Hemodynamic effects of long-term morphological changes in the human carotid sinus.

Previous investigations of morphology for human carotid artery bifurcation from infancy to young adulthood found substantial growth of the internal carotid artery with advancing age, and the development of the carotid sinus at the root of the internal carotid artery during teenage years. Although the reasons for the appearance of the carotid sinus are not clearly understood yet, it has been hypothesized that the dilation of the carotid sinus serves to support pressure sensing, and slows the blood flow to reduce pulsatility to protect the brain. In order to understand this interesting evolvement at the carotid bifurcation in the aspects of fluid mechanics, we performed in vitro phase-contrast MR flow experiments using compliant silicone replicas of age-dependent carotid artery bifurcations. The silicone models in childhood, adolescence, and adulthood were fabricated using a rapid prototyping technique, and incorporated with a bench-top flow mock circulation loop using a computer-controlled piston pump. The results of the in vitro flow study showed highly complex flow characteristics at the bifurcation in all age-dependent models. However, the highest magnitude of kinetic energy was found at the internal carotid artery in the child model. The high kinetic energy in the internal carotid artery during childhood might be one of the local hemodynamic forces that initiate morphological long-term development of the carotid sinus in the human carotid bifurcation.

The mixability of angiographic contrast with arterial blood.

PURPOSE: Angiographic contrast that is routinely injected into arteries is used not only to evaluate arterial geometry but also in many cases to assess perfusion. The authors conducted two experiments to examine the dispersion of angiographic contrast injected antegradely into an artery under conditions similar to those found in selective (carotid artery) or superselective (circle of Willis) angiography in order to determine the distance from the catheter tip at which the contrast can be considered fully mixed with the blood. A third experiment investigated whether the contrast once mixed with blood will separate from the mixture under the gravitational field due to a density mismatch. METHODS: Experiment I--Under high-speed angiographic acquisition, a bolus of contrast was injected through a catheter along the flow direction of a blood analog fluid flowing through a straight, long, cylindrical tube. The variation in grayscale intensity along the length of the tube was acquired and modeled as the step response to a second-order system. The distance from the catheter tip at which the contrast mixes with the working fluid, the mixing length, was determined as the length along the tube after which the step response settles to within 3% of the steady state value. Experiment II--A bolus of angiographic contrast was injected at rates varying from 0.1 to 1 cc/s through three different catheter sizes in the left common carotid artery of three rabbits. The average cross-sectional grayscale intensity over one cardiac cycle was calculated at four locations along the artery: Immediately distal to the catheter tip, at location of maximum grayscale intensity, and at 10 and 20 arterial diameters from the catheter tip. The status of mixing within 10 arterial diameters was assessed by differences between the grayscale value at this location and that at the maximum and 20 arterial diameter location. Experiment III--Angiographic contrast was premixed by agitation in three separate vials containing normal saline, canine blood, and glycerol/distilled-water mixture. The vials were then stationed vertically and angiographic images obtained every 5 min for 1 h. The average intensity of contrast along the vertical length of each vial was obtained for every time point to record any changes in the distribution of contrast over time. RESULTS: The first experiment shows that angiographic contrast completely mixes with steady flowing blood analog fluid within about eight tube diameters of the injection site. The second experiment shows that contrast completely mixes with blood within ten arterial diameters under appropriate injection parameters. The third experiment shows that angiographic contrast does not separate from, or settle out of, contrast-carrying fluid mixtures for a period of 1 h. CONCLUSIONS: The results demonstrate that under typical injection conditions in the clinical setting, contrast issuing from the catheter completely mixes with the blood within ten artery diameters downstream of the catheter tip. Once mixed, it does not separate from the blood due to gravity.

Treatment of rabbit elastase-induced aneurysm models by flow diverters: development of quantifiable indexes of device performance using digital subtraction angiography.

It has been known for more than a decade that intracranial aneurysms can be successfully treated by deploying a porous meshed tube in the parent vessel of the aneurysm. Such devices are currently called flow diverters because they promote intraneurysmal flow stasis and thrombosis by diverting blood flow away from the aneurysm sac. The objective of this study was to use angiographic data to quantify and compare the performance of flow diverters of original design in successfully occluding an experimental aneurysm model. Three different configurations of a novel flow diverter with varying porosities and pore densities were implanted in 30 rabbit elastase-induced aneurysms. Temporal variations in angiographic contrast intensity within the aneurysms were fit to a mathematical model. Optimized model parameters were supplemented by the angiographic percentage aneurysm occlusion and an angiographic measure of device flexibility to derive composite scores of performance. Angiographic quantification further suggested a parameter, which could be employed to estimate long-term aneurysm occlusion probabilities immediately after treatment. Performance scores showed that the device with a porosity of 70% and pore density of 18 pores/mm (2) performed better than devices with 65% porosity, 14 pores/mm (2), and 70% porosity, 12 pores/mm (2) with relative efficacies of 100%, 84%, and 76%, respectively. The pore density of flow diverters, rather than porosity, may thus be a critical factor modulating device efficacy. A value of the prognostic parameter of less than 30 predicted greater than 97% angiographic aneurysm occlusion over six months with a sensitivity of 73% and specificity of 82%.

