# Virtual Prototyping: Computational Device Placements within Detailed Human Heart Models
## 2 Materials and Methods  
Human hearts deemed not viable for transplant were gifted to the Visible Heart(r) Laboratories for research through LifeSource, a regional organ procurement agency (St. Paul, Minnesota, MN, USA). Occasionally, these cardiac specimens were reanimated on an external perfusion apparatus utilizing Visible Heart(r) methodologies, allowing for capture of functional internal anatomy videos [8]. These isolated cardiac samples were perfusion fixed in an end-diastolic state and subsequently placed in agar gel, then MRI scanned utilizing a 3T MRI scanner at a resolution of 100 micrometers (Siemens Trio, Washington, DC, USA). Utilizing MRI scans of perfusion-fixed samples allows us to achieve high anatomic resolution, which is critical to perform virtual prototyping. Note that this is 10\(\times\) greater resolution than can be obtained with clinical imaging, since the patient heart is living and moving. The DICOM generated from these scans was segmented utilizing Mimics software (version 20.0; Materialise). The process of segmentation involved creating 2D masks by classifying pixels as to whether they represent cardiac tissue on each scan slice. The 2D masks were compiled within Mimics to create a 3D anatomical model of the cardiac specimen. The model was then imported into 3-Matic software (version 14.0; Materialise) for processing, editing, and analysis of the 3D anatomical mesh (Figure 1).  
To date, the Visible Heart(r) Laboratories have generated over 100 detailed 3D models of human cardiac anatomies, including a wide range of pathologies. These models can be utilized to gain critical insights into complex cardiac anatomies and alteration associated with disease states. Models of medical device prototypes can be computationally implanted in these anatomical models, allowing for analysis of device-tissue interactions and unique understanding of spatial relationships. The 3D models can offer distinctive views of specific internal anatomies and computationally placed devices.  
The Visible Heart(r) Laboratories have also generated 3D models of peripheral vasculatures (Figure 2). These datasets were obtained by scanning fresh cadavers that were donated through the Anatomy Request Program at the University of Minnesota. Large volumes of contrast dye (>2 L) were injected through the venous and arterial systems before or while obtaining CT scans. To date, 3D models of the major vasculatures between the subclavian veins and arteries down to the femoral veins and arteries have been generated from multiple cadaver scans. These vasculature models can be computationally added to previously generated heart models to simulate possible delivery pathways for a variety of cardiac devices, e.g., those commonly delivered through the femoral and subclavian veins or arteries.  
Finally, these models can be 3D printed utilizing either Stratasys (Rehovot, Israel) GrabCAD Print version 1.30 software and uPrint SE Plus 3D printers, or Ultimaker (Utrecht, The Netherlands) Cura 4.1.0 software and Ultimaker 3E 3D printers. Numerous models were printed utilizing polylactic acid (PLA) filament for the model material and polyvinyl alcohol (PVA) filament for the support material. These 3D printed models clearly depict three-dimensional spatial information between various patient anatomies and computationally placed devices, thus enabling further quantitative analysis of computationally implanted devices within a wide range of anatomies.  
Figure 1: (Left to right) 3D model generation pipeline starting with profusion-fixed human heart, cardiac MRI scan, 2D segmentation mask of the cardiac myocardium, and resulting 3D model of the heart.  
Figure 2: Example of a human heart model with computationally added vasculature.