Here we present a from-in vivo-4D PC MRI-to-computational hemodynamics approach to study blood fl... more Here we present a from-in vivo-4D PC MRI-to-computational hemodynamics approach to study blood flow in the human aorta. Our aim is the integration of 4D in vivo measurements into patient specific hemodynamic models, complementing detailed in vivo ...
Journal of Vascular and Interventional Radiology, 2014
ABSTRACT Purpose Over 25% of prevalent U.S. hemodialysis patients receive renal replacement throu... more ABSTRACT Purpose Over 25% of prevalent U.S. hemodialysis patients receive renal replacement through catheters. Symmetrical tip dialysis catheters have become alternatives to split tip and step tip designs owing to low solute recirculation and ease of positioning. We compared flow characteristics and recirculation of two symmetrical tip dialysis catheters using computational flow dynamics (CFD). Materials and Methods We compared the VectorFlow catheter (with helically contoured distal lumens which offset the vectors of blood entering and leaving the device) with the Palindrome catheter (with symmetrically cross-cut tips within a dual-D configuration). A previously validated CFD model was used to compare these catheters for recirculation (as percent blood flow), Platelet Activation State (PAS) (a computational metric of thrombogenicity) and Helical Flow Index (HFI, to quantify the helical content of the streaming blood) using a steady-state superior vena model assuming catheter flow rates of 400 mL/min. Results Both catheters were associated with a recirculation close to zero. Arterial and venous lumen outflow Platelet Activation State (PAS) (70th percentile) of VectorFlow catheter vs. Palindrome was 1.88 x 10-6 vs. 2.09 x 10-6 (arterial); and 5.08 x 10-6 vs. 1.14 x 10-5 (venous), respectively. Both catheters exhibited a symmetrical venous flow structure away from the catheter tip and coherent helical trajectories entering the arterial lumen, but transitioning rapidly in the VectorFlow catheter to fully developed flow. HFI analysis showed that both the Palindrome and VectorFlow catheters exhibited helical flow, with HFI of 0.032 and 0.024, respectively; the helically contoured lumens of the VectorFlow were also effective in deflecting the venous flow away from the arterial lumen. Conclusion Both VectorFlow and Palindrome catheters showed minimal recirculation rates compared to conventional step tip and split tip alternatives. The VectorFlow catheter was associated with lower Platelet Activation State (PAS) levels and helical deflection of blood from the venous lumen away from the arterial lumen.
Spinocerebellar ataxia (SCA) 3, the most common form of SCA, is a neurodegenerative rare disease ... more Spinocerebellar ataxia (SCA) 3, the most common form of SCA, is a neurodegenerative rare disease characterized by polyglutamine tract expansion and self-assembly of Ataxin3 (At3) misfolded proteins into highly organized fibrillar aggregates. The At3 N-terminal Josephin Domain (JD) has been suggested as being responsible for mediating the initial phase of the At3 double-step fibrillogenesis. Several issues concerning the residues involved in the JD's aggregation and, more generally, the JD clumping mechanism have not been clarified yet. In this paper we present an investigation focusing on the JD protein-protein interaction by means of molecular modeling. Our results suggest possible aminoacids involved in JD contact together with local and non-local effects following JD dimerization. Surprisingly, JD conformational changes following the binding may involve ubiquitin binding sites and hairpin region even though they do not pertain to the JD interaction surfaces. Moreover, the JD ...
Parallel to the massive use of image-based computational hemodynamics to study the complex flow e... more Parallel to the massive use of image-based computational hemodynamics to study the complex flow establishing in the human aorta, the need for suitable experimental techniques and ad hoc cases for the validation and benchmarking of numerical codes has grown more and more. Here we present a study where the 3D pulsatile flow in an anatomically realistic phantom of human ascending aorta is investigated both experimentally and computationally. The experimental study uses 3D particle tracking velocimetry (PTV) to characterize the flow field in vitro, while finite volume method is applied to numerically solve the governing equations of motion in the same domain, under the same conditions. Our findings show that there is an excellent agreement between computational and measured flow fields during the forward flow phase, while the agreement is poorer during the reverse flow phase. In conclusion, here we demonstrate that 3D PTV is very suitable for a detailed study of complex unsteady flows as in aorta and for validating computational models of aortic hemodynamics. In a future step, it will be possible to take advantage from the ability of 3D PTV to evaluate velocity fluctuations and, for this reason, to gain further knowledge on the process of transition to turbulence occurring in the thoracic aorta.
