Search

Decision support systems for the assisted medical diagnosis offer the main feature of giving assessments which are poorly affected from arbitrary clinical reasoning. Aim of this work was to assess the feasibility of a decision support system for the assisted diagnosis of brain cancer, such approach presenting potential for early diagnosis of tumors and for the classification of the degree of the disease progression. For this purpose, a supervised learning algorithm combined with a pattern recognition method was developed and cross-validated in ¹⁸F-FDG PET studies of a model of a brain tumour implantation.

SPM has been widely used for the operator independent assessment of functional and molecular differences in human PET or MRI brain images. Despite the large diffusion of dedicated image systems and protocols, the use of SPM methodology to preclinical studies have been described in a limited number of studies, particularly for PET. Aim of this work was to optimize and adopt SPM analysis for the identification of patterns of altered metabolism due to acute stress in rat brain using PET with F-18-FDG

Slope instability and erosion, mass transport, volcanic and tectonic activity, fast sediment accumulation fluid escape are the main processes responsible for the geohazard in marine environment. A major knowledge about the geological setting of the offshore areas and related processes can be crucial to assess and manage the potential geological risks. High resolution morphobathymetric surveys, yielded in the frame of the MaGIC project (Marine Geohazards along the Italian Coasts), integrated with previously acquired data, single-channel seismic reflection profiles, backscatter data and sediments sampling, allow to define the geomorphological, stratigraphic and structural features in the offshore sector located in the north-western Sicilian continental margin and in the Ustica offshore (Southern Tyrrhenian). The main goals are: 1) to identify and map the main morphological-structural lineaments of the studied area; 2) to correlate the main structural lineaments on-and offshore; 3) to highlight the instability phenomena of the continental slope, being the area seismically active; 4) to draw up risk maps and to individuate the main dangerous sites; Morphostructural features recognized along the continental shelf to slope system highlighted erosional and depositional morphologies, structural elements at regional and local scale, submerged volcanic edifices, structures related to fluid escape as mud volcanoes and pockmarks. On the basis of the mapping of morphostructural elements and their integration with seismic data and sampling we identified the most likely elements of geological hazard. In the study area we individuated: 1) in the Gulf of Palermo, canyons making the continental slope very rough, also due to the occurrence of widespread mass wasting; 2) between the Gulf of Castellammare and the offshore of the Palermo Mountains, channels and erosional furrows, slumpings, turbiditic fans, landslides, pockmarks and tectonic lineaments; 3) in the offshore of Ustica island, volcanic structures, some of which aligned parallel to tectonic lineaments as Arso fault. The quantitative, GIS analysis allowed a better assessment of the real geohazard. Further investigation on the geological processes, ages of paroxysmal phenomena (eruption, landslides and earthquakes) are necessary to define the most appropriate monitoring strategies in order to assess possible risks for the coastal area and its infrastructures.

MaGIC è un progetto quinquennale (2007-2012) finanziato dal Dipartimento Nazionale della Protezione Civile per l'acquisizione di dati morfobatimetrici ad alta risoluzione. Lo scopo principale del progetto è quello di definire e rappresentare i principali elementi morfologici dei fondali marini, in particolar modo quelli derivanti da dinamiche morfo-sedimentarie che implicano mobilità e/o instabilità dei sedimenti e conseguenti situazioni di pericolosità per le infrastrutture e le aree costiere urbanizzate. I rilievi morfobatimetrici vengono realizzati con un sistema ecoscandaglio radiale multifascio (Multibeam echosounder systems) calibrato ad hoc nell’area di lavoro e corretto in velocità mediante sonda in continuo (SVPC) e profilo verticale della velocità del suono (SVP). I dati batimetrici acquisiti sono inizialmente elaborati e filtrati, attraverso appositi software, e successivamente vengono esportati in maniera tale da poterli interfacciare con altre piattaforme software GIS. Il software Global Mapper è utilizzato per l’interpretazione dei dati e la realizzazione di modelli digitali 3D. Tale software è stato implementato di specifici tools realizzati unicamente per il progetto Magic dalla casa produttrice. Vengono mostrate immagini dei fondali marini del settore centro occidentale del margine continentale nord-siciliano (offshore di Palermo) e delle morfologie sommerse dell’edificio vulcanico dell’Isola di Ustica, che evidenziano le aree a maggiore rischio geologico.

