A bypass flow model to study endothelial cell mechanotransduction across diverse flow environments.

Disturbed flow is one of the pathological initiators of endothelial dysfunction in intimal hyperplasia (IH) which is commonly seen in vascular bypass grafts, and arteriovenous fistulas. Various in vitro disease models have been designed to simulate the hemodynamic conditions found in the vasculature. Nonetheless, prior investigations have encountered challenges in establishing a robust disturbed flow model, primarily attributed to the complex bifurcated geometries and distinctive flow dynamics. In the present study, we aim to address this gap by introducing an in vitro bypass flow model capable of inducing disturbed flow and other hemodynamics patterns through a pulsatile flow in the same model. To assess the model's validity, we employed computational fluid dynamics (CFD) to simulate hemodynamics and compared the morphology and functions of human umbilical venous endothelial cells (HUVECs) under disturbed flow conditions to those in physiological flow or stagnant conditions. CFD analysis revealed the generation of disturbed flow within the model, pinpointing the specific location in the channel where the effects of disturbed flow were observed. High-content screening, a single-cell morphological profile assessment, demonstrated that HUVECs in the disturbed flow area exhibited random orientation, and morphological features were significantly distinct compared to cells in the physiological flow or stagnant condition after a two days of flow exposure. Furthermore, HUVECs exposed to disturbed flow underwent extensive remodeling of the adherens junctions and expressed higher levels of endothelial cell activation markers compared to other hemodynamic conditions. In conclusion, our in vitro bypass flow model provides a robust platform for investigating the associations between disturbed flow pattern and vascular diseases.

An Implantable Magnetic Drive Mechanism for Non-Invasive Arteriovenous Conduit Blood Flow Control.

OBJECTIVE: Hemodialysis patients usually receive an arteriovenous fistula (AVF) in the arm as vascular access conduit to allow dialysis 2-3 times a week. This AVF introduces the high flow necessary for dialysis, but over time the ever-present supraphysiological flow is the leading cause of complications. This study aims to develop an implantable device able to non-invasively remove the high flow outside dialysis sessions. METHODS: The developed prototype features a magnetic ring allowing external coupling and torque transmission to non-invasively control an AVF valve. Mock-up devices were implanted into arm and sheep cadavers to test sizes and locations. The transmission torque, output force, and valve closure are measured for different representative skin thicknesses. RESULTS: The prototype was placed successfully into arm and sheep cadavers. In the prototype, a maximum output force of 78.9 ± 4.2 N, 46.7 ± 1.9 N, 25.6 ± 0.7 N, 13.5 ± 0.6 N and 6.3 ± 0.4 N could be achieved non-invasively through skin thicknesses of 1-5 mm respectively. The fistula was fully collapsible in every measurement through skin thickness up to the required 4 mm. CONCLUSION: The prototype satisfies the design requirements. It is fully implantable and allows closure and control of an AVF through non-invasive torque transmission. In vivo studies are pivotal in assessing functionality and understanding systemic effects. SIGNIFICANCE: A method is introduced to transfer large amounts of energy to a medical implant for actuation of a mechanical valve trough a closed surface. This system allows non-invasive control of an AVF to reduce complications related to the permanent high flow in conventional AVFs.

Click-on fluorescence detectors: using robotic surgical instruments to characterize molecular tissue aspects.

Fluorescence imaging is increasingly being implemented in surgery. One of the drawbacks of its application is the need to switch back-and-forth between fluorescence- and white-light-imaging settings and not being able to dissect safely under fluorescence guidance. The aim of this study was to engineer 'click-on' fluorescence detectors that transform standard robotic instruments into molecular sensing devices that enable the surgeon to detect near-infrared (NIR) fluorescence in a white-light setting. This NIR-fluorescence detector setup was engineered to be press-fitted onto standard forceps instruments of the da Vinci robot. Following system characterization in a phantom setting (i.e., spectral properties, sensitivity and tissue signal attenuation), the performance with regard to different clinical indocyanine green (ICG) indications (e.g., angiography and lymphatic mapping) was determined via robotic surgery in pigs. To evaluate in-human applicability, the setup was also used for ICG-containing lymph node specimens from robotic prostate cancer surgery. The resulting Click-On device allowed for NIR ICG signal identification down to a concentration of 4.77 × 10-6 mg/ml. The fully assembled system could be introduced through the trocar and grasping, and movement abilities of the instrument were preserved. During surgery, the system allowed for the identification of blood vessels and assessment of vascularization (i.e., bowel, bladder and kidney), as well as localization of pelvic lymph nodes. During human specimen evaluation, it was able to distinguish sentinel from non-sentinel lymph nodes. With this introduction of a NIR-fluorescence Click-On sensing detector, a next step is made towards using surgical instruments in the characterization of molecular tissue aspects.

A realistic 3-D gated cardiac phantom for quality control of gated myocardial perfusion SPET: the Amsterdam gated (AGATE) cardiac phantom.

A realistic 3-D gated cardiac phantom with known left ventricular (LV) volumes and ejection fractions (EFs) was produced to evaluate quantitative measurements obtained from gated myocardial single-photon emission tomography (SPET). The 3-D gated cardiac phantom was designed and constructed to fit into the Data Spectrum anthropomorphic torso phantom. Flexible silicone membranes form the inner and outer walls of the simulated left ventricle. Simulated LV volumes can be varied within the range 45-200 ml. The LV volume curve has a smooth and realistic clinical shape that is produced by a specially shaped cam connected to a piston. A fixed 70-ml stroke volume is applied for EF measurements. An ECG signal is produced at maximum LV filling by a controller unit connected to the pump. This gated cardiac phantom will be referred to as the Amsterdam 3-D gated cardiac phantom, or, in short, the AGATE cardiac phantom. SPET data were acquired with a triple-head SPET system. Data were reconstructed using filtered back-projection following pre-filtering and further processed with the Quantitative Gated SPECT (QGS) software to determine LV volume and EF values. Ungated studies were performed to measure LV volumes ranging from 45 ml to 200 ml. The QGS-determined LV volumes were systematically underestimated. For different LV combinations, the stroke volumes measured were consistent at 60-61 ml for 8-frame studies and 63-65 ml for 16-frame studies. QGS-determined EF values were slightly overestimated between 1.25% EF units for 8-frame studies and 3.25% EF units for 16-frame studies. In conclusion, the AGATE cardiac phantom offers possibilities for quality control, testing and validation of the whole gated cardiac SPET sequence, and testing of different acquisition and processing parameters and software.