In this thesis, we aim to develop fundamentally new techniques and algorithms for efficiently computing rotating-shield brachytherapy (RSBT) treatment plans. We propose that these algorithms will pave the way for making RSBT available in clinical practices. RSBT is an intensity modulated high-dose-rate brachytherapy (HDR-BT) technique. Theoretically, RSBT offers advantages over the conventional HDR-BT. Although this technique is promising in theory, its application in practice is still at an early stage. The RSBT technique entails rotating a radiation-attenuating shield about a brachytherapy source to directionally modulate the radiation in an optimized fashion. The unshielded brachytherapy source used in conventional HDR-BT delivers radially symmetric dose distributions, thus the intensity modulation capability of the conventional HDR-BT is limited. With the capability of making anisotropic radiation, RSBT will revolutionize the brachytherapy technique through superior dose conformity, increased flexibility and inherent accuracy. Due to the enhanced power of intensity-modulation, RSBT will also enable dose escalation without increasing toxicity to the organs-at-risk, thus improving quality of life for millions of cancer patients. Although the first conceptual RSBT method was proposed more than ten years ago, there are still tremendous challenges for applying it in clinical practices. Creating efficient and automated treatment planning system is one of the major technical obstacles for making RSBT deliverable in the clinic. The time-critical nature of the application significantly increases the difficulty of RSBT treatment planning, demanding innovative techniques for information integration. Therefore, we propose that fundamentally novel technology and algorithms for RSBT treatment planning can make RSBT clinically accessible. The fundamental concept used for this thesis is to decompose the dose optimization step for RSBT treatment planning into two steps, namely anchor plan optimization and optimal sequencing. The degree of freedom in anchor plan optimization is controlled at a low level compared to single-step dose optimization, and the optimal sequencing algorithms can efficiently calculate treatment plans by reusing the solutions from anchor plan optimization. Thus, by decomposing the dose optimization, the computational complexity in the two-step method is greatly reduced compared to the single-step method. In the anchor plan optimization, an abstract RSBT delivery model is assumed. The abstract RSBT delivery model assumes that only beams with fixed small azimuthal emission angle, which are called beamlets, will be used during the delivery. An anchor plan is created based on this assumption that only these beamlets will be used. Generally, an anchor plan will be of high quality in the sense of dose distribution, but of low quality in the sense that it has prohibitory long delivery time. In the optimal sequencing step, beamlets will be superposed into beams to reduce the delivery time. By limiting the delivery time to a clinically acceptable level, the anchor plans turn into deliverable plans. Unlike anchor plan optimization, where an abstract RSBT delivery model is assumed, the optimal sequencing step depends on more concrete RSBT delivery models. Specifically, we will study three methods of RSBT, namely the single rotating-shield brachytherapy (S-RSBT), the dynamic rotating-shield brachytherapy (D-RSBT) and the paddle rotating-shield brachytherapy (P-RSBT). We proposed a novel anchor plan dose optimization method as well as novel optimal sequencing methods for each of the RSBT delivery methods studied in this work. We have implemented all the proposed algorithms and experimented with them using real medical data. With the methods proposed in this thesis, the optimization time for creating delivery plans can be controlled within 15 minutes based on the data from our experiments. Compared to the conventional brachytherapy techniques, the three methods studied in this work can produce more conformal dose distributions at an acceptable level of delivery time increase. With 15 min/fx delivery time, S-RSBT, D-RSBT and P-RSBT averagely increased the D90 (the minimum dose received by the hottest 90% of the tumor) by 17, 9 and 5 Gy compared to conventional interstitial plus intracavitary brachytherapy, whose D90 is 79 Gy. The best choice depends on the specified delivery time or quality requirement, as well as the complexity of building the equipment. Roughly speaking, among the three RSBT methods studied in this thesis, P-RSBT has the most complex applicators as well as the highest plan qualities. S-RSBT has the simplest applicators, and its plan qualities is generally better than D-RSBT with limited delivery time (/fx). With sufficient delivery time (~30 min/fx), D-RSBT may be considered as the best solution in the sense of balancing the complexity of applicators and the dose qualities.

No description available.

