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 physicians' 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' 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' training as well as for pre-interventional therapy planning.
Printed models showed a high printing resolution (~30 µm) 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.
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.
Ethical approval was considered by the ethical committee of the Ludwig-Maximilians-Universität München and was waived given that the radiological datasets used in this study were retrospectively collected and fully anonymized.
Please refer to the institute's MRI safety guidelines, especially regarding the used LVAD ventricle and metal components of the flow loop.
1. Data acquisition
2. 3D-model creation
NOTE: The creation of a 3D-model from a radiological dataset is called the segmentation process, and a special software is required. The segmentation of medical images bases itself upon Hounsfield units, to form 3-dimensional models9. This study uses a commercial segmentation and 3D-modeling software (see Table of Materials), but similar results can be achieved using available freeware. The following steps will be described for modeling from a contrast-enhanced CT dataset.
3. 3D-printing and flow loop setup
4. Clinical imaging
NOTE: To prevent artifacts in clinical imaging, it has to be ensured that there are no air pockets in the fluid circuit.
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 mm³. The aortic aneurysm models' wall thickness was set at 2.5 mm complying with comparative tensile testing results of the printing material (tensile strength: 0.62 ± 0.01 N/mm2; Fmax: 1. 55 ± 0.02 N; elongation: 9.01 ± 0.34 %) and porcine aortic samples (width: 1 mm; Fmax: 1.62 ± 0.83 N; elongation: 9.04 ± 2.76 %).
The presented 3D-printed models offer a wide range of possibilities in CT-imaging. The printed material can easily be distinguished from the surrounding agar and possible metallic implants (Figure 3A). Therefore, the use of a contrast agent is normally not required, except for generating dynamic imaging sequences. This can be especially useful for the evaluation of endovascular stentgrafts, since it allows for the visualization of possible prosthesis mismatches and subsequently appearing endoleaks.
As a staple in daily clinical work, sonographic imaging is a prime example for the application of 3D-printed models as training setup. It can be used for both the evaluation of heart valve dynamics, as well as investigation of the whole heart, particularly in pediatrics. Ultrasonic imaging of the 3D-printed model reveals a good permeability of the ultrasonic waves. Furthermore, it is possible to distinguish between the model's wall, the surrounding agar and thin dynamic objects, like heart valve leaflets (Figure 3B). The agar layer on top of the model provides realistic haptic feedback during the scanning process.
The usage of 4D-MRI in the flow analysis within the flow loop offers a wide range of possible applications in pre-interventional imaging. 4D-MRI sequence enables visualization of fluid flow, turbulences, and wall shear stress within the 3D-printed model. This allows for the analysis of flow patterns following artificial heart valves, which can lead to high wall shear stress and turbulence in the ascending aorta and aortic arch (Figure 3C). The impact of turbulence and high wall shear stress is specifically interesting for the analysis of aortic aneurysms. Thus, the 3D-models can help to better understand the occurrence of aneurysms in both the thoracic and abdominal aorta.
3D-printed cardiovascular models provide a realistic training environment for diagnostic and interventional cardiology. The simulation setup allows the trainees to practice the handling of guiding wires/catheters and maneuvering through the vessels and heart structures, intracardiac pressure measurements, balloon dilatation of stenotic vessels or valves, positioning and dilation of stents, as well as angiographic imaging (visualization of inner structures of the 3D-model, e.g., heart valves). The skills and tasks for both roles, first and second operator, as well as the communication amongst the two are included during the training. Modification of the 3D-printed models in the 3D-modeling software enables the adaptation of the model structure and size (infant to adult) to any training level and goals. Therefore, students as well as proficient practitioners benefit from the training to the same extent. Workshops for all training levels – medical students to pediatric cardiologists with years of experience – have successfully been carried out on 3D-models representing the most common congenital defects, which include patent ductus arteriosus (PDA), pulmonary valve stenosis (PS), aortic valve stenosis (AS), coarctation of the aorta (CoA) and atrial septal defect (ASD). The appearance of the 3D-models under X-ray imaging, as well as the haptic feedback from the manipulation of the instruments inside the model, were assessed as extremely realistic. Repetitive training on 3D-models leads to well-versed orientation in 3D, improved perception of haptic feedback and – most important for the patient – minimization of radiation exposure.
