Cerebral blood volume MRI with intravascular superparamagnetic iron oxide nanoparticles

The cerebral blood volume (CBV) is a crucial physiological indicator of tissue viability and vascular reactivity. Thus, noninvasive CBV mapping has been of great interest. For this, ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles, including monocrystalline iron oxide nanoparticles, can be used as long-half-life, intravascular susceptibility agents of CBV MRI measurements. Moreover, CBV-weighted functional MRI (fMRI) with USPIO nanoparticles provides enhanced sensitivity, reduced large vessel contribution and improved spatial specificity relative to conventional blood oxygenation level-dependent fMRI, and measures a single physiological parameter that is easily interpretable. We review the physiochemical and magnetic properties, and pharmacokinetics, of USPIO nanoparticles in brief. We then extensively discuss quantifications of baseline CBV, vessel size index and functional CBV change. We also provide reviews of dose-dependent sensitivity, vascular filter function, specificity, characteristics and impulse response function of CBV fMRI. Examples of CBV fMRI specificity at the laminar and columnar resolution are provided. Finally, we briefly review the application of CBV measurements to functional and pharmacological studies in animals. Overall, the use of USPIO nanoparticles can determine baseline CBV and its changes induced by functional activity and pharmacological interventions.