133 research outputs found

    Non-invasive prenatal testing: a multifaceted assessment

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    Item does not contain fulltextRU Radboud Universiteit, 05 juli 2016Promotor : Vugt, J.M.G. van Co-promotores : Bekker, M.N., Faas, B.H.W

    Prenatal genetic care: debates and considerations of the past, present and future

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    Item does not contain fulltextAfter karyotyping invasively obtained fetal material for decades, the field of prenatal genetic care has changed tremendously since the turn of the century. The introduction of novel technologies and strategies went along with concerns and debates, in which key issues were costs, the finding of variants of unknown or uncertain clinical relevance, commercialization and ethical and social issues. At present, there is an explosion of new genomic technologies, which need critical assessment prior to implementation, especially in the prenatal field. The key issues of the debates we had in the past will again play a major role in guiding us toward careful implementation of these new techniques in future

    Diffuse Reflectance Spectroscopy for Intraoperative Tumor Margin Assessment: Workflow Analysis and Effect of Coagulation on Tissue Sensing

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    The aim of this graduation project is to assess the feasibility of the photonic technology called diffuse reflectance spectroscopy (DRS) to aid in intraoperative margin assessment with the goal of obtaining clear margins for liver, breast and soft tissue tumors. The idea is to integrate optical fibers in the existing and widely used electrosurgical knife, which consists of a pencil holder and a blade electrode. The work consists of workflow analyses and experiments. Based on the former the role of DRS in clinical practice can be specified. The main object of the experiments is to find out if DRS is still usable when a layer of coagulated tissue due to electrosurgical activity is present. Lumpectomy workflows using four techniques are investigated. For palpable tumors intraoperative ultrasound (US) and palpation are used, while non-palpable tumors require iodine seeds or placement of a guidewire. The most important limitations of current methods include: no information about the actual margin for iodine seeds and guidewire procedures, complex patient preparation, expertise required to understand US images and lack of reinforced learning for palpation. One advantage of all techniques is that they provide extra information, allowing the surgeon to create a more detailed mental image of the tumor. Ultrasound provides continuous information on the margin, while palpation is very intuitive. DRS integrated into the electrosurgical instrument provides distinct benefits in the local assessment phase, including direct feedback on whether or not to make a cut without losing information. DRS sensing should be directed forward, parallel to the axis of the pencil. In the experimental phase the shape and size of the tissue area influenced by electrosurgical treatment is inves- tigated first. It is found that layers of coagulation up to 1.4 mm may occur in surgery. Next, experiments are performed to identify the effect of coagulation on DRS spectra. Protein denaturation and reduced water con- tent are clearly visible in the diffuse reflectance spectra, resulting in a decreased slope and increased intensities of peaks in the near-infrared (NIR) range. Spectral alterations are severe, requiring further investigation using Monte Carlo (MC) simulations. Two-layered MC models that consist of coagulated tissue on top of normal tissue are build for coagulation up to 1.5 mm. Using the slope and peaks described above a predictive model is created, based on a sigmoid fit of these so-called predictors. Coagulation depth is predicted with R2 values up to 0.99, indicating a valid model. Two-layered MC models of normal and tumor tissue show that breast tumors can be detected up to 4 mm, liver tumors are visible at 2 mm and lipoma in skeletal muscle can be seen at 5 mm when the fiber distance (FD) = 6 mm. Finally, three-layered MC models of coagulated, normal and tumor tissue yield predictors that strongly differ from tissue without tumor presence. No predictive model for tumor depth is created. The results from this project show that accurate depth determination of coagulation is possible as well as sensing the presence of a tumor within the sensing zone. The latter ensures that DRS may bring at least the same qual- ities as iodine seeds and the guidewire. An important benefit is that DRS provides information on the complete margin, rather than a discrete point. Quantitative depth prediction is required to compete with intraoperative US for invasive tumors. Overall, it was shown that if DRS is successfully developed it can bring important benefits to clinical practice. The effect of tissue coagulation on diffuse reflectance spectra is large, but can be accounted for with a mathemat- ical predictive model. The next crucial step is further investigation of tumor depth sensing and investigation of a complete predictive model. The depth sensing requirements are only completely met for breast tumors. For liver resection, tumors are only detected up to 2 mm. This means that the desired 1 cm margin cannot be safeguarded with DRS. Close margins however are often accepted in clinical practice and do improve patient outcome. DRS integration should not be considered as a replacement for current margin assessment techniques but rather as a complement. Overall, integration of DRS into electrosurgical instruments seems promising. More research is required to see if DRS can truly perform in the OR.Bio-Inspired DesignBioMechanical EngineeringMechanical, Maritime and Materials Engineerin

