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| 3. |
- Burgunder, J-M, et al.
(författare)
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EFNS guidelines for the molecular diagnosis of neurogenetic disorders : motoneuron, peripheral nerve and muscle disorders
- 2011
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Ingår i: European Journal of Neurology. - : Wiley-Blackwell. - 1351-5101 .- 1468-1331. ; 18:2, s. 207-E20
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: These EFNS guidelines on the molecular diagnosis of motoneuron disorders, neuropathies and myopathies are designed to summarize the possibilities and limitations of molecular genetic techniques and to provide diagnostic criteria for deciding when a molecular diagnostic work-up is indicated. Search strategy: To collect data about planning, conditions and performance of molecular diagnosis of these disorders, a literature search in various electronic databases was carried out and original papers, meta-analyses, review papers and guideline recommendations reviewed. Results: The best level of evidence for genetic testing recommendation (B) can be found for the disorders with specific presentations, including familial amyotrophic lateral sclerosis, spinal and bulbar muscular atrophy, Charcot-Marie-Tooth 1A, myotonic dystrophy and Duchenne muscular dystrophy. For a number of less common disorders, a precise description of the phenotype, including the use of immunologic methods in the case of myopathies, is considered as good clinical practice to guide molecular genetic testing. Conclusion: These guidelines are provisional and the future availability of molecular-genetic epidemiological data about the neurogenetic disorders under discussion in this article will allow improved recommendation with an increased level of evidence.
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| 4. |
- Burgunder, J-M., et al.
(författare)
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Molecular diagnosis of neurogenetic disorders : motoneuron, peripheral nerve and muscle disorders
- 2012. - 2
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Ingår i: European handbook of neurological management. - Oxford, UK : Wiley-Blackwell. - 9781444346268 - 9781405185349 ; , s. 97-109
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Bokkapitel (refereegranskat)abstract
- Objectives: The EFNS guidelines on the molecular diagnosis of motoneuron disorders, neuropathies and myopathies are designed to summarize the possibilities and limitations of molecular genetic techniques and to provide diagnostic criteria for deciding when a molecular diagnostic work-up is indicated.Search strategy: To collect data about the planning, conditions and performance of molecular diagnosis of these disorders, a literature search in various electronic databases was carried out and original papers, meta-analyses, review papers and guideline recommendations reviewed.Results: The best level of evidence for genetic testing recommendation (Level B) can be found for the disorders with specific presentations, including familial ALS, spinal and bulbar muscular atrophy, Charcot-Marie-Tooth 1A, myotonic dystrophy and Duchenne muscular dystrophy. For a number of less common disorders a precise description of the phenotype, including the use of immunological methods in the case of myopathies, is considered good clinical practice to guide molecular genetic testing.Conclusion: These guidelines are provisional and the availability of molecular-genetic epidemiological data in the future about the neurogenetic disorders under discussion in the present paper will allow improved recommendation with an increased level of evidence.
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| 5. |
- Hyhlik-Dürr, A., et al.
(författare)
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Finite Element Analysis of Abdominal Aortic Aneurysms : Preliminary Results of Intra and Inter observer Validation
- 2010
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Konferensbidrag (refereegranskat)abstract
- Objective: Treatment of abdominal aortic aneurysm (AAA) is indicated if risk for rupture exceeds the risk for aortic repair. Estimation of the individual risk for rupture in AAA is therefore essential. The diameter of AAA is known as an independent risk factor for rupture and therefore the base of indication for surgical or endovascular therapy. For more sensitive patient selection, other morphological or hemodynamic predictors such as volume or peak wall stress have to be evaluated. The purpose of this study was to analyze the reproducibility of diameter measurement, volume estimation and peak wall stress calculation in AAA by finite element analysis. Methods: Computed tomography angiography (CTA) scans of 10 patients with AAA and 4 volunteers with healthy infrarenal aortas were analyzed by three independent investigators. A semiautomatic reconstruction using two- and three-dimensional deformable (active) contour models was used to segment vascular bodies from CTA data. Centreline calculated maximal diameter and volume measurements, as extracted from the reconstructed abdominal aorta, as well as peak wall stress, as predicted by three-dimensional non-linear finite element models, were analyzed. Specifically, aortic wall and thrombus tissue were captured by isotropic, non-linear