A late Neanderthal tooth from northeastern Italy.

The site of Riparo Broion (Vicenza, northeastern Italy) preserves a stratigraphic sequence documenting the Middle-to-Upper Paleolithic transition, in particular the final Mousterian and the Uluzzian cultures. In 2018, a human tooth was retrieved from a late Mousterian level, representing the first human remain ever found from this rock shelter (Riparo Broion 1). Here, we provide the morphological description and taxonomic assessment of Riparo Broion 1 with the support of classic and virtual morphology, 2D and 3D analysis of the topography of enamel thickness, and DNA analysis. The tooth is an exfoliated right upper deciduous canine, and its general morphology and enamel thickness distribution support attribution to a Neanderthal child. Correspondingly, the mitochondrial DNA sequence from Riparo Broion 1 falls within the known genetic variation of Late Pleistocene Neanderthals, in accordance with newly obtained radiocarbon dates that point to approximately 48 ka cal BP as the most likely minimum age for this specimen. The present work describes novel and direct evidence of the late Neanderthal occupation in northern Italy that preceded the marked cultural and technological shift documented by the Uluzzian layers in the archaeological sequence at Riparo Broion. Here, we provide a new full morphological, morphometric, and taxonomic analysis of Riparo Broion 1, in addition to generating the wider reference sample of Neanderthal and modern human upper deciduous canines. This research contributes to increasing the sample of fossil remains from Italy, as well as the number of currently available upper deciduous canines, which are presently poorly documented in the scientific literature.

Validation of [Formula: see text]Tc and [Formula: see text]Lu quantification parameters for a Monte Carlo modelled gamma camera.

PURPOSE: Monte Carlo (MC) simulation in Nuclear Medicine is a powerful tool for modeling many physical phenomena which are difficult to track or measure directly. MC simulation in SPECT/CT imaging is particularly suitable for optimizing the quantification of activity in a patient, and, consequently, the absorbed dose to each organ. To do so, validating MC results with real data acquired with gamma camera is mandatory. The aim of this study was the validation of the calibration factor (CF) and the recovery coefficient (RC) obtained with SIMIND Monte Carlo code for modeling a Siemens Symbia Intevo Excel SPECT-CT gamma camera to ensure optimal [Formula: see text]Tc and [Formula: see text]Lu SPECT quantification. METHODS: Phantom experiments using [Formula: see text]Tc and [Formula: see text]Lu have been performed to measure spatial resolution and sensitivity, as well as to evaluate the CF and RC from acquired data. The geometries used for 2D planar imaging were (1) Petri dish and (2) capillary source while for 3D volumetric imaging were (3) a uniform filled cylinder phantom and (4) a Jaszczack phantom with spheres of different volumes. The experimental results have been compared with the results obtained from Monte Carlo simulations performed in the same geometries. RESULTS: Comparison shows good accordance between simulated and experimental data. The measured planar spatial resolution was 8.3[Formula: see text] mm for [Formula: see text]Tc and 11.8±0.6 mm for [Formula: see text]Lu. The corresponding data obtained by SIMIND for [Formula: see text]Tc was 7.8±0.1 mm, while for [Formula: see text]Lu was 12.4±0.4 mm. The CF was 110.1±5.5 cps/MBq for Technetium and 18.3±1.0 cps/MBq for Lutetium. The corresponding CF obtained by SIMIND for [Formula: see text]Tc was 107.3±0.3 cps/MBq, while for [Formula: see text]Lu 20.4±0.7 cps/MBq. Moreover, a complete curve RCs vs Volume (ml) both for Technetium and Lutetium was determined to correct the PVE for all volumes of clinical interest. In none of the cases, a RC coefficient equal to 100 was found. CONCLUSIONS: The validation of quantification parameters shows that SIMIND can be used for simulating both gamma camera planar and SPECT images of Siemens Symbia Intevo using [Formula: see text]Tc and [Formula: see text]Lu radionuclides for different medical purposes and treatments.

Styloid Jugular Nutcracker: The Possible Role of the Styloid Process Spatial Orientation-A Preliminary Morphometric Computed Study.

