Radioisotopic purity and imaging properties of cyclotron-produced 99mTc using direct 100Mo(p,2n) reaction.

Evaluation of the radioisotopic purity of technetium-99m (99mTc) produced in GBq amounts by proton bombardment of enriched molibdenum-100 (100Mo) metallic targets at low proton energies (i.e. within 15-20 MeV) is conducted. This energy range was chosen since it is easily achievable by many conventional medical cyclotrons already available in the nuclear medicine departments of hospitals. The main motivation for such a study is in the framework of the research activities at the international level that have been conducted over the last few years to develop alternative production routes for the most widespread radioisotope used in medical imaging. The analysis of technetium isotopes and isomeric states (9xTc) present in the pertechnetate saline Na99mTcO4 solutions, obtained after the extraction/purification procedure, reveals radionuclidic purity levels basically in compliance with the limits recently issued by European Pharmacopoeia 9.3 (2018 Sodium pertechnetate (99mTc) injection 4801-3). Moreover, the impact of 9xTc contaminant nuclides on the final image quality is thoroughly evaluated, analyzing the emitted high-energy gamma rays and their influence on the image quality. The spatial resolution of images from cyclotron-produced 99mTc acquired with a mini-gamma camera was determined and compared with that obtained using technetium-99m solutions eluted from standard 99Mo/99mTc generators. The effect of the increased image background contribution due to Compton-scattered higher-energy gamma rays (E γ > 200 keV), which could cause image-contrast deterioration, was also studied. It is concluded that, due to the high radionuclidic purity of cyclotron-produced 99mTc using 100Mo(p,2n)99mTc reaction at a proton beam energy in the range 15.7-19.4 MeV, the resulting image properties are well comparable with those from the generator-eluted 99mTc.

Observation of polarization-maintaining light propagation in depoled compositionally disordered ferroelectrics.

We investigate the evolution of the state of polarization of light propagating through bulk depoled composite ferroelectrics below the Curie temperature. In contrast to standard depoled ferroelectrics, where random birefringence causes depolarization and scattering, light is observed to suffer varying degrees of depolarization and remains fully polarized when linearly polarized along the crystal principal axes. The effect is found to be supported by the formation of polarized speckles organized into a spatial lattice and occurs as the ferroelectric settles into a spontaneous super-crystal, a three-dimensional coherent mosaic of ferroelectric clusters. The polarization lattices gradually disappear as the ferroelectric state reduces to a disordered distribution of polar nanoregions above the critical point.

Miniaturized photogenerated electro-optic axicon lens Gaussian-to-Bessel beam conversion.

We experimentally demonstrate an electro-optic Gaussian-to-Bessel beam-converter miniaturized down to a 30×30 µm pixel in a potassium-lithium-tantalate-niobate (KLTN) paraelectric crystal. The converter is based on the electro-optic activation of a photoinduced and reconfigurable volume axicon lens achieved using a prewritten photorefractive funnel space-charge distribution. The transmitted light beam has a tunable depth of field that can be more than twice that of a conventional beam with the added feature of being self-healing.

Turbulent Transitions in Optical Wave Propagation.

We report the direct observation of the onset of turbulence in propagating one-dimensional optical waves. The transition occurs as the disordered hosting material passes from being linear to one with extreme nonlinearity. As the response grows, increased wave interaction causes a modulational unstable quasihomogeneous flow to be superseded by a chaotic and spatially incoherent one. Statistical analysis of high-resolution wave behavior in the turbulent regime unveils the emergence of concomitant rogue waves. The transition, observed in a photorefractive ferroelectric crystal, introduces a new and rich experimental setting for the study of optical wave turbulence and information transport in conditions dominated by large fluctuations and extreme nonlinearity.

Intrinsic Negative Mass from Nonlinearity.

We propose and provide experimental evidence of a mechanism able to support negative intrinsic effective mass. The idea is to use a shape-sensitive nonlinearity to change the sign of the mass in the leading linear propagation equation. Intrinsic negative-mass dynamics is reported for light beams in a ferroelectric crystal substrate, where the diffusive photorefractive nonlinearity leads to a negative-mass Schrödinger equation. The signature of inverted dynamics is the observation of beams repelled from strongly guiding integrated waveguides irrespective of wavelength and intensity and suggests shape-sensitive nonlinearity as a basic mechanism leading to intrinsic negative mass.

Super-crystals in composite ferroelectrics.

