Particle Accelerators and Detectors for medical Diagnostics and Therapy

This Habilitationsschrift (Habilitation thesis) is focused on my research activities on medical applications of particle physics and was written in 2013 to obtain the Venia Docendi (Habilitation) in experimental physics at the University of Bern. It is based on selected publications, which represented at that time my major scientific contributions as an experimental physicist to the field of particle accelerators and detectors applied to medical diagnostics and therapy. The thesis is structured in two parts. In Part I, Chapter 1 presents an introduction to accelerators and detectors applied to medicine, with particular focus on cancer hadrontherapy and on the production of radioactive isotopes. In Chapter 2, my publications on medical particle accelerators are introduced and put into their perspective. In particular, high frequency linear accelerators for hadrontherapy are discussed together with the new Bern cyclotron laboratory. Chapter 3 is dedicated to particle detectors with particular emphasis on three instruments I contributed to propose and develop: segmented ionization chambers for hadrontherapy, a proton radiography apparatus with nuclear emulsion films, and a beam monitor detector for ion beams based on doped silica fibres. Selected research and review papers are contained in Part II. For copyright reasons, they are only listed and not reprinted in this on-line version. They are available on the websites of the journals.

Dark matter sensitivity of multi-ton liquid xenon detectors

We study the sensitivity of multi ton-scale time projection chambers using a liquid xenon target, e.g., the proposed DARWIN instrument, to spin-independent and spin-dependent WIMP-nucleon scattering interactions. Taking into account realistic backgrounds from the detector itself as well as from neutrinos, we examine the impact of exposure, energy threshold, background rejection efficiency and energy resolution on the dark matter sensitivity. With an exposure of 200 t x y and assuming detector parameters which have been already demonstrated experimentally, spin-independent cross sections as low as 2.5×10−49 cm2 can be probed for WIMP masses around 40 GeV/c2. Additional improvements in terms of background rejection and exposure will further increase the sensitivity, while the ultimate WIMP science reach will be limited by neutrinos scattering coherently off the xenon nuclei.

Development and Implementation of the Use of Optically Stimulated Luminescent Detectors in the Radiological Physics Center Anthropomorphic Quality Assurance Phantoms

The Radiological Physics Center (RPC) uses both on-site and remote reviews to credential institutions for participation in clinical trials. Anthropomorphic quality assurance (QA) phantoms are one tool the RPC uses to remotely audit institutions, which include thermoluminescent dosimeters (TLDs) and radiochromic film. The RPC desires to switch from TLD as the absolute dosimeter in the phantoms, to optically stimulated luminescent dosimeters (OSLDs), but a problem lies in the angular dependence exhibited by the OSLD. The purpose of this study was to characterize the angular dependence of OSLD and establish a correction factor if necessary, to provide accurate dosimetric measurements as a replacement for TLD in the QA phantoms. A 10 cm diameter high-impact polystyrene spherical phantom was designed and constructed to hold an OSLD to study the angular response of the dosimeter under the simplest of circumstances for both coplanar and non-coplanar treatment deliveries. OSLD were irradiated in the spherical phantom, and the responses of the dosimeter from edge-on angles were normalized to the response when irradiated with the beam incident normally on the surface of the dosimeter. The average normalized response was used to establish an angular correction factor for 6 MV and 18 coplanar treatments, and for 6 MV non-coplanar treatments specific to CyberKnife. The RPC pelvic phantom dosimetry insert was modified to hold OSLD, in addition to the TLD, adjacent to the planes of film. Treatment plans of increasing angular beam delivery were developed, three in Pinnacle v9.0 (4-field box, IMRT, and VMAT) and one in Accuray’s MultiPlan v3.5.3 (CyberKnife). The plans were delivered to the pelvic phantom containing both TLD and OSLD in the target volume. The pelvic phantom was also sent to two institutions to be irradiated as trials, one delivering IMRT, and the other a CyberKnife treatment. For the IMRT deliveries and the two institution trials, the phantom also included film in the sagittal and coronal planes. The doses measured from the TLD and OSLD were calculated for each irradiation, and the angular correction factors established from the spherical phantom irradiations were applied to the OSLD dose. The ratio of the TLD dose to the angular corrected OSLD dose was calculated for each irradiation. The corrected OSLD dose was found to be within 1% of the TLD measured dose for all irradiations, with the exception of the in-house CyberKnife deliveries. The films were normalized to both TLD measured dose and the corrected OSLD dose. Dose profiles were obtained and gamma analysis was performed using a 7%/4 mm criteria, to compare the ability of the OSLD, when corrected for the angular dependence, to provide equivalent results to TLD. The results of this study indicate that the OSLD can effectively be used as a replacement for TLD in the RPC’s anthropomorphic QA phantoms for coplanar treatment deliveries when a correction is applied for the dosimeter’s angular dependence.