Styloid Jugular Nutcracker (SJN, also known as Eagle Jugular Syndrome EJS) derives from a jugular stenosis caused by an abnormal styloid process, compressing the vessel in its superior portion (J3) against the C1 anterior arch. It could be considered a venous vascular variant of Eagle Syndrome (ES). Main clinical features of this ES variant are headache, pulsatile tinnitus and dizziness, possibly related to venous hypertension and impaired cerebral parenchyma drainage. In our opinion, conceptually, it is not the absolute length of the styloid bone that defines its abnormality, but its spatial direction. An elongated bone pointing outward far away from the midline could not compress the vein; vice versa, a short styloid process tightly adherent to the cervical spine could be pathological. To prove this hypothesis, we developed a semi-automatic software that processes CT-Angio images, giving quantitative information about distance and direction of the styloid process in three-dimensional space. We compared eight patients with SJN to a sample of healthy subjects homogeneous for sex and age. Our results suggest that SJN patients have a more vertically directed styloid, and this feature is more important than the absolute distance between the two bony structures. More studies are needed to expand our sample, including patients with the classic and carotid variants of Eagle Syndrome.

Dosimetric characterization of a mobile accelerator dedicated for intraoperative radiation therapy: Monte Carlo simulations and experimental validation.

PURPOSE: This Technical Note validates previously published data about the dosimetry of the electron beams produced by a mobile accelerator dedicated for intraoperative radiation therapy (IORT). The evaluation of the directional response of a PTW microDiamond detector is presented together with a detailed analysis of the output factors (OFs) for bevelled applicators. METHODS: The OFs of the 6, 8, 10 and 12 MeV electron beams produced by a light intraoperative accelerator (LIAC, SIT, Italy) were measured in a commercial water phantom using the microDiamond. A set of flat and bevelled applicators with sizes ranging from 4 to 10 cm was characterized. For bevelled applicators, a correction for the angular dependence of the microDiamond was calculated using a home-made spherical phantom. Correction factors were obtained through measurements performed rotating the accelerator treatment head at 0°, 15°, 30° and 45°. RESULTS: For flat applicators, the average deviation between measured and simulated OFs was (-1.1 ± 0.7)%. The microDiamond showed a higher angular dependence for the 6 MeV beam (∼8% for angles up to 45°, range 92 % ÷ 100 %), while the variations for 8, 10 and 12 MeV beams were âˆ¼ 4 % (range 97 % ÷ 101 %). Correcting for this dependence, the average deviation of the OFs for bevelled applicators was (-0.9 ± 1.6)%. CONCLUSIONS: The presented results were in very good agreement with those reported in literature. Very similar deviations were found between flat and bevelled applicators confirming the suitability of our method to determine the angular dependence correction factors of the microDiamond detector.

Mechanical Function of Internal Jugular Vein Valve: Post-analysis of M-Mode Imaging under Cardiac Monitoring.

Because the internal jugular vein (IJV) valve is the only protective valve between the brain and heart, recent studies have focused on the dynamic behaviour of the valve and its importance in regulating the cerebral blood outflow pathway. However, the mechanism underlying valve opening and closure, as well as the normal opening time, has not been investigated before. The aim of the study described here was to investigate IJV physiology in healthy young adults by means of ultrasound imaging. Twenty-four normal young adults (16 male, 8 female, 21.79 ± 0.79 y of age) were enrolled in this study. Each participant underwent IJV B- and M-mode ultrasound scans of the neck veins in supine position. Data on IJV leaflet movement and IJV blood velocity were extracted from images with the associated electrocardiogram traces to analyze the opening and closure cycles of IJV leaflets. The normal opening time calculated in this study includes 70% of the dynamic valve cycle. The normal opening time of the IJV valve could be a new physiologic metric and serves as a premise for further studies in the field of cerebral venous return.

Altered velocity gradient in lower limb chronic venous disease.

