Miniaturised dual-modality all-optical Laser Interstitial Thermal Therapy (LITT) and ultrasound imaging

Introduction: Laser Interstitial Thermal Therapy (LITT) is a minimally invasive procedure to treat kidney tumours that can be hard to reach with open surgery, with low risks and fast recovery time. This treatment requires robust real-time imaging modalities to track tumour treatment outcomes and avoid damage of healthy tissue during the procedure. All-optical ultrasound (OpUS) is an emerging imaging paradigm that exhibits high imaging resolution, ease of miniaturisation and immunity to electromagnetic interference [1]. With OpUS, the ultrasound wave is generated via photoacoustic effect, with pulsed excitation light delivered to an optically absorbing coating on the end of an optical fibre and received using a plano-concave microresonator on an optical fibre end face. The use of optical fibres allows laser ablation and OpUS imaging to be integrated into a miniaturised device, suitable for the real-time monitoring of tissue damage during LITT procedures. In this work, we developed an optical-fibre-based miniaturised device that combines LITT and OpUS imaging. To assess the capability, the device was used to perform LITT with in situ OpUS lesion imaging on an ex vivo lamb kidney. / Methods: The OpUS device comprised three optical fibres; a multimode optical fibre (200 µm core) coated with Candle soot nanoparticles (CSNPs)-polydimethylsiloxane (PDMS) composite for ultrasound transmission, an single mode optical fibre with a plano-concave microresonator for ultrasound reception and a multimode optical fibre (400 µm core) for delivery of laser ablation light. The distal end face of the ultrasound transmitter and receiver were aligned at their distal tips, whilst the ablation fibre was advanced 10 mm, allowing for the insertion into kidney tissue. Prior to carrying out LITT, a B-mode OpUS image of the kidney tissue was acquired. For LITT experiments, the ablation fibre was inserted into the ex vivo kidney tissue and laser treatment was applied (808 nm, 3.0 W, 60 s) whilst performing concurrent M-mode imaging with the OpUS probe to track the lesion formation. / Results & Discussion: B-mode OpUS imaging provided an imaging depth > 15 mm and high imaging resolution that delineated the structure boundaries inside the kidney (Fig 1. a). M-mode OpUS imaging allowed visualisation of the tissue throughout the procedure. When the ablation laser was switched on the tissue contrast changed immediately, indicating the formation of an ablated lesion (Fig 1. b). Throughout the ablation period, the lesion grew bidirectional from the optical fibre tip in the vertical dimension, which was visible on the M-mode image as increasing brightness and changing contrast. This work demonstrated the feasibility of OpUS imaging to monitor the lesion growth during LITT

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

Enhanced Photoacoustic Visualisation of Clinical Needles by Combining Interstitial and Extracorporeal Illumination of Elastomeric Nanocomposite Coatings

Ultrasound (US) image guidance is widely used for minimally invasive procedures, but the invasive medical devices (such as metallic needles), especially their tips, can be poorly visualised in US images, leading to significant complications. Photoacoustic (PA) imaging is promising for visualising invasive devices and peripheral tissue targets. Light-emitting diodes (LEDs) acting as PA excitation sources facilitate the clinical translation of PA imaging, but the image quality is degraded due to the low pulse energy leading to insufficient contrast with needles at deep locations. In this paper, photoacoustic visualisation of clinical needles was enhanced by elastomeric nanocomposite coatings with superficial and interstitial illumination. Candle soot nanoparticle-polydimethylsiloxane (CSNP-PDMS) composites with high optical absorption and large thermal expansion coefficients were applied onto the needle exterior and the end-face of an optical fibre placed in the needle lumen. The excitation light was delivered at the surface by LED arrays and through the embedded optical fibre by a pulsed diode laser to improve the visibility of the needle tip. The performance was validated using an ex-vivo tissue model. An LED-based PA/US imaging system was used for imaging the needle out-of-plane and in-plane insertions over approach angles of 20 deg to 55 deg. The CSNP-PDMS composite conferred substantial visual enhancements on both the needle shaft and the tip, with an average of 1.7- and 1.6-fold improvements in signal-to-noise ratios (SNRs), respectively. With the extended light field involving extracorporeal and interstitial illumination and the highly absorbing coatings, enhanced visualisation of the needle shaft and needle tip was achieved with PA imaging, which could be helpful in current US-guided minimally invasive surgeries

Comparison of Fabrication Methods for Fiber‐Optic Ultrasound Transmitters Using Candle‐Soot Nanoparticles

Candle-soot nanoparticles (CSNPs) have shown great promise for fabricating optical ultrasound (OpUS) transmitters. They have a facile, inexpensive synthesis whilst their unique, porous structure enables a fast heat diffusion rate which aids high-frequency ultrasound generation necessary for high-resolution clinical imaging. These composites have demonstrated high ultrasound generation performance showing clinically relevant detail, when applied as macroscale OpUS transmitters comprising both concave and planar surfaces, however, less research has been invested into the translation of this material's technology to fabricate fiber-optic transmitters for image guidance of minimally invasive interventions. Here, are reported two fabrication methods of nanocomposites composed of CSNPs embedded within polydimethylsiloxane (PDMS) deposited onto fiber-optic end-faces using two different optimized fabrication methods: “All-in-One” and “Direct Deposition.” Both types of nanocomposite exhibit a smooth, black domed structure with a maximum dome thickness of 50 µm, broadband optical absorption (>98% between 500 and 1400 nm) and both nanocomposites generated high peak-to-peak ultrasound pressures (>3 MPa) and wide bandwidths (>29 MHz). Further, high-resolution (<40 µm axial resolution) B-mode ultrasound imaging of ex vivo lamb brain tissue demonstrating how CSNP-PDMS OpUS transmitters can allow for high fidelity minimally invasive imaging of biological tissues is demonstrated

