Imaging of Glioma Tumor with Endogenous Fluorescence Tomography

Tomographic imaging of a glioma tumor with endogenous fluorescence is demonstrated using a noncontact single-photon counting fan-beam acquisition system interfaced with microCT imaging. The fluorescence from protoporphyrin IX (PpIX) was found to be detectable, and allowed imaging of the tumor from within the cranium, even though the tumor presence was not visible in the microCT image. The combination of single-photon counting detection and normalized fluorescence to transmission detection at each channel allowed robust imaging of the signal. This demonstrated use of endogenous fluorescence stimulation from aminolevulinic acid (ALA) and provides the first in vivo demonstration of deep tissue tomographic imaging with protoporphyrin IX. Fluorescence tomography provides a tool for preclinical molecular contrast agent assessment in oncology.1, 2, 3, 4 Systems have advanced in complexity to where noncontact imaging,5 automated boundary recovery,6 and sophisticated internal tissue shapes can be included in the recovered images. The translation of this work to humans will require molecular contrast agents that are amenable to regulatory approval and maintain tumor specificity in humans, where often nonspecific uptake of molecular imaging agents can decrease their utility. In this study, a new fluorescence tomography system coupled to microCT7 was used to illustrate diagnostic detection of orthotopic glioma tumors that were not apparent in the microCT images, using endogenous fluorescent contrast from protoporphyrin IX (PpIX). Glioma tumors provide significant endogenous fluorescence from PpIX,8, 9, 10, 11 and this is enhanced when the subject imaged has been administered aminolevulinic acid (ALA). The endogenous production process of PpIX is known to stem from the administered, ALA bypassing the regulatory inhibition of ALA synthase, allowing the heme synthesis pathway to proceed uninhibited. Since there is a limited supply of iron in the body, this process produces overabundance of PpIX rather than heme, and many tumors have been shown to have high yields of PpIX. Clinical trials with PpIX fluorescence guided resection of tumors have shown significant promise,12 and yet deep tissue imaging with PpIX fluorescence has not been exploited in clinical use. Early studies have shown that detection of these tumors with PpIX is feasible,13, 14 but no tomographic imaging has been used. This limitation in development has largely been caused by problems in wavelength filtering and low signal intensity, as well as background fluorescence from the skin limiting sensitivity to deeper structures. In the system developed and used here, this feasibility is demonstrated by imaging a human xenograft glioma model. To solve the sensitivity problem and study the ability to diagnostically image PpIX in vivo, time-correlated single-photon counting was used in the fluorescence tomography system, which provides maximum sensitivity. Figure 1a shows the system designed to match up with a microCT, allowing both x-ray structural and optical functional imaging sequentially. Lens-coupled detection of signals is acquired from the mouse using five time-resolved photomultiplier tubes (H7422P-50, Hamamatsu, Japan) with single-photon counting electronics (SPC-134 modules, Becker and Hickl GmbH, Germany). The system has fan-beam transmission geometry similar to a standard CT scanner, with single source delivery of a1-mW role= presentation \u3e1-mW pulsed diode laser light at 635nm role= presentation \u3e635nm , collimated to a 1-mm role= presentation \u3e1-mm effective area on the animal. The five detection lenses were arranged in an arc, each with 22.5-deg role= presentation \u3e22.5-deg angular separation, centered directly on the opposite side of the animal with long working distance pickup,7 allowing noncontact measurement of the diffuse light through the animal. The diffuse intensity signals collected at each of the five channels were then translated via 400-μm role= presentation \u3e400-μm fibers and split using beamsplitters to be directed toward the fluorescence (95%) and transmission (5%) channel detectors. A 650-nm role= presentation \u3e650-nm long-pass filter was used in the fluorescence channels to isolate the signal, and in the transmitted intensity signals, a neutral density filter (2 OD) was used to attenuate the signals. This latter filtering was necessary to ensure that the fluorescence and transmission. Intensity signals fell within the same dynamic range, allowing a single 1s role= presentation \u3e1s acquisition for each detector. Scans were then performed by rotating the fan-beam around the specimen to 32 locations. A GE eXplore Locus SP scanner (GE Healthcare, London, Ontario, Canada) that incorporated a detector with 94-micronpixel role= presentation \u3e94-micronpixel resolution, a 80-kV role= presentation \u3e80-kV peak voltage, and a tube current of 450μAs role= presentation \u3e450μAs , was used in acquiring the microCT data, as displayed in Fig. 2 . In this example, since soft tissue was being imaged, the CT data was largely used to image the exterior of the animal, although in future studies, it could be used to isolate the cranium region as well

Overview of cattle diseases listed under category C, D or E in the animal health law for wich control programmes are in place within Europe