BACKGROUND: In physiology, velocity of the deep venous compartment is higher than the one in the saphenous compartment which is higher than the one in the tributaries. Considering that velocity variation is associated with changes in the pressure gradient, aim of the present study is to assess changes in venous kinetics in case of superficial chronic venous disease, so to provide further clues in venous drainage direction determination. METHODS: Venous ultrasound scanning was performed on 40 lower limbs of 28 chronic venous disease patients (C2-6Ep,As,Pr). Velocities were measured in three different venous segments: great saphenous vein at 2 cm above the origin of the incompetent tributary (Group-A). great saphenous vein at 2 cm below the origin of tributary (Group-B). tributary at 2 cm from its origin from the great saphenous vein (Group-C.). RESULTS: Diastolic time average velocity was higher in group-C (-21.3 ± 8.5 cm/s) than in group-A (-15.7 ± 5.2 cm/s; p = .0001) and group-B (-11.1 ± 2.9 cm/s; p = .0001), thus indicating an inversion of the physiological velocity gradient in chronic venous disease patients. DISCUSSION: Chronic venous disease presents a subverted velocity gradient. These data introduce objective hemodynamics data, paving the way for further investigation in venous drainage direction determination.

Lower limbs venous kinetics and consequent impact on drainage direction.

Background Literature concerning the lower limbs physiological venous haemodynamics is still lacking of reference velocity values and consequent impact on drainage direction. Aim of the present study is to assess the flow velocities in the different venous compartments, evaluating the possible Venturi effect role, thus finding clues for the identification of the physical model governing the flow direction. Methods Thirty-six lower limbs underwent a velocity and diameters echo-color-Doppler assessment in several anatomical point of analysis along both the deep and superficial venous systems. The investigation protocol included and compared two different manoeuvres to elicit the flow: manual calf compression/relaxation (CR) and active foot dorsiflexion (AFD). Both peak systolic (PSV) and time average velocities (TAV) were measured. Results The different venous segments demonstrated an overlap among the velocity values and the anatomical subdivision of the deep and superficial compartments. At the CR, TAV was 34 ± 12 cm/s in the deep venous system (N1), 15 ± 7 cm/s in the saphenous system (N2), 5 ± 2 cm/s in the saphenous tributaries (N3); PSV was 89 ± 35 cm/s in N1, 34 ± 16 cm/s in N2, 11 ± 4 cm/s in N3, p < 0.05. At the AFD, TAV was 33 ± 13 cm/s in N1, 15 ± 7 in N2, 9 ± 5 in N3; PSV was 83 ± 35 in N1, 32 ± 17 in N2, 15 ± 4 in N3, p < 0.05. A diameter decrease was reported from N1 to N3 ( p < 0.05). Conclusion This investigation provides evidences of the velocity decrease from the deepest to the most superficial compartments. These data introduce the Venturi effect as potential factor in the flow aspiration from the tributary to the deeper veins. The reported data represent a first step towards an objective evaluation of the physic laws governing the drainage. These values can constitute the basis for further investigations in pathological and post-procedural scenarios.

Psychostimulant Effect of the Synthetic Cannabinoid JWH-018 and AKB48: Behavioral, Neurochemical, and Dopamine Transporter Scan Imaging Studies in Mice.

JWH-018 and AKB48 are two synthetic cannabinoids (SCBs) belonging to different structural classes and illegally marketed as incense, herbal preparations, or chemical supply for theirs psychoactive cannabis-like effects. Clinical reports from emergency room reported psychomotor agitation as one of the most frequent effects in people assuming SCBs. This study aimed to investigate the psychostimulant properties of JWH-018 and AKB48 in male CD-1 mice and to compare their behavioral and biochemical effects with those caused by cocaine and amphetamine. In vivo studies showed that JWH-018 and AKB48, as cocaine and amphetamine, facilitated spontaneous locomotion in mice. These effects were prevented by CB1 receptor blockade and dopamine (DA) D1/5 and D2/3 receptors inhibition. SPECT-CT studies on dopamine transporter (DAT) revealed that, as cocaine and amphetamine, JWH-018 and AKB48 decreased the [123I]-FP-CIT binding in the mouse striatum. Conversely, in vitro competition binding studies revealed that, unlike cocaine and amphetamine, JWH-018 and AKB48 did not bind to mouse or human DAT. Moreover, microdialysis studies showed that the systemic administration of JWH-018, AKB48, cocaine, and amphetamine stimulated DA release in the nucleus accumbens (NAc) shell of freely moving mice. Finally, unlike amphetamine and cocaine, JWH-018 and AKB48 did not induce any changes on spontaneous [3H]-DA efflux from murine striatal synaptosomes. The present results suggest that SCBs facilitate striatal DA release possibly with different mechanisms than cocaine and amphetamine. Furthermore, they demonstrate, for the first time, that JWH-018 and AKB48 induce a psychostimulant effect in mice possibly by increasing NAc DA release. These data, according to clinical reports, outline the potential psychostimulant action of SCBs highlighting their possible danger to human health.

