Background: The optimal extent of the prostate biopsy remains controversial. There is a need to avoid detection of insignificant cancer but not to miss significant and curable tumors. In alternative treatments of prostate cancer, repeated sextant biopsies are used to estimate the response. The aim of this study was to investigate the reliability of a repeated systematic sextant biopsy as the standard biopsy technique in patients with significant tumors which are being considered for curative treatment. Methods: Systematic sextant biopsy was performed in vitro in 92 radical prostatectomy specimens. Of these patients, 81 (88.0%) had palpable lesions. Results: Of the 92 investigated patients, 70 (76.1%) had potentially curable pT2-3pN0 prostate cancers. In these patients, the cancer was detected only in 72.9% of cases by a repeated in vitro biopsy. In the pT2 tumors, there was a detection rate of only 66.7%. Conclusions: This study underlines the fact that a considerable number of significant and potentially curable tumors remain undetected by the conventional sextant biopsy. A negative sextant biopsy does not rule out significant prostate cancer. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Die Stanzbiopsie ist ein etabliertes minimalinvasives Verfahren im Rahmen der interventionellen Diagnostik, bei der Proben menschlichen Gewebes für histologische Untersuchungen zur Erkennung bzw. zum Nachweis u. a. karzinogener Gewebe entnommen werden. Zur Gewebeentnahme wird ein zweiteilig aufgebautes Nadelsystem in das Zielgewebe eingeschossen. Bei der Beobachtung dieses Prozesses sind auffällige Nadelablenkungen des Systems erkennbar. Ursächlich dafür sind die an der Nadelspitze unsymmetrisch angreifenden Kräfte in Verbindung mit der geringen Biegesteifigkeit des Nadelsystems. Im Rahmen eines öffentlich geförderten Projektes konnten an realitätsnahen Gewebephantomen experimentelle Untersuchungen zur Quantifizierung der Nadelablenkungen durchgeführt sowie ein mathematischer Ansatz zur Simulation dieses Effekts entwickelt werden. Darauf aufbauend wurde ein neuer Nadelschliff entwickelt, der eine wesentliche Verbesserung des aktuellen Status bringt. / Biopsy is an established method of the minimally invasive medicine to take human tissue samples for examination determining the presence or extent of a disease. Frequently applied method to detect a prostate or breast cancer is the punch biopsy. The components of the used devices include an inner needle with a notch sampling the tissue and an outer cannula to cut the tissue. During the biopsy, the doctor inserts the needle system into the human tissue under supervision by sonography to support the needle steering. After pushing the trigger, the components of the needle system move successively and penetrate the desired area. The device consists of a two-part spring mechanism to generate the needle movement. Observations of the needle movement by a highspeed camera shows a considerable deflection of the needle tip which makes tapping and tissue sampling more difficult. This is caused by unbalanced forces acting on the needle tip and the low bending stiffness of the needle. Publicly financed experimental studies in the quantification of the needle deflection were undertaken and a mathematical approach for the simulation of these effects was developed. The model, which consists of a flexible needle and a parameterized tissue model, is implemented in the multibody simulation software Recurdyn.

Prenatal diagnostics is headed in several directions - towards visualization of fetuses and biochemical, cytogenetic and molecular genetic diagnostics in laboratories. Whereas visualization of fetuses does not a priori represent any direct risk for pregnancy and does not increase the number of potential pregnancy complications, this is not always the case with the laboratory testing. There are known risks connected with invasive methods of prenatal diagnostics. The number of potential unintentional pregnancy complications and losses as well as the technical and economic aspects of invasive prenatal diagnostics lead to attempts of identifying ways of detecting any potentially affected individuals by screening methods, thus minimizing the undesirable impact of invasive diagnostics on the pregnant population. The more precise the selective criteria, the lesser the number of pregnant women exposed to invasive exams. Another way of decreasing the number of unintentional complications in relation to invasive diagnostics is to simplify and improve the fetal samples harvesting methods during pregnancy. The work primarily focused on two areas: Determination of the relation between fraction shortening of the left and right ventricles and a fetal chromosomal complement, and verification of reliability of a new method...

