Assessment of Open Surgery Suturing Skill: Image-based Metrics Using Computer Vision.

OBJECTIVE: This paper presents a computer vision algorithm for extraction of image-based metrics for suturing skill assessment and the corresponding results from an experimental study of resident and attending surgeons. DESIGN: A suturing simulator that adapts the radial suturing task from the Fundamentals of Vascular Surgery (FVS) skills assessment is used to collect data. The simulator includes a camera positioned under the suturing membrane, which records needle and thread movement during the suturing task. A computer vision algorithm processes the video data and extracts objective metrics inspired by expert surgeons' recommended best practice, to "follow the curvature of the needle." PARTICIPANTS AND RESULTS: Experimental data from a study involving subjects with various levels of suturing expertise (attending surgeons and surgery residents) are presented. Analysis shows that attendings and residents had statistically different performance on 6 of 9 image-based metrics, including the four new metrics introduced in this paper: Needle Tip Path Length, Needle Swept Area, Needle Tip Area and Needle Sway Length. CONCLUSION AND SIGNIFICANCE: These image-based process metrics may be represented graphically in a manner conducive to training. The results demonstrate the potential of image-based metrics for assessment and training of suturing skill in open surgery.

Objective and Automated Quantification of Instrument Handling for Open Surgical Suturing Skill Assessment: A Simulation-Based Study.

Goal: Vascular surgical procedures are challenging and require proficient suturing skills. To develop these skills, medical training simulators with objective feedback for formative assessment are gaining popularity. As hardware advancements offer more complex, unique sensors, determining effective task performance measures becomes imperative for efficient suturing training. Methods: 97 subjects of varying clinical expertise completed four trials on a suturing skills measurement and feedback platform (SutureCoach). Instrument handling metrics were calculated from electromagnetic motion trackers affixed to the needle driver. Results: The results of the study showed that all metrics significantly differentiated between novices (no medical experience) from both experts (attending surgeons/fellows) and intermediates (residents). Rotational motion metrics were more consistent in differentiating experts and intermediates over traditionally used tooltip motion metrics. Conclusions: Our work emphasizes the importance of tool motion metrics for open suturing skills assessment and establishes groundwork to explore rotational motion for quantifying a critical facet of surgical performance.

Nonlinear Adaptive Optimal Controller Design for Anti-Angiogenic Tumor Treatment.

Angiogenesis is an important process in tumor growth as it represents the regime when the tumor recruits blood vessels from the surrounding tissue to support further tumor growth. Anti-angiogenic treatments aim to shrink the tumor by interrupting the vascularization of the tumor; however, the anti-angiogenic agents are costly and the tumor response to these agents is nonlinear. Simple dosing schemes, e.g., a constant dose, may yield higher cost or lower efficacy than an approach that considers the tumor system dynamics. Hence, in this study, the administration of anti-angiogenic treatment is considered as a nonlinear control problem. The main aim of the controller design is to optimize the anti-angiogenic tumor therapy, specifically, to minimize the tumor volume and drug dose. Toward this aim, two nonlinear optimal controllers are presented. The first controller ensures exponential tracking of a desired, optimal tumor volume profile under the assumption that all parameters in the system model are known. The second controller, on the other hand, assumes all the parameters are unknown and provides asymptotic tracking. Both controllers take pharmacokinetics and pharmacodynamics into account, as well as the carrying capacity of the vascular network. Lyapunov based arguments are used to design the controllers, using stability arguments, and numerical simulation results are presented to demonstrate the effectiveness of the proposed method.

Measuring hand movement for suturing skill assessment: A simulation-based study.

BACKGROUND: To maximize patient safety, surgical skills education is increasingly adopting simulation-based curricula for formative skills assessment and training. However, many standardized assessment tools rely on human raters for performance assessment, which is resource-intensive and subjective. Simulators that provide automated and objective metrics from sensor data can address this limitation. We present an instrumented bench suturing simulator, patterned after the clock face radial suturing model from the Fundamentals of Vascular Surgery, for automated and objective assessment of open suturing skills. METHODS: For this study, 97 participants (35 attending surgeons, 32 residents, and 30 novices) were recruited at national vascular conferences. Automated hand motion metrics, especially focusing on rotational motion analysis, were developed from the inertial measurement unit attached to participants' hands, and the proposed suite of metrics was used to differentiate between the skill levels of the 3 groups. RESULTS: Attendings' and residents' performances were found to be significantly different from novices for all metrics. Moreover, most of our novel metrics could successfully distinguish between finer skill differences between attending and resident groups. In contrast, traditional operative skill metrics, such as time and path length, were unable to distinguish attendings from residents. CONCLUSION: This study provides evidence for the effectiveness of rotational motion analysis in assessing suturing skills. The suite of inertial measurement unit-based hand motion metrics introduced in this study allows for the incorporation of hand movement data for suturing skill assessment.

