Real-time dual MRI for predicting and subsequent validation of intra-arterial stem cell delivery to the central nervous system

Stem cell therapy for neurological disorders reached a pivotal point when the efficacy of several cell types was demonstrated in small-animal models. Translation of stem cell therapy is contingent upon overcoming the challenge of effective cell delivery to the human brain, which has a volume of ~1000 times larger than that of the mouse. Intra-arterial (IA) injection can achieve a broad, global, but if needed also spatially targeted biodistribution; however, its utility has been limited by unpredictable cell destination and homing as dictated by the vascular territory, as well as by safety concerns. We show here that high-speed MRI can be used to visualize the intravascular distribution of a superparamagnetic iron oxide contrast agent and can thus be used to accurately predict the distribution of IA administered stem cells. Moreover, high-speed MRI enables the real-time visualization of cell homing, providing the opportunity for immediate intervention in the case of undesired biodistribution.