13 páginas, 5 figuras, 3 tablas.The COST action “Standardising output-based surveillance to control non-regulated diseases of cattle in the European Union (SOUND control),” aims to harmonise the results of surveillance and control programmes (CPs) for non-EU regulated cattle diseases to facilitate safe trade and improve overall control of cattle infectious diseases. In this paper we aimed to provide an overview on the diversity of control for these diseases in Europe. A non-EU regulated cattle disease was defined as an infectious disease of cattle with no or limited control at EU level, which is not included in the European Union Animal health law Categories A or B under Commission Implementing Regulation (EU) 2020/2002. A CP was defined as surveillance and/or intervention strategies designed to lower the incidence, prevalence, mortality or prove freedom from a specific disease in a region or country. Passive surveillance, and active surveillance of breeding bulls under Council Directive 88/407/EEC were not considered as CPs. A questionnaire was designed to obtain country-specific information about CPs for each disease. Animal health experts from 33 European countries completed the questionnaire. Overall, there are 23 diseases for which a CP exists in one or more of the countries studied. The diseases for which CPs exist in the highest number of countries are enzootic bovine leukosis, bluetongue, infectious bovine rhinotracheitis, bovine viral diarrhoea and anthrax (CPs reported by between 16 and 31 countries). Every participating country has on average, 6 CPs (min–max: 1–13) in place. Most programmes are implemented at a national level (86%) and are applied to both dairy and non-dairy cattle (75%). Approximately one-third of the CPs are voluntary, and the funding structure is divided between government and private resources. Countries that have eradicated diseases like enzootic bovine leukosis, bluetongue, infectious bovine rhinotracheitis and bovine viral diarrhoea have implemented CPs for other diseases to further improve the health status of cattle in their country. The control of non-EU regulated cattle diseases is very heterogenous in Europe. Therefore, the standardising of the outputs of these programmes to enable comparison represents a challenge.Peer reviewe

A microcomputed tomography guided fluorescence tomography system for small animal molecular imaging

A prototype small animal imaging system was created for coupling fluorescence tomography (FT) with x-ray microcomputed tomography (microCT). The FT system has the potential to provide synergistic information content resultant from using microCT images as prior spatial information and then allows overlay of the FT image onto the original microCT image. The FT system was designed to use single photon counting to provide maximal sensitivity measurements in a noncontact geometry. Five parallel detector locations are used, each allowing simultaneous sampling of the fluorescence and transmitted excitation signals through the tissue. The calibration and linearity range performance of the system are outlined in a series of basic performance tests and phantom studies. The ability to image protoporphyrin IX in mouse phantoms was assessed and the system is ready for in vivo use to study biological production of this endogenous marker of tumors. This multimodality imaging system will have a wide range of applications in preclinical cancer research ranging from studies of the tumor microenvironment and treatment efficacy for emerging cancer therapeutics

Imaging of glioma tumor with endogenous fluorescence tomography

Tomographic imaging of a glioma tumor with endogenous fluorescence is demonstrated using a non-contact single photon counting fan-beam acquisition system interfaced with microCT imaging. The fluorescence from protoporphyrin IX was found to be detectable, and allowed imaging of the tumor from within the cranium, even though the tumor presence was not visible in the microCT image. The combination of single photon counting detection and normalized fluorescence to transmission detection at each channel allowed robust imaging of the signal. This demonstrated use of endogenous fluorescence stimulation from aminolevulinic acid, provides the first in vivo demonstration of deep tissue tomographic imaging with protoporphyrin IX

Laser treatment of a-SiC:H thin films for optoelectronic applications

Amorphous and hydrogenated (a-SiC:H) as well as crystalline silicon carbide are widespread materials for optoelectronic applications. In this paper, we studied the effect of laser/RF plasma jet treatment of a-SiC:H thin films deposited by Plasma Enhanced Chemical Vapor Deposition (PECVD), on Si wafers. A Nd:YAG laser (λ = 1.06 μ, tFWHM = 14 ns, E0 equals 0.015 J/pulse) was used with a fluence of 4 mJ/cm2 incident on the sample, the number of pulses being varied. Plasma treatments were performed in a plasma jet generated by a capacity coupled RF discharge in N2. Different analysis techniques were used to investigate the films, before and after the irradiation: X-ray diffraction, X-ray photoelectron spectroscopy and transmission electron microscopy (ThM). We followed the modification of their structure and composition as an effect of the laser/plasma treatment. A comparison with the excimer and also with the RF treatments was performed. ©2003 Copyright SPIE - The International Society for Optical Engineering

Overview of Cattle Diseases Listed Under Category C, D or E in the Animal Health Law for Which Control Programmes Are in Place Within Europe

