Cerebral blood volume MRI with intravascular superparamagnetic iron oxide nanoparticles

Cerebral blood volume (CBV) is a crucial physiological indicator of tissue viability and vascular reactivity. Thus, non-invasive CBV mapping has been of great interest. For this, ultrasmall superparamagnetic iron oxide nanoparticles (USPIO) including monocrystalline iron oxide nanoparticles (MION) can be used as long half-life, intravascular susceptibility agents of CBV MRI measurements. Also, CBV-weighted fMRI with USPIO provides enhanced sensitivity, reduced large vessel contribution, and improved spatial specificity compared to conventional blood oxygenation-level dependent (BOLD) fMRI, and measures a single physiological parameter that is easily interpretable. We review physiochemical and magnetic properties as well as pharmacokinetics of USPIO 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 application of CBV measurements to functional and pharmacological studies in animals. Overall, the use of USPIO can determine baseline CBV and its changes induced by functional activity and pharmacological interventions.