Investigation of time-resolved volumetric MRI to enhance MR-guided radiotherapy of moving lung tumors

In photon radiotherapy of lung cancer, respiratory-induced motion introduces systematic and statistical uncertainties in treatment planning and dose delivery. By integrating magnetic resonance imaging (MRI) in the treatment planning process in MR-guided radiotherapy (MRgRT), uncertainties in target volume definition can be reduced with respect to state-of-the-art X-ray-based approaches. Furthermore, MR-guided linear accelerators (MR-Linacs) offer dose delivery with enhanced accuracy and precision through daily treatment plan adaptation and gated beam delivery based on real-time MRI. Today, the potential of MRgRT of moving targets is, however, not fully exploited due to the lack of time-resolved four-dimensional MRI (4D-MRI) in clinical practice. Therefore, the aim of this thesis was to develop and experimentally validate new methods for motion characterization and estimation with 4D-MRI for MRgRT of lung cancer. Different concepts were investigated for all phases of the clinical workflow - treatment planning, beam delivery, and post-treatment analysis. Firstly, a novel internal target volume (ITV) definition method based on the probability-of-presence of moving tumors derived from real-time 4D-MRI was developed. The ability of the ITVs to prospectively account for changes occurring over the course of several weeks was assessed in retrospective geometric analyses of lung cancer patient data. Higher robustness of the probabilistic 4D-MRI-based ITVs against interfractional changes was observed compared to conventional target volumes defined with four-dimensional computed tomography (4D-CT). The study demonstrated that motion characterization over extended times enabled by real-time 4D-MRI can reduce systematic and statistical uncertainties associated with today’s standard workflow. Secondly, experimental validation of a published motion estimation method - the propagation method - was conducted with a porcine lung phantom under realistic patient-like conditions. Estimated 4D-MRIs with a temporal resolution of 3.65 Hz were created based on orthogonal 2D cine MRI acquired at the scanner unit of an MR-Linac. A comparison of these datasets with ground truth respiratory-correlated 4D-MRIs in geometric analyses showed that the propagation method can generate geometrically accurate estimated 4D-MRIs. These could decrease target localization errors and enable 3D motion monitoring during beam delivery at the MR-Linac in the future. Lastly, the propagation method was extended to create continuous time-resolved estimated synthetic CTs (tresCTs). The proposed method was experimentally tested with the porcine lung phantom, successively imaged at a CT scanner and an MR-Linac. A high agreement of the images and corresponding dose distributions of the tresCTs and measured ground truth 4D-CTs was found in geometric and dosimetric analyses. The tresCTs could be used for post-treatment time-resolved reconstruction of the delivered dose to guide treatment adaptations in the future. These studies represent important steps towards a clinical application of time-resolved 4D-MRI methods for enhanced MRgRT of lung tumors in the near future

Optimization of Operation Sequencing in CAPP Using Hybrid Genetic Algorithm and Simulated Annealing Approach

In any CAPP system, one of the most important process planning functions is selection of the operations and corresponding machines in order to generate the optimal operation sequence. In this paper, the hybrid GA-SA algorithm is used to solve this combinatorial optimization NP (Non-deterministic Polynomial) problem. The network representation is adopted to describe operation and sequencing flexibility in process planning and the mathematical model for process planning is described with the objective of minimizing the production time. Experimental results show effectiveness of the hybrid algorithm that, in comparison with the GA and SA standalone algorithms, gives optimal operation sequence with lesser computational time and lesser number of iterations

Optimization of Operation Sequencing in CAPP Using Hybrid Genetic Algorithm and Simulated Annealing Approach

In any CAPP system, one of the most important process planning functions is selection of the operations and corresponding machines in order to generate the optimal operation sequence. In this paper, the hybrid GA-SA algorithm is used to solve this combinatorial optimization NP (Non-deterministic Polynomial) problem. The network representation is adopted to describe operation and sequencing flexibility in process planning and the mathematical model for process planning is described with the objective of minimizing the production time. Experimental results show effectiveness of the hybrid algorithm that, in comparison with the GA and SA standalone algorithms, gives optimal operation sequence with lesser computational time and lesser number of iterations

