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There is a present and future need for the medical isotope Actinium-225, currently in short supply worldwide.  Only a couple manufacturers produce it in very low quantities.  In roughly the past 10 years the medical community has explored the use of Ac-225 and its daughter Bismuth-213 for targeting a number of differing cancers by way of Targeted Alpha Therapy (TAT). This method utilizes the alpha-decay of both Ac-225 (half-life 10 days) and Bi-213 (half-life 46 min) to kill cancerous cells on a localized basis.  Maximum energy is delivered to the cancer cells thereby greatly minimizing healthy tissue damage. This research proposes a production method using a high-energy photon spectrum (generated by a linear accelerator or LINAC) to irradiate a sample of Radium-226 (half-life 1600yrs).  The photo-neutron reaction liberates neutrons from Ra-226 atoms leaving behind Radium-225 (half-life 14.7 days).  Ra-225 decays naturally through beta emission to Ac-225.  Previous research demonstrated it is possible to produce Ac-225 using a LINAC; however, very low yields resulted which questioned the feasibility of this production method.  This research proposes a number of LINAC and radium sample modifications that could be greatly increase yield amounts for practical use. Additionally, photo-neutron cross-section data for Ra-226 was used, which led to improved yield calculations for Ra-225.  A MATLAB® model was also created, which enables users to perform quick yield estimates given several key model parameter inputs.  Obtaining a sufficient supply of radium material is also of critical importance to this research.  Therefore information was gathered regarding availability and inventory of Radium-226.  This production method would serve as a way to not only eliminate many hazardous radium sources destined for interim storage, but provide a substantial supply of Ac-225 for future cancer treatment. / Master of Science

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The aim of the project was to compare the workflow for an Elekta Linac with and without the surfacescanning system Catalyst and describe pros and cons with both workflows. The findings in the reportcan be used as decision support in development of Elekta products and workflow improvements. The method for the project was to do interviews, observations and time measurements at Södersjukhuset(not using Catalyst) and Sundsvalls sjukhus (using Catalyst). The workflows were graded in an as-sessment protocol covering time efficiency, comfort, noise, resources, reliability, cost, dosage and sideeffects. Different workflow scenarios were simulated in AnyLogic. The result of the project was that, according to our protocol, the workflow with Catalyst was ratedhigher than without it. The simulations in Anylogic showed that minimizing gaps in the treatment sched-ule generated the same number of patients treated per day, if the positioning could not be done faster.The simulations also showed that removing position verification with cone beam computer tomography(CBCT), an imaging system which is used in addition to the Catalyst system, would increase the numberof treated patients with approximately 33%. The conclusion was that there were no great differences in time efficiency between the workflows. How-ever, considering the higher reliability and comfort for the patient, optical surface scanning can improvethe positioning for Elekta Linac and is therefore worth implementing. Minimizing treatment gaps wouldnot improve the workflow. Removing the use of CBCT would increase the number of treated patientsper day.

Aujourd'hui, les Lasers à Electrons Libres (LELs) en simple passage permettent d'étudier la structure de la matière dans le domaine de la femtoseconde. Cependant, le rayonnement produit, l'émission spontanée auto-amplifiée (SASE), bien que hautement brillante, possède une cohérence longitudinale partielle ; les profils temporel et spectral sont composés d'une série de pics, appelés « spikes », et présentent d'importantes fluctuations statistiques. Nous démontrons ici la forte amplification cohérente de la 5ème harmonique d'un laser Ti: Sa (800 nm, 10 Hz, 100 fs) générée dans une cellule de gaz, i.e. 160 nm, puis injectée dans un LEL. Ce phénomène spectaculaire s'accompagne de la génération d'Harmoniques Non Linéaires LELs (HNL) intenses et cohérentes à 54 nm et 32 nm. L'expérience a été réalisée sur le prototype de l'accélérateur SCSS (source SASE compacte de SPring-8, Japon). Cette installation est principalement constituée d'un canon à électrons à cathode thermo-ionique, d'un LINAC et d'un onduleur sous vide (2 sections de 4,5 m de long), au niveau duquel la source externe harmonique est superposée transversalement, spectralement et temporellement avec le faisceau d'électrons (150 MeV, 10 Hz, 1 ps). Avec une seule section d'onduleur, le rayonnement à 160 nm en mode injecté atteint une intensité de trois ordres de grandeur supérieure à celle obtenue sans injection, et présente une distribution spectrale quasi-Gaussienne. De plus, la longueur de saturation du LEL est deux fois plus courte. Vu le faible niveau d'injection requis, une telle amplification couplée à des schémas HNL permettrait de générer des rayonnements X-mous totalement cohérents jusqu'à la « fenêtre de l'eau ».

