Additive Manufacturing of Anatomical Models from Computed Tomography Scan Data

The purpose of the study presented here was to investigate the manufacturability of human anatomical models from Computed Tomography (CT) scan data via a 3D desktop printer which uses fused deposition modelling (FDM) technology. First, Digital Imaging and Communications in Medicine (DICOM) CT scan data were converted to 3D Standard Triangle Language (STL) format by using InVaselius digital imaging program. Once this STL file is obtained, a 3D physical version of the anatomical model can be fabricated by a desktop 3D FDM printer. As a case study, a patient’s skull CT scan data was considered, and a tangible version of the skull was manufactured by a 3D FDM desktop printer. During the 3D printing process, the skull was built using acrylonitrile-butadiene-styrene (ABS) co-polymer plastic. The printed model showed that the 3D FDM printing technology is able to fabricate anatomical models with high accuracy. As a result, the skull model can be used for preoperative surgical planning, medical training activities, implant design and simulation to show the potential of the FDM technology in medical field. It will also improve communication between medical stuff and patients. Current result indicates that a 3D desktop printer which uses FDM technology can be used to obtain accurate anatomical models.     

Three-dimensional printing: technologies,applications, and limitations in neurosurgery

Three-dimensional (3D) printers are a developing technology penetrating a variety of markets, including the medical sector. Since its introduction to the medical field in the late 1980s, 3D printers have constructed a range of devices, such as dentures, hearing aids, and prosthetics. With the ultimate goals of decreasing healthcare costs and improving patient care and outcomes, neurosurgeons are utilizing this dynamic technology, as well. Digital Imaging and Communication in Medicine (DICOM) can be translated into Stereolithography (STL) files, which are then read and methodically built by 3D Printers. Vessels, tumors, and skulls are just a few of the anatomical structures created in a variety of materials, which enable surgeons to conduct research, educate surgeons in training, and improve pre-operative planning without risk to patients. Due to the infancy of the field and a wide range of technologies with varying advantages and disadvantages, there is currently no standard 3D printing process for patient care and medical research. In an effort to enable clinicians to optimize the use of additive manufacturing (AM) technologies, we outline the most suitable 3D printing models and computer-aided design (CAD) software for 3D printing in neurosurgery, their applications, and the limitations that need to be overcome if 3D printers are to become common practice in the neurosurgical field.     

A Simple,Low-Cost Conductive Composite Material for 3D Printing of Electronic Sensors

3D printing technology can produce complex objects directly from computer aided digital designs. The technology has traditionally been used by large companies to produce fit and form concept prototypes (‘rapid prototyping’) before production. In recent years however there has been a move to adopt the technology as full-scale manufacturing solution. The advent of low-cost, desktop 3D printers such as the RepRap and emoH@baF has meant a wider user base are now able to have access to desktop manufacturing platforms enabling them to produce highly customised products for personal use and sale. This uptake in usage has been coupled with a demand for printing technology and materials able to print functional elements such as electronic sensors. Here we present formulation of a simple conductive thermoplastic composite we term ‘carbomorph’ and demonstrate how it can be used in an unmodified low-cost 3D printer to print electronic sensors able to sense mechanical flexing and capacitance changes. We show how this capability can be used to produce custom sensing devices and user interface devices along with printed objects with embedded sensing capability. This advance in low-cost 3D printing with offer a new paradigm in the 3D printing field with printed sensors and electronics embedded inside 3D printed objects in a single build process without requiring complex or expensive materials incorporating additives such as carbon nanotubes.     

Additive manufacturing for lab applications in environmental sciences: Pushing the boundaries of rapid prototyping

Fused Deposition Modeling (FDM), better known as 3D printing, has revolutionized modern manufacturing processes and the ever-increasing use of 3D printers is popular not least because of the wide range of materials available for printing. When applying the FDM process to the development of prototypes, it is possible to go from an idea to a first iteration of the product within a few hours, and from an initial concept to a final product within a few days depending on the complexity of the desired structure. We applied FDM-related open-source 3D software and a 3D printer to produce parts for devices being applied in wood anatomy and dendroecology. In this paper, we present the basic requirements for prototyping by showing detailed examples of new devices developed and produced using a 3D printer and related modeling software.     

