This publication was supported by the German Heart Foundation/German Foundation of Heart Research.

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D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Tissue+mimicking+materials+for+a+multi-imaging+modality+prostate+phantom.">Tissue mimicking materials for a multi-imaging modality prostate phantom.</a> Medical Physics. 28 (4), 688-700 (2001).</li><li>Tejo-Otero, A., Buj-Corral, I., Fenollosa-Art&#233;s, F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=3D+printing+in+medicine+for+preoperative+surgical+planning:+A+review.">3D printing in medicine for preoperative surgical planning: A review.</a> Annals of Biomedical Engineering. 48 (2), 536-555 (2020).</li><li>Rotman, O. 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The authors declare no conflict of interest.

The presented workflow allows to establish individualized models and thereby perform pre-interventional therapy planning, as well as physician training on individualized anatomies. To achieve this, patient-specific tomographic data can be used for segmentation and 3D-printing of flexible cardiovascular phantoms. By implementation of these 3D-printed models in a mock circulation, different clinical situations can be realistically simulated.
Nowadays, many therapy planning procedures focus upon ...

Individualized therapies are gaining increasing importance in modern clinical practice. Essentially, they can be classified in two groups: genetic and morphologic approaches. For individualized therapies based on unique personal DNA, either genome sequencing or the quantification of gene expression levels is necessary1. One can find these methods in oncology, for example, or in metabolic disorder treatment2. The unique morphology (i.e., anatomy) of each individual plays an important role in interventional, surgical, and prosthetic medicine. The development of individualized prostheses and pre-interventional/-operative therapy planning represent central focusses of research groups today3,4,5.
Coming from industrial prototype production, 3D-printing is ideal for this field of personalized medicine6. 3D-printing is classified as an additive manufacturing method and normally based on a layer-by-layer deposition of material. Nowadays, a broad variety of 3D-printers with different printing techniques is available, enabling processing of polymeric, biologic, or metallic materials. Due to increasing printing speeds as well as the continuous widespread availability of 3D-printers, manufacturing costs are becoming progressively less expensive. Therefore, the use of 3D-printing for pre-interventional planning in daily routines has become economically feasible7.
The aim of this study was to establish a method for generating patient-specific or disease-specific phantoms, usable in individualized therapy planning in cardiovascular medicine. These phantoms should be compatible with common imaging methods, as well as for different therapeutic approaches. A further goal was the use of the individualized anatomies as training models for physicians.

