Characterization and optimization of a ß detector for 18F radio-guided surgery.

Radio-Guided Surgery (RGS) is a nuclear medicine technique to support the surgeon during surgery towards a complete tumor resection. It is based on intraoperative detection of radiation emitted by a radio-pharmaceutical that bounds selectively to tumoral cells. In the past years, an approach that exploits ß- emitting radiotracers has been pursued to overtake some limitations of the traditional RGS based on γ emission. A particle detector dedicated to this application, demonstrating very high efficiency to ß- particles and remarkable transparency to photons, has been thus developed. As a by-product, its characteristics suggested the possibility to utilize it with ß+ emitting sources, more commonly in use in nuclear medicine. In this paper, performances of such detector on 18F liquid sources are estimated by means of Monte Carlo simulations (MC) and laboratory measurements. The experimental setup with a 18F saline solution comprised a "positron signal" spot (a 7 × 10 mm cylinder representing the tumor residual), and a surrounding "far background" volume, that represented for the detector an almost isotropic source of annihilation photons. Experimental results show good agreement with MC predictions, thus confirming the expected performances of the detector with 18F, and the validity of the developed MC simulation as a tool to predict the gamma background determined by a diffuse source of annihilation photons.

GPU-accelerated Monte Carlo simulation of electron and photon interactions for radiotherapy applications.

Objective. The Monte Carlo simulation software is a valuable tool in radiation therapy, in particular to achieve the needed accuracy in the dose evaluation for the treatment plans optimisation. The current challenge in this field is the time reduction to open the way to many clinical applications for which the computational time is an issue. In this manuscript we present an innovative GPU-accelerated Monte Carlo software for dose valuation in electron and photon based radiotherapy, developed as an update of the FRED (Fast paRticle thErapy Dose evaluator) software.Approach. The code transports particles through a 3D voxel grid, while scoring their energy deposition along their trajectory. The models of electromagnetic interactions in the energy region between 1 MeV-1 GeV available in literature have been implemented to efficiently run on GPUs, allowing to combine a fast tracking while keeping high accuracy in dose assessment. The FRED software has been bench-marked against state-of-art full MC (FLUKA, GEANT4) in the realm of two different radiotherapy applications: Intra-Operative Radio Therapy and Very High Electron Energy radiotherapy applications.Results. The single pencil beam dose-depth profiles in water as well as the dose map computed on non-homogeneous phantom agree with full-MCs at 2% level, observing a gain in processing time from 200 to 5000.Significance. Such performance allows for computing a plan with electron beams in few minutes with an accuracy of ∼%, demonstrating the FRED potential to be adopted for fast plan re-calculation in photon or electron radiotherapy applications.

Tumor-non-tumor discrimination by a ß- detector for Radio Guided Surgery on ex-vivo neuroendocrine tumors samples.

This paper provides a first insight of the potential of the ß- Radio Guided Surgery (ß--RGS) in a complex surgical environment like the abdomen, where multiple sources of background concur to the signal at the tumor site. This case is well reproduced by ex-vivo samples of 90Y-marked Gastro-Entero-Pancreatic Neuroendocrine Tumors (GEP NET) in the bowel. These specimens indeed include at least three wide independent sources of background associated to three anatomical districts (mesentery, intestine, mucose). The study is based on the analysis of 37 lesions found on 5 samples belonging to 5 different patients. We show that the use of electrons, a short range particle, instead of γ particles, allows to limit counts read on a lesion to the sum of the tumor signal plus the background generated by the sole hosting district.The background on adjacent districts in the same specimen/patient is found to differ up to a factor 4, showing how the specificity and sensitivity of the ß--RGS technique can be fully exploited only upon a correct measurement of the contributing background. This locality has been used to set a site-specific cut-off algorithm to discriminate tumor and healthy tissue with a specificity of 100% and a sensitivity, on this test data sample, close to 100%. Factors influencing the sensitivity are also discussed. One of the specimens set allowed us evaluate the volume of the lesions, thus concluding that the probe was able to detect lesions as small as 0.04 mL in that particular case.

Inter-fractional monitoring of [Formula: see text]C ions treatments: results from a clinical trial at the CNAO facility.

The high dose conformity and healthy tissue sparing achievable in Particle Therapy when using C ions calls for safety factors in treatment planning, to prevent the tumor under-dosage related to the possible occurrence of inter-fractional morphological changes during a treatment. This limitation could be overcome by a range monitor, still missing in clinical routine, capable of providing on-line feedback. The Dose Profiler (DP) is a detector developed within the INnovative Solution for In-beam Dosimetry in hadronthErapy (INSIDE) collaboration for the monitoring of carbon ion treatments at the CNAO facility (Centro Nazionale di Adroterapia Oncologica) exploiting the detection of charged secondary fragments that escape from the patient. The DP capability to detect inter-fractional changes is demonstrated by comparing the obtained fragment emission maps in different fractions of the treatments enrolled in the first ever clinical trial of such a monitoring system, performed at CNAO. The case of a CNAO patient that underwent a significant morphological change is presented in detail, focusing on the implications that can be drawn for the achievable inter-fractional monitoring DP sensitivity in real clinical conditions. The results have been cross-checked against a simulation study.