As atoms and molecules condense to form solids, a crystalline state can emerge with its highly ordered geometry and subnanometric lattice constant. In some physical systems, such as ferroelectric perovskites, a perfect crystalline structure forms even when the condensing substances are non-stoichiometric. The resulting solids have compositional disorder and complex macroscopic properties, such as giant susceptibilities and non-ergodicity. Here, we observe the spontaneous formation of a cubic structure in composite ferroelectric potassium-lithium-tantalate-niobate with micrometric lattice constant, 10(4) times larger than that of the underlying perovskite lattice. The 3D effect is observed in specifically designed samples in which the substitutional mixture varies periodically along one specific crystal axis. Laser propagation indicates a coherent polarization super-crystal that produces an optical X-ray diffractometry, an ordered mesoscopic state of matter with important implications for critical phenomena and applications in miniaturized 3D optical technologies.

Experimental and Monte Carlo simulated spectra of a liquid-metal-jet x-ray source.

A prototype x-ray system based on a liquid-metal-jet anode was evaluated within the framework of the LABSYNC project. The generated spectrum was measured using a CZT-based spectrometer and was compared with spectra simulated by three Monte Carlo codes: MCNPX, PENELOPE and EGS5. Notable differences in the simulated spectra were found. These are mainly attributable to differences in the models adopted for the electron-impact ionization cross section. The simulation that more closely reproduces the experimentally measured spectrum was provided by PENELOPE.

Effect of the carrier-envelope-offset dynamics on the stabilization of a diode-pumped solid-state frequency comb.

We investigate the dynamics of the carrier-envelope-offset (CEO) frequency, f(CEO), controlled by a pump current on the self-referencing of an optical frequency comb generated from a diode-pumped solid-state laser at 1.56 µm. We observe a reversal point in the tuning of f(CEO) with the pump current. Between the low- and high-frequency region in the dynamic response of f(CEO) to pump current modulation, we observe a significant phase shift of ≈180 deg in the transfer function. As a result, it is impossible to stabilize f(CEO) at a pump current above the reversal point, although the free-running CEO beat at this point has a higher signal-to-noise ratio than underneath the reversal point at which the locking is straightforward. Our results indicate that a high signal-to-noise ratio and a low-noise CEO beat are not sufficient indicators for the feasibility of comb self-referencing in cases for which CEO dynamics play a dominant role.

Frequency noise of free-running 4.6 µm distributed feedback quantum cascade lasers near room temperature.

The frequency noise properties of commercial distributed feedback quantum cascade lasers emitting in the 4.6 µm range and operated in cw mode near room temperature (277 K) are presented. The measured frequency noise power spectral density reveals a flicker noise dropping down to the very low level of <100 Hz(2)/Hz at 10 MHz Fourier frequency and is globally a factor of 100 lower than data recently reported for a similar laser operated at cryogenic temperature. This makes our laser a good candidate for the realization of a mid-IR ultranarrow linewidth reference.

Optimization of radiography applications using x-ray beams emitted by compact accelerators. Part I. Monte Carlo study of the hard x-ray spectrum.

PURPOSE: A 3-year project called LABSYNC has been recently funded by the European Commission, with the aim of designing a radiation facility based on a compact light source, i.e., a laboratory-sized commercial synchrotron, capable of accelerating electrons up to 6 or 20 MeV. An accurate spectral description of hard x rays emitted from thin targets, irradiated by electron beams circulating in the storage ring, is of primary interest for the design and the characterization of a beamline. This article, Part I, aims at optimizing some of the parameters which are critical for the design of medical applications based on the above compact light source. The goal was to evaluate the dependence of photon fluence and beam monochromaticity on electron-beam energy, target material, and thickness. METHODS: The transport of 6 and 20 MeV electrons in a thin molybdenum, rhodium, and tungsten target is studied by means of Monte Carlo simulations using MCNPX. Configurations of the x-ray output port, different from the default forward-directed emission of the beam, are also investigated. A comparison with reference spectra for general diagnostic radiology and mammography is carried out. RESULTS: It is shown that the emitted x-ray beams can be far more intense than those generated by conventional x-ray tubes for radiography applications. The profiles of the calculated polychromatic spectra resemble those generated by conventional x-ray tubes, with x-ray energies up to the energy of the incident-electron beam. An appreciable improvement in the monochromaticity of the beams can be obtained by viewing the x-ray emission from an output port antiparallel to the direction of the incident-electron beam. CONCLUSIONS: The optimum target thickness for tungsten target spectra is practically constrained by a trade-off between bremsstrahlung efficiency and focal-spot size requirements. A larger margin for optimization of target thickness is probably available for mammographic spectra. The constraint of a backward-directed (or, to a lesser extent, orthogonal) output port is to be considered mandatory for minimizing the high-energy tail of the spectral distribution and keeping the radiation dose to a reasonable level. It is also fundamental to evaluate the impact of the high-energy tail of the emitted spectra in x-ray imaging applications, since the energy range involved is significantly beyond the diagnostic range. This topic will be dealt with in Part II of the article.

