Advanced radiation measurement techniques in diagnostic radiology and molecular imaging.

This paper reports some technological advances recently achieved in the fields of micro-CT and small animal PET instrumentation. It highlights a balance between image-quality improvement and dose reduction. Most of the recent accomplishments in these fields are due to the use of novel imaging sensors such as CMOS-based X-ray detectors and silicon photomultipliers (SiPM). Some of the research projects carried out at the University of Pisa for the development of such advanced radiation imaging technology are also described

Cherenkov luminescence measurements with digital silicon photomultipliers: a feasibility study.

BackgroundA feasibility study was done to assess the capability of digital silicon photomultipliers to measure the Cherenkov luminescence emitted by a β source. Cherenkov luminescence imaging (CLI) is possible with a charge coupled device (CCD) based technology, but a stand-alone technique for quantitative activity measurements based on Cherenkov luminescence has not yet been developed. Silicon photomultipliers (SiPMs) are photon counting devices with a fast impulse response and can potentially be used to quantify β-emitting radiotracer distributions by CLI.MethodsIn this study, a Philips digital photon counting (PDPC) silicon photomultiplier detector was evaluated for measuring Cherenkov luminescence. The PDPC detector is a matrix of avalanche photodiodes, which were read one at a time in a dark count map (DCM) measurement mode (much like a CCD). This reduces the device active area but allows the information from a single avalanche photodiode to be preserved, which is not possible with analog SiPMs. An algorithm to reject the noisiest photodiodes and to correct the measured count rate for the dark current was developed.ResultsThe results show that, in DCM mode and at (10-13) °C, the PDPC has a dynamic response to different levels of Cherenkov luminescence emitted by a β source and transmitted through an opaque medium. This suggests the potential for this approach to provide quantitative activity measurements. Interestingly, the potential use of the PDPC in DCM mode for direct imaging of Cherenkov luminescence, as a opposed to a scalar measurement device, was also apparent.ConclusionsWe showed that a PDPC tile in DCM mode is able to detect and image a β source through its Cherenkov radiation emission. The detector's dynamic response to different levels of radiation suggests its potential quantitative capabilities, and the DCM mode allows imaging with a better spatial resolution than the conventional event-triggered mode. Finally, the same acquisition procedure and data processing could be employed also for other low light levels applications, such as bioluminescence

Fast 3D-EM reconstruction using Planograms for stationary planar positron emission mammography camera

Summary At the University of Pisa we are building a PEM prototype, the YAP–PEM camera, consisting of two opposite 6×6×3 cm 3 detector heads of 30×30 YAP:Ce finger crystals, 2×2×30 mm 3 each. The camera will be equipped with breast compressors. The acquisition will be stationary. Compared with a whole body PET scanner, a planar Positron Emission Mammography (PEM) camera allows a better, easier and more flexible positioning around the breast in the vicinity of the tumor: this increases the sensitivity and solid angle coverage, and reduces cost. To avoid software rejection of data during the reconstruction, resulting in a reduced sensitivity, we adopted a 3D-EM reconstruction which uses all of the collected Lines Of Response (LORs). This skips the PSF distortion given by data rebinning procedures and/or Fourier methods. The traditional 3D-EM reconstruction requires several times the computation of the LOR-voxel correlation matrix, or probability matrix { p ij }; therefore is highly time-consuming . We use the sparse and symmetry properties of the matrix { p ij } to perform fast 3D-EM reconstruction. Geometrically, a 3D grid of cubic voxels (FOV) is crossed by several divergent 3D line sets (LORs). The symmetries occur when tracing different LORs produces the same p ij value. Parallel LORs of different sets cross the FOV in the same way, and the repetition of p ij values depends on the ratio between the tube and voxel sizes. By optimizing this ratio, the occurrence of symmetries is increased. We identify a nucleus of symmetry of LORs: for each set of symmetrical LORs we choose just one LOR to be put in the nucleus , while the others lie outside. All of the possible p ij values are obtainable by tracking only the LORs of this nucleus . The coordinates of the voxels of all of the other LORs are given by means of simple translation rules. Before making the reconstruction, we trace the LORs of the nucleus to find the intersecting voxels, whose p ij values are computed and stored with their voxel coordinates on a hard disk. Only the non-zero p ij are considered and their computation is performed just once. During the reconstruction, the stored values are loaded and are available in the random access memory for all of the operations of normalization, backprojection and projection: these are now performed rapidly, because the application of the translation rules is much faster than the probability computations. We tested the algorithm on Monte Carlo data fully simulating the typical YAP–PEM clinical condition. The adopted algorithm gives an excellent positioning capability for hot spots in the camera FOV. To use all of the possible skew LORs in the FOV avoids the software rejection of collected data. Reconstructed images indicate that a 5 mm diameter tumor of 37 kBq/cm 3 , in an active breast with a 10:1 Tissue to Background ratio (T/B), with a 10 min acquisition, for a head distance of 5 cm, can be detected by the YAP–PEM with a SNR of 8.7±1.0. The obtained SNR values depend linearly on the tumor volume. The algorithm allows one to discriminate between two hot sources of 5.0 mm diameter if they do not lie on the same axis. The YAP–PEM is now in the assembly stage

