Assessment of cerebrovascular reactivity by dynamic susceptibility contrast-enhanced MR imaging

Abstract

In patients with cerebrovascular disease the acetazolamide (ACZ) test is performed to evaluate the decrease in cerebral perfusion pressure (CPP) through the investigation of the vasomotor reactivity (VMR). This latter is currently assessed with ACZ with several methods. Recently, magnetic resonance imaging (MRI) techniques have been developed that are sensitive to stimulus-induced changes in blood flow. Dynamic susceptibility contrast material-enhanced gradient-echo MRI techniques (DSC-MRI) might be an attractive tool to assess VMR. We aimed to test the ability of DSC-MRI in the assessment of VMR. Relative hemodynamic parameters rCBV, MTT, and rCBF were evaluated at baseline after the first injection of gadopentetate dimeglumine and 10 min after the intravenous administration of ACZ (1 g) with a second bolus of contrast agent. Assessment of hemodynamic parameters was performed over the whole hemisphere and also within regions of interest. The significances of the mean differences, before and after ACZ, were assessed with repeated-measures ANOVA with two within factors: laterality (right–left) and ACZ. DSC-MRI with ACZ test was performed in ten healthy controls (aged 51.4±16.2 years). The cerebral hemispheric ratio for the three parameters (cerebral blood volume (CBV), mean transit time (MTT), and cerebral blood flow (CBF)) ranged between 1.01 and 1.03. The mean gray matter-to-white matter ratio for CBV, CBF and MTT were 2.44, 2.41 and 1.05, respectively. As the laterality effect was not significant, left and right hemispheric values were averaged. A significant increase of all hemodynamic parameters was observed after ACZ (P<0.01–0.001). The same changes for CBV, CBF and MTT were observed after ACZ according to the regions of interest (P<0.006–0.015). DSC-MRI is a non-invasive method which enables the assessment of VMR. This technique may be added to any conventional MRI in order to detect a hemodynamic impact of an ICA stenosis. Therefore, it might be useful in determining the appropriate management when the indication for surgical versus medical therapy is in question.

Introduction

In human subjects, and specifically in patients with cerebrovascular disease, the acetazolamide (ACZ) test is performed to evaluate the decrease in cerebral perfusion pressure (CPP) through the investigation of the vasomotor reactivity (VMR), which is thought to reflect compensatory vasodilatation (Gibbs et al., 1984; Vorstrup et al., 1986; Pedersen, 1987; Clifton et al., 1988; Chollet et al., 1989; Kleiser et al., 1991; Weiller et al., 1991; Knop et al., 1992; Yonas et al., 1993; Ringelstein et al., 1994). In patients with occlusion or stenosis of more than 90% of the internal carotid artery (ICA), diminished VMR was reported to be significantly associated with low flow infarctions (Kleiser et al., 1991; Weiller et al., 1991; Knop et al., 1992; Ringelstein et al., 1994) and a higher rate of future ipsilateral stroke compared with patients with a normal or only slightly disturbed VMR. The quantification of the response of the blood vessels to the stimulus can be obtained by measuring cerebral blood flow (CBF), cerebral blood volume (CBV) or blood flow velocity. The ideal technique for testing should be simple, repeatable and non-invasive. Several methods have been used to assess reactivity by measuring the VMR with physiological stimuli that affect tissue acidosis (Rogg et al., 1989). VMR assessment with ACZ was performed with positron emission tomography (Hirano et al., 1994), single photon emission computed tomography (Hasegawa et al., 1992), Xenon computed tomography (Yamashita et al., 1991) and transcranial Doppler ultrasonography (TCD) (Bishop et al., 1986; Widder et al., 1986; Piepgras et al., 1990).

Dynamic susceptibility contrast material-enhanced gradient-echo MRI techniques (DSC-MRI) might be an attractive tool that combines the good spatial resolution of MRI with an ability to assess tissue microcirculation, which is comparable to that of PET. The basic principles were described in the pioneering works of other groups (Rosen et al., 1989; Rosen et al., 1990; Larson et al., 1994). The assessment of cerebral hemodynamics is supported by the study of signal-intensity changes after the first pass of a paramagnetic contrast medium. While passing through the capillary network, a short bolus of contrast material produces local magnetic field inhomogeneities that lead to a reduction in the transverse relaxation time T₂* of the bulk tissue. This susceptibility effect can be recorded by a series of rapid T₂*-weighted gradient echo images. The resulting signal-intensity time curves can be converted into concentration time curves. By using the indicator dilution theory (Rempp et al., 1994; Stewart, 1994) one can determine two important dynamic parameters, CBV and mean transit time (MTT), and thus calculate CBF as CBV/MTT. Though this method is well established and has been extensively examined (Zierler, 1965a; Aronen et al., 1992) most results have been obtained in animal studies and there is only preliminary experience with patients (Pike et al., 1992; Zhong et al., 1992; Tzika et al., 1993; Gückel et al., 1994). Recently, magnetic resonance imaging (MRI) methods have been developed that are sensitive to stimulus-induced changes in blood flow (Society of Magnetic Resonance in Medicine, 1993).