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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new wearable device designed to map blood flow in the brain. The researchers aim to understand how factors like aging and sex affect brain blood flow in healthy individuals. Volunteers will undergo various tests, such as breathing exercises and posture changes (orthostatic challenge), to evaluate the device's effectiveness. Ideal participants are healthy individuals with no history of brain or blood vessel diseases. As an unphased study, this trial provides a unique opportunity to contribute to innovative research on brain health.

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 prior data suggests that this device is safe for cerebral mapping?

Research shows that the treatments in this study are generally manageable and have been used safely in other contexts. For example, one test involves gently pressing on the neck to check blood flow. When performed correctly, this is safe, although it might cause brief changes in blood flow. Studies have found it to be safe, with no serious side effects reported.

Another test, the orthostatic challenge, involves moving from lying down to standing up to study blood flow changes. Some people might feel slightly dizzy or lightheaded, but these sensations are temporary.

Vascular chemo-reactivity tests involve altering breathing to observe blood vessel reactions. Participants might notice temporary changes in breathing or heart rate, but research suggests these are not harmful.

Lastly, neurovascular coupling tests how blood flows in the brain during tasks like naming colors. Research indicates this is safe and doesn't cause any long-term effects.

Overall, these techniques have been used in many studies and are considered safe for healthy participants. However, as with any procedure, mild, temporary discomforts might occur. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the non-invasive cerebral mapping techniques being studied because they offer a fresh approach to understanding and potentially improving cerebral autoregulation without the need for invasive procedures. Unlike traditional methods that may require surgical interventions or direct measurements, these techniques, like neurovascular coupling and orthostatic challenges, utilize external stimuli and cognitive tests to assess brain function and blood flow dynamics in real time. This approach could lead to safer, quicker, and more cost-effective ways to diagnose and monitor conditions affecting cerebral blood flow, ultimately paving the way for more personalized treatments.

What evidence suggests that this device is effective for cerebral autoregulation?

This trial will investigate various methods to understand how blood flow in the brain is regulated. Research has shown that measuring changes in blood flow after gently pressing on neck arteries, known as transient hyperemic response testing, can reveal how well the brain controls its blood supply. Studies have found that this control remains steady even when positions change, such as standing up, assessed through orthostatic challenge responses. How blood vessels react to different levels of carbon dioxide, evaluated through vascular chemo-reactivity, is also important for understanding brain health. Additionally, the connection between brain activity and blood flow, known as neurovascular coupling, is crucial for thinking tasks and behaves predictably during mental tests. Together, these methods enhance understanding of cerebral autoregulation and could be useful for studying various brain conditions. ^{6 7 8 9 10}

Who Is on the Research Team?

Frederick A Zeiler, MD PhD FRCSC

Principal Investigator

University of Manitoba

Are You a Good Fit for This Trial?

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 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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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 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]

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 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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6055030/

Neurovascular coupling response to cognitive examination ... The aim of this study was to investigate the changes in subcomponents that occur with cognitive stimulation with the Addenbrooke's Cognitive Examination (ACE‐ ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11542125/

Cerebral blood flow regulation and cognitive performance ... We examined the relation between transcranial Doppler (TCD) markers of cerebral blood flow regulation and cognitive performance in hypertension (HT) patients.

3. journals.physiology.org journals.physiology.org/doi/full/10.1152/japplphysiol.00100.2018

Neurovascular coupling during cognitive activity in adults ... Accuracy and reaction times were computed to assess cognitive performance. Stroop performance was similar between groups (P > 0.01). Aortic and carotid PWV ...

4. journals.sagepub.com journals.sagepub.com/doi/10.1177/0271678X241270452

Neurovascular coupling methods in healthy individuals ... Neurovascular coupling (NVC) is the process ensuring metabolic demands induced by neuronal activity are met via rises in cerebral blood flow ( ...

5. frontiersin.org frontiersin.org/journals/physiology/articles/10.3389/fphys.2024.1350832/pdf

Cognitive activity significantly affects the dynamic cerebral ... In this study, we aimed to analyze changes in the regulation mechanisms of CBv that are stimulated via cognitive paradigms of the attention, ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11572172/

Neurovascular coupling methods in healthy individuals using ... Neurovascular coupling (NVC) is the process ensuring metabolic demands induced by neuronal activity are met via rises in cerebral blood flow (CBF). This is ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4821024/

Neurovascular coupling in humans: Physiology ... Neurovascular coupling reflects the close temporal and regional linkage between neural activity and cerebral blood flow.

8. mdpi.com mdpi.com/2409-9279/6/3/58

Non-Invasive Mapping of Cerebral Autoregulation Using ... Neurovascular Coupling Test (10 min). The neurovascular coupling is evaluated using the ANAM Stroop test to assess the processing speed, selective attention ...

9. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0301562901003556

Neurovascular coupling in terms of a control system We showed, for the first time, that cerebral blood flow regulation due to neurovascular coupling or dynamic cerebral autoregulation mechanisms can be expressed ...

10. umbjournal.org umbjournal.org/article/S0301-5629(24)00089-9/fulltext

Assessment of Neurovascular Coupling by Spectral ... The aim here was to describe a new approach to non-invasive measurement of NVC by spectral analysis of the cerebral blood flow velocity (CBFV) with ...