Volumetric microscopy of cerebral arteries with a miniaturized optical coherence tomography imaging probe.

Endovascular interventions are increasingly becoming the preferred approach for treating strokes and cerebral artery diseases. These procedures rely on sophisticated angiographical imaging guidance, which encounters challenges because of limited contrast and spatial resolution. Achieving a more precise visualization of the underlying arterial pathology and neurovascular implants is crucial for accurate procedural decision-making. In a human study involving 32 patients, we introduced the clinical application of a miniaturized endovascular neuro optical coherence tomography (nOCT) imaging probe. This technology was designed to navigate the tortuous paths of the cerebrovascular circulation and to offer high-resolution imaging in situ. The nOCT probe is compatible with standard neurovascular microcatheters, integrating with the procedural workflow used in clinical routine. Equipped with a miniaturized optical fiber and a distal lens, the probe illuminates the tissue and collects the backscattered, near-infrared light. While rotating the fiber and the lens at high speed, the probe is rapidly retracted, creating a spiral-shaped light pattern to comprehensively capture the arterial wall and implanted devices. Using nOCT, we demonstrated volumetric microscopy of cerebral arteries in patients undergoing endovascular procedures. We imaged the anterior and posterior circulation of the brain, including distal segments of the internal carotid and middle-cerebral arteries, as well as the vertebral, basilar, and posterior cerebral arteries. We captured a broad spectrum of neurovascular pathologies, such as brain aneurysms, ischemic stroke, arterial stenoses, dissections, and intracranial atherosclerotic disease. nOCT offered artifact-free, high-resolution visualizations of intracranial artery pathology and neurovascular devices.

Longitudinal healing flow diverting stents with phosphorylcholine surface modification.

BACKGROUND: Flow diversion has become a standard treatment for cerebral aneurysms. However, major drawbacks include the need for dual antiplatelet therapy after implant and delayed complete occlusion of the aneurysm, which occurs when new tissue growth excludes the aneurysm from the parent artery. Biomimetic surface modifications such as the phosphorylcholine polymer (Shield surface modification) represent major advances in reducing thrombogenicity of these devices. However, in vitro studies have raised concerns that this modification may also delay endothelialization of flow diverters. METHODS: Bare metal Pipeline, Pipeline Shield, and Vantage with Shield devices were implanted in the common carotid arteries (CCAs) of 10 rabbits (two in the left CCA, one in the right CCA). Following implant and at 5, 10, 15, and 30 days, the devices were imaged with high-frequency optical coherence tomography and conventional angiography to evaluate tissue growth. At 30 days the devices were explanted and their endothelial growth was assessed with scanning electron microscopy (SEM) at five locations along their length using a semi-quantitative score. RESULTS: The average tissue growth thickness (ATGT) was not different between the three devices. Neointima was apparent at 5 days and all devices demonstrated similar ATGT at each time point. On SEM, no difference was found in the endothelium scores between the device types. CONCLUSION: In vivo, neither the Shield surface modification nor the device design (Vantage) altered the longitudinal healing of the flow diverter.

Active drug-coated flow diverter in a preclinical model of intracranial stenting.

BACKGROUND: Flow diverters carry the risk of thromboembolic complications (TEC). We tested a coating with covalently bound heparin that activates antithrombin to address TEC by locally downregulating the coagulation cascade. We hypothesized that the neuroimaging evidence of TEC would be reduced by the coating. METHODS: 16 dogs were implanted with overlapping flow diverters in the basilar artery, separated into two groups: heparin-coated (n=9) and uncoated (n=7). Following implantation, high-frequency optical coherence tomography (HF-OCT) was acquired to quantify acute thrombus (AT) formation on the flow diverters. MRI was performed postoperatively and repeated at 1, 2, 3, 4, and 8 weeks, consisting of T1-weighted imaging, time-0f-flight (ToF), diffusion weighted imaging (DWI), susceptibility weighted imaging (SWI), and fluid attenuated inversion recovery (FLAIR) sequences. Neurological examinations were performed throughout the 8-week duration of the study. RESULTS: The mean AT volume on coated devices was lower than uncoated (0.014 vs 0.018 mm3); however, this was not significant (P=0.3). The mean number of foci of magnetic susceptibility artifacts (MSAs) on SWI was significantly different between the uncoated and coated groups at the 1-week follow-up (P<0.02), and remained statistically different throughout the duration of the study. The AT volume showed a direct linear correlation with the MSA count and 80% of the variance in the MSA could be explained by the AT volume (P<0.001). Pathological analysis showed evidence of ischemic injury at locations of MSA. CONCLUSIONS: Heparin-coated flow diverters significantly reduced the number of new MSAs after 1 week follow-up, showing the potential to reduce TEC.