and finite strain constitutive models. Likewise, mean arterial pressure was applied at the luminal surface, the vessels were fixed at the renal arteries and the aortic bifurcation and no contact with surrounding organs was considered. Inter- and intra-observer variabilities for diameter, volume and peak wall stress measurements were assessed by calculating the coefficient of variation (CV=SD*100/mean in %) of the five fold determinations. The methodological variation was expressed as deviation of diameter (mm), volume (ml) and peak wall stress (kPa) amongst the three observers. Results: Reproducibility measurements in healthy vessels of aortic diameters between 16.1mm to 16.6mm varied from CV=2.5% to CV=4.9%. Abdominal aortic volumes of 14ml to 15ml were measured in the healthy cohort with a reproducibility of CV=5.8% to CV=11.5%. Peak wall stress varied between 53 kPa and 55 kPa, where CV ranged from 3-13%. Inter-observer variation was <10% for diameter, volume and peak stress in healthy volunteers. Aortic diameter in three AAAs was measured to 58.9 mm; 54.6 mm; and 71.2 mm respectively. The coefficient of variation showed high agreement with values less than 5%. AAA volume varied between 130 ml and 300 ml (CV < 10%) and Peak wall stress was predicted between 172 kPa and 296 kPa (CV <10%). Variability between the 3 observers in AAA measurements was 0.7 mm – 6.0 mm for diameter, 11 – 28 ml for volume and 4-27 kPa for peak wall stress, respectively. Conclusions: Volume and diameter measurements based on geometrical models reconstructed from CTA scans showed quit good reproducibility for serial measurements in normal and degenerative arteries. Peak wall stress predictions exhibited high accordance between different observers, and in serial measurements within one observer. Volume and peak wall stress analysis could be an additionally module for assessment of individual rupture risk in AAA in the future, which however needs to be validated by additional studies.
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| 6. |
- Hyhlik-Dürr, A., et al.
(författare)
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Finite-Elemente-Analyse abdomineller Aortenaneurysmen : Erste Ergebnisse der Intra- und Interobserver Validierung
- 2010
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Konferensbidrag (refereegranskat)abstract
- Hintergrund: Die Therapie des abdominellen Aortenaneurysmas (AAA) ist indiziert, wenn das Rupturrisiko das Risiko der elektiven Operation übersteigt. Die Abschätzung des individuellen Rupturrisikos gilt als Basis der Indikationsstellung zur offenen oder endovaskulären Chirurgie. Bisher wird der Durchmesser des AAA als maßgeblicher Risikofaktor für die Ruptur herangezogen. Für eine sensitivere Indikationsstellung sollten jedoch andere morphologische oder biomechanische Faktoren wie die Volumenveränderung im Verlauf und/oder die Wandspannung im Aneurysma untersucht werden. Ziel dieser Studie ist die Analyse der Reproduzierbarkeit der Durchmesserbestimmung sowie der Volumen- und Wandspannungsberechnung anhand eines geometrischen Modells, basierend auf der Finite Elemente Methode. Methode: Computertomographische Daten von vier gesunden und zehn Patienten mit infrarenalen abdominellen Aneurysmen werden von drei unabhängigen Untersuchern analysiert. Die abdominelle Aorta wird semiautomatisch von Computertomographie-Angiographie (CTA) Bilddaten segmentiert, wobei zwei und drei-dimensionale aktive Konturmodelle, wie sie aus der Bildverarbeitung bekannt sind, zum Einsatz kommen. Der maximale Durchmesser (cernterline-basiert) sowie das aortale Volumen werden aus den rekonstruierten dreidimensionalen Modellen berechnet. Zusätzlich werden nicht-lineare Finite Elemente Modelle verwendet, um die mechanische Spannung in der Aortenwand zwischen der Aortenbifurkation und den Nierenarterien zu bestimmen. Zu diesen Zweck wird der mittlere arterielle Druck als Belastung angenommen und nicht-lineare isotrope Materialmodelle erfassen die mechanischen Eigenschaften der Aortenwand und des Thrombusgewebes. Die Intra- und Interobserver Variabilität der fünf Messungen des maximalen Durchmessers, des Volumens und der maximalen Wandspannung wurden durch die Berechnung des Variationskoeffizienten (CV=SD*100/Arithmethisches Mittel in %) ausgedrückt. Die methodische Variation berechnet sich aus der Abweichung des Duchmessers (mm), des Volumens (ml) und der maximalen Wandspannung (kPA) zwischen den drei Untersuchern. Ergebnisse: Die Reproduzierbarkeit gesunder Gefäßen lag bei einem Durchmesser zwischen 16.1mm und 16.6mm zwischen CV=2,5% und CV=4,9%. Das aortale Volumen lag zwischen 14ml und 15ml, die Reproduzierbarkeit bei den gesunden Gefäßen streute zwischen CV=5.8% und CV=11.5%. Die maximale Wandspannung variierte zwischen 53 kPA and 55 kPa, der CV% lag hierbei zwischen 3 und 13. Die Interobserver Variabilität lag < 10% für den Durchmesser, die Volumenbestimmung und die Bestimmung der maximale Wandspannung. Der maximale Durchmesser der Aorta bei 3 Patienten mit infrarenalem Aneurysma wurde mit durchschnittlich 58.9mm, 54.6mm und 71.2mm berechnet (Stand bei Abstracteinreichung). Der Variationskoeffizient zeigte dabei eine hohe Übereinstimmung mit Werten unter 5%. Das Volumen der Aneurysmen schwankte zwischen 130 ml und 300 ml (CV<10%), die berechnete Wandspannung lag zwischen 172 kPA und 296 kPA (CV<10%). Die Variabilität zwischen den drei Untersuchern betrug 0,7-6,0 mm für den Durchmesser, 11-28 ml für das Volumen und 4-27 kPA für die maximale Wandspannung. Zusammenfassung: Sowohl an gesunden als auch an degenerativ veränderten Gefäßen ergibt die Reproduzierbarkeit des Aortendurchmessers und des aortalen Volumens basierend auf dem dreidimensionalen rekonstruierten Modellen eine hohe Übereinstimmung. Die berechnete Wandspannung basierend auf den Finiten Elemente Modellen zeigt einen geringen Grad an Variabilität sowohl zwischen verschiedenen Untersuchern als auch bei wiederholter Messung. Daher könnten die Volumenbestimmung und die Analyse der Wandspannung zusätzliche Größen bei der Bestimmung des individuellen Rupturrisikos bei Patienten mit Aortenaneurysmen darstellen, um eine präzisere Indikationsstellung zu ermöglichen.
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| 7. |
- Auer, M., et al.
(författare)
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Reconstruction and Finite Element Mesh Generation of Abdominal Aortic Aneurysms From Computerized Tomography Angiography Data With Minimal User Interactions
- 2010
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Ingår i: IEEE Transactions on Medical Imaging. - : Institute of Electrical and Electronics Engineers (IEEE). - 0278-0062 .- 1558-254X. ; 29:4, s. 1022-1028
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Tidskriftsartikel (refereegranskat)abstract
- Evaluating rupture risk of abdominal aortic aneurysms is critically important in reducing related mortality without unnecessarily increasing the rate of elective repair. According to the current clinical practice aneurysm rupture risk is (mainly) estimated from its maximum diameter and/or expansion rate; an approach motivated from statistics but known to fail often in individuals. In contrast, recent research demonstrated that patient specific biomechanical simulations can provide more reliable diagnostic parameters, however current structural model development is cumbersome and time consuming. This paper used 2D and 3D deformable models to reconstruct aneurysms from computerized tomography angiography data with minimal user interactions. In particular, formulations of frames and shells, as known from structural mechanics, were used to define deformable modes, which in turn allowed a direct mechanical interpretation of the applied set of reconstruction parameters. Likewise, a parallel finite element implementation of the models allows the segmentation of clinical cases on standard personal computers within a few minutes. The particular topology of the applied 3D deformable models supports a fast and simple hexahedral-dominated meshing of the arising generally polyhedral domain. The variability of the derived segmentations (luminal: 0.50(SD 0.19) mm; exterior 0.89(SD 0.45) mm) with respect to large variations in elastic properties of the deformable models was in the range of the differences between manual segmentations as performed by experts (luminal: 0.57(SD 0.24) mm; exterior: 0.77(SD 0.58) mm), and was particularly independent from the algorithm's initialization. The proposed interaction of deformable models and mesh generation defines finite element meshes suitable to perform accurate and efficient structural analysis of the aneurysm using mixed finite element formulations.
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| 8. |
- Biasetti, Jacopo, et al.
(författare)
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An Integrated Fluid-Chemical Model Toward Modeling the Formation of Intra-Luminal Thrombus in Abdominal Aortic Aneurysms
- 2012
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Ingår i: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 3:266
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Tidskriftsartikel (refereegranskat)abstract
- Abdominal Aortic Aneurysms (AAAs) are frequently characterized by the presence of an Intra-Luminal Thrombus (ILT) known to influence their evolution biochemically and biomechanically. The ILT progression mechanism is still unclear and little is known regarding the impact of the chemical species transported by blood flow on this mechanism. Chemical agonists and antagonists of platelets activation, aggregation, and adhesion and the proteins involved in the coagulation cascade (CC) may play an important role in ILT development. Starting from this assumption, the evolution of chemical species involved in the CC, their relation to coherent vortical structures (VSs) and their possible effect on ILT evolution have been studied. To this end a fluid-chemical model that simulates the CC through a series of convection-diffusion-reaction (CDR) equations has been developed. The model involves plasma-phase and surface-bound enzymes and zymogens, and includes both plasma-phase and membrane-phase reactions. Blood is modeled as a non-Newtonian incompressible fluid. VSs convect thrombin in the domain and lead to the high concentration observed in the distal portion of the AAA. This finding is in line with the clinical observations showing that the thickest ILT is usually seen in the distal AAA region. The proposed model, due to its ability to couple the fluid and chemical domains, provides an integrated mechanochemical picture that potentially could help unveil mechanisms of ILT formation and development.
