Hunterian ligation affecting hemodynamics in vessels was proposed to avoid rebleeding in a case of a fenestrated basilar artery aneurysm after incomplete coil occlusion. We studied the hemodynamics in vitro to predict the hemodynamic changes near the aneurysm remnant caused by Hunterian ligation. A transparent model was fabricated based on three-dimensional rotational angiography imaging. Arteries were segmented and reconstructed. Pulsatile flow in the artery segments near the partially occluded (coiled) aneurysm was investigated by means of particle image velocimetry. The hemodynamic situation was investigated before and after Hunterian ligation of either the left or the right vertebral artery (LVA/RVA). Since post-ligation flow rate in the basilar artery was unknown, reduced and retained flow rates were simulated for both ligation options. Flow in the RVA and in the corresponding fenestra vessel is characterized by a vortex at the vertebrobasilar junction, whereas the LVA exhibits undisturbed laminar flow. Both options (RVA or LVA ligation) cause a significant flow reduction near the aneurysm remnant with a retained flow rate. The impact of RVA ligation is, however, significantly higher. This in vitro case study shows that flow reduction near the aneurysm remnant can be achieved by Hunterian ligation and that this effect depends largely on the selection of the ligated vessel. Thus the ability of the proposed in vitro pipe-line to improve hemodynamic impact of the proposed therapy was successfully proved.
Int J Artif Organs 2014; 37(4): 325 - 335
Article Type: ORIGINAL RESEARCH ARTICLE
AuthorsLeonid Goubergrits, Andreas Spuler, Jens Schaller, Nils Wiegmann, Andre Berthe, Hans-Christian Hege, Klaus Affeld, Ulrich Kertzscher
- • Accepted on 04/02/2014
- • Available online on 05/04/2014
- • Published in print on 08/05/2014
This article is available as full text PDF.
Cerebral aneurysm rupture causing life-threatening subarachnoid hemorrhage (SAH) is associated with high mortality and morbidity (1). The major therapy options are surgical clip placement or endovascular coil embolization, both aiming at separating the aneurysm from the parent vessel blood flow and thereby preventing rebleeding (2). Recently, a new endovascular aneurysm treatment using a flow diverting stent has been introduced (3). The idea behind this method is to avoid or reduce blood inflow from the parent vessel into the aneurysm. Further treatment options include the use of aneurysm filling with hardening polymers or glue (2). Hunterian ligation, which is considered the father of modern neurosurgical clipping, is also an option (4, 5). Choosing the optimal treatment depends on many risk factors associated with SAH, including sex, age, ethnicity, aneurysm size, location, shape, and patient history (2, 6). Due to the huge inter-patient variability, the choice of therapy option is best left to a team of clinicians familiar with neurovascular surgery, endovascular treatment techniques, and neurologic critical care (7). The objective of treatment selection is to predict patient-specific post-treatment changes of intra-aneurysmal and parent vessel hemodynamics due to luminal changes caused by artificial devices (coils, stents, flow diverting stents, or clips). This requires an image-based flow analysis using an experimental model or computational fluid dynamics. Here, the expertise of engineers in hemodynamics – of biofluid mechanics, for example – comes into play. Without a hemodynamic analysis before the intervention, the effect of such an treatment decision, even in the case of Hunterian ligation, can be clinically unexpected and disastrous (8).
In this study, we describe an experimental pipeline using an
MATERIAL AND METHODS
Data and reconstruction, model cast
An aneurysm was detected on a fenestrated basilar artery of a 45-year-old female. Computed tomography (CT) angiography was performed by means of a Siemens CT VA0 device (Siemens, Forchheim, Germany) using an 18 s 1.25 H21f sequence with 512 x 512 px in-plane slice resolution and 1.25 mm slice thickness, resulting in the voxel size of 0.5 mm x 0.5 mm x 0.9 mm. Due to the low resolution of the CT data and the difficult segmentation caused by the proximity of the skull base, these data were not accurate enough to allow for an appropriate three-dimensional (3D) reconstruction.
a) CT slice with a reconstructed aneurysm at fenestrated basilar artery. b) Angiogram of the coiled aneurysm after a successful exclusion of the aneurysm from blood circulation. c) Angiogram showing failed (contrast agent enters the aneurysm) coiling therapy 21 months after the treatment.