Experimental observation of optical rotation generated in vacuum by a magnetic field.

We report the experimental observation of a light polarization rotation in vacuum in the presence of a transverse magnetic field. Assuming that data distribution is Gaussian, the average measured rotation is (3.9 +/- 0.5) x 10(-12) rad/pass, at 5 T with 44 000 passes through a 1 m long magnet, with lambda = 1064 nm. The relevance of this result in terms of the existence of a light, neutral, spin-zero particle is discussed.

Differential expression and cytoplasm/membrane distribution of endoglin (CD105) in human tumour cell lines: Implications in the modulation of cell proliferation.

Endoglin (CD105, an accessory component of the TGF-beta receptor complex) expression and distribution on different human tumour cells and its role in cellular proliferation were evaluated. We examined: 1) sixteen human carcinoma cell lines, 2) eight human sarcoma cell lines, 3) five miscellaneous tumour cell lines. HECV (endothelial cells) were employed as a positive control for endoglin expression. Normal Human Dermal Fibroblasts (NHDF) and 293 cells (epithelial kidney cells) were used as normal controls for connective and epithelial tissues, respectively. The results showed that CD105 was poorly expressed in the majority of human carcinoma cells (10/16), whereas it was highly expressed in most human sarcoma cells (7/8), and differently expressed by miscellaneous tumour cell lines. These data reflect endoglin expression by the normal counterparts of tumour cell lines, i.e. NHDF and 293 cells. However, CD105 levels in sarcoma cell lines, even though consistently lower than in NHDF, were significantly higher than those observed in carcinoma cells. Interestingly, CD105 presented a strong expression in the cytoplasm of MDA-MB-453 (breast carcinoma), NPA (papillary thyroid carcinoma), COLO-853 (melanoma) and SaOS-2 (osteosarcoma), but was weakly expressed on their cell membrane. This differential expression in the cytoplasm and on the membrane of some tumour cells, suggests a complex mechanism of translocation for this protein. The analysis of clonal growth in soft agar of some cell lines, characterized by high CD105 expression, showed an increased colony formation potential that was antagonized by the addition of anti-CD105 blocking mAb. The results indicated that endoglin is differentially expressed in human carcinoma and sarcoma cells and its overexpression modulates the proliferative rate of human solid tumour cells. Moreover, these data suggest that CD105 is involved in the regulation of TGF-beta effects in human solid malignancies, and therefore it could play an important role in tumour diagnosis and treatment.

Different titanium surfaces modulate the bone phenotype of SaOS-2 osteoblast-like cells.

Commercially pure titanium implants presenting a relatively smooth, machined surface or a roughened endosseous surface show a large percentage of clinical success. Surface properties of dental implants seem to affect bone cells response. Implant topography appears to modulate cell growth and differentiation of osteoblasts affecting the bone healing around the titanium implant. The aim of the present study was to examine the effects of 1cm diameter and 1mm thick titanium disks on cellular morphology, adhesion and bone phenotypic expression of human osteoblast-like cells, SaOS-2. SaOS-2 cells were cultured on commercially 1 cm pure titanium disks with three different surface roughness: smooth (S), sandblasted (SB) and titanium plasma sprayed (TPS). Differences in the cellular morphology were found when they were grown on the three different surfaces. An uniform monolayer of cells recovered the S surface, while clusters of multilayered irregularly shaped cells were distributed on the rough SB and TPS surfaces. The adhesion of SaOS-2 cells, as measured after 3h of culture, was not affected by surface roughness. ECM components such as Collagen I (CoI), Fibronectin (FN), Vitronectin (VN) and Tenascin (TN) were secreted and organized only on the SB and TPS surfaces while they remained into the cytoplasm on the S surfaces. Osteopontin and BSP-II were largely detected on the SB and TPS surfaces, while only minimal production was observed on the S ones. These data show that titanium surface roughness affects bone differentiation of osteoblast like-cells, SaOS-2, indicating that surface properties may be able to modulate the osteoblast phenotype. These observations also suggest that the bone healing response around dental implants can be affected by surface topography.