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| 9. |
- Biasetti, Jacopo, et al.
(författare)
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Blood flow and coherent vortices in the normal and aneurysmatic aortas : a fluid dynamical approach to intraluminal thrombus formation
- 2011
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Ingår i: Journal of the Royal Society Interface. - : The Royal Society. - 1742-5689 .- 1742-5662. ; 8:63, s. 1449-1461
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Tidskriftsartikel (refereegranskat)abstract
- Abdominal aortic aneurysms (AAAs) are frequently characterized by the development of an intra-luminal thrombus (ILT), which is known to have multiple biochemical and biomechanical implications. Development of the ILT is not well understood, and shear-stress-triggered activation of platelets could be the first step in its evolution. Vortical structures (VSs) in the flow affect platelet dynamics, which motivated the present study of a possible correlation between VS and ILT formation in AAAs. VSs educed by the lambda(2)-method using computational fluid dynamics simulations of the backward-facing step problem, normal aorta, fusiform AAA and saccular AAA were investigated. Patient-specific luminal geometries were reconstructed from computed tomography scans, and Newtonian and Carreau-Yasuda models were used to capture salient rheological features of blood flow. Particularly in complex flow domains, results depended on the constitutive model. VSs developed all along the normal aorta, showing that a clear correlation between VSs and high wall shear stress (WSS) existed, and that VSs started to break up during late systole. In contrast, in the fusiform AAA, large VSs developed at sites of tortuous geometry and high WSS, occupying the entire lumen, and lasting over the entire cardiac cycle. Downward motion of VSs in the AAA was in the range of a few centimetres per cardiac cycle, and with a VS burst at that location, the release (from VSs) of shear-stress-activated platelets and their deposition to the wall was within the lower part of the diseased artery, i.e. where the thickest ILT layer is typically observed. In the saccular AAA, only one VS was found near the healthy portion of the aorta, while in the aneurysmatic bulge, no VSs occurred. We present a fluid-dynamics-motivated mechanism for platelet activation, convection and deposition in AAAs that has the potential of improving our current understanding of the pathophysiology of fluid-driven ILT growth.
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| 10. |
- Biasetti, Jacopo, et al.
(författare)
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Hemodynamics of the Normal Aorta Compared to Fusiform and Saccular Abdominal Aortic Aneurysms with Emphasis on a Potential Thrombus Formation Mechanism
- 2010
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Ingår i: Annals of Biomedical Engineering. - : Springer Science and Business Media LLC. - 0090-6964 .- 1573-9686. ; 38:2, s. 380-390
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Tidskriftsartikel (refereegranskat)abstract
- Abdominal Aortic Aneurysms (AAAs), i.e., focal enlargements of the aorta in the abdomen are frequently observed in the elderly population and their rupture is highly mortal. An intra-luminal thrombus is found in nearly all aneurysms of clinically relevant size and multiply affects the underlying wall. However, from a biomechanical perspective thrombus development and its relation to aneurysm rupture is still not clearly understood. In order to explore the impact of blood flow on thrombus development, normal aortas (n = 4), fusiform AAAs (n = 3), and saccular AAAs (n = 2) were compared on the basis of unsteady Computational Fluid Dynamics simulations. To this end patient-specific luminal geometries were segmented from Computerized Tomography Angiography data and five full heart cycles using physiologically realistic boundary conditions were analyzed. Simulations were carried out with computational grids of about half a million finite volume elements and the Carreau-Yasuda model captured the non-Newtonian behavior of blood. In contrast to the normal aorta the flow in aneurysm was highly disturbed and, particularly right after the neck, flow separation involving regions of high streaming velocities and high shear stresses were observed. Naturally, at the expanded sites of the aneurysm average flow velocity and wall shear stress were much lower compared to normal aortas. These findings suggest platelets activation right after the neck, i.e., within zones of pronounced recirculation, and platelet adhesion, i.e., thrombus formation, downstream. This mechanism is supported by recirculation zones promoting the advection of activated platelets to the wall.
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