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Quantitative pharmacologic MRI in mice

Perles-Barbacaru, Teodora-Adriana and Procissi, Daniel and Demyanenko, Andrey V. and Jacobs, Russell E. (2012) Quantitative pharmacologic MRI in mice. NMR in Biomedicine, 25 (4). pp. 498-505. ISSN 0952-3480. PMCID PMC3292675.

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Pharmacologic MRI (phMRI) uses functional MRI techniques to provide a noninvasive in vivo measurement of the hemodynamic effects of drugs. The cerebral blood volume change (ΔCBV) serves as a surrogate for neuronal activity via neurovascular coupling mechanisms. By assessing the location and time course of brain activity in mouse mutant studies, phMRI can provide valuable insights into how different behavioral phenotypes are expressed in deferring brain activity response to drug challenge. In this report, we evaluate the utility of three different intravascular ultrasmall superparamagnetic iron oxide (USPIO) contrast agents for phMRI using a gradient-echo technique, with temporal resolution of one min at high magnetic field. The tissue half-life of the USPIOs was studied using a nonlinear detrending model. The three USPIOs are candidates for CBV weighted phMRI experiments, with r_2/r_1 ratios ≥ 20 and apparent half-lives ≥ 1.5 h at the described doses. An echo-time of about 10 ms or longer results in a functional contrast to noise ratio (fCNR) > 75 after USPIO injection, with negligible decrease between 1.5-2 h. phMRI experiments were conducted at 7 T using cocaine as a psychotropic substance and acetazolamide, a global vasodilator, as a positive control. Cocaine acts as a dopamine-serotonin-norepinephrine reuptake inhibitor, increasing extracellular concentrations of these neurotransmitters, and thus increasing dopaminergic, serotonergic and noradrenergic neurotransmission. phMRI results showed that CBV was reduced in the normal mouse brain after cocaine challenge, with the largest effects in the nucleus accumbens, whereas after acetazolamide, blood volume was increased in both cerebral and extracerebral tissue.

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URLURL TypeDescription CentralArticle
Jacobs, Russell E.0000-0002-1382-8486
Additional Information:© 2011 John Wiley & Sons, Ltd. Issue published online: 23 MAR 2012; Article first published online: 25 JUL 2011; Manuscript Accepted: 19 MAY 2011; Manuscript Revised: 3 MAY 2011; Manuscript Received: 8 NOV 2010. The authors thank Hargun Sohi and Thomas Ng for their technical assistance, Davit Janvelyan for help with the AIR software, and Guerbet Research (Aulnay-Sous-Bois, France) for providing the P904 contrast agent. George Uhl and Scott Hall (National Institute on Drug Abuse, Intramural Research Program) for discussions concerning reward pathway. This project was funded in part by the Beckman Institute, NIDA R01 DA 18184, and NCRR U24 RR021760 Mouse BIRN.
Funding AgencyGrant Number
Caltech Beckman InstituteUNSPECIFIED
National Institute on Drug AbuseR01 DA 18184
National Center for Research Resources (NCRR)U24 RR021760
Subject Keywords:Pharmacologic MRI; mice; USPIO; cocaine; reward circuitry
Issue or Number:4
PubMed Central ID:PMC3292675
Record Number:CaltechAUTHORS:20120426-103457199
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Official Citation:Perles-Barbacaru, T.-A., Procissi, D., Demyanenko, A. V. and Jacobs, R. E. (2012), Quantitative pharmacologic MRI in mice. NMR Biomed., 25: 498–505. doi: 10.1002/nbm.1760
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:30369
Deposited By: Jason Perez
Deposited On:26 Apr 2012 19:17
Last Modified:03 Oct 2019 03:49

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