Background-Cell labeling with superparamagnetic iron oxide (SPIO) nanoparticles enables noninvasive MRI and tracking of transplanted stem cells. We sought to determine whether mesenchymal stem cell (MSC) outcome is affected by SPIO labeling in a rat model of myocardial infarction. Methods and Results-Rat MSCs were labeled with SPIO (ferumoxides; Endorem; Guerbet, Villepinte, France). By trypan-blue exclusion assay, almost 100% of the cells remained viable after labeling. Seven days after MI, rats were randomized to injections of 2ϫ10 6 SPIO-labeled MSCs, 2ϫ10 6 unlabeled MSCs, or saline. Labeled cells were visualized in the infarcted myocardium as large black spots by serial MRI studies throughout the 4-week follow-up. The presence of labeled cells was confirmed by iron staining and real-time polymerase chain reaction on postmortem specimens. At 4 weeks after transplantation, the site of cell injection was infiltrated by inflammatory cells. Costaining for iron and ED1 (resident macrophage marker) showed that the iron-positive cells were cardiac macrophages. By real-time polymerase chain reaction, the Y-chromosome-specific SRY DNA of MSCs from male donors was not detected in infarcted hearts of female recipients. Serial echocardiography studies at baseline and 4 weeks after cell transplantation showed that both unlabeled and labeled MSCs attenuated progressive left ventricular dilatation and dysfunction compared with controls. Conclusions-At

On the basis of our data we suggest that CED of paclitaxel in patients with recurrent malignant gliomas is associated with a high antitumor response rate, although it is associated with a significant incidence of treatment-associated complications. Diffusion-weighted MR images may be used to predict a response by demonstrating the extent of convection during treatment. Optimization of this therapeutic approach to enhance its efficacy and reduce its toxicity should be explored further.

The significant correlation between changes in diffusion parameters 1 week after initiating treatment and later tumor response or no response suggests the feasibility of using DWMRI for early, noninvasive prediction of tumor response. The ability to predict response may enable early termination of treatment in nonresponding patients, prevent additional toxicity, and allow for early changes in treatment.

High-b-value diffusion-weighted MR imaging has potential use for the early detection of response to therapy and for predicting treatment outcome prior to initiation of chemotherapy.

Background-Activated macrophages have a significant role in wound healing and damaged tissue repair. We sought to explore the ability of ex vivo activated macrophages to promote healing and repair of the infarcted myocardium. Methods and Results-Human activated macrophage suspension (AMS) was prepared from a whole blood unit obtained from young donors in a closed sterile system and was activated by a novel method of hypo-osmotic shock. The AMS (Ϸ4ϫ10 5 cells) included up to 43% CD14-positive cells and was injected into the ischemic myocardium of rats (nϭ8) immediately after coronary artery ligation. The control group (nϭ9) was treated with saline injection. The human cells existed in the infarcted heart 4 to 7 days after injection, as indicated by histology, human growth hormone-specific polymerase chain reaction, and magnetic resonance imaging (MRI) tracking of iron oxide-nanoparticle-labeled cells.

We measured simultaneously pp elastic and quasielastic ͑ p, 2p͒ scattering in hydrogen, deuterium, and carbon for momentum transfers of 4.8 to 6.2 ͑GeV͞c͒ 2 at incoming momenta of 5.9 and 7.5 GeV͞c and center-of-mass scattering angles in the range u c.m. 83.7 ± 90 ± . The nuclear transparency is defined as the ratio of the quasielastic cross section to the free pp cross section. At incoming momentum of 5.9 GeV͞c, the transparency of carbon decreases by a factor of 2 from u c.m. Ӎ 85 ± to u c.m. Ӎ 89 ± . At the largest angle the transparency of carbon increases from 5.9 to 7.5 GeV͞c by more than 50%. The transparency in deuterium does not depend on incoming momentum nor on u c.m. . [S0031-9007 (98)07818-1] PACS numbers: 24.85. + p, 25.40. -h, 24.10. -iNuclear transparency is a measure of the initial and final state interactions that the incoming and outgoing protons undergo before and after the main ͑p, 2p͒ reaction. Conventional theoretical calculations of the nuclear transparency within the Glauber picture [1,2] predict that above an incident momentum of approximately 5 GeV͞c the nuclear transparency does not depend on the incoming momentum nor on the pp c.m. scattering angle, u c.m. . The expectation from QCD based models of proton dynamics in hard exclusive interactions is that the initial and final state scattering may be smaller than the Glauber theory would predict. It is also expected that nuclear transparency should increase with incoming momentum reaching an asymptotic value of 1. These QCD phenomena have been referred to as color transparency [3].

Convection-enhanced drug delivery (CED) is a novel approach to directly deliver drugs into brain tissue and brain tumors. It is based on delivering a continuous infusion of drugs via intracranial catheters, enabling convective distribution of high drug concentrations over large volumes of the target tissue while avoiding systemic toxicity. Efficient formation of convection depends on various physical and physiologic variables. Previous convection-based clinical trials showed significant diversity in the extent of convection among patients and drugs. Monitoring convection has proven to be an essential, yet difficult task. The current study describes the application of magnetic resonance imaging for immediate assessment of convection efficiency and early assessment of cytotoxic tissue response in a rat brain model. Immediate assessment of infusate distribution was obtained by mixing Gd-diethylenetriaminepentaacetic acid in the infusate prior to infusion. Early assessment of cytotoxic tissue response was obtained by subsequent diffusion-weighted magnetic resonance imaging. In addition, the latter imaging methodologies were used to establish the correlation between CED extent and infusate's viscosity. It was found that low-viscosity infusates tend to backflow along the catheter track, whereas highviscosity infusates tend to form efficient convection. These results suggest that CED formation and extent may be significantly improved by increasing the infusate's viscosities, thus increasing treatment effects. (Cancer Res 2005; 65(15): 6858-63)

Diffusion-weighted magnetic resonance imaging (DWMRI) is sensitive to tissues' biophysical characteristics, including apparent diffusion coefficients (ADCs) and volume fractions of water in different populations. In this work, we evaluate the clinical efficacy of DWMRI and high diffusion-weighted magnetic resonance imaging (HDWMRI), acquired up to b = 4000 sec/mm(2) to amplify sensitivity to water diffusion properties, in pretreatment prediction of brain tumors' response to radiotherapy. Twelve patients with 20 brain lesions were studied. Six ring-enhancing lesions were excluded due to their distinct diffusion characteristics. Conventional and DWMRI were acquired on a 0.5-T MRI. Response to therapy was determined from relative changes in tumor volumes calculated from contrast-enhanced T1-weighted MRI, acquired before and a mean of 46 days after beginning therapy. ADCs and a diffusion index, R(D), reflecting tissue viability based on water diffusion were calculated from DWMRIs. Pretreatment values of ADC and R(D) were found to correlate significantly with later tumor response/nonresponse (r = 0.76, P <.002 and r = 0.77, P <.001). This correlation implies that tumors with low pretreatment diffusion values, indicating high viability, will respond better to radiotherapy than tumors with high diffusion values, indicating necrosis. These results demonstrate the feasibility of using DWMRI for pretreatment prediction of response to therapy in patients with brain tumors undergoing radiotherapy.