All-optical ultrasound imaging has emerged as paradigm that is well-suited to highly miniaturized applications. With this technique, ultrasound is both generated and received using light, allowing the use of optical fibres for device fabrication. Ultrasound generation typically requires multimode light delivery to provide the pulse energies needed for high pressure generation. Whilst ultrasound reception typically requires single mode light delivery to provide high sensitivity. This means that devices have typically comprised two optical fibres, one multimode for ultrasound generation and one single mode for ultrasound reception. Recently, we demonstrated an all-optical ultrasound imaging device based on a single dual-clad optical fibre. In this work, we build on our previous study and demonstrate rotational imaging with this device. Two copper wire phantoms were imaged, and the wire were well-resolved, demonstrating a signal-to-noise >20 dB. The presented device and system are well-suited for use in minimally invasive and intravascular imaging applications and future work will focus on translating the device.
All-Optical Ultrasound (OpUS) has emerged as an imaging paradigm well-suited for minimally invasive procedures. In particular, OpUS has demonstrated potential in endovascular imaging due to its high degree of miniaturization and mechanical flexibility, high imaging resolution and immunity to electromagnetic interference. Here, we present the first human thrombus imaging using an OpUS device, which was performed on an extracted clot. The results demonstrate the feasibility of using OpUS for thrombus imaging, with the ultimate goal of guiding minimally invasive endovascular clot retrieval procedures.
Ultrasound (US) imaging is commonly used to guide minimally invasive surgeries but has poor contrast of the invasive devices such as clinical needles. Photoacoustic (PA) imaging promises to be efficient for visualising needles. Elastomeric coatings can also be applied on the needle surface to improve its visibility, however, strong signals generated from the highly absorbing coatings sometimes introduce image artefacts which affect needle identification. In this work, we developed a deep learning-based method to enhance the needle visualisation by removing the artefacts. We anticipated that the proposed methods could be useful for guiding percutaneous needle insertions.
We have developed a clinically compatible, real-time ultrasound needle tracking system (UNT) that can be appended to a clinical ultrasound system, superimposing a crosshair onto the ultrasound image at the needle tip position. The UNT was developed under the ISO 13485 Medical Devices quality standard for deployment in the clinic. During handheld ultrasound guidance, the location of the needle tip within the imaging plane is determined from the acoustic signals received by an embedded fibre-topic hydrophone. Assessment of tracking accuracy found that the mean distance between tracked and true positions was 0.7 ± 0.4 mm with a repeatability of 0.3 ± 0.2 mm.
Accurate identification of the interventional medical device during ultrasound-guided minimally-invasive procedures is of critical importance. A real-time 3D needle tracking system has been developed that utilises a fiber-optic, photoacoustic US transmitter integrated into the needle tip and a custom 2D, 4x4 receiver array attached to a clinical US imaging probe. Ultrasound signals received by the array are used to determine the location of source, which is then registered to the imaging probe and visualised. During initial laboratory measurements of tracking accuracy, the mean displacement between tracked and true distances from the array face was 0.8 ± 0.8 mm.
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.
Purpose: Alterations in the optical absorption behavior of liver tissue secondary to pathological processes can be evaluated by multispectral analysis, which is increasingly being explored as an imaging adjunct for use in liver surgery. Current methods are either invasive or have a limited wavelength spectrum, which restricts utility. This proof of concept study describes the development of a multispectral imaging (MSI) method called multispectral tissue mapping (MTM) that addresses these issues.
Approach: The imaging system consists of a tunable excitation light source and a near-infrared camera. Following the development stage, proof of concept experiments are carried out where absorption spectra from colorectal cancer liver metastasis (CRLM), hepatocellular carcinoma (HCC), and liver steatosis specimen are acquired and compared to controls. Absorption spectra are compared to histopathology examination as the current gold standard for tissue assessment. Generalized linear mixed modeling is employed to compare absorption characteristics of individual pixels and to select wavelengths for false color image processing with the aim of visually enhancing cancer tissue.
Results: Analysis of individual pixels revealed distinct absorption spectra therefore suggesting that MTM is possible. A prominent absorption peak at 1210 nm was found in lipid-rich animal tissues and steatotic liver specimen. Liver cancer tissue had a heterogeneous appearance on MSI. Subsequent statistical analysis suggests that measuring changes in absorption behavior may be a feasible method to estimate the pixel-based probability of cancer being present. In CRLM, this was observed throughout 1100 to 1700 nm, whereas in HCC it was concentrated around 1140 and 1430 nm. False color image processing visibly enhances contrast between cancer and normal liver tissues.