    Developing a Breast Phantom to Test and Validate the Smart Electrosurgical Knife

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    Previous studies show that the smart electrosurgical knife, which adds diffuse reflectance spectroscopy to the traditional electrosurgical knife, is a promising technique for breast-conserving surgery, namely it enables real-time tissue characterization while cutting. More specifically, based on the fat/water-ratio, it enables intraoperative healthy from malignant tissue discrimination, therefore potentially reducing the re-excision rate with breast-conserving surgery procedures. However, the smart electrosurgical knife cannot be used on patients yet since it has not been validated yet. Several studies suggest phantoms are ideal for validation of systems including imaging systems like diffuse reflectance spectroscopy. Hence, for this master thesis, the objective was to develop a breast phantom that enables validation of the smart electrosurgical knife.Firstly, it was found that a study which enables validation of the smart electrosurgical knife, should mimic a breast-conserving surgery procedure including a breast phantom, so that the potential of the intraoperative margin assessment technique ‘’ diffuse reflectance spectroscopy ‘’, added to the traditional electrosurgical knife, could sufficiently be tested. For such a study to take place, it was found that the phantom should have a similar size and shape as human breasts containing a tumour. With regard to pre- and postoperative margin assessment, the phantom should have a contrast between the tumour and healthy phantom, which enables size, border, and location assessment of the phantom tumour upfront and residual tumour inspection after surgery. Intraoperatively, the phantom should have a significant difference in fat/water-ratio between the tumour and healthy phantom. This enables us to assess diffuse reflectance spectroscopy with its capability in discriminating healthy from malignant tissue. Furthermore, visually and mechanically, there should be a minimal difference between the tumour and healthy phantom, which eliminates the possibility of using the intraoperative margin assessment techniques, palpation and visual inspection. Finally, the phantom should have similar mechanical- electrically conductive and thermo tolerance properties as real breast tissue. This will result in realistic haptic feedback and tissue effects with electrosurgery.To develop such a phantom, various fat/water-ratios of water and lard, in combination with various additives such as guar gum, agar, gelatin and barium sulphate, were produced and tested. It turned out that agar in combination with water, lard, and the contrast agent barium sulphate, enables breast phantom production, that meets all the aforementioned phantom requirements. More specifically, the final phantom is a breast-shaped phantom with a realistic size and shape, consisting of healthy tissue with a tumour inclusion. The healthy tissue is composed of 50% lard, 50% water and then 5% agar by weight of water, whereas the tumour is composed of 20% lard, 80% water and then 3% agar- and 5% barium sulphate by weight of water. Since this phantom meets all requirements, it enables the design of a study that subsequently enables extensive testing and further validation of the smart electrosurgical knife.Biomedical Engineerin

    Evaluating the Translation of Diffuse Reflectance Spectroscopy into Hyperspectral Imaging: Bridging the gaps between the two technologies

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    Breast cancer is the most prevalent cancer in women with about 1.7 million new cases reported worldwide in 2012. The two main types of surgical treatment for breast cancer are mastectomy and lumpectomy. In mastectomy, the entire affected breast is excised whereas in lumpectomy only the tumor along with a rim of healthy tissue is excised. This rim of healthy tissue surrounding the tumor is called a ‘surgical margin’ and to prevent recurrence of cancer, it is necessary that there are no cancer cells remaining after the surgery. Owing to this purpose, many techniques have been developed to discriminate between healthy tissue and tumor. Two noteworthy techniques are namely, diffuse reflectance spectroscopy (DRS) and Hyperspectral Imaging (HSI), which use spectral information to discriminate between healthy and cancerous tissues. Both techniques have the potential to be used for real time intraoperative characterization of breast tissue in vivo but each technique has its respective limitations. While HSI provides non-contact tissue imaging which DRS does not, DRS provides spatially resolved depth information that HSI does not.The goal of the thesis is to evaluate the translation of Diffuse Reflectance Spectroscopy into Hyperspectral imaging by bridging the gaps between the two technologies. For this purpose, three main research questions were answered. First, the changes in spectral shapes were observed when moving from contact DRS to HSI by acquiring data from two intermediate DRS set ups that emulated the non-contact and illumination settings of HSI. Second, the scope of a spatially resolved non-contact DRS tool was assessed. And third, the spatially resolved non-contact DRS in a clinical setting was put into perspective. A multitude of experiments were performed to answer these three research questions. All experiments were performed on commercial butter or ex vivo porcine adipose tissue samples. DRS measurements were obtained for a wavelength range spanning 400 nm to 1600 nm.Biomedical Engineerin

