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.

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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 ...

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Cancer cells invade by secreting degradative enzymes, which are sequestered in lysosomal vesicles. In this study, the impact of an acidic extracellular environment on lysosome size, number, and distance from the nucleus in human mammary epithelial cells (HMECs) and breast cancer cells of different degrees of malignancy was characterized because the physiological microenvironment of tumors is frequently characterized by extracellular acidity. An acidic extracellular pH (pH(e)) resulted in a distinct shift of lysosomes from the perinuclear region to the cell periphery irrespective of the HMECs' degree of malignancy. With decreasing pH, larger lysosomal vesicles were observed more frequently in highly metastatic breast cancer cells, whereas smaller lysosomes were observed in poorly metastatic breast cancer cells and HMECs. The number of lysosomes decreased with acidic pH values. The displacement of lysosomes to the cell periphery driven by extracellular acidosis may facilitate exocytosis of these lysosomes and increase secretion of degradative enzymes. Filopodia formations, which were observed more frequently in highly metastatic breast cancer cells maintained at acidic pH(e), may also contribute to invasion.

It is shown that diffusion tensor MR imaging (DTI) can discretely delineate the microstructure of white matter and gray matter in embryonic and early postnatal mouse brains based on the existence and orientation of ordered structures. This order was found not only in white matter but also in the cortical plate and the periventricular zone, which are precursors of the cerebral cortex. This DTI-based information could be used to accomplish the automated spatial definition of the cortical plate and various axonal tracts. The DTI studies also revealed a characteristic evolution of diffusion anisotropy in the cortex of the developing brain. This ability to detect changes in the organization of the brain during development will greatly enhance morphological studies of transgenic and knockout models of cortical dysfunction. With the advent of murine models of disease and development generated by gene engineering, a new noninvasive technique is needed to characterize 3D morphological changes appearing over time in the brain. At present, the microscopic anatomical analyses of mammalian developmental studies are almost exclusively based on the histological examination. While this technique is most effective for examining microscopic changes in developing brains, it is not particularly suitable to characterize large-scale morphology, such as the anatomy of the entire brain. Although it is possible to reconstruct a macroscopic 3D-volume dataset using serial histological sections and stereology, this is an extremely labor-intensive process (1,2). To examine global anatomy in developing mouse brains, MRI technology is especially promising (3,4) because it can provide a 3D dataset without sectioning and is free of artifacts related to brain deformation or missing tissue due to imperfect sectioning. The data are intrinsically numerical and quantification for shape and volume analyses is more straightforward. Similar to various staining techniques for histological preparations, MRI also provides a family of contrast types based on the physical properties of water. For example, mouse embryonic imaging has been performed using proton density T 1 -and T 2 -weighted images (3-6). While these imaging methods can provide clear contrast for various tissue compartments in the entire body, it is not always optimal for the differentiation of compartments within the brain because of small differences in T 1 and T 2 relaxation parameters in young brains (7,8). Moreover, even in adult brains conventional MRI methods are not suitable to differentiate various white matter tracts within the brain white matter.In this report, we apply an MRI technology called diffusion tensor imaging (DTI) (9,10) to study mouse brain development from a period starting at embryonic day 15.5 in utero to adult. This technique uses water diffusion to probe tissue microstructure. For example, in regions where axon tracts form an ordered environment, water diffusion has directionality (anisotropy). Application of this technique to the adult brain has revealed that whi...

Numerous methods to segment tumors using F-fluorodeoxyglucose positron emission tomography (FDG PET) have been introduced. Metabolic tumor volume (MTV) refers to the metabolically active volume of the tumor segmented using FDG PET, and has been shown to be useful in predicting patient outcome and in assessing treatment response. Also, tumor segmentation using FDG PET has useful applications in radiotherapy treatment planning. Despite extensive research on MTV showing promising results, MTV is not used in standard clinical practice yet, mainly because there is no consensus on the optimal method to segment tumors in FDG PET images. In this review, we discuss currently available methods to measure MTV using FDG PET, and assess the advantages and disadvantages of the methods.

The authors used diffusion-tensor imaging to examine central white matter pathways in two children with spastic quadriplegic cerebral palsy. Corticospinal tracts projecting from cortex to brainstem resembled controls. In contrast, posterior regions of the corpus callosum, internal capsule, and corona radiata were markedly reduced, primarily in white matter fibers connected to sensory cortex. These findings suggest that the motor impairment in periventricular leukomalacia may, in part, reflect disruption of sensory connections outside classic pyramidal motor pathways.