Conclusions: The system’s ability to enable no-touch MSI at 1100 to 1700 nm was demonstrated. Preliminary data suggest that MTM warrants further exploration as a potential imaging tool for the detection of liver cancer during surgery.
A 3D high resolution scanner has been developed specifically for clinical use. The novel scanner architecture employing multiple interrogation beams can acquire a 3D image in less than 1 second. An initial technical validation study has been undertaken in human volunteers to determine repeatability, reproducibility and patient acceptability. Thereafter, a first-in-man clinical study aimed at assessing diagnostic accuracy in patients with inflammatory diseases has been completed.
Emerging optical imaging techniques such as hyperspectral imaging (HSI) provide a promising non-invasive solution for intraoperative tissue characterisation with the potential to provide rich tissue-differentiation information over the entire surgical field. Neuro-oncology surgery would especially benefit from detailed real-time in vivo tissue characterisation, improving the accuracy with which boundaries of safe surgical resection are delineated and thereby improving patient outcomes. Current systems are limited by challenges with processing the HSI data because of incomplete characterisation of the optical properties of tissue across the complete visible and near-infrared wavelength spectrum. In this study, we characterised the optical properties of various freshly-excised brain tumours and normal cadaveric human brain tissue using a dual-beam integrating sphere spectrophotometer and the inverse adding-doubling technique. We adapted an integrating sphere to analyse 2 mm-thick tissue samples measuring 4 – 7 mm in diameter and validated the experimental setup with a tissue-mimicking optical phantom. We investigated the different spectral signatures of freshly-excised tumour tissues including pituitary adenoma, meningioma and vestibular schwannoma and compared these to normal grey and white matter, pons, pituitary, dura and cranial nerve tissues across the wavelength range of 400 – 1800 nm. It was found that brain and tumour tissues could be differentiated by their optical properties but the freezing process did alter the tissues’ relative absorption and reduced scattering coefficients. In this work, we have demonstrated a method to characterise the optical properties of small human brain and tumour specimens that may be used as a reference dataset for developing optical imaging techniques.
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.
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.
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.
Fluorescence-guided brain tumour resection, notably using 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) for high-grade gliomas, has been demonstrated to provide better tissue differentiation, thereby improving patient outcomes when compared to white-light guidance. Novel fluorescence imaging devices aiming to increase detection specificity and sensitivity and targeting applications beyond high-grade gliomas are typically assessed by measurements using tissue-mimicking optical phantoms. The field currently lacks adequate phantoms with well-characterised tuneable optical properties. In this study, we developed soft tissue-mimicking fluorescence phantoms (TMFP) highly suitable for this purpose. We investigated: 1) the ability to independently tune optical and fluorescent properties; 2) the stability of the fluorescence signal over time; and 3) the potential of the proposed phantoms for imaging device validation. The TMFP is based on gel-wax which is an optically transparent mineral-oil based soft material. We embedded TiO2 as scattering material, carbon black oil-paint as background absorber, and CdTe Quantum Dots (QDs) as fluorophore because of its similar fluorescence spectrum to PpIX. Scattering and absorption properties were measured by a spectrophotometer, while the fluorescence was assessed by a wide-field fluorescence imaging system (WFFI) and a spectrometer. We demonstrated that: 1) the addition of QDs didn’t alter the phantom’s scattering which was only defined by the concentration of TiO2, whereas its absorption was defined by both QDs and colour oil paint; 2) the measured fluorescence intensity was linearlyproportional to the concentration of QDs; 3) the fluorescence intensity was stable over time (up to eight months); and 4) the fluorescence signal measured by the WFFI were strongly correlated to spectrometer measurements.
