Electron Cyclotron Heating and Suprathermal Electron Dynamics in the TCV Tokamak

This thesis is concerned with the physics of suprathermal electrons in thermonuclear, magnetically confined plasmas. Under a variety of conditions, in laboratory as well as space plasmas, the electron velocity distribution function is not in thermodynamic equilibrium owing to internal or external drives. Accordingly, the distribution function departs from the equilibrium Maxwellian, and in particular generally develops a high-energy tail. In tokamak plasmas, this occurs especially as a result of injection of high-power electromagnetic waves, used for heating and current drive, as well as a result of internal magnetohydrodynamic (MHD) instabilities. The physics of these phenomena is intimately tied to the properties and dynamics of this suprathermal electron population. This motivates the development of instrumental apparatus to measure its properties as well as of numerical codes to simulate their dynamics. Both aspects are reflected in this thesis work, which features advanced instrumental development and experimental measurements as well as numerical modeling. The instrumental development consisted of the complete design of a spectroscopic and tomographic system of four multi-detector hard X-ray (HXR) cameras for the TCV tokamak. The goal is to measure bremsstrahlung emission from suprathermal electrons with energies in the 10-300 keV range, with the ultimate aim of providing the first full tomographic reconstruction at these energies in a noncircular plasma. In particular, suprathermal electrons are generated in TCV by a high-power electron cyclotron heating (ECH) system and are also observed in the presence of MHD events, such as sawtooth oscillations and disruptive instabilities. This diagnostic employs state-of-the-art solid-state detectors and is optimized for the tight space requirements of the TCV ports. It features a novel collimator concept that combines compactness and flexibility as well as full digital acquisition of the photon pulses, greatly enhancing its potential for full spectral analysis in high-fluency scenarios. Additional flexibility is afforded by the possibility to rotate the orientation of two of the cameras, permitting the crucial comparison of radiation emitted perpendicular and parallel to the primary magnetic field. The design of the HXR system was optimized through an extensive iterative simulation process with the aid of tomographic reconstruction codes as well as quasilinear Fokker-Planck modeling of ECH-driven TCV plasmas. In parallel, the selection of the detectors for this system was performed through comprehensive laboratory testing of several candidate detectors available on the market. While the design was completed in the course of the thesis work, commissioning of the system has only commenced recently with one of the four cameras installed on TCV. The first preliminary results, discussed in the last part of this thesis, include basic parameter scans of ECH wave-plasma interaction and the investigation of the dynamic response of suprathermal electrons to modulated ECH. In addition, the cameras possess the novel ability to discriminate against very high-energy γ-ray radiation that cannot be collimated and must thus be excluded from spatial distribution analysis. A basic study of the conditions for γ-ray suppression was conducted in preparation for future experiments. The Fokker-Planck modeling tool used in this diagnostic development was acquired through a collaboration with CEA-Cadarache, initially with the primary motivation of studying the simultaneous plasma heating by 2nd and 3rd harmonic electron cyclotron waves that is uniquely possible on TCV. This motivated a dedicated study, both theoretical and experimental, of one particular instance of this combined heating, which became a second primary subject of this thesis work. The particular scenario studied here is one in which a single ECH frequency is resonant at both harmonics in the same plasma. The primary objective of this study was to determine whether a synergy effect existed, permitting an enhancement of the intrinsically weak 3rd harmonic absorption by the suprathermal electrons generated at the 2nd harmonic resonance. An associated question was whether this effect, if it existed, was experimentally measurable or was in fact observed in TCV. The simulations performed in the course of this study indeed predict the existence of such a synergy, although the answer to the second question was ultimately negative, at least within the current technical limitations. This study has proven nevertheless highly valuable in providing new insight into the complex velocity-space dynamics that govern ECH wave-particle interaction and suprathermal electron dynamics

Medical physicists' implication in radiological diagnostic procedures: results after 1 y of experience

Since January 2008—de facto 2012—medical physics experts (MPEs) are, by law, to be involved in the optimisation process of radiological diagnostic procedures in Switzerland. Computed tomography, fluoroscopy and nuclear medicine imaging units have been assessed for patient exposure and image quality. Large spreads in clinical practice have been observed. For example, the number of scans per abdominal CT examination went from 1 to 9. Fluoroscopy units showed, for the same device settings, dose rate variations up to a factor of 3 to 7. Quantitative image quality for positron emission tomography (PET)/CT examinations varied significantly depending on the local image reconstruction algorithms. Future work will be focused on promoting team cooperation between MPEs, radiologists and radiographers and on implementing task-oriented objective image quality indicator

Suprathermal electron studies in the TCV tokamak: design of a tomographic hard-X-ray spectrometer

