All-optical ultrasound catheter for rapid B-mode oesophageal imaging.

All-optical ultrasound (OpUS) is an imaging paradigm that uses light to both generate and receive ultrasound, and has progressed from benchtop to in vivo studies in recent years, demonstrating promise for minimally invasive surgical applications. In this work, we present a rapid pullback imaging catheter for side-viewing B-mode ultrasound imaging within the upper gastrointestinal tract. The device comprised an ultrasound transmitter configured to generate ultrasound laterally from the catheter and a plano-concave microresonator for ultrasound reception. This imaging probe was capable of generating ultrasound pressures in excess of 1 MPa with corresponding -6 dB bandwidths > 20 MHz. This enabled imaging resolutions as low as 45 µm and 120 µm in the axial and lateral extent respectively, with a corresponding signal-to-noise ratio (SNR) of 42 dB. To demonstrate the potential of the device for clinical imaging, an ex vivo swine oesophagus was imaged using the working channel of a mock endoscope for device delivery. The full thickness of the oesophagus was resolved and several tissue layers were present in the resulting ultrasound images. This work demonstrates the promise for OpUS to provide rapid diagnostics and guidance alongside conventional endoscopy.

Miniaturised dual-modality all-optical ultrasound probe for laser interstitial thermal therapy (LITT) monitoring.

All-optical ultrasound (OpUS) has emerged as an imaging paradigm well-suited to minimally invasive imaging due to its ability to provide high resolution imaging from miniaturised fibre optic devices. Here, we report a fibre optic device capable of concurrent laser interstitial thermal therapy (LITT) and real-time in situ all-optical ultrasound imaging for lesion monitoring. The device comprised three optical fibres: one each for ultrasound transmission, reception and thermal therapy light delivery. This device had a total lateral dimension of <1 mm and was integrated into a medical needle. Simultaneous LITT and monitoring were performed on ex vivo lamb kidney with lesion depth tracked using M-mode OpUS imaging. Using one set of laser energy parameters for LITT (5 W, 60 s), the lesion depth varied from 3.3 mm to 8.3 mm. In all cases, the full lesion depth could be visualised and measured with the OpUS images and there was a good statistical agreement with stereomicroscope images acquired after ablation (t=1.36, p=0.18). This work demonstrates the feasibility and potential of OpUS to guide LITT in tumour resection.

High-resolution sub-millimetre diameter side-viewing all-optical ultrasound transducer based on a single dual-clad optical fibre.

All-optical ultrasound (OpUS), where ultrasound is both generated and received using light, has emerged as a modality well-suited to highly miniaturised applications. In this work we present a proof-of-concept OpUS transducer built onto a single optical fibre with a highly miniaturised lateral dimension (<0.8 mm). A key innovation was to use a dual-clad optical fibre (DCF) to provide multimode light for ultrasound generation and single mode light for ultrasound reception. The transducer comprised a proximal section of DCF spliced to a short section of single mode fibre (SMF). Multimode light was outcoupled at the splice joint and guided within a square capillary to provide excitation for ultrasound generation. Whilst single mode light was guided to the distal tip of the SMF to a plano-concave microresonator for ultrasound reception. The device was capable of generating ultrasound with pressures >0.4 MPa and a corresponding bandwidth >27 MHz. Concurrent ultrasound generation and reception from the transducer enabled imaging via motorised pull-back allowing image acquisition times of 4 s for an aperture of 20 mm. Image resolution was as low as ~50 µm and 190 µm in the axial and lateral extents, respectively, without the need for image reconstruction. Porcine aorta was imaged ex vivo demonstrating detailed ultrasound images. The unprecedented level of miniaturisation along with the high image quality produced by this device represents a radical new paradigm for minimally invasive imaging.

PDMS composites with photostable NIR dyes for multi-modal ultrasound imaging.

