In vitro patient-specific model of cerebral artery for evaluating procedures of endovascular intervention

We propose an in vitro patient-specific anatomical model of the human cerebral artery and its simulation of endovascular intervention, a potent treatment modality for cerebrovascular diseases. Our proposed model reproduces the 3-dimensional vasculature lumen, using computed tomography (CT) and magnetic resonance (MR) fluoroscopic information, within a thin artery-like membranous configuration having material properties close to arterial tissue. This cerebral arterial model reproduces an exceedingly realistic surgical feel, dynamic vascular deformation and, other important aspects involving endovascular intervention, realizing a highly realistic surgical simulation. We also propose another vasculature model that reproduces the subarachnoid space around the cerebral arteries. This version simulates endovascular intervention realistically. The model is compatible with current major imaging modalities such as CT, MR, and transcranial Doppler (TDC), and should provide effective platforms for applications, such as diagnosis, surgical planning, medical training, hemodynamic analysis and medical system development and evaluation, especially surgical robots.

Download Full-text

Expanding clinical phage microbiology: simulating phage inhalation for respiratory tract infections

ERJ Open Research ◽

10.1183/23120541.00367-2021 ◽

2021 ◽

pp. 00367-2021

Author(s):

Shira Ben Porat ◽

Daniel Gelman ◽

Ortal Yerushalmy ◽

Sivan Alkalay-Oren ◽

Shunit Coppenhagen-Glazer ◽

...

Keyword(s):

Respiratory Tract ◽

Respiratory Tract Infections ◽

Phage Therapy ◽

Specific Model ◽

Patient Specific ◽

Diverse Range ◽

Jet Nebulizer ◽

Tract Infections ◽

Therapy Success

Phage therapy is a promising antibacterial strategy for resistant respiratory tract infections. Phage inhalation may serve this goal; however, it requires a careful assessment of their delivery by this approach. Here we present an in-vitro model to evaluate phage inhalation. Eight phages, most of which target cystic fibrosis (CF)-common pathogens, were aerosolized by jet nebulizer and administered to a real-scale computed tomography (CT)-derived 3D airways model with a breathing simulator. Viable phage loads reaching the output of the nebulizer and the tracheal level of the model were determined and compared to the loaded amount. Phage inhalation resulted in a diverse range of titer reduction, primarily associated with the nebulization process. No correlation was found between phage delivery to the phage physical or genomic dimensions. These findings highlight the need for tailored simulations of phage delivery, ideally by a patient-specific model in addition to proper phage matching, to increase the potential of phage therapy success.

Download Full-text

Structural and Ultrastructural Analysis of the Multiple Myeloma Cell Niche and a Patient-Specific Model of Plasma Cell Dysfunction

Microscopy and Microanalysis ◽

10.1017/s1431927621013805 ◽

2021 ◽

pp. 1-11

Author(s):

Katrina A. Harmon ◽

Sara Roman ◽

Harrison D. Lancaster ◽

Saeeda Chowhury ◽

Elizabeth Cull ◽

...

Keyword(s):

Multiple Myeloma ◽

Cancer Progression ◽

Plasma Cells ◽

Myeloma Cell ◽

Specific Model ◽

Patient Specific ◽

Multiple Myeloma Cell ◽

Cell Niche

Multiple myeloma (MM) is a deadly, incurable malignancy in which antibody-secreting plasma cells (PCs) become neoplastic. Previous studies have shown that the PC niche plays a role cancer progression. Bone marrow (BM) cores from MM and a premalignant condition known as monoclonal gammopathy of unknown significance (MGUS) patients were analyzed with confocal and transmission electron microscopy. The BM aspirates from these patients were used to generate 3D PC cultures. These in vitro cultures were then assayed for the molecular, cellular, and ultrastructural hallmarks of dysfunctional PC at days 1 and 5. In vivo, evidence of PC endoplasmic reticulum stress was found in both MM and MGUS BM; however, evidence of PC autophagy was found only in MM BM. Analysis of in vitro cultures found that MM PC can survive and maintain a differentiated phenotype over an unprecedented 5 days, had higher levels of paraprotein production when compared to MGUS-derived cultures, and showed evidence of PC autophagy as well. Increased fibronectin deposition around PC associated with disease severity and autophagy dysregulation was also observed. 3D cultures constructed from BM aspirates from MGUS and MM patients allow for long-term culture of functional PC while maintaining their distinct morphological phenotypes.

