The application of doppler Hα spectroscopy to the prediction of experimental fusion rates in a deuterium-filled inertial electrostatic confinement device

Trabalho final de mestrado integrado em Medicina (Bioquímica), apresentado à Faculdade de Medicina da Universidade de CoimbraO défice da desoxiguanosina cinase (dGUOK), causado por mutações no gene DGUOK, leva ao desenvolvimento da forma hepatocerebral da Síndrome de depleção de DNA mitocondrial (MDS), ligadas a uma redução drástica no número de cópias do genoma mitocondrial (mtDNA), associada a elevada mortalidade e sem estratégias terapêuticas disponíveis, na criança. Apesar de se terem vindo a identificar novas mutações no gene DGUOK ao longo dos últimos anos, uma correlação genótipo-fenótipo precisa e exequível, nunca foi estabelecida. Um padrão reprodutível de associação entre o tipo e localização das mutações genéticas no gene DGUOK e a clínica apresentada pelo doente facultaria aos clínicos a capacidade de estimar, num estádio neonatal, ou mesmo pré-natal, o diagnóstico e a gravidade da doença, provendo os clínicos com ferramentas mais racionais para aconselhamento genético adequado às famílias e aos futuros pais. Procedeu-se a uma busca extensiva na base de dados de referências MEDLINE para procurar todas as mutações no gene DGUOK, publicadas até à data. Estas alterações foram analisadas quanto à sua localização no gene e o seu impacto na função e estrutura da proteína, assim como nas manifestações clínicas apresentadas pelos doentes e foi efetuado um estudo da correlação genótipo-fenótipo. Verificou-se a inexistência de uma correlação genótipo-fenótipo precisa e clara em doentes com MDS causado por mutações no gene DGUOK, revelando a existência de mecanismos mais complexos e ainda desconhecidos, que estarão subjacentes ao início e à progressão da doençaDeoxyguanosine kinase (coded by DGUOK) deficiency, caused by DGUOK gene mutations, leads to development of the hepatocerebral form of mitochondrial DNA depletion syndrome (MDS), linked to mitochondrial genome (mtDNA) copy number severe decline, associated to high mortality and absence of available therapeutic strategies in infants. In spite of the continuous identification of new DGUOK mutations over the years, an accurate and feasible genotype-phenotype correlation in DGUOK patients is lacking. A reproducible pattern of association between the type and localization of DGUOK gene mutation and its effect on patients´ clinic would ground physicians with the capacity to foresee, at a neonatal or even pre-natal stage, the disease diagnostics and severity, providing the clinicians, therefore, with more rationale tools for adequate genetic counselling in families and future parents. An extensive search on MEDLINE database was performed in order to search for all published DGUOK gene mutations to date. These alterations were analysed for their localization in the gene and their impact on protein structure and function and the clinical manifestations and a genotype-phenotype correlation study has been carried out. It was evident the absence of a clear and accurate genotype-phenotype correlation in patients with MDS caused by DGUOK mutations, unmasking, likely, more complex and unknown mechanisms underlying disease onset and progressio

An in silico performance characterization of respiratory motion guided 4DCT for high-quality low-dose lung cancer imaging.

This work aims to characterize the performance of an improved 4DCT technique aiming to overcome irregular breathing-related image artifacts. To address this, we have developed respiratory motion guided (RMG) 4DCT, which uses real-time breathing motion analysis to prospectively gate scans based on detection of irregular breathing. This is the first investigation of RMG-4DCT using a real-time software prototype, testing the hypothesis that it can reduce breathing irregularities during imaging, reduce image oversampling and improve image quality compared to a 'conventional' 4DCT protocol without breathing guidance. RMG-4DCT scans were simulated based on 100+  hours of breathing motion acquired for 20 lung cancer patients. Scan performance was quantified in terms of the beam on time (a surrogate for imaging dose), total scan time and the breathing irregularity during imaging (via RMSE of the breathing motion during acquisition). A conventional 4DCT protocol was also implemented using the same software prototype for a direct comparator to the RMG-4DCT results. We investigated the impact of key RMG-4DCT parameters such as gating tolerance, gantry rotation time and the use of baseline drift correction. Using a representative set of algorithm parameters, RMG-4DCT achieved significant mean reductions in estimated imaging dose (-17.8%, p  <  0.001) and breathing RMSE during imaging (-12.6%, p  <  0.001) compared to conventional 4DCT. These improvements came with increased scan times, roughly doubled on average (104%, p  <  0.001). Image quality simulations were performed using the deformable digital XCAT phantom, with image quality quantified based on the normalized cross correlation (NCC) between axial slices. RMG-4DCT demonstrated qualitative image quality improvements for three out of 10 phase bins, however the improvement was not significant across all 10 phases (p  =  0.08) at a population level. In choosing RMG-4DCT scan parameters, the trade-off between gating sensitivity and scan time may be optimized, demonstrating potential for RMG-4DCT as a viable pathway to improve clinical 4DCT imaging

The impact of breathing guidance and prospective gating during thoracic 4DCT imaging: An XCAT study utilizing lung cancer patient motion