Behavior of SaOS-2 cells cultured on different titanium surfaces.

Surface properties may affect the clinical outcome of titanium dental implants. The aim of the present study was to investigate the effects of 3 different titanium surfaces-smooth (S), sandblasted (SB), and titanium plasma-sprayed (TPS)-on proliferation, differentiation, and apoptosis of human osteoblast-like cells, SaOS-2. Cell proliferation was significantly (p < 0.05) higher on the S surface, and synthesis of extracellular matrix proteins was more abundant on TPS and SB than on S surfaces. Analysis of integrin receptors showed a higher expression of alpha2, alpha5, alphaVbeta3, and ss1 on TPS as compared with SB and S surfaces. An increase in alkaline phosphatase activity was detected only on SB and TPS surfaces. Analysis of cell apoptosis did not demonstrate any significant difference among the 3 different surfaces. The results indicate that titanium surface topography affects proliferation and differentiation of osteoblast-like SaOS-2 cells, suggesting that surface properties might be important for bone response around dental implants in vivo.

Immunophenotypic analysis of human gingival fibroblasts and its regulation by Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF).

BACKGROUND: The aim of the present study was to perform an immunophenotypic analysis of human gingival fibroblast cells and its eventual modulation by Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF). METHODS: Gingival fibroblasts were derived from gingival biopsy of 15 healthy subjects. The presence of fibroblast cells in culture and the absence of epithelial cells was performed with fluorescence microscopy using vimentin and cytokeratin markers, respectively. Molecular expression of gingival fibroblast cell membrane was carried out with monoclonal antibodies by flow cytometry analysis. Human recombinant GM-CSF at the concentration of 200 ng/ml was used for the in vitro stimulation of gingival fibroblasts. Statistical analysis was performed using the Student "t"-test. RESULTS: Human gingival fibroblasts express a wide surface molecular panel including mainly CD59, CD99, CD9, CD95, CD55, CD63, CD26, CD117, CD71 and CD86. The GM-CSF seems to regulate the CD49B expression positively and the CD40 and CD103 expression negatively. CONCLUSIONS: Results show that GM-CSF is able to modulate the in vitro expression of some membrane molecules of gingival fibroblasts and therefore it may regulate, in vivo, peculiar specific biological functions of gingival tissue.

Effect of human granulocyte macrophage-colony stimulating factor on differentiation and apoptosis of the human osteosarcoma cell line SaOS-2.

We investigated the effects of human granulocyte macrophage-colony stimulating factor (GM-CSF) on the relation between differentiation and apoptosis in SaOS-2 cells, an osteoblast-like cell line. To determine the relationship between these cellular processes, SaOS-2 cells were treated in vitro for 1, 7 and 14 days with 200 ng/mL GM-CSF and compared with untreated cells. Five nM insulin-like growth factor (IGF-I) and 30 nM okadaic acid were used as negative and positive controls of apoptosis, respectively. Effects on cell differentiation were determined by ECM (extracellular matrix) mineralization, morphology of some typical mature osteoblast differentiation markers, such as osteopontin and sialoprotein II (BSP-II), and production of bone ECM components such as collagen I. The results showed that treatment with GM-CSF caused cell differentiation accompanied by increased production of osteopontin and BSP-II, together with increased ECM deposition and mineralization. Flow cytometric analysis of annexin V and propidium iodide incorporation showed that GM-CSF up-regulated apoptotic cell death of SaOS-2 cells after 14 days of culture in contrast to okadaic acid, which stimulated SaOS-2 apoptosis only during the early period of culture. Endonucleolytic cleavage of genomic DNA, detected by "Aúladdering analysis"Aù, confirmed these data. The results suggest that GM-CSF induces osteoblastic differentiation and long-term apoptotic cell death of the SaOS-2 human osteosarcoma cell line, which in turn suggests a possible in vivo physiological role for GM-CSF on human osteoblast cells.

Use of a fast EM algorithm for 3D image reconstruction with the YAP-PET tomograph.

