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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test a new method for visualizing and measuring brown fat using a special MRI scan with xenon gas. Brown fat helps burn calories and produce heat, playing a crucial role in managing obesity. The study will evaluate whether this MRI method can effectively detect brown fat activity. Participants should be healthy adults who haven't smoked in the last five years and have no lung or heart issues. As a Phase 1 trial, the research focuses on understanding how this new MRI method works in people, offering participants the opportunity to experience this innovative approach firsthand.

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 prior data suggests that this MRI technique is safe for detecting brown fat?

Research shows that xenon gas, used in this trial, is generally safe and well-tolerated. Studies have found that hyperpolarized xenon gas, similar to what is used in MRI scans, is safe for people during medical imaging. No serious side effects have been reported in studies using it to image brown fat, a type of body fat. However, since this is an early-phase study, the researchers are primarily assessing the safety and practicality of xenon MRI. So far, the data suggests that breathing in hyperpolarized xenon gas is safe and doesn't cause major issues. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using Xenon MRI to detect brown fat in obesity because it offers a non-invasive and precise way to visualize and quantify brown fat activity, something current methods struggle with. Unlike standard imaging techniques like PET scans, which can be expensive and involve radiation exposure, Xenon MRI uses hyperpolarized 129Xe gas, making it safer and potentially more accessible. This novel approach could lead to a better understanding of brown fat's role in metabolism and help develop targeted obesity treatments.

What evidence suggests that xenon MRI is effective for detecting brown fat in obesity?

Research has shown that a special type of MRI using hyperpolarized xenon gas can image brown fat in mice. This technique detects a significant increase in xenon uptake when brown fat is active. One study found that xenon uptake by brown fat increased more than 15 times during heat production. These findings suggest that xenon MRI, which participants in this trial will undergo through xenon inhalation, could also identify active brown fat in humans. This method might aid in understanding obesity by revealing the presence and activity of brown fat. ^{3 6 7 8 9}

Who Is on the Research Team?

Rosa Tamara Branca, PhD

Principal Investigator

University of North Carolina, Chapel Hill

Are You a Good Fit for This Trial?

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

I am under 18 years old.

Severe claustrophobia

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: Xenon inhalation Experimental Treatment 1 Intervention

Inhalation up to 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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. withpower.com withpower.com/trial/phase-1-8-2015-01afd

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 ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02220426

Hyperpolarized Xenon-129 Magnetic Resonance Imaging ... 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.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02220426?cond=%22Body%20Mass%20Index%20Quantitative%20Trait%20Locus%2020%22&intr=%22anesthetics,%20inhalation%22&viewType=Table&rank=4

Study Details | Hyperpolarized Xenon-129 Magnetic Resonance ... Types of outcome measures include primary outcome measure and secondary outcome measure. ... A type of intervention model describing a clinical trial in which two ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4273360/

Detection of brown adipose tissue and thermogenic activity ... We detect a greater than 15-fold increase in xenon uptake by BAT during stimulation of BAT thermogenesis, which enables us to acquire background ...

5. cds.ismrm.org cds.ismrm.org/protected/17MProceedings/PDFfiles/3430.html

Hyperpolarized 129Xe MRI vs Xenon Enhanced CT Here we demonstrate the combined used of hyperpolarized xenon gas (HP129Xe) MRI and xenon enhanced CT for the detection of BAT thermogenic activity and mass ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02220426

Hyperpolarized Xenon-129 Magnetic Resonance Imaging ... 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.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10582175/

Absolute thermometry of human brown adipose tissue by ... Here, we report direct measurement of absolute BAT temperature in humans during cold exposure by magnetic resonance (MR) with laser polarized xenon gas.

8. mdpi.com mdpi.com/1422-0067/25/3/1939

Hyperpolarized Xenon-129 Chemical Exchange Saturation ... It provides superior contrast and sensitivity in imaging, making HP 129Xe MRI a valuable tool for the early detection and characterization of various ...

9. pubs.acs.org pubs.acs.org/doi/10.1021/acs.accounts.6b00309

An Expanded Palette of Xenon-129 NMR Biosensors This review summarizes recent developments in the production of hyperpolarized xenon and the design and detection schemes of xenon biosensors.