In den letzten Jahren wurde die Sentinel Node Biopsie in Studien zur Diagnostik und Behandlung des N0-Halses als Stagingverfahren untersucht. Ziel der vorliegenden Studie war der Vergleich der postoperativen Lebensqualität und des funktionellen Status bei Patienten mit oralen und oropharyngealen Karzinomen, die sich einer Sentinelbiopsie, bzw. einer selektiven Neck Dissection bei N0-Hals unterzogen haben. 57 Patienten mit primär operativ behandeltem Karzinom wurden im Rahmen der Studie untersucht, 29 nach Sentinel Node Biopsie und 28 nach selektiver Neck Dissection. Es wurde die postoperative gesundheitsbezogene (EORTC QLQ-C30) und krankheitsspezifische Lebensqualität (EORTC QLQ-H&N35) erfasst. Patientenbezogene psychosoziale Variablen wurden anhand der „Hospital Anxiety and Depression Scale“ (HADS) und der Kurzform des „Progredienzangst-Fragebogens“ (PA-F-KF) ermittelt. Die Erhebung des klinischen Gesundheitszustandes erfolgte unter besonderer Berücksichtigung des funktionellen Status nach zervikaler Lymphknotendissektion. Bezüglich der gesundheitsbezogenen Lebensqualität sowie der Angst und Depression existierten keine signifikanten Unterschiede. Hinsichtlich der krankheitsspezifischen Lebensqualität zeigte sich, dass die Patienten nach Sentinel Node Biopsie weniger Schluckbeschwerden angaben (p=0,037). Ebenso zeigte sich bei der klinischen Untersuchung eine geringere Beeinträchtigung durch die zervikalen Narben. Die Sentinel Node Biopsie bietet, neben dem geringeren operativen Aufwand, der schnelleren Rekonvaleszenz und der geringeren funktionellen Minderung der Patienten, eine tendenzielle Verbesserung der krankheitsspezifischen Lebensqualität. Als Grund für die subjektiv weniger beeinträchtigte Schluckfunktion kann die fehlende Präparation der suprahyoidalen Muskulatur und der entsprechend innervierenden Nerven in Erwägung gezogen werden.

Head and neck cancers (HNSCC) are highly heterogeneous disease, results from two major carcinogens - tobacco and/or alcohol, or HR HPV infection. This thesis was based on 60 biopsies of head and neck tumours embedded into paraffin after histological verification. HPV infection, including particular types was monitored in different HNSCC regions by multiplex qPCR. Subsequent IHC demonstrated expression of p16INK4A and p53 as a possible diagnostic biomarker. Based on the information, patients with HNSCC can benefit from antiEGFR therapy by Cetuximab, but so far without defined predictors, the analysis of point mutations of Ras gene family (Kras, Nras) and Braf gene was performed. These mutations were monitored as potential predictive biomarkers, in correlation with gender, age and other risk factors. For all statistical processing the Chi-x2 test was used. Key words: Head and neck cancers, biopsy, HPV types, PCR, p16INK4A, p53, molecular predictors, Kras, Nras, Braf

Pancreatic cancer (PC) is extremely severe malignant disease with a five-year survival of less than 5%. Currently there is no reliable tool for the diagnosis of PC in its early stages. At the time of clinical symptoms most patients are in an advanced stage of the disease and the treatment does not usually have a significant effect. For these reasons emphasis is gradually shifting to the search for the suitable molecular markers for improvement of the diagnosis and assessment of the survival prognosis with respect to a possibility of surgical treatment. MiRNA represent one of the most promising markers, although, their examination in pancreatic tissue is a complicated process. One of the reasons is the very small amount of the source material coming from a fine needle biopsy. A second cause of problems is the subtle character of the pancreatic tissue resulting in significantly lower yields of molecular genetic analysis when compared to other epithelial tissues. An additional negative factor is heterogeneity of the tissue resulting in disproportionate representation of tumor cells within the sample. A suitable choice of procedures for isolation of nucleic acids (NA) and subsequent analysis including quantification of tumor cells is critical for accurate evaluation of the miRNA levels. This work is...

