Development of experimental ground truth and quantification of intracranial aneurysm pulsation in a patient.

Aneurysm wall motion has been reported to be associated with rupture. However, its quantification with medical imaging is challenging and should be based on experimental ground-truth to avoid misinterpretation of results. In this work a time-resolved CT angiography (4D-CTA) acquisition protocol is proposed to detect the pulsation of intracranial aneurysms with a low radiation dose. To acquire ground-truth data, the accuracy of volume pulsation detection and quantification in a silicone phantom was assessed by applying pressure sinusoidal waves of increasing amplitudes. These experiments were carried out using a test bench that could reproduce pulsatile waveforms similar to those inside the internal carotid arteries of human subjects. 4D-CTA acquisition parameters (mAs, kVp) were then selected to achieve reliable pulsation detection and quantification with the lowest radiation dose achievable. The resulting acquisition protocol was then used to image an anterior communicating artery aneurysm in a human subject. Data reveals that in a simplified in vitro setting 4D-CTA allows for an effective and reproducible method to detect and quantify aneurysm volume pulsation with an inferior limit as low as 3 mm3 and a background noise of 0.5-1 mm3. Aneurysm pulsation can be detected in vivo with a radiation dose approximating 1 mSv.

Does the gravity orientation of saccular aneurysms influence hemodynamics? An experimental study with and without flow diverter stent.

Most intracranial aneurysms morphologic studies focused on characterization of size, location, aspect ratio, relationship to the surrounding vasculature and hemodynamics. However, the spatial orientation with respect to the gravity direction has not been taken into account although it could trigger various hemodynamic conditions. The present work addresses this possibility. It was divided in two parts: 1) the orientations of 18, 3D time-of-flight MRI (3D TOF MRI), scans of saccular aneurysms were analyzed. This investigation suggested that there was no privileged orientation for cerebral aneurysms. The aneurysms were oriented in the brain as follows: 9 - down, 9 - up; 11 - right, 7 - left; 6 - front, 12 - back. 2) Based on these results, subsidiary in vitro experiments were performed, analyzing the behavior of red blood cells (RBCs) within a silicone model of aneurysm before and after flow diverter stent (FDS) deployment in the parent vessel. These experiments used a test bench that reproduces physiological pulsatile flow conditions for two orientations: an aneurysm sack pointing either up (opposite to gravitational force) and down (along the gravitational force). The results showed that the orientation of an aneurysm significantly affects the intra-aneurysmal RBCs behavior after stenting, and therefore that gravity can affect the intra-aneurysm behavior of RBCs. This suggests that the patient׳s aneurysm orientation could impact the outcome of the FDS treatment. The implementation of this effect in patient-specific numerical and preoperative decision support techniques could contribute to better understand the intrasaccular biological and hemodynamic events induced by FDS.

Hemodynamic numerical simulations of the disturbance due to intracoronary flow measurements by a Doppler guide wire.

BACKGROUND: Since hemodynamics plays a key role in the development and evolution of cardiovascular pathologies, physician's decision must be based on proper monitoring of relevant physiological flow quantities. METHODS: A numerical analysis of the error introduced by an intravascular Doppler guide wire on the peak velocity measurements has been carried out. The effect of probe misalignment (±10°) with respect to the vessel axis was investigated. Numerical simulations were performed on a realistic 3D geometry, reconstructed from coronary angiography images. Furthermore, instead of using Poiseuille or Womersley approximations, the unsteady pulsatile inlet boundary condition has been calculated from experimental peak-velocity measurements inside the vessel through a new approach based on an iterative Newton's algorithm. RESULTS: The results show that the presence of the guide modifies significantly both the maximum velocity and the peak position in the section plane; the difference is between 6 and 17 % of the maximum measured velocity depending on the distance from the probe tip and the instantaneous vessel flow rate. Furthermore, a misalignment of the probe may lead to a wrong estimation of the peak velocity with an error up to 10 % depending on the probe orientation angle. CONCLUSIONS: The Doppler probe does affect the maximum velocity and its position during intravascular Doppler measurements. Moreover, the Doppler-probe-wire sampling volume at 5.2 and 10 mm far from the probe tip is not sufficient to prevent its influence on the measurement. This should be taken into account in clinical practice by physicians during intravascular Doppler quantification. The new numerical approach used in this work could potentially be helpful in future numerical simulations to set plausible inlet boundary conditions.