Development of an in-vitro model based on patient vessel geometry for simulated use testing in neurointerventional surgery.

BACKGROUND: Neurointerventionalists use in-vitro vascular models to train for worst-case scenarios and test new devices in a simulated use environment to predict clinical performance. According to the Food and Drug Administration (FDA), any neurovascular navigation device should be able to successfully navigate two 360-degree turns and two 180-degree turns at the distal portion of the anatomical model. Here, we present a device benchmarking vascular model that complies with FDA recommendations. METHODS: Our vascular model was assembled from quantitative characterization of 49 patients who underwent CT angiography either for acute ischemic stroke caused by large vessel occlusion or for aneurysm treatment. Following complete characterization of these data, the vascular segments were 3D reconstructed from CT angiograms of 6 selected patients that presented with challenging anatomy. The curvature and total rotational angle were calculated for each segment and the anatomical parts that complied with FDA recommendations were fused together into a single in-vitro model. RESULTS: The model was constructed containing two common carotid branches arising from a type two aortic arch and the dimensions of the overall model exceeded the recommendations of the FDA. Two experienced neurointerventionalists tested the model for navigation difficulty using several devices on an in-vitro perfusion system and concluded that the model provided a realistic, challenging scenario. CONCLUSIONS: This model provides a first prototype designed according to FDA recommendations of cumulative angle while also integrating an aggregation of actual patient-specific anatomy. The availability of this clinically relevant benchmark model presents a potential standardized approach for neurovascular device testing.

Development of a clot-adhesive coating to improve the performance of thrombectomy devices.

BACKGROUND: The first-pass complete recanalization by mechanical thrombectomy (MT) for the treatment of stroke remains limited due to the poor integration of the clot within current devices. Aspiration can help retrieval of the main clot but fails to prevent secondary embolism in the distal arterial territory. The dense meshes of extracellular DNA, recently described in stroke-related clots, might serve as an anchoring platform for MT devices. We aimed to evaluate the potential of a DNA-reacting surface to aid the retention of both the main clot and small fragments within the thrombectomy device to improve the potential of MT procedures. METHODS: Device-suitable alloy samples were coated with 15 different compounds and put in contact with extracellular DNA or with human peripheral whole blood, to compare their binding to DNA versus blood elements in vitro. Clinical-grade MT devices were coated with two selected compounds and evaluated in functional bench tests to study clot retrieval efficacy and quantify distal emboli using an M1 occlusion model. RESULTS: Binding properties of samples coated with all compounds were increased for DNA (≈3-fold) and decreased (≈5-fold) for blood elements, as compared with the bare alloy samples in vitro. Functional testing showed that surface modification with DNA-binding compounds improved clot retrieval and significantly reduced distal emboli during experimental MT of large vessel occlusion in a three-dimensional model. CONCLUSION: Our results suggest that clot retrieval devices coated with DNA-binding compounds can considerably improve the outcome of the MT procedures in stroke patients.

A micro-channel array in a tissue engineered vessel graft guides vascular morphogenesis for anastomosis with self-assembled vascular networks.

Vascularization of 3D engineered tissues poses a great challenge in the field of tissue engineering. One promising approach for vascularizing engineered tissue is cocultivation with endothelial cells (ECs), which spontaneously self-assemble into a natural capillary network in the presence of supportive cells. However, the ECs do not self-assemble according to physiological hierarchy which is required to support blood supply. This work describes the design and fabrication of an AngioTube, a biodegradable engineered macro-vessel surrounded by cylindrical micro-channel array, which is designed to support physiological flow distribution and enable the integration with living capillaries. The well-defined geometry of the engineered micro-channels guides endothelial cells to form patent micro-vessels which sprouted in accordance with the channel orientation. Three different in-vitro models were used to demonstrate anastomosis of these engineered micro-vessels with self-assembled vascular networks. Finally, in-vivo functionality was demonstrated by direct anastomosis with the femoral artery in a rat hindlimb model. This unique approach proposes a new micro-fabrication strategy which introduces uncompromised micro-fluidic device geometrical accuracy at the tissue-scale level. STATEMENT OF SIGNIFICANCE: This study proposes a micro-fabrication strategy suitable for processing real-scale cylindrical implants with very high accuracy, which will enable translation of the high-resolution geometry of micro-fluidic devices to clinically relevant implants containing functional multi-scale vascular networks. Moreover, this approach promises to advance the field of tissue engineering by opening new opportunities to explore the impact of well controlled and uncompromised 3D micro-geometry on cellular behavior.

