Design Optimization for Accurate Flow Simulations in 3D Printed Vascular Phantoms Derived from Computed Tomography Angiography.

3D printing has been used to create complex arterial phantoms to advance device testing and physiological condition evaluation. Stereolithographic (STL) files of patient-specific cardiovascular anatomy are acquired to build cardiac vasculature through advanced mesh-manipulation techniques. Management of distal branches in the arterial tree is important to make such phantoms practicable. We investigated methods to manage the distal arterial flow resistance and pressure thus creating physiologically and geometrically accurate phantoms that can be used for simulations of image-guided interventional procedures with new devices. Patient specific CT data were imported into a Vital Imaging workstation, segmented, and exported as STL files. Using a mesh-manipulation program (Meshmixer) we created flow models of the coronary tree. Distal arteries were connected to a compliance chamber. The phantom was then printed using a Stratasys Connex3 multimaterial printer: the vessel in TangoPlus and the fluid flow simulation chamber in Vero. The model was connected to a programmable pump and pressure sensors measured flow characteristics through the phantoms. Physiological flow simulations for patient-specific vasculature were done for six cardiac models (three different vasculatures comparing two new designs). For the coronary phantom we obtained physiologically relevant waves which oscillated between 80 and 120 mmHg and a flow rate of ~125 ml/min, within the literature reported values. The pressure wave was similar with those acquired in human patients. Thus we demonstrated that 3D printed phantoms can be used not only to reproduce the correct patient anatomy for device testing in image-guided interventions, but also for physiological simulations. This has great potential to advance treatment assessment and diagnosis.

Initial Simulated FFR Investigation Using Flow Measurements in Patient-specific 3D Printed Coronary Phantoms.

PURPOSE: Accurate patient-specific phantoms for device testing or endovascular treatment planning can be 3D printed. We expand the applicability of this approach for cardiovascular disease, in particular, for CT-geometry derived benchtop measurements of Fractional Flow Reserve, the reference standard for determination of significant individual coronary artery atherosclerotic lesions. MATERIALS AND METHODS: Coronary CT Angiography (CTA) images during a single heartbeat were acquired with a 320×0.5mm detector row scanner (Toshiba Aquilion ONE). These coronary CTA images were used to create 4 patient-specific cardiovascular models with various grades of stenosis: severe, <75% (n=1); moderate, 50-70% (n=1); and mild, <50% (n=2). DICOM volumetric images were segmented using a 3D workstation (Vitrea, Vital Images); the output was used to generate STL files (using AutoDesk Meshmixer), and further processed to create 3D printable geometries for flow experiments. Multi-material printed models (Stratasys Connex3) were connected to a programmable pulsatile pump, and the pressure was measured proximal and distal to the stenosis using pressure transducers. Compliance chambers were used before and after the model to modulate the pressure wave. A flow sensor was used to ensure flow rates within physiological reported values. RESULTS: 3D model based FFR measurements correlated well with stenosis severity. FFR measurements for each stenosis grade were: 0.8 severe, 0.7 moderate and 0.88 mild. CONCLUSIONS: 3D printed models of patient-specific coronary arteries allows for accurate benchtop diagnosis of FFR. This approach can be used as a future diagnostic tool or for testing CT image-based FFR methods.

3D Printed Abdominal Aortic Aneurysm Phantom for Image Guided Surgical Planning with a Patient Specific Fenestrated Endovascular Graft System.

