The Effect of Respiratory Challenge on the BOLD Signal

Study Overview
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Brief Summary
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The purpose of this research study is to better understand how blood flow and metabolism are different between normal controls and patients with disease. The investigators will examine brain blood flow and metabolism using magnetic resonance imaging (MRI). The brain's blood vessels expand and constrict to regulate blood flow based on the brain's needs. The amount of expanding and contracting the blood vessels can do varies by age. The brain's blood flow changes in small ways during everyday activities, such as normal brain growth, exercise, or deep concentration. Significant illness or physiologic stress may increase the brain's metabolic demand or cause other bigger changes in blood flow. If blood vessels are not able to expand to give more blood flow when metabolic demand is high, the brain may not get all of the oxygen it needs. In less extreme circumstances, not having as much oxygen as it wants may cause the brain to grow and develop more slowly than it should. One way to test the ability of the blood vessels to expand is by measuring blood flow while breathing in carbon dioxide (CO2). CO2 causes blood vessels in the brain to dilate without increasing brain metabolism. The study team will use a special mask to control the amount of oxygen and carbon dioxide patients breath in so that we can study how their brain reacts to these changes. This device designed to simulate carbon dioxide levels achieved by a breath-hold and target the concentration of carbon dioxide in the blood in breathing patients. The device captures exhaled gas and provides an admixture of fresh gas and neutral/expired gas to target different carbon dioxide levels while maintaining a fixed oxygen level. The study team will obtain MRI images of the brain while the subjects are breathing air controlled by the device.

Official Title
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The Effect of Respiratory Challenge on the BOLD Signal

Conditions
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Hypoxia, Brain, Hyperoxia, Hypercapnia, Hypocapnia

Intervention / Treatment
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* Other: Carbon Dioxide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy adult subjects (>18 years old) OR adult patients (>18 years old) diagnosed with vascular pathology of the brain willing to participate and sign a consent form. Able to participate in MRI scan without sedation Not on stimulant medications No psychiatric history, as defined by seeing a psychiatrist for medical evaluation and treatment, or taking anti-depressant medications No seizure history May have occasional headaches if not taking a daily preventative medication for headaches Not on vasodilatory medication, such as sildenafil or verapamil Exclusion Criteria: Subjects refusing to undergo testing Subjects with obstructive or resistive lung disease whose PaCO2 at rest is greater than 50mmHg or whose venous serum bicarbonate is greater than 26 mEq/L Subjects with pre-existing respiratory or metabolic acidosis Subjects who require portable oxygen at rest or with exercise Subjects with chronic heart failure or severe pulmonary disease who are unable to climb one flight of stairs due to shortness of breath Subjects with severe heart failure or restrictive lung disease with resting respiratory rate over 15 breaths/min 2. Patients that cannot participate in a course of rehabilitation therapy. Subjects that cannot undergo an MRI scan due to one of the following indications: Pregnancy Obtundation, or Coma Confusion, Delirium, or Dementia Unable to understand or carry out commands regarding keeping still and breathing pattern Increased intracranial pressure due to space occupying lesion or obstruction of outflow of CSF Claustrophobia History of kidney problems Pace makers Skin tattoos Neurostimulators (TENS-unit) Implanted drug infusion device (i.e., insulin pump) Exposure of metal fragments to your eye Artificial heart valves Aneurysm clips Cochlear implants Metallic implants and prosthesis Vascular stent or stent graft History as a metal worker Shrapnel or bullet wounds Dorsal column stimulators

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: All arms will receive the same study conditions.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Healthy Adults<br> | Other: Carbon Dioxide<br>* The study team will administer inhaled carbon dioxide to the participants during an MRI at a level<br>|
| Active Comparator: Adults diagnosed with vascular pathology of the brain<br> | Other: Carbon Dioxide<br>* The study team will administer inhaled carbon dioxide to the participants during an MRI at a level<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cerebral Oxygen Metabolism |  | From the beginning of the MRI scan to the completion of the MRI scan -- 75 minutes. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cerebrovascular Reactivity |  | From administration of carbon dioxide to end of inhalation of carbon dioxide -- 15 minutes. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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brain metabolism, oxygen extraction fraction, cerebral vascular reactivity, carbon dioxide