35 results on '"Favaretto, C."'
Search Results
2. Cyclotron production and radiochemical purification of terbium-155 for SPECT imaging
- Author
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Favaretto, C., Talip, Z., Borgna, F., Grundler, P. V., Dellepiane, G., Sommerhalder, A., Zhang, H., Schibli, R., Braccini, S., Müller, C., and van der Meulen, N. P.
- Published
- 2021
- Full Text
- View/download PDF
3. Experimental investigation on non-breaking wave forces and overtopping at the recurved parapets of vertical breakwaters
- Author
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Martinelli, L., Ruol, P., Volpato, M., Favaretto, C., Castellino, M., De Girolamo, P., Franco, L., Romano, A., and Sammarco, P.
- Published
- 2018
- Full Text
- View/download PDF
4. Dynamic Changes in Brain and Body Variables Predict Recovery in Acute Traumatic Brain Injury Coma
- Author
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Monai, E, Favaretto, C, Salvalaggio, A, Munari, M, and Corbetta, M
- Published
- 2020
5. Altered Brain Network Dynamics in Stroke Predict Behavior
- Author
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Favaretto, C, Allegra, M, Brovelli, A, Deco, G, and Corbetta, M
- Published
- 2020
6. Product ion of Carrier Free Copper Nuclides with the ISOL Method for Nuclear Medicine
- Author
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Borgna, F., Ballan, M., Andrighetto, A., Scorradetti, Favaretto, C., Vettorato, E., Manzolaro, M., Monetti, A., Scarpa, D., Rossignoli, M., D’Agostini, F., Turcato, D., Lollo, M., Conventi, D., Pasquato, F., Prete, G., Biasetto, L., Oboe, R., Nicolosi, P., Meneghetti, G., Colombo, P., Realdon, N., Tomaselli, A., Guerzoni, M., Michinelli, R., Margotti, A., Cristofolini, I., Mariotti, E., and Zenoni, M. Ferrari and A.
- Published
- 2018
7. Innovative sand groin beach nourishment with environmental, defense and recreational purposes
- Author
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Ruol, P., LUCA MARTINELLI, Favaretto, C., and Scroccaro, D.
- Subjects
Sand groin ,Nourishment ,X-Beach ,Mechanical Engineering ,Wave basin ,Energy Engineering and Power Technology ,Ocean Engineering - Published
- 2018
8. OVERTOPPING AND STABILITY OF A RUBBLE MOUND BREAKWATER WITH CORELOC ARMOUR UNDER OBLIQUE CYCLONIC WAVES
- Author
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Martinelli, L., primary, Ruol, P., additional, Favaretto, C., additional, and Volpato, M., additional
- Published
- 2018
- Full Text
- View/download PDF
9. Investigation on possible layouts of a catamaran floating breakwater behind a wave energy converter
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Favaretto, C., LUCA MARTINELLI, Ruol, P., and Cortellazzo, G.
- Subjects
Floating breakwater ,Physical model tests ,Power take off ,Wave energy converter ,Wave flume ,Energy Engineering and Power Technology ,Ocean Engineering ,Mechanical Engineering - Published
- 2017
10. Cooling of a Honeycomb Shroud Seal in Order to Reduce Oxidation
- Author
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Davis, A. W., primary, Dawson, A., additional, Bunn, L., additional, Bonaldo, A., additional, Hill, M., additional, Favaretto, C. F., additional, and Backhouse, R., additional
- Published
- 2013
- Full Text
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11. Viscous Layer Meshes from Level Sets on Cartesian Meshes
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Dawes, William, primary, Harvey, Simon, additional, Fellows, S., additional, Favaretto, C., additional, and Velivelli, Aditya, additional
- Published
- 2007
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12. Application of Genetic Algorithms to Design of an Internal Turbine Cooling System
- Author
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Favaretto, C. F. F., primary and Funazaki, K., additional
- Published
- 2003
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13. Effects of Flow Injection From Outer Casing Upon Turbine Nozzle Vane Flow Field
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Funazaki, K., primary, Favaretto, C. F. F., additional, and Tanuma, T., additional
- Published
- 2002
- Full Text
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14. Run up on beaches through simplified shallow water model
- Author
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Favaretto, C., LUCA MARTINELLI, and Ruol, P.
- Subjects
Raster based ,GPU ,Coastal flooding hazard ,Solitary wave ,Run-up
15. Additional file 1 of Cyclotron production and radiochemical purification of terbium-155 for SPECT imaging
- Author
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Favaretto, C., Talip, Z., Borgna, F., Grundler, P. V., Dellepiane, G., Sommerhalder, A., Zhang, H., Schibli, R., Braccini, S., M��ller, C., and van der Meulen, N. P.
