TRADITIONAL POSTER - ismrm

Poster Sessions
1224. De Novo Buprenorphine Phmri Effects in Conscious Rats Parallels Brain Activation in Humans
Lino Becerra 1,2 , Pei-Ching Chang 1 , James Bishop 1 , Jaymin Upadhyay 1 , Julie Anderson 1 , Gautam Pendse 1 ,
Smriti Iyengar 3 , Alexandre Coimbra 4 , Richard Baumgartner 4 , Adam Schwarz 3 , Jeffrey Evelhoch 4 , Erci
Nisenbaum 3 , Brigitte Robertson 5 , Thomas Large 5 , David Bleakman 3 , Richard Hargreaves 4 , David
Borsook 1,2
1 Imaging Consortium for Drug Development, McLean Hospital, Belmont, MA, United States; 2 A A Martinos Center for Biomed.
Imaging, MGH, Harvard Medical School, Charlestown, MA, United States; 3 Eli Lilly and Co., Indianapolis, IN, United States; 4 Merck
and Co, West Point, PA, United States; 5 Sepracor Inc., Marlborough, MA, United States
fMRI studies of rodents are confounded by the use of anesthetics, especially for the study of analgesics. Furthermore, there are no studies comparing
pharmacological brain effects in humans and rodents of the same analgesics. In this work, we present results of pharmacological MRI (phMRI) of an opioid
analgesic (buprenorphine) in conscious rats and compare the brain activations with results obtained in humans. Although brain structure and function differ
between humans and rodents, some parallelism does exist and this thesis underpins much pre-clinical research. Translational results as presented here have
the potential to bridge pre-clinical with clinical imaging studies.
1225. A FMRI Study to Decipher the Regional Effects of an Intraperitoneal Glucose Dose in the Fasted Rat
Model
Kim O'Toole 1 , Diana Cash 1 , Steve C R Williams 1 , Po-Wah So 1
1 Neuroimaging Department, Institute of Psychiatry, KCL, London, United Kingdom
Glucosensing neurones regulate membrane potential and firing rates in response to ambient glucose levels, and generally located in areas involved in
neuroendocrine function, nutrient metabolism and energy homeostasis. Using BOLD-MRI, we have studied the effects of a single intraperitoneal glucose
tolerance dose in the brain of a fasted rat model. Glucose induced BOLD-MRI signal increases in various regions of the brain, including the hypothalamus
and hippocampus, which are known to contain glucosensing neurones. Thus, BOLD-MRI may be used to a non-invasive tool assess the functional role of
nutrients in the brain under different physiological states.
1226. Effect of the Novel Anti-Depressant Agomelatine Determined by Pharmacological MRI in the Rat.
Karen Elizabeth Davies 1 , Inna V. Linnik 1 , Shane Mckie 2 , Jennifer A. Stark 3 , Simon Luckman 3 , Laure
Sequin 4 , Elisabeth Mocaer 4 , Mark Millan 4 , Bill Deakin 2 , Steve R. Williams 1
1 Imaging Science & Biomedical Engineering, University of Manchester, Manchester, United Kingdom; 2 Neuroscience and Psychiatry
Unit, University of Manchester, Manchester, United Kingdom; 3 Faculty of Life Science, University of Manchester, Manchester,
United Kingdom; 4 Institut de Recherches Internationales, Servier, Courbevoie, France
phMRI was used to determine brain areas activated by the novel anti-depressant agomelatine at 3 doses. T2*-weighted GE images were acquired
continuously before and after injection of agomelatine or vehicle in isoflurane-anaesthetized rats. A pseudoblock analysis was performed in SPM5, revealing
significant areas of activation and deactivation including cortical, hippocampal and caudate regions. There was a marked effect of dose with more brain
areas, more total voxels and higher Z-scores at a dose of 20mg/kg compared to either 10 or 40mg/kg. Agomelatine acts at both melatonin and serotonin
receptors and both receptors are likely to be involved in these responses.
1227. Concurrent Pharmacological MRI and Electrophysiology to Investigate Neuropharmacological
Modulation of Brain Function in the Rat
Christopher James Martin 1 , Nicola R. Sibson 1
1 Radiation Oncology and Biology, University of Oxford, Oxford, Oxfordshire, United Kingdom
The aim of this work was to combine pharmacological magnetic resonance imaging with electrophysiological recording of neuronal activity such that we
might improve our understanding of: (1) the neural basis of neuroimaging signals; (2) the effects of neuropharmacological manipulations on neurovascular
coupling and neuroimaging signals; and (3) neuroanatomical differences in the relationship between neuronal activity and neuroimaging signals. We report
data from studies in which we use the serotonin (5-HT) releasing agent fenfluramine to increase endogenous 5HT levels and investigate the effects of this
modulation on both baseline and stimulus-evoked fMRI signals and neuronal activity.
1228. BOLD PhMRI in the Rat on a Clinical 3T Scanner Using Cocaine Challenge
Edwin Heijman 1 , Duncan Jack Hodkinson 2 , Roland van de Molengraaf 3 , Brian Henry 4 , Shane McKie 5 ,
Charles Sio 1
1 Philips Research Europe, Philips, Eindhoven, Netherlands; 2 Imaging Science and Biomedical Engineering, The University of
Manchester, Manchester, United Kingdom; 3 Life Science Facilities, Philips Research, Philips, Eindhoven, Netherlands; 4 Translational
Medicine Research Centre, Schering-Plough, Singapore, Singapore; 5 Neuroscience and Psychiatry Unit, The University of
Manchester, Manchester, United Kingdom
In this study we investigated the potential applications of a clinical 3T system for pharmacological MRI (phMRI) in the rat brain. Using a human 3T MRI
scanner, a dynamic SE-EPI BOLD sequence was implemented to determine alterations between pre- and post-injection of 5 mg/kg cocaine in male Sprague-
Dawley rats under isoflurane anesthesia. Data analysis was performed using pseudoblock analyses. Cocaine-saline subtraction across the time series, showed
significant activations in cortico-limibc areas of the motor, retrosplenial, and piriform cortex, extending to subcortical areas of the antero-dorsal
hippocampus. We conclude that pre-clinical phMRI studies can be performed using 3T clinical scanners.