Methods for rapid prototyping novel labware: using CAD and desktop 3D printing in the microbiology laboratory

Although the microbiology laboratory paradigm has increasingly changed from manual to automated procedures, and from functional to molecular methods, traditional culture methods remain vital. Using inexpensive desktop fused filament fabrication 3D printing, we designed, produced and tested rapid prototypes of customised labware for microbial culture namely frames to make dip slides, inoculation loops, multi-pin replicators, and multi-well culture plates for solid medium. These customised components were used to plate out samples onto solid media in various formats, and we illustrate how they can be suitable for many microbiological methods such as minimum inhibitory concentration tests, or for directly detecting pathogens from mastitis samples, illustrating the flexibility of rapid-prototyped culture consumable parts for streamlining microbiological methods. We describe the methodology needed for microbiologists to develop their own novel and unique tools, or to fabricate and customise existing consumables. A workflow is presented for designing and 3D printing labware and quickly producing easy-to-sterilise and re-useable plastic parts of great utility in the microbiology laboratory.     

3D Printing and Its Urologic Applications

3D printing is the development of 3D objects via an additive process in which successive layers of material are applied under computer control. This article discusses 3D printing, with an emphasis on its historical context and its potential use in the field of urology.Key words: Medical applications of 3D printing, Urologic applications of 3D printing, BiofabricationA 3D printer is unlike the printers most commonly used in a urology office. 3D printing is also known as desktop fabrication or additive manufacturing. It is a prototyping process whereby a real object is created from a 3D computer-created design. The digital 3D model file is sent to the 3D printer, which prints the design one layer at a time, forming a 3D object.¹The smallest 3D printer weighs 1.5 kg and costs approximately ≥1600. The biggest drawback for the individual small practice user is the relatively high cost of the printer.² In addition to the cost of the hardware, the professional 3D software and 3D model design are likewise expensive³ and is beyond the budget of most urologic practices. A list of commercial 3D printers currently available is shown in

3D-printed applicators for high dose rate brachytherapy: Dosimetric assessment at different infill percentage

PurposeDosimetric assessment of high dose rate (HDR) brachytherapy applicators, printed in 3D with acrylonitrile butadiene styrene (ABS) at different infill percentage.Materials and methodsA low-cost, desktop, 3D printer (Hamlet 3DX100, Hamlet, Dublin, IE) was used for manufacturing simple HDR applicators, reproducing typical geometries in brachytherapy: cylindrical (common in vaginal treatment) and flat configurations (generally used to treat superficial lesions). Printer accuracy was investigated through physical measurements. The dosimetric consequences of varying the applicator’s density by tuning the printing infill percentage were analysed experimentally by measuring depth dose profiles and superficial dose distribution with Gafchromic EBT3 films (International Specialty Products, Wayne, NJ). Dose distributions were compared to those obtained with a commercial superficial applicator.ResultsMeasured printing accuracy was within 0.5 mm. Dose attenuation was not sensitive to the density of the material. Surface dose distribution comparison of the 3D printed flat applicators with respect to the commercial superficial applicator showed an overall passing rate greater than 94% for gamma analysis with 3% dose difference criteria, 3 mm distance-to-agreement criteria and 10% dose threshold.ConclusionLow-cost 3D printers are a promising solution for the customization of the HDR brachytherapy applicators. However, further assessment of 3D printing techniques and regulatory materials approval are required for clinical application.     

STORMSeq: An Open-Source,User-Friendly Pipeline for Processing Personal Genomics Data in the Cloud

The increasing public availability of personal complete genome sequencing data has ushered in an era of democratized genomics. However, read mapping and variant calling software is constantly improving and individuals with personal genomic data may prefer to customize and update their variant calls. Here, we describe STORMSeq (Scalable Tools for Open-Source Read Mapping), a graphical interface cloud computing solution that does not require a parallel computing environment or extensive technical experience. This customizable and modular system performs read mapping, read cleaning, and variant calling and annotation. At present, STORMSeq costs approximately $2 and 5–10 hours to process a full exome sequence and $30 and 3–8 days to process a whole genome sequence. We provide this open-access and open-source resource as a user-friendly interface in Amazon EC2.     

GLUCOCORTICOID-INDUCED ALTERATION OF THE SURFACE MEMBRANE OF CULTURED HEPATOMA CELLS

Glucocorticoids induce an alteration of the surface of hepatoma tissue culture (HTC) cells as expressed by changes in cell electrophoretic, antigenic, and adhesive properties. The alteration is assayed by the increased adhesiveness of induced cells for a glass surface. The induction process has a lag period of about 3 hr and attains a plateau level after 24–30 hr when 50–80% of the steroid-treated cells are firmly adhered. Less than 10% of untreated cells adhere under the same conditions. Induction is inhibited by actinomycin D and cycloheximide, demonstrates both pH and temperature dependence, and responds to changes in steroid concentration and structure. By contrast, the attachment per se of preinduced cells is not affected by inhibitors of RNA and protein synthesis, fluctuations of temperature and pH, and the presence or absence of the hormone. When the induction process is reversed by removal of steroid or addition of actinomycin D, preinduced adhesiveness is lost with a half-life of 13–24 hr, but in the presence of cycloheximide the loss is accelerated (t_1/2 3–5.5 hr). These results suggest that glucocorticoids induce the biosynthesis of a protein which either modifies the cell surface (an enzyme) or is incorporated into surface structures (structural protein).     

