Motion Calculations on Stent Grafts in AAA

Endovascular aortic repair (EVAR) is a technique which uses stent grafts to treat aortic aneurysms in patients at risk of aneurysm rupture. Although this technique has been shown to be very successful on the short term, the long term results are less optimistic due to failure of the stent graft. The pulsating blood flow applies stresses and forces to the stent graft, which can cause problems such as breakage, leakage, and migration. Therefore it is of importance to gain more insight into the in vivo motion behavior of these devices. If we know more about the motion patterns in well-behaved stent graft as well as ill-behaving devices, we shall be better able to distinguish between these type of behaviors These insights will enable us to detect stent-related problems and might even be used to predict problems beforehand. Further, these insights will help in designing the next generation stent grafts. Firstly, this work discusses the applicability of ECG-gated CT for measuring the motions of stent grafts in AAA. Secondly, multiple methods to segment the stent graft from these data are discussed. Thirdly, this work proposes a method that uses image registration to apply motion to the segmented stent mode

Enzyme prodrug therapy achieves site-specific, personalized physiological responses to the locally produced nitric oxide

Nitric oxide (NO) is a highly potent but short-lived endogenous radical with a wide spectrum of physiological activities. In this work, we developed an enzymatic approach to the site-specific synthesis of NO mediated by biocatalytic surface coatings. Multilayered polyelectrolyte films were optimized as host compartments for the immobilized β-galactosidase (β-Gal) enzyme through a screen of eight polycations and eight polyanions. The lead composition was used to achieve localized production of NO through the addition of β-Gal–NONOate, a prodrug that releases NO following enzymatic bioconversion. The resulting coatings afforded physiologically relevant flux of NO matching that of the healthy human endothelium. The antiproliferative effect due to the synthesized NO in cell culture was site-specific: within a multiwell dish with freely shared media and nutrients, a 10-fold inhibition of cell growth was achieved on top of the biocatalytic coatings compared to the immediately adjacent enzyme-free microwells. The physiological effect of NO produced via the enzyme prodrug therapy was validated ex vivo in isolated arteries through the measurement of vasodilation. Biocatalytic coatings were deposited on wires produced using alloys used in clinical practice and successfully mediated a NONOate concentration-dependent vasodilation in the small arteries of rats. The results of this study present an exciting opportunity to manufacture implantable biomaterials with physiological responses controlled to the desired level for personalized treatment

The de novo FAIRification process of a registry for vascular anomalies

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Effective low-dose sirolimus regimen for kaposiform haemangioendothelioma with Kasabach-Merritt phenomenon in young infants

Aims Management of kaposiform haemangioendotheliomas (KHE) with Kasabach-Merritt phenomenon is challenging in young infants who are subjected to developmental pharmacokinetic changes. Sirolimus, sometimes combined with corticosteroids, can be used as an effective treatment of KHE. Simultaneously, toxicities such as interstitial pneumonitis related to the use of sirolimus may be fatal. As infants have a very low CYP3-enzyme expression at birth, which rises during ageing, we hypothesize that a reduced metabolization of sirolimus might lead to high sirolimus serum levels and low dose may be sufficient without the side effects. Methods A case series of 5 infants with kaposiform haemangioendothelioma with Kasabach-Merritt phenomenon was analysed retrospectively. All infants were treated with sirolimus 0.2 mg/m(2) every 24 or 48 hours according to their age. Prednisone was added to the therapy for additional effect in 4 patients. Results In all patients, low dose of sirolimus led to therapeutic sirolimus levels (4-6 ng/mL). All infants (aged 4 days-7 months) had a complete haematological response, without serious adverse events. In all patients, the Kasabach-Merritt phenomenon resolved, the coagulation profile normalized and tumour size reduction was seen. Conclusion Low-dose sirolimus treatment is safe for infants with kaposiform haemangioendothelioma and Kasabach-Merritt phenomenon. It is essential to realize that during the first months of life, metabolism is still developing and enzymes necessary to metabolise drugs like sirolimus still have to mature. To avoid toxic levels, the sirolimus dosage should be based on age and the associated pharmacological developments

