A compact scintillator-based detector with collimator and shielding for dose monitoring in boron neutron capture therapy.

Boron neutron capture therapy exploits 10B(n,α)7Li reactions for targeted tumor destruction. In this work, we aimed at developing a dose monitoring system based on the detection of 478 keV gamma rays emitted by the reactions, which is very challenging due to the severe background present. We investigated a compact gamma-ray detector with a pinhole collimator and shielding housing. Experimental nuclear reactor measurements involved varying boron concentrations and artificial shifts of the sources. The system successfully resolved the 478 keV photopeak and detected 1 cm lateral displacements, confirming its suitability for precise boron dose monitoring.

First experimental demonstration of real-time neutron capture discrimination in helium and carbon ion therapy.

This work provides the first experimental proof of an increased neutron capture photon signal following the introduction of boron to a PMMA phantom during helium and carbon ion therapies in Neutron Capture Enhanced Particle Therapy (NCEPT). NCEPT leverages [Formula: see text]B neutron capture, leading to the emission of detectable 478 keV photons. Experiments were performed at the Heavy Ion Medical Accelerator in Chiba, Japan, with two Poly(methyl methacrylate) (PMMA) targets, one bearing a boron insert. The BeNEdiCTE gamma-ray detector measured an increase in the 478 keV signal of 45 ± 7% and 26 ± 2% for carbon and helium ion irradiation, respectively. Our Geant4 Monte Carlo simulation model, developed to investigate photon origins, found less than 30% of detected photons originated from the insert, while boron in the detector's circuit boards contributed over 65%. Further, the model investigated detector sensitivity, establishing its capability to record a 10% increase in 478 keV photon detection at a target [Formula: see text]B concentration of 500 ppm using spectral windowing alone, and 25% when combined with temporal windowing. The linear response extended to concentrations up to 20,000 ppm. The increase in the signal in all evaluated cases confirm the potential of the proposed detector design for neutron capture quantification in NCEPT.

Potentialities of CdZnTe Quasi-Hemispherical Detectors for Hard X-ray Spectroscopy of Kaonic Atoms at the DAΦNE Collider.

Kaonic atom X-ray spectroscopy is a consolidated technique for investigations on the physics of strong kaon-nucleus/nucleon interaction. Several experiments have been conducted regarding the measurement of soft X-ray emission (<20 keV) from light kaonic atoms (hydrogen, deuterium, and helium). Currently, there have been new research activities within the framework of the SIDDHARTA-2 experiment and EXCALIBUR proposal focusing on performing precise and accurate measurements of hard X-rays (>20 keV) from intermediate kaonic atoms (carbon, aluminum, and sulfur). In this context, we investigated cadmium-zinc-telluride (CdZnTe or CZT) detectors, which have recently demonstrated high-resolution capabilities for hard X-ray and gamma-ray detection. A demonstrator prototype based on a new cadmium-zinc-telluride quasi-hemispherical detector and custom digital pulse processing electronics was developed. The detector covered a detection area of 1 cm2 with a single readout channel and interesting room-temperature performance with energy resolution of 4.4% (2.6 keV), 3% (3.7 keV), and 1.4% (9.3 keV) FWHM at 59.5, 122.1, and 662 keV, respectively. The results from X-ray measurements at the DAΦNE collider at the INFN National Laboratories of Frascati (Italy) are also presented with particular attention to the effects and rejection of electromagnetic and hadronic background.

A 64k pixel CMOS-DEPFET module for the soft X-rays DSSC imager operating at MHz-frame rates.

The 64k pixel DEPFET module is the key sensitive component of the DEPFET Sensor with Signal Compression (DSSC), a large area 2D hybrid detector for capturing and measuring soft X-rays at the European XFEL. The final 1-megapixel camera has to detect photons with energies between [Formula: see text] and [Formula: see text], and must provide a peak frame rate of [Formula: see text] to cope with the unique bunch structure of the European XFEL. This work summarizes the functionalities and properties of the first modules assembled with full-format CMOS-DEPFET arrays, featuring [Formula: see text] hexagonally-shaped pixels with a side length of 136 µm. The pixel sensors utilize the DEPFET technology to realize an extremely low input capacitance for excellent energy resolution and, at the same time, an intrinsic capability of signal compression without any gain switching. Each pixel of the readout ASIC includes a DEPFET-bias current cancellation circuitry, a trapezoidal-shaping filter, a 9-bit ADC and a 800-word long digital memory. The trimming, calibration and final characterization were performed in a laboratory test-bench at DESY. All detector features are assessed at [Formula: see text]. An outstanding equivalent noise charge of [Formula: see text]e-rms is achieved at 1.1-MHz frame rate and gain of 26.8 Analog-to-Digital Unit per keV ([Formula: see text]). At [Formula: see text] and [Formula: see text], a noise of [Formula: see text] e-rms and a dynamic range of [Formula: see text] are obtained. The highest dynamic range of [Formula: see text] is reached at [Formula: see text] and [Formula: see text]. These values can fulfill the specification of the DSSC project.