A novel approach to background subtraction in contrast-enhanced dual-energy digital mammography with commercially available mammography devices: Noise minimization.

PURPOSE: Dual-energy image subtraction represents a useful tool to improve the detectability of small lesions, especially in dense breasts. A feature it shares with all x-ray imaging techniques is the appearance of fluctuations in the texture of the background, which can obscure the visibility of interesting details. The aim of the work is to investigate the main noise sources, in order to create a better performing subtraction mechanism. In particular, the structural noise cancellation was achieved by means of a suitable extension of the dual-energy algorithm. METHODS: The effect of the cancellation procedure was tested on an analytical simulation of a target with varying structural composition. Subsequently, the subtraction algorithm was also applied to a set of actual radiographs of a breast phantom exhibiting a nonuniform background pattern. The background power spectra of the outcomes were computed and compared to the ones obtained from a standard subtraction algorithm. RESULTS: The comparison between the standard and the proposed cancellations showed an overall suppression of the magnitudes of the spectra, as well as a flattening of the frequency dependence of the structural component of the noise. CONCLUSIONS: The proposed subtraction procedure provides an effective cancellation of the residual background fluctuations. When combined with the polychromatic correction already described in a companion publication, it results in a high performing dual-energy subtraction scheme for commercial mammography units.

X-ray focal spot reconstruction by circular penumbra analysis-Application to digital radiography systems.

PURPOSE: The quality of a radiography system is affected by several factors, a major one being the focal spot size of the x-ray tube. In fact, the measurement of such size is recognized to be of primary importance during acceptance tests and image quality evaluations of clinical radiography systems. The most common device providing an image of the focal spot emission distribution is a pin-hole camera, which requires a high tube loading in order to produce a measurable signal. This work introduces an alternative technique to obtain an image of the focal spot, through the processing of a single radiograph of a simple test object, acquired with a suitable magnification. METHODS: The radiograph of a magnified sharp edge is a well-established method to evaluate the extension of the focal spot profile along the direction perpendicular to the edge. From a single radiograph of a circular x-ray absorber, it is possible to extract simultaneously the radial profiles of several sharp edges with different orientations. The authors propose a technique that allows to obtain an image of the focal spot through the processing of these radial profiles by means of a pseudo-CT reconstruction technique. In order to validate this technique, the reconstruction has been applied to the simulated radiographs of an ideal disk-shaped absorber, generated by various simulated focal spot distributions. Furthermore, the method has been applied to the focal spot of a commercially available mammography unit. RESULTS: In the case of simulated radiographs, the results of the reconstructions have been compared to the original distributions, showing an excellent agreement for what regards both the overall distribution and the full width at half maximum measurements. In the case of the experimental test, the method allowed to obtain images of the focal spot that have been compared with the results obtained through standard techniques, namely, pin-hole camera and slit camera. CONCLUSIONS: The method was proven to be effective for simulated images and the results of the experimental test suggest that it could be considered as an alternative technique for focal spot distribution evaluation. The method offers the possibility to measure the actual focal spot size and emission distribution at the same exposure conditions as clinical routine, avoiding high tube loading as in the case of the pin-hole imaging technique.

A novel approach to background subtraction in contrast-enhanced dual-energy digital mammography with commercially available mammography devices: Polychromaticity correction.