A quantitative metric for pattern fidelity of bioprinted cocultures.

This article describes a quantitative metric for coculture pattern fidelity and its use in the assessment of bioprinting systems. Increasingly, bioprinting is used to create in vitro cell and tissue models for the purpose of studying cell behavior and cell-cell interaction. To create meaningful models, a bioprinting system must be able to place cells in biologically relevant patterns with sufficient fidelity. A metric for assessing fidelity would be valuable for tuning experimental processes and parameters within a bioprinting system and for comparing performance between different systems. Toward this end, the "bioprinting fidelity index" (BFI), a metric which rates a bioprinted patterned coculture with a single number based on the proportions of correctly placed cells, is proposed. Additionally, a mathematical model of drop-on-demand printing is introduced, which predicts an upper bound on the BFI based on drop placement statistics. A proof-of-concept study was conducted in which patterned cocultures of D1 and 4T07 cells were produced in two different demonstration patterns. The BFI for the patterned cocultures was calculated and compared to the printing model fidelity prediction. The printing model successfully predicted the best BFI observed in the samples, and the BFI showed quantitatively that post-processing techniques negatively impacted the final fidelity of the samples. The BFI provides a principled method for comparing printing and post-processing methods.

Sensitive real-time on-line estimator for oxygen transfer rates in fermenters.

Recombinant Escherichia coli grown in large-scale fermenters are used extensively to produce plasmids and biopharmaceuticals. One method commonly used to control culture growth is predefined glucose feeding, often an exponential feeding profile. Predefined feeding profiles cannot adjust automatically to metabolic state changes, such as the metabolic burden associated with recombinant protein expression or high-cell density associated stresses. As the culture oxygen consumption rates indicates a culture's metabolic state, there exist several methods to estimate the oxygen uptake rate (OUR). These common OUR methods have limited application since these approaches either disrupt the oxygen supply, rely on empirical relationships, or are unable to account for latency and filtering effects. In this study, an oxygen transfer rate (OTR) estimator was developed to aid OUR prediction. This non-disruptive OTR estimator uses the dissolved oxygen and the off-gas oxygen concentration, in parallel. This new OTR estimator captures small variations in OTR due to physical and chemical manipulations of the fermenter, such as in stir speed variation, glucose feeding rate change, and recombinant protein expression. Due its sensitivity, this non-disruptive real-time OTR estimator could be integrated with feed control algorithms to maintain the metabolic state of a culture to a desired setpoint.

Assessment of open surgery suturing skill: Simulator platform, force-based, and motion-based metrics.

Objective: This paper focuses on simulator-based assessment of open surgery suturing skill. We introduce a new surgical simulator designed to collect synchronized force, motion, video and touch data during a radial suturing task adapted from the Fundamentals of Vascular Surgery (FVS) skill assessment. The synchronized data is analyzed to extract objective metrics for suturing skill assessment. Methods: The simulator has a camera positioned underneath the suturing membrane, enabling visual tracking of the needle during suturing. Needle tracking data enables extraction of meaningful metrics related to both the process and the product of the suturing task. To better simulate surgical conditions, the height of the system and the depth of the membrane are both adjustable. Metrics for assessment of suturing skill based on force/torque, motion, and physical contact are presented. Experimental data are presented from a study comparing attending surgeons and surgery residents. Results: Analysis shows force metrics (absolute maximum force/torque in z-direction), motion metrics (yaw, pitch, roll), physical contact metric, and image-enabled force metrics (orthogonal and tangential forces) are found to be statistically significant in differentiating suturing skill between attendings and residents. Conclusion and significance: The results suggest that this simulator and accompanying metrics could serve as a useful tool for assessing and teaching open surgery suturing skill.

Surgical Suturing with Depth Constraints: Image-based Metrics to Assess Skill.