Photon-shot-noise-limited transient absorption soft X-ray spectroscopy at the European XFEL.

Femtosecond transient soft X-ray absorption spectroscopy (XAS) is a very promising technique that can be employed at X-ray free-electron lasers (FELs) to investigate out-of-equilibrium dynamics for material and energy research. Here, a dedicated setup for soft X-rays available at the Spectroscopy and Coherent Scattering (SCS) instrument at the European X-ray Free-Electron Laser (European XFEL) is presented. It consists of a beam-splitting off-axis zone plate (BOZ) used in transmission to create three copies of the incoming beam, which are used to measure the transmitted intensity through the excited and unexcited sample, as well as to monitor the incoming intensity. Since these three intensity signals are detected shot by shot and simultaneously, this setup allows normalized shot-by-shot analysis of the transmission. For photon detection, an imaging detector capable of recording up to 800 images at 4.5 MHz frame rate during the FEL burst is employed, and allows a photon-shot-noise-limited sensitivity to be approached. The setup and its capabilities are reviewed as well as the online and offline analysis tools provided to users.

Prompt-gamma fall-off estimation with C-ion irradiation at clinical energies, using a knife-edge slit camera: A Monte Carlo study.

PURPOSE: In-vivo range verification has been a hot topic in particle therapy since two decades. Many efforts have been done for proton therapy, while fewer studies were conducted considering a beam of carbon ions. In the present work, a simulation study was performed to show whether it is possible to measure the prompt-gamma fall-off inside the high neutron background typical of carbon-ion irradiation, using a knife-edge slit camera. In addition to this, we wanted to estimate the uncertainty in retrieving the particle range in the case of a pencil beam of C-ions at clinically relevant energy of 150 MeVu. METHODS: For these purposes, the Monte Carlo code FLUKA was adopted for simulations and three different analytical methods were implemented to get the accuracy in the range retrieval of the simulated set-up. RESULTS: The analysis of simulation data has brought to the promising and desired precision of about 4 mm in the determination of the dose profile fall-off in case of a spill irradiation, for which all the three cited methods were coherent in their predictions. CONCLUSIONS: The Prompt Gamma Imaging technique should be further studied as a tool to reduce range uncertainties affecting carbon ion radiation therapy.

Detection and discrimination of neutron capture events for NCEPT dose quantification.

Neutron Capture Enhanced Particle Therapy (NCEPT) boosts the effectiveness of particle therapy by capturing thermal neutrons produced by beam-target nuclear interactions in and around the treatment site, using tumour-specific [Formula: see text]B or [Formula: see text]Gd-based neutron capture agents. Neutron captures release high-LET secondary particles together with gamma photons with energies of 478 keV or one of several energies up to 7.94 MeV, for [Formula: see text]B and [Formula: see text]Gd, respectively. A key requirement for NCEPT's translation is the development of in vivo dosimetry techniques which can measure both the direct ion dose and the dose due to neutron capture. In this work, we report signatures which can be used to discriminate between photons resulting from neutron capture and those originating from other processes. A Geant4 Monte Carlo simulation study into timing and energy thresholds for discrimination of prompt gamma photons resulting from thermal neutron capture during NCEPT was conducted. Three simulated [Formula: see text] mm[Formula: see text] cubic PMMA targets were irradiated by [Formula: see text]He or [Formula: see text]C ion beams with a spread out Bragg peak (SOBP) depth range of 60 mm; one target is homogeneous while the others include [Formula: see text] mm[Formula: see text] neutron capture inserts (NCIs) of pure [Formula: see text]B or [Formula: see text]Gd located at the distal edge of the SOBP. The arrival times of photons and neutrons entering a simulated [Formula: see text] mm[Formula: see text] ideal detector were recorded. A temporal mask of 50-60 ns was found to be optimal for maximising the discrimination of the photons resulting from the neutron capture by boron and gadolinium. A range of candidate detector and thermal neutron shielding materials were simulated, and detections meeting the proposed acceptance criteria (i.e. falling within the target energy window and arriving 60 ns post beam-off) were classified as true or false positives, depending on their origin. The ratio of true/false positives ([Formula: see text]) was calculated; for targets with [Formula: see text]B and [Formula: see text]Gd NCIs, the detector materials which resulted in the highest [Formula: see text] were cadmium-shielded CdTe and boron-shielded LSO, respectively. The optimal irradiation period for both carbon and helium ions was 1 µs for the [Formula: see text]B NCI and 1 ms for the [Formula: see text]Gd NCI.

