Obesity
Conditions
Keywords
Brown adipose tissue, Hyperpolarized xenon gas MRI
Brief summary
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.
Detailed description
In the fight against obesity, brown adipose tissue (BAT) is considered to be the newest target. The hypothesis is that this tissue is partially responsible for the imbalance between energy intake and energy expenditure that keeps lean people lean and obese people obese. As the detection of this tissue in adult humans is difficult, this study aim to evaluate the use of hyperpolarized xenon gas MRI for the detection of this tissue. Hyperpolarized xenon gas MRI is currently used for lung ventilation studies. For this study subjects will undergo an MRI scan for which they will also inhaled hyperpolarized xenon. Scans will be done before and during stimulation of thermogenic activity by cold exposure, while MR images and spectra will be acquired from the supraclavicular area. We expect that the inhaled gas will diffuse into blood and eventually reach BAT in a manner proportional to the metabolic activity of this tissue. Objectives of this studies are: * To detect BAT volume using hyperpolarized xenon MRI * To detect BAT thermogenic activity by hyperpolarized xenon Nuclear Magnetic Resonance (NMR) spectroscopy
Interventions
DRUGXenon
Inhalation of hyperpolarized xenon gas
Sponsors
North Carolina Translational and Clinical Sciences Institute
University of North Carolina, Chapel Hill
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
* Ability to give informed consent * Willing to participate in this study * Male or female ≥ 18 years of age at the time of the interview. * Subject has no diagnosed pulmonary condition * Subject has not smoked in the previous 5 years * 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 * Healthy subject that may or may not have undergone an fluorodeoxyglucose -Positron Emission Tomography (PET) scan
Exclusion criteria
* Any contraindication to MRI (presence of any non-removable metal implant, stents, pacemaker, clips, staples, or piercings, etc. ) * Subject does not fit in the magnet * Pregnancy or breast feeding * Severe claustrophobia * Subject is less than 18 years old * MRI is contraindicated based on responses to MRI screening questionnaire * Subject is pregnant or lactating * Respiratory illness of a bacterial or viral etiology within 15 days of MRI * Subject has received an investigational medicinal product (not including 129Xe) within 30 days of MRI * Subject has any form of known cardiovascular disease * Subject cannot hold their breath for 15 seconds * Subject deemed unlikely to be able to comply with instructions during imaging * Subject is taking beta blockers * Subject underwent an fluorodeoxyglucose-PET examination less than one week before the HP xenon MRI scan
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Brow Adipose Tissue Surface Area | Day 1 | For each subject, the brown adipose tissue (BAT) surface area is derived from 2D MR images acquired without slice selection, obtained before and during cold exposure. Each image consists of Nx × Ny pixels, each having an in-plane pixel area (Apixel, in millimeters squared) calculated as: Apixel=(FOVx/Nx)×(FOVy/Ny), where FOVx and FOXy are the field-of-view dimensions in millimeters in the x and y directions, respectively. BAT-positive pixels are defined as those whose signal intensity increases by more than 5% during cold stimulation relative to baseline. The total BAT surface area (ABAT, in millimeters squared) is then computed as: ABAT=NBAT×Apixel where NBAT is the number of BAT-positive pixels for each subject. This approach yields the total in-plane area of activated BAT within the 2D field of view for each subject. The value obtained for all subjects was then averaged. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in BAT Temperature | Day 1 | Change in BAT temperature (in degree Celsius) will be estimated from xenon nuclear magnetic resonance (NMR) spectra acquired at thermoneutrality and during cold exposure. Both proton (1H) and xenon (129Xe) spectra are required to perform the temperature calculation. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Xenon Inhalation Inhalation of up to 5 doses of 750ml of hyperpolarized 129Xe gas
Xenon: Inhalation of hyperpolarized xenon gas | 13 |
| Total | 13 |
Baseline characteristics
| Characteristic | Xenon Inhalation |
|---|---|
| Age, Continuous | 26.6 years STANDARD_DEVIATION 8.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 11 Participants |
| Region of Enrollment United States | 13 Participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 13 |
| other Total, other adverse events | 12 / 13 |
| serious Total, serious adverse events | 0 / 13 |
Outcome results
Primary
Brow Adipose Tissue Surface Area
For each subject, the brown adipose tissue (BAT) surface area is derived from 2D MR images acquired without slice selection, obtained before and during cold exposure. Each image consists of Nx × Ny pixels, each having an in-plane pixel area (Apixel, in millimeters squared) calculated as: Apixel=(FOVx/Nx)×(FOVy/Ny), where FOVx and FOXy are the field-of-view dimensions in millimeters in the x and y directions, respectively. BAT-positive pixels are defined as those whose signal intensity increases by more than 5% during cold stimulation relative to baseline. The total BAT surface area (ABAT, in millimeters squared) is then computed as: ABAT=NBAT×Apixel where NBAT is the number of BAT-positive pixels for each subject. This approach yields the total in-plane area of activated BAT within the 2D field of view for each subject. The value obtained for all subjects was then averaged.
Time frame: Day 1
Population: No imaging data were collected for 9 participants because the Xenon signal did not reach the needed threshold required for imaging.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Xenon Inhalation | Brow Adipose Tissue Surface Area | 3541 millimiters squared | Standard Deviation 2474 |
Secondary
Change in BAT Temperature
Change in BAT temperature (in degree Celsius) will be estimated from xenon nuclear magnetic resonance (NMR) spectra acquired at thermoneutrality and during cold exposure. Both proton (1H) and xenon (129Xe) spectra are required to perform the temperature calculation.
Time frame: Day 1
Population: Temperature measurements were not performed because the xenon and proton spectra were acquired with different magnet settings, which prevented alignment of the signals required for calculation.