The COST action “Standardising output-based surveillance to control non-regulated diseases of cattle in the European Union (SOUND control),” aims to harmonise the results of surveillance and control programmes (CPs) for non-EU regulated cattle diseases to facilitate safe trade and improve overall control of cattle infectious diseases. In this paper we aimed to provide an overview on the diversity of control for these diseases in Europe. A non-EU regulated cattle disease was defined as an infectious disease of cattle with no or limited control at EU level, which is not included in the European Union Animal health law Categories A or B under Commission Implementing Regulation (EU) 2020/2002. A CP was defined as surveillance and/or intervention strategies designed to lower the incidence, prevalence, mortality or prove freedom from a specific disease in a region or country. Passive surveillance, and active surveillance of breeding bulls under Council Directive 88/407/EEC were not considered as CPs. A questionnaire was designed to obtain country-specific information about CPs for each disease. Animal health experts from 33 European countries completed the questionnaire. Overall, there are 23 diseases for which a CP exists in one or more of the countries studied. The diseases for which CPs exist in the highest number of countries are enzootic bovine leukosis, bluetongue, infectious bovine rhinotracheitis, bovine viral diarrhoea and anthrax (CPs reported by between 16 and 31 countries). Every participating country has on average, 6 CPs (min–max: 1–13) in place. Most programmes are implemented at a national level (86%) and are applied to both dairy and non-dairy cattle (75%). Approximately one-third of the CPs are voluntary, and the funding structure is divided between government and private resources. Countries that have eradicated diseases like enzootic bovine leukosis, bluetongue, infectious bovine rhinotracheitis and bovine viral diarrhoea have implemented CPs for other diseases to further improve the health status of cattle in their country. The control of non-EU regulated cattle diseases is very heterogenous in Europe. Therefore, the standardising of the outputs of these programmes to enable comparison represents a challenge. © Copyright © 2021 Hodnik, Acinger-Rogić, Alishani, Autio, Balseiro, Berezowski, Carmo, Chaligiannis, Conrady, Costa, Cvetkovikj, Davidov, Dispas, Djadjovski, Duarte, Faverjon, Fourichon, Frössling, Gerilovych, Gethmann, Gomes, Graham, Guelbenzu, Gunn, Henry, Hopp, Houe, Irimia, Ježek, Juste, Kalaitzakis, Kaler, Kaplan, Kostoulas, Kovalenko, Kneževič, Knific, Koleci, Madouasse, Malakauskas, Mandelik, Meletis, Mincu, Mõtus, Muñoz-Gómez, Niculae, Nikitović, Ocepek, Tangen-Opsal, Ózsvári, Papadopoulos, Papadopoulos, Pelkonen, Polak, Pozzato, Rapaliuté, Ribbens, Niza-Ribeiro, Roch, Rosenbaum Nielsen, Saez, Nielsen, van Schaik, Schwan, Sekovska, Starič, Strain, Šatran, Šerić-Haračić, Tamminen, Thulke, Toplak, Tuunainen, Verner, Vilček, Yildiz and Santman-Berends

Corrigendum: Overview of Cattle Diseases Listed Under Category C, D or E in the Animal Health Law for Which Control Programmes Are in Place Within Europe (Front. Vet. Sci., (2021), 8, (688078), 10.3389/fvets.2021.688078)

In the original article, there was an error. We used the phrase “non-regulated” for cattle diseases that are in fact listed in the New Animal Health Law that went into force in 2021. A correction has beenmade toAbstract. The corrected section is shown below. Copyright © 2022, Hodnik, Acinger-Rogić, Alishani, Autio, Balseiro, Berezowski, Carmo, Chaligiannis, Conrady, Costa, Cvetkovikj, Davidov, Dispas, Djadjovski, Duarte, Faverjon, Fourichon, Frössling, Gerilovych, Gethmann, Gomes, Graham, Guelbenzu, Gunn, Henry, Hopp, Houe, Irimia, Ježek, Juste, Kalaitzakis, Kaler, Kaplan, Kostoulas, Kovalenko, Kneževič, Knific, Koleci, Madouasse, Malakauskas, Mandelik, Meletis, Mincu, Mõtus, Muñoz-Gómez, Niculae, Nikitović, Ocepek, Tangen-Opsal, Ózsvári, Papadopoulos, Papadopoulos, Pelkonen, Polak, Pozzato, Rapaliuté, Ribbens, Niza-Ribeiro, Roch, Rosenbaum Nielsen, Saez, Nielsen, van Schaik, Schwan, Sekovska, Starič, Strain, Šatran, Šerić-Haračić, Tamminen, Thulke, Toplak, Tuunainen, Verner, Vilček, Yildiz and Santman-Berends