Renal Embolization-Induced Uremic Swine Model for Assessment of Next-Generation Implantable Hemodialyzers.

Reliable models of renal failure in large animals are critical to the successful translation of the next generation of renal replacement therapies (RRT) into humans. While models exist for the induction of renal failure, none are optimized for the implantation of devices to the retroperitoneal vasculature. We successfully piloted an embolization-to-implantation protocol enabling the first implant of a silicon nanopore membrane hemodialyzer (SNMHD) in a swine renal failure model. Renal arterial embolization is a non-invasive approach to near-total nephrectomy that preserves retroperitoneal anatomy for device implants. Silicon nanopore membranes (SNM) are efficient blood-compatible membranes that enable novel approaches to RRT. Yucatan minipigs underwent staged bilateral renal arterial embolization to induce renal failure, managed by intermittent hemodialysis. A small-scale arteriovenous SNMHD prototype was implanted into the retroperitoneum. Dialysate catheters were tunneled externally for connection to a dialysate recirculation pump. SNMHD clearance was determined by intermittent sampling of recirculating dialysate. Creatinine and urea clearance through the SNMHD were 76-105 mL/min/m2 and 140-165 mL/min/m2, respectively, without albumin leakage. Normalized creatinine and urea clearance measured in the SNMHD may translate to a fully implantable clinical-scale device. This pilot study establishes a path toward therapeutic testing of the clinical-scale SNMHD and other implantable RRT devices.

Near infrared fluorescence imaging with ICG in TECAB surgery using the da Vinci Si surgical system in a canine model.

BACKGROUND: This study assessed the clinical utility of near-infrared fluorescence imaging using indocyanine green in off-pump beating heart total endoscopic and robotic-assisted coronary artery bypass using the fluorescence imaging system for the da Vinci Si on a canine model for vessel identification, graft patency, and correlation of graft patency with ultrasound transit-time flow measurement probe. METHODS: Beating heart total endoscopic robotic-assisted coronary artery bypass was performed on eight canine using indocyanine green and fluorescence imaging to identify the internal mammary artery prior to harvesting, the coronary vessel anatomy, and the patency of the beating heart total endoscopic coronary artery bypass anastomosis. Three to four injections of indocyanine green with a dose of 1.25 mg to 2.5 mg were administered per animal. Transit-time flow was measured in each of the dogs. RESULTS: High definition 3D images were obtained. The camera working distance, indocyanine green dosage, internal mammary artery visualization, coronary artery visualization, patency by indocyanine green injection, and patency by transit-time flow were recorded. Six cases were completed successfully, and all demonstrated correlation between indocyanine green measurements of flow, and the transit-time flow measurement. CONCLUSION: Use of near-infrared fluorescence with indocyanine green was feasible in our study, and would be of great benefit during total endoscopic robotic-assisted coronary artery bypass using the fluorescence imaging-capable da Vinci Si system to help identify the internal mammary artery, delineate the coronary anatomy, and also determine patency of the anastomoses. This procedure correlated well with transit-time flow measurement.

Identifying a minimal rheological configuration: a tool for effective and efficient constitutive modeling of soft tissues.

We describe a modeling methodology intended as a preliminary step in the identification of appropriate constitutive frameworks for the time-dependent response of biological tissues. The modeling approach comprises a customizable rheological network of viscous and elastic elements governed by user-defined 1D constitutive relationships. The model parameters are identified by iterative nonlinear optimization, minimizing the error between experimental and model-predicted structural (load-displacement) tissue response under a specific mode of deformation. We demonstrate the use of this methodology by determining the minimal rheological arrangement, constitutive relationships, and model parameters for the structural response of various soft tissues, including ex vivo perfused porcine liver in indentation, ex vivo porcine brain cortical tissue in indentation, and ex vivo human cervical tissue in unconfined compression. Our results indicate that the identified rheological configurations provide good agreement with experimental data, including multiple constant strain rate load/unload tests and stress relaxation tests. Our experience suggests that the described modeling framework is an efficient tool for exploring a wide array of constitutive relationships and rheological arrangements, which can subsequently serve as a basis for 3D constitutive model development and finite-element implementations. The proposed approach can also be employed as a self-contained tool to obtain simplified 1D phenomenological models of the structural response of biological tissue to single-axis manipulations for applications in haptic technologies.

Universal suprapubic approach for complete mesocolic excision and central vascular ligation using the da Vinci Xi® system: from cadaveric models to clinical cases.