- Subjects
3. Good health - Abstract
Additional file 1. Supplementary Material.
16. Planning the Past. Rimini and Forlì in the 1920s: The Replanning of Two Squares in Romagna
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G. Favaretto, C. Mariotti, C.M. Enss, L. Monzo, and G. Favaretto, C. Mariotti
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Revival, 1920s, Rimini, Forlì, Piazza Cavour, Piazza Saffi - Abstract
In the 1920s, the bases of contemporary architecture were being laid in America and in central Europe. Nevertheless, architectural interventions were still closely linked to 19th-century culture. In the Italian region of Emilia-Romagna, this phenomenon can be observed in different historical squares: here, restoration works rediscovered, recovered or reinvented the stylistic features of an idealized past. As a matter of fact, squares were an ideal place to bring about and convey new political and moral contents by using that past, whose supposed meaning proved extremely useful for political propaganda and tourism. In Rimini, the destruction caused by the earthquake of 1916 presented a chance to recover the ‘medieval’ appearance of the Town Hall buildings surrounding Piazza Cavour; in Forlì, the Fascist regime redeveloped the Piazza Saffi in a ‘traditional’ way, reviving a glorious past through the restoration work. Starting from the analysis and comparison of these case studies, this article considers the ideological and pragmatic dynamics that led, between the two World Wars, to the partial transformation of these two city centers in Romagna, and investigates the reasons behind this rewriting of the past as well as the relation between the new buildings and their historical context.
- Published
- 2019
17. First-in-human administration of terbium-161-labelled somatostatin receptor subtype 2 antagonist ([ 161 Tb]Tb-DOTA-LM3) in a patient with a metastatic neuroendocrine tumour of the ileum.
- Author
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Fricke J, Westerbergh F, McDougall L, Favaretto C, Christ E, Nicolas GP, Geistlich S, Borgna F, Fani M, Bernhardt P, van der Meulen NP, Müller C, Schibli R, and Wild D
- Subjects
- Humans, Male, Neoplasm Metastasis, Organometallic Compounds therapeutic use, Radiopharmaceuticals, Aged, Ileal Neoplasms diagnostic imaging, Neuroendocrine Tumors diagnostic imaging, Neuroendocrine Tumors pathology, Receptors, Somatostatin metabolism, Receptors, Somatostatin antagonists & inhibitors
- Published
- 2024
- Full Text
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18. Cross-section measurement of thulium radioisotopes with an 18 MeV medical PET cyclotron for an optimized 165 Er production.
- Author
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Dellepiane G, Casolaro P, Favaretto C, Gottstein A, Grundler PV, Mateu I, Renaldin E, Scampoli P, Talip Z, van der Meulen NP, and Braccini S
- Abstract
165 Er is a pure Auger-electron emitter with promising characteristics for therapeutic applications in nuclear medicine. The short penetration path and high Linear Energy Transfer (LET) of the emitted Auger electrons make165 Er particularly suitable for treating small tumor metastases. Several production methods based on the irradiation with charged particles of Er and Ho targets can be found in the literature. In this paper, we report on the study of165 Er indirect production performed via the166 Er(p,2n)165 Tm →165 Er reaction at the 18 MeV Bern medical cyclotron. Despite the use of highly enriched166 Er2 O3 targets, several Tm radioisotopes are produced during the irradiation, making the knowledge of the cross sections involved crucial. For this reason, a precise investigation of the cross sections of the relevant nuclear reactions in the energy range of interest was performed by irradiating Er2 O3 targets with different isotopic enrichment levels and using a method based on the inversion of a linear system of equations. For the reactions164 Er(p, γ)165 Tm,166 Er(p,n)166 Tm,166 Er(p, γ)167 Tm,167 Er(p,3n)165 Tm,167 Er(p, γ)168 Tm,168 Er(p,2n)167 Tm and170 Er(p,3n)168 Tm, the nuclear cross section was measured for the first time. From the results obtained, the production yield and purity of the parent radioisotope165 Tm were calculated to assess the optimal irradiation conditions. Several production tests with solid targets were performed to confirm these findings., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Saverio Braccini, Zeynep Talip, Nicholas P. van der Meulen reports financial support was provided by Swiss National Science Foundation., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)- Published
- 2023
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19. Pupillary dynamics predict long-term outcome in a cohort of acute traumatic brain injury coma patients.
