Cell aggregates are a tool for in vitro studies of morphogenesis, cancer invasion, and tissue engineering. They respond to mechanical forces as a complex rather than simple liquid. To change an aggregate's shape, cells have to overcome energy barriers. If cell shape fluctuations are active enough, the aggregate spontaneously relaxes stresses (“fluctuation-induced flow”). If not, changing the aggregate's shape requires a sufficiently large applied stress (“stress-induced flow”). To capture this distinction, we develop a mechanical model of aggregates based on their cellular structure. At stress lower than a characteristic stress τ*, the aggregate as a whole flows with an apparent viscosity η*, and at higher stress it is a shear-thinning fluid. An increasing cell–cell tension results in a higher η* (and thus a slower stress relaxation time tc ). Our constitutive equation fits experiments of aggregate shape relaxation after compression or decompression in which irreversibility can be measured; we find tc of the order of 5 h for F9 cell lines. Predictions also match numerical simulations of cell geometry and fluctuations. We discuss the deviations from liquid behavior, the possible overestimation of surface tension in parallel-plate compression measurements, and the role of measurement duration.
We previously reported the synthesis of gadolinium-based nanoparticles (NPs) denoted AGuIX (activation and guiding of irradiation by X-ray) NPs and demonstrated their potential as an MRI contrast agent and their efficacy as radiosensitizing particles during X-ray cancer treatment. Here we focus on the elimination kinetics of AGuIX NPs from the subcellular to whole-organ scale using original and complementary methods such as laser-induced breakdown spectroscopy (LIBS), intravital two-photon microscopy, inductively coupled plasma optical emission spectrometry (ICP-OES), transmission electron microscopy (TEM), and electrospray ionization mass spectrometry (ESI-MS). This combination of techniques allows the exact mechanism of AGuIX NPs elimination to be elucidated, including their retention in proximal tubules and their excretion as degraded or native NPs. Finally, we demonstrated that systemic AGuIX NP administration induced moderate and transient effects on renal function. These results provide useful and promising preclinical information concerning the safety of theranostic AGuIX NPs.
1 April 2006 in International Journal of Radiation Oncology - Biology - Physics (IJROBP)
A novel water-soluble Ru(II) complex has been prepared, which represents a promising new class of selective two-photon sensitizers for use in photodynamic therapy within a confined space.
31 October 2001 in Journal of Magnetic Resonance Imaging
The present review has been compiled to highlight the role of magnetic resonance imaging (MRI) and MR spectroscopy (MRS) for the investigation of cerebral ischemia in the animal experimental field of basic research. We have focused on stroke investigations analyzing the pathomechanisms of the disease evolution and on new advances in both nuclear MR (NMR) methodology or genetic engineering of transgenic animals for the study of complex molecular relationships and causes of the disease. Furthermore, we have tried to include metabolic and genetic aspects, as well as the application of functional imaging, for the investigation of the disturbance or restitution of functional brain activation under pathological conditions as relates to controlled animal experiments. J. Magn. Reson. Imaging 2001;14:491–509.
19 March 2003 in Journal of Magnetic Resonance Imaging
Purpose: To investigate the physiological origins responsible for the varying blood oxygenation level dependent (BOLD) magnetic resonance imaging (MRI) responses to carbogen (95% O2/5% CO2) breathing observed with different tumor types.Materials and Methods: Susceptibility contrast‐enhanced MRI using the exogenous blood pool contrast agent NC100150 to determine blood volume and vessel size, and immunohistochemical‐derived morphometric parameters, were determined in GH3 prolactinomas and RIF‐1 fibrosarcomas, both grown in mice, which exhibited very different BOLD responses to carbogen.Results: Administration of NC100150 increased the R2* and R2 rates of both tumor types, and indicated a significant four‐fold larger blood volume in the GH3 tumor. The ratio ΔR2*/ΔR2 showed that the capillaries in the GH3 were two‐fold larger than those in the RIF‐1, in agreement with morphometric analysis. Carbogen breathing induced a significant 25% decrease in R2* in the GH3 prolactinoma, whereas the response in the RIF‐1 fibrosarcoma was negligible.Conclusion: Low blood volume and small vessel size (and hence reduced hematocrit) are two reasons for the lack of R2* change in the RIF‐1 with carbogen breathing. BOLD MRI is sensitive to erythrocyte‐perfused vessels, whereas exogenous contrast agents interrogate the total perfused vascular volume. BOLD MRI, coupled with a carbogen challenge, provides information on functional, hemodynamic tumor vasculature. J. Magn. Reson. Imaging 2003;17:445–454.