Transvascular in vivo microscopy of the subarachnoid space.

BACKGROUND: The micro-architectonics of the subarachnoid space (SAS) remain partially understood and largely ignored, likely the result of the inability to image these structures in vivo. We explored transvascular imaging with high-frequency optical coherence tomography (HF-OCT) to interrogate the SAS. METHODS: In vivo HF-OCT was performed in 10 dogs in both the posterior and anterior cerebral circulations. The conduit vessels used were the basilar, anterior spinal, and middle and anterior cerebral arteries through which the perivascular SAS was imaged. The HF-OCT imaging probe was introduced via a microcatheter and images were acquired using a contrast injection (3.5 mL/s) for blood clearance. Segmentation and three-dimensional rendering of HF-OCT images were performed to study the different configurations and porosity of the subarachnoid trabeculae (SAT) as a function of location. RESULTS: Of 13 acquisitions, three were excluded due to suboptimal image quality. Analysis of 15 locations from seven animals was performed showing six distinct configurations of arachnoid structures in the posterior circulation and middle cerebral artery, ranging from minimal presence of SAT to dense networks and membranes. Different locations showed predilection for specific arachnoid morphologies. At the basilar bifurcation, a thick, fenestrated membrane had a unique morphology. SAT average thickness was 100 µm and did not vary significantly based on location. Similarly, the porosity of the SAT averaged 91% and showed low variability. CONCLUSION: We have demonstrated the feasibility to image the structures of the SAS with transvascular HF-OCT. Future studies are planned to further map the SAT to increase our understanding of their function and possible impact on neurovascular pathologies.

Biophysical targeting of high-risk cerebral aneurysms.

Localized delivery of diagnostic/therapeutic agents to cerebral aneurysms, lesions in brain arteries, may offer a new treatment paradigm. Since aneurysm rupture leading to subarachnoid hemorrhage is a devastating medical emergency with high mortality, the ability to noninvasively diagnose high-risk aneurysms is of paramount importance. Moreover, treatment of unruptured aneurysms with invasive surgery or minimally invasive neurointerventional surgery poses relatively high risk and there is presently no medical treatment of aneurysms. Here, leveraging the endogenous biophysical properties of brain aneurysms, we develop particulate carriers designed to localize in aneurysm low-shear flows as well as to adhere to a diseased vessel wall, a known characteristic of high-risk aneurysms. We first show, in an in vitro model, flow guided targeting to aneurysms using micron-sized (2 µm) particles, that exhibited enhanced targeting (>7 folds) to the aneurysm cavity while smaller nanoparticles (200 nm) showed no preferable accumulation. We then functionalize the microparticles with glycoprotein VI (GPVI), the main platelet receptor for collagen under low-medium shear, and study their targeting in an in vitro reconstructed patient-specific aneurysm that contained a disrupted endothelium at the cavity. Results in this model showed that GPVI microparticles localize at the injured aneurysm an order of magnitude (>9 folds) more than control particles. Finally, effective targeting to aneurysm sites was also demonstrated in an in vivo rabbit aneurysm model with a disrupted endothelium. Altogether, the presented biophysical strategy for targeted delivery may offer new treatment opportunities for cerebral aneurysms.

Preclinical modeling of mechanical thrombectomy.

Mechanical thrombectomy to treat large vessel occlusions (LVO) causing a stroke is one of the most effective treatments in medicine, with a number needed to treat to improve clinical outcomes as low as 2.6. As the name implies, it is a mechanical solution to a blocked artery and modeling these mechanics preclinically for device design, regulatory clearance and high-fidelity physician training made clinical applications possible. In vitro simulation of LVO is extensively used to characterize device performance in representative vascular anatomies with physiologically accurate hemodynamics. Embolus analogues, validated against clots extracted from patients, provide a realistic simulated use experience. In vitro experimentation produces quantitative results such as particle analysis of distal emboli generated during the procedure, as well as pressure and flow throughout the experiment. Animal modeling, used mostly for regulatory review, allows estimation of device safety. Other than one recent development, nearly all animal modeling does not incorporate the desired target organ, the brain, but rather is performed in the extracranial circulation. Computational modeling of the procedure remains at the earliest stages but represents an enormous opportunity to rapidly characterize and iterate new thrombectomy concepts as well as optimize procedure workflow. No preclinical model is a perfect surrogate; however, models available can answer important questions during device development and have to date been successful in delivering efficacious and safe devices producing excellent clinical outcomes. This review reflects on the developments of preclinical modeling of mechanical thrombectomy with particular focus on clinical translation, as well as articulate existing gaps requiring additional research.