OBJECTIVE: We would like to improve the image reconstructions for both signal-to-noise ratio (SNR) and spatial resolution characteristics for the small animal positron emission tomograph YAP-PET, built at the Department of Physics of Ferrara University. The three-dimensional (3D) filtered backprojection (FBP) algorithm, usually used for image reconstruction, has a limited angle restriction due to the tomograph geometry, which causes a serious loss in sensitivity. METHODS: We implemented a 3D iterative reconstruction program using the symmetry and sparse properties of the 'probability matrix', which correlates the emission from each voxel to the detector within a coincidence tube. A fraction only of matrix elements are calculated before the reconstruction and stored on disk: this allows us to avoid on-line computation. A depth dependent function differentiates the voxels in a coincidence tube. Three experimental phantoms with no background were reconstructed by using the program, in comparison with traditionally used FBP. RESULTS: The adopted method allowed us to reduce the computation time significantly. Furthermore, the simple depth dependent function improved the spatial resolution. With 64 x 64 x 20 voxels of 0.625 x 0.625 x 2.0 mm(3) in the field of view, the computation time was less than 4 min per iteration on a Sparc Ultra 450 Workstation, and less than 6 min per iteration on a Mac-PPC G3 300 MHz: the spatial resolution measured with a 0.8 mm diameter 18F-FDG filled capillary reconstructed in this way was 2.0 mm FWHM. By decreasing the voxel size to 0.3125 x 0.3125 x 2.0 mm(3) per voxel the transaxial FWHM was 1.7 mm with a computation time of 15 min per iteration on a Sparc Ultra 450. By using all the acquired data, the SNR improves from 1.3 to 6.0 in the worst measured case, a pair of 0.8mm diameter 18F-FDG filled capillaries, which are 2.5 mm apart each other. CONCLUSION: The adoption of iterative reconstruction allowed us to overcome the loss in sensitivity of previously used FBP: this improved the SNR. The studies of symmetry and sparse properties avoided a severe increase of the reconstruction time and of storing space on disk. This fast EM Algorithm is now routinely used for the image reconstruction with the YAP-PET tomograph.

Clodronate treatment reduces serum levels of interleukin-6 soluble receptor in Paget's disease of bone.

OBJECTIVE: Interleukin-6 (IL-6) and its soluble receptor (sIL-6R) stimulate osteoclast formation and activity. The primary cell abnormality in Paget's disease of bone (PDB) involves osteoclasts. Pagetic osteoclasts overproduce IL-6 and IL-6 receptor in vitro. In vivo, IL-6 serum levels are very high in the acute phase of PDB. The aim of this study was to evaluate the modification in the serum levels of IL-6, sIL-6R and osteotropic hormones (parathormone, 25OHD3 and 1,25(OH)2D3) as a in long-term response to clodronate treatment in patients with PDB. METHODS: 16 patients (8 females) with polyostotic PDB were studied. IL-6, sIL-6R and osteotropic hormones serum levels were evaluated in active PDB and after clodronate treatment (300 mg injected intravenously for 5 consecutive days). The sequential changes in total alkaline phosphatase (tALP) serum levels were used to assess the maximal pharmacological response to treatment. RESULTS: In untreated pagetic patients, mean serum levels of IL-6 (3.20+/-1.18 pg/ml) and sIL-6R (35.02+/-8.33 ng/ml) were significantly increased. Serum osteotropic hormone levels fell within the normal range. Eight weeks after treatment, the maximal pharmacological response to clodronate was associated with a significant reduction of sIL-6R serum levels in all patients, without a significant variation in serum IL-6 and osteotropic hormone levels. Moreover, we observed a correlation between lower sIL-6R serum levels before clodronate therapy and complete remission of PBD, defined as a decrease of tALP serum levels within the normal range. CONCLUSION: The decrease in serum sIL-6R levels could be one of the molecular mechanisms that play a role in the clinical response to clodronate treatment in PDB.

Principal component analysis of large layer density in Compton scattering measurements

A multivariate approach based on Principal Component Analysis (PCA) was used to analyze the energy distribution of n Monte Carlo simulated Compton scattered photon spectra describing the electron density of large layers. Three to five layers with different density distribution were used to test the algorithm; each layer was obtained by collecting 25 Compton spectra coming from sensitive volumes (SVs) where the complementary conditions of high and low density were realized (respectively full and void SV). The density variation inside a single layer is described by a two principal components (PCs) linear model that depicts the electron density of each SV: the layer density distribution appears to be correctly described even in the presence of very low signal-to-noise Compton spectra. Density profiles for layers at different depths were comparatively analyzed in order to show that, at least within one mean-free-path distance, it is possible to describe the layer density distribution by the PCA without any correction for the beam attenuation.