<table><tbody><tr><td>3-matic</td><td>Materialise AB</td><td></td><td>Software Version 15.0 - Commercial 3D-Modeling Software</td></tr><tr><td>Affiniti 50</td><td>Philips Medical Systems GmbH</td><td></td><td>Ultrasonic Imaging System</td></tr><tr><td>Agilista W3200</td><td>Keyence Co.</td><td></td><td>Polyjet 3D-Printer with a spatial resolution of 30&amp;micro;m</td></tr><tr><td>AR-G1L</td><td>Keyence Co.</td><td></td><td>flexible 3D-Printing material</td></tr><tr><td>Artis Zee</td><td>Siemens Healthcare GmbH</td><td></td><td>Angiographic X-ray Scanner</td></tr><tr><td>cvi42</td><td>CCI Inc.</td><td></td><td>Software Version 5.12 - 4D Flow Analysis Software</td></tr><tr><td>Diagnostic Catheter, Multipurpose MPA 2</td><td>Cordis, A Cardinal Health company</td><td></td><td>Catheter for pediatric training models, Sizes 4F for infants and 5F for children, young adults</td></tr><tr><td>Excor Ventricular Assist Device</td><td>Berlin Heart GmbH</td><td></td><td>80 -100ml stroke volume</td></tr><tr><td>Imeron 400 Contrast Agent</td><td>Bracco Imaging</td><td></td><td>CT - Contrast Agent</td></tr><tr><td>IntroGuide F</td><td>Angiokard Medizintechnik GmbH</td><td></td><td>Guidewire with J-tip; diameter: 0.035&quot; length: 220cm</td></tr><tr><td>Lunderquist Guidewire</td><td>Cook Medical Inc.</td><td></td><td>(T)EVAR interventional guidewire</td></tr><tr><td>MAGNETOM Aera</td><td>Siemens Healthcare GmbH</td><td></td><td>MRI Scanner</td></tr><tr><td>Magnevist Contrast Agent</td><td>Bayer Vital GmbH</td><td></td><td>MRI - Contrast Agent</td></tr><tr><td>Mimics</td><td>Materialise AB</td><td></td><td>Software Version 23.0 - Commercial Segmentation Software</td></tr><tr><td>Modeling Studio</td><td>Keyence Co.</td><td></td><td>3D-Printer Slicing Software</td></tr><tr><td>PVC tubing</td><td></td><td></td><td></td></tr><tr><td>Radifocus Guide Wire M</td><td>Terumo Europe NV</td><td></td><td>Straight guidewire; diameter: 0.035&quot; length: 260cm</td></tr><tr><td>Really useful box 9L</td><td>Really useful products Ltd.</td><td></td><td></td></tr><tr><td>Rotigarose - Standard Agar</td><td>Carl Roth GmbH</td><td>3810.4</td><td></td></tr><tr><td>Solidworks</td><td>Dassault Systemes SE</td><td></td><td>Software Version 2019-2020; CAD Design Software</td></tr><tr><td>SOMATOM Force</td><td>Siemens Healthcare GmbH</td><td></td><td>Computed Tomography Scanner</td></tr><tr><td>syngo via</td><td>Siemens Healthcare GmbH</td><td></td><td>Radiological Imaging Software</td></tr></tbody></table>

development and evaluation of 3d-printed cardiovascular phantoms for interventional planning and training

Catheter-based interventions are standard treatment options for cardiovascular pathologies. Therefore, patient-specific models could help training physicians&#39; wire-skills as well as improving planning of interventional procedures. The aim of this study was to develop a manufacturing process of patient-specific 3D-printed models for cardiovascular interventions.
To create a 3D-printed elastic phantom, different 3D-printing materials were compared to porcine biological tissues (i.e., aortic tissue) in terms of mechanical characteristics. A fitting material was selected based on comparative tensile tests and specific material thicknesses were defined. Anonymized contrast-enhanced CT-datasets were collected retrospectively. Patient-specific volumetric models were extracted from these datasets and subsequently 3D-printed. A pulsatile flow loop was constructed to simulate the intraluminal blood flow during interventions. Models&#39; suitability for clinical imaging was assessed by x-ray imaging, CT, 4D-MRI and (Doppler) ultrasonography. Contrast medium was used to enhance visibility in x-ray-based imaging. Different catheterization techniques were applied to evaluate the 3D-printed phantoms in physicians&#39; training as well as for pre-interventional therapy planning.
Printed models showed a high printing resolution (~30 &#181;m) and mechanical properties of the chosen material were comparable to physiological biomechanics. Physical and digital models showed high anatomical accuracy when compared to the underlying radiological dataset. Printed models were suitable for ultrasonic imaging as well as standard x-rays. Doppler ultrasonography and 4D-MRI displayed flow patterns and landmark characteristics (i.e., turbulence, wall shear stress) matching native data. In a catheter-based laboratory setting, patient-specific phantoms were easy to catheterize. Therapy planning and training of interventional procedures on challenging anatomies (e.g., congenital heart disease (CHD)) was possible.
Flexible patient-specific cardiovascular phantoms were 3D-printed, and the application of common clinical imaging techniques was possible. This new process is ideal as a training tool for catheter-based (electrophysiological) interventions and can be used in patient-specific therapy planning.