Objectifs : L’objectif a été de d’optimiser les protocoles d’acquisition des examens d’angiomammographie double-énergie, d’étudier la faisabilité de l’angiotomosynthèse pour la détection et la caractérisation des tumeurs mammaires, et d’étudier la faisabilité des biopsies stéréotaxiques sous guidage de l’angiomammographie. Méthodes : Une étude d’optimisation des paramètres d’acquisition de l’angiomammographie a été réalisée dans 4 situations cliniques pour lesquelles la qualité diagnostique requise des images de basse énergie et la dose totale délivrée à la patiente ne sont pas identiques. L’optimisation des paramètres d'exposition (anode/filtre, kVp, mAs) des images de basse énergie (BE) et haute énergie (HE) a été réalisée à partir d’une modélisation théorique de la chaîne d’acquisition. Une validation a été effectuée par mesures expérimentales sur des images de fantôme d’inserts d’iode. Nous avons ensuite étudié la technique d’angiotomosynthèse mammaire basée sur une approche double-énergie. Un nouveau fantôme anthropomorphique numérique du sein et de ses lésions, basé sur l’utilisation de primitives géométriques complexes et d’une technique de maillage surfacique, a été amélioré et utilisé pour évaluer les performances de l’angiomammographie optimisée, puis de l’angiotomosynthèse en comparaison à l’angiomammographie. Enfin, nous avons proposé un scénario pour la réalisation d’un examen de stéréotaxie avec injection d’un agent de contraste iodé et étudié la faisabilité de recombinaison d’image de haute et de basse énergie acquises à des temps différents de l’injection.Résultats et conclusion : Les optima des paramètres d’exposition trouvés par simulation avec les valeurs de SDNRpixel et SDNR2pixel /Dosetotale qui en résultent, ont été confirmés expérimentalement. Les valeurs de SDNR par pixel dans les images recombinées sont augmentées pour toutes les indications cliniques en comparaison à celle obtenues avec SenoBright ® (produit commercial de référence). L'impact sur la qualité de l’image de BE, évalué par des expérimentations sur fantôme CDMAM, a montré que les paramètres optimisés fournissent une détection similaire ou acceptable par rapport à la mammographie standard, à l’exception de l'indication de dépistage lorsque l’on considère les objets de très petits diamètres.L’étude de lecture humaine d’images simulées d’un fantôme anthropomorphique du sein incluant le rehaussement glandulaire physiologique et différents modèle tumoraux n’a pas montré d’augmentation significative de sensibilité de détection des acquisition 3D d’angiotomosynthèse comparativement aux acquisitions 2D d’angiomammographie. Les deux paramètres qui influençaient le plus la sensibilité était la concentration en iode des tumeurs et la densité du sein. L’angiomammographie était par ailleurs significativement plus spécifique que l’angiotomosynthèse. Une perspective d’amélioration pour l’angiotomosynthèse pourrait donc être l’utilisation d’algorithmes de reconstruction 3D spécifiques de cette modalité qui minimiseraient le bruit de reconstruction. Le scénario proposé pour la réalisation de biopsies sous guidage de l’angiomammographie, a mis en évidence deux contraintes techniques que sont l’échauffement du tube à rayons X et le surcroit de dose dû à la répétition des paires d’acquisitions en haute et basse énergies. Une des solutions envisagées a été de limiter le nombre d’acquisitions de BE. Notre étude a montré que la recombinaison d’une image HE avec une image BE acquise antérieurement modifiait le SDNR des lésions simulées comparativement à une recombinaison appariée d’images BE et HE acquises au même temps de l’injection. Ces modifications dépendaient du temps du pic de rehaussement maximal et du washout de la