Characterisation of a ß detector on positron emitters for medical applications.

PURPOSE: Radio Guided Surgery (RGS) is a technique that helps the surgeon to achieve an as complete as possible tumor resection, thanks to the intraoperative detection of particles emitted by a radio tracer that bounds to tumoral cells. In the last years, a novel approach to this technique has been proposed that, exploiting ß- emitting radio tracers, overtakes some limitations of established γ-RGS. In this context, a first prototype of an intraoperative ß particle detector, based on a high light yield and low density organic scintillator, has been developed and characterised on pure ß- emitters, like 90Y. The demonstrated very high efficiency to ß- particles, together with the remarkable transparency to photons, suggested the possibility to use this detector also with ß+ emitting sources, that have plenty of applications in nuclear medicine. In this paper, we present upgrades and optimisations performed to the detector to reveal such particles. METHODS: Laboratory measurement have been performed on liquid Ga68 source, and were used to validate and tune a Monte Carlo simulation. RESULTS: The upgraded detector has an ~80% efficiency to electrons above ~110keV, reaching a plateau value of ~95%. At the same time, the probe is substantially transparent to photons below ~200keV, reaching a plateau value of ~3%. CONCLUSIONS: The new prototype seems to have promising characteristics to perform RGS also with ß+ emitting isotopes.

Secondary radiation measurements for particle therapy applications: Charged secondaries produced by 16O ion beams in a PMMA target at large angles.

Particle therapy is a therapy technique that exploits protons or light ions to irradiate tumor targets with high accuracy. Protons and 12C ions are already used for irradiation in clinical routine, while new ions like 4He and 16O are currently being considered. Despite the indisputable physical and biological advantages of such ion beams, the planning of charged particle therapy treatments is challenged by range uncertainties, i.e. the uncertainty on the position of the maximal dose release (Bragg Peak - BP), during the treatment. To ensure correct 'in-treatment' dose deposition, range monitoring techniques, currently missing in light ion treatment techniques, are eagerly needed. The results presented in this manuscript indicate that charged secondary particles, mainly protons, produced by an 16O beam during target irradiation can be considered as candidates for 16O beam range monitoring. Hereafter, we report on the first yield measurements of protons, deuterons and tritons produced in the interaction of an 16O beam impinging on a PMMA target, as a function of detected energy and particle production position. Charged particles were detected at 90° and 60° with respect to incoming beam direction, and homogeneous and heterogeneous PMMA targets were used to probe the sensitivity of the technique to target inhomogeneities. The reported secondary particle yields provide essential information needed to assess the accuracy and resolution achievable in clinical conditions by range monitoring techniques based on secondary charged radiation.

Review and performance of the Dose Profiler, a particle therapy treatments online monitor.

Particle therapy (PT) can exploit heavy ions (such as He, C or O) to enhance the treatment efficacy, profiting from the increased Relative Biological Effectiveness and Oxygen Enhancement Ratio of these projectiles with respect to proton beams. To maximise the gain in tumor control probability a precise online monitoring of the dose release is needed, avoiding unnecessary large safety margins surroundings the tumor volume accounting for possible patient mispositioning or morphological changes with respect to the initial CT scan. The Dose Profiler (DP) detector, presented in this manuscript, is a scintillating fibres tracker of charged secondary particles (mainly protons) that will be operating during the treatment, allowing for an online range monitoring. Such monitoring technique is particularly promising in the context of heavy ions PT, in which the precision achievable by other techniques based on secondary photons detection is limited by the environmental background during the beam delivery. Developed and built at the SBAI department of "La Sapienza", within the INSIDE collaboration and as part of a Centro Fermi flagship project, the DP is a tracker detector specifically designed and planned for clinical applications inside a PT treatment room. The DP operation in clinical like conditions has been tested with the proton and carbon ions beams of Trento proton-therapy center and of the CNAO facility. In this contribution the detector performances are presented, in the context of the carbon ions monitoring clinical trial that is about to start at the CNAO centre.

Chemotherapeutic agents with an imidazole moiety. III. Synthesis and microbiological activity of new 1,4-diarylimidazole and 1,4-pyrrolimidazolphenylene derivatives.