In this report, an optical wireless multiple-input multiple-output communication system employing intensity-modulation direct-detection is considered. The performance of direct current offset space-time block codes (DC-STBC) is studied in terms of pairwise error probability (PEP). It is shown that among the class of DC-STBCs, the worst case PEP corresponding to the minimum distance between two codewords is minimized by repetition coding (RC), under both electrical and optical individual power constraints. It follows that among all DC-STBCs, RC is optimal in terms of worst-case PEP for static channels and also for varying channels under any turbulence statistics. This result agrees with previously published numerical results showing the superiority of RC in such systems. It also agrees with previously published analytic results on this topic under log-normal turbulence and further extends it to arbitrary turbulence statistics. This shows the redundancy of the time-dimension of the DCSTBC in this system. This result is further extended to sum power constraints with static and turbulent channels, where it is also shown that the time dimension is redundant, and the optimal DC-STBC has a spatial beamforming structure. Numerical results are provided to demonstrate the difference in performance for systems with different numbers of receiving apertures and different throughput.

<p>Biological treatment optimization aim at improving radiation therapy by accounting for the radiobiological tumour and normal tissues response properties when optimizing the dose delivery. Generally traditional methods, using only dosimetrical measures, disregard the nonlinear radiation response of different tumours and normal tissues. The accumulated knowledge on tissue response to radiation, in the form of more accurate dose response relations, cell survival models and their associated biological parameters, alongside with the tools for biological treatment plan optimization, has allowed the present investigation on the potential merits of biologically based treatment optimization in radiation therapy.</p><p>With a more widespread implementation of intensity modulated radiation therapy in the clinic, there is an increasing demand for faster and safer treatment delivery techniques. In this thesis biological treatment plan optimization, using the probability to achieve complication free tumour control as the quantifier for treatment outcome, was applied to radiation therapy of early breast cancer and advanced cervix cancer. It is shown that very conformal dose distributions can generally be produced with 3 or 4 optimally orientated coplanar intensity modulated beams, without having clinically significant losses in treatment outcome from the optimal dose distribution.</p><p>By using exhaustive search methods, the optimal coplanar beam directions for intensity modulated photon beams for early breast cancer and the optimal non-coplanar directions for an advanced cervix cancer were investigated. Although time consuming, exhaustive search methods have the advantage of revealing most features involving interactions between a small number of beams and how this may influence the treatment outcome. Thus phase spaces may serve as a general database for selecting an almost optimal treatment configuration for similar patients. Previous knowledge acquired with physically optimized uniform beam radiation therapy may not apply when intensity modulated biological optimization is used. Thus unconventional treatment directions were sometimes found.</p>

<p>Optical fibre sensors can be used to measure a wide variety of properties. In some cases they have replaced conventional electronic sensors due to their possibility of performing measurements in environments suffering from electromagnetic disturbance, or in harsh environments where electronics cannot survive. In other cases they have had less success mainly due to the higher cost involved in fibre-optic sensor systems. Intensity modulated fibre-optic sensors normally require only low-cost monitoring systems principally based on light emitting diodes and photo diodes. The sensor principle itself is very simple when based on coupling between fibres, and coupling based intensity modulated sensors have found applications over a long time, mainly within position and vibration sensing. In this thesis new concepts and applications for intensity modulated fibre-optic sensors based on coupling between fibres are presented. From a low-cost and standard component perspective alternative designs are proposed and analyzed in order to find improved performance. The development of a sensor for an industrial temperature sensing application, involving aspects on multiplexing and fibre network installation, is presented. Optical time domain reflectometry (OTDR) is suggested as an efficient technique for multiplexing several coupling based sensors, and sensor network installation with blown fibre in micro ducts is proposed as a flexible and cost-efficient alternative to traditional cabling. A new sensor configuration using a fibre to a multicore fibre coupling and an image sensor readout system is proposed. With this system a high-performance sensor setup with a large measurement range can be realised without the need for precise fibre alignment often needed in coupling based sensors involving fibres with small cores. The system performance is analyzed theoretically with complete system simulations on different setups. An experimental setup is made based on standard fibre and image acquisition components, and differences from the theoretical performance are analyzed. It is shown that sub-µm accuracy should be possible to obtain, being the theoretical limit, and it is further suggested that the experimental performance is mainly related to two error sources: core position instability and differences between the real and the expected optical power distribution. Methods to minimize the experimental error are proposed and evaluated.</p>

