Comparing deposition characteristics of various embolic particles using an in vitro prostate microvasculature model.

PURPOSE: To compare spatial distributions of radiopaque glass (RG) microspheres, trisacryl gelatin (TAG) microspheres, and polyvinyl alcohol (PVA) foam particles within a planar in vitro microvascular model of the hyperplastic hemiprostate. MATERIALS AND METHODS: A microvascular model simulating hyperplastic hemiprostate was perfused with a water-glycerin mixture. A microcatheter was positioned distal to the model's prostatic artery origin and embolic particles (RG: 50 µm, 100 µm, and 150 µm; TAG: 100-300 µm and 300-500 µm; and PVA: 90-180 µm and 180-300 µm) were administered using a syringe pump. Microscopic imaging and subsequent semantic segmentation were performed to quantify particle distributions within the models. Distal penetrations were quantified statistically via modal analysis of the particle distributions. RESULTS: Maximum distal penetration was observed for RG 50, followed by RG 100 and then TAG 100-300 and RG 150. TAG 300-500, PVA 90-180, and PVA 180-300 particles exhibited the lowest distal penetrations. The distal penetration metrics between groups were significantly different (p < 0.05) except between TAG 100-300 and RG 150 and between PVA 90-180 and PVA 180-300. CONCLUSIONS: Comparing the spatial distributions of embolic particles in an in vitro microvascular model simulating the hyperplastic hemiprostate revealed that noncompressible particles and those with narrower size calibrations and smaller relative diameters exhibited higher degrees of distal packing. The embolization front was less distinct for particles with wider size calibrations, which resulted in smaller, more distal emboli along with larger, more proximal emboli. PVA and TAG 300-500 particles both exhibited relatively low overall distal penetration.

Comparison of Bolus Versus Dual-Syringe Administration Systems on Glass Yttrium-90 Microsphere Deposition in an In Vitro Microvascular Hepatic Tumor Model.

PURPOSE: To utilize an in vitro microvascular hepatic tumor model to compare the deposition characteristics of glass yttrium-90 microspheres using the dual-syringe (DS) and traditional bolus administration methods. MATERIALS AND METHODS: The microvascular tumor model represented a 3.5-cm tumor in a 1,400-cm3 liver with a total hepatic flow of 160 mL/min and was dynamically perfused. A microcatheter was placed in a 2-mm artery feeding the tumor model and 2 additional nontarget arteries. Glass microspheres with a diameter of 20-30 µm were administered using 2 methods: (a) DS delivery at a concentration of 50 mg/mL in either a single, continuous 2-mL infusion or two 1-mL infusions and (b) bolus delivery (BD) of 100 mg of microspheres in a single 3-mL infusion. RESULTS: Overall, the degree of on-target deposition of the microspheres was 85% ± 11%, with no significant differences between the administration methods. Although the distal penetration into the tumor arterioles was approximately 15 mm (from the second microvascular bifurcation of the tumor model) for all the cases, the distal peak particle counts were significantly higher for the DS delivery case (approximately 5 × 105 microspheres achieving distal deposition vs 2 × 105 for the BD case). This resulted in significantly higher deposition uniformity within the tumor model (90% for the DS delivery case vs 80% for the BD case, α = 0.05). CONCLUSIONS: The use of this new in vitro microvascular hepatic tumor model demonstrated that the administration method can affect the deposition of yttrium-90 microspheres within a tumor, with greater distal deposition and more uniform tumor coverage when the microspheres are delivered at consistent concentrations using a DS delivery device. The BD administration method was associated with less favorable deposition characteristics of the microspheres.

Gastric artery embolization: studying the effects of catheter type and injection method on microsphere distributions within a benchtop arterial model.

AIMS: The objective of the study is to investigate the effect of catheter type and injection method on microsphere distributions, specifically vessel targeting accuracy. MATERIALS AND METHODS: The study utilized three catheter types (a standard end-hole micro-catheter, a Surefire anti-reflux catheter, and an Endobar occlusion balloon catheter) and both manual and computer-controlled injection schemes. A closed-loop, dynamically pressurized surrogate arterial system was assembled to replicate arterial flow for bariatric embolization procedures. Four vessel branches immediately distal to the injection site were targeted for embolization. Embolic microspheres were injected into the model using these  three catheter types and both manual and computer-controlled injections. RESULTS: Across all injection methods, the catheter effect on the proportion of microspheres to target vessels (vs. non-target vessels) was significant (p = 0.005). The catheter effect on the number of non-target vessels embolized was nearly significant (p = 0.059). Across all catheter types, the injection method effect was not statistically significant for either of two outcome measures (percent microspheres to target vessels: p = 0.265, number of non-target vessels embolized: p = 0.148). CONCLUSION: Catheter type had a significant effect on targeting accuracy across all injection methods. The Endobar catheter exhibited a higher targeting accuracy in pairwise comparisons with the other two injection catheters across all injection schemes and when considering the Endobar catheter with the manifold injection method vs. each of the catheters with the manual injection method; the differences were significant in three of four analyses. The injection method effect was not statistically significant across all catheter types and when considering the Endobar catheter/Endobar manifold combination vs. Endobar catheter injections with manual and pressure-replicated methods.