New 1,4-diarylimidazole and 1,4-pyrrolimidazol-phenylene derivatives were prepared in attempt to deepen S.A.R. study on chemotherapeutic agents with an imidazole moiety. Antimicrobial data in comparison with antifungal antibiotic pyrrolnitrin showed that all tested compounds are practically inactive against blastomycetes but some derivatives exhibited selective activity against strains of gram-negative bacteria. The results obtained are discussed on the basis of structure-activity relationships.

[Substances with antibacterial and antifungal activity. VI. Synthesis and microbiologic activity of new derivatives of 1,5-diarylpyrrole and 1,4-pyrrolphenylene]. / Richerche su sostanze ad attività antibatterica ed antifungina. Nota VI--Sintesi ed attività microbiologica di nuovi derivati dell'1,5-diarilpirrolo ed 1,4-pirrolfenilene.

New 1,5-diarylpyrrole and 1,4-pyrrolphenylene derivatives were prepared to study influence on the microbiological activity of an unsubstituted pyrrole nucleus or of a double identical molecular structure. Antimicrobial data in comparision with antifungal antibiotic pyrrolnitrin showed that all tested compounds exhibited very poor antifungal and antibacterial activity. Only some derivatives showed a selective activity against strains of Candida sp. and against strains of gram-positive or gram-negative bacteria.

Research on antibacterial and antifungal agents. XII--Synthesis and antimicrobial activity of some Mannich bases of diarylpyrroles.

The synthesis and antimicrobial activity of some Mannich bases of diarylpyrroles are reported. The obtained data show that activity is closely connected to molecular basicity. Results are discussed on the basis of structure activity relationships.

[Biliary perforations caused by acute pancreatitis: considerations apropos of a case of necrosis of the intrapancreatic choledochus caused by acute cephalopancreatitis secondary to a transduodenal sphincterotomy]. / Perforazioni biliari da pancreatite acuta: considerazioni a proposito di un caso di necrosi del coledoco intrapancreatico da cefalopancreatite acuta secondaria a sfinterotomia transduodenale.

The AA. refear a case of massive necrosis of intrapancreatic biliary tract secondary to an acute necrotizing postoperative cephalopancreatitis. The high mortality lesion risk was successfully treated by many factors: surgicals and medicals. The AA. think that the wise use of Somatostatine was the most important factor.

[Immune protection against rubella in a group of women in Latium]. / Sulla protezione immunitaria contro la rosolia in un gruppo di donne del Lazio.

This paper reports data concerning the immune status of 252 pregnant women with regard to rubella infection. The inverse haemagglutination was used to titrate rubella virus-antibodies and it was carried out for each pregnant woman on two blood samples, collected at three weeks' interval. Thirty-nine of the 252 pregnant women (15.50%) contracted the infection in the first trimester of pregnancy. Fifty-seven women (22.60%) showed a low degree of protection against the infection while only forty-five women had a protective rubella virus-antibody titre. Finally, 111 of the 252 (44.60%) pregnant women were rubella virus seronegative and therefore susceptible to the infection.

[Up-date on the epidemiology of rheumatic diseases]. / Aggiornamento epidemiologico sulla malattia reumatica.

The present study is an up-date on rheumatic fever for the last ten years. The disease has erroneously been considered to have largely or completely disappeared whereas epidemiological data show it to be still prevalent especially in the developing countries. However, in the industrialized countries, too, its prevalence is by no means negligible; e.g. in the US the last ten years have witnessed an alarming recrudescence involving vast strata of the population and especially children, although this is masked by the paucity of reports, as is the case also in Italy. Chemoprophylaxis is then discussed. This is highly successful, especially if applied at an early stage, and finally therapy is described in great detail.

[Legionellosis]. / Le legionellosi.

In the above review, the authors intended to stress the epidemiologic importance of legionellosis which has become a frequent cause of respiratory pathology in the short time since its first appearance (1976), reaching a for from negligible proportion among respiratory disorders (2-8% of acute bronchopulmonary diseases) and a considerable death rate (10-40%). Clinical and diagnostic as well as therapeutic aspects and especially prophylaxis all discussed, the latter concerning above all the environment and adequate maintenance of heating and air-conditioning equipment in community centers, and particularly in hospitals and hotels.

[Yersiniosis]. / Le yersinosi.

The authors' objective in the above review was to stress the epidemiological importance of Yersinia enterocolitica infections. They therefore detail the clinical and epidemiologic features of acute or primary as well as of secondary forms and complications of Yersinia enterocolitica infections. Further, they dwell on the management of these infections and illustrate the properties, toxic effects and other side effects of the antibiotics commonly used in therapy and for the prevention of complications. Finally, they take stock of the regulations to be applied for the prevention of this complex and multifaceted infection.