Function of GCIP (CCNDBP1), a helix -loop -helix leucine -zip protein, in cell differentiation and tumorigenesis

Cell growth and differentiation are complex and well-organized processes in which cells respond to stimuli from the environment by carrying out genetic programs. Transcription factors with helix-loop-helix (HLH) motif play critical roles in controlling the expression of genes involved in lineage commitment, cell fate determination, proliferation and tumorigenesis. This study has examined the roles of GCIP (CCNDBP1) in cell differentiation and tumorigenesis. GCIP is a recently identified HLH-leucine zipper protein without a basic region like the Id family of proteins. However, GCIP shares little sequence homology with the Id proteins and has domains with high acidic amino acids and leucine-rich regions following the HLH domain like c-Myc. Here we firstly demonstrate that GCIP is a transcription regulator related to muscle differentiation program. Overexpression of GCIP in C2C12 cells not only promotes myotube formation but also upregulates myogenic differentiation biomarkers, including MHC and myogenein. On the other hand, our finding also suggests that GCIP is a potential tumor suppressor related to cell cycle control. Expression of GCIP was significantly down-regulated in colon tumors as compared to normal colon tissues. Overexpression of GCIP in SW480 colon cancer cell line resulted in a significant inhibition on tumor cell colony formation on soft agar assays while silencing of GCIP expression by siRNA can promote cell proliferation and colony formation. In addition, results from transgenic mice specifically expressing GCIP in liver also support the idea that GCIP is involved in the early stage of hepatocarcinogenesis and decreased susceptibility to chemical hepatocarcinogenesis. ^

Characterization of the dose distribution in the halo region of a clinical proton pencil beam using emulsion film detectors

Proton therapy is a high precision technique in cancer radiation therapy which allows irradiating the tumor with minimal damage to the surrounding healthy tissues. Pencil beam scanning is the most advanced dose distribution technique and it is based on a variable energy beam of a few millimeters FWHM which is moved to cover the target volume. Due to spurious effects of the accelerator, of dose distribution system and to the unavoidable scattering inside the patient's body, the pencil beam is surrounded by a halo that produces a peripheral dose. To assess this issue, nuclear emulsion films interleaved with tissue equivalent material were used for the first time to characterize the beam in the halo region and to experimentally evaluate the corresponding dose. The high-precision tracking performance of the emulsion films allowed studying the angular distribution of the protons in the halo. Measurements with this technique were performed on the clinical beam of the Gantry1 at the Paul Scherrer Institute. Proton tracks were identified in the emulsion films and the track density was studied at several depths. The corresponding dose was assessed by Monte Carlo simulations and the dose profile was obtained as a function of the distance from the center of the beam spot.

Emulsion detectors for the antihydrogen detection in AEgIS

The AEgIS experiment at CERN aims to perform the first direct measurement of gravitational interaction between matter and antimatter by measuring the deviation of a cold antihydrogen beam in the Earth gravitational field. The design of the experiment has been recently updated to include emulsion films as position sensitive detector. The submicrometric position accuracy of emulsions leads indeed to a significant improvement of the experimental sensitivity. We present results of preliminary tests and discuss perspectives for the final measurement.