Download Full-text

Expanding Clinical Phage Microbiology:‎ Simulating Phage Inhalation for Respiratory Tract Infections ‎

10.1101/2021.06.14.448272 ◽

2021 ◽

Author(s):

Shira Ben-Porat ◽

Daniel Gelman ◽

Ortal Yerushalmy ◽

Sivan Alkalay-Oren ◽

Shunit Coppenhagen-Glazer ◽

...

Keyword(s):

Respiratory Tract ◽

Respiratory Tract Infections ◽

Phage Therapy ◽

Specific Model ◽

Patient Specific ◽

Diverse Range ◽

Vitro Model ◽

Tract Infections ◽

Therapy Success

Phage therapy is a promising antibacterial strategy for resistant respiratory tract infections. Phage inhalation may serve this goal; however, it requires a careful assessment of their delivery by this approach. Here we present an in-vitro model to evaluate phage inhalation. Eight phages, most of which target CF-common pathogens, were aerosolized and administered to a real-scale CT derived 3D airways model with a breathing simulator. Viable phage loads reaching the output of the nebulizer and the tracheal level of the model were determined and compared to the loaded amount. Phage inhalation resulted in a diverse range of titer reduction, primarily associated with the nebulization process. No correlation was found between phage delivery to the phage physical or genomic dimensions. These findings highlight the need for tailored simulations of phage delivery, ideally by a patient-specific model in addition to proper phage matching, to increase the potential of phage therapy success.

Download Full-text

Role of distal cerebral vasculature in vessel constriction after aneurysm treatment with flow diverter stents

Journal of NeuroInterventional Surgery ◽

10.1136/neurintsurg-2019-015447 ◽

2020 ◽

Vol 12 (8) ◽

pp. 818-826

Author(s):

Ana Paula Narata ◽

Fernando Moura ◽

Ignacio Larrabide ◽

René Chapot ◽

Christophe Cognard ◽

...

Keyword(s):

Clinical Outcome ◽

Vascular Resistance ◽

Intracranial Aneurysms ◽

Demographic Data ◽

Power Doppler ◽

Flow Diverter ◽

Specific Model ◽

Patient Specific ◽

Flow Diverter Stent

BackgroundTreatment of intracranial aneurysms with flow diverter stent (FDS) procedures can lead to caliber changes of jailed vessels. The reason some branches remain unchanged and others are affected by narrowing remains unknown.ObjectiveTo investigate the influence of resistance to flow from distal vasculature on stent-induced hemodynamic modifications affecting bifurcating vessels.Materials and methodsRadiological images and demographic data were acquired for 142 aneurysms treated with a FDS. Vascular resistance was estimated from patient-specific anatomic data. Correlation analysis was used to identify correspondence between anatomic data and clinical outcome. Computational Fluid Dynamics was performed on a typical patient-specific model to evaluate the influence of FDS on flow. Relevant hemodynamic variables along the bifurcating vessels were quantitatively analyzed and validated with in vitro data obtained using power Doppler ultrasound.ResultsStatistical analysis showed a correlation between clinical outcome and FDS resistance to flow considering overall jailed vessel vascular resistance (r=0.5, P<0.001). Computational predictions of blood flow showed that hemodynamics is minimally affected by FDS treatment in the ophthalmic artery.ConclusionsJailed vessels are affected by narrowing when resistance to flow from the FDS constitutes a larger proportion of the overall vessel resistance to flow. This knowledge may contribute to better understanding of intracranial hemodynamics after a FDS procedure and reinforce indications for flow diversion in the treatment of intracranial aneurysms.

