Spatial Frequency Domain Tomography of Protoporphyrin IX Fluorescence in Preclinical Glioma Models

Multifrequency (0 to 0.3  mm−1), multiwavelength (633, 680, 720, 800, and 820 nm) spatial frequency domain imaging (SFDI) of 5-aminolevulinic acid-induced protoporphyrin IX (PpIX) was used to recover absorption, scattering, and fluorescence properties of glioblastoma multiforme spheroids in tissue-simulating phantoms and in vivo in a mouse model. Three-dimensional tomographic reconstructions of the frequency-dependent remitted light localized the depths of the spheroids within 500 μm, and the total amount of PpIX in the reconstructed images was constant to within 30% when spheroid depth was varied. In vivo tumor-to-normal contrast was greater than ∼ 1.5 in reduced scattering coefficient for all wavelengths and was ∼ 1.3 for the tissue concentration of deoxyhemoglobin (ctHb). The study demonstrates the feasibility of SFDI for providing enhanced image guidance during surgical resection of brain tumors

Combined fluorescence and reflectance spectroscopy for in vivo quantification of cancer biomarkers in low - and high- grade glioma surgery

Biomarkers are indicators of biological processes and hold promise for the diagnosis and treatment of disease. Gliomas represent a heterogeneous group of brain tumors with marked intra- and inter-tumor variability. The extent of surgical resection is a significant factor influencing post-surgical recurrence and prognosis. Here, we used fluorescence and reflectance spectral signatures for in vivo quantification of multiple biomarkers during glioma surgery, with fluorescence contrast provided by exogenously-induced protoporphyrin IX (PpIX) following administration of 5-aminolevulinic acid. We performed light-transport modeling to quantify multiple biomarkers indicative of tumor biological processes, including the local concentration of PpIX and associated photoproducts, total hemoglobin concentration, oxygen saturation, and optical scattering parameters.We developed a diagnostic algorithm for intra-operative tissue delineation that accounts for the combined tumor-specific predictive capabilities of these quantitative biomarkers. Tumor tissue delineation achieved accuracies of up to 94% (specificity=94%, sensitivity=94%) across a range of glioma histologies beyond current state-of-the-art optical approaches, including state-of-the-art fluorescence image guidance. This multiple biomarker strategy opens the door to optical methods for surgical guidance that use quantification of well-established neoplastic processes. Future work would seek to validate the predictive power of this proof-of-concept study in a separate larger cohort of patients

Use of high hydrostatic pressure (HHP) to obtain an ingredient rich in bioactive compounds from cv. Tempranillo red pomace

With the aim to obtain an ingredient rich in bioactive compounds to be used in meat products, a red grape pomace (RGP) cv. Tempranillo, was subjected to the application of different hydrostatic high pressure (HHP) treatments: i) 600 MPa/1s; ii) 600 MPa/300s and two others treatments of 2 cycles of HHP, iii) 2 cycles of 600MPa/1s and iv) 1 first cycle of 400 MPa/1s and second cycle 600 MPa/1s. The microbiological population and polyphenoloxidase activity (PPO) of treated RGP was studied immediately after the treatments and at 270 days after the treatments at temperatures of 4 and 20 ºC respect a control sample untreated. The treatments significantly reduced the microbial population; the effect of HHP3 and HHP4 (two cycles) did not differ from those of HHP1 and HHP2 (1 cycle). Phenolic compounds (anthocyanins, flavanols, flavonols, phenolic acids and stilbenes) were extracted from GRP, identified and quantified by HPLC. The values of all these phenolic families were maintained immediately after HHP with exception of a decrease of anthocyanins in HHP3. However, the HHP treatments did not affect the polyphenoloxidase enzyme, since the phenolic compounds were notably reduced during storage although phenolic compounds were better well-preserved at refrigeration than at room temperature

Spatial frequency domain tomography of protoporphyrin IX fluorescence in preclinical glioma models