Many percutaneous needle-based procedures such as foetal interventions, tumor biopsies, nerve blocks, and central venous catheterizations are guided by ultrasound (US) imaging to identify the procedural target and to visualize the needle. A key challenge associated with ultrasound-guided needle insertions is accurate and efficient identification of the needle tip, as thin needles can readily stray from the imaging plane and can have poor visibility at large insertion angles. Ultrasonic tracking is a method for localising the needle tip relative to the imaging plane in real-time, using an ultrasonic transmitter or receiver integrated into the needle that is in communication with an external ultrasound imaging probe. This study had two foci. The first was to increase the sensitivity with which ultrasound reception was performed, using a custom fiber optic hydrophone with a high-finesse Fabry-Pérot cavity based ultrasound sensor. This sensor, which comprised of a polymer layer sandwiched between dielectric mirrors, was interrogated continuously during insertions into tissue. The second focus of the study was to develop a custom needle stylet into which the fiber optic hydrophone was integrated, which was fully compatible with clinical practice and which could be adapted to different needles. We tested the sensitivity of the sensorized stylet across a wide range of needle angulations, depths and insertion angles in different biological tissues. We demonstrated, for the first time, needle tip localization in ex-vivo tissues at depths beyond 6 cm and insertion angles steeper than 80°. We conclude that ultrasonic tracking with high-finesse Fabry-Pérot fiber optic hydrophone is very promising for use in clinical practice.
White light endoscopy is widely used both as a diagnostic tool for the assessment of abdominal cancers and to help guide their surgical excision using minimally invasive procedures. However, the information it provides is limited to visual inspection of the tissue surface. Endoscopic ultrasonography provides depth-resolved morphological images but exhibits poor label-free microvascular contrast thus limiting its ability to identify and delineate deep seated tumours. These drawbacks can potentially be addressed by using a laparoscopic probe that provides co-registered photoacoustic (PA) and white light endoscopy images. With the help of PA contrast, the probe can visualise depth-resolved microvasculature and thus offers the prospect of more sensitive detection of tumours based on abnormal vascular anatomy and function. However, it is challenging to implement such a probe using conventional piezoelectric transducers. Their opaque nature makes it difficult to achieve forward-viewing capability in a small footprint as required for laparoscopic use as well as incorporate videoscopy. Furthermore, achieving sufficiently widebandwidth (tens of MHz) and λ/2 spatial sampling as required for high resolution endoscopic PA imaging present further challenges.
To address these challenges, we present a rigid miniature forward-viewing endoscope that is based on a transparent optical ultrasound sensor which offers a wideband response up to 50 MHz with sub-100 µm spatial sampling. The probe is designed for laparoscopic use. It is 260 mm long and 9 mm in outer diameter to permit insertion via a standard 12 mm abdominal trochar and comprises a lens relay system with a high-finesse FP ultrasound sensor at its distal end. The sensor is designed to operate in the 1500 – 1600 nm spectral range with high transmission in the visible to near-infrared region (550 – 1200 nm). The latter not only enables delivery of near-infrared pulsed excitation light through the sensor to acquire PA images but also transmission of visible CW light for simultaneous acquisition of wide-field video images at the probe tip. A MEMS scanning mirror located at the proximal end of the probe scans the FP sensor via the optical relay with 8 focused beams from a CW tunable laser source (1550 nm centre wavelength) to map the generated photoacoustic waves. High-resolution 3D tomographic images are reconstructed using a time reversal algorithm and fused with the white light video images.
The probe has 8 mm lateral field-of-view and the NEP is 200 Pa over 20 MHz bandwidth. The lateral spatial resolution is 52 µm at a depth of 1 mm decreasing to 110µm at a depth of 7 mm. The axial resolution is 29 µm over this depth range. To demonstrate potential clinical applicability, the probe was evaluated in an in vivo sheep study and shown to provide excellent high resolution 3D images of vascular structures in the liver, kidney and placentomes. This novel forward-viewing PAE probe could provide new opportunities for the photoacoustic assessment of tumours in the liver, cancer in the GI tract and guiding minimally invasive procedures in abdominal surgery and foetal medicine.
KEYWORDS: Scanners, Imaging systems, Photoacoustic spectroscopy, Ultrasonography, Fabry–Perot interferometers, 3D image processing, Tissues, Laser scanners, 3D scanning, In vivo imaging
Compared to piezoelectric based photoacoustic (PA) scanners, the planar Fabry-Perot (FP) scanner has several advantages. It can provide small element size with high sensitivity, a smooth broadband frequency response, and is transparent to excitation light. This enables the FP scanner to provide excellent high-resolution in vivo PA images of soft tissue to depths up to approximately 10 mm. However, unlike piezoelectric scanners, the FP scanner in its current form cannot provide a pulse-echo ultrasound (US) as well as a PA image, which is useful because of the additional tissue contrast it provides. To address this, a dual mode FP scanner-based system that, for the first time, can acquire co-registered 3D PA and US images has been developed.