Analysis of time-profiles with in-beam PET monitoring in charged particle therapy

Background: Treatment verification with PET imaging in charged particle therapy is conventionally done by comparing measurements of spatial distributions with Monte Carlo (MC) predictions. However, decay curves can provide additional independent information about the treatment and the irradiated tissue. Most studies performed so far focus on long time intervals. Here we investigate the reliability of MC predictions of space and time (decay rate) profiles shortly after irradiation, and we show how the decay rates can give an indication about the elements of which the phantom is made up. Methods and Materials: Various phantoms were irradiated in clinical and near-clinical conditions at the Cyclotron Centre of the Bronowice proton therapy centre. PET data were acquired with a planar 16x16 cm$^2$ PET system. MC simulations of particle interactions and photon propagation in the phantoms were performed using the FLUKA code. The analysis included a comparison between experimental data and MC simulations of space and time profiles, as well as a fitting procedure to obtain the various isotope contributions in the phantoms. Results and conclusions: There was a good agreement between data and MC predictions in 1-dimensional space and decay rate distributions. The fractions of $^{11}$C, $^{15}$O and $^{10}$C that were obtained by fitting the decay rates with multiple simple exponentials generally agreed well with the MC expectations. We found a small excess of $^{10}$C in data compared to what was predicted in MC, which was clear especially in the PE phantom.Comment: 9 pages, 5 figures, 1 table. Proceedings of the 20th International Workshop on Radiation Imaging Detectors (iWorid2018), 24-28 June 2018, Sundsvall, Swede

DNA-repair deficient cells identification with a multiwire proportional chamber

Abstract Tritium labelled mammalian cells with defective repair of UV-induced damage have been identified by using a MWPC as a position sensitive radioactivity detector. The resolving power (≅1.5mm FWHM), sensitivity (≅101Bq/cm2), efficiency (≅10%) and uniformity (≅4%) of the detection system are shown and "electronic autoradiograms" of normal and mutant cultures are presented; cells, rescued after the radioactivity measurement, retain their cloning ability

Anti-Advanced glycation end-product and free radical scavenging activity of plants from the yucatecan flora

Background: Formation and accumulation of advanced glycation end-products (AGE) is recognized as a major pathogenic process in diabetic complications, atherosclerosis and cardiovascular diseases. In addition, reactive oxygen species and free radicals have also been reported to participate in AGE formation and in cell damage. Natural products with antioxidant and antiAGE activity have great therapeutic potential in the treatment of diabetes, hypertension and related complications. Objective: to test ethanolic extracts and aqueous-traditional preparations of plants used to treat diabetes, hypertension and obesity in Yucatecan traditional medicine for their anti-AGE and free radical scavenging activities. Materials and Methods: ethanolic extracts of leaves, stems and roots of nine medicinal plants, together with their traditional preparations, were prepared and tested for their anti-AGE and antioxidant activities using the inhibition of advanced glycation end products and DPPH radical scavenging assays, respectively. Results: the root extract of C. fistula (IC50= 0.1 mg/mL) and the leaf extract of P. auritum (IC50= 0.35 mg/mL) presented significant activity against vesperlysine and pentosidine-like AGE. Although none of the aqueous traditional preparations showed significant activity in the anti-AGE assay, both the traditional preparations and the ethanolic extracts of E. tinifolia, M. zapota, O. campechianum and P. auritum showed significant activity in the DPPH reduction assay. <65Conclusions: the results suggest that the metabolites responsible for the detected radical-scavenging activity are different to those involved in inhibiting AGE formation; however, the extracts with antioxidant activity may contain other metabolites which are able to prevent AGE formation through a different mechanism

Epigenetic regulation of PPARGC1A in human type 2 diabetic islets and effect on insulin secretion

Aims/hypothesis Insulin secretion in pancreatic islets is dependent upon mitochondrial function and production of ATP. The transcriptional coactivator peroxisome proliferator activated receptor gamma coactivator-1 alpha (protein PGC-1 alpha; gene PPARGC1A) is a master regulator of mitochondrial genes and its expression is decreased and related to impaired oxidative phosphorylation in muscle from patients with type 2 diabetes. Whether it plays a similar role in human pancreatic islets is not known. We therefore investigated if PPARGC1A expression is altered in islets from patients with type 2 diabetes and whether this expression is influenced by genetic (PPARGC1A Gly482Ser polymorphism) and epigenetic (DNA methylation) factors. We also tested if experimental downregulation of PPARGC1A expression in human islets influenced insulin secretion. Methods The PPARGC1A Gly482Ser polymorphism was genotyped in human pancreatic islets from 48 non-diabetic and 12 type 2 diabetic multi-organ donors and related to PPARGC1A mRNA expression. DNA methylation of the PPARGC1A promoter was analysed in pancreatic islets from ten type 2 diabetic and nine control donors. Isolated human islets were transfected with PPARGC1A silencing RNA (siRNA). Results PPARGC1A mRNA expression was reduced by 90% (p < 0.005) and correlated with the reduction in insulin secretion in islets from patients with type 2 diabetes. After downregulation of PPARGC1A expression in human islets by siRNA, insulin secretion was reduced by 41% (p <= 0. 01). We were able to ascribe reduced PPARGC1A expression in islets to both genetic and epigenetic factors, i.e. a common PPARGC1A Gly482Ser polymorphism was associated with reduced PPARGC1A mRNA expression (p < 0.00005) and reduced insulin secretion (p < 0.05). In support of an epigenetic influence, the PPARGC1A gene promoter showed a twofold increase in DNA methylation in diabetic islets compared with non-diabetic islets (p < 0.04). Conclusions/Interpretation We have shown for the first time that PPARGC1A might be important in human islet insulin secretion and that expression of PPARGC1A in human islets can be regulated by both genetic and epigenetic factors