Radiation-induced damage to the genomic DNA of cells may lead to errors in transcription and replication and, if not repaired correctly, these may result in mutations, genomic instability and cell death. Laser microbeams have generally been used by many research groups to investigate the real-time dynamics of protein recruitment in response to DNA insults in mammalian cells; however, such irradiations induce a plethora of DNA damage (including UV base damage, base damage, SSBs and DSBs and complex damage). A novel experimental setup has been designed capable of following the dynamics of protein recruitment in response to DNA insults in mammalian cells shortly following submicrosecond- pulsed electron irradiation of living mammalian cells, not possible using conventional irradiation techniques. This arrangement was developed based on a 6 MeV electron pulse linear accelerator, to deliver sparsely ionising radiation, coupled to an automated, time-lapse inverted epifluorescence microscope imaging system. An integrated robotic system contained within a physiological environment of 37°C and 5% CO₂ was used to transfer remotely and repetitively custom-designed cell dishes containing the mammalian cells between irradiation and imaging locations. Following the development of the linear accelerator and associated imaging devices, preliminary ‘proof-of-principle’ investigations were carried out using living HT1080 mammalian cells containing YFP-tagged 53BP1, an established biomarker of DSB, to follow the recruitment and loss of 53BP1 to sites of radiation-induced DNA damage in real-time. This novel experimental setup has allowed for the first time observations of the appearance and disappearance of radiation-induced foci in the same cell population at very early times. These single-foci studies have provided evidence for the formation of not only promptly formed DSBs but also late appearing DNA damage signalled by 53BP1. These data highlight different classes of DSBs formed in response radiation damage. Additionally, the role of cell cycle on the repair kinetics was undertaken using HT1080- 53BP1-YFP cells which also express Geminin-mCherry under appropriate selection. Geminin is increasingly expressed from early S-phase onwards, but is degraded following mitosis. Geminin-associated fluorescence can be used as a marker of progression through the cell cycle. 53BP1 repair kinetics were characterised in response to radiation damage in combination with ATM and PARP inhibitors. These studies provided supporting evidence for the existence of different classes of DSBs, potentially assigned to radiation-induced replication breaks and DSBs formed by enzymatic conversion of clustered damage. These preliminary ‘proof-of-principle’ findings using DNA damage repair as an example, emphasize the use of this novel technology to explore the dynamics of numerous other biochemical processes in living cells in real-time with the knowledge of being able to quantify the range of damage induced by IR coupled with accurate dosimetry. The knowledge obtained may be used to identify potential biological targets coupled with drug discovery for translation into adjuncts for radiotherapy.

