Biomaterials Used in Injectable Implants (Liquid Embolics) for Percutaneous Filling of Vascular Spaces

The biomaterials currently used in injectable implants (liquid embolics) for minimally invasive image-guided treatment of vascular lesions undergo, once injected in situ, a phase transition based on a variety of physicochemical principles. The mechanisms leading to the formation of a solid implant include polymerization, precipitation and cross-linking through ionic or thermal process. The biomaterial characteristics have to meet the requirements of a variety of treatment conditions. The viscosity of the liquid is adapted to the access instrument, which can range from 0.2 mm to 3 mm in diameter and from a few centimeters up to 200 cm in length. Once such liquid embolics reach the vascular space, they are designed to become occlusive by inducing thrombosis or directly blocking the lesion when hardening of the embolics occurs. The safe delivery of such implants critically depends on their visibility and their hardening mechanism. Once delivered, the safety and effectiveness issues are related to implant functions such as biocompatibility, biodegradability or biomechanical properties. We review here the available and the experimental products with respect to the nature of the polymer, the mechanism of gel cast formation and the key characteristics that govern the choice of effective injectable implant

PMMA cementoplasty in symptomatic metastatic lesions of the S1 vertebral body

We describe a lateral transiliac direct puncture approach to the SI vertebral body for polymethylmethacrylate (PMMA) cernentoplasty of painful metastatic lesions. This approach was performed using a 15-cm-long trocar needle with 3-mm outer diameter, introduced under general anesthesia and fluoroscopic control. A lateral projection was used to center the needle just in front of the spinal canal and subjacent to the superior plate of the S1 vertebral body. Needle progression was controlled using anteroposterior and lateral fluoroscopic projections alternately with a needle course parallel to an axial plane, avoiding conflict with the S1 foramen. After needle tip placement in the center of the S1 vertebral body, diluted PMMA with a setting time of 8 min was delivered. Ipsilateral lesions of the lateral sacral compartment were filled with the same needle by stepwise withdrawal and continuous PMMA injectio

Multiple Coaxial Catheter System for Reliable Access in Interventional Stroke Therapy

In some patients with acute cerebral vessel occlusion, navigating mechanical thrombectomy systems is difficult due to tortuous anatomy of the aortic arch, carotid arteries, or vertebral arteries. Our purpose was to describe a multiple coaxial catheter system used for mechanical revascularization that helps navigation and manipulations in tortuous vessels. A triple or quadruple coaxial catheter system was built in 28 consecutive cases presenting with acute ischemic stroke. All cases were treated by mechanical thrombectomy with the Penumbra System. In cases of unsuccessful thrombo-aspiration, additional thrombolysis or angioplasty with stent placement was used for improving recanalization. The catheter system consisted of an outermost 8-Fr and an intermediate 6-Fr guiding catheter, containing the inner Penumbra reperfusion catheters. The largest, 4.1-Fr, reperfusion catheter was navigated over a Prowler Select Plus microcatheter. The catheter system provided access to reach the cerebral lesions and provided stability for the mechanically demanding manipulations of thromboaspiration and stent navigation in all cases. Apart from their mechanical role, the specific parts of the system could also provide access to different types of interventions, like carotid stenting through the 8-Fr guiding catheter and intracranial stenting and thrombolysis through the Prowler Select Plus microcatheter. In this series, there were no complications related to the catheter system. In conclusion, building up a triple or quadruple coaxial system proved to be safe and efficient in our experience for the mechanical thrombectomy treatment of acute ischemic strok

Effect of Flow Diverter Porosity on Intraaneurysmal Blood Flow

Abstract : Background and Purpose: : Growth and rupture, the two events that dominate the evolution of an intracranial aneurysm, are both dependent on intraaneurysmal flow. Decrease of intraaneurysmal flow is considered an attractive alternative for treating intracranial aneurysms by minimally invasive techniques. Such modification can be achieved by inserting stents or flow diverters alone. In the present paper, the effect of different commercial and innovative flow diverters' porosity was studied in intracranial aneurysm models. Material and Methods: : Single and stent-in-stent combination of Neuroform II as well as single and stent-in-stent combination of a new innovative, low-porosity, intracranial stent device (D1, D2, D1 + D2) were inserted in models of intracranial aneurysms under shear-driven flow and inertia-driven flow configurations. Steady and pulsating flow rates were applied using a blood-like fluid. Particle image velocimetry was used to measure velocity vector fields in the aneurysm midplane along the vessel axis. Flow and vorticity patterns, velocity and vorticity magnitudes were quantified and their value compared with the same flows in absence of the flow diverter. Results: : In absence of flow diverters, a solid-like rotation could be observed in both shear-driven and inertia-driven models under steady and pulsatile flow conditions. The flow effects due to the insertion of low-porous devices such as D1 or D2 provoked a complete alteration of the flow patterns and massive reduction of velocity or vorticity magnitudes, whereas the introduction of clinically adopted high-porous devices provoked less effect in the aneurysm cavity. As expected, results showed that the lower the porosity the larger the reduction in velocity and vorticity within the aneurysm cavity. The lowest-porosity device combination (D1 and D2) reached an averaged reduction of flow parameters of 80% and 88% under steady and pulsatile flow conditions, respectively. The reduction in mean velocity and vorticity was much more significant in the shear-driven flows as compared to the inertia-driven flows. Conclusion: : Although device porosity is the main parameter influencing flow reduction, other parameters such as device design and local flow conditions may influence the level of flow reduction within intracranial aneurysm