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Monai E, Favaretto C, Salvalaggio A, Pini L, Munari M, and Corbetta M
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- Humans, Coma etiology, Pupil, Prognosis, Brain Injuries, Traumatic complications, Brain Injuries
- Abstract
Objective: Examining the size and reactivity of the pupils of traumatic brain injury coma patients is fundamental in the Neuro-intensive care unit (ICU). Pupil parameters on admission predict long-term clinical outcomes. However, little is known about the dynamics of pupillary parameters and their potential value for outcome prediction., Methods: This study applied a time-course analysis of pupillary signals (size and photo-reactivity) in acute traumatic brain injury coma patients (n = 20) to predict outcome at 6 months., Results: The time course of pupillary signals was informative in discriminating favorable (F) versus unfavorable (U) outcomes, with the highest correlation within the 1st week notwithstanding pharmacological sedation. Patients with favorable outcome at 6 months showed more consistent in time isochoric and photo-reactive pupils. In contrast, patients with an unfavorable outcome showed more variable measures that tended to stabilize toward pathological values., Interpretation: Time-dependent tracking of pupils' size and reactivity is a promising application for ICU monitoring and long-term prognosis. These findings support the usefulness of automatic tools for the dynamic, quantitative, and objective measurements of pupils., (© 2023 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)
- Published
- 2023
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20. 161 Tb-DOTATOC Production Using a Fully Automated Disposable Cassette System: A First Step Toward the Introduction of 161 Tb into the Clinic.
- Author
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Favaretto C, Grundler PV, Talip Z, Landolt S, Sepini L, Köster U, Müller C, Schibli R, Geistlich S, and van der Meulen NP
- Subjects
- Humans, Isotope Labeling methods, Radioisotopes chemistry, Octreotide, Radiopharmaceuticals chemistry, Neoplasms drug therapy
- Abstract
161 Tb is an interesting radionuclide for application in the treatment of neuroendocrine neoplasms' small metastases and single cancer cells because of its conversion and Auger-electron emission. Tb has coordination chemistry similar to that of Lu; therefore, like177 Lu, it can stably radiolabel DOTATOC, one of the leading peptides used for the treatment of neuroendocrine neoplasms. However,161 Tb is a recently developed radionuclide that has not yet been specified for clinical use. Therefore, the aim of the current work was to characterize and specify161 Tb and to develop a protocol for the synthesis and quality control of161 Tb-DOTATOC with a fully automated process conforming to good-manufacturing-practice guidelines, in view of its clinical use. Methods:161 Tb, produced by neutron irradiation of160 Gd in high-flux reactors followed by radiochemical separation from its target material, was characterized regarding its radionuclidic purity, chemical purity, endotoxin level, and radiochemical purity (RCP) in analogy to what is described in the European Pharmacopoeia for no-carrier-added177 Lu. In addition,161 Tb was introduced into a fully automated cassette-module synthesis to produce161 Tb-DOTATOC, as used for177 Lu-DOTATOC. The quality and stability of the produced radiopharmaceutical in terms of identity, RCP, and ethanol and endotoxin content were assessed by means of high-performance liquid chromatography, gas chromatography, and an endotoxin test, respectively. Results:161 Tb produced under the described conditions showed, as the no-carrier-added177 Lu, a pH of 1-2, radionuclidic purity and RCP of more than 99.9%, and an endotoxin level below the permitted range (175 IU/mL), indicating its appropriate quality for clinical use. In addition, an efficient and robust procedure for the automated production and quality control of161 Tb-DOTATOC with clinically applicable specifications and activity levels, that is, 1.0-7.4 GBq in 20 mL, was developed. The radiopharmaceutical's quality control was also developed using chromatographic methods, which confirmed the product's stability (RCP ≥ 95%) over 24 h. Conclusion: The current study demonstrated that161 Tb has appropriate features for clinical use. The developed synthesis protocol guarantees high yields and safe preparation of injectable161 Tb-DOTATOC. The investigated approach could be translated to other DOTA-derivatized peptides; thus,161 Tb could be successfully applied in clinical practice for radionuclide therapy., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)- Published
- 2023
- Full Text
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21. Activity Measurement of 44 Sc and Calibration of Activity Measurement Instruments on Production Sites and Clinics.
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Juget F, Durán T, Nedjadi Y, Talip Z, Grundler PV, Favaretto C, Casolaro P, Dellepiane G, Braccini S, Bailat C, and van der Meulen NP
- Abstract
44 Sc is a promising radionuclide for positron emission tomography (PET) in nuclear medicine. As a part of the implementation of a production site for44 Sc, precise knowledge of the activity of the product is necessary. At the Paul Scherrer Institute (PSI) and the University of Bern (UniBE),44 Sc is produced by enriched44 CaO-target irradiation with a cyclotron. The two sites use different techniques for activity measurement, namely a dose calibrator at the PSI and a gamma-ray spectrometry system at UniBE and PSI. In this work, the44 Sc was produced at the PSI, and samples of the product were prepared in dedicated containers for onsite measurements at PSI, UniBE, and the Institute of Radiation Physics (IRA) in Lausanne for precise activity measurement using primary techniques and for the calibration of the reference ionization chambers. An accuracy of 1% was obtained for the activity measurement, allowing for a precise calibration of the dose calibrator and gamma-ray spectrometry of the two production sites. Each production site now has the capability of measuring44 Sc activity with an accuracy of 2%.- Published
- 2023
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22. A common low dimensional structure of cognitive impairment in stroke and brain tumors.
