All-optical ultrasound imaging, in which ultrasound is generated and received using light, is well-suited to minimally invasive surgical procedures. Here we present a device that can provide real-time M-mode ultrasound images, and demonstrate its use imaging a dynamic heart valve phantom. This device, comprising two optical fibres, one with a graphene-polydimethylsiloxane composite coating for ultrasound generation, and a second with a concave Fabry-Perot cavity for ultrasound reception, had a diameter of < 1 mm. This provided a wide ultrasound transmission bandwidth (> 30 MHz) that enabled imaging with high axial resolution (< 50 μm) and large imaging depths (> 2 cm). M-mode imaging with an A-line rate of 100 Hz was demonstrated on a heart valve phantom with realistic mitral valve motion. This work demonstrates the potential for all-optical ultrasound imaging to be used for guidance of intracardiac interventions.
Direct and continuous measurements of blood flow are of significant interest in many medical specialties. In cardiology, intravascular physiological measurements can be of critical importance to determine whether coronary stenting should be performed. Intravascular pressure is a physiological parameter that is frequently measured in clinical practice. An increasing body of evidence suggests that direct measurements of blood flow, as additional physiological parameters, could improve decision making. In this study, we developed a novel fibre optic intravascular flow sensor, which enabled time-of-flight measurements by upstream thermal tagging of blood. This flow sensor comprised a temperature sensitive polymer dome at the distal end of a single mode optical fibre. The dome was continuously interrogated by low coherence interferometry to measure thermally-induced length changes with nanometre-scale resolution. Flow measurements were performed by delivering heat upstream from the sensor with a separate optical fibre, and monitoring the temperature downstream at the dome with a sample rate of 50 Hz. A fabricated flow sensor was characterized and tested within a benchtop phantom, which comprised vessels with lumen diameters that ranged from 2.5 to 5 mm. Water was used as a blood mimicking fluid. For each vessel diameter, a pump provided constant volumetric flow at rates in the range of 5 to 200 ml/min. This range was chosen to represent flow rates encountered in healthy human vessels. Laser light pulses with a wavelength of 1470 nm and durations of 0.4 s were used to perform upstream thermal tagging. These pulses resulted in downstream temperature profiles that varied with the volumetric flow rate.
Radiofrequency ablation is widely used in cardiology as an effective minimally invasive treatment for atrial fibrillation. However, radiofrequency noise, electronic interference, low resolution and poor tissue contrast complicate real-time lesion monitoring using conventional imaging modalities such as magnetic resonance imaging or ultrasound imaging based on electronic transducers. Recently, a bench-top all-optical ultrasound imaging system, where ultrasound is both generated and detected using light, was presented (doi:10.1364/BOE.9.003481) that achieved high-resolution, video-rate 2D images. In this system, pulsed excitation light was focussed onto a nanocomposite membrane, where it was converted into ultrasound via the photoacoustic effect. Using scanning optics, the resulting optical ultrasound source was translated to synthesise a 1D source aperture comprising irregularly spaced ultrasound sources. Back-scattered ultrasound was detected using a single fibre-optic Fabry-Pérot cavity. Here, this system (which is inherently insensitive to electromagnetic interference) was used to achieve the first video-rate, depth-resolved 2D images acquired during RF ablation using an all-optical ultrasound imaging setup. We used this system to monitor the formation of radiofrequency ablation lesions (max 30 W, 65°C, 60 s) in ex vivo chicken breast samples, at a frame rate of 9 Hz, resolution of 100 µm, an imaging depth >15 mm, and a contrast of up to 30 dB. With its high miniaturisation potential, all-optical ultrasound imaging shows great promise for guiding interventional procedures, where real-time ablation lesion visualisation could improve lesion delivery and patient outcome.
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.
Small form-factor invasive pressure sensors are widely used in minimally invasive surgery, for example to guide decision making in coronary stenting procedures. Current fiber-optic sensors can have high manufacturing complexities and costs, which severely constrains their adoption outside of niche fields. A particular challenge is the ability to rapidly prototype and iterate upon sensor designs to optimize performance for different applications and medical devices. Here, we present a new sensor fabrication method, which involves two-photon polymerization printing and integration of the printed structure onto the end-face of a single-mode optical fiber. The active elements of the sensor were a pressure-sensitive diaphragm and an intermediate temperature-sensitive spacer that was insensitive to changes in external pressure. Deflection of the diaphragm and thermal expansion the spacer relative to the fiber end-face were monitored using phase-resolved low coherence interferometry. A pressure sensitivity of 0.031 rad/mmHg across the range of 760 to 1060 mmHg (absolute pressure), and a temperature sensitivity of 1.2 mrad/°C across the range 20 to 45°C were observed. This method will enable the fabrication of a wide range of fiber-optic sensors with pressure and temperature sensitivities suitable for guiding minimally invasive surgery.
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.
Phantoms are crucial for developing photoacoustic imaging systems and for training practitioners. Advances in 3D printing technology have allowed for the generation of detailed moulds for tissue-mimicking materials that represent anatomically realistic tissue structures such as blood vessels. Here, we present methods to generate phantoms for photoacoustic and ultrasound imaging based on patient-specific anatomy and mineral oil based compounds as tissue-mimicking materials. Moulds were created using a 3D printer with fused deposition modelling. Optical and acoustic properties were independently tuned to match different soft tissue types using additives: inorganic dyes for optical absorption, TiO2 particles for optical scattering, paraffin wax for acoustic attenuation, and solid glass spheres for acoustic backscattering. Melted mineral oil compounds with additives were poured into the 3D printed moulds to fabricate different anatomical structures. Optical absorption and reduced scattering coefficients across the wavelength range of 400 to 1600 nm were measured using a spectrophotometer with an integrating sphere, and inverse adding-doubling. The acoustic attenuation and speed-of-sound were measured in reflection mode using a 10 MHz transducer. Three phantoms were created to represent nerves and adjacent blood vessels, a human placenta obtained after caesarean section, and a human heart based on an MRI image volume. Co-registered multi-wavelength photoacoustic and ultrasound images were acquired with a system that comprised a clinical ultrasound imaging scanner, an optical parametric oscillator, and linear-array ultrasound imaging probes. We conclude that mineral oil based compounds can be well suited to create anatomically-realistic phantoms for photoacoustic and ultrasound imaging using 3D printed moulds.
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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