3D Bioprinting of Engineered Tissue Flaps with Hierarchical Vessel Networks (VesselNet) for Direct Host-To-Implant Perfusion.

Engineering hierarchical vasculatures is critical for creating implantable functional thick tissues. Current approaches focus on fabricating mesoscale vessels for implantation or hierarchical microvascular in vitro models, but a combined approach is yet to be achieved to create engineered tissue flaps. Here, millimetric vessel-like scaffolds and 3D bioprinted vascularized tissues interconnect, creating fully engineered hierarchical vascular constructs for implantation. Endothelial and support cells spontaneously form microvascular networks in bioprinted tissues using a human collagen bioink. Sacrificial molds are used to create polymeric vessel-like scaffolds and endothelial cells seeded in their lumen form native-like endothelia. Assembling endothelialized scaffolds within vascularizing hydrogels incites the bioprinted vasculature and endothelium to cooperatively create vessels, enabling tissue perfusion through the scaffold lumen. Using a cuffing microsurgery approach, the engineered tissue is directly anastomosed with a rat femoral artery, promoting a rich host vasculature within the implanted tissue. After two weeks in vivo, contrast microcomputer tomography imaging and lectin perfusion of explanted engineered tissues verify the host ingrowth vasculature's functionality. Furthermore, the hierarchical vessel network (VesselNet) supports in vitro functionality of cardiomyocytes. Finally, the proposed approach is expanded to mimic complex structures with native-like millimetric vessels. This work presents a novel strategy aiming to create fully-engineered patient-specific thick tissue flaps.

Transforming a well into a chip: A modular 3D-printed microfluidic chip.

Organ-on-a-Chip platforms provide rich opportunities to observe interactions between different cell types under in vivo-like conditions, i.e., in the presence of flow. Yet, the costs and know-how required for the fabrication and implementation of these platforms restrict their accessibility. This study introduces and demonstrates a novel Insert-Chip: a microfluidic device that provides the functionality of an Organ-on-a-Chip platform, namely, the capacity to co-culture cells, expose them to flow, and observe their interactions-yet can easily be integrated into standard culture systems (e.g., well plates or multi-electrode arrays). The device is produced using stereolithograpy 3D printing and is user-friendly and reusable. Moreover, its design features overcome some of the measurement and imaging challenges characterizing standard Organ-on-a-Chip platforms. We have co-cultured endothelial and epithelial cells under flow conditions to demonstrate the functionality of the device. Overall, this novel microfluidic device is a promising platform for the investigation of biological functions, cell-cell interactions, and response to therapeutics.

In Vitro 3D Cell-Cultured Arterial Models for Studying Vascular Drug Targeting Under Flow.

The use of three-dimensional (3D) models of human arteries, which are designed with the correct dimensions and anatomy, enables the proper modeling of various important processes in the cardiovascular system. Recently, although several biological studies have been performed using such 3D models of human arteries, they have not been applied to study vascular targeting. This paper presents a new method to fabricate real-sized, reconstructed human arterial models using a 3D printing technique, line them with human endothelial cells (ECs), and study particle targeting under physiological flow. These models have the advantage of replicating the physiological size and conditions of blood vessels in the human body using low-cost components. This technique may serve as a new platform for studying and understanding drug targeting in the cardiovascular system and may improve the design of new injectable nanomedicines. Moreover, the presented approach may provide significant tools for the study of targeted delivery of different agents for cardiovascular diseases under patient-specific flow and physiological conditions.

A converging artery-sized model for shear adhesion mapping of particles.