Bragg grating reflectors etched in amorphous silicon overlay films have been integrated with Ti:LiNbO3 optical waveguides. With a 12.5 mm long grating segment and an etch depth of ~ 93 nm in a 105 nm-thick silicon film, a narrow (0.05 nm) spectral bandwidth with a record high transmission dip (> 20 dB) was achieved at a wavelength of ~1542 nm for TE polarization on an x-cut, y-propagating substrate. The reflectance in the channel waveguides is found to be strongly dependent on the depth of the etched grating. The 3-dB bandwidth of 0.05 nm obtained for all tested samples is the smallest reported for waveguides in LiNbO3. The effect of the Bragg waveguide loss factor on the transmittance and reflectance spectra is investigated using a model for contra-directional coupling that includes an attenuation coefficient. The Bragg grating spectral characteristics are exploited to fabricate distributed Bragg feedback modulators (DBFM) and Bragg reflector Fabry-Perot modulators (BFPM). The sharp cut-off in transmission and reflection spectra, which is an inherent characteristic of Bragg grating, was tuned by applying voltage via the linear electrooptic effect, to produce intensity modulation. The Bragg grating based modulators consume less electric power compared to polarization intensity modulators (PIMs). The DBFM demonstrates 1/1.6 times the modulating voltage of a PIM with identical waveguide and electrode structure. The BFPM shows 1/3.3 times the modulating voltage of the PIM. No difference in the frequency response is observed among the three modulators. Comparison of the modulation sensitivity in the linear region indicates that the Bragg grating based modulators provide better sensitivity than that of the PIM with identical waveguide and electrode structure. These results indicate the potential advantage of the Bragg grating based modulators for enhanced modulation efficiency over conventional modulators. Further improvements can be expected from the optimization of the electrode design.

Optical fibre sensors can be used to measure a wide variety of properties. In some cases they have replaced conventional electronic sensors due to their possibility of performing measurements in environments suffering from electromagnetic disturbance, or in harsh environments where electronics cannot survive. In other cases they have had less success mainly due to the higher cost involved in fibre-optic sensor systems. Intensity modulated fibre-optic sensors normally require only low-cost monitoring systems principally based on light emitting diodes and photo diodes. The sensor principle itself is very simple when based on coupling between fibres, and coupling based intensity modulated sensors have found applications over a long time, mainly within position and vibration sensing. In this thesis new concepts and applications for intensity modulated fibre-optic sensors based on coupling between fibres are presented. From a low-cost and standard component perspective alternative designs are proposed and analyzed in order to find improved performance. The development of a sensor for an industrial temperature sensing application, involving aspects on multiplexing and fibre network installation, is presented. Optical time domain reflectometry (OTDR) is suggested as an efficient technique for multiplexing several coupling based sensors, and sensor network installation with blown fibre in micro ducts is proposed as a flexible and cost-efficient alternative to traditional cabling. A new sensor configuration using a fibre to a multicore fibre coupling and an image sensor readout system is proposed. With this system a high-performance sensor setup with a large measurement range can be realised without the need for precise fibre alignment often needed in coupling based sensors involving fibres with small cores. The system performance is analyzed theoretically with complete system simulations on different setups. An experimental setup is made based on standard fibre and image acquisition components, and differences from the theoretical performance are analyzed. It is shown that sub-µm accuracy should be possible to obtain, being the theoretical limit, and it is further suggested that the experimental performance is mainly related to two error sources: core position instability and differences between the real and the expected optical power distribution. Methods to minimize the experimental error are proposed and evaluated.

