Development of novel radiotherapy techniques in combination with magnetic resonance imaging (MRI) in order to optimize the monitoring and treatment procedures in central nervous system malignancies

Nowadays, a continuous improvement on modern radiotherapy techniques is observed. Therefore, 3D dose verification and accurate determination of the tumor target volume are essential. The aim of the current study was twofold: (a) to assure the radiotherapy dosimetric results by the utilization of MRI polymer gel dosimetry methodologies and (b) to optimize the dosimetric radiotherapy results in conformal radiotherapy by the utilization of Magnetic Resonance Imaging in special phantoms. Nowadays, polymer gel dosimeters have been proven a valuable tool for the beam-dose characteristics measurements and 3D radiation dose verification in radiotherapy. The overall polymer gel dosimetry procedure resides in the field of chemical dosimetry and consists of: (a) the preparation of a certain chemical composition polymer gel, (b) the irradiation of the gel, (c) the readout process and (d) the mathematical analysis method used for the estimation of the final irradiated doses. A typical gel dosimeter consists of water, a gelatin agent, monomers and a cross-linker co-monomer. Upon irradiation, the monomers are polymerized (radiation-induced polymerization). The extent of polymerization is related to the absorbed dose. The changes in the polymer gel can be visualized utilizing different imaging modalities such as Magnetic Resonance Imaging (MRI), Optical Computed Tomography (CT), x-ray CT and Ultrasound. The appropriate processing of the results for each modality generates a relation between the absorbed dose and the contrast parameter basis of each method. The estimation of the uncertainty in each implementation step is going to increase the reliability of this dosimetric procedure. The increased sophistication of modern radiotherapy planning techniques such as conformal (CFRT) necessitates improved means of defining target volumes for treatment. This step remains the most crucial and difficult part of the radiotherapy planning process, otherwise a geographical miss of the tumor or systematic error will be perpetuated throughout therapy. MRI is being increasingly used in oncology for staging, assessing tumor response and evaluating disease recurrence. Similarly, the improvement characterization of soft tissues and visualization of tumor extent using MRI can be used to benefit the radiotherapy treatment planning (RTP) process from delineation and treatment response. Unfortunately, there are some limitations in MRI methodologies for the unique utilization of MRI in radiotherapy treatment planning. For this reason last years, coregistration images of MRI and CT are used for the radiotherapy treatment planning. The current study can be divided into three parts. The first part was focused on the optimization of the chemical formula, the preparation methodology of the N-vinylpyrrolidone polymer gels for the utilization in 3D verification of modern radiotherapy techniques. Also, the optimum time intervals between ‘gel manufacture’ – ‘irradiation’ – ‘MR scanning’ were assessed, based on the optimum sensitivity of the dosimetric system. Amongst these intervals, beam profile measurements have been performed in order to assess the effect of the gel system dose characteristics in clinical beam measurements. It has been shown that the increase of the N-vinylpyrrolidone concentration enhanced the dosimetric characteristics at low level doses. Unfortunately, this increase in concentration resulted in a dose range response restriction. Regarding the influence of preparation conditions in dosimetric characteristics of these gels, it was revealed that under anoxic preparation conditions the dose sensitivity and the dose resolution at one day post-irradiation were improved as compared to the same gel manufacturing under normal atmospheric conditions. The temporal stability was also improved under anoxic preparation conditions for the time period of one month post-irradiation. These results validated the importance of anoxic and normal atmospheric manufacturing conditions in the dosimetric performance of normoxic Nvinylpyrrolidone- based polymer gels. Moreover, it was presented that the dosimetric characteristics of the evaluated polymer gel system were rapidly deteriorated if the irradiation process took place for a period more than 1 week after gel manufacturing. On the other hand, it seemed that the time between irradiation and MR scanning didn’t affect the gel system dose characteristics. It has been confirmed that the %dose profiles measured with the presented polymer gel system within the mentioned ‘gel manufacture – irradiation – MR scanning’ time periods were rather reliable and valuable. Polymer gels seemed to h ave a c ertain r ole for modern radiotherapy techniques treatment plan validation and relative dose distribution measurements. The presented [VIPET / MR-PHAPS / weighted-linear-regression] polymer gel system accompanied with the derived characteristics and practical limitations of use, could be conveniently and reliably used in clinical practice. The second part was focused on the optimization of the readout process and the mathematical analysis method used for the estimation of the final irradiation doses utilizing of the proposed polymer gel system. Nowadays, different imaging modalities applied for the readout and analysis processes are used. These include Magnetic Resonance Imaging (MRI), Optical Computed Tomography (opt-CT), x-ray CT and Ultrasound. Amongst them, MRI is an established methodology for the readout process in polymer gel dosimetry. The last ten years the multiple echo spin echo (MESE) pulse sequence is well-established in MRI polymer gel dosimetry. The main drawback of this pulse sequence is the relatively long acquisition time. In order to overcome this problem a new Multi- Echo Half Fourier Acquisition Single Shot Turbo Spin Echo sequence (MEHASTE) was presented. Three fitting regression algorithms were utilized for the assessment of the dosimetric characteristics with MEHASTE sequence. It was finally presented that the most accurate algorithm was the one that minifies the effect on the image background and noise. This algorithm was utilized for the comparison of the dosimetric characteristics of the polymer gel system using the new pulse sequence (MEHASTE) and with the standard one (MESE). These results revealed that the two methods did not exhibit large deviations and MEHASTE could be an alternative faster and qualitative method for MRI polymer gel dosimetry. Furthermore in this part, the dosimetric results between the treatment planning calculations and polymer gel dosimeter measurements were compared, using the new pulse sequence (MEHASTE) and the most accurate fitting regression algorithm. The two comparison methods were the isodose lines and the gamma index factor. The results between the qualitative (isodose lines) and the quantitative (gamma index factor) comparison method didn’t deviate. In the third part of the current study, the co-registration procedure of MRI and CT images was presented and their implementation in radiotherapy treatment planning was assessed. It seemed that the resulted co-registration images can present the anatomical characteristics of hard as well as soft tissues. Moreover, the dose maps of the polymer gel dosimeters were co-registrated with the CT and MRI images of the selected series of phantoms. This procedure revealed the ability of the fused images to present the dosimetric results co-registrated with the anatomical information. Finally, it was confirmed that the complementary role of MRI in radiotherapy treatment planning is crucial for the precise definition of tumor volumes in RTP