lésion. / Objectives: The purpose was to optimize the exposure parameters of CESM examinations, to assess the feasibility of contrast-enhanced DBT (CE-DBT) for the detection and the characterization of breast tumors, and to assess CESM-guided stereotactic biopsies. Methods: At first, we optimized the CESM exposure parameters in four different clinical applications for which different levels of average glandular dose and different low energy image quality are required. The optimization of exposure parameters (anode/filter, kVp, mAs) for low energy (LE) and high energy (HE) images at different levels of average glandular dose and different ratios between LE and total doses has been conducted using a simulator of the x-ray mammographic image chain. An experimental validation was then performed through phantom experiments. Secondly, we assessed the potential of CE-DBT based on a dual-energy approach. A new mesh-based anthropomorphic breast phantom was improved and used to evaluate the performance of CESM and then to compare CESM and CE-DBT. Finally, we evaluated the technical feasibility of CESM-guided biopsy. After identifying some technical constraints, we assessed the performance of the recombination of LE and HE images acquired at different times after injection, using simulated images of a geometric phantom with uniform texture, and simulated images of an anthropomorphic textured phantom with and without motion artifacts.Results and conclusion : For the four different clinical indications, optima found by simulation, with resulting SDNRpixel and SDNR2pixel/Dosetotal, were confirmed through real acquisition of images on phantoms. Our results indicate that the SDNR per pixel in recombined CESM images increased in all of the four clinical indications compared to recombined images obtained using SenoBright ® (commercial product used as reference). This result suggests the possibility to detect more subtle contrast enhancements and to decrease the number of false negatives found in clinical CESM examinations. The impact of a new dose allocation between LE and HE exposures was also evaluated on LE image quality. Results from CDMAM phantom experiments indicate that optimized parameters provide similar or acceptable detection compared to standard mammography, except for screening indication when considering the very small diameter objects.The human observer study on anthropomorphic phantom images, taking into account tumor and breast parenchyma enhancement, revealed that detection and characterization sensitivity of iodine-enhanced lesions are not statistically different between 2D CESM and 3D CE-DBT. The most influencing parameters for the detectability and the lesion size assessment were the lesion iodine concentration and the breast density. CESM was significantly more specific than CE-DBT. One of the assumptions to explain this result is the presence of higher noise in CE-DBT than in CESM images. A future improvement for CE-DBT could therefore be the design of a specific reconstruction algorithm minimizing reconstructed noise.With respect to CESM-guided biopsy the proposed scenario pointed out two major constraints, one related to the thermal load of the x-ray tube, the second related to the increased dose due to the repetition of LE and HE images. One proposed solution was to limit the number of LE exposures, requiring the possibility to recombined LE and HE images acquired at different injection time points. Our study showed that the recombination of a HE image with a LE image acquired earlier leads to SDNR changes compared to paired recombination. These changes are function of the enhancement time to peak and the washout of the lesion, and had a limited impact on the lesion detectability.

