Sharing brain imaging data in the Open Science era:how and why?

The sharing of human neuroimaging data has great potential to accelerate the development of imaging biomarkers in neurological and psychiatric disorders; however, major obstacles remain in terms of how and why to share data in the Open Science context. In this Health Policy by the European Cluster for Imaging Biomarkers, we outline the current main opportunities and challenges based on the results of an online survey disseminated among senior scientists in the field. Although the scientific community fully recognises the importance of data sharing, technical, legal, and motivational aspects often prevent active adoption. Therefore, we provide practical advice on how to overcome the technical barriers. We also call for a harmonised application of the General Data Protection Regulation across EU countries. Finally, we suggest the development of a system that makes data count by recognising the generation and sharing of data as a highly valuable contribution to the community.</p

Hybrid imaging in pediatric central nervous system disorders

Modern neuroimaging techniques represent an essential tool in the evaluation of pediatric central nervous system disorders. The use of magnetic resonance imaging (MRI) has led to an enormous increase in our comprehensive knowledge of several pathological entities and currently represents the gold standard method because of its uniquely detailed tissue contrast differentiation and lack of invasiveness

Time-dependent recovery of brain hypometabolism in neuro-COVID-19 patients

Purpose: We evaluated brain metabolic dysfunctions and associations with neurological and biological parameters in acute, subacute and chronic COVID-19 phases to provide deeper insights into the pathophysiology of the disease. Methods: Twenty-six patients with neurological symptoms (neuro-COVID-19) and [18F]FDG-PET were included. Seven patients were acute (< 1 month (m) after onset), 12 subacute (4 ≥ 1-m, 4 ≥ 2-m and 4 ≥ 3-m) and 7 with neuro-post-COVID-19 (3 ≥ 5-m and 4 ≥ 7–9-m). One patient was evaluated longitudinally (acute and 5-m). Brain hypo- and hypermetabolism were analysed at single-subject and group levels. Correlations between severity/extent of brain hypo- and hypermetabolism and biological (oxygen saturation and C-reactive protein) and clinical variables (global cognition and Body Mass Index) were assessed. Results: The “fronto-insular cortex” emerged as the hypometabolic hallmark of neuro-COVID-19. Acute patients showed the most severe hypometabolism affecting several cortical regions. Three-m and 5-m patients showed a progressive reduction of hypometabolism, with limited frontal clusters. After 7–9 months, no brain hypometabolism was detected. The patient evaluated longitudinally showed a diffuse brain hypometabolism in the acute phase, almost recovered after 5 months. Brain hypometabolism correlated with cognitive dysfunction, low blood saturation and high inflammatory status. Hypermetabolism in the brainstem, cerebellum, hippocampus and amygdala persisted over time and correlated with inflammation status. Conclusion: Synergistic effects of systemic virus-mediated inflammation and transient hypoxia yield a dysfunction of the fronto-insular cortex, a signature of CNS involvement in neuro-COVID-19. This brain dysfunction is likely to be transient and almost reversible. The long-lasting brain hypermetabolism seems to reflect persistent inflammation processes

Fundamental Role of Pentose Phosphate Pathway within the Endoplasmic Reticulum in Glutamine Addiction of Triple-Negative Breast Cancer Cells

Cancer utilization of large glutamine equivalents contributes to diverging glucose-6-P flux toward the pentose phosphate shunt (PPP) to feed the building blocks and the antioxidant responses of rapidly proliferating cells. In addition to the well-acknowledged cytosolic pathway, cancer cells also run a largely independent PPP, triggered by hexose-6P-dehydrogenase within the endoplasmic reticulum (ER), whose activity is mandatory for the integrity of ER–mitochondria networking. To verify whether this reticular metabolism is dependent on glutamine levels, we complemented the metabolomic characterization of intermediates of the glucose metabolism and tricarboxylic acid cycle with the estimation of proliferating activity, energy metabolism, redox damage, and mitochondrial function in two breast cancer cell lines. ER-PPP activity and its determinants were estimated by the ER accumulation of glucose analogs. Glutamine shortage decreased the proliferation rate despite increased ATP and NADH levels. It depleted NADPH reductive power and increased malondialdehyde content despite a marked increase in glucose-6P-dehydrogenase. This paradox was explained by the deceleration of ER-PPP favored by the decrease in hexose-6P-dehydrogenase expression coupled with the opposite response of its competitor enzyme glucose-6P-phosphatase. The decreased ER-PPP activity eventually hampered mitochondrial function and calcium exchanges. These data configure the ER-PPP as a powerful, unrecognized regulator of cancer cell metabolism and proliferation

Prevention of systemic toxicity in hyperthermic isolated lung perfusion using radioisotopic leakage monitoring

