With intravascular Optical Coherence Tomography (IVOCT), phantom models are invaluable for system characterization and clinical training. However, accurately simulating 3D tissue geometries and heterogeneous optical properties has been challenging with phantom fabrication methods used to date. Anatomical phantom models typically require mesoscale structures integrated with heterogenous materials to simulate optical scattering and absorption by vascular tissue. In this study, we showed that two photon polymerisation (2PP) 3D printing offers the potential to generate complex tissue phantom scaffolds with sub-micron resolution (<200 nm), and that microinjection of tissue mimicking materials into these scaffolds allows for creation of realistic mesoscale anatomical phantom models of both healthy and diseased tissues. We developed three types of IVOCT phantom models: a free-standing wire model, a vessel side-branch model and an arterial plaque model. The free-standing wires ranged in diameter from 5 to 34 microns. Integration of tissue mimicking materials was performed using micropipettes with a tip diameter of 50 to 60 microns. Healthy vascular tissue was simulated using a mixture of PDMS, silicone oil and TiO2. Coconut oil was used to simulate a pathological lipid inclusion. All models were examined using optical microscopy and scanning electron microscopy, prior to imaging with a commercial IVOCT system. To our knowledge, this is the first phantom study to use 2PP 3D printing for OCT phantoms. The combination of optically-generated 3D scaffolds and microinjection of tissue mimicking materials will enable complex imaging phantoms for a wide range of microscopic and mesoscale optical imaging techniques.
Microscopic and mesoscale optical imaging techniques allow for three-dimensional (3-D) imaging of biological tissue across millimeter-scale regions, and imaging phantom models are invaluable for system characterization and clinical training. Phantom models that replicate complex 3-D geometries with both structural and molecular contrast, with resolution and lateral dimensions equivalent to those of imaging techniques (<20 μm), have proven elusive. We present a method for fabricating phantom models using a combination of two-photon polymerization (2PP) to print scaffolds, and microinjection of tailored tissue-mimicking materials to simulate healthy and diseased tissue. We provide a first demonstration of the capabilities of this method with intravascular optical coherence tomography, an imaging technique widely used in clinical practice. We describe the design, fabrication, and validation of three types of phantom models: a first with subresolution wires (5- to 34-μm diameter) arranged circumferentially, a second with a vessel side-branch, and a third containing a lipid inclusion within a vessel. Silicone hybrid materials and lipids, microinjected within a resin framework created with 2PP, served as tissue-mimicking materials that provided realistic optical scattering and absorption. We demonstrate that optical phantom models made with 2PP and microinjected tissue-mimicking materials can simulate complex anatomy and pathology with exquisite detail.