MRI-based methods for response assessment to neoadjuvant therapy in esophageal cancer

Esophageal cancer is known to have low 5-year overall survival rates. Furthermore, the degree of response is associated with patient prognosis, with the most favorable long-term prognosis for the 29% of patients reaching pathologic complete response. For the introduction of personalized treatment schemes accurate prediction or assessment of response is required in which, depending on response, patients could follow a different treatment path. This could include for example a wait-and-see approach with omission of surgery, intensification of neoadjuvant therapy or primary surgery. In this thesis a range of topics has been discussed with a main focus on using MR-based (functional) techniques to predict response to neoadjuvant treatment for patients with esophageal cancer. The studies presented in this thesis showed the potential of functional MRI in the prediction of response in patients with esophageal cancer undergoing neoadjuvant chemoradiotherapy. Furthermore, it was found that different modalities (e.g. DCE-MRI, DW-MRI and 18F-FDG PET/CT) could be of complementary value in predicting response, each visualizing different physiological processes in the tumor. Therefore, the use of multi-parametric multimodality models should be further researched in larger patient cohorts. In addition, a methodical study on fitting methods for IVIM-MRI was researched. This study showed that differences in trend in fitted parameters occurred between the different fitting approaches. It is expected that these differences influence the accuracy and precision in longitudinal studies for response assessment in which IVIM will be used. Therefore, it was concluded that it is of great importance to explicit report specifications of fitting approaches used in IVIM studies to be able to compare outcomes between studies. Finally, esophageal tumor motion was researched on different time scales. Large variations were found in tumor motion both between and within patients with esophageal cancer. The stochastic nature of the variations in motion demonstrated the importance of real-time tumor motion management during radiotherapy in order to safely reduce treatment margins

MRI-based methods for response assessment to neoadjuvant therapy in esophageal cancer

Esophageal cancer is known to have low 5-year overall survival rates. Furthermore, the degree of response is associated with patient prognosis, with the most favorable long-term prognosis for the 29% of patients reaching pathologic complete response. For the introduction of personalized treatment schemes accurate prediction or assessment of response is required in which, depending on response, patients could follow a different treatment path. This could include for example a wait-and-see approach with omission of surgery, intensification of neoadjuvant therapy or primary surgery. In this thesis a range of topics has been discussed with a main focus on using MR-based (functional) techniques to predict response to neoadjuvant treatment for patients with esophageal cancer. The studies presented in this thesis showed the potential of functional MRI in the prediction of response in patients with esophageal cancer undergoing neoadjuvant chemoradiotherapy. Furthermore, it was found that different modalities (e.g. DCE-MRI, DW-MRI and 18F-FDG PET/CT) could be of complementary value in predicting response, each visualizing different physiological processes in the tumor. Therefore, the use of multi-parametric multimodality models should be further researched in larger patient cohorts. In addition, a methodical study on fitting methods for IVIM-MRI was researched. This study showed that differences in trend in fitted parameters occurred between the different fitting approaches. It is expected that these differences influence the accuracy and precision in longitudinal studies for response assessment in which IVIM will be used. Therefore, it was concluded that it is of great importance to explicit report specifications of fitting approaches used in IVIM studies to be able to compare outcomes between studies. Finally, esophageal tumor motion was researched on different time scales. Large variations were found in tumor motion both between and within patients with esophageal cancer. The stochastic nature of the variations in motion demonstrated the importance of real-time tumor motion management during radiotherapy in order to safely reduce treatment margins

Rénovation urbaine à Utrecht. Evolution des outils, problèmes et perspectives

In this article there will be examined if urban renewal is the solution for the problems concerning the elder housing stock. Therefore first a summary of the instruments of urban renewal in the Netherlans will be given, next a case study of the revowal of the housingstock in the municipality Utrecht will be dealt with and finally conclusions and perspectives will be given.Dans cet article, nous verrons si la rénovation urbaine apporte une réponse au problème du parc immobilier ancien. Nous présenterons donc d'abord les outils de la rénovation urbaine aux Pays-Bas ; suivra une étude de cas de la rénovation du parc immobilier dans la commune d'Utrecht. Nous donnerons ensuite nos conclusions et envisagerons les perspectives d'avenir.Ter Welle-Heethuis A. Rénovation urbaine à Utrecht. Evolution des outils, problèmes et perspectives. In: Hommes et Terres du Nord, 1984/4. Spécial Pays-Bas. pp. 251-258