Biological treatment optimization aim at improving radiation therapy by accounting for the radiobiological tumour and normal tissues response properties when optimizing the dose delivery. Generally traditional methods, using only dosimetrical measures, disregard the nonlinear radiation response of different tumours and normal tissues. The accumulated knowledge on tissue response to radiation, in the form of more accurate dose response relations, cell survival models and their associated biological parameters, alongside with the tools for biological treatment plan optimization, has allowed the present investigation on the potential merits of biologically based treatment optimization in radiation therapy. With a more widespread implementation of intensity modulated radiation therapy in the clinic, there is an increasing demand for faster and safer treatment delivery techniques. In this thesis biological treatment plan optimization, using the probability to achieve complication free tumour control as the quantifier for treatment outcome, was applied to radiation therapy of early breast cancer and advanced cervix cancer. It is shown that very conformal dose distributions can generally be produced with 3 or 4 optimally orientated coplanar intensity modulated beams, without having clinically significant losses in treatment outcome from the optimal dose distribution. By using exhaustive search methods, the optimal coplanar beam directions for intensity modulated photon beams for early breast cancer and the optimal non-coplanar directions for an advanced cervix cancer were investigated. Although time consuming, exhaustive search methods have the advantage of revealing most features involving interactions between a small number of beams and how this may influence the treatment outcome. Thus phase spaces may serve as a general database for selecting an almost optimal treatment configuration for similar patients. Previous knowledge acquired with physically optimized uniform beam radiation therapy may not apply when intensity modulated biological optimization is used. Thus unconventional treatment directions were sometimes found.

This thesis explores the benefits of intensity modulation for the purpose of extending the range of applications of fluorescence spectroscopy and imaging in cellular and molecular biology and medicine. Long-lived transient states of fluorescent molecules can, because of their long lifetimes, be used to detect subtle changes in the microenvironment of the molecule. A method for determining the kinetic rates for transitions to and from such states by registration of changes in the average fluorescence intensity related to different modulation of the excitation source is introduced. It combines the detection sensitivity of fluorescence with the environmental sensitivity of the long-lived transient states and allows the use of slow detectors such as CCD cameras, making parallelization and wide-field imaging possible developments. An extension of this method, generating image contrast based on triplet state population using a standard laser scanning microscope, is also shown. A strategy to combine fluorescence correlation spectroscopy (FCS) with modulated excitation, in a way that allows extraction of correlation data for all correlation times, is presented. This enables the use of modulation to optimize measurement conditions with respect to photophysical properties of the dyes used. FCS with modulated excitation will probably prove useful in future studies involving multiple kinetic processes occurring in overlapping time ranges. One of the ideas from this project also constitutes a powerful method for generating artifact free correlation curves from data sets where sections have been removed. This is potentially very useful in biological studies where spikes in the measurements often cause problems. In the final project, cross-correlation and alternating excitation are combined in measurements on a pH-sensitive ratiometric dye to clearly distinguish the protonation–deprotonation dynamics from other processes. The presented approach makes the protonation related fluctuations manifest themselves as a very distinct anti-correlating component in the correlation curve. This enables robust data analysis using a simple model. / QC 20100805

Bragg grating reflectors etched in amorphous silicon overlay films have been integrated with Ti:LiNbO3 optical waveguides. With a 12.5 mm long grating segment and an etch depth of ~ 93 nm in a 105 nm-thick silicon film, a narrow (0.05 nm) spectral bandwidth with a record high transmission dip (> 20 dB) was achieved at a wavelength of ~1542 nm for TE polarization on an x-cut, y-propagating substrate. The reflectance in the channel waveguides is found to be strongly dependent on the depth of the etched grating. The 3-dB bandwidth of 0.05 nm obtained for all tested samples is the smallest reported for waveguides in LiNbO3. The effect of the Bragg waveguide loss factor on the transmittance and reflectance spectra is investigated using a model for contra-directional coupling that includes an attenuation coefficient. The Bragg grating spectral characteristics are exploited to fabricate distributed Bragg feedback modulators (DBFM) and Bragg reflector Fabry-Perot modulators (BFPM). The sharp cut-off in transmission and reflection spectra, which is an inherent characteristic of Bragg grating, was tuned by applying voltage via the linear electrooptic effect, to produce intensity modulation. The Bragg grating based modulators consume less electric power compared to polarization intensity modulators (PIMs). The DBFM demonstrates 1/1.6 times the modulating voltage of a PIM with identical waveguide and electrode structure. The BFPM shows 1/3.3 times the modulating voltage of the PIM. No difference in the frequency response is observed among the three modulators. Comparison of the modulation sensitivity in the linear region indicates that the Bragg grating based modulators provide better sensitivity than that of the PIM with identical waveguide and electrode structure. These results indicate the potential advantage of the Bragg grating based modulators for enhanced modulation efficiency over conventional modulators. Further improvements can be expected from the optimization of the electrode design.