Design and testing of a centrifugal fluidic device for populating microarrays of spheroid cancer cell cultures.

BACKGROUND: In current cancer spheroid culturing methods, the transfer and histological processing of specimens grown in 96-well plates is a time consuming process. A centrifugal fluidic device was developed and tested for rapid extraction of spheroids from a 96-well plate and subsequent deposition into a molded agar receiver block. The deposited spheroids must be compact enough to fit into a standard histology cassette while also maintaining a highly planar arrangement. This size and planarity enable histological processing and sectioning of spheroids in a single section. The device attaches directly to a 96-well plate and uses a standard centrifuge to facilitate spheroid transfer. The agar block is then separated from the device and processed. RESULTS: Testing of the device was conducted using six full 96-well plates of fixed Pa14C pancreatic cancer spheroids. On average, 80% of spheroids were successfully transferred into the agar receiver block. Additionally, the planarity of the deposited spheroids was evaluated using confocal laser scanning microscopy. This revealed that, on average, the optimal section plane bisected individual spheroids within 27% of their mean radius. This shows that spheroids are largely deposited in a planar fashion. For rare cases where spheroids had a normalized distance to the plane greater than 1, the section plane either misses or captures a small cross section of the spheroid volume. CONCLUSIONS: These results indicate that the proposed device is capable of a high capture success rate and high sample planarity, thus demonstrating the capabilities of the device to facilitate rapid histological evaluation of spheroids grown in standard 96-well plates. Planarity figures are likely to be improved by adjusting agar block handling prior to imaging to minimize deformation and better preserve the planarity of deposited spheroids. Additionally, investigation into media additives to reduce spheroid adhesion to 96-well plates would greatly increase the capture success rate of this device.

Solid Tumor Embolotherapy in Hepatic Arteries with an Anti-reflux Catheter System.

Unresectable hepatoma accounts for the majority of malignant liver tumor cases for which embolization therapy is considered a viable treatment option. However, the potential risk of aberrant particle deposition in non-target regions could cause severe side-effects, alongside diminished efficacy. A computational model has been developed to analyze the particle-hemodynamics before and after deployment of an FDA-approved anti-reflux catheter. The catheter features a retractable, porous cone-like tip designed to allow forward blood flow while preventing microsphere reflux. A patient-specific hepatic artery system, with different daughter branches connected to a liver tumor, was chosen as a representative test bed. In vitro as well as in vivo measurements were used to validate the computer simulation model. The model captures the effect of tip-deployment on blood perfusion and pressure drop in an interactive manner under physiologically realistic conditions. A relationship between the pressure drop and embolization level was established, which can be used to provide clinicians with real-time information on the best infusion-stop point. However, the results show that the present procedure for embolization of downstream vessels which feed a tumor is quite arbitrary. Nevertheless, a method to recycle aberrant particles captured by the deployed tip was proposed to minimize side-effects.

Innovation in catheter design for intra-arterial liver cancer treatments results in favorable particle-fluid dynamics.

BACKGROUND: Liver tumors are increasingly treated with radioembolization. Here, we present first evidence of catheter design effect on particle-fluid dynamics and downstream branch targeting during microsphere administrations. MATERIALS AND METHODS: A total of 7 experiments were performed in a bench-top model of the hepatic arterial vasculature with recreated hemodynamics. Fluorescent microspheres and clinically used holmium microspheres were administered with a standard microcatheter (SMC) and an anti-reflux catheter (ARC) positioned at the same level along the longitudinal vessel axis. Catheter-related particle flow dynamics were analyzed by reviewing video recordings of UV-light illuminated fluorescent microsphere administrations. Downstream branch distribution was analyzed by quantification of collected microspheres in separate filters for two first-order branches. Mean deviation from a perfectly homogenous distribution (DHD) was used to compare the distribution homogeneity between catheter types. RESULTS: The SMC administrations demonstrated a random off-centered catheter position (in 71 % of experiments), and a laminar particle flow pattern with an inhomogeneous downstream branch distribution, dependent on catheter position and injection force. The ARC administrations demonstrated a fixed centro-luminal catheter position, and a turbulent particle flow pattern with a more consistent and homogenous downstream branch distribution. Quantitative analyses confirmed a significantly more homogeneous distribution with the ARC; the mean DHD was 40.85 % (IQR 22.76 %) for the SMC and 15.54 % (IQR 6.46 %) for the ARC (p = 0.047). CONCLUSION: Catheter type has a significant impact on microsphere administrations in an in-vitro hepatic arterial model. A within-patient randomized controlled trial has been initiated to investigate clinical catheter-related effects during radioembolization treatment.