Uncertainty and Variability of Energy and Material Use by Fused Deposition Modeling Printers in Makerspaces

Desktop‐grade fused deposition modeling (FDM) printers are popular because of compact sizes and affordable prices. If we are moving toward a future where desktop FDM printers are in every school and office, like conventional printers, then these machines will consume a large amount of energy and material. However, it is very difficult to evaluate the environmental impacts of FDM printers since there are so many different brands and types of printers using different raw materials under different scenarios. This study uses data from two different printing sites to evaluate the scenario and parameter uncertainty and variability in energy and material balances for FDM printers. Data from the two makerspaces provide insight into the material and energy consumption data using polylactic acid and acrylonitrile butadiene styrene (ABS) with four types of printers. The use of actual performance data allowed for the additional study of scrap ratio. Regressions provide insight into predictive factors for energy and material consumption. Monte Carlo simulations show the range of energy life cycle inventory values for the desktop‐grade FDM printers. From the regressions, Type A Pro was the most energy‐intensive machine. For material waste, an open‐access makerspace using ABS was associated with higher scrap ratio. Regression analysis indicates that the rate of material usage is not a strong predictor of waste rates. The amount of waste generated across both sites indicates that more ubiquitous access to FDM printing may create a significant addition to the waste stream.     

3‐D visualisation,printing, and volume determination of the tracheal respiratory system in the adult desert locust,Schistocerca gregaria

Here, we describe a single micro‐CT scan with a spatial resolution of 10 μm of a 10‐day‐old adult male Schistocerca gregaria (Forskål) (Orthoptera: Acrididae) and we compare our tracheal volume (V_T) determination with published work on the subject. We also illustrate the feasibility of performing non‐invasive ‘virtual dissection’ on insects after performing micro‐CT. These post‐processing steps can be performed using free downloadable 3‐D software. Finally, the values of producing stereo‐lithography (STL) files that can be viewed or used to print out 3‐D models as teaching aids are discussed.     

3D‐printed individual labware in biosciences by rapid prototyping: In vitro biocompatibility and applications for eukaryotic cell cultures

Three‐dimensional (3D) printing techniques are continuously evolving, thus their application fields are also growing very fast. The applications discussed here highlight the use of rapid prototyping in a dedicated biotechnology laboratory environment. The combination of improving prototypes using fused deposition modeling printers and producing useable parts with selective laser sintering printers enables a cost‐ and time‐efficient use of such techniques. Biocompatible materials for 3D printing are already available and the printed parts can directly be used in the laboratory. To demonstrate this, we tested 3D printing materials for their in vitro biocompatibility. To exemplify the versatility of the 3D printing process applied to a biotechnology laboratory, a normal well plate design was modified in silico to include different baffle geometries. This plate was subsequently 3D printed and used for cultivation. In the near future, this design and print possibility will revolutionize the industry. Advanced printers will be available for laboratories and can be used for creating individual labware or standard disposables on demand. These applications have the potential to change the way research is done and change the management of stock‐keeping, leading to more flexibility and promoting creativity of the scientists.     

Technical note: The use of 3D printing in dental anthropology collections

Objectives

Rapid prototyping (RP) technology is becoming more affordable, faster, and is now capable of building models with a high resolution and accuracy. Due to technological limitations, 3D printing in biological anthropology has been mostly limited to museum displays and forensic reconstructions. In this study, we compared the accuracy of different 3D printers to establish whether RP can be used effectively to reproduce anthropological dental collections, potentially replacing access to oftentimes fragile and irreplaceable original material.

Methods

We digitized specimens from the Yuendumu collection of Australian Aboriginal dental casts using a high‐resolution white‐light scanning system and reproduced them using four different 3D printing technologies: stereolithography (SLA); fused deposition modeling (FDM); binder‐jetting; and material‐jetting. We compared the deviations between the original 3D surface models with 3D print scans using color maps generated from a 3D metric deviation analysis.

Results

The 3D printed models reproduced both the detail and discrete morphology of the scanned dental casts. The results of the metric deviation analysis demonstrate that all 3D print models were accurate, with only a few small areas of high deviations. The material‐jetting and SLA printers were found to perform better than the other two printing machines.