Handheld Magnetic-Compliant Gamma-Ray Spectrometer for Environmental Monitoring and Scrap Metal Screening.

Spotting radioactive material in waste is of paramount importance for environment protection. This is particularly challenging when orphan sources are hidden in scrap metal that shields their activity from the traditional detectors in the portals scanning incoming trucks. In order to address this issue, we present a wireless and compact SiPM-based gamma spectrometer compatible with strong magnetic fields (0.1 T) to be installed in the bore of the lifting electromagnets to scan reduced volumes of metal and thus achieve higher sensitivity. The microcontroller-based instrument provides 11% energy resolution (at 662 keV), an energy range from 60 keV to 1.5 MeV, a max. count rate of 30 kcps, a weight <1 kg, and a power consumption <1 W. The results of its extensive characterization in the laboratory and its validation in the field, including operation in a scrap yard as well as on a drone, are reported.

Miniaturized USB-powered multi-channel module for gamma spectroscopy and imaging.

LAILA is a miniaturized eight-channel electronic readout system for compact γ-ray detectors, combining high-resolution spectroscopy capability with position sensitivity. Compactness is achieved by the combination of a novel CMOS front-end ASIC (Application-Specific Integrated Circuit) for analog processing of a large signal current from Silicon PhotoMultiplier (SiPM) solid-state photodetectors, with a microcontroller-based data acquisition system. The adoption of automatic gain regulation in the gated-integrator stage of the ASIC offers an 84 dB dynamic range, combining single-photon sensitivity with an extended input photon energy range (20 keV-4 MeV, using 30 µm-cell SiPMs). Using this module with properly merged 144 SiPM pixels coupled to a 3 in.-thick lanthanum bromide scintillation crystal, a 3% energy resolution at 662 keV and 1 cm spatial resolution in the estimation of the interaction coordinates are experimentally demonstrated in this work.

VIP-2 -High-Sensitivity Tests on the Pauli Exclusion Principle for Electrons.

The VIP collaboration is performing high sensitivity tests of the Pauli Exclusion Principle for electrons in the extremely low cosmic background environment of the underground Gran Sasso National Laboratory INFN (Italy). In particular, the VIP-2 Open Systems experiment was conceived to put strong constraints on those Pauli Exclusion Principle violation models which respect the so-called Messiah-Greenberg superselection rule. The experimental technique consists of introducing a direct current in a copper conductor, and searching for the X-rays emission coming from a forbidden atomic transition from the L shell to the K shell of copper when the K shell is already occupied by two electrons. The analysis of the first three months of collected data (in 2018) is presented. The obtained result represents the best bound on the Pauli Exclusion Principle violation probability which fulfills the Messiah-Greenberg rule.

Challenges for Microelectronics in Non-Invasive Medical Diagnostics.

Microelectronics is emerging, sometimes with changing fortunes, as a key enabling technology in diagnostics. This paper reviews some recent results and technical challenges which still need to be addressed in terms of the design of CMOS analog application specific integrated circuits (ASICs) and their integration in the surrounding systems, in order to consolidate this technological paradigm. Open issues are discussed from two, apparently distant but complementary, points of view: micro-analytical devices, combining microfluidics with affinity bio-sensing, and gamma cameras for simultaneous multi-modal imaging, namely scintigraphy and magnetic resonance imaging (MRI). The role of integrated circuits is central in both application domains. In portable analytical platforms, ASICs offer miniaturization and tackle the noise/power dissipation trade-off. The integration of CMOS chips with microfluidics poses multiple open technological issues. In multi-modal imaging, now that the compatibility of the acquisition chains (thousands of Silicon Photo-Multipliers channels) of gamma detectors with Tesla-level magnetic fields has been demonstrated, other development directions, enabled by microelectronics, can be envisioned in particular for single-photon emission tomography (SPECT): a faster and simplified operation, for instance, to allow transportable applications (bed-side) and hardware pre-processing that reduces the number of output signals and the image reconstruction time.

Development of clinical simultaneous SPECT/MRI.

