Brain Hypoxia
Conditions
Keywords
Functional MRS, Glutamate
Brief summary
The primary objective of this research is to measure changes in neurochemical concentrations during stimulation of the primary visual cortex, in both conditions of normoxia (normal oxygen availability) and induced mild hypoxia (reduced oxygen availability).
Detailed description
The goal is to determine the effect of mild hypoxia on human brain energy metabolism of healthy young adult subjects. For this purpose, the Investigator will utilize non-invasive imaging modalities based on functional magnetic resonance spectroscopy (fMRS) to estimate metabolic changes during a visual stimulus, while subjects are exposed to well-controlled gas mixtures that resembles conditions of either normoxia or mild hypoxia. Identifying the impact of mild hypoxia on functional brain energy metabolism in the healthy human brain is a crucial step for generating hypotheses in multiple patient populations that experience mild hypoxia as consequence of their pathological condition, such as in sleep apnea and traumatic brain injury. The Investigator hypothesize that the energetic demands of neuronal activation as revealed by fMRS will not be affected by mild hypoxia.
Interventions
DEVICEMild Hypoxia
During normoxia, the computer-controlled gas blender provides a gas mixture that generates pressures of expired O2 and CO2 similar to the resting values measured for each subject (32-35mmHg and 100-110 mmHg, respectively). During mild hypoxia, we will target the same expired CO2 of normoxia and a 60 mmHg reduction of expired O2 from the resting value (to a minimum limit of 50 mmHg), which is expected to reduce arterial oxygen saturation to 82-85%. In mild hypoxia, the fraction of inspired oxygen is reduced from \ 21% (room air) to \ 12% (equivalent to an altitude of 4000 meters). During both conditions of normoxia and mild hypoxia, the brain activity of subjects is monitored with functional magnetic resonance spectroscopy (fMRS) while they are presented with visual stimuli.
Sponsors
University of Minnesota
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
* Those volunteers who are evaluated as normal and not met
Exclusion criteria
will be potential candidates for this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Glutamate Concentration During a Visual Stimulus Measured by fMRS at Normoxia | Baseline and Visual Stimulation at 4 minutes | Relative change in glutamate concentration from rest to visual stimulation as measured by fMRS (with water suppression) in the primary visual cortex during conditions of normoxia. |
| Change in Glutamate Concentration During a Visual Stimulus Measured by Functional MRS at Hypoxia | Baseline and Visual Stimulation at 4 minutes | Relative change in glutamate concentration from rest to visual stimulation as measured by fMRS (with water suppression) in the primary visual cortex during conditions of hypoxia. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Brain Activity Measured by Blood Oxygenation Level Dependent (BOLD) Signal at Normoxia | Baseline and Visual Stimulation at 30 seconds | Relative change in water signal intensity from rest to visual stimulation as measured by fMRS (without water suppression) in the primary visual cortex during conditions of normoxia. |
| Brain Activity Measured by Blood Oxygenation Level Dependent (BOLD) Signal at Hypoxia | Baseline and Visual Stimulation at 30 seconds | Relative change in water signal intensity from rest to visual stimulation as measured by fMRS (without water suppression) in the primary visual cortex during conditions of hypoxia. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Mild Hypoxia During normoxia, the computer-controlled gas blender provides a gas mixture that generates pressures of expired O2 and CO2 similar to the resting values measured for each subject (32-35mmHg and 100-110 mmHg, respectively). During mild hypoxia, we will target the same expired CO2 of normoxia and a 60 mmHg reduction of expired O2 from the resting value (to a minimum limit of 50 mmHg), which is expected to reduce arterial oxygen saturation to 82-85%. In mild hypoxia, the fraction of inspired oxygen is reduced from \
21% (room air) to \
12% (equivalent to an altitude of 4000 meters). During both conditions of normoxia and mild hypoxia, the brain activity of subjects is monitored with functional magnetic resonance spectroscopy (fMRS) while they are presented with visual stimuli. | 25 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Scanner or Respiract failure | 3 |
| Overall Study | Withdrawal by Subject | 4 |
Baseline characteristics
| Characteristic | Mild Hypoxia |
|---|---|
| Age, Continuous | 25.4 years STANDARD_DEVIATION 5.9 |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 25 |
| other Total, other adverse events | 16 / 25 |
| serious Total, serious adverse events | 1 / 25 |
Outcome results
Primary
Change in Glutamate Concentration During a Visual Stimulus Measured by fMRS at Normoxia
Relative change in glutamate concentration from rest to visual stimulation as measured by fMRS (with water suppression) in the primary visual cortex during conditions of normoxia.
Time frame: Baseline and Visual Stimulation at 4 minutes
Population: Out of the 17 experimental sessions that were successfully completed, 4 had data of insufficient quality. Therefore, a total of 13 sessions was used for final analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mild Hypoxia | Change in Glutamate Concentration During a Visual Stimulus Measured by fMRS at Normoxia | 4 percentage of concentration (micromol/g) | Standard Deviation 2.4 |
Primary
Change in Glutamate Concentration During a Visual Stimulus Measured by Functional MRS at Hypoxia
Relative change in glutamate concentration from rest to visual stimulation as measured by fMRS (with water suppression) in the primary visual cortex during conditions of hypoxia.
Time frame: Baseline and Visual Stimulation at 4 minutes
Population: Out of the 17 experimental sessions that were successfully completed, 4 had data of insufficient quality. Therefore, a total of 13 sessions was used for final analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mild Hypoxia | Change in Glutamate Concentration During a Visual Stimulus Measured by Functional MRS at Hypoxia | 2.9 percentage of concentration (micromol/g) | Standard Deviation 1.9 |
Secondary
Brain Activity Measured by Blood Oxygenation Level Dependent (BOLD) Signal at Hypoxia
Relative change in water signal intensity from rest to visual stimulation as measured by fMRS (without water suppression) in the primary visual cortex during conditions of hypoxia.
Time frame: Baseline and Visual Stimulation at 30 seconds
Population: Out of the 17 experimental sessions that were successfully completed, 4 had data of insufficient quality. Therefore, a total of 13 sessions was used for final analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mild Hypoxia | Brain Activity Measured by Blood Oxygenation Level Dependent (BOLD) Signal at Hypoxia | 1.2 percentage of signal intensity | Standard Deviation 1.2 |
Secondary
Brain Activity Measured by Blood Oxygenation Level Dependent (BOLD) Signal at Normoxia
Relative change in water signal intensity from rest to visual stimulation as measured by fMRS (without water suppression) in the primary visual cortex during conditions of normoxia.
Time frame: Baseline and Visual Stimulation at 30 seconds
Population: Out of the 17 experimental sessions that were successfully completed, 4 had data of insufficient quality. Therefore, a total of 13 sessions was used for final analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mild Hypoxia | Brain Activity Measured by Blood Oxygenation Level Dependent (BOLD) Signal at Normoxia | 3.3 percentage of signal intensity | Standard Deviation 2 |