Conclusions

The quality of current commercial 3D printers has reached a good level of accuracy and detail reproduction. However, the costs and printing times limit its application to produce large sample numbers for use in most anthropological studies. Nonetheless, RP offers a viable option to preserve numerically constraint fragile skeletal and dental material in paleoanthropological collections.

     

A Highlights from MBoC Selection: αE-catenin actin-binding domain alters actin filament conformation and regulates binding of nucleation and disassembly factors

The actin-binding protein αE-catenin may contribute to transitions between cell migration and cell–cell adhesion that depend on remodeling the actin cytoskeleton, but the underlying mechanisms are unknown. We show that the αE-catenin actin-binding domain (ABD) binds cooperatively to individual actin filaments and that binding is accompanied by a conformational change in the actin protomer that affects filament structure. αE-catenin ABD binding limits barbed-end growth, especially in actin filament bundles. αE-catenin ABD inhibits actin filament branching by the Arp2/3 complex and severing by cofilin, both of which contact regions of the actin protomer that are structurally altered by αE-catenin ABD binding. In epithelial cells, there is little correlation between the distribution of αE-catenin and the Arp2/3 complex at developing cell–cell contacts. Our results indicate that αE-catenin binding to filamentous actin favors assembly of unbranched filament bundles that are protected from severing over more dynamic, branched filament arrays.     

Rapid Short-Read Sequencing and Aneuploidy Detection Using MinION Nanopore Technology

MinION is a memory stick–sized nanopore-based sequencer designed primarily for single-molecule sequencing of long DNA fragments (>6 kb). We developed a library preparation and data-analysis method to enable rapid real-time sequencing of short DNA fragments (<1 kb) that resulted in the sequencing of 500 reads in 3 min and 40,000–80,000 reads in 2–4 hr at a rate of 30 nt/sec. We then demonstrated the clinical applicability of this approach by performing successful aneuploidy detection in prenatal and miscarriage samples with sequencing in <4 hr. This method broadens the application of nanopore-based single-molecule sequencing and makes it a promising and versatile tool for rapid clinical and research applications.     

Specific Loss of Histone H3 Lysine 9 Trimethylation and HP1γ/Cohesin Binding at D4Z4 Repeats Is Associated with Facioscapulohumeral Dystrophy (FSHD)

Facioscapulohumeral dystrophy (FSHD) is an autosomal dominant muscular dystrophy in which no mutation of pathogenic gene(s) has been identified. Instead, the disease is, in most cases, genetically linked to a contraction in the number of 3.3 kb D4Z4 repeats on chromosome 4q. How contraction of the 4qter D4Z4 repeats causes muscular dystrophy is not understood. In addition, a smaller group of FSHD cases are not associated with D4Z4 repeat contraction (termed “phenotypic” FSHD), and their etiology remains undefined. We carried out chromatin immunoprecipitation analysis using D4Z4–specific PCR primers to examine the D4Z4 chromatin structure in normal and patient cells as well as in small interfering RNA (siRNA)–treated cells. We found that SUV39H1–mediated H3K9 trimethylation at D4Z4 seen in normal cells is lost in FSHD. Furthermore, the loss of this histone modification occurs not only at the contracted 4q D4Z4 allele, but also at the genetically intact D4Z4 alleles on both chromosomes 4q and 10q, providing the first evidence that the genetic change (contraction) of one 4qD4Z4 allele spreads its effect to other genomic regions. Importantly, this epigenetic change was also observed in the phenotypic FSHD cases with no D4Z4 contraction, but not in other types of muscular dystrophies tested. We found that HP1γ and cohesin are co-recruited to D4Z4 in an H3K9me3–dependent and cell type–specific manner, which is disrupted in FSHD. The results indicate that cohesin plays an active role in HP1 recruitment and is involved in cell type–specific D4Z4 chromatin regulation. Taken together, we identified the loss of both histone H3K9 trimethylation and HP1γ/cohesin binding at D4Z4 to be a faithful marker for the FSHD phenotype. Based on these results, we propose a new model in which the epigenetic change initiated at 4q D4Z4 spreads its effect to other genomic regions, which compromises muscle-specific gene regulation leading to FSHD pathogenesis.     