However, 21 months later, routine follow-up 3D rotational digital subtraction angiography (3DRA with 126 frames, 1.6° between two frames) found incomplete aneurysm occlusion (
a) Reconstructed post-coil surface with aneurysm remnants. Black arrows show flow direction. b) and c) Dashed lines show locations of two laser light sheets (A-plane and B-plane) acquired by PIV.
During reconstruction we preserved inlet segments as long as possible (8 x
a) Experimental setup including (1) PC for data storing, (2) computer controlled piston pump, (3) throttles to set flow rates, (4) rigid inlet ducts, (5) collecting reservoirs, (6) laser, (7) optic generating laser light sheet, (8) flow rate probe Transonic, (9) camera, and (10) Plexiglas® box containing silicone model and filled with glycerol/water mixture. Black arrows show flow directions. b) In vitro scaled inlet flow waveform. Four time steps (end-diastole – t1 (176 ml/min); acceleration phase – t2 (266 ml/min); peak-systole – t3 (388 ml/min); deceleration phase – t4 (266 ml/min)) represent characteristic flow states during heart cycle.
Patient-specific flow data were not available. Therefore, a total mean flow rate of 133 ml/min derived from magnetic resonance imaging (MRI) for both VAs (flow in basilaris artery) was simulated for an original unclamped situation (14, 15). The waveform (
Three setups were investigated: the original unclamped model, the model with ligated LVA, and the model with ligated RVA. Since the flow rate after Hunterian ligation can be reduced due to the treatment, two mean post-ligation flow rates were simulated for both clamped configurations:
the flow rate of the respective unclamped LVA (
a total mean flow rate of both VA simulated in the unclamped configuration (
Standard 2D-PIV (17) was used to investigate the flow in the fenestra vessel segment with aneurysm neck remnant (
As mentioned above, five experimental flow setups were investigated. Inter-experimental reproducibility was proved.
Flow profiles with error bars in the A-plane for time step t2 with in vivo flow rate of 133 ml/min at three specific positions during original unclamped flow configuration. Dashed lines mark vessel segment centers.
Velocity vector fields are shown in
Flow fields in A-plane visualized at four characteristic time steps t1-t4 with a total in vivo flow rate of 133 ml/min in all three configurations: a) and b) original unclamped, c) ligated LVA, and d) ligated RVA. The aneurysm remnant is beneath the plane. Grey areas mark the recirculation zone (vortex).
Flow profiles at four characteristic time steps t1-t4 from up to down with the total in vivo flow rate of 133 ml/min at three specific positions: a) original unclamped flow configuration, b) superimposed profiles of three configuration (original unclamped – dashed; ligated LVA – black; ligated RVA – gray line), and c) flow profiles of the ligated LVA configuration with two flow rates in the RVA (in vivo 133 ml/min – black line and in vivo 49 ml/min – gray line). Velocity profiles of the lower flow rate were scaled by a factor of 133/49 for a direct comparison.
In contrast, LVA flow stream enters LFVS (
The recirculation zone increases in both configurations of unilateral clipping (
Flow field in the B-plane at four characteristic time steps t1-t4 with the total in vivo flow rate of 133 ml/min in all three configurations a) and b) original unclamped, c) ligated LVA, and d) ligated RVA. Grey frame (see t1, b) shows the region used to quantify the flow reduction due to ligation near the aneurysm remnant.
The flow profiles at different positions show the quantitative impact of the treatment options (
Flow at the aneurysm site is shown in
Near remnant velocity magnitude values at four characteristic time steps t1-t4 with the total in vivo flow rate of 133 ml/min in all three configurations: original unclamped – black circles ligated LVA – black squares and ligated RVA – black triangles. Values are shown without standard deviation (s.d.) bars for a better visibility. All s.d. ranged between 10 and 20 mm/s. Flow rate curve is added for a better data representation.
The case of a post-coiling aneurysm remnant at a fenestrated basilar artery was investigated. This seems to be a rare case. Wollschlaeger et al found more than 5% of fenestrated cases in a post-mortem study (20). In contrast, angiography studies show only a prevalence of about 1% of this anatomic variant. This is explained by the challenge to identify fenestrations in angiography data. Nevertheless, there are quite a few published cases (21-22-23-24-25). A case of this type was also a part of the Virtual Intracranial Stenting Challenge 2009 (26). It seems that fenestration promotes the genesis of aneurysms: Tsuei et al found aneurysms in 8 of 32 patients (25%) with the fenestrated vertebrobasilar junction (25). Another study, however, found aneurysms in only 7% of fenestrated basilar arteries (27).