Arterial geometry has long been considered as a pragmatic alternative for inferring arterial flow... more Arterial geometry has long been considered as a pragmatic alternative for inferring arterial flow disturbances, and their impact on the natural history and treatment of vascular diseases. Traditionally, definition of geometric variables is based on convenient shape descriptors, with only superficial consideration of their influence on flow and wall shear stress patterns. In the present study we demonstrate that a more studied consideration of the actual (cf. nominal) local hemodynamics can lead to substantial improvements in the prediction of disturbed flow by geometry. Starting from a well-characterized computational fluid dynamics (CFD) dataset of 50 normal carotid bifurcations, we observed that disturbed flow tended to be confined proximal to the flow divider, whereas geometric variables previously shown to be significant predictors of disturbed flow included features distal to the flow divider in their definitions. Flaring of the bifurcation leading to flow separation was redefined as the maximum relative expansion of the common carotid artery (CCA), proximal to the flow divider. The beneficial effect of primary curvature on flow inertia, via suppression of flow separation, was characterized by the in-plane tortuosity of CCA as it enters the flare region. Multiple linear regressions of these redefined geometric variables against various metrics of disturbed flow revealed R(2) values approaching 0.6, better than the roughly 0.3 achieved using the conventional shape-based variables, while maintaining their demonstrated real-world reproducibility. Such a hemodynamically-inspired approach to the definition of geometric variables may reap benefits for other applications where geometry is used as a surrogate marker of local hemodynamics.
Controversy exists regarding the suitability of fully developed versus measured inlet velocity pr... more Controversy exists regarding the suitability of fully developed versus measured inlet velocity profiles for image-based computational fluid dynamics (CFD) studies of carotid bifurcation hemodynamics. Here, we attempt to resolve this by investigating the impact of the reconstructed common carotid artery (CCA) inlet length on computed metrics of "disturbed" flow. Twelve normal carotid bifurcation geometries were reconstructed from contrast-enhanced angiograms acquired as part of the Vascular Aging--The Link That Bridges Age to Atherosclerosis study (VALIDATE). The right carotid artery lumen geometry was reconstructed from its brachiocephalic origin to well above the bifurcation, and the CCA was truncated objectively at locations one, three, five, and seven diameters proximal to where it flares into the bifurcation. Relative to the simulations carried out using the full CCA, models truncated at one CCA diameter strongly overestimated the amount of disturbed flow. Substantial improvement was offered by using three CCA diameters, with only minor further improvement using five CCA diameters. With seven CCA diameters, the amounts of disturbed flow agreed unambiguously with those predicted by the corresponding full-length models. Based on these findings, we recommend that image-based CFD models of the carotid bifurcation should incorporate at least three diameters of CCA length if fully developed velocity profiles are to be imposed at the inlet. The need for imposing measured inlet velocity profiles would seem to be relevant only for those cases where the CCA is severely truncated.
Here we present a from-in vivo-4D PC MRI-to-computational hemodynamics approach to study blood fl... more Here we present a from-in vivo-4D PC MRI-to-computational hemodynamics approach to study blood flow in the human aorta. Our aim is the integration of 4D in vivo measurements into patient specific hemodynamic models, complementing detailed in vivo ...
Journal of Vascular and Interventional Radiology, 2014
ABSTRACT Purpose Over 25% of prevalent U.S. hemodialysis patients receive renal replacement throu... more ABSTRACT Purpose Over 25% of prevalent U.S. hemodialysis patients receive renal replacement through catheters. Symmetrical tip dialysis catheters have become alternatives to split tip and step tip designs owing to low solute recirculation and ease of positioning. We compared flow characteristics and recirculation of two symmetrical tip dialysis catheters using computational flow dynamics (CFD). Materials and Methods We compared the VectorFlow catheter (with helically contoured distal lumens which offset the vectors of blood entering and leaving the device) with the Palindrome catheter (with symmetrically cross-cut tips within a dual-D configuration). A previously validated CFD model was used to compare these catheters for recirculation (as percent blood flow), Platelet Activation State (PAS) (a computational metric of thrombogenicity) and Helical Flow Index (HFI, to quantify the helical content of the streaming blood) using a steady-state superior vena model assuming catheter flow rates of 400 mL/min. Results Both catheters were associated with a recirculation close to zero. Arterial and venous lumen outflow Platelet Activation State (PAS) (70th percentile) of VectorFlow catheter vs. Palindrome was 1.88 x 10-6 vs. 2.09 x 10-6 (arterial); and 5.08 x 10-6 vs. 1.14 x 10-5 (venous), respectively. Both catheters exhibited a symmetrical venous flow structure away from the catheter tip and coherent helical trajectories entering the arterial lumen, but transitioning rapidly in the VectorFlow catheter to fully developed flow. HFI analysis showed that both the Palindrome and VectorFlow catheters exhibited helical flow, with HFI of 0.032 and 0.024, respectively; the helically contoured lumens of the VectorFlow were also effective in deflecting the venous flow away from the arterial lumen. Conclusion Both VectorFlow and Palindrome catheters showed minimal recirculation rates compared to conventional step tip and split tip alternatives. The VectorFlow catheter was associated with lower Platelet Activation State (PAS) levels and helical deflection of blood from the venous lumen away from the arterial lumen.