Following new trends in precision medicine, Juxatarenal Abdominal Aortic Aneurysm (JAAA) treatment has been enabled by using patient-specific fenestrated endovascular grafts. The X-ray guided procedure requires precise orientation of multiple modular endografts within the arteries confirmed via radiopaque markers. Patient-specific 3D printed phantoms could familiarize physicians with complex procedures and new devices in a risk-free simulation environment to avoid periprocedural complications and improve training. Using the Vascular Modeling Toolkit (VMTK), 3D Data from a CTA imaging of a patient scheduled for Fenestrated EndoVascular Aortic Repair (FEVAR) was segmented to isolate the aortic lumen, thrombus, and calcifications. A stereolithographic mesh (STL) was generated and then modified in Autodesk MeshMixer for fabrication via a Stratasys Eden 260 printer in a flexible photopolymer to simulate arterial compliance. Fluoroscopic guided simulation of the patient-specific FEVAR procedure was performed by interventionists using all demonstration endografts and accessory devices. Analysis compared treatment strategy between the planned procedure, the simulation procedure, and the patient procedure using a derived scoring scheme. RESULTS: With training on the patient-specific 3D printed AAA phantom, the clinical team optimized their procedural strategy. Anatomical landmarks and all devices were visible under x-ray during the simulation mimicking the clinical environment. The actual patient procedure went without complications. CONCLUSIONS: With advances in 3D printing, fabrication of patient specific AAA phantoms is possible. Simulation with 3D printed phantoms shows potential to inform clinical interventional procedures in addition to CTA diagnostic imaging.

3D Printed Cardiac Phantom for Procedural Planning of a Transcatheter Native Mitral Valve Replacement.

3D printing an anatomically accurate, functional flow loop phantom of a patient's cardiac vasculature was used to assist in the surgical planning of one of the first native transcatheter mitral valve replacement (TMVR) procedures. CTA scans were acquired from a patient about to undergo the first minimally-invasive native TMVR procedure at the Gates Vascular Institute in Buffalo, NY. A python scripting library, the Vascular Modeling Toolkit (VMTK), was used to segment the 3D geometry of the patient's cardiac chambers and mitral valve with severe stenosis, calcific in nature. A stereolithographic (STL) mesh was generated and AutoDesk Meshmixer was used to transform the vascular surface into a functioning closed flow loop. A Stratasys Objet 500 Connex3 multi-material printer was used to fabricate the phantom with distinguishable material features of the vasculature and calcified valve. The interventional team performed a mock procedure on the phantom, embedding valve cages in the model and imaging the phantom with a Toshiba Infinix INFX-8000V 5-axis C-arm bi-Plane angiography system. RESULTS: After performing the mock-procedure on the cardiac phantom, the cardiologists optimized their transapical surgical approach. The mitral valve stenosis and calcification were clearly visible. The phantom was used to inform the sizing of the valve to be implanted. CONCLUSION: With advances in image processing and 3D printing technology, it is possible to create realistic patient-specific phantoms which can act as a guide for the interventional team. Using 3D printed phantoms as a valve sizing method shows potential as a more informative technique than typical CTA reconstruction alone.

Nucleosome effects on mesangial cell matrix and proliferation: a possible role in early lupus nephritis.

BACKGROUND: Oligonucleosomes (ON) have been demonstrated in the circulation and biopsies of lupus nephritis patients. Their presence as immune complexes is an early and persistent finding in lupus nephritis as are changes in mesangial matrix. Since ON competitively bind to glomerular mesangial cells (MC) in a receptor-like fashion, the purpose of our study was to investigate what effects ON have on MC matrix and proliferation. METHODS: Rat and mouse MCs grown with ON or DNA for 1 week were dissociated from their matrices with Triton-X and their proteins were determined. MC collagen production, using collagenase sensitive 3H-proline incorporation, was measured after 48-hour incubation with ON and DNA. Similar experiments using 10-fold excess DNA were done to assess its blocking effect on ON induced collagen synthesis. ON interaction with matrix was evaluated by incubated 125I-ON with MC matrix grown with ON or media alone for 1 week. RESULTS: MCs stimulated by ON but not DNA significantly increased total matrix protein, total collagen and specifically, collagen type I synthesis. DNA inhibited ON-stimulated collagen synthesis. MC matrix incubated with ON binds 3 times more 125I-ON than matrix generated in media alone. Histone, a major component of nucleosomes, significantly increased 3H-thymidine incorporation. CONCLUSIONS: Oligonucleosomes, both qualitatively and quantitatively, influence mesangial cell function. These findings for the first time suggest ON to be pathogenic independent of their IC construct. DNA inhibition of ON induced mesangial matrix changes suggests participation of the ON/DNA receptor. Increased production of collagen type I may contribute to glomerulosclerosis.