Non-Invasive Cerebral Mapping for Cerebral Autoregulation

Overseen By Frederick A Zeiler, MD PhD FRCSC

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Manitoba

Disqualifiers: Neurological illness, Vascular, Cerebrovascular, others

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

Compensation: Varies

Number of Visits: 1

250 Participants Needed

Trial Summary

What is the purpose of this trial?

The investigators propose to employ advanced multi-channel near non-invasive near infrared spectroscopy (NIRS) system married with entirely non-invasive continuous arterial blood pressure (niABP) monitor to create a new wearable and portable imaging system that derives CA maps of the entire brain with high sampling rates at each point. The objectives of this project are as follows: 1. To perform in vivo testing and optimization of the device using a block-trial design to evaluate the CA mapping system's performance during various perturbations. 2. To explore the impact of aging and sex on regional disparities in CA in a healthy volunteer population using static recording along with perturbation testing.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, since the trial is for healthy volunteers without a history of certain illnesses, it's possible that you may not need to change your current medication routine.

What data supports the effectiveness of the treatment Neurovascular coupling, Cerebral autoregulation, and related tests for cerebral autoregulation?

Research shows that cerebral autoregulation and neurovascular coupling are important for maintaining stable blood flow to the brain, even when blood pressure changes. Tests like the Transient Hyperemic Response Test (THRT) and others help assess how well these mechanisms work, which can be useful in predicting and managing conditions like syncope (fainting) in patients with orthostatic hypotension (a condition where blood pressure drops when standing up). ^{1 2 3 4 5}

Is non-invasive cerebral mapping for cerebral autoregulation safe for humans?

The studies suggest that non-invasive tests like transcranial Doppler (TCD) and vasodilatory tests are generally safe for assessing cerebral blood flow and autoregulation in humans. These tests have been widely used to evaluate brain blood flow responses and have practical applications in various conditions, indicating a good safety profile. ^{1 5 6 7 8}

How does the treatment for cerebral autoregulation differ from other treatments?

The treatment for cerebral autoregulation using non-invasive cerebral mapping is unique because it focuses on assessing and maintaining stable blood flow to the brain without the need for invasive procedures. This approach is different from other treatments that might involve pharmacological interventions or invasive monitoring techniques, as it uses non-invasive neuroimaging to study cerebral circulation and autoregulation. ^{1 2 3 5 9}

Research Team

Frederick A Zeiler, MD PhD FRCSC

Principal Investigator

University of Manitoba

Eligibility Criteria

This trial is for healthy volunteers over the age of 17 who want to help test a new brain mapping system. People with a history of cerebrovascular or neurological illness, or systemic vascular issues cannot participate.

Inclusion Criteria

I am 18 years old or older.

I am a healthy volunteer.

Exclusion Criteria

I have a history of blood vessel diseases.

I have had a stroke or other brain blood flow problems.

I have a history of neurological illness.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

In Vivo Testing and Optimization

In vivo testing and optimization of the device using a block-trial design to evaluate the CA mapping system's performance during various perturbations

18 months

Multiple visits for testing and optimization

Impact Assessment

Explore the impact of aging and sex on regional disparities in Cerebral Autoregulation using static recording along with perturbation testing

3 years

1-hour session per volunteer

Follow-up

Participants are monitored for safety and effectiveness after testing

4 weeks

Treatment Details

Interventions

• Neurovascular coupling
• Orthostatic challenge
• Transient hyperemic response
• Vascular chemo-reactivity

Trial Overview Researchers are testing a wearable device that uses light (NIRS) and blood pressure monitoring to map how well blood flow in the brain responds to changes like standing up quickly or increased carbon dioxide levels.

Participant Groups

Group I: Block Testing Experimental Treatment 4 Interventions

Perturbations to the system will be investigated through a series of testing (block design separated by baseline rest): A. transient hyperemic response testing via carotid compression methods, B. orthostatic challenge responses (lying-to-sit, sit-to-stand),8 C. vascular chemo-reactivity via fast and slow breathing exercises and D. impact of neurovascular coupling through cognitive/Stroop testing. Work here will establish areas for improvement in real time.

Who Is Running the Clinical Trial?

University of Manitoba

Lead Sponsor

Trials

628

Recruited

209,000+

Health Sciences Centre, Winnipeg, Manitoba

Collaborator

Trials

18

Recruited

11,600+

Natural Sciences and Engineering Research Council, Canada

Collaborator

Trials

63

Recruited

3,000+

Findings from Research

In a study involving 15 healthy volunteers, cerebral blood flow (CBF) remained stable across different body positions (sitting, supine, upright) despite significant changes in blood pressure and heart rate, indicating effective cerebral autoregulation (CA).

The results suggest that CA allows for independent regulation of neurovascular coupling (NC), ensuring that CBF adapts to the brain's metabolic needs during stimulation tasks, regardless of orthostatic changes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interplay of cerebral autoregulation and neurovascular coupling evaluated by functional TCD in different orthostatic conditions. Azevedo, E., Rosengarten, B., Santos, R., et al.[2018]

Cerebrovascular CO2 reactivity remains unchanged during different tilt positions, indicating that the body's ability to regulate blood flow in the brain is maintained despite changes in posture.