Correlation between angiographic and particle image velocimetry quantifications of flow diverters in an in vitro model of elastase-induced rabbit aneurysms.

The rupture of a cerebral aneurysm can result in a hemorrhagic stroke. A flow diverter, which is a porous tubular mesh, can be placed across the neck of a cerebral aneurysm to induce the cessation of flow and initiate the formation of an intra-aneurysmal thrombus. By finding a correlation between particle image velocimetry (PIV) and digital subtraction angiography, a better assessment of how well an aneurysm is excluded from the parent artery can be made in the clinical setting. A model of a rabbit elastase-induced aneurysm was connected to a mock circulation loop. The model was then placed under angiography. Recorded angiograms were analyzed so that a contrast concentration-time curve based on the average grayscale intensity inside the aneurysm could be determined. That curve was then fitted to a mathematical model that quantifies the influence of convection and diffusion on contrast transport. Optimized parameters were correlated with the intraneurysmal mean kinetic energy measured by PIV in the same aneurysm model. A strong correlation was observed between the convection and diffusion time constants and the mean kinetic energy inside the aneurysm. Analyzing the flow of angiographic contrast into and out of the aneurysm after implantation of a flow diverter allows for prediction of the efficacy of the device in excluding the aneurysm. Correlating hydrodynamic measures obtained by angiography to those obtained by detailed techniques such as PIV increases confidence in such predictions.

An original flow diversion device for the treatment of intracranial aneurysms: evaluation in the rabbit elastase-induced model.

BACKGROUND AND PURPOSE: The potential for successful treatment of intracranial aneurysms by flow diversion is gradually being recognized in the clinical setting; however, the devices currently available (stents) are not designed for flow diversion. We evaluate the long-term response of an appropriately designed flow diversion device in producing thrombotic occlusion of experimental aneurysms. METHODS: Three different configurations of an original flow diversion device were implanted across thirty elastase-induced aneurysm models in rabbits. Ten animals per device configuration were followed-up for 3 weeks (n=3), 3 months (n=3), or 6 months (n=4), and tissue explanted postsacrifice was sent for histology. The temporal variation in angiographic contrast intensity within each aneurysm was fitted with a mathematical model to quantify the alteration in local hemodynamics caused by the implanted device. A predictive index, called the washout coefficient, was constructed to estimate long-term aneurysm occlusion probabilities immediately after treatment with any flow diversion device. RESULTS: The device with a porosity of 70% and pore density of 18 pores/mm(2) performed better at occluding aneurysms than devices with 70% porosity, 12 pores/mm(2) and 65% porosity, 14 pores/mm(2). A value of the washout coefficient less than 30 predicted greater than 97% angiographic aneurysm occlusion over a period of 6 months with a sensitivity of 73% and specificity of 82%. CONCLUSIONS: The flow diversion devices effected successful and stable aneurysm occlusion. Pore density, rather than porosity, may be the critical factor modulating efficacy of such devices.

In vitro evaluation of flow divertors in an elastase-induced saccular aneurysm model in rabbit.

Endovascular coiling is an acceptable treatment of intracranial aneurysms, yet long term follow-ups suggest that endovascular coiling fails to achieve complete aneurysm occlusions particularly in wide-neck and giant aneurysms. Placing of a stentlike device across the aneurysm neck may be sufficient to occlude the aneurysm by promoting intra-aneurysmal thrombosis; however, conclusive evidence of its efficacy is still lacking. In this study, we investigate in vitro the efficacy of custom designed flow divertors that will be subsequently implanted in a large cohort of animals. The aim of this study is to provide a detailed database against which in vivo results can be analyzed. Six custom designed flow divertors were fabricated and tested in vitro. The design matrix included three different porosities (75%, 70%, and 65%). For each porosity, there were two divertors with one having a nominal pore density double than that of the other. To quantify efficacy, the divertors were implanted in a compliant elastomeric model of an elastase-induced aneurysm model in rabbit and intra-aneurysmal flow changes were evaluated by particle image velocimetry (PIV). PIV results indicate a marked reduction in intra-aneurysmal flow activity after divertor implantation in the innominate artery across the aneurysm neck. The mean hydrodynamic circulation after divertor implantation was reduced to 14% or less of the mean circulation in the control and the mean intra-aneurysmal kinetic energy was reduced to 29% or less of its value in the control. The intra-aneurysmal wall shear rate in this model is low and implantation of the flow divertor did not change the wall shear rate magnitude appreciably. This in vitro experiment evaluates the characteristics of local flow phenomena such as hydrodynamic circulation, kinetic energy, wall shear rate, perforator flow, and changes of these parameters as a result of implantation of stentlike flow divertors in an elastomeric replica of elastase-induced saccular aneurysm model in rabbit. These initial findings offer a database for evaluation of in vivo implantations of such devices in the animal model and help in further development of cerebral aneurysm bypass devices.

Angiographic assessment of the performance of flow divertors to treat cerebral aneurysms.

