The body growth of animals is regulated by growth hormone and IGF-I. The classical theory of this regulation is that most IGF-I in the blood originates in the liver and that body growth is controlled by the concentration of IGF-I in the blood. We have abolished IGF-I production in the livers of mice by using the Cre͞loxP recombination system. These mice demonstrated complete inactivation of the IGF-I gene in the hepatocytes. Although the liver accounts for less than 5% of body mass, the concentration of IGF-I in the serum was reduced by 75%. This finding confirms that the liver is the principal source of IGF-I in the blood. However, the reduction in serum IGF-I concentration had no discernible effect on postnatal body growth. We conclude that postnatal body growth is preserved despite complete absence of IGF-I production by the hepatocytes.

There is rapid growth in the use of MRI for molecular and cellular imaging. Much of this work relies on the high relaxivity of nanometer-sized, ultrasmall dextran-coated iron oxide particles. Typically, millions of dextran-coated ultrasmall iron oxide particles must be loaded into cells for efficient detection. Here we show that single, micrometer-sized iron oxide particles (MPIOs) can be detected by MRI in vitro in agarose samples, in cultured cells, and in mouse embryos. Experiments studying effects of MRI resolution and particle size from 0.76 to 1.63 m indicated that T 2 * effects can be readily detected from single MPIOs at 50-m resolution and significant signal effects could be detected at resolutions as low as 200 m. Cultured cells were labeled with fluorescent MPIOs such that single particles were present in individual cells. These single particles in single cells could be detected both by MRI and fluorescence microscopy. Finally, single particles injected into singlecell-stage mouse embryos could be detected at embryonic day 11.5, demonstrating that even after many cell divisions, daughter cells still carry individual particles. These results demonstrate that MRI can detect single particles and indicate that single-particle detection will be useful for cellular imaging.N umerous recent studies (1-4) indicate that there is a wide range of applications for MRI in molecular and cellular imaging. A key requirement for these applications is the availability of high-relaxivity MRI contrast agents that have a large effect on the MRI signal. One of the agents with very high relaxivity is nanometer-sized, ultrasmall dextran-coated iron oxide particles (USPIOs). These nanometer-sized particles have a large effect on MRI signal intensities due to the fact that they are superparamagnetic and disrupt magnetic field homogeneity to an extent much larger than their size. A growing number of studies have demonstrated the usefulness of USPIOs and MRI to detect receptors (3, 5-8) and monitor cell migration (9-11). Indeed, when a cell is labeled with millions of USPIOs, single cells can be detected by MRI even though the MRI is acquired at low resolution (50-100 m) compared with the size of the cells (5-20 m; refs. 12-14).A drawback of techniques that use USPIOs is that for significant signal changes, many particles need to be within an imaging voxel. Recently, we have shown that micrometer-sized iron oxide particles (MPIOs), which are commercially available, are efficiently endocytosed by a variety of cells, and these particles can be used for cellular imaging by MRI (14). Because these particles are polymer-coated and are impregnated with a fluorescent agent, it becomes possible to do both fluorescence microscopy and MRI on cells labeled with such particles. Empirical observations suggest that an iron oxide particle disrupts the magnetic field enough for MRI detectability for a distance at least 50 times its size, ¶ leading to the conclusion that cells harboring single, micrometer-sized particles should be detectable by ...