Assessment of cerebrovascular reactivity with functional magnetic resonance imaging: comparison of CO2 and breath holding
Introduction
With the advent of functional neuroimaging techniques the field of human brain mapping and neuroscience has experienced tremendous changes in the past decade. Standing out in this context are newly developed functional magnetic resonance imaging (fMRI) techniques, which uniquely combine the capabilities of high resolution anatomic imaging with noninvasive mapping of hemodynamic responses underlying neuronal events. Most fMRI techniques are based on the blood oxygenation level dependent (BOLD) contrast, using paramagnetic deoxyhemoglobin as an endogenous contrast agent [1]. A focal neuronal activation causes an increase in cerebral blood flow (CBF) without commensurate increase in oxygen extraction and changes the absolute deoxyhemoglobin concentration, which in turn alters the local magnetic field susceptibility and T2∗. Since the BOLD technique does not measure tissue perfusion directly, a number of CBF-based fMRI techniques have been developed, such as the flow-sensitive alternating inversion recovery technique (FAIR) [2], [3], which allow to determine relative and absolute CBF changes during brain activation.
Besides solely mapping cognitive brain functions an increasing number of studies indicate that fMRI techniques could potentially become useful clinically [4]. In the past few years, these techniques have been employed to map BOLD signal intensity and CBF changes during vascular challenges, such as inhalation of CO2 gas mixtures or injection of acetazolamide [5], [6], [7], [8], [9]. Although the cerebrovascular reserve capacity can also be measured with positron emission tomography (PET), single photon emission-computed tomography or xenon computed tomography, these methods suffer from several disadvantages such as the necessity to use radioisotopes, poor spatial and/or temporal resolution, limited availability and costly examination. In contrast to transcranial Doppler sonography (TCD) fMRI techniques have a high spatial resolution, so that impaired reactivity can be identified in very small brain regions. The measurement of cerebrovascular reserve potentially permits clinicians to identify subgroups of patients with carotid artery stenoses who may be at an increased risk of stroke [10]. These patients may benefit from therapeutic measures to improve poststenotic CBF, such as carotid endarterectomy or extracranial-intracranial bypass surgery.
Recently, we demonstrated that cerebral blood flow and oxygenation changes during breath holding can be detected reliably by means of fMRI at 1.5 T [11], [12]. While previous studies have generally used CO2 inhalation or injection of acetazolamide to assess cerebrovascular reactivity, the breath holding test (BHT) has the advantage that it is easy to perform in an MR setting and does not require a source of CO2 or acetazolamide injection. Using TCD preliminary experience suggests that the BHT can be helpful for obtaining functional information in patients with carotid artery diseases [13], [14], [15], [16]. However, before this test is applied to clinical practice further validation is required by comparison against established techniques.
The aim of this study was to compare BOLD signal intensity and CBF changes during either repeated challenges of breath holding or 5% CO2 inhalation in healthy volunteers. Employing a newly developed pulse sequence we simultaneously determined BOLD and CBF signals in a single trial [17].
Section snippets
Materials and methods
The study comprised 9 healthy volunteers (7 males, 2 females) ranging in age from 27 to 35 years. All volunteers underwent comprehensive medical and neurologic screening and none had used any medication with vasoconstrictor or vasodilating properties for 72 h before the examination. The subjects were pretrained to assure familiarity with the task prior to scanning and were examined after they gave informed consent. The human protocol was approved by the Institutional Review Board of our
Results
In all volunteers BOLD signal intensities and relative CBF increased globally during either CO2 inhalation or repeated challenges of breath holding for 36 s. Representative BOLD and FAIR activation maps for a typical subject are shown in Fig. 1. CBF and BOLD signal intensity changes were primarily found in cortical gray matter areas. Although the spatial extent of activation appears to be quite similar for both vascular challenges, a quantitative analysis revealed that the number of activated
Discussion
The present fMRI study was performed to clarify whether the BHT can potentially be employed clinically to determine cerebrovascular reactivity to CO2 with fMRI. We assessed cerebral blood flow and oxygenation changes during either repeated challenges of breath holding or 5% CO2-inhalation and directly compared both types of vasomotor stimuli.
During inhalation of 5% CO2 there was a mean rise in PetCO2 of 13 ± 2 mmHg, a value which has previously been obtained in healthy volunteers using the same
Acknowledgements
This study was supported by research grants from the Deutsche Forschungsgemeinschaft (Ka 1419/1–1; Kr 1896/1–1; Ne 569/2–1) and NIH RR09789. We thank the volunteers for their participation in the study.
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