In-loop Feature Tracking for Structure and Motion with Out-of-core Optimization

In this paper, a novel and approach for obtaining 3D models from video sequences captured with hand-held cameras is addressed. We define a pipeline that robustly deals with different types of sequences and acquiring devices. Our system follows a divide and conquer approach: after a frame decimation that pre-conditions the input sequence, the video is split into short-length clips. This allows to parallelize the reconstruction step which translates into a reduction in the amount of computational resources required. The short length of the clips allows an intensive search for the best solution at each step of reconstruction which robustifies the system. The process of feature tracking is embedded within the reconstruction loop for each clip as opposed to other approaches. A final registration step, merges all the processed clips to the same coordinate frame

Room temperature absorption in laterally biased Quantum Infrared Detectors fabricated by MBE regrowth

In this paper, we show room temperature operation of a quantum well infrared photodetector (QWIP) using lateral conduction through ohmic contacts deposited at both sides of two n-doped quantum wells. To reduce the dark current due to direct conduction in the wells, we apply an electric field between the quantum wells and two pinch-off Schottky gates, in a fashion similar to a field effect device. Since the normal incidence absorption is strongly reduced in intersubband transitions in quantum wells, we first analyze the response of a detector based on quantum dots (QD). This QD device shows photocurrent signal up to 150 K when it is processed in conventional vertical detector. However, it is possible to observe room temperature signal when it is processed in a lateral structure. Finally, the room temperature photoresponse of the QWIP is demonstrated, and compared with theory. An excellent agreement between the estimated and measured characteristics of the device is found

Projector Model for Efficient List-Mode Reconstruction in PET Scanners with Parallel Planar Detectors

We have developed a new projector model specifically tailored for fast list-mode tomographic reconstructions in Positron emission tomography (PET) scanners with parallel planar detectors. The model provides an accurate estimation of the probability distribution of coincidence events defined by pairs of scintillating crystals. This distribution is parameterized with 2D elliptical Gaussian functions defined in planes perpendicular to the main axis of the tube of response (TOR). The parameters of these Gaussian functions have been obtained by fitting Monte Carlo simulations that include positron range, acolinearity of gamma rays, as well as detector attenuation and scatter effects. The proposed model has been applied efficiently to list-mode reconstruction algorithms. Evaluation with Monte Carlo simulations over a rotating high resolution PET scanner indicates that this model allows to obtain better recovery to noise ratio in OSEM (ordered-subsets, expectation-maximization) reconstruction, if compared to list-mode reconstruction with symmetric circular Gaussian TOR model, and histogram-based OSEM with precalculated system matrix using Monte Carlo simulated models and symmetries.

Experiences on using closed-loop control systems for smoke control

The main objective of ventilation systems in case of fire is the reduction of the possible consequences by achieving the best possible conditions for the evacuation of the users and the intervention of the emergency services. In the last years, the required quick response of the ventilation system, from normal to emergency mode, has been improved by the use of automatic and semi-automatic control systems, what reduces the response times through the support to the operators decision taking, and the use of pre-defined strategies. A further step consists on the use of closedloop algorithms, which takes into account not only the initial conditions but their development (air velocity, traffic situation, etc), optimizing the quality of the smoke control process

Comments and remarks over classic linear loop-gain method for oscillator design and analysis. New proposed method based on NDF/RRT

Abstract. This paper describes a new and original method for designing oscillators based on the Normalized Determinant Function (NDF) and Return Relations (RRT)- Firstly, a review of the loop-gain method will be performed. The loop-gain method pros, cons and some examples for exploring wrong solutions provided by this method will be shown. This method produces in some cases wrong solutions because some necessary conditions have not been fulfilled. The required necessary conditions to assure a right solution will be described. The necessity of using the NDF or the Transpose Return Relations (RRT), which are related with the True Loop-Gain, to test the additional conditions will be demonstrated. To conclude this paper, the steps for oscillator design and analysis, using the proposed NDF/RRj method, will be presented. The loop-gain wrong solutions will be compared with the NDF/RRj and the accuracy of this method to estimate the oscillation frequency and QL will be demonstrated. Some additional examples of plane reference oscillators (Z/Y/T), will be added and they will be analyzed with the new NDF/RRj proposed method, even these oscillators cannot be analyzed using the classic loop gain method.