Project description:PurposeOur purpose was to assess the suitability of airway-implanted internal fiducial markers and an external surrogate of respiratory motion for motion management during radiation therapy of lung tumors.Methods and materialsWe analyzed 4-dimensional computed tomography scans acquired during radiation therapy simulation for 28 patients with lung tumors who had anchored fiducial markers bronchoscopically implanted inside small airways in or near the tumor in a prospective trial. We used a linear mixed model to build population-based correlative models of tumor and surrogate motion. The first 24 of the 28 patients were used to build correlative models, and 4 of the 28 consecutive patients were excluded and used as an internal validation cohort. Of the 24 patients from the model building cohort, all were used for the models based on the internal fiducial. The external surrogate was completely visualized in 11 patients from the model building cohort, so only those were used for the models based on the external surrogate. Furthermore, we determined the predicted residual error sum of squares for our correlative models, which may serve as benchmarks for future research.ResultsThe motion of the internal fiducials was significantly associated with the tumor motion in the anterior-posterior (P < .0001) and superior-inferior (SI) directions (P < .0001). We also observed a strong correlation of the external surrogate anterior-posterior motion to the tumor dominant SI motion (P < .0001). In the validation cohort, the internal fiducial SI motion was the only reliable predictor of lung tumor motion.ConclusionsThe internal fiducials appear to be more reliable predictors of lung tumor motion than the external surrogate. The suitability of such airway-implanted internal fiducial markers for advanced motion management techniques should be further investigated. Although the external surrogate seems to be less reliable, its wide availability and noninvasive application support its clinical utility, albeit the greater uncertainty will need to be compensated for.
Project description:The ability for cells to self-synthesize metal-core nanoclusters (mcNCs) offers increased imaging and identification opportunities. To date, much work has been done illustrating the ability for human tumorigenic cell lines to synthesize mcNCs; however, this has not been illustrated for nontumorigenic cell lines. Here, we present the ability for human nontumorigenic microglial cells, which are the major immune cells in the central nervous system, to self-synthesize gold (Au) and iron (Fe) core nanoclusters, following exposures to metallic salts. We also show the ability for cells to internalize presynthesized Au and Fe mcNCs. Cellular fluorescence increased in most exposures and in a dose dependent manner in the case of Au salt. Scanning transmission electron microscopic imaging confirmed the presence of the metal within cells, while transmission electron microscopy images confirmed nanocluster structures and self-synthesis. Interestingly, self-synthesized nanoclusters were of similar size and internal structure as presynthesized mcNCs. Toxicity assessment of both salts and presynthesized NCs illustrated a lack of toxicity from Au salt and presynthesized NCs. However, Fe salt was generally more toxic and stressful to cells at similar concentrations.
Project description:Quantifying small, rapidly evolving forces generated by cells is a major challenge for the understanding of biomechanics and mechanobiology in health and disease. Traction force microscopy remains one of the most broadly applied force probing technologies but typically restricts itself to slow events over seconds and micron-scale displacements. Here, we improve >2-fold spatially and >10-fold temporally the resolution of planar cellular force probing compared to its related conventional modalities by combining fast two-dimensional total internal reflection fluorescence super-resolution structured illumination microscopy and traction force microscopy. This live-cell 2D TIRF-SIM-TFM methodology offers a combination of spatio-temporal resolution enhancement relevant to forces on the nano- and sub-second scales, opening up new aspects of mechanobiology to analysis.