Tsuei et al found no difference in hemodynamics of pre- and post-coiled geometries (25). Unfortunately, they do not describe the flow in detail. As we found, flow in a fenestrated basilar artery is a complex 3D disturbed flow, which is often associated with vessel wall remodeling, atherosclerosis, and aneurysm formation (28). In contrast, flow at a normal vertebrobasilar junction is described as parallel laminar flow in 80% of cases or as flow with secondary flow features (spiral flow), but without recirculation zones (29, 30). Consequently, it can be speculated that disturbed flow formed by a vortex as found in our case is associated with a degenerative, irregular shape of the RFVS vessel segment and with aneurysm development. Summarizing, hemodynamics and treatment of fenestrated artery aneurysms are of great interest.
Studies indicate that high wall shear stress associated with high velocities at the aneurysm neck is associated with aneurysm recanalization (31, 32). Hence, lowering of flow velocity near the neck or the remnant of an aneurysm due to post-ligation changes of hemodynamics (flow profiles or flow rate divisions at bifurcations) or due to reduction of total flow might reduce the recanalization rate. In our case, flow reduction near the aneurysm remnant was achieved by both ligation options (LVA or RVA ligation) even when total flow was not reduced. However, the impact of RVA ligation was significantly higher than that of LVA ligation. Flow reduction near the aneurysm remnant due to ligation of the LVA or RVA seems to result from a combined effect of the vortex preexisting at the junction and the curvature of VAs. Such an effect of flow manipulation cannot be predicted without extensive flow investigations.
A further possible effect of therapeutic interventions is the impact of altered hemodynamics on endothelial cells. Substantial flow reduction diminishes endothelial wall shear stress, thus decreasing local nitric oxide production (33). Nitric oxide inhibits platelet adherence and aggregation as well as leukocyte adhesion and infiltration (34). Therefore, velocity reduction at the aneurysmal neck might promote thrombus formation or inflammation.
The reliability of the proposed
We only investigated the neurosurgical treatment option of Hunterian ligation. The definite treatment decision has not been made in this patient, who is currently in clinical and angiographical follow-up. The same pipeline can be used to study any other endovascular treatment option, for instance, like balloon occlusion or implantation of a flow diverting stent.
This study has some limitations. The patient-specific flow waveform was unknown. Therefore, we used literature data. It should be noted that Hunterian ligation may also affect the flow waveform. It was shown that the waveform affects time-dependent flow parameters, whereas time-averaged flow parameters are independent (38). We found different flow conditions during different phases (compare results for time steps
Standard in-plane PIV was used in our study. Quantitative results obtained by PIV are limited by the spatial and temporal resolution of the respective techniques, including particle size and time intervals used for the data averaging (41). The PIV setting used is a compromise between data resolution and time costs of experiments, allowing an accurate velocity field assessment (17-18-19, 41).
Max-min images show regions (stripes) without tracers (see
Alternative to the PIV technique used, other visualization techniques including LDV, holographic PIV, point-based 3D volumetric measurements or Tomo-PIV are possible (42-43-44). The measurement technique used is also a compromise between data resolution, technique availability, and time costs of experiments, including post-processing.
As illustrated by the current PIV study,
- Goubergrits, Leonid [PubMed] [Google Scholar] 1, *
- Spuler, Andreas [PubMed] [Google Scholar] 2, *
- Schaller, Jens [PubMed] [Google Scholar] 1
- Wiegmann, Nils [PubMed] [Google Scholar] 1
- Berthe, Andre [PubMed] [Google Scholar] 1
- Hege, Hans-Christian [PubMed] [Google Scholar] 3
- Affeld, Klaus [PubMed] [Google Scholar] 1
- Kertzscher, Ulrich [PubMed] [Google Scholar] 1, * Corresponding Author (firstname.lastname@example.org)
Biofluid Mechanics Laboratory, Charité – Universitätsmedizin Berlin, Berlin - Germany
Department of Neurosurgery, Helios Hospital Berlin-Buch, Berlin - Germany
Visualization and Data Analysis, Zuse Institute Berlin, Berlin - Germany
These authors contributed equally to this manuscript