Abstract: All-optical ultrasound (OpUS) imaging has emerged as an imaging paradigm well-suited for minimally invasive surgical procedures. With this modality, ultrasound is generated when pulsed or modulated light is absorbed within a coating material. By engineering wavelength-selective coatings, complementary imaging and therapeutic modalities can be integrated with OpUS. Here, we present a wavelength-selective composite material comprising a near-infrared absorbing dye and polydimethylsiloxane. The optical absorption for this material peaked in the vicinity of 1064 nm, with up to 91% of incident light being absorbed, whilst maintaining lower optical absorption at other wavelengths. This material was used to generate ultrasound, demonstrating ultrasound pressures > 1  MPa, consistent with those used for imaging applications. Crucially, long exposure photostability and device performance were found to be stable over a one hour period (peak pressure variation < 10 %), longer than required for standard clinical imaging applications.

Dual-modality fibre optic probe for simultaneous ablation and ultrasound imaging.

All-optical ultrasound (OpUS) is an emerging high resolution imaging paradigm utilising optical fibres. This allows both therapeutic and imaging modalities to be integrated into devices with dimensions small enough for minimally invasive surgical applications. Here we report a dual-modality fibre optic probe that synchronously performs laser ablation and real-time all-optical ultrasound imaging for ablation monitoring. The device comprises three optical fibres: one each for transmission and reception of ultrasound, and one for the delivery of laser light for ablation. The total device diameter is < 1 mm. Ablation monitoring was carried out on porcine liver and heart tissue ex vivo with ablation depth tracked using all-optical M-mode ultrasound imaging and lesion boundary identification using a segmentation algorithm. Ablation depths up to 2.1 mm were visualised with a good correspondence between the ultrasound depth measurements and visual inspection of the lesions using stereomicroscopy. This work demonstrates the potential for OpUS probes to guide minimally invasive ablation procedures in real time.

CuInS2 Quantum Dot and Polydimethylsiloxane Nanocomposites for All-Optical Ultrasound and Photoacoustic Imaging.

Dual-modality imaging employing complementary modalities, such as all-optical ultrasound and photoacoustic imaging, is emerging as a well-suited technique for guiding minimally invasive surgical procedures. Quantum dots are a promising material for use in these dual-modality imaging devices as they can provide wavelength-selective optical absorption. The first quantum dot nanocomposite engineered for co-registered laser-generated ultrasound and photoacoustic imaging is presented. The nanocomposites developed, comprising CuInS2 quantum dots and medical-grade polydimethylsiloxane (CIS-PDMS), are applied onto the distal ends of miniature optical fibers. The films exhibit wavelength-selective optical properties, with high optical absorption (> 90%) at 532 nm for ultrasound generation, and low optical absorption (< 5%) at near-infrared wavelengths greater than 700 nm. Under pulsed laser irradiation, the CIS-PDMS films generate ultrasound with pressures exceeding 3.5 MPa, with a corresponding bandwidth of 18 MHz. An ultrasound transducer is fabricated by pairing the coated optical fiber with a Fabry-Pérot (FP) fiber optic sensor. The wavelength-selective nature of the film is exploited to enable co-registered all-optical ultrasound and photoacoustic imaging of an ink-filled tube phantom. This work demonstrates the potential for quantum dots as wavelength-selective absorbers for all-optical ultrasound generation.

Flexible and directional fibre optic ultrasound transmitters using photostable dyes.