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Facchini S, Favaretto C, Castellaro M, Zangrossi A, Zannin M, Bisogno AL, Baro V, Anglani MG, Vallesi A, Baracchini C, D'Avella D, Della Puppa A, Semenza C, and Corbetta M
- Subjects
- Humans, Executive Function, Brain, Memory, Short-Term, Neuropsychological Tests, Magnetic Resonance Imaging, Cognitive Dysfunction etiology, Cognitive Dysfunction complications, Stroke complications, Stroke diagnostic imaging, Stroke pathology, Brain Neoplasms complications, Brain Neoplasms diagnostic imaging, Brain Neoplasms pathology
- Abstract
Introduction: Neuropsychological studies infer brain-behavior relationships from focal lesions like stroke and tumors. However, these pathologies impair brain function through different mechanisms even when they occur at the same brain's location. The aim of this study was to compare the profile of cognitive impairment in patients with brain tumors vs. stroke and examine the correlation with lesion location in each pathology., Methods: Patients with first time stroke (n = 77) or newly diagnosed brain tumors (n = 76) were assessed with a neuropsychological battery. Their lesions were mapped with MRI scans. Test scores were analyzed using principal component analysis (PCA) to measure their correlation, and logistic regression to examine differences between pathologies. Next, with ridge regression we examined whether lesion features (location, volume) were associated with behavioral performance., Results: The PCA showed a similar cognitive impairment profile in tumors and strokes with three principal components (PCs) accounting for about half of the individual variance. PC1 loaded on language, verbal memory, and executive/working memory; PC2 loaded on general performance, visuo-spatial attention and memory, and executive functions; and, PC3 loaded on calculation, reading and visuo-spatial attention. The average lesion distribution was different, and lesion location was correlated with cognitive deficits only in stroke. Logistic regression found language and calculation more affected in stroke, and verbal memory and verbal fluency more affected in tumors., Conclusions: A similar low dimensional set of behavioral impairments was found both in stroke and brain tumors, even though each pathology caused some specific deficits in different domains. The lesion distribution was different for stroke and tumors and correlated with behavioral impairment only in stroke., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2023
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23. Subcortical-cortical dynamical states of the human brain and their breakdown in stroke.
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Favaretto C, Allegra M, Deco G, Metcalf NV, Griffis JC, Shulman GL, Brovelli A, and Corbetta M
- Subjects
- Basal Ganglia pathology, Brain diagnostic imaging, Humans, Magnetic Resonance Imaging methods, Thalamus, Cerebral Cortex pathology, Stroke
- Abstract
The mechanisms controlling dynamical patterns in spontaneous brain activity are poorly understood. Here, we provide evidence that cortical dynamics in the ultra-slow frequency range (<0.01-0.1 Hz) requires intact cortical-subcortical communication. Using functional magnetic resonance imaging (fMRI) at rest, we identify Dynamic Functional States (DFSs), transient but recurrent clusters of cortical and subcortical regions synchronizing at ultra-slow frequencies. We observe that shifts in cortical clusters are temporally coincident with shifts in subcortical clusters, with cortical regions flexibly synchronizing with either limbic regions (hippocampus/amygdala), or subcortical nuclei (thalamus/basal ganglia). Focal lesions induced by stroke, especially those damaging white matter connections between basal ganglia/thalamus and cortex, provoke anomalies in the fraction times, dwell times, and transitions between DFSs, causing a bias toward abnormal network integration. Dynamical anomalies observed 2 weeks after stroke recover in time and contribute to explaining neurological impairment and long-term outcome., (© 2022. The Author(s).)
- Published
- 2022
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24. Chelation of Theranostic Copper Radioisotopes with S-Rich Macrocycles: From Radiolabelling of Copper-64 to In Vivo Investigation.
