, but effective delivery methods are needed for broader clinical applications.

Preliminary results suggest that injecting polarized xenon can achieve significantly higher local concentrations in tissues compared to delivering it through respiration, potentially enhancing imaging capabilities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vivo NMR and MRI using injection delivery of laser-polarized xenon. Goodson, BM., Song, Y., Taylor, RE., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Two-point magnitude MRI for rapid mapping of brown adipose tissue and its application to the R6/2 mouse model of Huntington disease. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Accurate quantification of brown adipose tissue mass by xenon-enhanced computed tomography. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

Detection of brown adipose tissue and thermogenic activity in mice by hyperpolarized xenon MRI. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

MRI characteristics of supraclavicular brown adipose tissue in relation to cold-induced thermogenesis in healthy human adults. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

Measurement of brown adipose tissue mass using a novel dual-echo magnetic resonance imaging approach: a validation study. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Physiological response of rats to delivery of helium and xenon: implications for hyperpolarized noble gas imaging. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

A thermally polarized 129 Xe phantom for quality assurance in multi-center hyperpolarized gas MRI studies. [2020]

8. United States pubmed.ncbi.nlm.nih.gov

Large production system for hyperpolarized 129Xe for human lung imaging studies. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Chronic obstructive pulmonary disease: safety and tolerability of hyperpolarized 129Xe MR imaging in healthy volunteers and patients. [2022]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Development of hyperpolarized noble gas MRI. [2019]

11. United States pubmed.ncbi.nlm.nih.gov

Feasibility of human lung ventilation imaging using highly polarized naturally abundant xenon and optimized three-dimensional steady-state free precession. [2022]

12. United States pubmed.ncbi.nlm.nih.gov

Measurement of 129Xe T1 in blood to explore the feasibility of hyperpolarized 129Xe MRI. [2019]

13. United States pubmed.ncbi.nlm.nih.gov

Brain MRI with laser-polarized 129Xe. [2019]

14. United States pubmed.ncbi.nlm.nih.gov

Magnetization and diffusion effects in NMR imaging of hyperpolarized substances. [2019]

15. United States pubmed.ncbi.nlm.nih.gov

In vivo NMR and MRI using injection delivery of laser-polarized xenon. [2023]