The study suggests that sympathetic nervous system activation or balanced pressures in the blood vessels, rather than cerebral autoregulation, are key factors in maintaining cerebral blood flow during tilting and CO2 changes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Steady-state tilt has no effect on cerebrovascular CO2 reactivity in anterior and posterior cerebral circulations. Tymko, MM., Skow, RJ., MacKay, CM., et al.[2022]

In a study of 29 patients with orthostatic hypotension (OH), those who experienced syncope had significantly lower cerebral vasomotor reactivity (VMR) compared to those without syncope, indicating impaired cerebral autoregulation.

The findings suggest that assessing VMR can help identify patients with OH who are at higher risk of fainting, potentially guiding more aggressive treatment strategies to prevent falls.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vasomotor reactivity as a predictor for syncope in patients with orthostatism. Gur, AY., Auriel, E., Korczyn, AD., et al.[2016]

In a study of 74 patients with carotid artery disease, the breath-holding maneuver was found to be a clinically useful method for estimating cerebrovascular vasomotor reactivity, correlating well with blood flow changes measured by transcranial Doppler ultrasound.

While both the breath-holding maneuver and acetazolamide challenge indicated reduced vasomotor reactivity with more severe carotid artery lesions, the acetazolamide challenge provided more precise differentiation between the severity of these lesions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of cerebral vasomotor reactivity by transcranial Doppler ultrasound and breath-holding. A comparison with acetazolamide as vasodilatory stimulus. Müller, M., Voges, M., Piepgras, U., et al.[2019]

Transcranial Doppler sonography (TCD) combined with vasodilatory tests like the Diamox test can effectively assess cerebral vasomotor reactivity, which is crucial for understanding cerebral autoregulation and predicting ischemic brain events in patients with carotid occlusive disease.

The study highlights several practical applications of TCD and vasodilatory tests, including evaluating hemodynamic status before and after carotid endarterectomy and predicting dementia risk after stroke, indicating their potential clinical significance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TCD and the Diamox test for testing vasomotor reactivity: clinical significance. Gur, AY., Bornstein, NM.[2015]

In a study of 16 patients with neurocardiogenic syncope (NCS) and 20 normal controls, it was found that patients with postural tachycardia syndrome (POTS) had significantly lower pulsatility indices in arterial blood pressure (ABP) and higher ratios of cerebral blood flow velocity (CBFV) to ABP, indicating altered cerebrovascular responses during standing.

Despite these changes, cerebral autoregulation remained intact in NCS patients, suggesting that their fainting episodes are linked to central hypovolemia and increased cerebrovascular resistance rather than a failure of autoregulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cerebrovascular mechanisms in neurocardiogenic syncope with and without postural tachycardia syndrome. Diehl, RR., Linden, D., Chalkiadaki, A., et al.[2019]

Cerebrovascular reactivity (CVR) measurements can be influenced by mean arterial pressure (MAP), which may confound results, as MAP increased with CO2 in some subjects during the study.

The method of CO2 stimulus (step vs. ramp) significantly affects CVR calculations, with ramp responses yielding higher CVR values compared to step responses, while subject position (sitting vs. supine) did not impact CVR outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Factors affecting the determination of cerebrovascular reactivity. Regan, RE., Fisher, JA., Duffin, J.[2021]

In a study of 58 healthy adults aged 20 to 80, it was found that age and gender do not significantly influence the mechanisms of cerebrovascular regulation, including cerebral autoregulation, vasomotor reactivity, and neurovascular coupling.

The results indicate that neurovascular stress tests assess different aspects of cerebrovascular control and their outputs are uncorrelated, suggesting they cannot be used interchangeably in research on cerebrovascular conditions, particularly in the aging brain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Demographic and Systemic Hemodynamic Influences in Mechanisms of Cerebrovascular Regulation in Healthy Adults. Madureira, J., Castro, P., Azevedo, E.[2017]

The primary cause of syncope (loss of consciousness) is insufficient blood flow to the brain, particularly affecting the reticular activating system, which is crucial for maintaining consciousness.

In cases of neurally mediated syncope, the brain's autoregulation system can malfunction, leading to increased cerebrovascular resistance and further reducing blood flow, highlighting the complex relationship between blood pressure and cerebral perfusion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cerebral autoregulation and syncope. Franco Folino, A.[2022]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Interplay of cerebral autoregulation and neurovascular coupling evaluated by functional TCD in different orthostatic conditions. [2018]

2. England pubmed.ncbi.nlm.nih.gov

Steady-state tilt has no effect on cerebrovascular CO2 reactivity in anterior and posterior cerebral circulations. [2022]

3. Denmark pubmed.ncbi.nlm.nih.gov

Vasomotor reactivity as a predictor for syncope in patients with orthostatism. [2016]

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

Assessment of cerebral vasomotor reactivity by transcranial Doppler ultrasound and breath-holding. A comparison with acetazolamide as vasodilatory stimulus. [2019]

5. Poland pubmed.ncbi.nlm.nih.gov

TCD and the Diamox test for testing vasomotor reactivity: clinical significance. [2015]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Cerebrovascular mechanisms in neurocardiogenic syncope with and without postural tachycardia syndrome. [2019]

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

Factors affecting the determination of cerebrovascular reactivity. [2021]

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

Demographic and Systemic Hemodynamic Influences in Mechanisms of Cerebrovascular Regulation in Healthy Adults. [2017]

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

Cerebral autoregulation and syncope. [2022]