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Tosato M, Verona M, Favaretto C, Pometti M, Zanoni G, Scopelliti F, Cammarata FP, Morselli L, Talip Z, van der Meulen NP, Di Marco V, and Asti M
- Subjects
- Animals, Chelating Agents, Mice, Mice, Nude, Positron-Emission Tomography methods, Radiopharmaceuticals metabolism, Tissue Distribution, Copper Radioisotopes, Precision Medicine
- Abstract
Copper radioisotopes are generally employed for cancer imaging and therapy when firmly coordinated via a chelating agent coupled to a tumor-seeking vector. However, the biologically triggered Cu
2+ -Cu+ redox switching may constrain the in vivo integrity of the resulting complex, leading to demetallation processes. This unsought pathway is expected to be hindered by chelators bearing N, O, and S donors which appropriately complements the borderline-hard and soft nature of Cu2+ and Cu+ . In this work, the labelling performances of a series of S-rich polyazamacrocyclic chelators with [64 Cu]Cu2+ and the stability of the [64 Cu]Cu-complexes thereof were evaluated. Among the chelators considered, the best results were obtained with 1,7-bis [2-(methylsulfanyl)ethyl]-4,10,diacetic acid-1,4,7,10-tetraazacyclododecane (DO2A2S). DO2A2S was labelled at high molar activities in mild reaction conditions, and its [64 Cu]Cu2+ complex showed excellent integrity in human serum over 24 h. Biodistribution studies in BALB/c nude mice performed with [64 Cu][Cu(DO2A2S)] revealed a behavior similar to other [64 Cu]Cu-labelled cyclen derivatives characterized by high liver and kidney uptake, which could either be ascribed to transchelation phenomena or metabolic processing of the intact complex.- Published
- 2022
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25. Cross section measurement of terbium radioisotopes for an optimized 155 Tb production with an 18 MeV medical PET cyclotron.
- Author
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Dellepiane G, Casolaro P, Favaretto C, Grundler PV, Mateu I, Scampoli P, Talip Z, van der Meulen NP, and Braccini S
- Subjects
- Humans, Positron-Emission Tomography methods, Radioisotopes chemistry, Tomography, Emission-Computed, Single-Photon methods, Cyclotrons, Terbium chemistry
- Abstract
155 Tb [t1/2 = 5.32 d, Eγ = 87 keV (32%); 105 keV (25%) (IAEA, 2021)] is a novel promising radionuclide for theranostic applications in nuclear medicine. Its physical properties make it suitable for single photon emission computed tomography (SPECT) imaging, while its chemistry allows it to be used as a diagnostic partner for therapeutic radiolanthanides or pseudo-radiolanthanides, such as177 Lu and90 Y. Moreover,155 Tb could be used as a precise diagnostic match for the β- -emitter161 Tb, opening doors for the true theranostics concept. The availability of155 Tb in quantity and quality suitable for medical applications is an open issue and its production with medical cyclotrons via the155 Gd(p,n)155 Tb and156 Gd(p,2n)155 Tb nuclear reactions represents a possible but challenging solution. For this purpose, an accurate knowledge of the production cross sections is mandatory. In this paper, we report on the measurement of the production cross sections of155 Tb and other terbium radionuclides formed by proton irradiation ofnat Gd2 O3 ,155 Gd2 O3 and156 Gd2 O3 enriched targets, performed at the Bern University Hospital cyclotron laboratory. On the basis of the obtained results, the production yield and purity were calculated to assess the optimal irradiation conditions. The results of several production tests are also presented., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)- Published
- 2022
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26. Topographical functional correlates of interindividual differences in executive functions in young healthy twins.
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Menardi A, Reineberg AE, Smith LL, Favaretto C, Vallesi A, Banich MT, and Santarnecchi E
- Subjects
- Brain diagnostic imaging, Cognition, Humans, Magnetic Resonance Imaging, Connectome, Executive Function
- Abstract
Executive functions (EF) are a set of higher-order cognitive abilities that enable goal-directed behavior by controlling lower-level operations. In the brain, those functions have been traditionally associated with activity in the Frontoparietal Network, but recent neuroimaging studies have challenged this view in favor of more widespread cortical involvement. In the present study, we aimed to explore whether the network that serves as critical hubs at rest, which we term network reliance, differentiate individuals as a function of their level of EF. Furthermore, we investigated whether such differences are driven by genetic as compared to environmental factors. For this purpose, resting-state functional magnetic resonance imaging data and the behavioral testing of 453 twins from the Colorado Longitudinal Twins Study were analyzed. Separate indices of EF performance were obtained according to a bifactor unity/diversity model, distinguishing between three independent components representing: Common EF, Shifting-specific and Updating-specific abilities. Through an approach of step-wise in silico network lesioning of the individual functional connectome, we show that interindividual differences in EF are associated with different dependencies on neural networks at rest. Furthermore, these patterns show evidence of mild heritability. Such findings add knowledge to the understanding of brain states at rest and their connection with human behavior, and how they might be shaped by genetic influences., (© 2021. The Author(s).)