Suturing is one of the most fundamental surgical skills, requiring careful and systematic instruction for skilled performance. In this paper, we evaluate the performance of attending surgeons and surgical residents on an open surgery suturing task to examine if the introduction of different depth levels affects their performance. A vision algorithm is used to extract metrics meaningful in the assessment of suturing skill. As subjects perform a suturing task on the platform, our vision algorithm computes metrics identified to be potentially useful in assessing suturing skill: distances from optimal entry and optimal exit points, stitch length, stitch time, idle time, needle swept area, needle tip trace distance, needle tip area, and needle sway length. Preliminary experimental data from a study with 5 attending surgeons and 7 surgical residents are presented. Results demonstrate that the metrics of distance from optimal exit points, idle time, needle swept area, needle tip trace distance, needle tip area, and needle sway length are useful in quantifying the effect of depth constraints on suturing performance.

Design and optimization of a novel bio-loom to weave melt-spun absorbable polymers for bone tissue engineering.

Bone graft procedures are currently among the most common surgical procedures performed worldwide, but due to high risk of complication and lack of viable donor tissue, there exists a need to develop alternatives for bone defect healing. Tissue engineering, for example, combining biocompatible scaffolds with mesenchymal stem cells to achieve new bone growth, is a possible solution. Recent work has highlighted the potential for woven polymer meshes to serve as bone tissue engineering scaffolds; since, scaffolds can be iteratively designed by adjusting weave settings, material types, and mesh parameters. However, there are a number of material and system challenges preventing the implementation of such a tissue engineering strategy. Fiber compliance, tensile strength, brittleness, cross-sectional geometry, and size present specific challenges for using traditional textile weaving methods. In the current work, two potential scaffold materials, melt-spun poly-l-lactide, and poly-l-lactide-co-ε-caprolactone, were investigated. An automated bio-loom was engineered and built to weave these materials. The bio-loom was used to successfully demonstrate the weaving of these difficult-to-handle fiber types into various mesh configurations and material combinations. The dobby-loom design, adapted with an air jet weft placement system, warp tension control system, and automated collection spool, provides minimal damage to the polymer fibers while overcoming the physical constraints presented by the inherent material structure. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1342-1351, 2017.

A CMI (cell metabolic indicator)-based controller for achieving high growth rate Escherichia coli cultures.

A large fraction of biopharmaceuticals are produced in Escherichia coli, where each new product and strain currently requires a high degree of growth characterization in benchtop and industrial bioreactors to achieve economical production protocols. The capability to use a standard set of sensors to characterize a system quickly without the need to conduct numerous experiments to determine stable growth rate for the strain would significantly decrease development time. This paper presents a cell metabolic indicator (CMI) which provides better insight into the E. coli metabolism than a growth rate value. The CMI is the ratio of the oxygen uptake rate (OUR) of the culture and the base addition rate (BAR) required to keep pH at a desired setpoint. The OUR and BAR are measured using a off-gas sensor and pH probe, respectively, and thus the CMI can be computed online. Experimental results demonstrate the relationship between CMI and the different cell metabolic states. A previously published model is augmented with acid production dynamics, allowing for comparison of the CMI-based controller with an open-loop controller in simulation. The CMI-based controller required little a priori knowledge about the E. coli strain in order to achieve a high growth rate. Since many different types of cells exhibit similar behaviors, the CMI concept can be extended to mammalian and stem cells.

A real-time adaptive oxygen transfer rate estimator for metabolism tracking in Escherichia coli cultures.

Oxygen transfer rate (OTR) is the most significant signal for aerobic bioprocess control, since most microbic metabolic activity relies on oxygen consumption. However, accurate estimation of OTR is challenging due to the difficulty of determining uncertain oxygen transfer parameters and system dynamics. This paper presents an adaptive estimator, which incorporates exhaust gas, stir speed and dissolved oxygen measurements, to predict the real-time OTR. The design of this estimator takes into account the headspace dilution effect, off-gas sensor dynamics and uncertain oxygen transfer parameters. Through simulation the estimated real-time OTR is shown to accurately track quick changes of oxygen demand in the culture. Thus, it can be applied to a variety of controls and estimation purposes, such as determining when the culture is in oxidative or overflow metabolism.

Characterizing the effects of cell settling on bioprinter output.

The time variation in bioprinter output, i.e. the number of cells per printed drop, was studied over the length of a typical printing experiment. This variation impacts the cell population size of bioprinted samples, which should ideally be consistent. The variation in output was specifically studied in the context of cell settling. The bioprinter studied is based on the thermal inkjet HP26A cartridge; however, the results are relevant to other cell delivery systems that draw fluid from a reservoir. A simple mathematical model suggests that the cell concentration in the bottom of the reservoir should increase linearly over time, up to some maximum, and that the cell output should be proportional to this concentration. Two studies were performed in which D1 murine stem cells and similarly sized polystyrene latex beads were printed. The bead output profiles were consistent with the model. The cell output profiles initially followed the increasing trend predicted by the settling model, but after several minutes the cell output peaked and then decreased. The decrease in cell output was found to be associated with the number of use cycles the cartridge had experienced. The differing results for beads and cells suggest that a biological process, such as adhesion, causes the decrease in cell output. Further work will be required to identify the exact process.