Selective internal radiation therapy: quantifying distal penetration and distribution of resin and glass microspheres in a surrogate arterial model.

PURPOSE: To experimentally investigate the effects of microsphere density and diameter on distal penetration. MATERIALS AND METHODS: A surrogate hepatic arterial system was developed to replicate the hemodynamics (pressures, flow rates, pulsatile flow characteristics) and anatomic geometry (vessel diameters) proximal and distal to the microsphere injection point. A planar tumor model, placed distal to the injection point, allowed visualization of deposited microspheres. Bland resin and glass microspheres, with physical characteristics approximating the characteristics of commercially available products, were injected into the surrogate system. Microsphere type, injection rate, systemic flow rate, and tumor model inclination were varied among tests (glass, n = 7; resin, n = 6) with replicates for 2 conditions. After injection, 254 micrographs were obtained at previously defined locations throughout the tumor model to document microsphere distributions. Average microsphere distributions and mass measurements of microspheres collected at the tumor outlet were analyzed to quantify distal penetration for each case. RESULTS: Across all test conditions, average penetration depths of resin microspheres were higher compared with glass microspheres (45.1 cm ± 11.8 vs 22.3 cm ± 9.9). The analysis of variance indicated that the observed difference between microsphere type (glass vs resin) was significant (P = .005, df = 1,2). The observed distance means did not differ significantly across flow rate or inclination angle. CONCLUSIONS: Penetration depths of resin microspheres were significantly higher than penetration depths of glass microspheres in the surrogate hepatic arterial system.

A laparoscopic knot-tying device for minimally invasive cardiac surgery.

OBJECTIVE: Intracorporeal suturing and knot tying can complicate, prolong or preclude minimally invasive surgical procedures, reducing their advantages over conventional approaches. An automated knot-tying device has been developed to speed suture fixation during minimally invasive cardiac surgery while retaining the desirable characteristics of conventional hand-tied surgeon's knots: holding strength and visual and haptic feedback. A rotating slotted disc (at the instrument's distal end) automates overhand throws, thereby eliminating the need to manually pass one suture end through a loop in the opposing end. The electronic actuation of this disc produces left or right overhand knots as desired by the operator. METHODS: To evaluate the effectiveness of this technology, seven surgeons with varying laparoscopic experience tied knots within a simulated minimally invasive setting, using both the automated knot-tying tool and conventional laparoscopic tools. Suture types were 2/0 braided and 4/0 monofilament. RESULTS: Mean knot-tying times were 246+/-116 s and 102+/-46 s for conventional and automated methods, respectively, showing an average 56% reduction in time per surgeon (p=0.003, paired t-test). The peak holding strength of each knot (the force required to break the suture or loosen the knot) was measured using tensile-testing equipment. These peak holding strengths were normalised by the ultimate tensile strength of each suture type (57.5 N and 22.1N for 2/0 braided and 4/0 monofilament, respectively). Mean normalised holding strengths for all knots were 68.2% and 71.8% of ultimate tensile strength for conventional and automated methods, respectively (p=0.914, paired t-test). CONCLUSIONS: Experimental data reveal that the automated suturing device has great potential for advancing minimally invasive surgery: it significantly reduced knot-tying times while providing equivalent or greater holding strength than conventionally tied knots.

Evaluation of a novel atrial retractor for exposure of the mitral valve in a porcine model.

OBJECTIVES: To describe a novel atrial retractor and compare 2 methods of intraoperative left atrial retraction for minimally invasive mitral valve repair. METHODS: Left atrial retraction was performed on 5 swine cadavers to evaluate performance (percent of mitral valve annulus accessible), complications encountered, ease of use, and surgical time for the minimally invasive atrial retractor and a HeartPort atrial retractor. RESULTS: Estimated accessibilities were 93.0% (standard error = 3.2) and 92.7% (standard error = 3.3) for the HeartPort and minimally invasive atrial retractor retractors, respectively, with a difference of 0.3% (standard error = 2.2%, P = .8832, df = 34). Tissue damage occurred in 1 case for the minimally invasive atrial retractor and 2 cases for the HeartPort retractor. The mean surgical times for retractor placement and mitral valve annulus exposure were 107.4 and 39.2 seconds for the HeartPort and minimally invasive atrial retractor retractors, respectively, with a difference of 68.2 seconds (P = .0092, df = 4). CONCLUSIONS: The minimally invasive atrial retractor is a suitable alternative for atrial retraction compared with standard techniques of retraction. It provides comparable exposure of the mitral valve annulus, is less time consuming to place, provides subjectively more working volume within the left atrium, and has the advantage of minimal atriotomy incision length and customizable retraction.