- Published
- 2022
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27. Inferring the dynamical effects of stroke lesions through whole-brain modeling.
- Author
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Idesis S, Favaretto C, Metcalf NV, Griffis JC, Shulman GL, Corbetta M, and Deco G
- Subjects
- Humans, Nerve Net diagnostic imaging, Brain, Neuroimaging, Magnetic Resonance Imaging, Connectome methods, Stroke
- Abstract
Understanding the effect of focal lesions (stroke) on brain structure-function traditionally relies on behavioral analyses and correlation with neuroimaging data. Here we use structural disconnection maps from individual lesions to derive a causal mechanistic generative whole-brain model able to explain both functional connectivity alterations and behavioral deficits induced by stroke. As compared to other models that use only the local lesion information, the similarity to the empirical fMRI connectivity increases when the widespread structural disconnection information is considered. The presented model classifies behavioral impairment severity with higher accuracy than other types of information (e.g.: functional connectivity). We assessed topological measures that characterize the functional effects of damage. With the obtained results, we were able to understand how network dynamics change emerge, in a nontrivial way, after a stroke injury of the underlying complex brain system. This type of modeling, including structural disconnection information, helps to deepen our understanding of the underlying mechanisms of stroke lesions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2022
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28. A low-dimensional structure of neurological impairment in stroke.
- Author
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Bisogno AL, Favaretto C, Zangrossi A, Monai E, Facchini S, De Pellegrin S, Pini L, Castellaro M, Basile AM, Baracchini C, and Corbetta M
- Abstract
Neurological deficits following stroke are traditionally described as syndromes related to damage of a specific area or vascular territory. Recent studies indicate that, at the population level, post-stroke neurological impairments cluster in three sets of correlated deficits across different behavioural domains. To examine the reproducibility and specificity of this structure, we prospectively studied first-time stroke patients ( n = 237) using a bedside, clinically applicable, neuropsychological assessment and compared the behavioural and anatomical results with those obtained from a different prospective cohort studied with an extensive neuropsychological battery. The behavioural assessment at 1-week post-stroke included the Oxford Cognitive Screen and the National Institutes of Health Stroke Scale. A principal component analysis was used to reduce variables and describe behavioural variance across patients. Lesions were manually segmented on structural scans. The relationship between anatomy and behaviour was analysed using multivariate regression models. Three principal components explained ≈50% of the behavioural variance across subjects. PC1 loaded on language, calculation, praxis, right side neglect and memory deficits; PC2 loaded on left motor, visual and spatial neglect deficits; PC3 loaded on right motor deficits. These components matched those obtained with a more extensive battery. The underlying lesion anatomy was also similar. Neurological deficits following stroke are correlated in a low-dimensional structure of impairment, related neither to the damage of a specific area or vascular territory. Rather they reflect widespread network impairment caused by focal lesions. These factors showed consistency across different populations, neurobehavioural batteries and, most importantly, can be described using a combination of clinically applicable batteries (National Institutes of Health Stroke Scale and Oxford Cognitive Screen). They represent robust behavioural biomarkers for future stroke population studies., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain.)
- Published
- 2021
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29. Multi-band MEG signatures of BOLD connectivity reorganization during visuospatial attention.
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Favaretto C, Spadone S, Sestieri C, Betti V, Cenedese A, Della Penna S, and Corbetta M
- Subjects
- Adult, Brain diagnostic imaging, Female, Humans, Magnetic Resonance Imaging methods, Male, Nerve Net diagnostic imaging, Photic Stimulation methods, Psychomotor Performance physiology, Random Allocation, Visual Perception physiology, Young Adult, Attention physiology, Brain physiology, Magnetoencephalography methods, Nerve Net physiology, Oxygen Consumption physiology, Space Perception physiology
- Abstract
The functional architecture of the resting brain, as measured with the blood oxygenation level-dependent functional connectivity (BOLD-FC), is slightly modified during task performance. In previous work, we reported behaviorally relevant BOLD-FC modulations between visual and dorsal attention regions when subjects performed a visuospatial attention task as compared to central fixation (Spadone et al., 2015). Here we use magnetoencephalography (MEG) in the same group of subjects to identify the electrophysiological correlates of the BOLD-FC modulation found in our previous work. While BOLD-FC topography, separately at rest and during visual attention, corresponded to neuromagnetic Band-Limited Power (BLP) correlation in the alpha and beta bands (8-30 Hz), BOLD-FC modulations evoked by performing the visual attention task (Spadone et al. 2015) did not match any specific oscillatory band BLP modulation. Conversely, following the application of an orthogonal spatial decomposition that identifies common inter-subject co-variations, we found that attention-rest BOLD-FC modulations were recapitulated by multi-spectral BLP-FC components. Notably, individual variability of alpha connectivity between Frontal Eye Fields and visual occipital regions, jointly with decreased interaction in the Visual network, correlated with visual discrimination accuracy. In summary, task-rest BOLD connectivity modulations match multi-spectral MEG BLP connectivity., Competing Interests: Declaration of Competing Interest None, (Copyright © 2021. Published by Elsevier Inc.)