La diffusion Compton inverse est l’interaction entre un photon et un électron de haute énergie. Il en résulte l’émission d’un nouveau photon d’énergie supérieure à celle du photon incident suivant la trajectoire de l’électron. Ces propriétés rendent possible la création d’une source de rayonnement X hautement directive, monochromatique accordable dans une large gamme spectrale. Il suffit d’accélérer les électrons sur quelques mètres pour leur faire gagner l’énergie minimale requise. Les photons proviennent d’une chaîne laser fortement amplifiée. Une telle source est donc relativement compacte, peu couteuse à mettre en oeuvre et facilement accessible aux utilisateurs. Elle est particulièrement adaptée aux besoins des musées ou des hôpitaux pour des applications comme l’analyse d’oeuvres historiques ou la radiothérapie. L’objectif de cette thèse est de mettre en oeuvre une source de rayonnement X par diffusion Compton inverse en bout de ligne de l’accélérateur ELSA (Electrons et Laser, Sources X et applications). L’installation ELSA comprend un accélérateur linéaire d’électrons appartenant à la Direction des Applications Militaires du Commissariat à l’Energie Atomique à Bruyères-le-Châtel (CEA DAM). Le but est de produire des impulsions de rayonnement X ultra-courtes dans une gamme énergétique allant de 10 à 100 keV. Elle servira notamment à la caractérisation de détecteurs à réponse ultra-rapide développés à la DAM. Un système optique destiné à augmenter le flux de rayonnement X produit a été développé. Il consiste à replier la trajectoire du laser pour empiler les impulsions au point d’interaction. Dans le même but, une mise à niveau de l’installation à été réalisée afin d’augmenter l’énergie des électrons de 18 à 30 MeV. Les résultats expérimentaux ont enfin été comparés aux résultats obtenus à l’aide de simulations PIC 3D. / X-ray sources based on inverse Compton scattering process produce tunable near-monochromatic and highly directive X-rays. Recent advances in laser and accelerator technologies make the development of such very compact hard X-ray sources possible. These sources are particularly attractive in several applications such as medical imaging, cancer therapy or culture-heritage study, currently performed in size-limited infrastructures. The main objective of this thesis is the development of an inverse Compton scattering source on the ELSA linac of CEA at Bruyères-le-Châtel as a calibration tool for ultra-fast detectors.A non-resonant cavity was designed to multiply the number of emitted X-ray photons. The laser optical path is folded to pile-up laser pulses at the interaction point, thus increasing the interaction probability. Another way of optimizing the X-ray yield consists in increasing the electron bunch density at the interaction point, which is strongly dependent on the electron energy. A facility up-grade was performed to increase the electron energy up to 30 MeV. The X-ray output gain obtained thanks to this system was measured and compared with calculated expectations and 3D PIC simulations.

The department of Radiation Sciences at Umeå University has obtained an old linear accelerator, intended for educational purposes. The goal of this thesis was to find proper reinforced radiation protection in an intended bunker (a room with thick concrete walls), to ensure that the radiation outside the bunker falls within acceptable levels. The main method was with the use of Monte Carlo-simulations. To properly simulate the accelerator, knowledge of the energy distribution of emitted radiation was needed. For this, a novel method for spectra determination, using several depth dose measurements including off-axis, was developed. A method that shows promising results in finding the spectra when measurements outside the primary beam are included. The found energy spectrum was then used to simulate the accelerator in the intended bunker. The resulting dose distribution was visualized together with 3D CAD-images of the bunker, to easily see in which locations outside the bunker where the dose was high. An important finding was that some changes are required to ensure that the public does not receive too high doses of radiation on a public outdoor-area that is located above the bunker. Otherwise, the accelerator is only allowed to be run 1.8 hours per year. A workaround to this problem could be to just plant a thorn bush, covering the dangerous area of radius 3m. After such a measure has been taken, which is assumed in the following results, the focus moves to the radiation that leaks into the accelerator’s intended control room, which is located right outside the bunker’s entrance door. The results show that the accelerator is only allowed to be run for a maximum of 6.1 or 3.3 hours per year (depending on the placement of the accelerator in the room), without a specific extra reinforced radiation protection consisting mainly of lead bricks. With the specific extra protection added, the accelerator is allowed to be run 44 or 54 hours per year instead, showing a distinct improvement. However, the dose rate to the control room was still quite high, 13.7 μGy/h or 11.2 μGy/h, compared to the average dose received by someone living in Sweden, which is 0.27 μGy/h. Therefore, further measures are recommended. This is however a worst case scenario, since the leakage spectrum from the accelerator itself was simulated as having the same energy spectrum as the primarybeam at 0.1 % of the intensity, which is the maximum leakage dose according to the specifications for the accelerator. This is probably an overestimation of the intensity. Also, the energy spectra of the leakage is probably of lower energy than the primary beam in at least some directions. Implementing more knowledge of the leak spectra in future work, should therefore result in more allowed run hours for the accelerator.