The described representative results focus on a few cardiovascular structures commonly used in planning, training, or testing settings. These were created using isotropic CT-datasets with a ST of 1.0 mm and a voxel size of 1.0 mm&#179;. The aortic aneurysm models&#39; wall thickness was set at 2.5 mm complying with comparative tensile testing results of the printing material (tensile strength: 0.62 &#177; 0.01 N/mm2; Fmax: 1. 55 &#177; 0.02 N; elongation: 9.01 &#177;...

Watch this Scientific Journal Video about Development and Evaluation of 3D-Printed Cardiovascular Phantoms for Interventional Planning and Training at JoVE.com

Development and Evaluation of 3D-Printed Cardiovascular Phantoms for Interventional Planning and Training

Here we present development of a mock circulation setup for multimodal therapy evaluation, pre-interventional planning, and physician-training on cardiovascular anatomies. With the application of patient-specific tomographic scans, this setup is ideal for therapeutic approaches, training, and education in individualized medicine.

Catheter-based interventions are standard treatment options for cardiovascular pathologies. Therefore, patient-specific models could help training ...

development-evaluation-3d-printed-cardiovascular-phantoms-for

Universidad de Cartagena UDEC

Research

JoVE Journal

Medicine

3.8K Views.  Ludwig Maximilian University Munich. Here we present development of a mock circulation setup for multimodal therapy evaluation, pre-interventional planning, and physician-training on cardiovascular anatomies. With the application of patient-specific tomographic scans, this setup is ideal for therapeutic approaches, training, and education in individualized medicine.

Video: Development and Evaluation of 3D-Printed Cardiovascular Phantoms for Interventional Planning and Training

Multimodal 3D Printing of Phantoms to Simulate Biological Tissue

Biomedical optical imaging is playing an important role in diagnosis and treatment of various diseases. However, the accuracy and the reproducibility of an optical imaging device are greatly affected by the performance characteristics of its components, the test environment, and the operations. Therefore, it is necessary to calibrate these devices by traceable phantom standards. However, most of the currently available phantoms are homogeneous phantoms that cannot simulate multimodal and dynamic characteristics of biological tissue. Here, we show the fabrication of heterogeneous tissue-simulating phantoms using a production line integrating a spin coating module, a polyjet module, a fused deposition modeling (FDM) module, and an automatic control framework. The structural information and the optical parameters of a &#34;digital optical phantom&#34; are defined in a prototype file, imported to the production line, and fabricated layer-by-layer with sequential switch between different printing modalities. Technical capability of such a production line is exemplified by the automatic printing of skin-simulating phantoms that comprise the epidermis, dermis, subcutaneous tissue, and an embedded tumor.

Spin coating, polyjet printing, and fused deposition modeling are integrated to produce multilayered heterogeneous phantoms that simulate structural and functional properties of biological tissue.

Biomedical optical imaging is playing an important role in diagnosis and treatment of various diseases. However, the accuracy and the reproducibility of ...

Engineering

Creation of Cardiac Tissue Exhibiting Mechanical Integration of Spheroids Using 3D Bioprinting

This protocol describes 3D bioprinting of cardiac tissue without the use of biomaterials, using only cells. Cardiomyocytes, endothelial cells and fibroblasts are first isolated, counted and mixed at desired cell ratios. They are co-cultured in individual wells in ultra-low attachment 96-well plates. Within 3 days, beating spheroids form. These spheroids are then picked up by a nozzle using vacuum suction and assembled on a needle array using a 3D bioprinter. The spheroids are then allowed to fuse on the needle array. Three days after 3D bioprinting, the spheroids are removed as an intact patch, which is already spontaneously beating. 3D bioprinted cardiac patches exhibit mechanical integration of component spheroids and are highly promising in cardiac tissue regeneration and as 3D models of heart disease.

This protocol describes 3D bioprinting of cardiac tissue without the use of biomaterials. 3D bioprinted cardiac patches exhibit mechanical integration of component spheroids and are highly promising in cardiac tissue regeneration and as 3D models of heart disease.

This protocol describes 3D bioprinting of cardiac tissue without the use of biomaterials, using only cells. Cardiomyocytes, endothelial cells and ...