- Published
- 2021
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30. Stroke-related alterations in inter-areal communication.
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Allegra M, Favaretto C, Metcalf N, Corbetta M, and Brovelli A
- Subjects
- Brain diagnostic imaging, Communication, Humans, Magnetic Resonance Imaging, Brain Mapping, Stroke diagnostic imaging
- Abstract
Beyond causing local ischemia and cell damage at the site of injury, stroke strongly affects long-range anatomical connections, perturbing the functional organization of brain networks. Several studies reported functional connectivity abnormalities parallelling both behavioral deficits and functional recovery across different cognitive domains. FC alterations suggest that long-range communication in the brain is altered after stroke. However, standard FC analyses cannot reveal the directionality and time scale of inter-areal information transfer. We used resting-state fMRI and covariance-based Granger causality analysis to quantify network-level information transfer and its alteration in stroke. Two main large-scale anomalies were observed in stroke patients. First, inter-hemispheric information transfer was significantly decreased with respect to healthy controls. Second, stroke caused inter-hemispheric asymmetries, as information transfer within the affected hemisphere and from the affected to the intact hemisphere was significantly reduced. Both anomalies were more prominent in resting-state networks related to attention and language, and they correlated with impaired performance in several behavioral domains. Overall, our findings support the hypothesis that stroke provokes asymmetries between the affected and spared hemisphere, with different functional consequences depending on which hemisphere is lesioned., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
- Full Text
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31. Developments toward the Implementation of 44 Sc Production at a Medical Cyclotron.
- Author
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van der Meulen NP, Hasler R, Talip Z, Grundler PV, Favaretto C, Umbricht CA, Müller C, Dellepiane G, Carzaniga TS, and Braccini S
- Subjects
- Albumins metabolism, Animals, Antigens, Surface, Calcium Compounds chemistry, Cation Exchange Resins chemistry, Equipment Design, Female, Glutamate Carboxypeptidase II, Helium chemistry, Humans, Isotope Labeling methods, Mice, Nude, Neoplasms, Experimental diagnostic imaging, Oxides chemistry, Proof of Concept Study, Radiopharmaceuticals chemistry, Xenograft Model Antitumor Assays, Cyclotrons, Positron-Emission Tomography methods, Radioisotopes chemistry, Scandium chemistry
- Abstract
44 Sc has favorable properties for cancer diagnosis using Positron Emission Tomography (PET) making it a promising candidate for application in nuclear medicine. The implementation of its production with existing compact medical cyclotrons would mean the next essential milestone in the development of this radionuclide. While the production and application of44 Sc has been comprehensively investigated, the development of specific targetry and irradiation methods is of paramount importance. As a result, the target was optimized for the44 Ca(p,n)44 Sc nuclear reaction using CaO instead of CaCO3 , ensuring decrease in target radioactive degassing during irradiation and increased radionuclidic yield. Irradiations were performed at the research cyclotron at the Paul Scherrer Institute (~11 MeV, 50 µA, 90 min) and the medical cyclotron at the University of Bern (~13 MeV, 10 µA, 240 min), with yields varying from 200 MBq to 16 GBq. The development of targetry, chemical separation as well as the practical issues and implications of irradiations, are analyzed and discussed. As a proof-of-concept study, the44 Sc produced at the medical cyclotron was used for a preclinical study using a previously developed albumin-binding prostate-specific membrane antigen (PSMA) ligand. This work demonstrates the feasibility to produce44 Sc with high yields and radionuclidic purity using a medical cyclotron, equipped with a commercial solid target station.- Published
