This dissertation deals with quantitative perfusion analysis of MRI contrast-enhanced image time sequences. It focuses on two so far separately used methods -- Dynamic contrast-enhanced MRI (DCE-MRI) and Dynamic susceptibility contrast MRI (DSC-MRI). The common problem of such perfusion analyses is the unreliability of perfusion parameters estimation. This penalizes usage of these unique techniques on a regular basis. The presented methods are intended to improve these drawbacks, especially the problems with quantification in DSC in case of contrast agent extravasation and instability of the deconvolution process in DCE using advanced pharmacokinetic models. There are a few approaches in literature combining DCE and DSC to estimate new parameters of the examined tissue, namely the relaxivity of the vascular and of the interstitial space. Originally, in this scheme, the 2CXM DCE model was used. Here various models for DCE analysis are tested keeping in mind the DCE-DSC combination. The ATH model was found to perform better in this setting compared to 2CXM. Finally, the ATH model was used in alternating DCE-DSC optimization algorithm and then in a truly fully simultaneous DCE-DSC. The processing was tested using simulated and in-vivo data. According to the results, the proposed simultaneous algorithm performs better in comparison with sequential DCE-DSC, unleashing full potential of perfusion analysis using MRI.

During recent years, significant advances have been made in the field of molecular therapy in urologic oncology, mainly for advanced renal cell carcinoma. In this hitherto largely treatment-refractory disease, several agents have been developed targeting the von Hippel-Lindau metabolic pathway which is involved in carcinogenesis and progression of the majority of renal cell carcinomas. Although cure may not be expected, new drugs, such as the multikinase inhibitors sorafenib and sunitinib and the mammalian target of rapamycine inhibitor temsirolimus, frequently stabilize the disease course and may improve survival. Fewer data are available supporting molecular therapies in prostate, bladder, and testicular cancers. Preliminary data suggest a potential role of high-dose calcitriol and thalidomide in hormone-refractory prostate cancer, whereas targeted therapies in bladder and testicular cancers are still more or less limited to single-case experiences. The great theoretical potential and the multitude of possible targets and drug combinations, however, support further research into this exciting field of medical treatment of urologic malignancies. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Surface-enhanced Raman scattering (SERS) microscopy is a novel method of optical imaging for the localization and quantification of target molecules in cells and tissue specimens. The major advantages of SERS over fluorescence are quantification and spectral multiplexing due to the small line width of vibrational Raman bands. The position of the plasmon band of both hollow gold/silver nanoshells and silica-encapsulated gold nanoclusters can be tuned for maximum SERS enhancement upon red laser excitation, which is optimal for minimizing the disturbing autofluorescence of tissue. In this work, silica-encapsulated and non-encapsulated SERS particles were used for the localization of target proteins in prostate tissue specimens. Two different biofunctionalization methods were established for each type of SERS particles. The cross-linking method based on s-NHS/EDC chemistry was modified for covalently conjugating proteins to hollow gold/silver nanoshells and gold nanostars in order to minimize the aggregation of SERS nanoparticles during and after cross-linking. As an alternative to covalent conjugation chemistry, the noncovalent binding of antibodies to the SERS particles via an adapter protein (protein A/G) was established. The influence of several factors that determine the quality of results obtained by SERS imaging, such as the number of immuno-SERS conjugates, incubation time, antigen retrieval and blocking buffer, were investigated. Rapid SERS microscopy with 30 msec acquisition time per pixel was enabled by using silica-encapsulated gold nanoclusters for the localization of p63 proteins on prostate tissue specimens from healthy donors. Two-color SERS experiments for the parallel localization of PSA and p63 were performed with silica-encapsulated and non-encapsulated nanoshells. The quality of the results depends less on the nature of the surface chemistry of the nanoparticles (with or without silica encapsulation), but more on the blocking buffer and the antigen retrieval method. Silica-encapsulated gold nanoclusters were also used for the simultaneous quantification of three cytokines (IL1, IL8 and TNF- α) in a SERS-based sandwich immunoassay with a detection limit of ca. 0.3 pM. Keywords: Raman, SERS microscopy, biocompatibility of nanoparticles, cross-linking, antigen unmasking methods, antigen detection, immunohistochemistry, immunoassay.

No description available.

The objective of the diploma thesis is the new building of Cancer Prevention Centre, first of its kind in the Czech Republic. The site is located on steep terrain of the south hillside of Žlutý kopec in Brno, which is a part of Masaryk Oncological Hospital complex. The aim of the Cancer Prevention Centre is to attract the citizens’ attention and invite them to undergo a preventive medical check-up with the potential to save hundreds of lives every year. The project takes this fact in consideration and strives to find ways leading not only towards establishing new relationship between the building and the public, but also towards connecting the city centre and nearby by residential area with the hospital complex. The three volumes of the buildings create a dynamic composition and therefore complete the characteristic development of Masaryk Oncological Centre. The main concept however revolves around the motive of instability, balance and journey which are all linked to tumour diseases.