Validation of deformable image registration algorithms on CT images of ex vivo porcine bladders with fiducial markers

The spatial accuracy of deformable image registration (DIR) is important in the implementation of image guided adaptive radiotherapy techniques for cancer in the pelvic region. Validation of algorithms is best performed on phantoms with fiducial markers undergoing controlled large deformations. Excised porcine bladders, exhibiting similar filling and voiding behavior as human bladders, provide such an environment. The aim of this study was to determine the spatial accuracy of different DIR algorithms on CT images of ex vivo porcine bladders with radiopaque fiducial markers applied to the outer surface, for a range of bladder volumes, using various accuracy metrics. Five excised porcine bladders with a grid of 30-40 radiopaque fiducial markers attached to the outer wall were suspended inside a water-filled phantom. The bladder was filled with a controlled amount of water with added contrast medium for a range of filling volumes (100-400 ml in steps of 50 ml) using a luer lock syringe, and CT scans were acquired at each filling volume. DIR was performed for each data set, with the 100 ml bladder as the reference image. Six intensity-based algorithms (optical flow or demons-based) implemented in theMATLAB platform DIRART, a b-spline algorithm implemented in the commercial software package VelocityAI, and a structure-based algorithm (Symmetric Thin Plate Spline Robust Point Matching) were validated, using adequate parameter settings according to values previously published. The resulting deformation vector field from each registration was applied to the contoured bladder structures and to the marker coordinates for spatial error calculation. The quality of the algorithms was assessed by comparing the different error metrics across the different algorithms, and by comparing the effect of deformation magnitude (bladder volume difference) per algorithm, using the Independent Samples Kruskal-Wallis test. The authors found good structure accuracy without dependency on bladder volume difference for all but one algorithm, and with the best result for the structure-based algorithm. Spatial accuracy as assessed from marker errors was disappointing for all algorithms, especially for large volume differences, implying that the deformations described by the registration did not represent anatomically correct deformations. The structure-based algorithm performed the best in terms of marker error for the large volume difference (100-400 ml). In general, for the small volume difference (100-150 ml) the algorithms performed relatively similarly. The structure-based algorithm exhibited the best balance in performance between small and large volume differences, and among the intensity-based algorithms, the algorithm implemented in VelocityAI exhibited the best balance. Validation of multiple DIR algorithms on a novel physiological bladder phantom revealed that the structure accuracy was good for most algorithms, but that the spatial accuracy as assessed from markers was low for all algorithms, especially for large deformations. Hence, many of the available algorithms exhibit sufficient accuracy for contour propagation purposes, but possibly not for accurate dose accumulatio

STABILIZATION OF STANDARD PLATELET CONCENTRATES AND MINIMIZATION OF THE PLATELET STORAGE LESION BY A PROSTACYCLIN ANALOG

Platelet concentrates were pretreated with a stable synthetic prostacyclin analogue (Iloprost) at two different concentrations before the second centrifugation step (pelleting step) of preparation. This resulted in loss. of platelet sensitivity to aggregating agents. To mimic the situation after transfusion and to assess the reversibility of platelet inhibition, platelets were washed during and after storage and resuspended in fresh-frozen autologous plasma. The Iloprost-treated and washed platelets exhibited an increased sensitivity to the aggregating agents, compared with the control platelets (p <0.01). Post-storage recovery of the synergistic aggregation was more than 80% of prestorage aggregation. Beta-thromboglobulin (beta-TG) release and thromboxane B2 (TXB2) formation were significantly inhibited in Iloprost-treated platelets (p <0.01). After the second centrifugation step, beta-TG release was 0.7% +/- 0.3%, compared with 2.7% +/- 0.9% for the controls. TXB2 was 99 +/- 91 pg/ml, compared with 495 +/- 356 pg/ml for the controls. Platelet morphology and ultrastructure were well preserved during 5-day storage. In addition, Iloprost exerted a cytoprotective effect, as evidenced by the significant reduction in lactate dehydrogenase leakage. Post-storage LDH was 378 +/- 159 and 415 +/- 239 U/l respectively by the two Iloprost concentrations, compared with 1180 +/- 937 U/l for the control platelets. The inhibitory and cytoprotective effects of Iloprost were sustained throughout storage, in contrast to the effect of PGE1 (Prostin) which was limited to the early phase of storage