Aim: K-ras proteins have been found mutated in about 35% of human tumors and appear to be an important factor for tumorigenesis. Its expression correlates with metabolic alterations such as increased glycolysis and glutamine consumption. This ability of cancer cells to decouple glucose and glutamine uptake reprogramming their metabolism leads to a more efficient use of nutrients in order to support cell proliferation and represents an interesting target for cancer therapy. Aim of this study is to investigate the metabolic alterations occurring in k-ras transformed fibroblasts combining in vivo and in vitro studies. Materials and methods: nu/nu mice were subcutaneously implanted with 2.5 x 105 k-ras transformed murine NIH3T3 fibroblasts (oncogenic k-ras) or with 2.5 x 105 murine fibroblasts with the dominant negative mutation on GEF protein that attenuates k-ras activation reverting to the wild type phenotype (reverted). Lesions size was constantly monitored with calliper and volumes calculated as (L x l2)/2 mm3. Animals performed [18F]FDG- and [18F]FLTPET studies at several time points starting with a tumor dimension consistent with animal PET spatial resolution (approximately 2mm). Images were calibrated, corrected for isotope half-life and elaborated with PMOD software to calculate Standardized Uptake Value (SUVmax). Finally, animals were sacrificed and tumor collected for metabolomic analysis. Results: All animals injected with oncogenic k-ras fibroblasts develop in few days fast growing, aggressive and highly glycolytic tumors that appear homogeneous for both [18F]FDG and [18F]FLT SUV values. On the contrary, 40% of k-ras reverted animals develop heterogeneous tumors at later time. Among k-ras reverted animals, two distinct tumor phenotypes can be observed: small, slow growing and poor glycolitic tumors with low uptake of both tracers, and small, slow growing but highly glycolytic and proliferating tumors that present SUVmax values comparable to those of k-ras oncogenic tumors. A good correlation, even if not significant, between tumor volume and [18F]FLT SUVmax has been observed for oncogenic k-ras animals. Conclusions:PET imaging is an accurate in vivo technique able to visualize and monitor tumor development in the k-Ras fibroblasts mouse model. K-Ras transformed fibroblasts give rise to aggressive and fast-growing tumors that represent a good model to study the efficacy of cell metabolism based therapy. Finally, K-Ras reverted tumors need further investigations to understand the interaction among tumor microenvironment, metabolic alterations and genetic component that may trigger tumor development.

PURPOSE: This study investigates whether positron emission tomography (PET) can be used to monitor the inflammatory response and its correlation with the later fibroproliferative phase in an experimental model of acute lung injury. METHODS: Hydrochloric acid (0.1 N, pH 1, 1.5 ml/kg) was instilled into the right bronchus of mice. A group of mice underwent a micro-computed tomography (CT) scan 1 h after lung injury and a series of 2-[(18)F]fluorine-2-deoxy-D: -glucose (FDG)-PET scans (6, 24 and 48 h and 7 days after surgery). After 21 days respiratory static compliance was assessed and lung tissue was collected in order to measure the hydroxy (OH)-proline content. Other groups of mice underwent micro-CT and micro-PET scans at the same time points, and then were immediately killed to assess arterial blood gases and histology. RESULTS: Histological analysis showed the recruitment of neutrophils and macrophages into the damaged lung, reaching the peak at 24 and 48 h, respectively. The time course of the [(18)F]FDG signal, used as a marker of inflammation, correlated with that of recruited inflammatory cells. In mice killed 21 days after the surgery, a correlation was found between reduced respiratory static compliance and high PET signal 7 days after lung injury. The PET signal also correlated with the OH-proline content. CONCLUSIONS: This study demonstrated that PET imaging is a valid means of tracking the inflammatory response, also in longitudinal studies. Moreover, a correlation was found between persistence of the inflammatory response and fibrotic evolution of the injury.

Aim: Aim of this study was to evaluate the effect of acute stress on rat brain metabolism using PET [18F]FDG and Foot-Shock (FS) paradigm. Regional stress effect was evaluated both by a statistical voxelbased analysis using a rat-model version of Statistical Parametric Mapping (SPM) optimized in our facility. Materials & Methods: 16 male CD rats, randomly assigned into two groups, 8 rats for Control Group (CG) and 8 rats for Stressed Group (SG), were injected with [18F]FDG in a lateral tail vein. Following the FS protocol, the SG was exposed, immediately after radiotracer injection, to the shock session. One hour after [18F]FDG injection, CG and SG were then subjected to a PET brain study for 30 minutes. All animals have been then sacrificed and corticosterone and circulating glucose were measured. A rat template was created using a control rat, outside of the two groups, who performed, in addition to the PET study, an and MRI study: the PET images for this rat, co-registered to his MRI, was used as [18F]FDG/MRI template. Statistical analysis were performed setting p

Decision support systems for the assisted medical diagnosis offer the main feature of giving assessments which are poorly affected from arbitrary clinical reasoning. Aim of this work was to assess the feasibility of a decision support system for the assisted diagnosis of brain cancer, such approach presenting potential for early diagnosis of tumors and for the classification of the degree of the disease progression. For this purpose, a supervised learning algorithm combined with a pattern recognition method was developed and cross-validated in F-18-FDG PET studies of a model of a brain tumour implantation.

