Mitigation of motion-induced artifacts in cone beam computed tomography using deep convolutional neural networks.

BACKGROUND: Cone beam computed tomography (CBCT) is often employed on radiation therapy treatment devices (linear accelerators) used in image-guided radiation therapy (IGRT). For each treatment session, it is necessary to obtain the image of the day in order to accurately position the patient and to enable adaptive treatment capabilities including auto-segmentation and dose calculation. Reconstructed CBCT images often suffer from artifacts, in particular those induced by patient motion. Deep-learning based approaches promise ways to mitigate such artifacts. PURPOSE: We propose a novel deep-learning based approach with the goal to reduce motion induced artifacts in CBCT images and improve image quality. It is based on supervised learning and includes neural network architectures employed as pre- and/or post-processing steps during CBCT reconstruction. METHODS: Our approach is based on deep convolutional neural networks which complement the standard CBCT reconstruction, which is performed either with the analytical Feldkamp-Davis-Kress (FDK) method, or with an iterative algebraic reconstruction technique (SART-TV). The neural networks, which are based on refined U-net architectures, are trained end-to-end in a supervised learning setup. Labeled training data are obtained by means of a motion simulation, which uses the two extreme phases of 4D CT scans, their deformation vector fields, as well as time-dependent amplitude signals as input. The trained networks are validated against ground truth using quantitative metrics, as well as by using real patient CBCT scans for a qualitative evaluation by clinical experts. RESULTS: The presented novel approach is able to generalize to unseen data and yields significant reductions in motion induced artifacts as well as improvements in image quality compared with existing state-of-the-art CBCT reconstruction algorithms (up to +6.3 dB and +0.19 improvements in peak signal-to-noise ratio, PSNR, and structural similarity index measure, SSIM, respectively), as evidenced by validation with an unseen test dataset, and confirmed by a clinical evaluation on real patient scans (up to 74% preference for motion artifact reduction over standard reconstruction). CONCLUSIONS: For the first time, it is demonstrated, also by means of clinical evaluation, that inserting deep neural networks as pre- and post-processing plugins in the existing 3D CBCT reconstruction and trained end-to-end yield significant improvements in image quality and reduction of motion artifacts.

Specific and reversible DNA-directed self-assembly of oil-in-water emulsion droplets.

Higher-order structures that originate from the specific and reversible DNA-directed self-assembly of microscopic building blocks hold great promise for future technologies. Here, we functionalized biotinylated soft colloid oil-in-water emulsion droplets with biotinylated single-stranded DNA oligonucleotides using streptavidin as an intermediary linker. We show the components of this modular linking system to be stable and to induce sequence-specific aggregation of binary mixtures of emulsion droplets. Three length scales were thereby involved: nanoscale DNA base pairing linking microscopic building blocks resulted in macroscopic aggregates visible to the naked eye. The aggregation process was reversible by changing the temperature and electrolyte concentration and by the addition of competing oligonucleotides. The system was reset and reused by subsequent refunctionalization of the emulsion droplets. DNA-directed self-assembly of oil-in-water emulsion droplets, therefore, offers a solid basis for programmable and recyclable soft materials that undergo structural rearrangements on demand and that range in application from information technology to medicine.

Hierarchical unilamellar vesicles of controlled compositional heterogeneity.

Eukaryotic life contains hierarchical vesicular architectures (i.e. organelles) that are crucial for material production and trafficking, information storage and access, as well as energy production. In order to perform specific tasks, these compartments differ among each other in their membrane composition and their internal cargo and also differ from the cell membrane and the cytosol. Man-made structures that reproduce this nested architecture not only offer a deeper understanding of the functionalities and evolution of organelle-bearing eukaryotic life but also allow the engineering of novel biomimetic technologies. Here, we show the newly developed vesicle-in-water-in-oil emulsion transfer preparation technique to result in giant unilamellar vesicles internally compartmentalized by unilamellar vesicles of different membrane composition and internal cargo, i.e. hierarchical unilamellar vesicles of controlled compositional heterogeneity. The compartmentalized giant unilamellar vesicles were subsequently isolated by a separation step exploiting the heterogeneity of the membrane composition and the encapsulated cargo. Due to the controlled, efficient, and technically straightforward character of the new preparation technique, this study allows the hierarchical fabrication of compartmentalized giant unilamellar vesicles of controlled compositional heterogeneity and will ease the development of eukaryotic cell mimics that resemble their natural templates as well as the fabrication of novel multi-agent drug delivery systems for combination therapies and complex artificial microreactors.

A quantitative analytical method to test for salt effects on giant unilamellar vesicles.

Today, free-standing membranes, i.e. liposomes and vesicles, are used in a multitude of applications, e.g. as drug delivery devices and artificial cell models. Because current laboratory techniques do not allow handling of large sample sizes, systematic and quantitative studies on the impact of different effectors, e.g. electrolytes, are limited. In this work, we evaluated the Hofmeister effects of ten alkali metal halides on giant unilamellar vesicles made of palmitoyloleoylphosphatidylcholine for a large sample size by combining the highly parallel water-in-oil emulsion transfer vesicle preparation method with automatic haemocytometry. We found that this new quantitative screening method is highly reliable and consistent with previously reported results. Thus, this method may provide a significant methodological advance in analysis of effects on free-standing model membranes.