AL’objectif de ce travail de recherche est le développement, la mise au point et la validation d’une méthode de spectroscopie multi-modalités en diffusion élastique et autofluorescence pour caractériser des tissus biologiques in vitro et in vivo. Ces travaux s’organisent en quatre axes. La première partie des travaux présente l’instrumentation : développement, réalisation et caractérisation expérimentale d’un système de spectrométrie bimodale multi-points fibrée permettant l’acquisition de spectres in vivo (distances variables, acquisition rapide). La deuxième partie porte sur la modélisation des propriétés optiques du tissu : développement et validation expérimentale sur fantômes d’un algorithme de simulation de propagation de photons en milieux turbides et multi-fluorescents. La troisième partie propose une étude expérimentale conduite ex vivo sur des anneaux artériels frais et cryoconservés. Elle confirme la complémentarité des mesures spectroscopiques en diffusion élastique et autofluorescence et valide la méthode de spectroscopie multi-modalités et l’algorithme de simulation de propagation de photons. Les résultats originaux obtenus montrent une corrélation entre propriétés rhéologiques et optiques. La quatrième partie développe une seconde étude expérimentale in vivo sur un modèle pré-clinique tumoral de vessie. Elle met en évidence une différence significative en réflectance diffuse et/ou en autofluorescence et/ou en fluorescence intrinsèque entre tissus sains, inflammatoires et tumoraux, sur la base de longueurs d’onde particulières. Les résultats de la classification non supervisée réalisée montrent que la combinaison de différentes approches spectroscopiques augmente la fiabilité du diagnostic. / This research activity aims at developing and validating a multimodal spectroscopy method in elastic scattering and autofluorescence to characterize biological tissues in vitro and in vivo. It is articulated in four axes. At first, instrumentation is considered with the development, the engineering and the experimental characterization of a fibers bimodal, multi-points spectrometry system allowing the acquisition of spectra in vivo (variable distances, fast acquisition). Secondly, the optical properties of tissues are modelled with the development and the experimental validation on phantoms of a photons propagation simulation algorithm in turbids media and multi-fluorescent. Thirdly, an experimental study has been conducted ex vivo on fresh and cryopreserved arterial rings. It confirms the complementarity of spectroscopic measurements in elastic scattering and autofluorescence, and validates the method of multi-modality spectroscopy and the simulation of photons propagation algorithm. Results have well proved a correlation between rheological and optical properties. Finally, one second experimental study in vivo related to a pre-clinical tumoral model of bladder has been carried out. It highlights a significant difference in diffuse reflectance and/or autofluorescence and/or intrinsic fluorescence between healthy, inflammatory and tumoral tissues, on the basis of specific wavelength. The results of not supervised classification show that the combination of various spectroscopic approaches increases the reliability of the diagnosis.

Brustkrebs stellt eine der am häufigsten vorkommenden Krebserkrankungen bei Frauen weltweit dar. Jährlich erkranken in Deutschland ca. 47.000 Frauen neu an Brustkrebs, ca. 18.000 fallen dieser Krankheit im gleichen Zeitraum zum Opfer. Die Brustkrebsdiagnostik basiert auf klinische und verschiedene bildgebende Methoden, die Magnetresonanztomographie (MRT) weist dabei die höchste Sensitivität speziell bei der Erkennung kleiner Tumore unter 5 mm auf. Im Hinblick auf zukünftige Verbesserungen der MR-Bildgebung wird bereits vermutet, dass im Jahr 2010 ca. 50% der neudetektierten Brustkrebse kleiner als 10 mm sein werden. Zur Erhöhung der Diagnosesicherheit werden suspekte Läsionen sowie unklare bildgestützte Befunde zusätzlich mittels Biopsie abgeklärt. In Bezug auf den Stand der Technik ist die sichere Biopsie von Tumoren unter 10 mm Größe jedoch schwierig. Mit dem Ziel, die MR-gestützte Biopsie im Hinblick auf eine höhere Effizienz und Präzision zu verbessern, wurde ein neuer Prototyp für minimal invasive Biopsien speziell in geschlossenen MR-Tomographen entwickelt. Dieses MR-kompatible System basiert auf verschiedene Neukonzeptionen, mit einem automatischen Positioniersystem und Biopsieinstrument zur Ausführung der Intervention. Die extrem hohen Anforderungen an dieses System konnten nur durch spezielle Konstruktionen und Kinematiken, sowie durch MR-kompatible Materialien, Aktoren und Sensoren gelöst werden. Das System ist modular aufgebaut und unterstützt Brustbiopsien