Aging is associated with an exaggerated response to peripheral inflammatory challenges together with behavioral and cognitive deficits. Studies considering both age and sex remain limited, despite sex dimorphism of astrocytes and microglial cells is largely recognized. To fill this knowledge gap, we investigated the effect of a single intraperitoneal lipopolysaccharide (LPS) administration in adult and aged mice. We assessed the expression of different inflammatory mediators, and the microglial response through binding of [18F]-VC701 tracer to translocator protein (TSPO) receptors in the male and female brain. Aged female brain showed a higher pro-inflammatory response to LPS compared to adult female and to aged male, as revealed by ex vivo binding to TSPO receptors and pro-inflammatory mediator transcript levels. The highest astroglial reaction was observed in the brain of aged females. Differently to the other groups of animals, in aged males LPS challenge did not affect transcription of triggering receptor expressed on myeloid cells 2 (TREM2). In conclusion, our study shows that in the mouse's brain the neuro-inflammatory response to an acute peripheral insult is sex- and age-dependent. Moreover, our results might set the basis for further studies aimed at identifying sex-related targets involved in the modulation of the aberrant neuro-inflammatory response that characterizes aging. This knowledge could be relevant for the treatment of conditions such as delirium and dementia.

Mutations in the TREM2 gene confer risk for Alzheimer's disease and susceptibility for Parkinson's disease (PD). We evaluated the effect of TREM2 deletion in a 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine (MPTP)–induced PD mouse model, measuring neurodegeneration and microglia activation using a combined invivo imaging and postmortem molecular approach. In wild-type mice, MPTP administration induced a progressive decrease of [11C]FECIT uptake, culminating at day 7. Neuronal loss was accompanied by an increase of TREM2, IL-1β, and translocator protein (TSPO) transcript levels, [11C]PK11195 binding and GFAP staining (from day 2), and an early and transient increase of TNF-α, Galectin-3, and Iba-1 (from day 1). In TREM2 null (TREM2−/−) mice, MPTP similarly affected neuron viability and microglial cells, as shown by the lower level of Iba-1 staining in basal condition, and reduced increment of Iba-1, TNF-α, and IL-1β in response to MPTP. Likely to compensate for TREM2 absence, TREM2−/− mice showed an earlier increment of [11C]PK11195 binding and a significant increase of IL-4. Taken together, our data demonstrate a central role of TREM2 in the regulation of microglia response to acute neurotoxic insults and suggest a potential modulatory role of TSPO in response to immune system deficit.

In the framework of the Vector National Italian Project (VulCost line), aimed to study the role of the morphology and the geology of the Ionian Calabrian margin in the coastline evolution, an oceanographic cruise was planned to collect geophysical data along two canyon systems: Caulonia and Marina di Gioiosa. The survey explored the continental shelf and slope from a depth of 15 m to more than 1150 m, using Multibeam Echosounder to investigate the seafloor topography. This work provides an outline of the erosive feature of the slope, shaped mostly by seasonal river input and by the connection to the structural and geological characteristics of the margin, made interesting by a narrow shelf and steep slope and influenced by a recent Quaternary tectonic, cause of the crustal regional seismicity. The collected data allowed us to perform a first characterisation of the geo-morphological peculiarities of the study area, constituting the base for the evaluation of the coastal zone evolution.

Brain energy metabolism actively regulates synaptic transmission and activity. We have previously shown that acute footshock (FS)-stress induces fast and long-lasting functional and morphological changes at excitatory synapses in prefrontal cortex (PFC). Here, we asked whether FS-stress increased energy metabolism in PFC, and modified related cognitive functions. Using positron emission tomography (PET), we found that FS-stress induced a redistribution of glucose metabolism in the brain, with relative decrease of [18F]FDG uptake in ventro-caudal regions and increase in dorso-rostral ones. Absolute [18F]FDG uptake was inversely correlated with serum corticosterone. Increased specific hexokinase activity was also measured in purified PFC synaptosomes (but not in total extract) of FS-stressed rats, which positively correlated with 2-Deoxy [3H] glucose uptake by synaptosomes. In line with increased synaptic energy demand, using an electron microscopy-based stereological approach, we found that acute stress induced a redistribution of mitochondria at excitatory synapses, together with an increase in their volume. The fast functional and metabolic activation of PFC induced by acute stress, was accompanied by rapid and sustained alterations of working memory performance in delayed response to T-maze test. Taken together, the present data suggest that acute stress increases energy consumption at PFC synaptic terminals and alters working memory.