    Breach detection using diffuse reflectance spectroscopy during spinal screw placement

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    The intraoperative guidance and placement of spinal screws is a complex procedure. High technical expertise is required fromthe surgeons in order to achieve adequate fixation and ensure patient safety by preventing vascular and neurological injuries. The conventional screw placement techniques face several challenges. Surgeons heavily rely on experience-based judgement, tactile feedback and X-ray guidance. The consequences of which are reflected in clinical literature via high risks associated with complications, screw placement accuracy variability and radiation exposure. Moreover, cost savings in terms of improved patient outcomes such as patient recovery times and fewer revision surgeries are major incentives towards development and clinical adoption of better intraoperative guidance technologies. The aim of this PhD work was to investigate the applicability of spectral sensing based technique namely Diffuse Reflectance Spectroscopy (DRS) for intraoperative instrument guidance and breach detection during pedicle screw placement procedures.Medical Instruments & Bio-Inspired Technolog

    The integration of diffuse reflectance spectroscopy into the electrosurgical knife used during breast-conserving surgery: Determining and overcoming the challenge of tissue debris adhering to the ‘smart’ electrosurgical knife

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    Among women, breast cancer has the highest incidence rate of all types of cancer worldwide. For 80% of these patients, a treatment option is the surgical procedure known as breast conserving surgery (BCS). Re-excision is required in 10-60% of these patients, as positive margins are encountered post-operatively, showing the need of an intra-operative margin assessment (IMA) technique. Diffuse Reflectance Spectroscopy (DRS) has proven to accurately discriminate real-time between malignant and non-malignant tissue. As electrosurgery (ES) is the main technique used for BCS, the incorporation of DRS into the electrosurgical knife (ESK) is desired. A ‘smart’ ESK has previously been developed, yet practical use was disturbed by tissue contamination of the integrated diffuse reflectance fibers during ES.This thesis, therefore, examines the characteristics of this contamination and the effects on the desired integration. Clinical and research analyses were done, obtaining requirements for a re-design of the ‘smart’ ESK. Instruments, settings and methods of cleaning the ESK in the operating room have been observed and the influence of clinical parameters on the amount of tissue debris has been investigated. Tissue contamination on ESK blades used for BCS was analyzed with the use of DRS and Fourier Transform – Infrared spectroscopy (FTIR). The impact of this contamination was additionally determined by power measurements of the ‘smart’ ESK after cutting on samples of subcutaneous porcine tissue for several time intervals.All measured spectra of the charring components adhering to the electrosurgical blades matched with proteins (best matching with hemoglobin and hydrolyzed proteins) and fatty acid esters adhering to the electrosurgical blades. Furthermore, significant decreased debris was found correlating with the date of surgery and the amount of times the ESK was cleaned. No significant influence was found of the amount of ES current used on the tissue debris, yet the intensity of the signal was expressively decreased with the increase of debris. During the power experiments, tissue debris on the ‘smart’ ES increased significantly over time while cutting. Polishing the fibers resulted in a fiber signal of only 43% of the maximal power.Disturbance occurred already early within the normal usage time of surgical procedures, with 1.9% of the maximal power left after 2 minutes of cutting. Prevention of fiber contamination seemed most effective by avoiding direct contact of the fibers with tissue during ES.Design challenges and requirements were obtained, resulting in three concepts aiming to overcome tissue adhering to the integrated fibers. Three prototypes were made and evaluated, which eventually led to a proposed re-design of the ‘smart’ ESK, containing integrated fibers which can be retracted into the casing when the knife is used to cut and is intermittently slided out for tissue contact to obtain DRS measurements. A working prototype was produced, which potentially overcomes the disrupted DRS measurements due to tissue contamination on the integrated fibers. Hence, a step is made towards the integration of DRS into the ESK. This will possibly have a positive impact on the margin assessment during surgery, which might reduce the number of re-excisions after BCS
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