Hyperthermic isolated lung Perfusion (ILuP) is used to deliver high-dose chemotherapy to pulmonary metastases while sparing systemic toxicity. Accurate leakage monitoring is however necessary. This study aimed to verify the accuracy of radionuclide leakage monitoring in patients undergoing ILuP, by comparing this method with serial blood sampling. METHODS: A total of 15 consecutive ILuP procedures were performed on eleven patients affected by lung metastases from soft tissue sarcoma. After establishing isolated perfusion, erythrocytes of systemic blood (SB) were labelled with 0.2 MBq/kg of 99mTc. The baseline SB counting rate (CR) was assessed using a \u3b3-probe. Subsequently, erythrocytes of the circuit blood (CB) were labelled with 2 Mbq/kg of 99mTc. Radioactivity leakage factor (RLF) was continuously measured using a formula, accounting for CR, systemic/circuit activity ratio and total/systemic volume ratio. The TNF-\u3b1 concentration in SB and CB was measured by enzymelinked immunosorbent assay (ELISA) throughout the procedure. RESULTS: RLF averaged 2.3\u2009\ub1\u20091.5%, while the systemic/circuit TNF-\u3b1 ratio was 0.05\u2009\ub1\u20090.12%. These two indices were strictly correlated in all of the procedures (average Rvalue 0.88\u2009\ub1\u20090.07). RLF exceeded 5% during three of 15 procedures, prompting the application of compensatory manoeuvres. ELISA confirmed a marked increase in systemic TNF-\u3b1 levels in these patients (2.6\u2009\ub1\u20093.5\u2009ng/ml). Conversely, patients whose RLF did not exceed the 5% threshold presented a mean TNF-\u3b1 of 0.02\u2009\ub1\u20090.005\u2009ng/ml (p\u2009&lt;\u20090.01). CONCLUSIONS: In patients submitted to ILuP, RLF monitoring is feasible and accurate. Moreover, it grants immediate results, permitting for the adoption of corrective manoeuvres for leakage, thus minimising toxicity

Prognostic power of the human psoas muscles FDG metabolism in amyotrophic lateral sclerosis

In Amyotrophic Lateral Sclerosis (ALS) spinal cord (SC) showed a moderate increase in FDG uptake with respect to healthy subjects. The main aim of our study is to integrate the information concerning the divergent behavior of SC with skeletal muscle metabolism improving the informative potential of 18F-fluoro-2-deoxy-glucose (FDG) PET/CT imaging regarding specific pathophysiological mechanisms underlying ALS progression. We analyzed 50 ALS patients with spinal onset consecutively submitted to FDG PET/CT imaging. Obtained data were compared to the corresponding findings in 36 age and sex-matched controls. A computational method was used to extract psoas volume and attenuation coefficient from CT images. Psoas volume was normalized for patient ideal body weight (IBW). In co-registered PET images, FDG accumulation was defined by average normalized standardized uptake value (N-SUV). Average Hounsfield values (AVH) in the psoas were similar in patients and controls (39\ub18 AHV vs 39\ub111 AHV, respectively, p=ns). By contrast, ALS was associated with a significant reduction in psoas volume normalized for IBW (8.8\ub12.9 mL/Kg IBW vs 10.3\ub12.7 mL/Kg IBW, respectively, p&lt;0.05). More interestingly, N-SUV was significantly higher in patients than in controls (0.44\ub10.19 vs 0.29\ub10.09; p&lt;0.001). These SUV values predicted overall survival rate at Kaplan-Meyer analysis (p&lt;0.05) with a predictive power that was confirmed by univariate as well as by multivariate Cox analysis (p&lt;0.02). ALS is therefore associated with a psoas reduction in volume and increase in FDG uptake. The intensity of FDG uptake within this muscular district is related to disease aggressiveness

The fate of patients with REM sleep behavior disorder and Mild Cognitive Impairment

Abstract Objective: To investigate clinical and dopaminergic pre-synaptic brain imaging characteristics of subjects with idiopathic rapid eye movement (REM) behavior disorder (iRBD) and mild cognitive impairment (MCI), and to evaluate the combined predictive value of risk factors for short-term conversion to synucleinopathy. Method: In sum, 44 polysomnography (PSG)-confirmed iRBD patients (68.5\ub17.2 years; 38 males) underwent 123I-FP-CIT-SPECT, comprehensive neuropsychological evaluation, clinical examination and clinical follow-up every six months (30.6\ub121.5 months). Step-wise logistic regression was applied to identify those features discriminating iRBD patients with (iRBD-MCI; n=14) and without MCI (normal cognition, iRBD-NC; n=30). The risk of neurodegeneration was estimated with Kaplan-Meier analysis. Predictors of phenoconversion were assessed with Cox proportional-hazards analysis, adjusting for age, gender and education. A generalized linear model (GLM) was applied to define the best combination of risk factors predicting conversion at followup. Results: At baseline, patients with iRBD-MCI showed reduced striatal dopamine transporter (DAT) specific to non-displaceable binding ratio (SBR) and more constipation compared with iRBD-NC patients (p&lt;0.0001). During the follow-up, 10 patients (22.7%) develop an overt synucleinopathy. GLM analysis showed that patients with orthostatic hypotension, non-motor experiences of daily living, reduced putaminal DAT-SPECT SBR, and cognitive impairment in verbal memory/visuoconstruction abilities were at higher risk of phenoconversion (Hazard Ratio 26.05; Sensitivity 90%; Specificity 100%; Accuracy 97.73%; Positive Predictive Value 100%; Negative Predictive Value 97.14%). Conclusions. iRBD-MCI patients showed a more severe dopaminergic neuroimaging and clinical phenotype. Combining clinical and neuroimaging markers allowed to achieve excellent ability in identifying iRBD patients at high risk of developing a synucleinopathy within about three years from diagnosis