All-optical ultrasound transducers are well-suited for use in imaging during minimally invasive surgical procedures. This requires highly miniaturised and flexible devices. Here we present optical ultrasound transmitters for imaging applications based on modified optical fibre distal tips which allow for larger transmitter element sizes, whilst maintaining small diameter proximal optical fibre. Three optical ultrasound transmitter configurations were compared; a 400 µm core optical fibre, a 200 µm core optical fibre with a 400 µm core optical fibre distal tip, and a 200 µm core optical fibre with a 400 µm core capillary distal tip. All the transmitters used a polydimethylsiloxane-dye composite material for ultrasound generation. The material comprised a photostable infra-red absorbing dye to provide optical absorption for the ultrasound transduction. The generated ultrasound beam profile for the three transmitters was compared, demonstrating similar results, with lateral beam widths <1.7 mm at a depth of 10 mm. The composite material demonstrates a promising alternative to previously reported materials, generating ultrasound pressures exceeding 2 MPa, with corresponding bandwidths ca. 30 MHz. These highly flexible ultrasound transmitters can be readily incorporated into medical devices with small lateral dimensions.

Optically Generated Ultrasound for Intracoronary Imaging.

Conventional intravascular ultrasound (IVUS) devices use piezoelectric transducers to electrically generate and receive US. With this paradigm, there are numerous challenges that restrict improvements in image quality. First, with miniaturization of the transducers to reduce device size, it can be challenging to achieve the sensitivities and bandwidths required for large tissue penetration depths and high spatial resolution. Second, complexities associated with manufacturing miniaturized electronic transducers can have significant cost implications. Third, with increasing interest in molecular characterization of tissue in-vivo, it has been challenging to incorporate optical elements for multimodality imaging with photoacoustics (PA) or near-infrared spectroscopy (NIRS) whilst maintaining the lateral dimensions suitable for intracoronary imaging. Optical Ultrasound (OpUS) is a new paradigm for intracoronary imaging. US is generated at the surface of a fiber optic transducer via the photoacoustic effect. Pulsed or modulated light is absorbed in an engineered coating on the fiber surface and converted to thermal energy. The subsequent temperature rise leads to a pressure rise within the coating, which results in a propagating ultrasound wave. US reflections from imaged structures are received with optical interferometry. With OpUS, high bandwidths (31.5 MHz) and pressures (21.5 MPa) have enabled imaging with axial resolutions better than 50 µm and at depths >20 mm. These values challenge those of conventional 40 MHz IVUS technology and show great potential for future clinical application. Recently developed nanocomposite coating materials, that are highly transmissive at light wavelengths used for PA and NIRS light, can facilitate multimodality imaging, thereby enabling molecular characterization.

All-Optical Rotational Ultrasound Imaging.

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.

Micron resolution, high-fidelity three-dimensional vascular optical imaging 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.

Optical fiber ultrasound transmitter with electrospun carbon nanotube-polymer composite.

All-optical ultrasound transducers are promising for imaging applications in minimally invasive surgery. In these devices, ultrasound is transmitted and received through laser modulation, and they can be readily miniaturized using optical fibers for light delivery. Here, we report optical ultrasound transmitters fabricated by electrospinning an absorbing polymer composite directly onto the end-face of optical fibers. The composite coating consisting of an aqueous dispersion of multi-walled carbon nanotubes (MWCNTs) in polyvinyl alcohol was directly electrospun onto the cleaved surface of a multimode optical fiber and subsequently dip-coated with polydimethylsiloxane (PDMS). This formed a uniform nanofibrous absorbing mesh over the optical fiber end-face wherein the constituent MWCNTs were aligned preferentially along individual nanofibers. Infiltration of the PDMS through this nanofibrous mesh onto the underlying substrate was observed and the resulting composites exhibited high optical absorption (>97%). Thickness control from 2.3 µm to 41.4 µm was obtained by varying the electrospinning time. Under laser excitation with 11 µJ pulse energy, ultrasound pressures of 1.59 MPa were achieved at 1.5 mm from the coatings. On comparing the electrospun ultrasound transmitters with a dip-coated reference fabricated using the same constituent materials and possessing identical optical absorption, a five-fold increase in the generated pressure and wider bandwidth was observed. The electrospun transmitters exhibited high optical absorption, good elastomer infiltration, and ultrasound generation capability in the range of pressures used for clinical pulse-echo imaging. All-optical ultrasound probes with such transmitters fabricated by electrospinning could be well-suited for incorporation into catheters and needles for diagnostics and therapeutic applications.