Fabrication of Composite Materials for Medical Imaging and Device Characterisation

This thesis describes the investigation of composite materials to design and fabricate imaging devices and their subsequent characterisation, in the context of image guidance for minimally invasive surgical interventions. Medical ultrasound is a widely used imaging modality that utilises high frequency sound waves to map a tissue’s shape and size. Optical ultrasound (OpUS) generation enables miniaturised ultrasound transmitters to be formed using facile syntheses, demonstrating high-resolution ultrasound imaging. First, fibre-optic OpUS transmitters capable of dual-modality ultrasound/photoacoustic imaging as integrated imaging probes are presented. The OpUS transmitters were formed from bilayer wavelength-selective quantum dot composites. Combined with a Fabry-Pérot hydrophone, these composites illustrated high-resolution overlaid ultrasound/photoacoustic images of a gel wax phantom. Two composite materials were then designed and synthesised to produce aorta and femoral artery phantoms, suitable for characterisation using particle image velocimetry and ultrasound imaging, respectively, with composites' Young Modulus and refractive indices characterised. Quantum dot composites were also deployed onto planar macroscale substrates using doctor-blading and spin-coating deposition techniques. These composites yielded clinically useful ultrasound pressures and bandwidths equivalent to those used in diagnostic ultrasound imaging. Fibre-optic OpUS transmitters comprising broadband optically absorbing candle-soot composites were fabricated. These composites performed high-resolution ultrasound imaging of lamb brain tissue. A fibre-optic OpUS transmitter was integrated into a candle-soot-coated needle. Visual enhancements of the needle shaft and tip were observed during in and out-of-plane needle insertions into ex vivo animal tissue. The work presented here, through interdisciplinary research, illustrates facile fabrication strategies for composite materials deposited onto miniaturised fibre-optic and macroscale substrates, that could easily be translated into clinical settings in the near future. These devices facilitate both high-resolution single and multi-modality imaging, and augmented imaging resolutions of surgical instruments. Further, synthesising patient-specific phantoms with material properties functionalised for specific imaging modalities illustrates the potential comprehensive characterisation of these imaging devices

Thermal Modelling of Fibre-Optic Laser Generated Ultrasound Transmitters - Data.zip

Optical generation of ultrasound has broad applicability in diagnostic and therapeutic clinical applications. With fibre-optic ultrasound transmitters, ultrasound waves are generated photoacoustically by laser pulses incident on an optically-absorbing coating at the distal end of an optical fibre. Energy from the laser pulses that is not converted to ultrasound raises the temperature of the transmitter coating and surrounding medium. Limiting the maximum temperature is important for tissue safety and the integrity of the transmitter. In this study, we used a finite element thermal model of a fibre-optic ultrasound transmitter to study the influence of three parameters on the temperature rises in the transmitter and the surrounding medium: the laser pulse energy, the laser pulse repetition frequency, and the coating absorption coefficient. To evaluate the validity of the model, the simulation results were compared with thermal imaging experiments of a carbon-polydimethylsiloxane composite-based fibre-optic ultrasound transmitter. Of the studied parameters, the pulse repetition frequency (PRF) has the greatest impact on the temperature rise in the surrounding medium, with a six-fold rise in temperature change resulting from an increase in PRF from 100 Hz to 1 kHz. Our findings have direct applicability to optimising the performance of fibre optic transmitters.</p

Comparison of Fabrication Methods for Fiber‐Optic Ultrasound Transmitters Using Candle‐Soot Nanoparticles

Abstract Candle‐soot nanoparticles (CSNPs) have shown great promise for fabricating optical ultrasound (OpUS) transmitters. They have a facile, inexpensive synthesis whilst their unique, porous structure enables a fast heat diffusion rate which aids high‐frequency ultrasound generation necessary for high‐resolution clinical imaging. These composites have demonstrated high ultrasound generation performance showing clinically relevant detail, when applied as macroscale OpUS transmitters comprising both concave and planar surfaces, however, less research has been invested into the translation of this material's technology to fabricate fiber‐optic transmitters for image guidance of minimally invasive interventions. Here, are reported two fabrication methods of nanocomposites composed of CSNPs embedded within polydimethylsiloxane (PDMS) deposited onto fiber‐optic end‐faces using two different optimized fabrication methods: “All‐in‐One” and “Direct Deposition.” Both types of nanocomposite exhibit a smooth, black domed structure with a maximum dome thickness of 50 µm, broadband optical absorption (>98% between 500 and 1400 nm) and both nanocomposites generated high peak‐to‐peak ultrasound pressures (>3 MPa) and wide bandwidths (>29 MHz). Further, high‐resolution (<40 µm axial resolution) B‐mode ultrasound imaging of ex vivo lamb brain tissue demonstrating how CSNP‐PDMS OpUS transmitters can allow for high fidelity minimally invasive imaging of biological tissues is demonstrated