Background— Recent results from animal studies suggest that stem cells may be able to home to sites of myocardial injury to assist in tissue regeneration. However, the histological interpretation of postmortem tissue, on which many of these studies are based, has recently been widely debated. Methods and Results— With the use of the high sensitivity of a combined single-photon emission CT (SPECT)/CT scanner, the in vivo trafficking of allogeneic mesenchymal stem cells (MSCs) colabeled with a radiotracer and MR contrast agent to acute myocardial infarction was dynamically determined. Redistribution of the labeled MSCs after intravenous injection from initial localization in the lungs to nontarget organs such as the liver, kidney, and spleen was observed within 24 to 48 hours after injection. Focal and diffuse uptake of MSCs in the infarcted myocardium was already visible in SPECT/CT images in the first 24 hours after injection and persisted until 7 days after injection and was validated by tissue counts of radioactivity. In contrast, MRI was unable to demonstrate targeted cardiac localization of MSCs in part because of the lower sensitivity of MRI. Conclusions— Noninvasive radionuclide imaging is well suited to dynamically track the biodistribution and trafficking of mesenchymal stem cells to both target and nontarget organs.

No abstract

Diffusion-tensor fiber tracking was used to identify the cores of several long-association fibers, including the anterior (ATR) and posterior (PTR) thalamic radiations, and the uncinate (UNC), superior longitudinal (SLF), inferior longitudinal (ILF), and inferior fronto-occipital (IFO) fasciculi. Tracking results were compared to existing anatomical knowledge, and showed good qualitative agreement. Guidelines were developed to reproducibly track these fibers in vivo. The interindividual variability of these reconstructions was assessed in a common spatial reference frame (Talairach space) using probabilistic mapping. Complex cognitive and behavioral processes that involve different functional areas of the brain are mediated by neural networks. The ability to identify and characterize the axonal fiber bundles comprising these networks is important for understanding normal as well as pathological processes affecting higher cerebral functions. Most studies of axonal fiber tracts to date have relied on invasive in vivo techniques in animals or ex vivo postmortem human tissue analyses (1,2). In addition, noninvasive radiological techniques, such as conventional MRI, have been able to parcellate only small portions of the white matter into specific tracts in restricted brain regions (3,4). Consequently, knowledge concerning these pathways in vivo is based mainly on primate-human extrapolations (2). In the last decade, diffusion imaging has been shown to be directionally dependent in the white matter (anisotropic diffusion) (5-7), which has been attributed to the organization of axonal fibers and their myelin sheaths. The magnitude and orientation of this anisotropy can be assessed using diffusion-tensor imaging (DTI) (8 -11), which has shown that brain regions with a high density of axonal fibers (e.g., deep white matter) have a high anisotropy. Using DTI and newly developed data processing (tract-tracing) techniques, we have recently shown the capability to perform delineation and 3D reconstruction of the cores of some axonal fiber bundles in animals (12,13), resulting in MR images that agree with standard anatomical data. Further application of this methodology to the study of healthy volunteers has confirmed the feasibility of this emerging technique for human studies (14 -19). However, several crucial steps are still necessary to allow a comprehensive use of this technique for the assessment of the anatomy of human connectivity. These steps include the establishment of procedures to reconstruct reproducibly the fiber trajectories in different individuals, and the validation of their origin through comparison with existing neuroanatomical knowledge. Although the latter validation can only be qualitative for human studies, it remains essential. This work describes our first efforts towards this goal, in which we illustrate the capability of the 3D tracking technique to identify the cores of several long-association fibers. The interindividual variability of these reconstructions is subsequently assessed in a common ...