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In This Article

  • Summary
  • Abstract
  • Introduction
  • Protocol
  • Representative Results
  • Discussion
  • Acknowledgements
  • Materials
  • References
  • Reprints and Permissions

Summary

Presented here is a protocol for imaging and measurement of cerebrovascular reactivity in humans with functional Near Infrared Spectroscopy (fNIRS). fNIRS is a novel imaging modality that captures the concentration changes of hemoglobin species in the brain’s outermost cortex under specific stimuli.

Abstract

Cerebrovascular reactivity (CVR) is the capacity of blood vessels in the brain to alter cerebral blood flow (either with dilation or constriction) in response to chemical or physical stimuli. The amount of reactivity in the cerebral microvasculature depends on the integrity of the capacitance vasculature and is the primary function of endothelial cells. CVR is, therefore, an indicator of the microvasculature’s physiology and overall health. Imaging methods that can measure CVR are available but can be costly, and require magnetic resonance imaging centers and technical expertise. In this study, we used fNIRS technology to monitor changes of oxyhemoglobin (HbO) and deoxyhemoglobin (HbR) in the cerebral microvasculature to assess the CVR of 15 healthy controls (HC) in response to a vasoactive stimulus (inhaled 5% carbon dioxide or CO2). Our results suggest that this is a promising imaging technology that offers a non-invasive, accurate, portable, and cost-effective method of mapping cortical CVR and associated microvasculature function, resulting from a traumatic brain injury or other conditions associated with cerebral microvasculopathy.

Introduction

Vascular health in the cerebral cortex can be measured via the vessels’ ability to constrict or dilate under varying physiological conditions. Measuring vascular reactivity can be useful in the diagnosis and management of neurological conditions associated with cerebral microvascular dysfunction, like dementia, traumatic brain injury (TBI) and even aging1,2,3,4. Additionally, CVR can be used as a predictive and/or pharmacodynamic biomarker for neurological disorders such as Alzheimer's5 or TBI

Protocol

The participants were recruited under an institutional review board approved protocol (ClinicalTrials.gov NCT01789164). The equipment described in the protocol is ethically approved by our institution.

1. Prepare the Materials used for the Hypercapnia Challenge (Figure 2)

  1. Inflate a 200 L Douglas bag (Item #1) with a pre-mixed canister of medical-grade gas which is comprised of 5% carbon dioxide, 21% oxygen, and 74% nitrogen until full.
  2. .......

Representative Results

fNIRS was performed with hypercapnia challenge on 15 healthy participants. Exclusion criteria were history of TBI, pre-existing disabling neurological or psychiatric disorders or pregnancy. The participants had a mean age of 37.7 ± 16 years (range 20-55) and 20% were female. As shown in a similar fMRI study28, a 60 s inhalation of 5% CO2 was accompanied by an increase in EtCO2 pressure as measured by capnography. In our study, the EtCO2 trace was accompanied b.......

Discussion

We were able to measure CVR using fNIRS and a CO2 gas inhalation technique in 15 healthy volunteers. The CVR value measured is the correlation between the acquired fNIRS signal and the EtCO2. The challenge is to accurately align the temporal EtCO2 trace with the fNIRS signal, in other words, to account for the time that it takes for blood to travel from the pulmonary vascular system to the heart and then to the cerebral vasculature. The inter-channel variability is low (30%) and shows a u.......

Acknowledgements

Work in the authors’ laboratory was supported by the Center for Neuroscience and Regenerative Medicine (CNRM), Uniformed Services University of the Health Sciences (USUHS), Bethesda, MD, by the Military Clinical Neuroscience Center of Excellence (MCNCoE), Department of Neurology, USUHS, and by the Intramural Research Program of the National Institutes of Health. The views expressed in this article are those of the author and do not reflect the official policy of the Department of Army/Navy/Air Force, Department of Defense, or U.S. Government.

....

Materials

NameCompanyCatalog NumberComments
Blue cuff22254Vacumed
CO2-Air Gas Mixture Size 200R012000 2003Roberts Oxygen
Diaphragm (Size: medium, Type: spiral)602021-2608Hans Rudolph
Douglas bag (200-liters capacity)500942Harvard Apparatus
Gas delivery Tube1011-108Vacumed
Gas sampling TubeT4305QoSINA
Hydrophobic filter9906-00Philips Medical Systems
Male luer11547QoSINA
Mouth piece (Silicone, Model #9061)602076Hans Rudolph
Nose clip (Plastic foam, Model #9014)201413Hans Rudolph
Three-way valve (100% plastic)CR1207Hans Rudolph
Two-way non-breathing valve (22mm/ 15mm ID)CR1480Hans Rudolph

References

  1. Amyot, F., et al. Imaging of Cerebrovascular Function in Chronic Traumatic Brain Injury. Journal of Neurotrauma. 35 (10), 1116-1123 (2017).
  2. Kassner, A., Roberts, T. P. Beyond perfusion: cereb....

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Cerebrovascular ReactivityCVRFunctional Near infrared SpectroscopyFNIRSCerebral Blood FlowEndothelial CellsMicrovasculatureVasoactive StimulusCarbon DioxideCO2Traumatic Brain InjuryCerebral Microvasculopathy

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