Breast phantoms for 2D digital mammography with realistic anatomical structures and attenuation characteristics based on clinical images using 3D printing.

The aim of this work was to develop a production process for breast phantoms for 2D digital mammography (DM) with realistic anatomical structures and attenuation characteristics based on clinical images using 3D printing. The presented production process is based on PolyJet 3D printing technology using a polypropylene like printing material. First, an attenuation calibration function for this material and the achievable lateral resolution of the printing process of about 200 µm was determined. Subsequently, to generate the digital 3D model of the breast phantom, the pixel intensities of the unprocessed clinical image that are related to the attenuation along the z-axis of the breast, were converted to corresponding phantom heights using the calibration function. To validate the process, an image of the 3D printed breast phantom was acquired on the full field digital mammography (FFDM) system used for calibration and compared with the clinical image in terms of anatomical structures and associated attenuation characteristics. The exposure parameters and image impression of the phantom were evaluated using five other FFDM systems of different manufacturers and types. Results demonstrated that the anatomical structures in the images and the attenuation characteristics of a female breast and the derived phantom agreed on the FFDM system used for calibration. The automatic exposure control segmentation, the automatically selected exposure parameters and the image postprocessing of the clinical and phantom image indicated a high level of conformity. As shown, the phantom is also suitable for other FFDM systems. In conclusion, an approach to produce anthropomorphic breast phantoms for DM offering realistic anatomical structures and attenuation characteristics based on clinical images was successfully developed. As shown, the phantom realistically simulated the original female breast. Therefore, it is expected that such phantoms are promising to support bridging the gap between physical-technical and diagnostic image quality assessment. In addition, they enable a variety of practical and scientific applications for which present technical phantoms are not suitable.

Optimizing radiation exposure for CT localizer radiographs.

INTRODUCTION: The trend towards submillisievert CT scans leads to a higher dose fraction of localizer radiographs in CT examinations. The already existing technical capabilities make dose optimization of localizer radiographs worthwhile. Modern CT scanners apply automatic exposure control (AEC) based on attenuation data in such a localizer. Therefore not only this aspect but also the detectability of anatomical landmarks in the localizer for the desired CT scan range adjustment needs to be considered. MATERIALS AND METHODS: The effective dose of a head, chest, and abdomen-pelvis localizer radiograph with standard factory settings and user-optimized settings was determined using Monte Carlo simulations. CT examinations of an anthropomorphic phantom were performed using multiple sets of acquisition parameters for the localizer radiograph and the AEC for the subsequent helical CT scan. Anatomical landmarks were defined to assess the image quality of the localizer. CTDIvol and effective mAs per slice of the helical CT scan were recorded to examine the impact of localizer settings on a helical CT scan. RESULTS: The dose of the localizer radiograph could be decreased by more than 90% while the image quality remained sufficient when selecting the lowest available settings (80kVp, 20mA, pa tube position). The tube position during localizer acquisition had a greater impact on the AEC than the reduction of tube voltage and tube current. Except for the use of a pa tube position, all changes of acquisition parameters for the localizer resulted in a decreased total radiation exposure. CONCLUSION: A dose reduction of CT localizer radiograph is necessary and possible. In the examined CT system there was no negative impact on the modulated helical CT scan when the lowest tube voltage and tube current were used for the localizer.

Image-Processing Scheme to Detect Superficial Fungal Infections of the Skin.

The incidence of superficial fungal infections is assumed to be 20 to 25% of the global human population. Fluorescence microscopy of extracted skin samples is frequently used for a swift assessment of infections. To support the dermatologist, an image-analysis scheme has been developed that evaluates digital microscopic images to detect fungal hyphae. The aim of the study was to increase diagnostic quality and to shorten the time-to-diagnosis. The analysis, consisting of preprocessing, segmentation, parameterization, and classification of identified structures, was performed on digital microscopic images. A test dataset of hyphae and false-positive objects was created to evaluate the algorithm. Additionally, the performance for real clinical images was investigated using 415 images. The results show that the sensitivity for hyphae is 94% and 89% for singular and clustered hyphae, respectively. The mean exclusion rate is 91% for the false-positive objects. The sensitivity for clinical images was 83% and the specificity was 79%. Although the performance is lower for the clinical images than for the test dataset, a reliable and fast diagnosis can be achieved since it is not crucial to detect every hypha to conclude that a sample consisting of several images is infected. The proposed analysis therefore enables a high diagnostic quality and a fast sample assessment to be achieved.