- 2020
- Full Text
- View/download PDF
32. Expanding the Scope of Pyclen-Picolinate Lanthanide Chelates to Potential Theranostic Applications.
- Author
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Nizou G, Favaretto C, Borgna F, Grundler PV, Saffon-Merceron N, Platas-Iglesias C, Fougère O, Rousseaux O, van der Meulen NP, Müller C, Beyler M, and Tripier R
- Subjects
- Ligands, Magnetic Resonance Spectroscopy, Molecular Structure, Azabicyclo Compounds chemistry, Chelating Agents chemistry, Lanthanoid Series Elements chemistry, Picolinic Acids chemistry, Precision Medicine
- Abstract
A family of three picolinate pyclen-based ligands, previously investigated for the complexation of Y
3+ and some lanthanide ions (Gd3+ , Eu3+ ), was studied with161 Tb and177 Lu in view of potential radiotherapeutic applications. The set of six Tb3+ and Lu3+ complexes was synthesized and fully characterized. The coordination properties in the solid state and in solution were thoroughly studied. Potentiometric titrations, supported by density functional theory (DFT) calculations, showed the very high stability constants of the Tb3+ and Lu3+ complexes, associated with remarkable kinetic inertness for up to 30 days in 1 M HCl. A complete radiolabeling study performed with both161 Tb and177 Lu radionuclides, including experiments with regard to the stability with and without scavengers and kinetic inertness using challenging agents, proved that the ligands could reasonably compete with the DOTA analogue. To conclude, the potential of using the same ligand for both radiotherapy and optical imaging was highlighted for the first time.- Published
- 2020
- Full Text
- View/download PDF
33. A Step-by-Step Guide for the Novel Radiometal Production for Medical Applications: Case Studies with 68 Ga, 44 Sc, 177 Lu and 161 Tb.
- Author
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Talip Z, Favaretto C, Geistlich S, and Meulen NPV
- Subjects
- Humans, Gallium Radioisotopes chemistry, Gallium Radioisotopes therapeutic use, Metals, Rare Earth chemistry, Metals, Rare Earth therapeutic use, Positron-Emission Tomography
- Abstract
The production of novel radionuclides is the first step towards the development of new effective radiopharmaceuticals, and the quality thereof directly affects the preclinical and clinical phases. In this review, novel radiometal production for medical applications is briefly elucidated. The production status of the imaging nuclide
44 Sc and the therapeutic β- -emitter nuclide161 Tb are compared to their more established counterparts,68 Ga and177 Lu according to their targetry, irradiation process, radiochemistry, and quality control aspects. The detailed discussion of these significant issues will help towards the future introduction of these promising radionuclides into drug manufacture for clinical application under Good Manufacturing Practice (GMP).- Published
- 2020
- Full Text
- View/download PDF
34. Fragility Limits Performance in Complex Networks.
- Author
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Pasqualetti F, Zhao S, Favaretto C, and Zampieri S
- Abstract
While numerous studies have suggested that large natural, biological, social, and technological networks are fragile, convincing theories are still lacking to explain why natural evolution and human design have failed to optimize networks and avoid fragility. In this paper we provide analytical and numerical evidence that a tradeoff exists in networks with linear dynamics, according to which general measures of robustness and performance are in fact competitive features that cannot be simultaneously optimized. Our findings show that large networks can either be robust to variations of their weights and parameters, or efficient in responding to external stimuli, processing noise, or transmitting information across long distances. As illustrated in our numerical studies, this performance tradeoff seems agnostic to the specific application domain, and in fact it applies to simplified models of ecological, neuronal, and traffic networks.
- Published
- 2020
- Full Text
- View/download PDF
35. Early Evaluation of Copper Radioisotope Production at ISOLPHARM.
- Author
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Borgna F, Ballan M, Favaretto C, Verona M, Tosato M, Caeran M, Corradetti S, Andrighetto A, Di Marco V, Marzaro G, and Realdon N
- Subjects
- Cyclotrons, Hot Temperature, Monte Carlo Method, Radiochemistry instrumentation, Copper Radioisotopes isolation & purification, Radiopharmaceuticals isolation & purification
- Abstract
The ISOLPHARM (ISOL technique for radioPHARMaceuticals) project is dedicated to the development of high purity radiopharmaceuticals exploiting the radionuclides producible with the future Selective Production of Exotic Species (SPES) Isotope Separation On-Line (ISOL) facility at the Legnaro National Laboratories of the Italian National Institute for Nuclear Physics (INFN-LNL). At SPES, a proton beam (up to 70 MeV) extracted from a cyclotron will directly impinge a primary target, where the produced isotopes are released thanks to the high working temperatures (2000 °C), ionized, extracted and accelerated, and finally, after mass separation, only the desired nuclei are collected on a secondary target, free from isotopic contaminants that decrease their specific activity. A case study for such project is the evaluation of the feasibility of the ISOL production of
64 Cu and67 Cu using a zirconium germanide target, currently under development. The producible activities of64 Cu and67 Cu were calculated by means of the Monte Carlo code FLUKA, whereas dedicated off-line tests with stable beams were performed at LNL to evaluate the capability to ionize and recover isotopically pure copper.- Published
- 2018
- Full Text
- View/download PDF
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