Past clinical and experimental evidence suggests that cerebral aneurysms can be successfully excluded from the circulation solely by the endovascular placement of a flow diverting device across the aneurysm neck. These devices promote intraaneurysmal flow stasis and concomitant thrombosis by redirecting flow away from the aneurysm. To comprehensively test the efficacy of such flow divertors, we are implanting devices with three different porosities in a large cohort of elastase-induced aneurysms in rabbits. Treatment efficacy is quantified by a mathematical model that is fit to aneurysmal angiographic contrast washout curves. Results from three animals implanted with different device porosities are presented here. The model competently captures the behavior of the aneurysmal washout curves and provides reliable indices of device efficacy. Preliminary analysis indicates that immediately after implantation, the device with medium porosity performs better than the devices with lower and higher porosities.

Morphology of elastase-induced cerebral aneurysm model in rabbit and rapid prototyping of elastomeric transparent replicas.

In this work, we describe a methodology to fabricate transparent elastomeric vascular replicas using rapid prototyping techniques. First, the three-dimensional morphology of an elastase-induced aneurysm model in rabbit is acquired. The morphology is reconstructed from in vivo rotational angiography and it is compared with three-dimensional reconstructions obtained by computerized tomography and magnetic resonance imaging of an intraluminal arterial cast that was obtained from the same animal at sacrifice. Results show that resolution of the imaging modality strongly influences the level of detail, such as small side branches, in the final reconstruction. We developed an average morphology model for elastase-induced aneurysms in rabbits including the surrounding vasculature and describe a method for rapid prototyping of vascular models from the three-dimensional morphology. Our replicas can be manufactured in a short period of time and the final product is optically clear. In addition, the elasticity of the models can be controlled to represent arterial elasticity, which makes them ideal for optical investigations of detailed flow dynamics using measurement tools such as particle image velocimetry.

Functional angiography.

The discovery of X-rays over a century ago enabled noninvasive examination of the human body. Contrast agents that enhanced X-ray images were soon developed that advanced angiology by allowing exploration of the vascular tree. Starting as a diagnostic tool, angiography underwent technological transformations over the last century and became a basis for interventional therapy as well. Initially a static two-dimensional record of the vasculature on screen films, angiography has evolved to real-time two-dimensional display of the vasculature on television monitors, three-dimensional reconstruction from computerized tomographic (CT) scans, and, more recently, three-dimensional cone-beam reconstruction. Cinematographic angiography is referred to as dynamic angiography in current terminology, but it essentially provides no more than images of vascular structures and changes therein. Although dynamic angiography has facilitated advances in image-guided interventions, the evaluation of blood flow rate, or perfusion, and blood flow velocity using angiography remains elusive. Many lines of research have been pursued toward enabling such evaluations, but none have found their way into clinical practice. This article reviews angiographic flow assessment methods attempted over the past several decades and explores some new avenues that may facilitate the transfer of such methods into the clinical practice of diagnostic and interventional angiography and, eventually, contribute to better patient care.

Morphological age-dependent development of the human carotid bifurcation.

The unique morphology of the adult human carotid bifurcation and its sinus has been investigated extensively, but its long-term, age-dependent development has not. It is important fundamentally and clinically to understand the hemodynamics and developmental forces that play a role in remodeling of the carotid bifurcation and maturation of the sinus in association with brain maturation. This understanding can lead to better prognostication and therapy of carotid disease. We analyzed the change of sinus morphology and the angle of the carotid bifurcation in four postnatal developmental stages (Group I: 0-2 years, Group II: 3-9 years, Group III: 10-19 years, and Group IV: 20-36 years, respectively) using multiprojection digital subtraction angiograms and image post-processing techniques. The most significant findings are the substantial growth of the internal carotid artery (ICA) with age and the development of a carotid sinus at the root of the ICA during late adolescence. The bifurcation angle remains virtually unchanged from infancy to adulthood. However, the angle split between the ICA and external carotid artery (ECA) relative to the common carotid artery (CCA) undergoes significant changes. Initially, the ICA appears to emanate as a side branch. Later in life, to reduce hydraulic resistance in response to increased flow demand by the brain, the bifurcation is remodeled to a construct in which both daughter vessels are a skewed continuation of the parent artery. This study provides a new analysis method to examine the development of the human carotid bifurcation over the developmental years, despite the small and sparse database. A larger database will enable in the future a more extensive analysis such as gender or racial differences.

Hemodynamics of carotid artery atherosclerotic occlusive disease.

Hemodynamic mechanisms for the initiation and progression of carotid bifurcation atherosclerotic occlusive disease have been extensively researched during the past few decades. Attention has focused on the carotid bulb, or sinus, where most atherosclerotic plaques are found. Herein, the authors review the seminal works that have led to an understanding of not only complex local hemodynamics but also the elicited specific biologic response. In addition, new analysis of the age-dependent morphologic maturation of the human carotid bifurcation is unveiled. Understanding the role of hemodynamics in atherogenesis may lead to the improvement of minimally invasive endovascular therapy and noninvasive strategies.