Bioengineering

Anatomically Realistic Neonatal Heart Model for Use in Neonatal Patient Simulators

Neonatal patient simulators (NPS) are artificial patient surrogates used in the context of medical simulation training. Neonatologists and nursing staff practice clinical interventions such as chest compressions to ensure patient survival in the case of bradycardia or cardiac arrest. The simulators used currently are of low physical fidelity and therefore cannot provide qualitative insight into the procedure of chest compressions. The embedding of an anatomically realistic heart model in future simulators enables the detection of cardiac output generated during chest compressions; this can provide clinicians with an output parameter, which can deepen the understanding of the effect of the compressions in relation to the amount of blood flow generated. Before this monitoring can be achieved, an anatomically realistic heart model must be created containing: two atria, two ventricles, four heart valves, pulmonary veins and arteries, and systemic veins and arteries. This protocol describes the procedure for creating such a functional artificial neonatal heart model by utilizing a combination of magnetic resonance imaging (MRI), 3D printing, and casting in the form of cold injection molding. Using this method with flexible 3D printed inner molds in the injection molding process, an anatomically realistic heart model can be obtained.

This protocol describes a procedure for creating functional artificial neonatal heart models by utilizing a combination of magnetic resonance imaging, 3D printing, and injection molding. The purpose of these models is for integration into the next generation of neonatal patient simulators and as a tool for physiological and anatomical studies.

Neonatal patient simulators (NPS) are artificial patient surrogates used in the context of medical simulation training. Neonatologists and nursing staff ...

Fabrication and Characterization of Optical Tissue Phantoms Containing Macrostructure

The rapid development of new optical imaging techniques is dependent on the availability of low-cost, customizable, and easily reproducible standards. By replicating the imaging environment, costly animal experiments to validate a technique may be circumvented. Predicting and optimizing the performance of in vivo and ex vivo imaging techniques requires testing on samples that are optically similar to tissues of interest. Tissue-mimicking optical phantoms provide a standard for evaluation, characterization, or calibration of an optical system. Homogenous polymer optical tissue phantoms are widely used to mimic the optical properties of a specific tissue type within a narrow spectral range. Layered tissues, such as the epidermis and dermis, can be mimicked by simply stacking these homogenous slab phantoms. However, many in vivo imaging techniques are applied to more spatially complex tissue where three dimensional structures, such as blood vessels, airways, or tissue defects, can affect the performance of the imaging system. 
This protocol describes the fabrication of a tissue-mimicking phantom that incorporates three-dimensional structural complexity using material with optical properties of tissue. Look-up tables provide India ink and titanium dioxide recipes for optical absorption and scattering targets. Methods to characterize and tune the material optical properties are described. The phantom fabrication detailed in this article has an internal branching mock airway void; however, the technique can be broadly applied to other tissue or organ structures.

Optical tissue phantoms are essential tools for calibration and characterization of optical imaging systems and validation of theoretical models. This article details a method for phantom fabrication that includes replication of tissue optical properties and three-dimensional tissue structure.

The rapid development of new optical imaging techniques is dependent on the availability of low-cost, customizable, and easily reproducible standards. By ...

Patient-Specific Polyvinyl Alcohol Phantom Fabrication with Ultrasound and X-Ray Contrast for Brain Tumor Surgery Planning

Phantoms are essential tools for clinical training, surgical planning and the development of novel medical devices. However, it is challenging to create anatomically accurate head phantoms with realistic brain imaging properties because standard fabrication methods are not optimized to replicate any patient-specific anatomical detail and 3D printing materials are not optimized for imaging properties. In order to test and validate a novel navigation system for use during brain tumor surgery, an anatomically accurate phantom with realistic imaging and mechanical properties was required. Therefore, a phantom was developed using real patient data as input and 3D printing of molds to fabricate a patient-specific head phantom comprising the skull, brain and tumor with both ultrasound and X-ray contrast. The phantom also had mechanical properties that allowed the phantom tissue to be manipulated in a similar manner to how human brain tissue is handled during surgery. The phantom was successfully tested during a surgical simulation in a virtual operating room.
The phantom fabrication method uses commercially available materials and is easy to reproduce. The 3D printing files can be readily shared, and the technique can be adapted to encompass many different types of tumor.

