Mapping of the cerebral response to hypoxia measured using graded asymmetric spin echo EPI Gavin C. Houston a , Nikolas G. Papadakis a,b , T. Adrian Carpenter d , Laurance D. Hall a , Bhashkar Mukherjee b , Michael F. James c , Christopher L-H. Huang b, * a Herchel Smith Laboratory for Medicinal Chemistry, University of Cambridge Clinical School, University Forvie Site, Robinson Way, Cambridge, CB2 2PZ, UK b Physiological Laboratory, University of Cambridge, Downing Street, Cambridge, CB2 3EG, UK c Neuroscience Research, SmithKline Beecham Pharmaceuticals, New Frontiers Science Park (North), Third Avenue, Harlow, Essex, CM19 5AW, UK d Present address: Wolfson Brain Imaging Centre, University of Cambridge, Box 65, Addenbrookes Hospital, Cambridge, CB2 2QQ, UK Received 14 June 2000; accepted 24 August 2000 Abstract Graded asymmetric spin echo-echo planar imaging (ASE-EPI) was used to measure transient alterations in cerebral oxygenation resulting from 60 seconds of anoxia in -chloralose anaesthetised rats. The anoxic period induced a transient fall (1 min) in signal intensity followed by a prolonged signal overshoot consistent with an autoregulatory response to oxygen deprivation. The magnitude of signal response, integrated over the entire brain, increased linearly with the echo asymmetry ( t ge ). However, that increase in sensitivity was offset by a reduced signal to noise ratio and quality of the image data. The responses of four regions of interest within the brain to the anoxic stimulus, and the effect of increasing the echo asymmetry, were compared. A comparable magnitude of signal decrease was observed in all brain regions except the superficial cortex that included pial vessels. As t ge was incremented differences in signal attenuation between regions became more pronounced. The signal overshoot observed upon restoration of normal breathing gases showed similar trends, producing similar normalised vascular responses for all regions of interest studied. Different regions of interest showed comparable time courses of the signal overshoot suggesting that similar autoregulatory vascular mechanisms operate in all brain regions. These findings additionally show that the use of graded ASE-EPI produced a characteristic profile of maximum signal change measured during and following the anoxic period for each brain region. They suggest that the shape of this profile was determined by the local vasculature within each region of interest; this feature could be exploited in activation studies to eliminate regions with significant signal changes originating from large draining vessels. Finally, the consistent physiological response observed, when the overshoot was compared to the magnitude of the signal drop, demonstrated that modification of the spin echo offset parameter did not mask or detrimentally alter the signal change resulting from the underlying physiological perturbation. © 2000 Elsevier Science Inc. All rights reserved. 1. Introduction Thulborn et al. first showed in vitro that the spin spin relaxation time (T 2 ) of the protons of blood in water de- pends on blood oxygenation [1,2]. Thus, increased levels of paramagnetic deoxyhaemoglobin (high spin ferrous state) produce field inhomogeneities in and around the red blood cell causing local dephasing of spin-coherance and therefore signal loss in T 2 *-weighted images. Conversely, diamag- netic oxyhaemoglobin (zero ferrous spin state) does not perturb the local magnetic field and no loss of signal is observed. The magnetic susceptibility difference between the blood vessel wall and surrounding tissue disrupts the phase coherence of the spins; this effect extends signifi- cantly beyond the vessel wall [3]. Ogawa et al. demon- strated the clinical potential of such blood oxygenation level dependent (BOLD) contrast with the first in vivo demon- stration of this phenomenon in the rodent brain [4]. Since the major part of cerebral blood volume is embedded within capillaries, the dephasing causes loss of signal from the surrounding tissue. Therefore, blood oxygenation contrast can be resolved at the voxel level giving high resolution functional maps of the brain. Image acquisition sequences sensitive to blood oxygen- ation changes broadly fall into three categories: gradient echo (GE), spin echo (SE) and fast imaging techniques such as rapid acquisition with relaxation enhancement (RARE) and echo planar imaging (EPI). The latter can be applied to * Corresponding author. Tel.: +44 (0)1223 333822; fax: +44 (0)1223 333840. E-mail address: clh11@cam.ac.uk (C.L-H. Huang). Magnetic Resonance Imaging 18 (2000) 1043–1054 0730-725X/00/$ – see front matter © 2000 Elsevier Science Inc. All rights reserved. PII: S0730-725X(00)00196-X