Measurement of Cerebrovascular Reactivity as Blood Oxygen Level-Dependent Magnetic Resonance Imaging Signal Response to a Hypercapnic Stimulus in Mechanically Ventilated Patients

https://doi.org/10.1016/j.jstrokecerebrovasdis.2017.08.035Get rights and content

Background

Impaired cerebrovascular reactivity (CVR) is an important prognostic marker of stroke. Most measures of CVR lack (1) a reproducible vasoactive stimulus and (2) a high time and spatial resolution measure of cerebral blood flow (CBF), particularly for mechanically ventilated patients. The aim of our study was to investigate the feasibility of measuring CVR using sequential gas delivery circuit and gas blender for precise targeting of end-tidal PCO2 (PetCO2), and blood oxygen level-dependent magnetic resonance imaging (BOLD-MRI) signal as a surrogate of CBF, in mechanically ventilated patients.

Methods

Four patients with known moyamoya disease requiring preoperative CVR measurements under general anesthesia were studied. All patients had standard anesthesia induction and maintenance with intravenous propofol and rocuronium. Patients were intubated and manually ventilated with a self-inflating bag connected to a sequential breathing circuit. A computer-controlled gas blender supplied the gas mixture in proportions to attain target PetCO2. BOLD-MRI was performed at 3.0 Tesla magnet. Changes in signal per change in PetCO2 were calculated, and their magnitude color-coded and mapped onto the anatomic scan to form CVR maps.

Results

CVR studies were successfully performed on all patients, and the CVR values were lower in both gray and white matter bilaterally when compared with healthy volunteers. In addition, CVR maps in 3 patients showed intracerebral steal phenomenon in spite of having had cerebral revascularization procedures, indicating that they are still at risk of cerebral ischemia.

Conclusions

BOLD-MRI CVR studies are feasible in mechanically ventilated patients anesthetized with propofol.

Introduction

Carbon dioxide (CO2) is a potent cerebral vasodilator, and increases or decreases in arterial PCO2 cause corresponding changes in CBF.1 The change in CBF in response to a vasodilatory stimulus is called cerebrovascular reactivity (CVR). Hypercapnia-induced increase in CBF, although not uniform throughout the brain, nevertheless, follows a consistent pattern in healthy brains.2, 3 In patients with intracranial steno-occlusive disease, the post-stenotic blood vessels often undergo compensatory vasodilation, encroaching on their vasodilatory reserve. Hence, global vasodilatory stimuli such as hypercapnia can lead to paradoxical decrease in CBF in these regions as the blood flow is redistributed from more affected to lesser affected vessels.4 This phenomenon is known as “intracerebral steal,” and is a strong marker of the risk of stroke and a useful parameter to follow in considerations of when to surgically revascularize symptomatic patients.5, 6 The reverse phenomenon where there is a paradoxical increase in CBF with hypocapnia is known as “inverse steal” or “Robin Hood phenomenon.” This phenomenon has been known for decades, but so far it has not been possible to demonstrate it visually, mainly because of nonavailability of titratable vasodilatory stimuli and also the lack of noninvasive method to measure CBF. We and others have shown CVR measurement using blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) and precise controlled changes in CO2 with a help of a computer-controlled gas blender and a sequential gas delivery breathing circuit (RespirAct; Thornhill Research Inc., Toronto, Canada) to be practical, safe, and reproducible in awake subjects.4, 7, 8, 9

However, CVR measurements may be indicated in some patients who cannot tolerate MRI and also in patients on mechanical ventilation in neurointensive care unit. Although it may seem easy to control PCO2 in anesthetized and mechanically ventilated patients, the manipulation of the alveolar ventilation to control the PCO2 is often slow, non-titratable, and final levels are difficult to predict. This is unsuitable for CVR studies using MRI where there can be a signal drift and, hence, the changes need to occur over seconds. In addition, anesthetic agents also have an effect on the cerebral blood flow and vascular reactivity, and it is unknown to what extent, if any, they would attenuate or mask the “intracerebral steal.”10, 11

The aim of our study was to demonstrate the feasibility of quantitatively measuring the CVR and to generate CVR color maps in mechanically ventilated patients under propofol anesthesia using precise, controlled changes in PCO2 as the vasoactive stimuli and regional BOLD-MRI signal changes as the surrogate for CBF. We hypothesize that under propofol anesthesia, intracerebral steal physiology can be seen in patients with intracranial steno-occlusive disease with the changes in ETCO2.

Section snippets

Materials and Methods

The hospital Research Ethics Board approved the study (UHN-REB No.12-5360 A), and every subject or substitute decision maker provided written informed consent. We studied 4 adults (ages between 18 and 21 years) with an intracranial steno-occlusive disease who required CVR assessment for clinical purposes and needed general anesthesia for MRI. The reason for general anesthesia includes development delay (3) and claustrophobia (1).

Results

Four patients (mean age 20 years, 1 man and 3 women) underwent measurement of CVR under general anesthesia. All patients had a diagnosis of moyamoya disease with previous strokes. The clinical presentation, results of angiography structural MRI findings, resting, and hypercapnic PetCO2 values are summarized in Table 1. We were able to achieve both hypo- and hypercapnia in all 4 patients within 10 seconds, with accuracy of 2 mm Hg.

Discussion

Our pilot data showed that it is feasible to quantitatively measure CVR and generate CVR color maps in anesthetized ventilated patients with precise controlled hypercapnic changes and high time and spatial resolution BOLD-MRI signals as surrogates for CBF. We were able to take advantage of the RespirAct algorithms targeting PetCO2 by replacing the sequential gas delivery circuit previously designed for spontaneous ventilation, with a newly constructed self-inflating bag modified into a

Conclusion

Our pilot data showed that BOLD-MRI CVR studies are feasible to quantitatively measure CVR and to map steal physiology in mechanically ventilated patients anesthetized with propofol.

Acknowledgment

The authors wish to thank MRI technicians at Toronto Western Hospital for their contribution to the data acquisition

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    Grant support: This study was funded in part by a grant from MSH-UHN AMO AFP Innovation fund 2013-15.

    Conflict of interest: RespirAct is currently a non-commercial research tool approved by Health Canada, assembled, and made available by Thornhill Research Inc. (TRI), a spin-off company from the University Health Network, to research institutions to enable CVR studies. J.A.F. is the Chief Scientist and J.D. is the Senior Scientist at (TRI), and J.P., O.S., J.S.H., K.S., and D.J.M. have contributed to the development of RespirAct and have received payments from, or shares in, TRI.

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