Imaging of regional metabolic activity by 18 F-FDG/PET in rats with transient cerebral ischemia Ying-Kai Fu a,b,Ã , Chia-Jung Chang a , Kuan-Yin Chen a , Li-Chung Hwang a , Kuo-Hung Wu a , Kang-Wei Chang a , Meei-Ling Jan a , Chia-Chieh Chen a , Chih-Hsien Chang a a Institute of Nuclear Energy Research, Tao-Yuan, Taiwan b Department of Chemistry, Chung Yuan Christian University, Chung-Li, Taiwan article info Article history: Received 1 July 2008 Received in revised form 6 March 2009 Accepted 10 March 2009 Keywords: 18 F-FDG MicroPET Rat ischemia model abstract Changes in regional metabolic activities induced by middle cerebral artery occlusion (MCAO) can influence patient outcome. Our aim was to demonstrate in a rat model that 18 F-FDG with positron emission tomography (PET) imaging is a quantitative, reproducible approach for identifying acute and sub-acute metabolic variations in infarct regions. We found that imaging with 18 F-FDG/PET enabled detection and quantification of ischemia-induced metabolic deficits and provided a sensitive and reliable means of assessing cerebral ischemic lesions compared with conventional neurological scoring systems in rodents. & 2009 Elsevier Ltd. All rights reserved. 1. Introduction Middle cerebral artery occlusion (MCAO) in rodents is an experimental model of cerebral ischemia that is used widely for the evaluation of treatment efficacy after brain injury (Ginsberg and Busto, 2004). It has been proven that transient ischemia in rats induced by MCAO can cause motor incoordination, reduced learning acquisition, and memory impairment (Sakai et al., 1996). The establishment of a reproducible rat model of either perma- nent or transient MCAO is a useful technique for investigating disorders related to the central nervous system. Histological studies of rats that had MCAO surgery indicated considerable variation in infarct size and location among different laboratories and among different experiments by a single investigator using the same MCAO technique (Ginsberg and Busto, 2004; Menzies et al., 1992). Because the status of the infarction is related to the extent and severity of cortical ischemia, identification of the triggered deficits is essential for such a model. To evaluate the cerebral ischemia results, traditional histopathological, biochem- ical, and physiological experiments often require invasive surgery to access the brain tissue. The application of a noninvasive, reproducible, and quantitative approach for the in vivo evaluation of neuronal lesions should greatly enhance the assessment of MCAO outcome. To delineate the infarction status and the dynamic pathophy- siological events that can occur over an extended time period, behavior observation and neurological tests have been developed (Menzies et al., 1992; Sakai et al., 1996). Menzies et al. proposed a neurological evaluation scale to predict the size of infarction and validated its accuracy with pathological grading. These authors suggested a scale of 04 to assess motor and behavioral changes in the neurological test. Briefly, rats that underwent the MCAO procedure and exhibited no apparent deficits were scored 0. Rats with light clinical motor deficits were scored 1 or 2, which corresponded with smaller lesions (o25 mm 2 ). Rats that showed contralateral circling were scored 3 or 4, and these scores correlated significantly with relatively large lesions. The accuracy of prediction of the size of infarction from neurological evaluation reached 91% in MCA-cauterized Sprague-Dawley (SD) rats (Men- zies et al., 1992). However, a lack of correlation between infarct size and neurological status has also been reported in some studies (Van der Staay et al., 1996; Yang et al., 2000). Changes in regional cerebral blood flow and metabolism are commonly associated with brain disorders, such as traumatic brain injury and focal cerebral ischemia (Bergsneider et al., 2001; Ginsberg et al., 1977; Marklund et al., 2002). In the normal state, glucose is the predominant substrate for energy metabolism in the brain and has a tightly controlled relationship with cerebral blood flow. Monitoring variations in local brain glucose utilization that result from focal cerebral ischemia might provide additional information for the evaluation of infarction status. Positron ARTICLE IN PRESS Contents lists available at ScienceDirect journal homepage: www.elsevier.com/locate/apradiso Applied Radiation and Isotopes 0969-8043/$ - see front matter & 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.apradiso.2009.03.002 Ã Corresponding author at: Institute of Nuclear Energy Research Atomic Energy Council, Executive Yuan No. 1000, Wunhua Rd., Jiaan Village, Longtan Township, Taoyuan, County 32546, Taiwan, ROC. Tel.: +886 3 4711400x2500; fax: +886 3 4713839. E-mail address: fufrank@iner.gov.tw (Y.-K. Fu). Applied Radiation and Isotopes 67 (2009) 1743–1747