DNA-mediated self-assembly of artificial vesicles.

BACKGROUND: Although multicompartment systems made of single unilamellar vesicles offer the potential to outperform single compartment systems widely used in analytic, synthetic, and medical applications, their use has remained marginal to date. On the one hand, this can be attributed to the binary character of the majority of the current tethering protocols that impedes the implementation of real multicomponent or multifunctional systems. On the other hand, the few tethering protocols theoretically providing multicompartment systems composed of several distinct vesicle populations suffer from the readjustment of the vesicle formation procedure as well as from the loss of specificity of the linking mechanism over time. METHODOLOGY/PRINCIPAL FINDINGS: In previous studies, we presented implementations of multicompartment systems and resolved the readjustment of the vesicle formation procedure as well as the loss of specificity by using linkers consisting of biotinylated DNA single strands that were anchored to phospholipid-grafted biotinylated PEG tethers via streptavidin as a connector. The systematic analysis presented herein provides evidences for the incorporation of phospholipid-grafted biotinylated PEG tethers to the vesicle membrane during vesicle formation, providing specific anchoring sites for the streptavidin loading of the vesicle membrane. Furthermore, DNA-mediated vesicle-vesicle self-assembly was found to be sequence-dependent and to depend on the presence of monovalent salts. CONCLUSIONS/SIGNIFICANCE: This study provides a solid basis for the implementation of multi-vesicle assemblies that may affect at least three distinct domains. (i) Analysis. Starting with a minimal system, the complexity of a bottom-up system is increased gradually facilitating the understanding of the components and their interaction. (ii) Synthesis. Consecutive reactions may be implemented in networks of vesicles that outperform current single compartment bioreactors in versatility and productivity. (iii) Personalized medicine. Transport and targeting of long-lived, pharmacologically inert prodrugs and their conversion to short-lived, active drug molecules directly at the site of action may be accomplished if multi-vesicle assemblies of predefined architecture are used.

[Cavity micro-morphology following caries removal]. / Kavitätenmikromorphologie nach Kariesexkavation.

The objective of this research was to observe the effect of different caries removal techniques on human dentin topography. Thirty-six dentin samples of bisected carious human molars were treated with six different caries removal techniques, replicated and then examined by using a scanning electron microscope. The surfaces were observed before and after the smear layer removal at a magnification of 200- and 1000-fold. At a magnification of 200 the sono-abraded samples showed a significantly more undulated dentin topography than samples treated with other techniques. Using Carisolv hand instruments for caries removal resulted both at a magnification of 200 and 1000 in a significantly rougher, flakier and more fissured dentin surface texture compared to other techniques. Microcracks were observed in samples from all excavation methods but most frequently when treated with Carisolv hand instruments. The excavation process results in a dentin topography marked by smooth, flaky and fissured surface textures as well as by microcracks. The relative incidence in which these textures occur may indicate whether the removed dentin was rather cut or fractured.

[Heat propagation in dentin during cavity preparation in vitro with oscillating instruments]. / Temperaturentwicklung im Dentin bei Kariesexkavation mit oszillierenden Instrumenten.

The purpose of this work was to study the temperature rise caused by preparation of human dentin using two different types of oscillating instruments. A newly designed tungsten carbide tip (Cariex TC, KaVo) and a diamond-coated tip (Cariex D, KaVo) in combination with an airscaler (Sonicflex 2003L, KaVo) and two different flow rates of two coolants were investigated. For both tips significant differences in temperature rise were found between cooling with waterspray or with Plakout Gel (Kerr, HaWe) and using no coolant. A flow of 7.3 ml water/min was found to be sufficient to avoid any critical temperature rise, an excavation of longer duration without coolant cannot be recommended. The use of water-based highly viscous substances over a defined period during the caries excavation process seems to be a viable alternative.

[Influence of magnification tools on the recognition of simulated preparation and filling errors]. / Einfluss von Vergrösserungshilfen auf die Erkennung nachgestellter Präparations- und Füllungsfehler.

37 mistakes or filling defects were mounted onto a phantom model. Three groups--each consisting of thirteen dentists--examined the jaws under clinical conditions using either no visual aid, magnifying glasses or a microscope. They were further asked if using magnifying tools had a positive effect on pains such as neck and back pain, headaches or sore eyes. The group using the microscope spent more time on examination and found significantly more defects than their colleagues using magnifying glasses. They also profited more from the ergonomical advantages. The main clinical use for microscopes is in endodontics. The group of dentists using magnifying glasses spent less time on examination but found more defects than their colleagues using no magnification tools at all. The positive effect on neck and back pain was less pronounced than in the group working with microscopes. Magnifying glasses are used in all kinds of clinical work.

[The operating microscope in dental practice: minimally invasive restorations]. / Das Operationsmikroskop in der zahnärztlichen Praxis: minimalinvasive Füllungen.

With the visualization provided by the operating microscope (OM), it is now possible to place fillings in formerly inaccessible areas and work in a way that preserves the most enamel and/or dentin. The OM enables working with full overview in interdental areas or in hard-to-reach areas around crowns. The good view not only enables new forms of therapy, but reduces stress while working. The two clinical cases cited show clearly how the OM can be used advantageously in a range of situations--from the economical repair of a large old filling to minimal-invasive initial treatment. As an added bonus, the OP allows a completely relaxed and upright working posture.