Cochlear imaging in the era of cochlear implantation : from silence to sound

Cochlear implants (CIs) are a well accepted treatment for hearing impaired people. In pre- and postoperative assessment of CI-candidates imaging plays an important role to analyze anatomy, rule out pathology and determine intracochlear positioning and integrity of the implant. Developments in CI-design, differences in surgical approach and broadening of treatment indications have raised new questions to radiologists, which were the subject of several studies described in this thesis. For optimal, a-traumatic positioning of a CI precise information about the inner ear anatomy is mandatory. We describe the development, validation and application of a method for 3-dimensional medical image exploration of the inner ear. This renders a tool to obtain cochlear dimensions on clinical computer tomography (CT) images. This will be useful for patientspecific implantplanning. It also shows an anatomical substrate for cochlear trauma during insertion. For postoperative imaging we studied the value of multislice-CT for optimal visualization of the implant within the cochlea. Its role to evaluate operation technique and electrode design, to study frequency mapping and to assess cochlear trauma is discussed. Moreover an international consensus for an objective cochlear framework is presented, forming a common ground for clear and easy exchange of findings in scientific and clinical studies.AB, de Nationale Hoorstichting/Sponsor Bingo Loterij, Foundation Imago, Bontius Stichting inz. Doelfonds BeeldverwerkingUBL - phd migration 201

PRELIMINARY FINDINGS OF A POTENZIATED PIEZOSURGERGICAL DEVICE AT THE RABBIT SKULL

The number of available ultrasonic osteotomes has remarkably increased. In vitro and in vivo studies have revealed differences between conventional osteotomes, such as rotating or sawing devices, and ultrasound-supported osteotomes (Piezosurgery®) regarding the micromorphology and roughness values of osteotomized bone surfaces. Objective: the present study compares the micro-morphologies and roughness values of osteotomized bone surfaces after the application of rotating and sawing devices, Piezosurgery Medical® and Piezosurgery Medical New Generation Powerful Handpiece. Methods: Fresh, standard-sized bony samples were taken from a rabbit skull using the following osteotomes: rotating and sawing devices, Piezosurgery Medical® and a Piezosurgery Medical New Generation Powerful Handpiece. The required duration of time for each osteotomy was recorded. Micromorphologies and roughness values to characterize the bone surfaces following the different osteotomy methods were described. The prepared surfaces were examined via light microscopy, environmental surface electron microscopy (ESEM), transmission electron microscopy (TEM), confocal laser scanning microscopy (CLSM) and atomic force microscopy. The selective cutting of mineralized tissues while preserving adjacent soft tissue (dura mater and nervous tissue) was studied. Bone necrosis of the osteotomy sites and the vitality of the osteocytes near the sectional plane were investigated, as well as the proportion of apoptosis or cell degeneration. Results and Conclusions: The potential positive effects on bone healing and reossification associated with different devices were evaluated and the comparative analysis among the different devices used was performed, in order to determine the best osteotomes to be employed during cranio-facial surgery

[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)

Lung cancer: sex difference in the lifetime risk and 10-year risk between 1995 and 2013 in a Swiss population

Introduction: In Switzerland, lung cancer is a leading cause of cancer death. Because smoking is the major cause of lung cancer, trends in lung cancer incidence are following trends in smoking habits in the population, with a latency time of about 30 years. In Switzerland, there was a peak in men’s lung cancer incidence in the 1980s, followed by a decrease until now. Among women, the incidence has increased since the 1970s and, apparently, has not yet reached a peak. Because cancers are feared diseases, an adequate communication about the individual risk of developing cancer is important. Mortality and incidence are traditionally used to assess cancer burden. However, these metrics are difficult to interpret at the individual level. Providing the lifetime and 10-year risk of cancer could improve risk communication for patients and health professionals. Our aim was to estimate trends in the lifetime and 10-year risk of lung cancer, in men and women, between 1995 and 2013

Is overdiagnosis of prostate cancer leveling off? Recent changes in incidence and surgery rates in Switzerland

Many western countries, including Switzerland. Various organizations have recently recommended against routine screening, notably due to the high risk of overdiagnosis or overtreatment. Our aim was to examine whether recent changes in secular trends in the incidence and mortality of prostate cancer, as well as prostatectomy rates have been observed in Switzerland