Two interventions to overcome the deleterious impact irregular breathing has on thoracic-abdominal 4D computed tomography (4DCT) are (1) facilitating regular breathing using audiovisual biofeedback (AVB), and (2) prospective respiratory gating of the 4DCT scan based on the real-time respiratory motion. The purpose of this study was to compare the impact of AVB and gating on 4DCT imaging using the 4D eXtended cardiac torso (XCAT) phantom driven by patient breathing patterns. We obtained simultaneous measurements of chest and abdominal walls, thoracic diaphragm, and tumor motion from 6 lung cancer patients under two breathing conditions: (1) AVB, and (2) free breathing. The XCAT phantom was used to simulate 4DCT acquisitions in cine and respiratory gated modes. 4DCT image quality was quantified by artefact detection (NCCdiff), mean square error (MSE), and Dice similarity coefficient of lung and tumor volumes (DSClung, DSCtumor). 4DCT acquisition times and imaging dose were recorded. In cine mode, AVB improved NCCdiff, MSE, DSClung, and DSCtumor by 20% (p  =  0.008), 23% (p  <  0.001), 0.5% (p  <  0.001), and 4.0% (p  <  0.003), respectively. In respiratory gated mode, AVB improved NCCdiff, MSE, and DSClung by 29% (p  <  0.001), 34% (p  <  0.001), 0.4% (p  <  0.001), respectively. AVB increased the cine acquisitions by 15 s and reduced respiratory gated acquisitions by 31 s. AVB increased imaging dose in cine mode by 10%. This was the first study to quantify the impact of breathing guidance and respiratory gating on 4DCT imaging. With the exception of DSCtumor in respiratory gated mode, AVB significantly improved 4DCT image analysis metrics in both cine and respiratory gated modes over free breathing. The results demonstrate that AVB and respiratory-gating can be beneficial interventions to improve 4DCT for cancer radiation therapy, with the biggest gains achieved when these interventions are used simultaneously.ISSN:1361-6560ISSN:0031-915

Image-based retrospective 4D MRI in external beam radiotherapy: A comparative study with a digital phantom

Purpose: Several image-based retrospective sorting methods of 4D magnetic resonance imaging (4D MRI) have been proposed for respiratory motion reconstruction in external beam radiotherapy. However, the optimal strategy for providing accurate and artifact-free 4D MRI, ideally corresponding to an average breathing cycle, is not yet defined. This study presents a proactive comparison of three published image-based sorting methods, to define a groundwork for benchmarking in 4D MRI. Methods: Three published 4D MRI methods were selected for image retrospective sorting: body area, mutual information, and navigator slice. The three image-based methods were compared against a conventional retrospective sorting method based on an external surrogate. Comparisons were performed by means of an MRI digital phantom, derived from the XCAT CT phantom generated with different patient-derived signals, for a total of 12 cases. Specific multislice MRI acquisitions were simulated for slice sorting and sagittal, coronal, and axial orientations were tested. An average 4D cycle was generated as ground truth. Results: Individual and grouped patient analyses showed better performance of the navigator slice and mutual information in amplitude binning with respect to the body area strategy. Binning artifacts were reduced on the diaphragm with the slice navigator method due to the acquired internal information. Tumor motion description accurately matched the ground truth in the mutual information strategy with amplitude binning. The body area method followed the performance of the external surrogate and presented larger errors, since was not correlated with the internal anatomy. Sagittal and coronal orientations reported lower errors than axial slicing. Individual analysis showed the need of a patient-specific evaluation for the selection of the best method. Conclusions: A comparison between three different image-based retrospective sorting methods for 4D MRI is proposed, providing guidelines for benchmark definition in MRI-guided radiotherapy

Feasibility study on 3D image reconstruction from 2D orthogonal cine-MRI for MRI-guided radiotherapy

Introduction: In-room MRI is a promising image guidance strategy in external beam radiotherapy to acquire volumetric information for moving targets. However, limitations in spatio-temporal resolution led several authors to use 2D orthogonal images for guidance. The aim of this work is to present a method to concurrently compensate for non-rigid tumour motion and provide an approach for 3D reconstruction from 2D orthogonal cine-MRI slices for MRI-guided treatments. Methods: Free-breathing sagittal/coronal interleaved 2D cine-MRI were acquired in addition to a pre-treatment 3D volume in two patients. We performed deformable image registration (DIR) between cine-MRI slices and corresponding slices in the pre-treatment 3D volume. Based on an extrapolation of the interleaved 2D motion fields, the 3D motion field was estimated and used to warp the pre-treatment volume. Due to the lack of a ground truth for patients, the method was validated on a digital 4D lung phantom. Results: On the phantom, the 3D reconstruction method was able to compensate for tumour motion and compared favourably to the results of previously adopted strategies. The difference in the 3D motion fields between the phantom and the extrapolated motion was 0.4 ± 0.3 mm for tumour and 0.8 ± 1.5 mm for whole anatomy, demonstrating feasibility of performing a 3D volumetric reconstruction directly from 2D orthogonal cine-MRI slices. Application of the method to patient data confirmed the feasibility of utilizing this method in real world scenarios. Conclusion: Preliminary results on phantom and patient cases confirm the feasibility of the proposed approach in an MRI-guided scenario, especially for non-rigid tumour motion compensation