Cyclooxygenase-2 (COX-2) is involved in the inflammatory response, and its recurrent overexpression in cancers as well as in neurodegenerative disorders has made it an important target for therapy. For this reason, noninvasive imaging of COX-2 expression may represent an important diagnostic tool. In this work, a COX-2 inhibitor analogue, VA426 [1-(4-fluorophenyl)-3-(2-methoxyethyl)-2-methyl-5-(4-(methylsulfonil)phenyl)-1H-pyrrole], was synthesized and radiolabelled with the 11C radioisotope. The ex vivo biodistribution profile of 11C-VA426 was evaluated in the brain and periphery of healthy rats and mice and in brain and periphery of inflammation models, based on the administration of LPS. 11C-VA426 synthesis with the tBuOK base showed optimal radiochemical yield (15 ± 2%) based on triflate activity, molar activity (range 37–148 GBq/μmol), and radiochemical purity (>95%). Ex vivo biodistribution studies showed a fast uptake of radioactivity but a rapid washout, except in regions expressing COX-2 (lungs, liver, and kidney) both in rats and in mice, with maximum values at 30 and 10 minutes p.i., respectively. LPS administration did not show significant effect on radioactivity accumulation. Celecoxib competition experiments performed in rats and mice treated with LPS produced a general target unrelated reduction of radioactivity concentration in all peripheral tissues and brain areas examined. Finally, in agreement with the negative results obtained from biodistribution experiments, radiometabolites analysis revealed that 11C-VA426 is highly unstable in vivo. This study indicates that the compound 11C-VA426 is not currently suitable to be used as radiopharmaceutical for PET imaging. This family of compounds needs further implementation in order to improve in vivo stability.

BACKGROUND Cardiac arrest is an important cause of morbidity and mortality. Brain injury severity and prognosis of cardiac arrest patients are related to the cerebral areas affected. To this aim, we evaluated the variability and the distribution of brain glucose metabolism after cardiac arrest and resuscitation in an adult rat model. METHODS Ten rats underwent 8-min cardiac arrest, induced with a mixture of potassium and esmolol, and resuscitation, performed with chest compressions and epinephrine. Eight sham animals received anesthesia and experimental procedures identical to the ischemic group except cardiac arrest induction. Brain metabolism was assessed using [(18)F]FDG autoradiography and small animal-dedicated positron emission tomography. RESULTS The absolute glucose metabolism measured with [(18)F]FDG autoradiography 2 h after cardiac arrest and resuscitation was lower in the frontal, parietal, occipital, and temporal cortices of cardiac arrest animals, showing, respectively, a 36% (p = 0.006), 32% (p = 0.016), 36% (p = 0.009), and 32% (p = 0.013) decrease compared to sham group. Striatum, hippocampus, thalamus, brainstem, and cerebellum showed no significant changes. Relative regional metabolism indicated a redistribution of metabolism from cortical area to brainstem and cerebellum. CONCLUSIONS Our data suggest that cerebral regions have different susceptibility to moderate global ischemia in terms of glucose metabolism. The neocortex showed a higher sensibility to hypoxia-ischemia than other regions. Other subcortical regions, in particular brainstem and cerebellum, showed no significant change compared to non-ischemic rats.

Background Positron emission tomography (PET) using translocator protein (TSPO) ligands has been used to detect neuroinflammatory processes in neurological disorders, including multiple sclerosis (MS). The aim of this study was to evaluate neuroinflammation in a mouse MS model (EAE) using TSPO-PET with 18F-VC701, in combination with magnetic resonance imaging (MRI). Methods MOG35-55/CFA and pertussis toxin protocol was used to induce EAE in C57BL/6 mice. Disease progression was monitored daily, whereas MRI evaluation was performed at 1, 2, and 4 weeks post-induction. Microglia activation was assessed in vivo by 18F-VC701 PET at the time of maximum disease score and validated by radioligand ex vivo distribution and immunohistochemistry at 2 and 4 weeks post-immunization. Results In vivo and ex vivo analyses show that 18F-VC701 significantly accumulates within the central nervous system (CNS), particularly in the cortex, striatum, hippocampus, cerebellum, and cervical spinal cord of EAE compared to control mice, at 2 weeks post-immunization. MRI confirmed the presence of focal brain lesions at 2 weeks post-immunization in both T1-weighted and T2 images. Of note, MRI abnormalities attenuated in later post-immunization phase. Neuropathological analysis confirmed the presence of microglial activation in EAE mice, consistent with the in vivo increase of 18F-VC701 uptake. Conclusion Increase of 18F-VC701 uptake in EAE mice is strongly associated with the presence of microglia activation in the acute phase of the disease. The combined use of TSPO-PET and MRI provided complementary evidence on the ongoing disease process, thus representing an attractive new tool to investigate neuronal damage and neuroinflammation at preclinical levels. Electronic supplementary material The online version of this article (10.1186/s12974-017-1044-x) contains supplementary material, which is available to authorized users.