In Vivo Radiobiological Investigations with the TOP-IMPLART Proton Beam on a Medulloblastoma Mouse Model.

Protons are now increasingly used to treat pediatric medulloblastoma (MB) patients. We designed and characterized a setup to deliver proton beams for in vivo radiobiology experiments at a TOP-IMPLART facility, a prototype of a proton-therapy linear accelerator developed at the ENEA Frascati Research Center, with the goal of assessing the feasibility of TOP-IMPLART for small animal proton therapy research. Mice bearing Sonic-Hedgehog (Shh)-dependent MB in the flank were irradiated with protons to test whether irradiation could be restricted to a specific depth in the tumor tissue and to compare apoptosis induced by the same dose of protons or photons. In addition, the brains of neonatal mice at postnatal day 5 (P5), representing a very small target, were irradiated with 6 Gy of protons with two different collimated Spread-Out Bragg Peaks (SOBPs). Apoptosis was visualized by immunohistochemistry for the apoptotic marker caspase-3-activated, and quantified by Western blot. Our findings proved that protons could be delivered to the upper part while sparing the deepest part of MB. In addition, a comparison of the effectiveness of protons and photons revealed a very similar increase in the expression of cleaved caspase-3. Finally, by using a very small target, the brain of P5-neonatal mice, we demonstrated that the proton irradiation field reached the desired depth in brain tissue. Using the TOP-IMPLART accelerator we established setup and procedures for proton irradiation, suitable for translational preclinical studies. This is the first example of in vivo experiments performed with a "full-linac" proton-therapy accelerator.

Polarization-maintaining reflection-mode THz time-domain spectroscopy of a polyimide based ultra-thin narrow-band metamaterial absorber.

This paper reports the design, the microfabrication and the experimental characterization of an ultra-thin narrow-band metamaterial absorber at terahertz frequencies. The metamaterial device is composed of a highly flexible polyimide spacer included between a top electric ring resonator with a four-fold rotational symmetry and a bottom ground plane that avoids misalignment problems. Its performance has been experimentally demonstrated by a custom polarization-maintaining reflection-mode terahertz time-domain spectroscopy system properly designed in order to reach a collimated configuration of the terahertz beam. The dependence of the spectral characteristics of this metamaterial absorber has been evaluated on the azimuthal angle under oblique incidence. The obtained absorbance levels are comprised between 67% and 74% at 1.092 THz and the polarization insensitivity has been verified in transverse electric polarization. This offers potential prospects in terahertz imaging, in terahertz stealth technology, in substance identification, and in non-planar applications. The proposed compact experimental set-up can be applied to investigate arbitrary polarization-sensitive terahertz devices under oblique incidence, allowing for a wide reproducibility of the measurements.