Algorithms used in medical image segmentation for 3D printing and how to understand and quantify their performance.

BACKGROUND: 3D printing (3DP) has enabled medical professionals to create patient-specific medical devices to assist in surgical planning. Anatomical models can be generated from patient scans using a wide array of software, but there are limited studies on the geometric variance that is introduced during the digital conversion of images to models. The final accuracy of the 3D printed model is a function of manufacturing hardware quality control and the variability introduced during the multiple digital steps that convert patient scans to a printable format. This study provides a brief summary of common algorithms used for segmentation and refinement. Parameters for each that can introduce geometric variability are also identified. Several metrics for measuring variability between models and validating processes are explored and assessed. METHODS: Using a clinical maxillofacial CT scan of a patient with a tumor of the mandible, four segmentation and refinement workflows were processed using four software packages. Differences in segmentation were calculated using several techniques including volumetric, surface, linear, global, and local measurements. RESULTS: Visual inspection of print-ready models showed distinct differences in the thickness of the medial wall of the mandible adjacent to the tumor. Volumetric intersections and heatmaps provided useful local metrics of mismatch or variance between models made by different workflows. They also allowed calculations of aggregate percentage agreement and disagreement which provided a global benchmark metric. For the relevant regions of interest (ROIs), statistically significant differences were found in the volume and surface area comparisons for the final mandible and tumor models, as well as between measurements of the nerve central path. As with all clinical use cases, statistically significant results must be weighed against the clinical significance of any deviations found. CONCLUSIONS: Statistically significant geometric variations from differences in segmentation and refinement algorithms can be introduced into patient-specific models. No single metric was able to capture the true accuracy of the final models. However, a combination of global and local measurements provided an understanding of important geometric variations. The clinical implications of each geometric variation is different for each anatomical location and should be evaluated on a case-by-case basis by clinicians familiar with the process. Understanding the basic segmentation and refinement functions of software is essential for sites to create a baseline from which to evaluate their standard workflows, user training, and inter-user variability when using patient-specific models for clinical interventions or decisions.

Impact of Clinician Personal Protective Equipment on Medical Device Use During Public Health Emergency: A Review.

The aim of this systematic review is to evaluate the impact of personal protective equipment (PPE) on medical device use during public health emergency responses. We conducted a systematic literature search of peer-reviewed journals in PubMed, Web of Science, and EBSCO databases. Twenty-nine of 92 articles published between 1984 and 2015 met the inclusion criteria for the review. Although many medical device use impacts were reported, they predominantly fell into 3 categories: airway management, drug administration, and diagnostics and monitoring. Chemical, biological, radiological, and nuclear (CBRN)-PPE increased completion times for emergency clinical procedures by as much as 130% and first attempt failure rates by 35% (anesthetist) versus 55% (non-anesthetist). Effects of CBRN-PPE use depend on device, CBRN-PPE level, and clinician experience and training. Continuous clinical training of responders in CBRN-PPE and device modifications can improve safety and effectiveness of medical device use during public health emergency response.

Current and Future Perspectives on Skin Tissue Engineering: Key Features of Biomedical Research, Translational Assessment, and Clinical Application.

The skin is responsible for several important physiological functions and has enormous clinical significance in wound healing. Tissue engineered substitutes may be used in patients suffering from skin injuries to support regeneration of the epidermis, dermis, or both. Skin substitutes are also gaining traction in the cosmetics and pharmaceutical industries as alternatives to animal models for product testing. Recent biomedical advances, ranging from cellular-level therapies such as mesenchymal stem cell or growth factor delivery, to large-scale biofabrication techniques including 3D printing, have enabled the implementation of unique strategies and novel biomaterials to recapitulate the biological, architectural, and functional complexity of native skin. This progress report highlights some of the latest approaches to skin regeneration and biofabrication using tissue engineering techniques. Current challenges in fabricating multilayered skin are addressed, and perspectives on efforts and strategies to meet those limitations are provided. Commercially available skin substitute technologies are also examined, and strategies to recapitulate native physiology, the role of regulatory agencies in supporting translation, as well as current clinical needs, are reviewed. By considering each of these perspectives while moving from bench to bedside, tissue engineering may be leveraged to create improved skin substitutes for both in vitro testing and clinical applications.

Regulating 3D-printed medical products.

Additive manufacturing [also known as three-dimensional (3D) printing] is the layer-wise deposition of material to produce a 3D object. This rapidly emerging technology has the potential to produce new medical products with unprecedented structural and functional designs. Here, we describe the U.S. regulatory landscape of additive manufactured (3D-printed) medical devices and biologics and highlight key challenges and considerations.

Rapid prototyping of biomimetic vascular phantoms for hyperspectral reflectance imaging.

