Miniaturised high-resolution imaging devices are valuable for guiding minimally invasive procedures such as vascular stent placements. Here, we present all-optical rotational B-mode pulse-echo ultrasound imaging. With this device, ultrasound transmission and reception are performed with light. The all-optical transducer in the probe comprised an optical fibre that delivered pulsed excitation light to an optical head at the distal end with a multi-walled carbon nanotube and polydimethylsiloxane composite coating. This coating was photoacoustically excited to generate a highly directional ultrasound beam perpendicular to the optical fibre axis. A concave Fabry-Pérot cavity at the distal end of an optical fibre, which was interrogated with a tuneable continuous-wave laser, served as an omnidirectional ultrasound receiver. The transmitted ultrasound had a −6 dB bandwidth of 31.3 MHz and a peak-to-peak pressure of 1.87 MPa, as measured at 1.5 mm from the probe. The receiver had a noise equivalent pressure <100 Pa over a 20 MHz bandwidth. With a maximum outer probe diameter of 1.25 mm, the probe provided imaging with an axial resolution better than 50 µm, and a real-time imaging rate of 5 frames per second. To investigate the capabilities of the probe, intraluminal imaging was performed in healthy swine carotid arteries. The results demonstrate that the all-optical probe is viable for clinical rotational ultrasound imaging.
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 mu m), 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-mu m 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. (c) The Authors. Published by SPIE under a Creative Commons Attribution 4.0 Unported License.
We report the development and characterisation of highly miniaturised fibre-optic sensors for simultaneous pressure and temperature measurement, and a compact interrogation system with a high sampling rate. The sensors, which have a maximum diameter of 250 µm, are based on multiple low-finesse optical cavities formed from polydimethylsiloxane (PDMS), positioned at the distal ends of optical fibres, and interrogated using phase-resolved low-coherence interferometry. At acquisition rates of 250 Hz, temperature and pressure changes of 0.0021 °C and 0.22 mmHg are detectable. An in vivo experiment demonstrated that the sensors had sufficient speed and sensitivity for monitoring dynamic physiological pressure waveforms. These sensors are ideally suited to various applications in minimally invasive surgery, where diminutive lateral dimensions, high sensitivity and low manufacturing complexities are particularly valuable.
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.
Intravascular imaging in percutaneous coronary interventions can be an invaluable tool in the treatment of coronary artery disease. It is of significant interest to provide molecular imaging contrast that is complementary to structural contrast provided by optical coherence tomography (OCT) and intravascular ultrasound imaging (IVUS). In this study, we developed a dual-modality intravascular imaging probe comprising a commercial OCT catheter and a high sensitivity fiber optic ultrasound sensor, to provide both photoacoustic (PA) and OCT imaging. With PA imaging, the lateral resolution varied from 18 μm to 40 μm; the axial resolution was consistently in the vicinity of 45 μm. We demonstrated the clinical potential of the probe with 2-D circumferential PA and OCT imaging, and with multispectral PA imaging.
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.
Our current understanding of the pathophysiology of pulmonary vascular disease is incomplete, since information about alterations of the pulmonary vasculature in pulmonary arterial hypertension (PAH) is primarily provided by autopsy or tissue specimens. The aim of this study was to compare the distal pulmonary vasculature of <2 mm in diameter in Systemic Sclerosis (SSc) patients with (n = 17) and without (n = 5) associated PAH using Optical Coherence Tomography during Right Heart catheterization. SSc-PAH patients showed significant thickening of Intima Media Thickening Area compared to patients without PAH (27 +/− 5.8% vs. 21 +/− 1.4%, p = 0.024). A good haemodynamic response to previous targeted PAH treatment was associated with a significantly greater number of small pulmonary artery side branches <300 μm per cm vessel (3.8 +/− 1.1 vs. 1.8 +/− 1.1; p = 0.010) and not associated with Intima Media thickening Area (26 +/− 5.4% vs. 28 +/− 6.7%; p = 0.6). Unexpected evidence of pulmonary artery thrombus formation was found in 19% of SSc-PAH patients. This is the first in-vivo study demonstrating a direct link between a structural abnormality of pulmonary arteries and a response to targeted treatment in PAH. Intravascular imaging may identify subgroups that may benefit from anticoagulation.
Aims To compare optical coherence tomography (OCT)-derived plaque characteristics of the culprit and non-culprit coronary arteries in patients with Non ST elevation myocardial infarction (NSTEMI) and stable angina pectoris (SA). Methods Assessment of clinical data, angiographic, and OCT imaging including the analysis of plaques was performed. Plaque composition, thickness, arc, length, volume and relative volume were recorded. The presence of thrombus, microvessels, macrophages, cholesterol crystals and calcific nodules were recorded (in percentage of frames) as well. Results To date, 12 patients (8 NSTEMI and 4 SA) were included and analysed. Mean age of this predominantly male group was 55.36 ± 7.9 years. In total OCT was performed in 31 coronary arteries (12 culprit and 19 non culprit) - corresponding to a total of 1992 frames were analysed. Artery level analysis revealed a higher lipid content in culprit arteries as documented by a wider maximum lipid arc (221.91 ± 87.5 vs. 139.2 ± 42.0; p = 0.009) and higher relative lipid volume index (6.35 ± 4.8 vs. 3.3 ± 2.8; p = 0.08). Furthermore, in culprit arteries average cap thickness was smaller (340μ±41μ vs. 400μ±81μ; p = 0.03), and the incidence of macrophages was higher (% of frames 7.8 ± 6.2 vs. 3.2 ± 4.6; p = 0.02). Conclusions In this three-vessel OCT study culprit arteries in both NSTEMI and SA were noted to have more vulnerable features than non-culprit arteries however, larger studies are required to establish this finding.