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The cerebral blood volume change (\u0394CBV) 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\u2010echo technique, with temporal resolution of one min at high magnetic field. The tissue half\u2010life of the USPIOs was studied using a nonlinear detrending model. The three USPIOs are candidates for CBV weighted phMRI experiments, with r<jats:sub>2<\/jats:sub>\/r<jats:sub>1<\/jats:sub> ratios\u2009\u2265\u200920 and apparent half\u2010lives\u2009\u2265\u20091.5\u2009h at the described doses. An echo\u2010time of about 10\u2009ms or longer results in a functional contrast to noise ratio (fCNR)\u2009&gt;\u200975 after USPIO injection, with negligible decrease between 1.5\u20102\u2009h. phMRI experiments were conducted at 7\u2009T using cocaine as a psychotropic substance and acetazolamide, a global vasodilator, as a positive control. Cocaine acts as a dopamine\u2010serotonin\u2010norepinephrine 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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