Cell settling effects on a thermal inkjet bioprinter.

This paper seeks to quantify cell settling in the print media reservoir of a bioprinter in order to determine its effect on consistent cell delivery per printed drop. The bioprinter studied here is based on the thermal inkjet HP26A cartridge, but any system that dispenses controlled volumes of fluid may be affected similarly. A simple model based on Stokes' law suggests that the cell concentration in the bottom of the reservoir should increase linearly up to some maximum and that the cell concentration in the printed drops should follow this trend. The results show that cell output initially followed the predicted increasing trend, but then peaked and decreased. The timing and rate of the decrease related to the number of use cycles for the cartridges. The results provide guidance for modifications to the printing process to ensure consistent printing of cells.

Post-bioprinting processing methods to improve cell viability and pattern fidelity in heterogeneous tissue test systems.

Bioprinted tissue test systems show promise as a powerful tool for studying cell-cell interaction in heterogeneous, tissue-like co-culture. Several challenges were encountered while attempting to consistently fabricate samples with high viability and pattern fidelity. This paper evaluates four methods for processing samples after bioprinting but prior to adding media for incubation. These methods, composed of various combinations of three techniques meant to promote cell hydration, are evaluated with respect to sample viability and pattern preservation. In the best performing method, Hank's Balanced Salt Solution was applied immediately after fabrication and a collagen overlayer was applied one hour thereafter. The success of this method highlights the ability of the collagen substrate to absorb moisture, which promotes cell health without disturbing the cell's printed location. An addendum to the main study is an investigation of the limits of an HP26 print cartridge to deposit cells at a faster rate for the purpose of creating cell layers with densities that approach confluence.

EDTA enhances high-throughput two-dimensional bioprinting by inhibiting salt scaling and cell aggregation at the nozzle surface.

Tissue-engineering strategies may be employed in the development of in vitro breast tissue models for use in testing regimens of drug therapies and vaccines. The physical and chemical interactions that occur among cells and extracellular matrix components can also be elucidated with these models to gain an understanding of the progression of transformed epithelial cells into tumours and the ultimate metastases of tumour cells. The modified inkjet printer may be a useful tool for creating three-dimensional (3D) in vitro models, because it offers an inexpensive and high-throughput solution to microfabrication, and because the printer can be easily manipulated to produce varying tissue attributes. We hypothesized, however, that when ink is replaced with a biologically based fluid (i.e. a 'bio-ink'), specifically a serum-free cell culture medium, printer nozzle failure can result from salt scale build-up as fluid evaporates on the printhead surface. In this study, ethylene diamine tetra-acetic acid (EDTA) was used as a culture medium additive to prevent salt scaling and cell aggregation during the bioprinting process. The results showed that EDTA, at a concentration typically found in commercially available trypsin solutions (0.53 mM), prevented nozzle failure when a serum-free culture medium was printed from a nozzle at 1000 drops/s. Furthermore, increasing concentrations of EDTA appeared to mildly decrease aggregation of 4T07 cells. Cell viability studies were performed to demonstrate that addition of EDTA did not result in significant cell death. In conclusion, it is recommended that EDTA be incorporated into bio-ink solutions containing salts that could lead to nozzle failure.

Design and implementation of a two-dimensional inkjet bioprinter.

Tissue engineering has the potential to improve the current methods for replacing organs and tissues and for investigating cellular process within the scope of a tissue test system. Bioprinting technology can aid in the difficult task of arranging live mammalian cells and biomaterials in viable structures for tissue engineering purposes. This paper describes a system, based on HP26 series print cartridge technology, capable of precisely depositing multiple cell types in precise patterns. The paper discusses the research, design, and implementation of the printing system, which permits control of droplet firing parameters, including firing energy, speed, and spacing. The results demonstrate the system's fine patterning ability of viable cells, including two-dimensional patterned co-cultures of two cell types. The system has been specifically designed with the flexibility to be extended to print more than two cell types and/or materials simultaneously and to layer printed patterns to form three-dimensional constructs. With these features, the printing system will serve as the foundation for a biofabrication system capable of three-dimensional cell co-cultures, i.e. tissue test systems.