Drug carriers for targeting cardiovascular diseases have been gaining a respectable attention, however, designing such carriers is challenging due to the biophysical complexity of the vascular system. Wall shear stress (WSS), exerted by blood flow on the endothelium surface, is a crucial factor in the circulatory system. WSS affects the adhesion and preferential accumulation of drug carriers. Here, we propose, an innovative approach to investigate particle adhesion in a converging artery-sized model, lined with human endothelial cells. Unlike widely used microfluidic and in vivo setups, our model enables to investigate particle accumulation in a continuous WSS range, performed in a single experiment, and at the right scale relevant for human arteries. First, we characterized the flow and the WSS map along the designed model, which can span along the entire arterial WSS range. We then used the model to examine the effect of particle size and the suspension buffer on particle adhesion distribution. The results demonstrated the role of particle size, where the same particles with a diameter of 2 µm exhibit shear-decreased adhesion while 500 nm particles exhibit shear-enhanced adhesion. Furthermore, under the same WSS, particles show a similar behavior when suspended in a Dextran buffer, having a viscosity analogous to blood, compared to a phosphate buffer solution without Dextran. Moreover, experiments with RBCs in the phosphate buffer, at a 40% physiological hematocrit, decreased particle adhesion and affected their deposition pattern. Altogether, our study suggests an original platform for investigating and optimizing intravascular drug carriers and their targeting properties.

Computational and experimental investigation of particulate matter deposition in cerebral side aneurysms.

Intracranial aneurysms frequently develop blood clots, plaque and inflammations, which are linked to enhanced particulate mass deposition. In this work, we propose a computational model for particulate deposition, that accounts for the influence of field forces, such as gravity and electrostatics, which produce an additional flux of particles perpendicular to the fluid motion and towards the wall. This field-mediated flux can significantly enhance particle deposition in low-shear environments, such as in aneurysm cavities. Experimental investigation of particle deposition patterns in in vitro models of side aneurysms, demonstrated the ability of the model to predict enhanced particle adhesion at these sites. Our results showed a significant influence of gravity and electrostatic forces (greater than 10%), indicating that the additional terms presented in our models may be necessary for modelling a wide range of physiological flow conditions and not only for ultra-low shear regions. Spatial differences between the computational model and the experimental results suggested that additional transport and fluidic mechanisms affect the deposition pattern within aneurysms. Taken together, the presented findings may enhance our understanding of pathological deposition processes at cardiovascular disease sites, and facilitate rational design and optimization of cardiovascular particulate drug carriers.

Glycoprotein VI (GPVI)-functionalized nanoparticles targeting arterial injury sites under physiological flow.

Thrombus formation at athero-thrombotic sites is initiated by the exposure of collagen followed by platelet adhesion mediated by the platelet-specific collagen receptor glycoprotein VI (GPVI). Here, dimeric GPVI was used as a targeting motif to functionalize polymeric nanoparticle-based drug carriers and to show that with proper design, such GPVI-coated nanoparticles (GPNs) can efficiently and specifically target arterial injury sites while withstanding physiological flow. In a microfluidic model, under physiological shear levels (1-40 dyne/cm2), 200 nm and 2 µm GPNs exhibited a >60 and >10-fold increase in binding to collagen compared to control particles, respectively. In vitro experiments in an arterial stenosis injury model, subjected to physiological pulsatile flow, showed shear-enhanced adhesion of 200 nm GPNs at the stenosis region which was confirmed in vivo in a mice ligation carotid injury model using intravital microscopy. Altogether, our results illustrate how engineering tools can be harnessed to design nano-carriers that efficiently target cardiovascular disease sites.

Mapping deposition of particles in reconstructed models of human arteries.

Targeted drug delivery to diseased vasculature, such as atherosclerotic lesions, is a multistep process, which is based on the transport of drug carriers to a selected region and their deposition at the desired destination. Current modeling approaches, including microfluidics and animal models, fail to accurately simulate this multi-scale process in human arteries, where blood flow is dominant. Here we study particle deposition in endothelialized 3D reconstructed models of the human carotid bifurcation under physiological hemodyamic conditions. Our results showed that particle localization is highly dependent on vessel geometry and local flow features. Additionally, while strongly adhesive particles tend to adhere more profoundly at high-shear regions, associated with athero-thrombosis, enhanced deposition at vascular flow regions, associated with inflammation and plaque accumulation, e.g., recirculation flows, can be achieved using weakly adhesive particles. Moreover, pulsatile flow as well as presence of blood cells significantly reduce particle adhesion and affect their deposition pattern. These findings highlight the key role of vessel geometry, hemodynamics and particle characteristics in the optimizing vascular targeting nano-carriers.

Endothelial Cell Activation in an Embolic Ischemia-Reperfusion Injury Microfluidic Model.

