With continued debate over the functional significance of adult neurogenesis, identifying an in vivo correlate of neurogenesis has become an important goal. Here we rely on the coupling between neurogenesis and angiogenesis and test whether MRI measurements of cerebral blood volume (CBV) provide an imaging correlate of neurogenesis. First, we used an MRI approach to generate CBV maps over time in the hippocampal formation of exercising mice. Among all hippocampal subregions, exercise was found to have a primary effect on dentate gyrus CBV, the only subregion that supports adult neurogenesis. Moreover, exercise-induced increases in dentate gyrus CBV were found to correlate with postmortem measurements of neurogenesis. Second, using similar MRI technologies, we generated CBV maps over time in the hippocampal formation of exercising humans. As in mice, exercise was found to have a primary effect on dentate gyrus CBV, and the CBV changes were found to selectively correlate with cardiopulmonary and cognitive function. Taken together, these findings show that dentate gyrus CBV provides an imaging correlate of exercise-induced neurogenesis and that exercise differentially targets the dentate gyrus, a hippocampal subregion important for memory and implicated in cognitive aging.hippocampus ͉ in vivo imaging ͉ cerebral blood volume ͉ angiogenesis T he hippocampal formation, a brain circuit made up of separate but interconnected subregions (1), is vital for memory function (2) and is targeted by the aging process (3). The dentate gyrus is the only hippocampal subregion that supports neurogenesis in the adult brain (4-6). Nevertheless, because neurogenesis can only be assessed in postmortem tissue, its functional significance remains undetermined. With this limitation in mind, we have explored different imaging approaches applicable to rodents and humans that might provide an in vivo correlate of neurogenesis.Although imaging radioligands designed to bind newly dividing cells is an attractive approach, positron emission tomography imaging suffers inherently poor resolution and cannot visualize the dentate gyrus. Additionally, radiolabeling newborn cells introduces potential safety concerns. For these reasons, we have focused on MRI technologies instead. Notably, a coupling has been established between neurogenesis and angiogenesis (7,8). The process of angiogenesis, in turn, gradually gives rise to the formation of new blood vessels, increasing regional microvascular density (9-12). Importantly, vascular density can be measured in vivo with imaging techniques that map regional blood volume. Numerous studies have established a tight relationship between angiogenesis and regional blood volume (13-17), including in the brain where regional angiogenesis is coupled to regional cerebral blood volume (CBV) (18)(19)(20)(21)(22)(23)(24)(25)(26).Because CBV can be measured with MRI, we hypothesized that a regionally selective increase in hippocampal CBV might provide an imaging correlate of neurogenesis. This hypothesis was tested in...