Figure 1: Design steps from a radiological dataset to a printed anatomical model (Pathology: infrarenal aortic aneurysm). (A) CT-dataset-based segmentation process (B) Rough 3D-model after segmentation (C) Smoothed model with added tubular connectors (D) Final model of the blood volume with connectors (E) Hollow model with defined wall thickness (F) 3D-printed flexible model. Please click here to view a larger version of this figure.
Figure 2: Setup of the flow loop. (A) Schematic model of the flow loop (B) Final flow loop setup with LVAD (1), embedded model (2), a reservoir (3) and a 3D-printed tube connector (optional) (4) Please click here to view a larger version of this figure.
Figure 3: Clinical imaging techniques. (A) CT-reconstruction of a 3D-printed aortic arch with a biological surgical heart valve (B) Ultrasonic image of a 3D-printed aortic root (1) with an open biological surgical heart valve (2) (C) 4D-MRI flow visualization in the aortic arch (D) X-ray imaging of a 3D-printed pediatric heart (1) during a catheter intervention (2) Please click here to view a larger version of this figure.
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 the digital simulation of different scenarios, in order to identify the most favorable outcome10,11. In contrast to these in-silico simulations, the described 3D-printed setup enables tactile feedback in training procedures; a material compliance close to the human original is possible in pulsatile perfusion. On the other hand, many published 3D-printed cardiovascular phantoms only use rigid material and therefore are limited to a mainly visual use12,13.
However, it must be understood that current 3D-printing techniques and materials remain the biggest limitation in reproducing biomechanical properties for the presented workflow14. While an exact recreation of the anatomical shape is possible, the mechanical behavior of the created models will still differ from native aortic tissue to an extent. To mimic different tissues with varying bio-mechanical properties in one phantom, so far as it is possible at all, can be accomplished only by a few sophisticated multi-material 3D-printers15. Creating tissue mimicking materials for 3D-printing remains a focus of scientific research; the development of novel materials will result in even more realistic results16,17. As long as, only commercially available printing material and/or one-component-printing is available, the mechanical properties of the phantom can be adjusted by means of variations of the wall thicknesses, as was conducted in this study. It is, therefore, not recommended only to duplicate the thickness of the tissue of interest from the underlying tomographic data. It is important to stress that there exists a wide range of different 3D-printers with different materials and varying mechanical properties on the market18. Comprehensive mechanical testing is, therefore, recommended, prior to 3D-printing. For printing of cardiovascular structures, (i.e., aortic or ventricular walls), different native tissue samples are required for reference. Following the described segmentation and printing workflow, the creation of flexible and anatomically accurate as well as engineered but realistic 3D-printed models of a wide range of cardiovascular anatomies is possible.
The cost-effectiveness of 3D-printed models depends significantly upon the material properties. In interventional training high durability of each model (even after balloon dilation) is necessary, to reduce overall costs. When looking at patient-specific therapy planning, one must take into account the beneficial effect of a printed model. A 3D-printed model will not prove cost-effective for a "standard" surgical patient, but might offer tremendous insight in patients with complex anatomies. Therefore, the costs of training models have to be weighed against their prospective benefits.
Until now, a few commercially available phantoms for clinical training exist on the market; some academic models have been published19,20. These models normally have pre-defined anatomies and usually prove difficult to employ in patient-specific settings. Furthermore, high acquisition costs complicate the widespread use of these tools in physicians' training. The presented customizable mock circulation can be created on a low budget if necessary. Tomographic, fluoroscopy and sonographic scanners, for acquisition of the patient-specific data as well as for the later use of the mock circulation, are standard equipment of any general or university hospital in developed countries. Segmentation of the cardiovascular anatomy and creation of the virtual 3D-model can be performed with the mentioned licensed software, but freeware is also available21. The freeware options offer excellent results when creating 3D-models from radiological datasets, although a high amount of initial work is required to adjust the software to individual needs. Furthermore, a subsequent editing of the digital 3D model requires an additional software, which is why a comprehensive software suite covering all these aspects is highly recommended for a quick and smooth workflow. If necessary, printing of the flexible phantoms can be done by contract 3D-manufacturing if there is no suitable 3D-printer on site. By anatomical reduction on the region of interest, the size of the 3D-printed phantom can be reduced, which comes with faster printing times and lower costs.