Download Full-text

Numerical Models Can Assist Choice of an Aortic Phantom for In Vitro Testing

Bioengineering ◽

10.3390/bioengineering8080101 ◽

2021 ◽

Vol 8 (8) ◽

pp. 101

Author(s):

Giulia Comunale ◽

Luigi Di Micco ◽

Daniela Paola Boso ◽

Francesca Maria Susin ◽

Paolo Peruzzo

Keyword(s):

Biological Tissue ◽

Mechanical Response ◽

Numerical Models ◽

Specific Model ◽

Patient Specific ◽

Minor Role ◽

Local Geometry ◽

The Real

(1) Background: The realization of appropriate aortic replicas for in vitro experiments requires a suitable choice of both the material and geometry. The matching between the grade of details of the geometry and the mechanical response of the materials is an open issue that deserves attention. (2) Methods: To explore this issue, we performed a series of Fluid–Structure Interaction simulations, which compared the dynamics of three aortic models. Specifically, we reproduced a patient-specific geometry with a wall of biological tissue or silicone, and a parametric geometry based on in vivo data made in silicone. The biological tissue and the silicone were modeled with a fiber-oriented anisotropic and isotropic hyperelastic model, respectively. (3) Results: Clearly, both the aorta’s geometry and its constitutive material contribute to the determination of the aortic arch deformation; specifically, the parametric aorta exhibits a strain field similar to the patient-specific model with biological tissue. On the contrary, the local geometry affects the flow velocity distribution quite a lot, although it plays a minor role in the helicity along the arch. (4) Conclusions: The use of a patient-specific prototype in silicone does not a priori ensure a satisfactory reproducibility of the real aorta dynamics. Furthermore, the present simulations suggest that the realization of a simplified replica with the same compliance of the real aorta is able to mimic the overall behavior of the vessel.

Download Full-text

iPSC-Cardiomyocyte Models of Brugada Syndrome—Achievements, Challenges and Future Perspectives

International Journal of Molecular Sciences ◽

10.3390/ijms22062825 ◽

2021 ◽

Vol 22 (6) ◽

pp. 2825

Author(s):

Aleksandra Nijak ◽

Johan Saenen ◽

Alain J. Labro ◽

Dorien Schepers ◽

Bart L. Loeys ◽

...

Keyword(s):

Cardiac Arrhythmia ◽

Brugada Syndrome ◽

Induced Pluripotent Stem Cell ◽

Specific Model ◽

Patient Specific ◽

Future Perspectives ◽

Human Patient ◽

Human Cardiomyocytes ◽

Heterologous Expression Systems

Brugada syndrome (BrS) is an inherited cardiac arrhythmia that predisposes to ventricular fibrillation and sudden cardiac death. It originates from oligogenic alterations that affect cardiac ion channels or their accessory proteins. The main hurdle for the study of the functional effects of those variants is the need for a specific model that mimics the complex environment of human cardiomyocytes. Traditionally, animal models or transient heterologous expression systems are applied for electrophysiological investigations, each of these models having their limitations. The ability to create induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs), providing a source of human patient-specific cells, offers new opportunities in the field of cardiac disease modelling. Contemporary iPSC-CMs constitute the best possible in vitro model to study complex cardiac arrhythmia syndromes such as BrS. To date, thirteen reports on iPSC-CM models for BrS have been published and with this review we provide an overview of the current findings, with a focus on the electrophysiological parameters. We also discuss the methods that are used for cell derivation and data acquisition. In the end, we critically evaluate the knowledge gained by the use of these iPSC-CM models and discuss challenges and future perspectives for iPSC-CMs in the study of BrS and other arrhythmias.

Download Full-text

Patient-Specific IVR Endovascular Simulator with Augmented Reality for Medical Training and Robot Evaluation

Journal of Robotics and Mechatronics ◽

10.20965/jrm.2008.p0441 ◽

2008 ◽

Vol 20 (3) ◽

pp. 441-448 ◽

Cited By ~ 13

Author(s):

Seiichi Ikeda ◽

◽

Carlos Tercero Villagran ◽

Toshio Fukuda ◽

Yuta Okada ◽

...