This protocol describes the fabrication of a patient specific skull, brain and tumor phantom. It uses 3D printing to create molds, and polyvinyl alcohol (PVA-c) is used as the tissue mimicking material.

Phantoms are essential tools for clinical training, surgical planning and the development of novel medical devices. However, it is challenging to create ...

Creation of Patient-Specific Silicone Cardiac Models with Applications in Pre-surgical Plans and Hands-on Training

Three dimensional&#160;models can be a valuable tool for surgeons as they develop surgical plans and medical fellows as they learn about complex cases. In particular, 3D models can play an important role in the field of cardiology, where complex congenital heart diseases occur. While many 3D printers can provide anatomically correct and detailed models, existing 3D printing materials fail to replicate myocardial tissue properties and can be extremely costly. This protocol aims to develop a process for the creation of patient-specific models of complex congenital heart defects using a low-cost silicone that more closely matches cardiac muscle properties. With improved model fidelity, actual surgical procedural training could occur in advance of the procedure. Successful creation of cardiac models begins with the segmentation of radiologic images to generate a virtual blood pool (blood that fills the chambers of the heart) and myocardial tissue mold. The blood pool and myocardial mold are 3D printed in acrylonitrile butadiene styrene (ABS), a plastic dissolvable in acetone. The mold is assembled around the blood pool, creating a negative space simulating the myocardium. Silicone with a shore hardness of 2A is poured into the negative space and allowed to cure. The myocardial mold is removed, and the remaining silicone/blood pool model is submerged in acetone. The described process results in a physical model in which all cardiac features, including intra-cardiac defects, are represented with more realistic tissue properties and are more closely approximated than a direct 3D printing approach. The successful surgical correction of a model with a ventricular septal defect (VSD) using a GORE-TEX patch (standard surgical intervention for defect) demonstrates the utility of the method.

Patient-specific models improve surgeon and fellow confidence when developing or learning surgical plans. Three-dimensional (3D) printers generate adequate detail for surgical preparation, but fail to replicate tissue haptic fidelity. A protocol is presented detailing the creation of patient-specific, silicone cardiac models, combining 3D printing precision with simulated silicone tissue.

Three dimensional&#160;models can be a valuable tool for surgeons as they develop surgical plans and medical fellows as they learn about complex cases. In ...

Three-Dimensional Printing of a Complex Aortic Anomaly

Complex congenital aortic anomalies include diverse types of malformations that may be clinically asymptomatic or present with respiratory or esophageal symptoms. These anomalies may be associated with other congenital heart diseases. It is hard to identify the accurate anatomic vessel location from two-dimensional imaging data, such as computed tomography. As an additive manufacturing method, three-dimensional (3-D) printing can covert the acquired imaging data into 3-D physical models. This protocol describes the procedure for modeling the volumetric DICOM imaging into 3-D data and printing it as an anatomically realistic 3-D model. Using this model, surgeons can identify the vessel location of complex aortic anomalies, which is helpful for pre-operative planning and intra-operative guidance.

Here, we present a protocol to use three dimensional printed models for pre-operative planning and intra-operative reorganization of complicated vascular locations when handling a congenital aortic anomaly.

Complex congenital aortic anomalies include diverse types of malformations that may be clinically asymptomatic or present with respiratory or esophageal ...