In vivo visualization and analysis of 3-D hemodynamics in cerebral aneurysms with flow-sensitized 4-D MR imaging at 3T

Introduction: Blood-flow patterns and wall shear stress (WSS) are considered to play a major role in the development and rupture of cerebral aneurysms. These hemodynamic aspects have been extensively studied in vitro using geometric realistic aneurysm models. The purpose of this study was to evaluate the feasibility of in vivo flow-sensitized 4-D MR imaging for analysis of intraaneurysmal hemodynamics. Methods: Five cerebral aneurysms were examined using ECG-gated, flow-sensitized 4-D MR imaging at 3T in three patients. Postprocessing included quantification of flow velocities, visualization of time-resolved 2-D vector graphs and 3-D particle traces, vortical flow analysis, and estimation of WSS. Flow patterns were analyzed in relation to aneurysm geometry and aspect ratio. Results: Magnitude, spatial and temporal evolution of vortical flow differed markedly among the aneurysms. Particularly unstable vortical flow was demonstrated in a wide-necked parophthalmic ICA aneurysm (high aspect ratio). Relatively stable vortical flow was observed in aneurysms with a lower aspect ratio. Except for a wide-necked cavernous ICA aneurysm (low aspect ratio), WSS was reduced in all aneurysms and showed a high spatial variation. Conclusion: In vivo flow-sensitized 4-D MR imaging can be applied to analyze complex patterns of intraaneurysmal flow. Flow patterns, distribution of flow velocities, and WSS seem to be determined by the vascular geometry of the aneurysm. Temporal and spatial averaging effects are drawbacks of the MR-based analysis of flow patterns as well as the estimation of WSS, particularly in small aneurysms. Further studies are needed to establish a direct link between definitive flow patterns and different aneurysm geometrie

Complications of Carotid Angioplasty and Stenting

The authors report the complications that occurred in their experience with performing recanalization procedures in the internal carotid artery and present their treatment strategies. The complications can be classified into those that were periprocedural and those that were postprocedural. The former include complications related to the vascular-approach access site of and those associated with the dilation and stenting procedure. Other complications observed included embolic events, dissection, vascular spasm, bradycardia, inappropriate dilation, occlusion of the external carotid artery, and rare, unusual complications such as the occurrence of iatrogenic cavernous carotid fistula. Postprocedure complications occurred in the hours and days following the procedure in the form of embolic and occlusive events, and hypotension and bradycardia were seen as late complications in the months following the procedure. The authors discuss how such complications occur and provide suggestions on how to avoid them. The role of stent placement and the potential use of protective devices are explored. Overall, adequate use of currently available systems allows for safe application of endovascular treatment techniques that avoid altogether or treat these potential complications. A reduced incidence of complications related to the initial individual learning curve may be obtained with preclinical training, in which use of invitro models should be considered. Surgical standby no longer seems required; however, early posttreatment surveillance in intensive care unit is mandatory to avoid the remaining primary complications

The predictive value of segmentation metrics on dosimetry in organs at risk of the brain.