Through-needle all-optical ultrasound imaging in vivo: a preclinical swine study.

High-frequency ultrasound imaging can provide exquisite visualizations of tissue to guide minimally invasive procedures. Here, we demonstrate that an all-optical ultrasound transducer, through which light guided by optical fibers is used to generate and receive ultrasound, is suitable for real-time invasive medical imaging in vivo. Broad-bandwidth ultrasound generation was achieved through the photoacoustic excitation of a multiwalled carbon nanotube-polydimethylsiloxane composite coating on the distal end of a 300-µm multi-mode optical fiber by a pulsed laser. The interrogation of a high-finesse Fabry-Pérot cavity on a single-mode optical fiber by a wavelength-tunable continuous-wave laser was applied for ultrasound reception. This transducer was integrated within a custom inner transseptal needle (diameter 1.08 mm; length 78 cm) that included a metallic septum to acoustically isolate the two optical fibers. The use of this needle within the beating heart of a pig provided unprecedented real-time views (50 Hz scan rate) of cardiac tissue (depth: 2.5 cm; axial resolution: 64 µm) and revealed the critical anatomical structures required to safely perform a transseptal crossing: the right and left atrial walls, the right atrial appendage, and the limbus fossae ovalis. This new paradigm will allow ultrasound imaging to be integrated into a broad range of minimally invasive devices in different clinical contexts.

Adaptive Light Modulation for Improved Resolution and Efficiency in All-Optical Pulse-Echo Ultrasound.

In biomedical all-optical pulse-echo ultrasound systems, ultrasound is generated with the photoacoustic effect by illuminating an optically absorbing structure with a temporally modulated light source. Nanosecond range laser pulses are typically used, which can yield bandwidths exceeding 100 MHz. However, acoustical attenuation within tissue or nonuniformities in the detector or source power spectra result in energy loss at the affected frequencies and in a reduced overall system efficiency. In this work, a laser diode is used to generate linear and nonlinear chirp optical modulations that are extended to microsecond time scales, with bandwidths constrained to the system sensitivity. Compared to those obtained using a 2-ns pulsed laser, pulse-echo images of a phantom obtained using linear chirp excitation exhibit similar axial resolution (99 versus 92 µm, respectively) and signal-to-noise ratios (SNRs) (10.3 versus 9.6 dB). In addition, the axial point spread function (PSF) exhibits lower sidelobe levels in the case of chirp modulation. Using nonlinear (time-stretched) chirp excitations, where the nonlinearity is computed from measurements of the spectral sensitivity of the system, the power spectrum of the imaging system was flattened and its bandwidth broadened. Consequently, the PSF has a narrower axial extent and still lower sidelobe levels. Pulse-echo images acquired with time-stretched chirps as optical modulation have higher axial resolution (64 µm) than those obtained with linear chirps, at the expense of a lower SNR (6.8 dB). Using a linear or time-stretched chirp, the conversion efficiency from optical power to acoustical pressure improved by a factor of 70 or 61, respectively, compared to that obtained with pulsed excitation.

Broadband miniature optical ultrasound probe for high resolution vascular tissue imaging.

An all-optical ultrasound probe for vascular tissue imaging was developed. Ultrasound was generated by pulsed laser illumination of a functionalized carbon nanotube composite coating on the end face of an optical fiber. Ultrasound was detected with a Fabry-Pérot (FP) cavity on the end face of an adjacent optical fiber. The probe diameter was < 0.84 mm and had an ultrasound bandwidth of ~20 MHz. The probe was translated across the tissue sample to create a virtual linear array of ultrasound transmit/receive elements. At a depth of 3.5 mm, the axial resolution was 64 µm and the lateral resolution was 88 µm, as measured with a carbon fiber target. Vascular tissues from swine were imaged ex vivo and good correspondence to histology was observed.