Novel Percutaneous Approach for Deployment of 3D Printed Coronary Stenosis Implants in Swine Models of Ischemic Heart Disease

Minimally invasive methods for creating models of focal coronary narrowing in large animals are challenging. Rapid prototyping using three-dimensionally (3D) printed coronary implants can be employed to percutaneously create a focal coronary stenosis. However, reliable delivery of the implants can be difficult without the use of ancillary equipment. We describe the use of a mother-and-child coronary guide catheter for stabilization of the implant and for effective delivery of the 3D printed implant to any desired location along the length of the coronary vessel. The focal coronary narrowing was confirmed under coronary cineangiography and the functional significance of the coronary stenosis was assessed using gadolinium-enhanced first-pass cardiac perfusion MRI. We showed that reliable delivery of 3D printed coronary implants in swine models (n = 11) of ischemic heart disease can be achieved through repurposing mother-and-child coronary guide catheters. Our technique simplifies the percutaneous delivery of coronary implants to create closed-chest swine models of focal coronary artery stenosis and can be performed expeditiously, with a low procedural failure rate.

We describe a novel, cost-effective, and efficient technique for percutaneous delivery of three-dimensionally printed coronary implants to create closed-chest swine models of ischemic heart disease. The implants were fixed in place using a mother-and-child extension catheter with high success rate.

Minimally invasive methods for creating models of focal coronary narrowing in large animals are challenging. Rapid prototyping using three-dimensionally ...

Creation of a High-Fidelity, Low-Cost, Intraosseous Line Placement Task Trainer via 3D Printing

The description of procedural task trainers includes their use as a training tool to hone technical skills through repetition and rehearsal of procedures in a safe environment before ultimately performing the procedure on a patient. Many procedural task trainers available to date suffer from several drawbacks, including unrealistic anatomy and the tendency to develop user-created &#39;landmarks&#39; after the trainer tissue undergoes repeated manipulations, potentially leading to inappropriate psychomotor skill development. To ameliorate these drawbacks, a process was created to produce a high-fidelity procedural task trainer, created from anatomy obtained from computed tomography (CT) scans, that utilize ubiquitous three-dimensional (3D) printing technology and off-the-shelf commodity supplies.
This method includes creating a 3D printed tissue mold capturing the tissue structure surrounding the skeletal element of interest to encase the bony skeletal structure suspended within the tissue, which is also 3D printed. A tissue medium mixture, which approximates tissue in both high-fidelity geometry and tissue density, is then poured into a mold and allowed to set. After a task trainer has been used to practice a procedure, such as intraosseous line placement, the tissue media, molds, and bones are reclaimable and may be reused to create a fresh task trainer, free of puncture sites and manipulation defects, for use in subsequent training sessions.

We describe a procedure to process computed tomography (CT) scans into high-fidelity, reclaimable, and low-cost procedural task trainers. The CT scan identification processes, export, segmentation, modeling, and 3D printing are all described, along with the issues and lessons learned in the process.

The description of procedural task trainers includes their use as a training tool to hone technical skills through repetition and rehearsal of procedures ...

A Personalized 3D-Printed Model for Preoperative Evaluation in Thyroid Surgery

The anatomic structure of the surgical area of thyroid cancer is complex. It is very important to comprehensively and carefully evaluate the tumor location and its relation with the capsule, trachea, esophagus, nerves, and blood vessels before operation. This paper introduces an innovative 3D-printed model establishment method based on computerized tomography (CT) DICOM images. We established a personalized 3D-printed model of the cervical thyroid surgery field for each patient who needed thyroid surgery to help clinicians evaluate the key points and difficulties of the surgery and select the operation methods of key parts as a basis. The results showed that this model is conducive to preoperative discussion and the formulation of operation strategies. In particular, as a result of the clear display of the recurrent laryngeal nerve and parathyroid gland locations in the thyroid operation field, injury to them can be avoided during surgery, the difficulty of thyroid surgery reduced, and the incidence of postoperative hypoparathyroidism and complications related to recurrent laryngeal nerve injury reduced too. Moreover, this 3D-printed model is intuitive and aids communication for the signing of informed consent by patients before surgery.

Here, a new method of establishing a personalized 3D-printed model for preoperative evaluation of thyroid surgery is proposed. It is conducive to preoperative discussion, reducing the difficulty of thyroid surgery.