Design and evaluation of a Monte Carlo based model of an orthovoltage treatment system.

The aim of this study was to develop a flexible framework of an orthovoltage treatment system capable of calculating and visualizing dose distributions in different phantoms and CT datasets. The framework provides a complete set of various filters, applicators and x-ray energies and therefore can be adapted to varying studies or be used for educational purposes. A dedicated user friendly graphical interface was developed allowing for easy setup of the simulation parameters and visualization of the results. For the Monte Carlo simulations the EGSnrc Monte Carlo code package was used. Building the geometry was accomplished with the help of the EGSnrc C++ class library. The deposited dose was calculated according to the KERMA approximation using the track-length estimator. The validation against measurements showed a good agreement within 4-5% deviation, down to depths of 20% of the depth dose maximum. Furthermore, to show its capabilities, the validated model was used to calculate the dose distribution on two CT datasets. Typical Monte Carlo calculation time for these simulations was about 10 minutes achieving an average statistical uncertainty of 2% on a standard PC. However, this calculation time depends strongly on the used CT dataset, tube potential, filter material/thickness and applicator size.

Development of a protective dermal drug delivery system for therapeutic DNAzymes.

RNA-cleaving DNAzymes are a potential novel class of nucleic acid-based active pharmaceutical ingredients (API). However, developing an appropriate drug delivery system (DDS) that achieves high bioavailability is challenging. Especially in a dermal application, DNAzymes have to overcome physiological barriers composed of penetration barriers and degrading enzymes. The focus of the present study was the development of a protective and penetration-enhanced dermal DDS that was tailor made for DNAzymes. DNAzyme Dz13 was used as a potential API for topical therapy against actinic keratosis. In the progress of development and selection, different preservatives, submicron emulsions (SMEs) and the physiological pH range were validated with respect to the API's integrity. A physicochemical stable SME of a pharmaceutical grade along with a high API integrity was achieved. Additionally, two developed protective systems, consisting of a liposomal formulation or chitosan-polyplexes, reduced the degradation of Dz13 in vitro. A combination of SME and polyplexes was finally validated at the skin and cellular level by in vitro model systems. Properties of penetration, degradation and distribution were determined. The result was enhanced skin penetration efficiency and increased cellular uptake with a high protective efficiency for DNAzymes due to the developed protective DDS.

Development of drug delivery systems for the dermal application of therapeutic DNAzymes.

DNAzymes are potent novel drugs for the treatment of inflammatory diseases such as atopic dermatitis. DNAzymes represent a novel class of pharmaceuticals that fulfil a causal therapy by interruption of the inflammation cascade at its origin. There are two challenges regarding the dermal application of DNAzymes: the large molecular weight and the sensitivity to DNases as part of the natural skin flora. To overcome these limitations suitable carrier systems have to be considered. Nano-sized drug carrier systems (submicron emulsions, microemulsions) are known to improve the skin uptake of drugs due to their ability to interact with the skin's lipids. To protect the drug against degradation, the hydrophilic drug may be incorporated into the inner aqueous phase of carrier systems, such as water-in-oil-in-water multiple emulsions. In the present study various emulsions of pharmaceutical grade were produced. Their physicochemical properties were determined and the influence of preservation systems on stability was tested. Drug release and skin uptake studies using various skin conditions and experimental set-ups were conducted. Furthermore, cellular uptake was determined by flow cytometric analysis. The investigations revealed that the developed multiple emulsion is a suitable and promising drug carrier system for the topical application of DNAzyme.