Experimental studies of optoacoustic effect on the model of erythrocytes in the presence of carbon nanoparticles

Experimental model has been developed to study optoacoustic signal from model blood cells presented by polystyrene microspheres with nanoparticles. It was found out that nanoparticles due to their strong absorption of light significantly affect the coefficient of cellular optical absorption, while the thermophysical parameters, namely the coefficient of thermal expansion, compressibility and isobaric specific heat of cells remain unchanged, since nanoparticles occupy a small intracellular volume compared to the cell volume. Optoacoustic signals were obtained using model solutions at various concentrations of cells and nanoparticles using 1064 nm laser. The results of experimental measurements using LIMO 100–532/1064-U system based on Nd:YAG showed that the amplitude of the optoacoustic signal increased without increasing the temperature in the laser area.

Quantitation of brain tumour microstructure response to Temozolomide therapy using non-invasive VERDICT MRI

ABSTRACTThere has been slow progress in the development of new therapeutic strategies for treating brain tumours, partly because assessment of treatment response is difficult and largely reliant on simple bi-dimensional measurements of MRI contrast-enhancing regions. Hence, there is a clinical need to develop improved imaging techniques for monitoring treatment response. In this study, we evaluate VERDICT (Vascular, Extracellular and Restricted Diffusion for Cytometry in Tumors) MRI in mouse glioblastomas for the quantification of tumour microstructure and assessment of response to Temozolomide (TMZ) chemotherapy, and, we investigate the feasibility of applying VERDICT MRI in a range of human gliomas. VERDICT MRI detected response to TMZ earlier than structural and apparent diffusion coefficient (ADC) measurements. A significant reduction in the cell radius parameter was detected three days earlier than ADC and six days earlier than structural MRI. Histological analysis showed the same trend as VERDICT of decreased intracellular volume fraction in the TMZ-treated mice. Vascular volume fraction was not altered by TMZ, which was consistent with optical projection tomography measurements. In patients, glioblastoma compartmental volume fractions showed good agreement with mouse glioblastoma parameters. The VERDICT parameters varied across the human gliomas, with raised intracellular volume fraction in the oligodendrogliomas and elevated cell radius in both low-grade tumours subtypes. In conclusion, our results suggest that VERDICT MRI is more sensitive at detecting TMZ response than structural or ADC measurements. In patients, VERDICT is feasible within clinical scan times, and performed best at characterising glioblastoma. Further optimisation should improve assessment of different glioma subtypes.

Moderate-to-severe ischemic conditions increase activity and phosphorylation of the cerebral microvascular endothelial cell Na+-K+-Cl− cotransporter

Brain edema that forms during the early stages of stroke involves increased transport of Na+ and Cl− across an intact blood-brain barrier (BBB). Our previous studies have shown that a luminal BBB Na+-K+-Cl− cotransporter is stimulated by conditions present during ischemia and that inhibition of the cotransporter by intravenous bumetanide greatly reduces edema formation in the rat middle cerebral artery occlusion model of stroke. The present study focused on investigating the effects of hypoxia, which develops rapidly in the brain during ischemia, on the activity and expression of the BBB Na+-K+-Cl− cotransporter, as well as on Na+-K+-ATPase activity, cell ATP content, and intracellular volume. Cerebral microvascular endothelial cells (CMECs) were assessed for Na+-K+-Cl− cotransporter and Na+-K+-ATPase activities as bumetanide-sensitive and ouabain-sensitive 86Rb influxes, respectively. ATP content was assessed by luciferase assay and intracellular volume by [3H]-3-O-methyl-d-glucose and [14C]-sucrose equilibration. We found that 30-min exposure of CMECs to hypoxia ranging from 7.5% to 0.5% O2 (vs. 19% normoxic O2) significantly increased cotransporter activity as did 7.5% or 2% O2 for up to 2 h. This was not associated with reduction in Na+-K+-ATPase activity or ATP content. CMEC intracellular volume increased only after 4 to 5 h of hypoxia. Furthermore, glucose and pyruvate deprivation increased cotransporter activity under both normoxic and hypoxic conditions. Finally, we found that hypoxia increased phosphorylation but not abundance of the cotransporter protein. These findings support the hypothesis that hypoxia stimulation of the BBB Na+-K+-Cl− cotransporter contributes to ischemia-induced brain edema formation.