Intracranial Sonodynamic Therapy With 5-Aminolevulinic Acid and Sodium Fluorescein: Safety Study in a Porcine Model

BackgroundSonodynamic therapy (SDT) is an emerging ultrasound-based treatment modality for malignant gliomas which combines ultrasound with sonosensitizers to produce a localized cytotoxic and modulatory effect. Tumor-specificity of the treatment is achieved by the selective extravasation and accumulation of sonosensitizers in the tumor-bearing regions. The aim of this study is to demonstrate the safety of low-intensity ultrasonic irradiation of healthy brain tissue after the administration of FDA-approved sonosensitizers used for SDT in experimental studies in an in vivo large animal model.MethodsIn vivo safety of fluorescein (Na-Fl)- and 5 aminolevulinic acid (5-ALA)-mediated low-intensity ultrasound irradiation of healthy brain parenchyma was assessed in two sets of four healthy swine brains, using the magnetic resonance imaging (MRI)-guided Insightec ExAblate 4000 220 kHz system. After administration of the sonosensitizers, a wide fronto-parietal craniotomy was performed in pig skulls to allow transmission of ultrasonic beams. Sonication was performed on different spots within the thalamus and periventricular white matter with continuous thermal monitoring. Sonication-related effects were investigated with MRI and histological analysis.ResultsPost-treatment MRI images acquired within one hour following the last sonication, on day one, and day seven did not visualize any sign of brain damage. On histopathology, no signs of necrosis or apoptosis attributable to the ultrasonic treatments were shown in target areas.ConclusionsThe results of the present study suggest that either Na-FL or 5-ALA-mediated sonodynamic therapies under MRI-guidance with the current acoustic parameters are safe towards healthy brain tissue in a large in vivo model. These results further support growing interest in clinical translation of sonodynamic therapy for intracranial gliomas and other brain tumors

Broadband Multi-wavelength Properties of M87 during the 2017 Event Horizon Telescope Campaign

Abstract: In 2017, the Event Horizon Telescope (EHT) Collaboration succeeded in capturing the first direct image of the center of the M87 galaxy. The asymmetric ring morphology and size are consistent with theoretical expectations for a weakly accreting supermassive black hole of mass ∼6.5 × 109 M ⊙. The EHTC also partnered with several international facilities in space and on the ground, to arrange an extensive, quasi-simultaneous multi-wavelength campaign. This Letter presents the results and analysis of this campaign, as well as the multi-wavelength data as a legacy data repository. We captured M87 in a historically low state, and the core flux dominates over HST-1 at high energies, making it possible to combine core flux constraints with the more spatially precise very long baseline interferometry data. We present the most complete simultaneous multi-wavelength spectrum of the active nucleus to date, and discuss the complexity and caveats of combining data from different spatial scales into one broadband spectrum. We apply two heuristic, isotropic leptonic single-zone models to provide insight into the basic source properties, but conclude that a structured jet is necessary to explain M87’s spectrum. We can exclude that the simultaneous γ-ray emission is produced via inverse Compton emission in the same region producing the EHT mm-band emission, and further conclude that the γ-rays can only be produced in the inner jets (inward of HST-1) if there are strongly particle-dominated regions. Direct synchrotron emission from accelerated protons and secondaries cannot yet be excluded

Sonodynamic Therapy for the Treatment of Intracranial Gliomas

High-grade gliomas are the most common and aggressive malignant primary brain tumors. Current therapeutic schemes include a combination of surgical resection, radiotherapy and chemotherapy; even if major advances have been achieved in Progression Free Survival and Overall Survival for patients harboring high-grade gliomas, prognosis still remains poor; hence, new therapeutic options for malignant gliomas are currently researched. Sonodynamic Therapy (SDT) has proven to be a promising treatment combining the effects of low-intensity ultrasound waves with various sound-sensitive compounds, whose activation leads to increased immunogenicity of tumor cells, increased apoptotic rates and decreased angiogenetic potential. In addition, this therapeutic technique only exerts its cytotoxic effects on tumor cells, while both ultrasound waves and sensitizing compound are non-toxic per se. This review summarizes the present knowledge regarding mechanisms of action of SDT and currently available sonosensitizers and focuses on the preclinical and clinical studies that have investigated its efficacy on malignant gliomas. To date, preclinical studies implying various sonosensitizers and different treatment protocols all seem to confirm the anti-tumoral properties of SDT, while first clinical trials will soon start recruiting patients. Accordingly, it is crucial to conduct further investigations regarding the clinical applications of SDT as a therapeutic option in the management of intracranial gliomas

Urban Forms of Life. Per una critica delle forme di vita urbana

Che forme assume la vita nei contesti urbani? Da che deriva la loro presunta, attuale «illeggibilità»? Che cosa impedisce il fiorire di forme di vita appaganti, degne, vitali? È possibile rendere visibile e articolabile l’«elemento» urbano in cui siamo immersi? Quali esperimenti tentare per risvegliare un nuovo senso (comune) di vita urbana? Che ruolo pos- sono assumere le forme di vita urbana nei confronti del contesto più ampio, umano e non-umano, da cui dipendono sotto molteplici aspetti? Quali opportunità e quali insidie si prospettano con l’inarrestabile penetrazione delle nuove tecnologie digitali e di intelligenza artificiale nel tessuto urbano? A partire da queste e altre domande è nato nel 2017 un progetto di ricerca in filosofia, presentato all’Ateneo della Sapienza – Università di Roma, che lo ha finanziato e di cui questo libro è uno dei risultati, insieme a una serie di incontri e seminari, a partire da quello tenutosi presso il Centre Marc Bloch di Berlino nel settembre del 2018What forms does life take in urban contexts? Where does their sup- posed, current “unreadability” come from? What prevents the flour- ishing of fulfilling, worthy, vital forms of life? Is it possible to make visible and articulable the urban “element” in which we are immersed? What experiments should be attempted to awaken a new (common) sense of urban life? What role can urban forms of life assume vis-à- vis the larger human and non-human context on which they depend in multiple respects? What opportunities and pitfalls lie ahead with the unstoppable penetration of new digital and artificial intelligence technologies into the urban fabric? Starting from these and other ques- tions, a research project in philosophy was presented to the Sapienza - University of Rome in 2017, of which this book is one of the results, along with a series of meetings and seminars, starting with the one held at the Marc Bloch Centre in Berlin in September 201