The emerging technique of rapid prototyping with three-dimensional (3-D) printers provides a simple yet revolutionary method for fabricating objects with arbitrary geometry. The use of 3-D printing for generating morphologically biomimetic tissue phantoms based on medical images represents a potentially major advance over existing phantom approaches. Toward the goal of image-defined phantoms, we converted a segmented fundus image of the human retina into a matrix format and edited it to achieve a geometry suitable for printing. Phantoms with vessel-simulating channels were then printed using a photoreactive resin providing biologically relevant turbidity, as determined by spectrophotometry. The morphology of printed vessels was validated by x-ray microcomputed tomography. Channels were filled with hemoglobin (Hb) solutions undergoing desaturation, and phantoms were imaged with a near-infrared hyperspectral reflectance imaging system. Additionally, a phantom was printed incorporating two disjoint vascular networks at different depths, each filled with Hb solutions at different saturation levels. Light propagation effects noted during these measurements­including the influence of vessel density and depth on Hb concentration and saturation estimates, and the effect of wavelength on vessel visualization depth­were evaluated. Overall, our findings indicated that 3-D-printed biomimetic phantoms hold significant potential as realistic and practical tools for elucidating light­tissue interactions and characterizing biophotonic system performance.

Prediction of contact mechanics in metal-on-metal Total Hip Replacement for parametrically comprehensive designs and loads.

Manufacturers and investigators of Total Hip Replacement (THR) bearings require tools to predict the contact mechanics resulting from diverse design and loading parameters. This study provides contact mechanics solutions for metal-on-metal (MoM) bearings that encompass the current design space and could aid pre-clinical design optimization and evaluation. Stochastic finite element (FE) simulation was used to calculate the head-on-cup contact mechanics for five thousand combinations of design and loading parameters. FE results were used to train a Random Forest (RF) surrogate model to rapidly predict the contact patch dimensions, contact area, pressures and plastic deformations for arbitrary designs and loading. In addition to widely observed polar and edge contact, FE results included ring-polar, asymmetric-polar, and transitional categories which have previously received limited attention. Combinations of design and load parameters associated with each contact category were identified. Polar contact pressures were predicted in the range of 0-200 MPa with no permanent deformation. Edge loading (with subluxation) was associated with pressures greater than 500 MPa and induced permanent deformation in 83% of cases. Transitional-edge contact (with little subluxation) was associated with intermediate pressures and permanent deformation in most cases, indicating that, even with ideal anatomical alignment, bearings may face extreme wear challenges. Surrogate models were able to accurately predict contact mechanics 18,000 times faster than FE analyses. The developed surrogate models enable rapid prediction of MoM bearing contact mechanics across the most comprehensive range of loading and designs to date, and may be useful to those performing bearing design optimization or evaluation.

Dynamic interfacial behavior of viscoelastic aqueous hyaluronic acid: effects of molecular weight, concentration and interfacial velocity.

An aqueous hyaluronic acid (HA(aq)) pericellular coat, when mediating the tactile aspect of cellular contact inhibition, has three tasks: interface formation, mechanical signal transmission and interface separation. To quantify the interfacial adhesive behavior of HA(aq), we induce simultaneous interface formation and separation between HA(aq) and a model hydrophobic, hysteretic Si-SAM surface. While surface tension γ remains essentially constant, interface formation and separation depend greatly on concentration (5 ≤ C ≤ 30 mg mL(-1)), molecular weight (6 ≤ MW ≤ 2000 kDa) and interfacial velocity (0 ≤ V ≤ 3 mm s(-1)), each of which affect shear elastic and loss moduli G' and G'', respectively. Viscoelasticity dictates the mode of interfacial motion: wetting-dewetting, capillary necking, or rolling. Wetting-dewetting is quantified using advancing and receding contact angles θ(A) and θ(R), and the hysteresis between them, yielding data landscapes for each C above the [MW, V] plane. The landscape sizes, shapes, and curvatures disclose the interplay, between surface tension and viscoelasticity, which governs interfacial dynamics. Gel point coordinates modulus G and angular frequency ω appear to predict wetting-dewetting (G < 75 ω0.2), capillary necking (75 ω0.2 < G < 200 ω0.075) or rolling (G > 200ω0.075). Dominantly dissipative HA(aq) sticks to itself and distorts irreversibly before separating, while dominantly elastic HA(aq) makes contact and separates with only minor, reversible distortion. We propose the dimensionless number (G'V)/(ω(r)γ), varying from 10(-5) to 10(3) in this work, as a tool to predict the mode of interface formation-separation by relating interfacial kinetics with bulk viscoelasticity. Cellular contact inhibition may be thus aided or compromised by physiological or interventional shifts in [C, MW, V], and thus in (G'V)/(ω(r)γ), which affect both mechanotransduction and interfacial dynamics. These observations, understood in terms of physical properties, may be broadened to probe interfacial dynamics of other viscoelastic aqueous biopolymers.