There has been little enthusiasm for performing robotic colectomy for colon cancer in recent years due to multiple factors, one being that the previous robotic systems such as the da Vinci Si® (dVSi) were poorly designed for multi-quadrant surgery. The new da Vinci Xi® (dVXi) system enables colectomy with central mesocolic excision to be performed easily in a single docking procedure. We developed a universal port placement strategy to allow right and left hemicolectomies to be performed via a suprapubic approach and a Pfannensteil extraction site. This proof of concept paper describes the development and subsequent clinical application of this setup. After extensive training on the dVXi system concepts in collaboration with clinical development engineers, we developed a port placement strategy which was tested and adapted after performing experimental surgery in three cadaveric models. Subsequently our port placement was used for two clinical cases of suprapubic right and left hemicolectomy. With some modifications of port placements after the initial cadaveric colectomies, we have developed a potentially universal suprapubic port placement strategy for robotic colectomy with complete mesocolic excision and central vascular ligation using the dVXi robotic system. This port placement strategy was applied successfully in our first two clinical cases. Based on our cadaveric laboratory as well as our initial clinical application, the suprapubic port placement strategy for the dVXi system with its improved features over the dVSi can feasibly perform right and left hemicolectomy with complete mesocolic excision and central vascular ligation. Further studies will be required to establish efficacy as well as safety profile of these procedures.

Effects of perfusion on the viscoelastic characteristics of liver.

Accurate characterization of soft tissue material properties is required to enable new computer-aided medical technologies such as surgical training and planning. The current means of acquiring these properties in the in vivo and ex vivo states is fraught with problems, including limited accessibility and unknown boundary conditions in the former, and unnatural behavior in the latter. This paper presents a new testing method where a whole porcine liver is perfused under physiologic conditions and tested in an ex vivo setting. To characterize the effects of perfusion on the viscoelastic response of liver, indentation devices made force and displacement measurements across four conditions: in vivo, ex vivo perfused, ex vivo post perfused, and in vitro on an excised section. One device imposed cyclic perturbations on the liver's surface, inducing nominal strains up to 5% at frequencies from 0.1 to 200 Hz. The other device measured 300 s of the organ's creep response to applied loads, inducing nominal surface stresses of 6.9-34.7 kPa and nominal strains up to 50%. Results from empirical models indicate that the viscoelastic properties of liver change with perfusion and that two time constants on the order of 1.86 and 51.3s can characterize the liver under large strains typical of surgical manipulation across time periods up to 300 s. Unperfused conditions were stiffer and more viscous than the in vivo state, resulting in permanent strain deformation with repeated indentations. Conversely, the responses from the ex vivo perfusion condition closely approximated the in vivo response.

Energetics and mechanics of human running on surfaces of different stiffnesses.

Mammals use the elastic components in their legs (principally tendons, ligaments, and muscles) to run economically, while maintaining consistent support mechanics across various surfaces. To examine how leg stiffness and metabolic cost are affected by changes in substrate stiffness, we built experimental platforms with adjustable stiffness to fit on a force-plate-fitted treadmill. Eight male subjects [mean body mass: 74.4 +/- 7.1 (SD) kg; leg length: 0.96 +/- 0.05 m] ran at 3.7 m/s over five different surface stiffnesses (75.4, 97.5, 216.8, 454.2, and 945.7 kN/m). Metabolic, ground-reaction force, and kinematic data were collected. The 12.5-fold decrease in surface stiffness resulted in a 12% decrease in the runner's metabolic rate and a 29% increase in their leg stiffness. The runner's support mechanics remained essentially unchanged. These results indicate that surface stiffness affects running economy without affecting running support mechanics. We postulate that an increased energy rebound from the compliant surfaces studied contributes to the enhanced running economy.

Truth cube: establishing physical standards for soft tissue simulation.

Accurate real-time models of soft tissue behavior are key elements in medical simulation systems. The need for fast computation in these simulations, however, often requires simplifications that limit deformation accuracy. Validation of these simplified models remains a challenge. Currently, real-time modeling is at best validated against finite element models that have their own intrinsic limitations. This study develops a physical standard to validate real-time soft tissue deformation models. We took CT images of a cube of silicone rubber with a pattern of embedded Teflon spheres that underwent uniaxial compression and spherical indentation tests. The known material properties, geometry and controlled boundary conditions resulted in a complete set of volumetric displacement data. The results were compared to a finite element model analysis of identical situations. This work has served as a proof of concept for a robust physical standard for use in validating soft tissue models. A web site has been created to provide access to our database: http://biorobotics.harvard.edu/truthcube/ (soon to be http://www.truthcube.org).