Electron cyclotron resonance heating (ECRH) and current drive (ECCD), disruptive events, and sawtooth activity are all known to produce suprathermal electrons in fusion devices, motivating increasingly detailed studies of the generation and dynamics of this suprathermal population. Measurements have been performed in past years in the TCV tokamak using a single pinhole hard-X-ray (HXR) camera and electron-cyclotron-emission (ECE) radiometers, leading in particular to the identification of the crucial role of spatial transport in the physics of ECCD. The observation of a poloidal asymmetry in the emitted suprathermal bremsstrahlung radiation motivates the design of a proposed new tomographic HXR spectrometer, reported in this poster. The design, which is based on a compact, modified Soller collimator concept, is being aided by simulations of tomographic reconstruction. Quantitative criteria have been developed to optimize the design for the greatly variable shapes and positions of TCV plasmas

18^{18}F-PSMA-1007 salivary gland dosimetry: Comparison between different methods for dose calculation and assessment of inter- and intra-patient variability

Dosimetry of salivary glands (SGs) is usually implemented using simplified calculation approaches and approximated geometries. Our aims were to compare different dosimetry methods to calculate SGs absorbed doses (ADs) following 18F-PSMA-1007 injection, and to assess the AD variation across patients and single SG components. Five patients with prostate cancer recurrence underwent PET/CT acquisitions of the head and neck, 0.5, 2 and 4 hours after 18F-PSMA-1007 injection. Parotid and submandibular glands were segmented on CT to derive SGs volumes and masses, while PETs were used to derive Time-Integrated Activity Coefficients. Average ADs to single SG components or total SG (tSG) were calculated with the following methods: i) direct Monte Carlo (MC) simulation with GATE/GEANT4; ii) spherical model (SM) of OLINDA/EXM 2.1, adopting either patient-specific or standard ICRP89 organ masses (SMstd); iii) ellipsoidal model (EM); iv) MIRD approach with organ S-factors from OLINDA/EXM 2.1 and OpenDose collaboration, with or without contribution from cross irradiation originating outside the SGs. The maximum percent AD difference across SG components ({\delta}max) and across patients ({\Delta}max) were calculated. Compared to MC, ADs to single SG components were significantly underestimated by all methods (average relative differences between -14.5% and -30.4%). Using MC, SM and EM, {\delta}max were never below 25% (up to 113%). {\delta}max up to 702% were obtained with SMstd. Concerning tSG, results within 10% of the MC were obtained only if cross irradiation from the remainder of the body or from the remainder of the head was accounted for. The {\Delta}max ranged between 58% and 78% across patients. Specific masses of single SG components should always be considered given their large intra- and inter- patient variability.Comment: 33 pages, 3 figures, sumbitted to "Physics in Medicine & Biology

Preclinical Evaluation and Dosimetry of [111In]CHX-DTPA-scFv78-Fc Targeting Endosialin/Tumor Endothelial Marker 1 (TEM1)

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EANM dosimetry committee recommendations for dosimetry of 177Lu-labelled somatostatin-receptor- and PSMA-targeting ligands

The purpose of the EANM Dosimetry Committee is to provide recommendations and guidance to scientists and clinicians on patient-specific dosimetry. Radiopharmaceuticals labelled with lutetium-177 (177Lu) are increasingly used for therapeutic applications, in particular for the treatment of metastatic neuroendocrine tumours using ligands for somatostatin receptors and prostate adenocarcinoma with small-molecule PSMA-targeting ligands. This paper provides an overview of reported dosimetry data for these therapies and summarises current knowledge about radiation-induced side effects on normal tissues and dose-effect relationships for tumours. Dosimetry methods and data are summarised for kidneys, bone marrow, salivary glands, lacrimal glands, pituitary glands, tumours, and the skin in case of radiopharmaceutical extravasation. Where applicable, taking into account the present status of the field and recent evidence in the literature, guidance is provided. The purpose of these recommendations is to encourage the practice of patient-specific dosimetry in therapy with 177Lu-labelled compounds. The proposed methods should be within the scope of centres offering therapy with 177Lu-labelled ligands for somatostatin receptors or small-molecule PSMA.</p

Phantom-based image quality assessment of clinical 18F-FDG protocols in digital PET/CT and comparison to conventional PMT-based PET/CT

Background We assessed and compared image quality obtained with clinical $^{18}$F-FDG whole-body oncologic PET protocols used in three different, state-of-the-art digital PET/CT and two conventional PMT-based PET/CT devices. Our goal was to evaluate an  improved trade-off between administered activity (patient dose exposure/signal-to-noise ratio) and acquisition time (patient comfort) while preserving diagnostic information achievable with the recently introduced digital detector technology compared to previous analogue PET technology. Methods We performed list-mode (LM) PET acquisitions using a NEMA/IEC NU2 phantom, with activity concentrations of 5 kBq/mL and 25 kBq/mL for the background (9.5 L) and sphere inserts, respectively. For each device, reconstructions were obtained varying the image statistics (10, 30, 60, 90, 120, 180, and 300 s from LM data) and the number of iterations (range 1 to 10) in addition to the employed local clinical protocol setup. We measured for each reconstructed dataset: the quantitative cross-calibration, the image noise on the uniform background assessed by the coefficient of variation (COV), and the recovery coefficients (RCs) evaluated in the hot spheres. Additionally, we compared the characteristic time-activity-product (TAP) that is the product of scan time per bed position × mass-activity administered (in min·MBq/kg) across datasets. Results Good system cross-calibration was obtained for all tested datasets with < 6% deviation from the expected value was observed. For all clinical protocol settings, image noise was compatible with clinical interpretation (COV < 15%). Digital PET showed an improved background signal-to-noise ratio as compared to conventional PMT-based PET. RCs were comparable between digital and PMT-based PET datasets. Compared to PMT-based PET, digital systems provided comparable image quality with lower TAP (from ~ 40% less and up to 70% less). Conclusions This study compared the achievable clinical image quality in three state-of-the-art digital PET/CT devices (from different vendors) as well as in two conventional PMT-based PET. Reported results show that a comparable image quality is achievable with a TAP reduction of ~ 40% in digital PET. This could lead to a significant reduction of the administered mass-activity and/or scan time with direct benefits in terms of dose exposure and patient comfort

