Abstract
Ultrasmall superparamagnetic iron oxide nanoparticles have been widely used during the past decade as MR intravascular contrast agents in the study of animal models. Such agents enhance both T~1~ and T~2~/T~2~* relaxation, although for animal studies it is the later type of enhancement that is most commonly exploited. Their strong microscopic intravascular susceptibility effect enables the local blood volume distribution to be mapped in various organs. High spatial resolution and sensitivity can be achieved, because the long halfโlife of these agents in blood, combined with anesthetization, permits steadyโstate measurements over extended periods. This capability has been utilized to study the cerebrovascular blood volume distributions and their changes in normal, activated, pathologic and pharmacologically or genetically modified states, particularly in rodent animal models. It has also been applied to study blood volume changes in other tissues, such as the myocardium. The relaxation rate shifts ฮ__R__~2~ and ฮ__R__~2~* induced by iron oxide agents may differ depending on certain morphological characteristics of the microvascular network, and sensitive ฮ__R__~2~ and ฮ__R__~2~* mapping can potentially provide, in addition to blood volume, measurement of other important microvascular parameters such as blood vessel density and size. This work aims to review the applications of ultrasmall superparamagnetic iron oxide contrast agents in MR animal studies, with an emphasis on the investigation of microvascular parameters. Copyright ยฉ 2004 John Wiley & Sons, Ltd.