Multifrequency (0 to [Formula: see text]), multiwavelength (633, 680, 720, 800, and 820 nm) spatial frequency domain imaging (SFDI) of 5-aminolevulinic acid-induced protoporphyrin IX (PpIX) was used to recover absorption, scattering, and fluorescence properties of glioblastoma multiforme spheroids in tissue-simulating phantoms and in vivo in a mouse model. Three-dimensional tomographic reconstructions of the frequency-dependent remitted light localized the depths of the spheroids within 500 μm, and the total amount of PpIX in the reconstructed images was constant to within 30% when spheroid depth was varied. In vivo tumor-to-normal contrast was greater than [Formula: see text] in reduced scattering coefficient for all wavelengths and was [Formula: see text] for the tissue concentration of deoxyhemoglobin (ctHb). The study demonstrates the feasibility of SFDI for providing enhanced image guidance during surgical resection of brain tumors

Scaler Rates from the Pierre Auger Observatory: A New Proxy of Solar Activity

The modulation of low-energy galactic cosmic rays reflects interplanetary magnetic field variations and can provide useful information on solar activity. An array of ground-surface detectors can reveal the secondary particles, which originate from the interaction of cosmic rays with the atmosphere. In this work, we present an investigation of the low-threshold rate (scaler) time series recorded in 16 yr of operation by the Pierre Auger Observatory surface detectors in Malargüe, Argentina. Through an advanced spectral analysis, we detected highly statistically significant variations in the time series with periods ranging from the decadal to the daily scale. We investigate their origin, revealing a direct connection with solar variability. Thanks to their intrinsic very low noise level, the Auger scalers allow a thorough and detailed investigation of the galactic cosmic-ray flux variations in the heliosphere at different timescales and can, therefore, be considered a new proxy of solar variability

Improving the photon sensitivity of the Pierre Auger Observatory with the AugerPrime Radio Detector

The AugerPrime upgrade represents a significant enhancement in the capability of the Pierre Auger Observatory to detect air showers. Central to this advancement is the installation of a radio antenna atop each existing Surface Detector station, constituting the Radio Detector (RD). The RD enhances the sensitivity of the Surface Detector to the electromagnetic component of air showers. Hence, the new detector presents an opportunity for the discovery of rare particles such as ultra-high-energy photons. This contribution shows the development efforts towards an RD trigger with focus on the detection of rare particles. The radio trigger designed for the detection of photon-induced events will be outlined, and the challenge of a radio background consisting of human-made noise is discussed. The trigger efficiency and reconstruction accuracy are studied with simulations. The presentation will conclude by summarizing the effectiveness of the new detector component

Drone-based calibration of AugerPrime radio antennas at the Pierre Auger Observatory

Radio emissions of extensive air showers can be observed at the Pierre Auger Observatory with the AugerPrime Radio Detector (RD). As part of the AugerPrime upgrade, RD is being installed on 1660 water-Cherenkov detectors on an area of about 3000 km2 and consists of dual-polarized Short Aperiodic Loaded Loop Antennas (SALLA). To achieve high measurement precision, RD needs to be well-calibrated, which requires the antenna response pattern to be well-known. We introduce a method to measure the directional response of the SALLA using a well-defined biconical antenna mounted to a drone. The drone-based setup possesses active stabilization and precise pointing with the use of a gimbal. Additionally, the drone’s position is tracked using differential GPS with O(cm) precision. This setup allows us to precisely extract the antenna response pattern from any direction in the frequency range of 30 − 80 MHz. In a recent in-situ campaign, calibration measurements of the AugerPrime radio detector have been performed. First results of these measurements are presented and compared to simulations

Towards a Cosmic-Ray Energy Scale with the Auger Engineering Radio Array

Radio detection of cosmic-ray (CR) induced extensive air showers with digital antenna arrays is a matured technique by now. At the Pierre Auger Observatory, the Auger Engineering Radio Array (AERA) has been measuring air-shower signals in conjunction with the particle detectors of the surface detector (SD) for over ten years. For an absolute determination of the CR energy with the Auger baseline detectors, the shower size estimator from the SD is calibrated with the energy scale of the fluorescence detector (FD). However, AERA has an independent access to the energy scale through the reconstructed radio signals. The hybrid detectors at the Pierre Auger Observatory offer the unique opportunity to compare the two independent energy scales. In this contribution, we present our envisaged methodology for cross-checking the agreement between the energy scales of the FD and AERA using hybrid SD-AERA shower data and simulations. We show individual steps of our radio signal reconstruction and highlight the key ingredients for calibrated energy measurements