Patrones de distribución de los caprélidos intermareales y de aguas someras asociados a macroalgas de la Península Ibérica

This study investigated the patterns of caprellids associated with macroalgae from the intertidal and shallow waters (0-5 m) of the Iberian Peninsula. Nineteen stations and 250 samples of algae demonstrated the presence of 46 algal species (22 intertidal and 24 subtidal). Eleven caprellid species dwelled in th ese macroalgae with Caprella penantis and C. acanthifera being the most abundant species. Caprella acanthifera , Phtisica marina and Pseudoprotella phasma inhabited the whole Peninsula; C. danilevskii , C. equilibra , C. fretensis and C. penantis showed Atlantic distribution, whereas C. grandimana , C. hirsuta , C. liparotensis and Deutella schieckei inhabited only Mediterranean sites and the Strait of Gibraltar. Caprellid species demonstrated low substrate specificity and associated themselves with many species of algae. Subtidal subtrates contained higher numbers of caprellid species than intertidal substrates. The highest number of caprellid species occurred on the algae Stypocaulon scoparium , Cystoseira spp., Corallina elongata , Jania rubens , Codium vermilara , Cladostephus spongiosus and Asparagopsis armata . Caprellid abundances were very high, both in the intertidal and shallow subtidal zones, reaching 12200 ind/ 1000 ml alga. In fact, caprellids are one of the dominant groups of associated fauna in the intertidal in comparison with other taxa. In spite of the high densities, caprellid diversity (in terms of number of species) in the intertidal and very shallow bottoms of the Iberian Peninsula is very low (11 species) in comparison with total caprellid diversity including deeper areas >5 m (ca. 40 species). Canonical Correspondence Analysis showed that temperature and conductivity are the environmental variables that explain a clear Atlantic-Mediterranean gradient for caprellid distribution.Se estudió el patrón de caprélidos asociados a macroalgas del intermareal y aguas someras (0-5 m) de la Península Ibérica. Un total de 19 estaciones y 250 muestras de algas reflejaron la presencia de 46 especies de algas (22 intermareales y 24 submareales). Once especies de caprélidos se asociaron a estas macroalgas, siendo Caprella penantis y C. acanthifera las más abundantes. Caprella acanthifera , Phtisica marina y Pseudoprotella phasma se distribuyeron por toda la Península; C. danilevskii , C. equilibra , C. fretensis y C. penantis mostraron distribución Atlántica, mientras que C. grandimana , C. hirsuta , C. liparotensis y Deutella schieckei se encontraron sólo en el Mediterráneo y el Estrecho de Gibraltar. Los caprélidos mostraron baja especificidad por el sustrato y se asociaron a distintas especies de algas. Los sustratos submareales albergaron mayor número de especies que los intermareales. Las mayores diversidades de especies se encontraron en las algas Stypocaulon scoparium , Cystoseira spp., Corallina elongata , Jania rubens , Codium vermilara , Cladostephus spongiosus y Asparagosis armata . Las abundancias registradas fueron muy altas, tanto en el intermareal como el submareal, alcanzando los 12200 ind/1000 ml de alga. De hecho, los caprélidos constituyen uno de los grupos dominantes de fauna asociada en el intermareal en comparación con otros taxa. A pesar de las altas densidades, la diversidad de los caprélidos (en términos de número de especies) en el intermareal y submareal somero de la Península Ibérica es bajo (11 espe- cies) si se compara con la diversidad total de caprélidos incluyendo aguas más profundas > 5 m (ca. 40 especies). El Análisis Canónico de Correspondencias mostró que la temperatura y la conductividad son las variables ambientales que mejor explican el claro gradiente Atlántico-Mediterráneo de distribución de caprélidos

Online monitoring for proton therapy: A real-time procedure using a planar PET system

In this study a procedure for range verification in proton therapy by means of a planar in-beam PET system is presented. The procedure consists of two steps: the measurement of the β+-activity induced in the irradiated body by the proton beam and the comparison of these distributions with simulations. The experimental data taking was performed at the CNAO center in Pavia, Italy, irradiating plastic phantoms. For two different cases we demonstrate how a real-time feedback of the delivered treatment plan can be obtained with in-beam PET imaging