PURPOSE: Contrast-enhanced digital mammography is an image subtraction technique that is able to improve the detectability of lesions in dense breasts. One of the main sources of error, when the technique is performed by means of commercial mammography devices, is represented by the intrinsic polychromaticity of the x-ray beams. The aim of the work is to propose an iterative procedure, which only assumes the knowledge of a small set of universal quantities, to take into account the polychromaticity and correct the subtraction results accordingly. METHODS: In order to verify the procedure, it has been applied to an analytical simulation of a target containing a contrast medium and to actual radiographs of a breast phantom containing cavities filled with a solution of the same medium. RESULTS: The reconstructed densities of contrast medium were compared, showing very good agreement between the theoretical predictions and the experimental results already after the first iteration. Furthermore, the convergence of the iterative procedure was studied, showing that only a small number of iterations is necessary to reach limiting values. CONCLUSIONS: The proposed procedure represents an efficient solution to the polychromaticity issue, qualifying therefore as a viable alternative to inverse-map functions.

Biodistribution of nanostructured lipid carriers: a tomographic study.

This study describes the preparation, characterization, and biodistribution of radiolabelled nanostructured lipid carriers (NLCs) especially designed for in vivo tomographic study. A preliminary formulative study was conducted in order to incorporate (99m)Tc based tracer in NLCs. At this aim a (99m)Tc complex containing a terminal (99m)Tc ≡ N multiple bond ([(99m)Tc]N-DBODC2) has been synthesized and included in NLCs produced by a stirring and ultrasonication method. The morphological and dimensional characteristics of the produced NLCs have been accurately investigated by a number of specific techniques, including: cryogenic transmission electron microscopy, X-ray, photon correlation spectroscopy and sedimentation field flow fractionation. The obtained NLCs were employed for achieving in vivo tomographic images of the rat body by small-animal SPECT scanner that enabled the investigation of NLC biodistribution after intraperitoneal, intravenous, intranasal and oral administration. NLC production protocol allowed to firmly encapsulate the radiotracer within the nanoparticles. In vivo studies evidenced that NLC remained stable in vivo, suggesting their suitability as controlled release system for drugs and radiochemical for therapeutic and diagnostic purposes. Moreover the high resolution images obtained by the SPECT technique allowed to detect NLC presence in brown fat tissue, suggesting NLC therapeutic application for treating human obesity and related metabolic disorders.

An ultrasonographic technique to assess the jugular venous pulse: a proof of concept.

The purpose of the work described here was to investigate the feasibility of assessing the jugular venous pulse (JVP) using ultrasound (US) equipment. Three young healthy subjects underwent a B-mode US scan of the internal jugular vein (IJV) to acquire a sonogram sequence in the transverse plane. On each acquired sonogram, the IJV contour was manually traced, and both the cross-sectional area (CSA) and the perimeter were measured. The CSA data set represents the US jugular diagram (USJD). The arterial distension waveform of the subjects was compared with its USJD. The correlation between the CSA and the perimeter was assessed during the cardiac cycle to verify IJV distension. For each subject, a short sonogram sequence of a few seconds was recorded, and the USJD obtained exhibited periodic behavior. Furthermore, for all subjects, the CSA was found to be correlated with the perimeter (Pearson coefficient, R > 0.9), indicating that the IJV in supine position is distended. We compared 390 manually traced contours of the IJV cross-sectional area with corresponding values semi-automatically calculated by an algorithm developed in-house. For all subjects, the sensitivity, specificity and accuracy were around 95%, 85% and 90% respectively. We found that a diagram reflecting the JVP can be obtained by analyzing a B-mode sonogram sequence of the IJV; such a diagram can result in a new methodology to assess the IJV functionality.

Synthesis and biologic evaluation of monocationic asymmetric 99mTc-nitride heterocomplexes showing high heart uptake and improved imaging properties.