Fifty Shades of Scandium: Comparative Study of PET Capabilities Using Sc-43 and Sc-44 with Respect to Conventional Clinical Radionuclides

Scandium-44 has been proposed as a valuable radionuclide for Positron Emission Tomography (PET). Recently, scandium-43 was introduced as a more favorable option, as it does not emit high-energy γ-radiation; however, its currently employed production method results in a mixture of scandium-43 and scandium-44. The interest in new radionuclides for diagnostic nuclear medicine critically depends on the option for image-based quantification. We aimed to evaluate and compare the quantitative capabilities of scandium-43/scandium-44 in a commercial PET/CT device with respect to more conventional clinical radionuclides (fluorine-18 and gallium-68). With this purpose, we characterized and compared quantitative PET data from a mixture of scandium-43/scandium-44 (~68% scandium-43), scandium-44, fluorine-18 and gallium-68, respectively. A NEMA image-quality phantom was filled with the different radionuclides using clinical-relevant lesion-to-background activity concentration ratios; images were acquired in a Siemens Biograph Vision PET/CT. Quantitative accuracy with scandium-43/scandium-44 in the phantom’s background was within 9%, which is in agreement with fluorine-18-based PET standards. Coefficient of variance (COV) was 6.32% and signal recovery in the lesions provided RCmax (recovery coefficient) values of 0.66, 0.90, 1.03, 1.04, 1.12 and 1.11 for lesions of 10-, 13-, 17-, 22-, 28- and 37-mm diameter, respectively. These results are in agreement with EARL reference values for fluorine-18 PET. The results in this work showed that accurate quantitative scandium-43/44 PET/CT is achievable in commercial devices. This may promote the future introduction of scandium-43/44-labelled radiopharmaceuticals into clinical use

EANM procedure guideline for the treatment of liver cancer and liver metastases with intra-arterial radioactive compounds

Abstract: Primary liver tumours (i.e. hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (ICC)) are among the most frequent cancers worldwide. However, only 10–20% of patients are amenable to curative treatment, such as resection or transplant. Liver metastases are most frequently caused by colorectal cancer, which accounts for the second most cancer-related deaths in Europe. In both primary and secondary tumours, radioembolization has been shown to be a safe and effective treatment option. The vast potential of personalized dosimetry has also been shown, resulting in markedly increased response rates and overall survival. In a rapidly evolving therapeutic landscape, the role of radioembolization will be subject to changes. Therefore, the decision for radioembolization should be taken by a multidisciplinary tumour board in accordance with the current clinical guidelines. The purpose of this procedure guideline is to assist the nuclear medicine physician in treating and managing patients undergoing radioembolization treatment. Preamble: The European Association of Nuclear Medicine (EANM) is a professional non-profit medical association that facilitates communication worldwide among individuals pursuing clinical and research excellence in nuclear medicine. The EANM was founded in 1985. These guidelines are intended to assist practitioners in providing appropriate nuclear medicine care for patients. They are notinflexible rules or requirements of practice and are not intended, nor should they be used, to establish a legal standard of care. The ultimate judgment regarding the propriety of any specific procedure or course of action must be made by medical professionals taking into account the unique circumstances of each case. Thus, there is no implication that an approach differing from the guidelines, standing alone, is below the standard of care. To the contrary, a conscientious practitioner may responsibly adopt a course of action different from that set out in the guidelines when, in the reasonable judgment of the practitioner, such course of action is indicated by the condition of the patient, limitations of available resources or advances in knowledge or technology subsequent to publication of the guidelines. The practice of medicine involves not only the science but also the art of dealing with the prevention, diagnosis, alleviation and treatment of disease. The variety and complexity of human conditions make it impossible to always reach the most appropriate diagnosis or topredict with certainty a particular response to treatment. Therefore, it should be recognised that adherence to these guidelines will not ensure an accurate diagnosis or a successful outcome. All that should be expected is that the practitioner will follow a reasonable course of action based on current knowledge, available resources and the needs of the patient to deliver effective and safe medical care. The sole purpose of these guidelines is to assist practitioners in achieving this objective.SCOPUS: ar.jinfo:eu-repo/semantics/publishe