Diplomová práce zpracovává komplexní návrh nového Centra prevence rakoviny v areálu Masarykova onkologického ústavu na Žlutém kopci v Brně. První stavba svého druhu v České republice doplňuje současnou zástavbu nemocničního areálu. Koncepce navrženého souboru budov se zaměřuje na kontakt hranice nemocničního areálu s nově vznikající obytnou čtvrtí v této lokalitě. Návrh obsahuje jak samotné centrum prevence, lůžkové oddělení nebo protonové centrum, tak pronajímatelné prostory pro další služby široké veřejnosti.

Hintergrund Subjektive Krankheitsannahmen beinhalten Annahmen über Symptome, emotionale Reaktionen, Verlauf, Konsequenzen und Kontrollierbarkeit einer Erkrankung. Aktuelle Studien zeigen, dass subjektive Krankheitsannahmen mit der Krankheitsverarbeitung und dem psychischen Wohlbefinden assoziiert sind. Bisher gibt es kein Erhebungsinstrument zur Befragung von Kindern, sodass hier oftmals nur der Bericht der Eltern verfügbar ist. Ziel der Arbeit Das Ziel ist die Entwicklung und psychometrische Überprüfung eines Puppeninterviews zur altersgerechten Erfassung subjektiver Krankheitsannahmen für Kinder ab 4 Jahren. Beschreibung von Durchführungsempfehlungen mit Indikation und Kontraindikation. Methode Das Puppeninterview zur Erfassung subjektiver Krankheitsannahmen wurde auf Grundlage des „Illness Perception Questionnaire“ (IPQ-R) und des „Berkeley Puppet Interviews“ entwickelt und an zwei Stichproben (n = 11 und n = 64) überprüft. Ergebnisse Die Anwendbarkeit, Verständlichkeit und Nützlichkeit des Puppeninterviews wurde für die Akut- und Nachsorgephase gezeigt, wobei sich die Krankheitsannahmen je nach Krankheitsphase unterscheiden können. Es zeigten sich erwartungskonforme Interskalenkorrelationen im Puppeninterview (z. B. Chronizität – Konsequenzen für die Lebensführung: r = 0,690, p ≤ 0,05), hypothesenkonforme Ergebnisse zur Konstruktvalidität (z. B. Chronizität – internale Kontrolle r = −0,711, p ≤ 0,05) und zufriedenstellende interne Konsistenzen. Mitunter besprachen die Kinder mit den Puppen mögliche Bewältigungsstrategien, was zu einer Entlastung beitrug. Schlussfolgerung Die Einschätzungen der Eltern können zukünftig durch eine zuverlässige Erhebung von subjektiven Krankheitsannahmen bei Kindern ab 4 Jahren ergänzt werden, um medikamentöse und psychosoziale Interventionen gezielt anzupassen. / Background Illness perceptions comprise assumptions about symptoms, timeline, consequences, controllability, and emotional responses of an illness. Recent evidence shows that illness perceptions are associated with coping and well-being. Until now, assessment is based on parental report only, since no instrument for the direct assessment of children is available. Objectives Development of a puppet interview for the age-appropriate assessment of illness perceptions in children up to the age of 4 years. Recommendations for the application (including indications and contraindications) and assessment of psychometric properties. Materials and methods The puppet interview was developed based on the Illness Perception Questionnaire (IPQ-R) and the Berkeley Puppet Interview and examined in two samples of patient–parent dyads (n = 11 und n = 64). Results The puppet interview is applicable (comprehensible, useful) in acute treatment and follow-up care. Illness perceptions may vary in different treatment phases. We saw confirming intercorrelation of scales (chronicity – consequences: r = 0.690, p ≤ 0.05) and adequate psychometric properties (construct validity: chronicity – internal control: r = −0.711, p ≤ 0.05, internal consistency). Some children even discussed potential coping strategies with the puppets. Conclusion Parental report can be complemented by a self-report measure of illness perceptions in affected children aged 4 years and older. This will allow for the further adaptation of medical and psychosocial treatment.

Objective: Recent evidence suggests that illness perceptions in paediatric patients and their parents may differ, with parents holding more negative views compared to their children. Little is known about illness perceptions of very young patients and their parents. This study investigates illness perceptions in paediatric cancer patients aged 4–18 years and their parents in acute treatment or follow‐up care, distinguishing patients by age (4–11, 12–18) and stage of medical treatment. - Methods: N = 45 patient–parent dyads in acute treatment and n = 95 dyads in follow‐up care were examined. Parents and older children aged 12–18 years completed the Illness Perception Questionnaire—Revised (IPQ‐R) and younger children aged 4–11 years were examined using an age‐adapted hand puppet interview containing the IPQ‐R questions. Difference scores of illness perceptions (symptoms, timeline‐acute/chronic, timeline‐cyclical, personal control, illness coherence, consequences, emotional representations) between children and parents were tested for significance using Wilcoxon signed‐rank tests. - Results: Overall, parents perceived more symptoms associated with their child's illness/treatment than the children themselves. In acute treatment, younger children indicated more negative and older children more positive views regarding chronicity than parents. Younger children held less negative views on consequences, and all children reported less negative emotional representations than parents. In follow‐up care, all children held less negative views on consequences and emotional representations. Older children reported less negative views on chronicity, cyclicity and illness coherence. - Conclusion: Differences in illness perceptions of paediatric patients and their parents should be considered during and after treatment/medication and psychosocial care to support illness coping in person‐ and family‐centred interventions.

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No description available.