Determination of a shear rate threshold for thrombus formation in intracranial aneurysms.

BACKGROUND: Particular intra-aneurysmal blood flow conditions, created naturally by the growth of an aneurysm or induced artificially by implantation of a flow diverter stent (FDS), can potentiate intra-aneurysmal thrombosis. The aim of this study was to identify hemodynamic indicators, relevant to this process, which could be used as a prediction of the success of a preventive endovascular treatment. METHOD: A cross sectional study on 21 patients was carried out to investigate the possible association between intra-aneurysmal spontaneous thrombus volume and the dome to neck aspect ratio (AR) of the aneurysm. The mechanistic link between these two parameters was further investigated through a Fourier analysis of the intra-aneurysmal shear rate (SR) obtained by computational fluid dynamics (CFD). This analysis was first applied to 10 additional patients (4 with and 6 without spontaneous thrombosis) and later to 3 patients whose intracranial aneurysms only thrombosed after FDS implantation. RESULTS: The cross sectional study revealed an association between intra-aneurysmal spontaneous thrombus volume and the AR of the aneurysm (R(2)=0.67, p<0.001). Fourier analysis revealed that in cases where thrombosis occurred, the SR harmonics 0, 1, and 2 were always less than 25/s, 10/s, and 5/s, respectively, and always greater than these values where spontaneous thrombosis was not observed. CONCLUSIONS: Our study suggests the existence of an SR threshold below which thrombosis will occur. Therefore, by analyzing the SR on patient specific data with CFD techniques, it may be potentially possible to predict whether or the intra-aneurysmal flow conditions, after FDS implantation, will become prothrombotic.

An in vitro test bench reproducing coronary blood flow signals.

BACKGROUND: It is a known fact that blood flow pattern and more specifically the pulsatile time variation of shear stress on the vascular wall play a key role in atherogenesis. The paper presents the conception, the building and the control of a new in vitro test bench that mimics the pulsatile flows behavior based on in vivo measurements. METHODS: An in vitro cardiovascular simulator is alimented with in vivo constraints upstream and provided with further post-processing analysis downstream in order to mimic the pulsatile in vivo blood flow quantities. This real-time controlled system is designed to perform real pulsatile in vivo blood flow signals to study endothelial cells' behavior under near physiological environment. The system is based on an internal model controller and a proportional-integral controller that controls a linear motor with customized piston pump, two proportional-integral controllers that control the mean flow rate and temperature of the medium. This configuration enables to mimic any resulting blood flow rate patterns between 40 and 700 ml/min. In order to feed the system with reliable periodic flow quantities in vivo measurements were performed. Data from five patients (1 female, 4 males; ages 44-63) were filtered and post-processed using the Newtonian Womersley's solution. These resulting flow signals were compared with 2D axisymmetric, numerical simulation using a Carreau non-Newtonian model to validate the approximation of a Newtonian behavior. RESULTS: This in vitro test bench reproduces the measured flow rate time evolution and the complexity of in vivo hemodynamic signals within the accuracy of the relative error below 5%. CONCLUSIONS: This post-processing method is compatible with any real complex in vivo signal and demonstrates the heterogeneity of pulsatile patterns in coronary arteries among of different patients. The comparison between analytical and numerical solution demonstrate the fair quality of the Newtonian Womersley's approximation. Therefore, Womersley's solution was used to calculate input flow rate for the in vitro test bench.

A new device to mimic intermittent hypoxia in mice.

Intermittent hypoxia (hypoxia-reoxygenation) is often associated with cardiovascular morbidity and mortality. We describe a new device which can be used to submit cohorts of mice to controlled and standardised hypoxia-normoxia cycles at an individual level. Mice were placed in individual compartments to which similar gas flow parameters were provided using an open loop strategy. Evaluations made using computational fluid dynamics were confirmed by studying changes in haemoglobin oxygen saturation in vivo. We also modified the parameters of the system and demonstrated its ability to generate different severities of cyclic hypoxemia very precisely, even with very high frequency cycles of hypoxia-reoxygenation. The importance of the parameters on reoxygenation was shown. This device will allow investigators to assess the effects of hypoxia-reoxygenation on different pathological conditions, such as obstructive sleep apnoea or chronic obstructive pulmonary disease.