Specific Loss of Histone H3 Lysine 9 Trimethylation and HP1γ/Cohesin Binding at D4Z4 Repeats Is Associated with Facioscapulohumeral Dystrophy (FSHD)

Facioscapulohumeral dystrophy (FSHD) is an autosomal dominant muscular dystrophy in which no mutation of pathogenic gene(s) has been identified. Instead, the disease is, in most cases, genetically linked to a contraction in the number of 3.3 kb D4Z4 repeats on chromosome 4q. How contraction of the 4qter D4Z4 repeats causes muscular dystrophy is not understood. In addition, a smaller group of FSHD cases are not associated with D4Z4 repeat contraction (termed “phenotypic” FSHD), and their etiology remains undefined. We carried out chromatin immunoprecipitation analysis using D4Z4–specific PCR primers to examine the D4Z4 chromatin structure in normal and patient cells as well as in small interfering RNA (siRNA)–treated cells. We found that SUV39H1–mediated H3K9 trimethylation at D4Z4 seen in normal cells is lost in FSHD. Furthermore, the loss of this histone modification occurs not only at the contracted 4q D4Z4 allele, but also at the genetically intact D4Z4 alleles on both chromosomes 4q and 10q, providing the first evidence that the genetic change (contraction) of one 4qD4Z4 allele spreads its effect to other genomic regions. Importantly, this epigenetic change was also observed in the phenotypic FSHD cases with no D4Z4 contraction, but not in other types of muscular dystrophies tested. We found that HP1γ and cohesin are co-recruited to D4Z4 in an H3K9me3–dependent and cell type–specific manner, which is disrupted in FSHD. The results indicate that cohesin plays an active role in HP1 recruitment and is involved in cell type–specific D4Z4 chromatin regulation. Taken together, we identified the loss of both histone H3K9 trimethylation and HP1γ/cohesin binding at D4Z4 to be a faithful marker for the FSHD phenotype. Based on these results, we propose a new model in which the epigenetic change initiated at 4q D4Z4 spreads its effect to other genomic regions, which compromises muscle-specific gene regulation leading to FSHD pathogenesis.     

The Accuracy of a Method for Printing Three-Dimensional Spinal Models

Background

To study the morphology of the human spine and new spinal fixation methods, scientists require cadaveric specimens, which are dependent on donation. However, in most countries, the number of people willing to donate their body is low. A 3D printed model could be an alternative method for morphology research, but the accuracy of the morphology of a 3D printed model has not been determined.

Methods

Forty-five computed tomography (CT) scans of cervical, thoracic and lumbar spines were obtained, and 44 parameters of the cervical spine, 120 parameters of the thoracic spine, and 50 parameters of the lumbar spine were measured. The CT scan data in DICOM format were imported into Mimics software v10.01 for 3D reconstruction, and the data were saved in .STL format and imported to Cura software. After a 3D digital model was formed, it was saved in Gcode format and exported to a 3D printer for printing. After the 3D printed models were obtained, the above-referenced parameters were measured again.

Results

Paired t-tests were used to determine the significance, set to P<0.05, of all parameter data from the radiographic images and 3D printed models. Furthermore, 88.6% of all parameters of the cervical spine, 90% of all parameters of the thoracic spine, and 94% of all parameters of the lumbar spine had Intraclass Correlation Coefficient (ICC) values >0.800. The other ICC values were <0.800 and >0.600; none were <0.600.

Conclusion

In this study, we provide a protocol for printing accurate 3D spinal models for surgeons and researchers. The resulting 3D printed model is inexpensive and easily obtained for spinal fixation research.     

Regulatory mechanism of length-dependent activation in skinned porcine ventricular muscle: role of thin filament cooperative activation in the Frank-Starling relation

Cardiac sarcomeres produce greater active force in response to stretch, forming the basis of the Frank-Starling mechanism of the heart. The purpose of this study was to provide the systematic understanding of length-dependent activation by investigating experimentally and mathematically how the thin filament “on–off” switching mechanism is involved in its regulation. Porcine left ventricular muscles were skinned, and force measurements were performed at short (1.9 µm) and long (2.3 µm) sarcomere lengths. We found that 3 mM MgADP increased Ca²⁺ sensitivity of force and the rate of rise of active force, consistent with the increase in thin filament cooperative activation. MgADP attenuated length-dependent activation with and without thin filament reconstitution with the fast skeletal troponin complex (sTn). Conversely, 20 mM of inorganic phosphate (Pi) decreased Ca²⁺ sensitivity of force and the rate of rise of active force, consistent with the decrease in thin filament cooperative activation. Pi enhanced length-dependent activation with and without sTn reconstitution. Linear regression analysis revealed that the magnitude of length-dependent activation was inversely correlated with the rate of rise of active force. These results were quantitatively simulated by a model that incorporates the Ca²⁺-dependent on–off switching of the thin filament state and interfilament lattice spacing modulation. Our model analysis revealed that the cooperativity of the thin filament on–off switching, but not the Ca²⁺-binding ability, determines the magnitude of the Frank-Starling effect. These findings demonstrate that the Frank-Starling relation is strongly influenced by thin filament cooperative activation.