Autonomous Navigation of Automated Guided Vehicle Using Monocular Camera

This paper presents a hybrid control algorithm for Automated Guided Vehicle (AGV) consisting of two independent control loops: Position Based Control (PBC) for global navigation within manufacturing environment and Image Based Visual Servoing (IBVS) for fine motions needed for accurate steering towards loading/unloading point. The proposed hybrid control separates the initial transportation task into global navigation towards the goal point, and fine motion from the goal point to the loading/unloading point. In this manner, the need for artificial landmarks or accurate map of the environment is bypassed. Initial experimental results show the usefulness of the proposed approach.COBISS.SR-ID 27383808

Autonomous Navigation of Automated Guided Vehicle Using Monocular Camera

This paper presents a hybrid control algorithm for Automated Guided Vehicle (AGV) consisting of two independent control loops: Position Based Control (PBC) for global navigation within manufacturing environment and Image Based Visual Servoing (IBVS) for fine motions needed for accurate steering towards loading/unloading point. The proposed hybrid control separates the initial transportation task into global navigation towards the goal point, and fine motion from the goal point to the loading/unloading point. In this manner, the need for artificial landmarks or accurate map of the environment is bypassed. Initial experimental results show the usefulness of the proposed approach.COBISS.SR-ID 27383808

[¹⁸F]fluorination of biorelevant arylboronic acid pinacol ester scaffolds synthesized by convergence techniques

Aim: The development of small molecules through convergent multicomponent reactions (MCR) has been boosted during the last decade due to the ability to synthesize, virtually without any side-products, numerous small drug-like molecules with several degrees of structural diversity.(1) The association of positron emission tomography (PET) labeling techniques in line with the “one-pot” development of biologically active compounds has the potential to become relevant not only for the evaluation and characterization of those MCR products through molecular imaging, but also to increase the library of radiotracers available. Therefore, since the [18F]fluorination of arylboronic acid pinacol ester derivatives tolerates electron-poor and electro-rich arenes and various functional groups,(2) the main goal of this research work was to achieve the 18F-radiolabeling of several different molecules synthesized through MCR. Materials and Methods: [18F]Fluorination of boronic acid pinacol esters was first extensively optimized using a benzaldehyde derivative in relation to the ideal amount of Cu(II) catalyst and precursor to be used, as well as the reaction solvent. Radiochemical conversion (RCC) yields were assessed by TLC-SG. The optimized radiolabeling conditions were subsequently applied to several structurally different MCR scaffolds comprising biologically relevant pharmacophores (e.g. β-lactam, morpholine, tetrazole, oxazole) that were synthesized to specifically contain a boronic acid pinacol ester group. Results: Radiolabeling with fluorine-18 was achieved with volumes (800 μl) and activities (≤ 2 GBq) compatible with most radiochemistry techniques and modules. In summary, an increase in the quantities of precursor or Cu(II) catalyst lead to higher conversion yields. An optimal amount of precursor (0.06 mmol) and Cu(OTf)2(py)4 (0.04 mmol) was defined for further reactions, with DMA being a preferential solvent over DMF. RCC yields from 15% to 76%, depending on the scaffold, were reproducibly achieved. Interestingly, it was noticed that the structure of the scaffolds, beyond the arylboronic acid, exerts some influence in the final RCC, with electron-withdrawing groups in the para position apparently enhancing the radiolabeling yield. Conclusion: The developed method with high RCC and reproducibility has the potential to be applied in line with MCR and also has a possibility to be incorporated in a later stage of this convergent “one-pot” synthesis strategy. Further studies are currently ongoing to apply this radiolabeling concept to fluorine-containing approved drugs whose boronic acid pinacol ester precursors can be synthesized through MCR (e.g. atorvastatin)