sowohl von cranial oder caudal im direkten Anschluss an die Tumorerkennung mit einer neuen doppelseitigen MR-Brustspule. Ein großer Vorteil dieses neuen Ansatzes liegt in der hohen Präzision und der Möglichkeit, sowohl die bildgebende Diagnostik als auch die Biopsie während eines Untersuchungstermines durchzuführen. Die vorklinische Erprobung in einem 1,5 T Hochfeld-MRT zeigte, dass die Zielabweichungen des Instrumentes geringer als 1 mm waren, so dass Interventionen mit hoher Genauigkeit und Reproduzierbarkeit durchführbar wären. Das System implementiert benutzerfreundliche Oberflächen für die Interventionsplanung und für die Gerätesteuerung. Das vorliegende Dissertation stellt die Konzepte und Ergebnisse dieser neuen Biopsieeinrichtung vor und nimmt Bezug auf zahlreiche wissenschaftliche Untersuchungen, insbesondere im Hinblick auf die Anwendung von Materialien und Aktoren im MRT-Magnetfeld. / Breast cancer is one of the most common cancer diseases which women suffer world wide. The incidence rate of breast cancer in Germany goes along with about 47.000 women per year, 18.000 fatal casualties were ascertained in the same period. The breast cancer diagnostic is based on clinical and different imaging methods, whereas Magnetic Resonance Imaging (MRI) is the most sensitive imaging modality in the detection of especially small lesions under 5 mm. Due to improvements of breast imaging - especially MRI - it has been predicted that by the year 2010 about 50% of newly diagnosed breast cancers will be less than 10 mm in size. However, to assure the image based breast cancer diagnosis, biopsies of tumor tissue are often necessary in order to avoid false specified results. With reference to the state of the art, it is still difficult to achieve sufficient accurate MRI-supported biopsies for tumor sizes of under 10 mm. To improve the MR-controlled diagnostic in respect of increasing the efficiency and precision of the biopsy method, a new apparatus for minimal invasive breast biopsies particularly for the use inside closed bore MRI-scanner was developed. This MR-compatible device is based on new concepts which meet the extremely high requirements on interventions in strong magnetic fields through special designs and kinematic concepts and the application of MR-compatible materials, actors and sensor systems. It is of a modular structure and consists mainly of an automated positioning unit and an integrated intervention tool. This new system makes it possible to do the breast interventions either from the cranial or the caudal position directly after tumor detecting with the use of a new double breast coil. A major advantage of this approach is the high accuracy and the possibility to realize image diagnostic and biopsy in one session. As the preclinical evaluation with a 1.5 T MRI-scanner showed, the deviation of the intervention device regarding instrument positioning to a located target was less than 1mm, so that interventions could be carried out precisely and reproducible. Furthermore there were no image interferences due to the additional materials in the MRI-isocenter. The system implements a user-interface for intervention planning on up-to-date MR images and device control. Besides the concepts and results of the new biopsy device, the present dissertation refers to numerous scientific investigations with a focus on material and actuator application in the magnetic field of a MRI-scanner.

1 ABSTRACT Background Breast cancer cell population characteristics are used in common clinical practice for estimation of prognosis of the malignant disease (prognostic factors) and for prediction of reactivity of the tumor to certain therapeutic modality (predictive factors). Also axillary lymph node status is an independent prognostic factor in women with early breast cancer. Therefore, surgical excision and following histopathological examination of the nodes is the obligatory part of primary breast cancer surgery. The extension of axillary surgery varies widely, although sentinel lymph node biopsy is considered to be the standard procedure. However, it must be admitted that this type of procedure need not be optimal for all the breast cancer patients. Aims of the study The aim of this study is the verify the hypothesis whether or not the axillary lymph node metastatic affection can be effectively estimated using non-surgical methods - i.e. by evaluation of the combination of prognostic and predictive factors of the primary breast tumor. Statistical model composed on the basis of data of early breast cancer patients is the basic tool for this prediction. Application of this model In everyday practice can enable to adjust the extent of axillary surgery for each individual patient. Patients and methods A...