The most critical point of the process described above is the initial image acquisition. As a result, the higher the quality of the tomographic data, the more accurate will prove the final 3D-printed phantom. There are two major factors in obtaining suitable data from CT or MRI: Prevention of artifacts and spatial resolution. To prevent artifacts, ideally no metallic materials (e.g., implants) will be next to the region of interest, if no specific artifact reduction techniques are available22. In order to reduce motion artifacts, ECG- and respiratory triggering should be performed during image acquisition23,24. Spatial resolution depends on the imaging device; however, a slice thickness of 1.0 mm or less is necessary to obtain suitable 3D-printed phantoms without excessive digital postprocessing.
The above-mentioned modularity, cost-effectiveness as well as versatility predisposes the individualizable mock circulation for supplementary use in daily clinical routine. The presented method can be beneficial for a wide range of clinical and basic research fields. The use of realistic models is excellent for teaching young doctors and students the basics of sonography, as well as interventional techniques. Especially with interventions, such a model will render the technology more accessible and increase the overall knowledge base of doctors, long-term. CT and MRI imaging, especially when looking at hemodynamic flow patterns in the aortic vessels, can be a major addition both in basic science, as well as determining the outcome of surgical and transcatheter interventions.
The authors have nothing to disclose.
This publication was supported by the German Heart Foundation/German Foundation of Heart Research.
3-matic | Materialise AB | Software Version 15.0 – Commercial 3D-Modeling Software | |
Affiniti 50 | Philips Medical Systems GmbH | Ultrasonic Imaging System | |
Agilista W3200 | Keyence Co. | Polyjet 3D-Printer with a spatial resolution of 30µm | |
AR-G1L | Keyence Co. | flexible 3D-Printing material | |
Artis Zee | Siemens Healthcare GmbH | Angiographic X-ray Scanner | |
cvi42 | CCI Inc. | Software Version 5.12 – 4D Flow Analysis Software | |
Diagnostic Catheter, Multipurpose MPA 2 | Cordis, A Cardinal Health company | Catheter for pediatric training models, Sizes 4F for infants and 5F for children, young adults | |
Excor Ventricular Assist Device | Berlin Heart GmbH | 80 -100ml stroke volume | |
Imeron 400 Contrast Agent | Bracco Imaging | CT – Contrast Agent | |
IntroGuide F | Angiokard Medizintechnik GmbH | Guidewire with J-tip; diameter: 0.035" length: 220cm | |
Lunderquist Guidewire | Cook Medical Inc. | (T)EVAR interventional guidewire | |
MAGNETOM Aera | Siemens Healthcare GmbH | MRI Scanner | |
Magnevist Contrast Agent | Bayer Vital GmbH | MRI – Contrast Agent | |
Mimics | Materialise AB | Software Version 23.0 – Commercial Segmentation Software | |
Modeling Studio | Keyence Co. | 3D-Printer Slicing Software | |
PVC tubing | |||
Radifocus Guide Wire M | Terumo Europe NV | Straight guidewire; diameter: 0.035" length: 260cm | |
Really useful box 9L | Really useful products Ltd. | ||
Rotigarose – Standard Agar | Carl Roth GmbH | 3810.4 | |
Solidworks | Dassault Systemes SE | Software Version 2019-2020; CAD Design Software | |
SOMATOM Force | Siemens Healthcare GmbH | Computed Tomography Scanner | |
syngo via | Siemens Healthcare GmbH | Radiological Imaging Software |