Detectability of motions in AAA with ECG-gated CTA: A quantitative study

Purpose: ECG-gated CT enables the visualization of motions caused by the beating of the heart. Although ECG gating is frequently used in cardiac CT imaging, this technique is also very promising for evaluating vessel wall motion of the aortic artery and the motions of (stent grafts inside) abdominal aortic aneurysms (AAA). Late stent graft failure is a serious complication in endovascular repair of aortic aneurysms. Better understanding of the motion characteristics of stent grafts will be beneficial for designing future devices. In addition, these data can be valuable in predicting stent graft failure in patients. To be able to reliably quantify the motion, however, it is of importance to know the performance and limitations of ECG gating, especially when the motions are small, as is the case in AAA. Since the details of the reconstruction algorithms are proprietary information on the CT manufacturers and not in the public domain, empirical experiments are required. The goal of this study is to investigate as to what extent the motions in AAA can be measured using ECG-gated CT. The authors quantitatively investigate four aspects of motion in ECG-gated CT: The detectability of the motion of objects at different amplitudes and different periodic motions, the temporal resolution, and the volume gaps that occur as a function of heart rate.\ud \ud Methods: They designed an experiment on a standard static phantom to empirically determine temporal resolution. To investigate motion amplitude and frequency, as well as patient heart rate, they designed dynamic experiments in which a home-made phantom driven by a motion unit moves in a predetermined pattern.\ud \ud Results: The duration of each ECG-gated phase was found to be 185 ms, which corresponds to half of the rotation time and is thus in accordance with half scan reconstruction applied by the scanner. By using subpixel localization, motions become detectable from amplitudes of as small as 0.4 mm in the x direction and 0.7 mm in the z direction. With the rotation time used in this study, motions up to 2.7 Hz can be reliably detected. The reconstruction algorithm fills volume gaps with noisy data using interpolation, but objects within these gaps remain hidden.\ud \ud Conclusions: This study gives insight into the possibilities and limitations for measuring small motions using ECG-gated CT. Application of the experimental method is not restricted to the CT scanner of a single manufacturer. From the results, they conclude that ECG-gated CTA is a suitable technique for studying the expected motions of the stent graft and vessel wall in AAA.\u

Semantic modelling of common data elements for rare disease registries, and a prototype workflow for their deployment over registry data

BACKGROUND: The European Platform on Rare Disease Registration (EU RD Platform) aims to address the fragmentation of European rare disease (RD) patient data, scattered among hundreds of independent and non-coordinating registries, by establishing standards for integration and interoperability. The first practical output of this effort was a set of 16 Common Data Elements (CDEs) that should be implemented by all RD registries. Interoperability, however, requires decisions beyond data elements - including data models, formats, and semantics. Within the European Joint Programme on Rare Diseases (EJP RD), we aim to further the goals of the EU RD Platform by generating reusable RD semantic model templates that follow the FAIR Data Principles. RESULTS: Through a team-based iterative approach, we created semantically grounded models to represent each of the CDEs, using the SemanticScience Integrated Ontology as the core framework for representing the entities and their relationships. Within that framework, we mapped the concepts represented in the CDEs, and their possible values, into domain ontologies such as the Orphanet Rare Disease Ontology, Human Phenotype Ontology and National Cancer Institute Thesaurus. Finally, we created an exemplar, reusable ETL pipeline that we will be deploying over these non-coordinating data repositories to assist them in creating model-compliant FAIR data without requiring site-specific coding nor expertise in Linked Data or FAIR. CONCLUSIONS: Within the EJP RD project, we determined that creating reusable, expert-designed templates reduced or eliminated the requirement for our participating biomedical domain experts and rare disease data hosts to understand OWL semantics. This enabled them to publish highly expressive FAIR data using tools and approaches that were already familiar to them

Metastatic potential of an aneurysmal bone cyst

Aneurysmal bone cysts (ABCs) are benign bone tumors consisting of blood-filled cavities lined by connective tissue septa. Recently, the hypothesis that ABCs are lesions reactive to local hemodynamics has been challenged after the discovery of specific recurrent chromosomal abnormalities. Multiple cases of malignant transformation of ABC into (osteo)sarcoma have been described, as well as a number of cases of telangiectatic osteosarcoma which had been misdiagnosed as ABC. We herewith document a case of a pelvic ABC metastatic to the lung, liver, and kidneys. Diagnosis was confirmed by the presence of a break in the USP6 gene, which is pathognomonic for ABC, in a pulmonary metastasis of our patient. Sarcomatous transformation as an explanation for this behavior was ruled out by demonstrating diploid DNA content in both the pulmonary lesion and the primary tumor