UNLABELLED: The preparation, characterization, and first biologic evaluation in rats of a novel class of monocationic (99m)Tc heart imaging agents are reported. The complexes are represented by the general formula [(99m)Tc(N)(PNP)(L)](+), where L is the monoanionic form of a dithiocarbamate ligand of the type [R(1)(R(2))-N-C(=S)S](-), PNP is a diphosphine ligand of the type [(R(3))(2)P-(CH(2))(2)](2)-N(R(4)), and R(1)-R(4) are organic functional groups. METHODS: The new complexes were prepared by use of both liquid and freeze-dried formulations through a 2-step procedure. The first step involved the formation of the [TcN](2+) group through the reaction of (99m)TcO(4)(-) with succinic dihydrazide as a donor of nitride nitrogen atoms (N(3-)) in the presence of Sn(2+) ions. This step was followed by the simultaneous addition to the reaction solution of the ligand PNP and of the sodium salt of the dithiocarbamate ligand (NaL) to afford the final products, [(99m)Tc(N)(PNP)(L)](+). The chemical identities of the resulting (99m)Tc complexes were determined by comparing their chromatographic properties with those of the corresponding (99g)Tc analogs prepared by use of the long-lived isotope (99g)Tc and characterized by spectroscopic and crystallographic techniques. Ex vivo biodistribution studies were conducted in rats. In vivo tomographic images of the rat heart were obtained by use of a small-animal SPECT scanner. RESULTS: The [(99m)Tc(N)(PNP)(L)](+) complexes are monocationic and possess a distorted square-pyramidal geometry in which the TcN multiple bond occupies an apical position and the diphosphine and dithiocarbamate ligands span the residual 4 coordination positions on the basal plane through the 2 phosphorus atoms and the 2 sulfur atoms, respectively. Imaging and biodistribution studies demonstrated that these radiopharmaceuticals localize selectively in the myocardium of rats and are retained in this region for a prolonged time. The kinetics of heart uptake and clearance were found to be influenced by variations in the lateral R(1)-R(4) groups. Blood and lung washouts were extremely fast. Elimination occurred mostly through the kidneys and the liver. Surprisingly, at 1 h after injection, liver activity was almost negligible. Analysis of heart-to-liver and heart-to-lung uptake ratios showed that these values increased exponentially over time and became much higher than those determined for (99m)Tc-sestamibi and (99m)Tc-tetrofosmin. These findings were confirmed by analysis of high-quality SPECT images collected in rats for the new complexes and compared with images obtained with (99m)Tc-sestamibi and (99m)Tc-tetrofosmin. CONCLUSION: The high myocardial uptake and the very high heart-to-lung and heart-to-liver uptake ratios indicate that the [(99m)Tc(N)(PNP)(L)](+) complexes exhibit very favorable distribution properties and could be used to obtain SPECT cardiac images with improved quality.

Preparation and first biological evaluation of novel Re-188/Tc-99m peptide conjugates with substance-P.

INTRODUCTION: New (188)Re and (99m)Tc peptide conjugates with substance- P (SP) were prepared and biologically evaluated. The radiopharmaceuticals have been labelled with the [M≡N](2+) (M=(99m)Tc, (188)Re) core using a combination of π-donor tridentate and π-acceptor monodentate ancillary ligands. METHODS: The new radiopharmaceuticals have been prepared through a two-step reaction by simultaneous addition of the tridentate and monodentate ligands to a vial containing a preformed [M≡N](2+) core. The tridentate ligand was formed by linking two cysteine residues to the terminal arginine of the undecapeptide SP, whereas the monodentate ligand was a tertiary phosphine. The preparation of the corresponding Re-188 derivative required developing a more complex chemical procedure to obtain the [Re≡N](2+) core in satisfactory yields. Characterization of the resulting products was obtained by chromatographic methods. Biological evaluation was performed for both Tc-99m and Re-188 derivatives by in-vitro studies on isolated cells expressing NK1-receptors. In-vivo imaging in mice was carried out using a small-animal YAP(S)PET tomograph. CONCLUSION: New Tc-99m and Re-188 peptide radiopharmaceuticals with SP have been prepared in high-yield and with high-specific activity. Both Tc-99m and Re-188 peptide radioconjugates exhibit high affinity for NK1 receptors, thus giving further evidence to the empirical rule that structurally related Tc-99m and Re-188 radiopharmaceuticals exhibit identical biological properties.