Category: IEEE Transactions on Biomedical Engineering

Objective: Skin is an attractive target tissue for gene transfer due to its size, accessibility, and its immune competence. One of the promising delivery methods is gene delivery by means of electroporation (EP), i.e., gene electrotransfer (GET). To assess the importance of different effects of electroporation for successful GET we investigated: stress response and transfection efficacy upon different pulse protocols. Moreover, numerical modeling was used to explain experimental results and to test the agreement of experimental results with current knowledge about GET. Methods: Double transgenic mice Hspa1b-LucF (+/+) Hspa1b-mPlum (+/+) were used to determine the level of stress sensed by the cell in the tissue in vivo that was exposed to EP. The effect of five different pulse protocols on stress levels sensed by the exposed cells and their efficacy for gene electrotransfer for two plasmids pEGFP-C1 (EGFP) and pCMV-tdTomato was tested. Results: Quantification of the bioluminescence signal intensity shows that EP, regardless of the electric pulse parameters used, increased mean bioluminescence compared to the baseline bioluminescence signal of the non-exposed skin. The results of numerical modeling indicate that thermal stress alone is not sufficient to explain the measured bioluminescence signal. Of the tested pulse protocols, the highest expression of EGFP and tdTomato was achieved with HV-MV (high voltage – medium voltage) protocols, which agrees also with numerical model. Significance: Although EP is widely used as a method for gene delivery, we show that the field could benefit from the use of mathematical modeling by introducing additional parameters such as EP induced stress and electrophoretic movement of plasmids.

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Objective: We aimed to develop a method for evaluating developmental changes in the synchronized activity of human induced pluripotent stem cell (hiPSC)-derived neurons without extrinsic signals from feeder astrocytes. Methods: Microelectrode arrays (MEAs) and microtunnels were fabricated with photolithography and soft lithography. hiPSCs were induced to differentiate into cortical neurons, and seeded to conventional and microtunnel MEAs. Spontaneous activity was recorded every ten days, and spiking and bursting activities were elucidated. Results: First, hiPSC-derived neurons were cultured on conventional MEAs. They formed aggregates and subsequently detached from the culture substrate. Hence, no MEAs showed spontaneous synchronized activity beyond 300 days post-induction. Next, we applied a microtunnel structure designed to keep the axons on the array. Synchronized activity was then recorded from all microtunnel MEAs by 450 days post-induction. The proportion of electrodes showing neural activity was greater than that in conventional MEAs. The activity pattern reached a steady state after approximately 330 days, which may be the maturation time of the human neuronal network. Conclusion: The use of a microtunnel MEA enables the monitoring of the long-term development of human neuronal networks of cell populations that are relatively natural given their lack of astrocyte feeders. Significance: We report a more accurate method for culturing cortical neurons differentiated from hiPSCs, validating their use in elucidating cortical development and pathogenic mechanisms in humans.

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In magnetic resonance imaging (MRI), system imperfections and eddy currents can cause gradient field deviation (GFD), leading to various image distortions, such as increased noise, ghosting artifacts, and geometric deformation. These distortions can degrade the clinical value of MR images. Generally, non-Cartesian image sequences, such as radial sampling, produce larger gradient deviations than Cartesian sampling, as a result of stronger eddy current-induced gradient delays and phase errors. In this paper, we developed a GFD encoding method to reduce image noise and artifacts for radial MRI. In the proposed method, a hybrid norm (combination of L2 and L1 norms) optimization problem was formed, which incorporated a wavelet sub-band adaptive regularization mechanism. The new approach seeks a regularized solution not only offering corrected images with reduced artifacts and geometric deformation, but also good preservation of anatomical structural details. The new method was evaluated with simulation and experiment at 9.4 T MRI. The results demonstrated that the proposed method can provide over 50% noise reduction and 15% artifact reduction compared with the traditional regridding method, suggesting substantially reduced GFD-induced distortions and improved image quality.