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.
Vascular phantoms are crucial tools for clinical training and for calibration and validation of medical imaging systems. With current methods, it can be challenging to replicate anatomically-realistic vasculature. Here, we present a novel method that enables the fabrication of complex vascular phantoms. Poly(vinyl alcohol) (PVA) in two forms was used to create wall-less vessels and the surrounding tissue mimicking material (TMM). For the latter, PVA cryogel (PVA-c) was used as the TMM, which was made from a solution of PVA (10% by weight), distilled water, and glass spheres for ultrasonic scattering (0.5% by weight). PVA-c is not water soluble, and after a freeze-thaw cycle it is mechanically robust. To form the wall-less vessels, vessel structures were 3D printed in water-soluble PVA and submerged in the aqueous solution of PVA-c. Once the PVA-c had solidified, the 3D printed PVA vessel structures were dissolved in water. Three phantoms were created, as initial demonstrations of the capabilities of this method: a straight vessel, a stenosed (narrowed), and a bifurcated (branched) vessel. Ultrasound images of the phantoms had realistic appearances. We conclude that this method is promising for creating wall-less, anatomically realistic, vascular phantoms.
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.
Intravascular (IV) imaging in percutaneous coronary interventions can be invaluable to treat coronary artery disease, to facilitate decision making and to guide stent placement. Intravascular ultrasound (IVUS) and optical coherence tomography (OCT) are both established IV imaging modalities. However, achieving contrast for specific structures such as lipid plaques can be challenging; with OCT, visualisation is typically limited to tissue depths less than 2 mm. Photoacoustic (PA) imaging provides contrast that is complementary to those of IVUS and OCT, and with previous demonstrations, visualisation of lipid plaques at depths greater than 4 mm has been achieved. In this study, we developed an intravascular PA probe that comprises a commercial OCT catheter and a high sensitivity miniature fibre optic ultrasound sensor with a Fabry-Pérot cavity. This probe, which can provide both PA imaging and OCT, had a maximum width of 1.2 mm. The PA excitation sources included both pulsed and modulated lasers at different wavelengths. The omni-directionality of the US sensor allowed for three-dimensional PA images. The PA-OCT probe was characterised using a series of resolution phantoms, including fine carbon fibres. It was found that with PA imaging, the probe can provide a lateral resolution better than 25 µm and an axial resolution better than 100 µm at the optical focus. Co-registered PA and OCT images of blood vessels ex-vivo with stents and lipid injections were acquired. We conclude that PA imaging with OCT catheters is viable and that it has strong potential to guide clinical interventions.
Intravascular ultrasound (IVUS) imaging probes can be invaluable for guiding minimally invasive procedures such as coronary stent placement. With current IVUS catheters, ultrasound is generated and received electrically. With electronic transducer elements, it is challenging to achieve wide bandwidths, high sensitivity, and small dimensions suitable for intracoronary imaging. Here we present an all-optical ultrasound (OpUS) transducer, which uses light within fibre-optics to generate and receive ultrasound. These devices have several distinguishing advantages, including the potential to generate and receive wideband ultrasound (tens of MHz) required for high resolution imaging. The side-viewing OpUS transducer is highly miniaturised (< 1.5 mm diameter) with two optical fibres for transmission and reception, and a rotational mechanism for circumferential imaging. The transmitter is a composite of carbon nanotubes and PDMS coated on a multimode fibre tip. Ultrasound is generated within this coating by the photoacoustic effect. The receiver comprises a concave Fabry-Pérot cavity on a single mode fibre tip. Images acquired with the OpUS transducer were characterised using wire phantoms and post-mortem vascular tissue with stents. The axial resolution of this device was less than 70 microns, and the sensitivity was found to be sufficient to resolve pathological features. Subsequently, imaging was conducted in a healthy swine model in vivo and pulsatile motions of the artery were visualised with high fidelity. These studies show the strong potential for all-optical ultrasound to guide minimally invasive surgery.
Percutaneous coronary interventions are widely performed minimally invasive procedures used to treat narrowing (stenosis) of arteries in the heart. Differential blood pressure measurements across a stenosis are invaluable to estimate the prognostic benefit of performing angioplasty and stenting via calculation of the fractional flow reserve. Achieving stable measurements from within pressure microcatheters and guidewires that are compatible with stenosed vessels, and which can be fabricated with low cost manufacturing methods, remains an important challenge. We have developed all-optical pressure and temperature sensors with a single optical fibre and sensing element. This approach provides simultaneous temperature and pressure measurements in a highly miniaturised device, with a simple construction method using low cost materials. Polymeric structures including membranes and domes are applied to the distal ends of single mode optical fibres. Temperature and pressure changes induce time-varying displacements of these structures, which are monitored using phase-resolved low-coherence interferometry. Phase measurements are acquired at 250 Hz with a sensitivity of approximately 0.2 rad/°C for temperature measurements between 20 and 45°C, and approximately 0.08 rad/mmHg for pressure between 760 and 1060 mmHg. In vivo studies in arteries and hearts of sheep and swine indicate that the sensors have sufficient sensitivity and speed for measurement of physiological pressure waveforms in clinical settings. We will discuss the integration of these sensors within medical devices, and the potential for providing additional physiological parameters with the same devices.
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