Targeting accuracy and PCD responses for 6 sonications of putamen in animal one.

<p>Conventions as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0084310#pone-0084310-g004" target="_blank">Figure 4</a>. The PCD for sonication 12 06 23 shows immediately elevated HEI values because by accident, the microbubbles were injection before sonication onset.</p

Targeting accuracy and PCD responses for 5 sonications of putamen in the second animal.

<p>Conventions as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0084310#pone-0084310-g004" target="_blank">Figure 4</a>.</p

Quantification of targeting accuracy.

<p>After calculating the raw result image that provides a normalized estimate of the increase in T1 contrast (<b>A</b>), the image is shifted and rotated in to a new coordinate frame (<b>B</b>) whose origin is defined by the coordinates of the intended target, and the z-axis corresponds to the approach angle. A voxel is considered opened if its T1 value was enhanced by ≥10%. The in-plane targeting accuracy was assessed by averaging the fraction of opened voxels across the z-axis (<b>C</b>). Targeting in the depth axis along the ultrasound beam was quantified by collapsing across the x- and y-axis (<b>D</b>).</p

BBB opening volume as a function of pressure (A) and the average harmonic energy increase, HEI (B).

<p>Two targets in the putamen and the caudate for two animal subjects (O and N) were marked separately. (<b>A</b>) There is a clear relationship between ultrasound pressure and opening size (r = 0.41). Due to the narrow range of pressures and low number of sonications, this effect does not reach significance. (<b>B</b>) There is no apparent relationship between average HEI and opening volume.</p

Targeting accuracy for 6 (4+2 for two monkeys O and N) sonications of caudate nucleus.

<p>The panels in the first row show the color-coded fraction of activated voxels (>10% enhancement of T1 signal) as a function of medio-lateral and antero-posterior deviation from the intended focal point in the x-y-plane. The panels collapse across voxels that are between −5 and 10 mm in depth from the intended depth. In all instances the opening of the BBB either overlaps with or is in immediate vicinity of the intended target. To quantify targeting accuracy along the direction of the ultrasound propagation, panels in the second row show the fraction of activated voxels collapsed around a 2 by 2 mm square region around the measured focal point (block dots in panels in A). The dotted horizontal line corresponds to the depth of the geometric ultrasound focus. As predicted from in-vitro experiments, the actual focal depth (solid horizontal line) is shifted ∼5 mm towards the ultrasound transducer. Panels in the third row depict the backscattered acoustic energy of the microbubbles excited in the ultrasound focus as a function of time from injection of the microbubbles. The blue line to the desired harmonic oscillations of the microbubbles (HEI) that have been associated with safe BBB opening. The black line corresponds to inertial cavitation (BEI) that has been linked to extravasation of red blood cells and tissue damage. The red line corresponds to the BEI detection threshold.</p

BBB opening procedure overview.

<p>(<b>A&B</b>) Timeline of sonication experiment with subsequent MRI-based verification. Briefly, the animals are sonicated for two minutes using a 500-kHz focused ultrasound transducer following the systemic injection of microbubbles. The opening location is then analyzed using contrast-enhanced T1 images (see D for details). Additional clinical scans were performed to detect potential damage. (<b>C</b>) Geometric ultrasound focus overlaid on a T1 structural scan in stereotaxic coordinate frame. Due to the geometry of the ultrasound transducer, the focal region is elongated along the axis of ultrasound propagation. Here the ultrasound was applied at an angle of 26° from the upper right to provide a close to normal incidence angle of the ultrasound and skull. (<b>D</b>) Increased blood-brain barrier (BBB) permeability for the T1 contrast agent gadodiamide following a single sonication of left caudate. Brighter colors indicate regions where gadodiamide was able to diffuse across the BBB into the brain tissue. The remaining regions of increased T1 signal indicate asymmetric vasculature. Note the close alignment between intended (C) and actual location (D) of the BBB opening. The axial shift in location of the BBB opening towards the transducer is close to the value predicted from in-vitro experiments.</p

Timeline of BBB closing for a single low-pressure sonication depicted in Figure 10.

<p>Voxels with a normalized pre-post enhancement of more than 10% were classified as “opened”. The total volume of opened voxels decreases as a function of time from the sonication. The opened volume in the contra-lateral control region is constant and close to the one predicted by a false detection rate of 5%.</p

Coronal (left row) and sagittal (right row) T1-weighted MR slices showing the evolution of the BBB opening volume along time.

<p>The area with contrast agent diffusion is overlaid in blue. The BBB is restored between day 2 and 4.</p

Harmonic (HEI) and broadband (BEI) energy increase plotted as a function of ultrasound pressure.

<p>Data was acquired using a series of brief pulses of ultrasound after the main sonication while micro-bubbles were still circulating. The blue dash line corresponds to the lowest pressure at which BBB opening was achieved, and the. The light blue area highlights the pressure range used in this study. The red line corresponds to the ultrasound pressure that would cause BEI to rise above levels that were found to be safe in the current set of sonications.</p

Toward Rollable Printed Perovskite Solar Cells for Deployment in Low-Earth Orbit Space Applications

The thin physical profile of perovskite-based solar cells (PSCs) fabricated on flexible substrates provides the prospect of a disruptive increase in specific power (power-to-mass ratio), an important figure-of-merit for solar cells to be used in space applications. In contrast to recent reports on space applications of PSCs which focus on rigid glass-based devices, in this work we investigate the suitability of flexible PSCs for low-earth orbit (LEO) applications, where the perovskite layer in the PSCs was prepared using either a Ruddlesden–Popper precursor composition (BA2MA3Pb4I13; BA = butylammonium, MA = methylammonium) or a mixed-cation precursor composition (Cs0.05FA0.81MA0.14Pb2.55Br0.45; FA = formamidinium). The flexible PSC devices display a tolerance to high-energy proton (14 MeV) and electron (>1 MeV) radiation comparable with, or superior to, equivalent glass-based PSC devices. The photovoltaic performance of the PSCs is found to be significantly less dependent on angle-of-incidence than GaAs-based triple-junction solar cells commonly used for space applications. Results from a preliminary test of the robustness of the perovskite film when subjected to LEO-like thermal environments are also reported. In addition, a unique deployment concept integrating printed flexible solar cells with titanium–nickel based shape memory alloy ribbons is presented for thermally actuated deployment of flexible solar cells from a rolled state