Helmholtz Zentrum Berlin (HZB) baut seit 2011 eine Testanlage Energy Recovery Linac (ERL) Project – BERLinPro. Das Ziel dieses Projektes ist den hohen Strom und hohe Brillanz von dem Elektronenstrahl in einem ERL zu demonstrieren. Die angestrebten Strahlparameter sind vergleichbar mit den Parametern von e.g. zukünftigen ERL-basierten Lichtquellen. Eine von solchen Anlagen ist Femto-Science Factory (FSF), die am HZB konzipiert wurde. FSF ist eine Lichtquelle in Röntgenbereich auf Basis von einem mehrumläufigen ERL mit zweistüfiger Injektion und Energie von einigen GeV. Die Quelle soll Diffraktionslimitiert sein und kurze (Femtosekundenbereich) Lichtpulse erzeugen. Die durchschnittliche und spitzen- Brillanz soll mindesten eine Größenordnung höher liegen als die Brillanz der modernen Speicherring-basierten Lichtquellen. Ein Überblick von BERLinPro und FSF ist gegeben. Eine potentielle Schwäche von ERL besteht in Strahlinstabilitäten, insbesondere regenerative Beam Break Up (BBU). Die Instabilität kann den erreichbaren durchschnittlichen Strom in einem ERL begrenzen. Der Grenzstrom von der BBU für BERLinPro ist berechnet in der Dissertation. Vergleich von zwei Linacs mit zwei verschiedenen supraleitenden Kavitätendesigns ist vorgestellt. Drei Methoden für Strahlstabilisierung (Einfluss von Strahlrotation mit einem Soleniod, Pseudoreflektor, und Tripleten von Quadrupolen in dem Linac auf den Grenzstrom) sind untersucht. Analytische Lösungen für die Twiss-Parameter wurden gefunden für die beste Linacoptik mit und ohne zusätzliche optische Elemente. Zukünftige große ERLs können unterschiedliche Beschleunigungsschemen benutzen. Diese Dissertation vergleicht drei Schemas: unmittelbare Injektion in einen 6 GeV Linac; zweistufige Injektion in einen 6 GeV Linac; und zweistufige Injektion in einen mehrumläufigen Beschleuniger mit geteiltem Hauptlinac in zwei 1 GeV Linacs. Der Basis für den Vergleich ist die Vollkostenanalyse sowie erreichbarer Grenzstrom von den Instabilitäten. / In January 2011 Helmholtz-Zentrum Berlin officially started the realization of the Berlin Energy Recovery Linac (ERL) Project – BERLinPro. The goal of this compact ERL is to develop the accelerator physics and technology required to accelerate a high-current (100 mA) low emittance beam. The parameters are desired for future large scale facilities based on ERLs, e.g. ERL-based synchrotron light sources. One of such large scale facilities is in the design phase at Helmholtz-Zentrum Berlin. This facility is called Femto-Science Factory (FSF). It is a GeV-scale multi-turn ERL-based light source. This light source will operate in the diffraction limited regime for X-rays and offer a short length of a light pulse in the femtosecond region. The average and peak brightness will be at least an order of magnitude higher than achievable from storage rings. In this work an overview of these two projects is given. One potential weakness of the Energy Recovery Linacs is a regenerative form of BBU – transverse beam break up instability. This instability can limit a beam current. In this work the threshold current of the BBU instability was calculated for BERLinPro. The comparison of two linacs based on different types of superconducting cavities is made. Different methods of BBU suppression are investigated (e.g. the influence of solenoid, pseudo-reflector and quadruple triplets in the linac structure on the BBU threshold). Analytic solutions of the Twiss parameters are used to find the best optic in the linac with and without external focusing are presented. Large scale ERL facilities can be realized on different schemes of beam acceleration. This dissertation compares a direct injection scheme with acceleration in a 6 GeV linac, a two-stage injection with acceleration in a 6 GeV linac and a multi-turn (3-turn) scheme with a two-stage injection and two main 1 GeV linacs. The key points of the comparison were total costs and BBU instability. Linac optic solutions are presented.