Serial in vivo MR tracking of magnetically labeled neural spheres transplanted in chronic EAE mice.

Neural stem cell (NSC) transplantation has been shown to attenuate the severity of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Central to the future success of NSC transplantation in MS is the ability of transplanted cells to migrate from the site of transplantation to relevant foci of disease. Using magnetically labeled mouse neurospheres and human embryonic stem cell (hESC)-derived neurospheres, we applied serial magnetic resonance imaging (MRI) to assess the biodynamics of transplanted cell migration in a chronic mouse EAE model. Magnetic labeling did not affect the in vitro and in vivo characteristics of cells as multipotential precursors. Cell migration occurred along white matter (WM) tracts (especially the corpus callosum (CC), fimbria, and internal capsule), predominantly early in the acute phase of disease, and in an asymmetric manner. The distance of cell migration correlated well with clinical severity of disease and the number of microglia in the WM tracts, supporting the notion that inflammatory signals promote transplanted cell migration. This study shows for the first time that hESC-derived neural precursors also respond to tissue signals in an MS model, similarly to rodent cells. The results are directly relevant for designing and optimizing cell therapies for MS, and achieving a better understanding of in vivo cell dynamics and cell-tissue interactions.     

An Automated Self‐Similarity Analysis of the Pulmonary Tree of the Sprague–Dawley Rat

We present the results of an automated analysis of the morphometry of the pulmonary airway trees of the Sprague–Dawley rat. Our work is motivated by a need to inform lower‐dimensional mathematical models to prescribe realistic boundary conditions for multiscale hybrid models of rat lung mechanics. Silicone casts were made from three age‐matched, male Sprague–Dawley rats, immersed in a gel containing a contrast agent and subsequently imaged with magnetic resonance (MR). From a segmentation of this data, we extracted a connected graph, representing the airway centerline. Segment statistics (lengths and diameters) were derived from this graph. To validate this MR imaging/digital analysis method, airway segment measurements were compared with nearly 1,000 measurements collected by hand using an optical microscope from one of the rat lung casts. To evaluate the reproducibility of the MR imaging/digital analysis method, two lung casts were each imaged three times with randomized orientations in the MR bore. Diameters and lengths of randomly selected airways were compared among each of the repeated imaging datasets to estimate the variability. Finally, we analyzed the morphometry of the airway tree by assembling individual airway segments into structures that span multiple generations, which we call branches. We show that branches not segments are the fundamental repeating unit in the rat lung and develop simple mathematical relationships describing these structures for the entire lung. Our analysis shows that airway diameters and lengths have both a deterministic and stochastic character. Anat Rec, 2008. © 2008 Wiley‐Liss, Inc.     

Efficacy and toxicity of concomitant cisplatin with external beam pelvic radiotherapy and two high-dose-rate brachytherapy insertions for the treatment of locally advanced cervical cancer

OBJECTIVE: There is no standard high-dose-rate (HDR) brachytherapy dose for locally advanced cervical cancer. The objective of this study was to determine the efficacy, toxicity and clinicopathologic predictive markers affecting survival using cisplatin (CDDP) concomitant with external beam pelvic radiotherapy (EBRT) and two 9-Gy HDR insertions for the treatment of locally advanced cervical cancer. METHODS: 77 consecutive patients with Stage IB2-IV cervical cancer treated with CDDP, EBRT and two 9-Gy HDR insertions were included. Kaplan-Meier methods and Cox proportional hazards models were applied for survival statistics. RESULTS: Median age was 53. 90% had squamous cell carcinoma. Median follow-up time was 3.5 years (range 0.5-12 years). Overall 5-year progression-free survival (PFS) was 75%. Local control rate and 5-year PFS were 88% and 83%, respectively, for Stages IB2/II, and 68% and 61%, respectively, for Stages III/IV. Grade 3/4 GI symptoms were the most common acute side effects (47%). Grade 3/4 late toxicities occurred in five (6%) patients. CONCLUSIONS: HDR brachytherapy regimens consisting of two 9-Gy HDR insertions have similar efficacy and side effect profiles as other brachytherapy regimens for the treatment of cervical cancer with improved safety and patient convenience.     

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