Exposure of natural rubber to personal lubricants--swelling and stress relaxation as potential indicators of reduced seal integrity of non-lubricated male condoms.

BACKGROUND: Male condoms act as mechanical barriers to prevent passage of body fluids. For effective use of condoms the mechanical seal is also expected to remain intact under reasonable use conditions, including with personal lubricants. Absorption of low molecular weight lubricant components into the material of male condoms may initiate material changes leading to swelling and stress relaxation of the polymer network chains that could affect performance of the sealing function of the device. Swelling indicates both a rubber-solvent interaction and stress relaxation, the latter of which may indicate and/or result in a reduced seal pressure in the current context. METHODS: Swelling and stress relaxation of natural rubber latex condoms were assessed in a laboratory model in the presence of silicone-, glycol-, and water-based lubricants. RESULTS: Within 15 minutes, significant swelling (≥6 %) and stress reduction (≥12 %) of condoms were observed with 2 out of 4 silicone-based lubricants tested, but neither was observed with glycol- or water-based lubricants tested. Under a given strain, reduction in stress was prominent during the swelling processes, but not after the process was complete. CONCLUSIONS: Lubricant induced swelling and stress relaxation may loosen the circumferential stress responsible for the mechanical seal. Swelling and stress relaxation behavior of latex condoms in the presence of personal lubricants may be useful tests to identify lubricant-rooted changes in condom-materials. IMPLICATION: For non-lubricated latex condoms, material characteristics--which are relevant to failure--may change in the presence of a few silicone-based personal lubricants. These changes may in turn induce a loss of condom seal during use, specifically at low strain conditions.

Total hip arthroplasty head-neck contact mechanics: a stochastic investigation of key parameters.

A variety of design and patient parameters have been implicated in recent reports of fretting corrosion at modular connections in total hip arthroplasty. We sought to identify the relative sensitivity of mechanical fretting to a comprehensive set of parameters such that attention may be focused on key variables. Stochastic finite element simulation of the head-neck taper-trunnion junction was performed. Four-hundred parameter sets were simulated using realistic variations of design variables, material properties and loading parameters to predict contact pressures (P), micromotions (M) and fretting work (coefficient of friction×P×M) over cycles of gait. Results indicated that fretting work was correlated with only three parameters: angular mismatch, center offset and body weight (r=0.47, 0.53 and 0.43, p<0.001). Maximum contact pressure increased by 85MPa for every 0.1° of angular mismatch. Maximum micromotion increased by 5µm per 10mm additional head offset and 1µm per 10kg increased body weight. Uncorrelated parameters included trunnion diameter, trunnion length and impaction forces. It was concluded that appropriate limiting of angular mismatch and center offset could minimize fretting, and hence its contribution to corrosion, at modular connections.

A mechanical study of rigid plate configurations for sternal fixation.

Rigid metal plates are a promising alternative to wires for reapproximating the sternum after open-heart surgery due to their potential ability to reduce motion at the wound site and thereby reduce the likelihood of post-operative healing complications. Despite initial clinical success, the use of plates has been limited, in part, by insufficient knowledge about their most effective placement. This study compares the ability of five plate configurations to provide stable closure by limiting sternal separation. Commercially available x-shaped and box-shaped plates were used and combinations of parameters (plate type, location, and number of plates) were investigated in vitro. Lateral distraction tests using controlled, uniform loading were conducted on 15 synthetic sterna and the distractions between separated sternum halves were measured at seven locations. Distractions at the xiphoid, a critical region clinically, varied widely from 0.03 +/- 0.53 mm to 4.24 +/- 1.26 mm depending on all three plate parameters. Of the configurations tested, three x-shaped plates and one box-shaped plate resisted sternal separation most effectively. These results provide the first comparison of plate configurations for stabilizing a sternotomy. However, basic mechanical analyses indicate that sternal loading in vivo is non-uniform; future studies will need to accurately quantify in vivo loading to improve in vitro test methods.

Biaxial mechanical evaluation of cholecyst-derived extracellular matrix: a weakly anisotropic potential tissue engineered biomaterial.