There is increasing clinical use of combined positron emission tomography and MRI, but to date there has been no clinical system developed capable of simultaneous single-photon emission computed tomography (SPECT) and MRI. There has been development of preclinical systems, but there are several challenges faced by researchers who are developing a clinical prototype including the need for the system to be compact and stationary with MRI-compatible components. The limited work in this area is described with specific reference to the Integrated SPECT/MRI for Enhanced stratification in Radio-chemo Therapy (INSERT) project, which is at an advanced stage of developing a clinical prototype. Issues of SPECT/MRI compatibility are outlined and the clinical appeal of such a system is discussed, especially in the management of brain tumour treatment.

Experimental Comparison of Knife-Edge and Multi-Parallel Slit Collimators for Prompt Gamma Imaging of Proton Pencil Beams.

More and more camera concepts are being investigated to try and seize the opportunity of instantaneous range verification of proton therapy treatments offered by prompt gammas emitted along the proton tracks. Focusing on one-dimensional imaging with a passive collimator, the present study experimentally compared in combination with the first, clinically compatible, dedicated camera device the performances of instances of the two main options: a knife-edge slit (KES) and a multi-parallel slit (MPS) design. These two options were experimentally assessed in this specific context as they were previously demonstrated through analytical and numerical studies to allow similar performances in terms of Bragg peak retrieval precision and spatial resolution in a general context. Both collimators were prototyped according to the conclusions of Monte Carlo optimization studies under constraints of equal weight (40 mm tungsten alloy equivalent thickness) and of the specificities of the camera device under consideration (in particular 4 mm segmentation along beam axis and no time-of-flight discrimination, both of which less favorable to the MPS performance than to the KES one). Acquisitions of proton pencil beams of 100, 160, and 230 MeV in a PMMA target revealed that, in order to reach a given level of statistical precision on Bragg peak depth retrieval, the KES collimator requires only half the dose the present MPS collimator needs, making the KES collimator a preferred option for a compact camera device aimed at imaging only the Bragg peak position. On the other hand, the present MPS collimator proves more effective at retrieving the entrance of the beam in the target in the context of an extended camera device aimed at imaging the whole proton track within the patient.

First clinical application of a prompt gamma based in vivo proton range verification system.

BACKGROUND AND PURPOSE: To improve precision of particle therapy, in vivo range verification is highly desirable. Methods based on prompt gamma rays emitted during treatment seem promising but have not yet been applied clinically. Here we report on the worldwide first clinical application of prompt gamma imaging (PGI) based range verification. MATERIAL AND METHODS: A prototype of a knife-edge shaped slit camera was used to measure the prompt gamma ray depth distribution during a proton treatment of a head and neck tumor for seven consecutive fractions. Inter-fractional variations of the prompt gamma profile were evaluated. For three fractions, in-room control CTs were acquired and evaluated for dose relevant changes. RESULTS: The measurement of PGI profiles during proton treatment was successful. Based on the PGI information, inter-fractional global range variations were in the range of ±2 mm for all evaluated fractions. This is in agreement with the control CT evaluation showing negligible range variations of about 1.5mm. CONCLUSIONS: For the first time, range verification based on prompt gamma imaging was applied for a clinical proton treatment. With the translation from basic physics experiments into clinical operation, the potential to improve the precision of particle therapy with this technique has increased considerably.

In vivo imaging of lymph node migration of MNP- and (111)In-labeled dendritic cells in a transgenic mouse model of breast cancer (MMTV-Ras).

PURPOSE: The authors present a protocol for the in vivo evaluation, using different imaging techniques, of lymph node (LN) homing of tumor-specific dendritic cells (DCs) in a murine breast cancer model. PROCEDURES: Bone marrow DCs were labeled with paramagnetic nanoparticles (MNPs) or (111)In-oxine. Antigen loading was performed using tumor lysate. Mature DCs were injected into the footpads of transgenic tumor-bearing mice (MMTV-Ras) and DC migration was tracked by magnetic resonance imaging (MRI) and single-photon emission computed tomography (SPECT). Ex vivo analyses were performed to validate the imaging data. RESULTS: DC labeling, both with MNPs and with (111)In-oxine, did not affect DC phenotype or functionality. MRI and SPECT allowed the detection of iron and (111)In in both axillary and popliteal LNs. Immunohistochemistry and γ-counting revealed the presence of DCs in LNs. CONCLUSIONS: MRI and SPECT imaging, by allowing in vivo dynamic monitoring of DC migration, could further the development and optimization of efficient anti-cancer vaccines.