n this study we report the integration of an all-optical ultrasound probe and robotic manipulator. The alloptical ultrasound probe comprised two optical fibres, a MWCNT/PDMS composite coated multimode fibre for ultrasound generation, and a concave Fabry-Perot fibre optic hydrophone for ultrasound reception. The ultrasound probe generated pressures in excess of 2 MPa at 1:5 mm, with a corresponding -6 dB bandwidth of ca. 30 MHz. The probe was built into a rigid endoscope (outer diameter: 5 mm, length: 300 mm) and mounted on a robotic manipulator. Ultrasound A-lines were acquired during robot manipulation in order to reconstruct a 3D image which was displayed as a point cloud. Large area images (80 × 80 mm) of a tissue mimicking gel wax phantom where acquired and displayed in real-time. This work demonstrates the potential for integrating miniature fibre optic ultrasound devices with robotics.
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.
All-optical ultrasound imaging uses optical generation and detection of ultrasound to acquire pulse-echo images. Recent advances have resulted in efficient optical ultrasound sources, emitting pressures and bandwidths rivalling those generated by conventional electronic transducers. Two-dimensional imaging of biological tissues was achieved using a fibre-optic Fabry-Pérot cavity and a nanocomposite generator membrane in which ultrasound was generated photoacoustically. Using scanning mirrors, excitation light was steered to consecutive locations, thus synthesising an acoustic source aperture with a geometry that could be arbitrarily and dynamically reconfigured. This unique capability of implementing different geometries on the same hardware allows for a direct comparison of the image quality obtained with different aperture geometries, which is difficult to achieve using conventional electronic transducers. Here we explore how the source aperture geometry affects the image quality through a set of numerical simulations and experiments. First, we determined that the image artefacts and corresponding contrast level depend strongly on the total number of A-scans (increasing from 200 to 1800 A-scans improved the contrast from 30 to 50 dB), irrespective of the number and locations of the detectors. Second, we demonstrated how parametric optimisation of the spatial optical ultrasound source distribution allowed for local (within a user-defined region of interest) or global image optimisation achieving an additional reduction in artefact level of up to 8 dB. Finally, we demonstrated video-rate, real-time 2D image acquisition using optimised source aperture geometries.
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.
Although molecularly targeted cancer therapies have shown great promise, it is now evident that responses are dependent upon the molecular genetic context. Spatial and temporal tumour heterogeneity renders biopsy of solid tumours unsuitable for determining the genetic profile of the disease, making adaptation of appropriate therapy difficult. We have utilized the tunable optical absorption characteristic of gold nanorods to assess the potential of photoacoustics for non-invasive multiplexed molecular imaging. Gold nanorods with resonance peaks at 700nm and 900nm were functionalised with in-house antibodies ICR55 and ICR62, targeted to HER2 and EGFR transmembrane receptors, respectively. Three human squamous carcinoma cell lines (LICR-LON-HN4 expressing high HER2 and low EGFR, LICR-LON-HN3 expressing intermediate levels of HER2 and EGFR and A431 expressing high EGFR and low HER2) were incubated with the targeted nanorods for 24 hours. Cells were then incorporated as simulated tumours in tissue-like phantoms composed of 7.5% gelatin containing 0.5% Intralipid® for optical scattering and imaged at a depth of 2.5 cm, using a new clinical in-house multi-spectral photoacoustic imaging system. Images were obtained from the cell inclusions for wavelengths ranging from 710 to 950 nm at 40 nm intervals, and the mean amplitude of the photoacoustic image was computed for each wavelength, to determine their relative receptor expression levels. The molecular profile of the cells obtained using multi-wavelength photoacoustics had substantial similarity to that obtained using flow cytometry. These preliminary results confirm selective uptake of the functionalised nanorods, which reflects the cellular expression of therapeutically important oncoproteins, and give an indication of the potential of photoacoustics for multiplexed molecular profiling.
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