Ischemia, lack of blood supply, is associated with a variety of life-threatening cardiovascular diseases, including acute ischemic stroke and myocardial infraction. While blood flow restoration is critical to prevent further damage, paradoxically, rapid reperfusion can increase tissue damage. A variety of animal models have been developed to investigate ischemia/reperfusion injury (IRI), however they do not fully recapitulate human physiology of IRI. Here, we present a microfluidic IRI model utilizing a vascular compartment comprising human endothelial cells, which can be obstructed via a human blood clot and then re-perfused via thrombolytic treatment. Using our model, a significant increase in the expression of the endothelial cell inflammatory surface receptors E-selectin and I-CAM1 was observed in response to embolic occlusion. Following the demonstration of clot lysis and reperfusion via treatment using a thrombolytic agent, a significant decrease in the number of adherent endothelial cells and an increase in I-CAM1 levels compared to embolic occluded models, where reperfusion was not established, was observed. Altogether, the presented model can be applied to allow better understanding of human embolic based IRI and potentially serve as a platform for the development of improved and new therapeutic approaches.

The Flow Dependent Adhesion of von Willebrand Factor (VWF)-A1 Functionalized Nanoparticles in an in Vitro Coronary Stenosis Model.

In arterial thrombosis, von Willebrand factor (VWF) bridges platelets to sites of vascular injury. The adhesive properties of VWF are controlled by its different domains, which may be engineered into ligands for targeting nanoparticles to vascular injuries. Here, we functionalized 200 nm polystyrene nanoparticles with the VWF-A1 domain and studied their spatial adhesion to collagen or collagen-VWF coated, real-sized coronary stenosis models under physiological flow. When VWF-A1 nano-particles (A1-NPs) were perfused through a 75% stenosis model coated with collagen-VWF, the particles preferentially adhered at the post stenotic region relative to the pre-stenosis region while much less adhesion was detected at the stenosis neck (~ 65-fold less). When infused through collagen-coated models or when the A1 coating density of nanoparticles was reduced by 100-fold, the enhanced adhesion at the post-stenotic site was abolished. In a 60% stenosis model, the adhesion of A1-NPs to collagen-VWF-coated models depended on the location examined within the stenosis. Altogether, our results indicate that VWF-A1 NPs exhibit a flow-structure dependent adhesion to VWF and illustrate the important role of studying cardiovascular nano-medicines in settings that closely model the size, geometry, and hemodynamics of pathological environments.

Multi-flow channel bioreactor enables real-time monitoring of cellular dynamics in 3D engineered tissue.

The key to understanding, harnessing, and manipulating natural biological processes for the benefit of tissue engineering lies in providing a controllable dynamic environment for tissue development in vitro while being able to track cell activity in real time. This work presents a multi-channel bioreactor specifically designed to enable on-line imaging of fluorescently labeled cells embedded in replicated 3D engineered constructs subjected to different flow conditions. The images are acquired in 3D using a standard upright confocal microscope and further analyzed and quantified by computer vision. The platform is used to characterize and quantify the pace and directionality of angiogenic processes induced by flow. The presented apparatus bears considerable potential to advance scientific research, from basic research pursuing the effect of flow versus static conditions on 3D scaffolds and cell types, to clinically oriented modeling in drug screening and cytotoxicity assays.

Mapping the Transport Kinetics of Molecules and Particles in Idealized Intracranial Side Aneurysms.

Intracranial side aneurysms (IA) are pathological blood-filled bulges in cerebral blood vessels. Unlike healthy blood vessels where mass transport is dominated by convection, both diffusion and convection can play an active role in aneurysm sites. Here, we study via dye washout experiments and numerical simulations, the transport characteristics of particles (1 micron) and small molecules (300 Da) into simplified side aneurysms models following bolus injection. Time-lapse fluorescent microscopy imaging performed in our idealized aneurysm models showed that the parent artery geometry (located on the inner vs. outer curvature) as well as the aneurysm aspect ratio (AR) affect the washout kinetics while the pulsatile nature of the flow, maintained within the physiological range, carries only a minor effect. Importantly, in the absence of effective diffusion, particles that are located on slow streamlines linger within the aneurysm cavity, a phenomenon that could be of importance in deposition of cells and nano/micro-particles within aneurysms. Altogether, mass transport studies may provide valuable insights for better understanding of aneurysm pathophysiology as well as for the design of new diagnostic and theranostic nano-medicines.