Quantitative evaluation of hemodynamic response after hypercapnia among different brain territories by fMRI R.F. Leoni, a K.C. Mazzeto-Betti, b K.C. Andrade, c and D.B. de Araujo a,b, ⁎ a Department of Physics and Mathematics, FFCLRP, Universidade de Sao Paulo, Ribeirao Preto, SP, Brazil b Department of Neurology, Psychiatry and Medical Psychology, FMRP, Universidade de Sao Paulo, Ribeirao Preto, SP, Brazil c Max Planck Institute of Psychiatry, Kraepelinstr. 2-10, 80804 Munich, Germany Received 13 October 2007; revised 10 March 2008; accepted 19 March 2008 Available online 3 April 2008 The brain vascular system has an autoregulatory mechanism that maintains blood perfusion within normal limits at the capillary level. Partially due to its clinical importance, it is of interest to better understand the mechanisms involved in vascular regulation. There- fore, using functional magnetic resonance imaging (fMRI), we quantitatively investigated hemodynamic response characteristics of regions supplied by the main cerebral arteries, during two breath holding tests (BHT): after inspiration and after expiration. We used an auto-regressive method capable of estimating four signal parameters: onset delay, full width at half maximum (FWHM), time-to-peak and amplitude. The onset delay was significantly longer for the posterior cerebral artery (PCA) than for middle cerebral artery (MCA) and anterior arteries (ACA). FWHM and time-to-peak were larger in the ACA territory, indicating a slower blood flow in this region. Differences were also observed in the amplitude among the three areas, where MCA and PCA territories showed the smallest and the highest amplitudes, respectively. Moreover, differences were found in amplitude and onset when BHT was performed after inspiration as compared to BHT after expiration. Time-to-peak and FWHM showed no statistical differences between these two challenges. Such results are related to regional anatomical specificities and biochemical mechan- isms responsible for vasodilation, such as those related to vascularity and vessel sizes. © 2008 Elsevier Inc. All rights reserved. Keywords: Functional MRI; fMRI; Breath holding; Perfusion Introduction The brain vascular system has unique physiologic character- istics, such as autoregulatory vasodilatation, to maintain blood perfusion within normal limits at the capillary level. The non invasive inspection of specific hemodynamic characteristics, such as Cerebral Blood Volume (CBV) and Cerebral Blood Flow (CBF), is of great importance as these variables have a significant impact on the diagnosis and treatment of patients with many cerebrovas- cular related diseases (Soinne et al., 2003; Ziyeh et al., 2005). Many techniques have been used to this end, and magnetic resonance imaging (MRI) has greatly contributed, mainly through dy- namic susceptibility contrast (DSC), and, more recently, Arterial Spin Labeling (ASL). In DSC, tissue perfusion measurements are obtained by acquiring sequential MR images, following intravenous injection of an intravascular contrast agent, such as Gd-DTPA. The computation of CBVand CBF is based on the temporal evolution of such contrast agent concentration through the brain capillary. On the other hand, ASL is emerging as an interesting alternative to quantify perfusion variables without the injection of a contrast agent. It is based on tagging spins from the inflowing artery to make blood itself an endogenous tracer (Golay et al., 2007; Silva and Seong-Gi, 1999; Williams, 2006). Another interesting alternative is functional magnetic resonance imaging (fMRI) which uses the twofold magnetic properties of hemoglobin, depending on whether it is bound to oxygen or not. Deoxyhemoglobin is paramagnetic, while oxyhemoglobin is dia- magnetic. As a result, an increase of regional cerebral blood flow (rCBF) surpassing an increase in cerebral metabolic rate of oxygen (CMRO 2 ) leads to a reduction of deoxyhemoglobin concentration, and a consequent local brightness increase of T2* weighted images (Ogawa et al., 1990). Although fMRI has been employed mainly to investigate human brain function, the temporal characteristics of induced hemo- dynamic changes, also known as hemodynamic response function (HRF), are closely related to cerebrovascular perfusion. Thus, recent studies have applied different challenges, such as breath holding (BH) (Emir et al., 2008; Kastrup et al., 1998; Li et al., 1999), injection of acetazolamide (Bruhn et al., 1994; Hedera et al., 1996) or CO 2 inhalation (Kemna and Posse, 2001; Lythgoe et al., 1999), to modulate cerebral perfusion and, consequently, to study HRF changes. www.elsevier.com/locate/ynimg NeuroImage 41 (2008) 1192 – 1198 ⁎ Corresponding author. DFM–FFCLRP, University of Sao Paulo, Av. Bandeirantes, 3900, 14.040-901, Ribeirao Preto, SP, Brazil. Fax: +55 16 3602 4887. E-mail address: draulio@usp.br (D.B. de Araujo). Available online on ScienceDirect (www.sciencedirect.com). 1053-8119/$ - see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.neuroimage.2008.03.035