Cerebrovascular Reactivity Measurement with Functional Near Infrared Spectroscopy

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 aging^1,2,3,4. 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. Insert two diaphragms (Item #3) into the two-way non-rebreathing valve (Item #4) to safeguard that the gas will only flow in one direction. Attac....

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 by an .......

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.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Blue cuff	22254	Vacumed
CO2-Air Gas Mixture Size 200	R012000 2003	Roberts Oxygen
Diaphragm (Size: medium, Type: spiral)	602021-2608	Hans Rudolph
Douglas bag (200-liters capacity)	500942	Harvard Apparatus
Gas delivery Tube	1011-108	Vacumed
Gas sampling Tube	T4305	QoSINA
Hydrophobic filter	9906-00	Philips Medical Systems
Male luer	11547	QoSINA
Mouth piece (Silicone, Model #9061)	602076	Hans Rudolph
Nose clip (Plastic foam, Model #9014)	201413	Hans Rudolph
Three-way valve (100% plastic)	CR1207	Hans Rudolph
Two-way non-breathing valve (22mm/ 15mm ID)	CR1480	Hans Rudolph