A new acellular, natural, biodegradable matrix has been discovered in the cholecyst-derived extracellular matrix (CEM). This matrix is rich in collagen and contains several other macromolecules useful in tissue remodeling. In this study, the principal material axes, collagen fiber orientations, and biaxial mechanical properties in a physiological loading regime were characterized. Fiber direction was determined by polarized light microscopy, and the principal axes and degree of anisotropy were determined mechanically. Macroscopic equibiaxial strain tests were then conducted on preconditioned specimens. While 13% of the area of CEM contains collagen fibers oriented between 50 degrees and 60 degrees from the neck-fundus axis, the principal material axis was oriented 63 degrees +/- 13.7 degrees , with an aspect ratio of 0.11 +/- 0.06, indicating a weak anisotropy in that direction. Under biaxial loading, CEM exhibited a large toe region followed by an exponential rise in stress in both principal and perpendicular axis directions, similar to other materials currently under research. There was no significant difference between the biaxial stress-strain profile and the burst stress-strain profile. The results demonstrate that CEM is weakly anisotropic and it has the ability to support large strains across a physiological loading regime.

Coordinate systems for the carpal bones of the wrist.

The eight small and complexly shaped carpal bones of the wrist articulate in six degrees of freedom with each other and to some extent with the radius and the metacarpals. With the increasing number and sophistication of studies of the carpus, a standardized definition for a coordinate system for each the carpal bones would aid in the reporting and comparison of findings. This paper presents a method for defining and constructing a coordinate system specific to each of the eight carpal bones based upon the inertial properties of the bone, derived from surface models constructed from three-dimensional (3-D) medical image volumes. Surface models from both wrists of 5 male and 5 female subjects were generated from CT image volumes in two neutral wrist positions (functional and clinical). An automated algorithm found the principal inertial axes and oriented them according to preset conditions in 85% of the bones, the remaining bones were corrected manually. Six of the eight carpal bones were significantly more extended in the functional neutral position than in the clinical neutral position. Gender had no significant effect on carpal bone posture in either wrist position. Correlations between the 3-D carpal posture and the commonly used 2-D clinical radiographic carpal angles are established. 3-D coordinate systems defined by the anatomy of the carpal bone, such as the ones presented here, are necessary to completely describe 3-D changes in the posture of the carpal bones.

In vivo radiocarpal kinematics and the dart thrower's motion.

BACKGROUND: Wrist motion is dependent on the complex articulations of the scaphoid and lunate at the radiocarpal joint. However, much of what is known about the radiocarpal joint is limited to the anatomically defined motions of flexion, extension, radial deviation, and ulnar deviation. The purpose of the present study was to determine the three-dimensional in vivo kinematics of the scaphoid and lunate throughout the entire range of wrist motion, with special focus on the dart thrower's wrist motion, from radial extension to ulnar flexion. METHODS: The three-dimensional kinematics of the capitate, scaphoid, and lunate were calculated from serial computed tomography scans of both wrists of fourteen healthy male subjects (average age, 25.6 years; range, twenty-two to thirty-four years) and fourteen healthy female subjects (average age, 23.6 years; range, twenty-one to twenty-eight years), which yielded data on a total of 504 distinct wrist positions. RESULTS: The scaphoid and lunate primarily flexed or extended in all directions of wrist motion, and their rotation varied linearly with the direction of wrist motion (R2= 0.90 and 0.82, respectively). Scaphoid and lunate motion was significantly less along the path of the dart thrower's motion than in any other direction of wrist motion (p < 0.01 for both carpal bones). The scaphoid and lunate translated radially (2 to 4 mm) when extended, but they did not translate appreciably when flexed. CONCLUSIONS: The dart thrower's path defined the transition between flexion and extension rotation of the scaphoid and lunate, and it identified wrist positions at which scaphoid and lunate motion approached zero. These findings indicate that this path of wrist motion confers a unique degree of radiocarpal stability and suggests that this direction, rather than the anatomical directions of wrist flexion-extension and radioulnar deviation, is the primary functional direction of the radiocarpal joint.

Carpal bone size and scaling in men versus in women.

PURPOSE: The purpose of this study was to quantify carpal bone size, to determine whether gender influences carpal size, and to determine whether small and large carpal bones differ in size only by simple isometric scaling. METHODS: Cortical surfaces of all carpal bones in both wrists of 14 women and 14 men (ages 22-34 y) were reconstructed from computed tomography (CT) volume images. Carpal volume and bounding-box dimensions in 3 orthogonal directions were calculated and compared across genders. An average set of carpal bones were then scaled mathematically by a single factor in all directions (scaled isometrically) and compared across carpal bones of all sizes. RESULTS: Although female carpal bones were significantly smaller than male carpal bones, individual carpal volume as a percentage of the volume of the entire carpus did not differ with gender. The 3 orthogonal bounding-box dimensions of the carpal bones scaled nearly isometrically from the smallest to the largest bones. CONCLUSIONS: Across the wide range of wrist sizes studied the individual carpal volumes were a consistent percentage of carpus volume and this percentage did not differ with gender. Despite their complex shape the bounding dimensions of the carpal bones increased isometrically with increasing volume. The extensive database of dimensions provided in this study should be useful in the design and insertion of fixation systems and implants.