Keyword(s):

Augmented Reality ◽

Blood Vessel ◽

Medical Training ◽

Refraction Index ◽

Endovascular Intervention ◽

Patient Specific ◽

Image Subtraction ◽

Vascular Model ◽

Behavior Simulation

Endovascular intervention using interventional radiology (IVR) is most commonly used in cerebralvascular treatment. Medical imaging such as digital subtraction angiography (DSA) and vascular mapping make vasculature and catheters easier to read from fluoroscopy during endovascular intervention. We propose simulating IVR using augmented reality, reproducing fluoroscopic images and a patient-specific blood vessel model without X-ray imaging. The advantages of the patient-specific vascular model reproducing the human vasculature lumen with 13 μm resolution include 1) a realistic “feel,” 2) excellent tool behavior simulation during intervention, and 3) surgical training alternative to physician training in-vitro. Simulated fluoroscopic images are created in two steps: First, the blood vessel model refraction index is matched to surrounding glycerin solution to conceal the vascular model, making the silicone vasculature appear human as seen in endovascular intervention. Second, an augmented reality (AR) environment is created using image subtraction and overlap, making model-based endovascular simulation more understandable for catheter use and fluoroscopy use and reading.

Download Full-text

CFD and MRI studies of hemodynamic changes after flow diverter implantation in a patient-specific model of the cerebral artery

Experiments in Fluids ◽

10.1007/s00348-018-2635-8 ◽

2018 ◽

Vol 59 (11) ◽

Cited By ~ 1

Author(s):

S. V. Frolov ◽

S. V. Sindeev ◽

J. S. Kirschke ◽

P. Arnold ◽

S. Prothmann ◽

...

Keyword(s):

Cerebral Artery ◽

Flow Diverter ◽

Specific Model ◽

Patient Specific ◽

Hemodynamic Changes ◽

Mri Studies

Download Full-text

Abstract TP57: Tenzing™ 7 Delivery Catheter: A Novel Delivery Assist Catheter Significantly Facilitates Catheter Delivery in an Anatomically Challenging Stroke Model

Stroke ◽

10.1161/str.51.suppl_1.tp57 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Andreas M Frölich ◽

Joey English ◽

Olav Jansen ◽

Markus Möhlenbruch ◽

István Szikora ◽

...

Keyword(s):

Carotid Artery ◽

Middle Cerebral Artery ◽

Cerebral Artery ◽

Ophthalmic Artery ◽

Carotid Bifurcation ◽

Patient Specific ◽

Target Vessel ◽

Vessel Occlusion ◽

Guide Catheter

Background: In large vessel occlusion stroke, intracranial navigation of large-bore aspiration catheters can be impeded by vessel curvature and ophthalmic artery origin. Novel conically-shaped delivery assist devices are designed to facilitate delivery. We assessed aspiration catheter deliverability in several patient-specific in vitro models. Methods: In a flow model replicating vascular access from the femoral to the middle cerebral artery, two different commercially available aspiration catheters were repeatedly advanced through a commercial 0.088” sheath from the carotid bifurcation to the middle cerebral artery by five neurointerventionalists under fluoroscopy. Three craniocervical access scenarios were manufactured based on challenging patient anatomy. Catheter deliverability was assessed with standard microwire/microcatheter combinations (MC) and the Tenzing™ 7 catheter (T7). Procedural characteristics were recorded, and operators rated carotid artery deflection, guide catheter pushback and difficulty passing the ophthalmic artery origin on a 5-point scale (1=none, 5=most severe). Results: Among 117 delivery attempts, the target vessel was reached significantly more often with T7 (96%) than with MC (66%, p<0.001). Successful delivery was faster with T7 (33s, 95%CI:30-35s) than with MC (69s, 95%CI:55-83s, p<0.001) and there was less need to cross the occlusion site with T7 (12%) than with MC (53%, p<0.001). Operators assigned superior ratings to T7 than to MC regarding carotid artery deflection (2, IQR1-3 vs. 3, IQR2-4, p=0.014), guide catheter pushback (2, IQR1-3,5 vs. 3, IQR3-4, p=0.005) and ophthalmic artery origin passage (2, IQR1-2 vs. 4, IQR3-5, p<0.001). Conclusion: Compared to microcatheter & microwire combinations, the T7 delivery assist catheter significantly facilitates aspiration catheter delivery to the target vessel in vitro.

Download Full-text