BACKGROUND Fully automatic medical image segmentation has been a long pursuit in radiotherapy (RT). Recent developments involving deep learning show promising results yielding consistent and time efficient contours. In order to train and validate these systems, several geometric based metrics, such as Dice Similarity Coefficient (DSC), Hausdorff, and other related metrics are currently the standard in automated medical image segmentation challenges. However, the relevance of these metrics in RT is questionable. The quality of automated segmentation results needs to reflect clinical relevant treatment outcomes, such as dosimetry and related tumor control and toxicity. In this study, we present results investigating the correlation between popular geometric segmentation metrics and dose parameters for Organs-At-Risk (OAR) in brain tumor patients, and investigate properties that might be predictive for dose changes in brain radiotherapy. METHODS A retrospective database of glioblastoma multiforme patients was stratified for planning difficulty, from which 12 cases were selected and reference sets of OARs and radiation targets were defined. In order to assess the relation between segmentation quality -as measured by standard segmentation assessment metrics- and quality of RT plans, clinically realistic, yet alternative contours for each OAR of the selected cases were obtained through three methods: (i) Manual contours by two additional human raters. (ii) Realistic manual manipulations of reference contours. (iii) Through deep learning based segmentation results. On the reference structure set a reference plan was generated that was re-optimized for each corresponding alternative contour set. The correlation between segmentation metrics, and dosimetric changes was obtained and analyzed for each OAR, by means of the mean dose and maximum dose to 1% of the volume (Dmax 1%). Furthermore, we conducted specific experiments to investigate the dosimetric effect of alternative OAR contours with respect to the proximity to the target, size, particular shape and relative location to the target. RESULTS We found a low correlation between the DSC, reflecting the alternative OAR contours, and dosimetric changes. The Pearson correlation coefficient between the mean OAR dose effect and the Dice was -0.11. For Dmax 1%, we found a correlation of -0.13. Similar low correlations were found for 22 other segmentation metrics. The organ based analysis showed that there is a better correlation for the larger OARs (i.e. brainstem and eyes) as for the smaller OARs (i.e. optic nerves and chiasm). Furthermore, we found that proximity to the target does not make contour variations more susceptible to the dose effect. However, the direction of the contour variation with respect to the relative location of the target seems to have a strong correlation with the dose effect. CONCLUSIONS This study shows a low correlation between segmentation metrics and dosimetric changes for OARs in brain tumor patients. Results suggest that the current metrics for image segmentation in RT, as well as deep learning systems employing such metrics, need to be revisited towards clinically oriented metrics that better reflect how segmentation quality affects dose distribution and related tumor control and toxicity

Rheological Changes After Stenting of a Cerebral Aneurysm: A Finite Element Modeling Approach

Hemodynamic changes in intracranial aneurysms after stent placement include the appearance of areas with stagnant flow and low shear rates. We investigated the influence of stent placement on blood flow velocity and wall shear stress of an intracranial aneurysm using a finite element modeling approach. To assess viscosity changes induced by stent placement, the rheology of blood as non-Newtonian fluid was taken into account in this model. A two-dimensional model with a parent artery, a smaller branching artery, and an aneurysm located at the bifurcation, before and after stent placement, was used for simulation. Flow velocity plots and wall shear stress before and after stent placement was calculated over the entire cardiac circle. Values for dynamic viscosity were calculated with a constitutive equation that was based on experimental studies and yielded a viscosity, which decreases as the shear rate increases. Stent placement lowered peak velocities in the main vortex of the aneurysm by a factor of at least 4 compared to peak velocities in the main artery, and it considerably decreased the wall shear stress of the aneurysm. Dynamic viscosity increases after stent placement persisted over a major part of the cardiac cycle, with a factor of up to 10, most pronounced near the dome of the aneurysm. Finite element modeling can offer insight into rheological changes induced by stent treatment of aneurysms and allows visualizing dynamic viscosity changes induced by stent placemen

Impact of random outliers in auto-segmented targets on radiotherapy treatment plans for glioblastoma.

AIMS To save time and have more consistent contours, fully automatic segmentation of targets and organs at risk (OAR) is a valuable asset in radiotherapy. Though current deep learning (DL) based models are on par with manual contouring, they are not perfect and typical errors, as false positives, occur frequently and unpredictably. While it is possible to solve this for OARs, it is far from straightforward for target structures. In order to tackle this problem, in this study, we analyzed the occurrence and the possible dose effects of automated delineation outliers. METHODS First, a set of controlled experiments on synthetically generated outliers on the CT of a glioblastoma (GBM) patient was performed. We analyzed the dosimetric impact on outliers with different location, shape, absolute size and relative size to the main target, resulting in 61 simulated scenarios. Second, multiple segmentation models where trained on a U-Net network based on 80 training sets consisting of GBM cases with annotated gross tumor volume (GTV) and edema structures. On 20 test cases, 5 different trained models and a majority voting method were used to predict the GTV and edema. The amount of outliers on the predictions were determined, as well as their size and distance from the actual target. RESULTS We found that plans containing outliers result in an increased dose to healthy brain tissue. The extent of the dose effect is dependent on the relative size, location and the distance to the main targets and involved OARs. Generally, the larger the absolute outlier volume and the distance to the target the higher the potential dose effect. For 120 predicted GTV and edema structures, we found 1887 outliers. After construction of the planning treatment volume (PTV), 137 outliers remained with a mean distance to the target of 38.5 ± 5.0 mm and a mean size of 1010.8 ± 95.6 mm3. We also found that majority voting of DL results is capable to reduce outliers. CONCLUSIONS This study shows that there is a severe risk of false positive outliers in current DL predictions of target structures. Additionally, these errors will have an evident detrimental impact on the dose and therefore could affect treatment outcome