Spinocerebellar ataxia (SCA) 3, the most common form of SCA, is a neurodegenerative rare disease ... more Spinocerebellar ataxia (SCA) 3, the most common form of SCA, is a neurodegenerative rare disease characterized by polyglutamine tract expansion and self-assembly of Ataxin3 (At3) misfolded proteins into highly organized fibrillar aggregates. The At3 N-terminal Josephin Domain (JD) has been suggested as being responsible for mediating the initial phase of the At3 double-step fibrillogenesis. Several issues concerning the residues involved in the JD's aggregation and, more generally, the JD clumping mechanism have not been clarified yet. In this paper we present an investigation focusing on the JD protein-protein interaction by means of molecular modeling. Our results suggest possible aminoacids involved in JD contact together with local and non-local effects following JD dimerization. Surprisingly, JD conformational changes following the binding may involve ubiquitin binding sites and hairpin region even though they do not pertain to the JD interaction surfaces. Moreover, the JD ...
Parallel to the massive use of image-based computational hemodynamics to study the complex flow e... more Parallel to the massive use of image-based computational hemodynamics to study the complex flow establishing in the human aorta, the need for suitable experimental techniques and ad hoc cases for the validation and benchmarking of numerical codes has grown more and more. Here we present a study where the 3D pulsatile flow in an anatomically realistic phantom of human ascending aorta is investigated both experimentally and computationally. The experimental study uses 3D particle tracking velocimetry (PTV) to characterize the flow field in vitro, while finite volume method is applied to numerically solve the governing equations of motion in the same domain, under the same conditions. Our findings show that there is an excellent agreement between computational and measured flow fields during the forward flow phase, while the agreement is poorer during the reverse flow phase. In conclusion, here we demonstrate that 3D PTV is very suitable for a detailed study of complex unsteady flows as in aorta and for validating computational models of aortic hemodynamics. In a future step, it will be possible to take advantage from the ability of 3D PTV to evaluate velocity fluctuations and, for this reason, to gain further knowledge on the process of transition to turbulence occurring in the thoracic aorta.
Arterial geometry has long been considered as a pragmatic alternative for inferring arterial flow... more Arterial geometry has long been considered as a pragmatic alternative for inferring arterial flow disturbances, and their impact on the natural history and treatment of vascular diseases. Traditionally, definition of geometric variables is based on convenient shape descriptors, with only superficial consideration of their influence on flow and wall shear stress patterns. In the present study we demonstrate that a more studied consideration of the actual (cf. nominal) local hemodynamics can lead to substantial improvements in the prediction of disturbed flow by geometry. Starting from a well-characterized computational fluid dynamics (CFD) dataset of 50 normal carotid bifurcations, we observed that disturbed flow tended to be confined proximal to the flow divider, whereas geometric variables previously shown to be significant predictors of disturbed flow included features distal to the flow divider in their definitions. Flaring of the bifurcation leading to flow separation was redefined as the maximum relative expansion of the common carotid artery (CCA), proximal to the flow divider. The beneficial effect of primary curvature on flow inertia, via suppression of flow separation, was characterized by the in-plane tortuosity of CCA as it enters the flare region. Multiple linear regressions of these redefined geometric variables against various metrics of disturbed flow revealed R(2) values approaching 0.6, better than the roughly 0.3 achieved using the conventional shape-based variables, while maintaining their demonstrated real-world reproducibility. Such a hemodynamically-inspired approach to the definition of geometric variables may reap benefits for other applications where geometry is used as a surrogate marker of local hemodynamics.
Controversy exists regarding the suitability of fully developed versus measured inlet velocity pr... more Controversy exists regarding the suitability of fully developed versus measured inlet velocity profiles for image-based computational fluid dynamics (CFD) studies of carotid bifurcation hemodynamics. Here, we attempt to resolve this by investigating the impact of the reconstructed common carotid artery (CCA) inlet length on computed metrics of "disturbed" flow. Twelve normal carotid bifurcation geometries were reconstructed from contrast-enhanced angiograms acquired as part of the Vascular Aging--The Link That Bridges Age to Atherosclerosis study (VALIDATE). The right carotid artery lumen geometry was reconstructed from its brachiocephalic origin to well above the bifurcation, and the CCA was truncated objectively at locations one, three, five, and seven diameters proximal to where it flares into the bifurcation. Relative to the simulations carried out using the full CCA, models truncated at one CCA diameter strongly overestimated the amount of disturbed flow. Substantial improvement was offered by using three CCA diameters, with only minor further improvement using five CCA diameters. With seven CCA diameters, the amounts of disturbed flow agreed unambiguously with those predicted by the corresponding full-length models. Based on these findings, we recommend that image-based CFD models of the carotid bifurcation should incorporate at least three diameters of CCA length if fully developed velocity profiles are to be imposed at the inlet. The need for imposing measured inlet velocity profiles would seem to be relevant only for those cases where the CCA is severely truncated.
Uploads
Papers