In order to provide an optical US generation capability, the FP ultrasound sensor was coated with a novel Gold-Nanoparticle-PDMS composite which was excited with nanosecond laser pulses to generate plane wave US pulses. By modifying the FP sensor in this way, it now acts as an US transmitter as well as a receiver. The coating is highly absorbing at the US generation wavelength (>95%) but transparent at the PA excitation wavelength, the latter to allow the system to also operate in PA imaging mode as before. The generated US pulses exhibited peak pressures in the MPa range, which is comparable to the output of conventional piezoelectric based medical US scanners. The pulses had a broad bandwidth (>40 MHz) and the emitted wavefront was planar to within λ/10 at 10 MHz. PA and pulse-echo US signals were mapped in turn by the FP scanner over centimetre scale areas with a step size of 100 μm and an element size of 64 μm. The -3dB bandwidth of the FP sensor was 30 MHz. Reconstruction methods using a k-space formulation recovered co-registered 3D PA and US images. The system’s lateral spatial resolution was evaluated by imaging a line target at depths up to 10 mm and ranged between 50 and 120 μm for both modes.
Arbitrarily shaped 3D objects were imaged to demonstrate the volumetric US imaging capability of the scanner. Tissue mimicking phantoms, with impedance mismatches representative of soft tissues, and ex vivo tissue samples were imaged with the system as well as a conventional clinical US scanner for comparison. Finally, the system obtained promising high-resolution 3D dual mode PA-US images for a variety of phantoms with contrast based on both optical absorption and acoustic impedance. This novel all-optical system has the potential to add complementary morphological contrast to photoacoustic vascular images which could aid the clinical assessment of superficial tumours, lymph node disease and other conditions.
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.
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.
The International Photoacoustic Standardisation Consortium (IPASC) emerged from SPIE 2018, established to drive consensus on photoacoustic system testing. As photoacoustic imaging (PAI) matures from research laboratories into clinical trials, it is essential to establish best-practice guidelines for photoacoustic image acquisition, analysis and reporting, and a standardised approach for technical system validation. The primary goal of the IPASC is to create widely accepted phantoms for testing preclinical and clinical PAI systems. To achieve this, the IPASC has formed five working groups (WGs). The first and second WGs have defined optical and acoustic properties, suitable materials, and configurations of photoacoustic image quality phantoms. These phantoms consist of a bulk material embedded with targets to enable quantitative assessment of image quality characteristics including resolution and sensitivity across depth. The third WG has recorded details such as illumination and detection configurations of PAI instruments available within the consortium, leading to proposals for system-specific phantom geometries. This PAI system inventory was also used by WG4 in identifying approaches to data collection and sharing. Finally, WG5 investigated means for phantom fabrication, material characterisation and PAI of phantoms. Following a pilot multi-centre phantom imaging study within the consortium, the IPASC settled on an internationally agreed set of standardised recommendations and imaging procedures. This leads to advances in: (1) quantitative comparison of PAI data acquired with different data acquisition and analysis methods; (2) provision of a publicly available reference data set for testing new algorithms; and (3) technical validation of new and existing PAI devices across multiple centres.
Ultrasound (US) imaging is widely used for guiding minimally invasive procedures. However, with this modality, there can be poor visibility of interventional medical devices such as catheters and needles due to back-reflections outside the imaging aperture and low echogenicity. Photoacoustic (PA) imaging has shown promise with visualising bare metallic needles. In this study, we demonstrate the feasibility of a light emitting diode (LED)-based PA and US dual-modality imaging system for imaging metallic needles and polymeric medical catheters in biological tissue. Four medical devices were imaged with the system: two 20-gauge spinal needles with and without a multi-walled carbon nanotube / polydimethylsiloxane (MWCNT/PDMS) composite coating, and two 18-gauge epidural catheters with and without the MWCNT/PDMS composite coating. These devices were sequentially inserted into layers of chicken breast tissue within the US imaging plane. Interleaved PA and US imaging was performed during insertions of the needle and catheter. With US imaging, the uncoated needle had very poor visibility at an insertion angle of 45°. With PA imaging, the uncoated needle was not visible, but its coated counterpart was clearly visualised up to depths of 35 mm. Likewise, both catheters were not visible with US imaging. The uncoated catheter was not visible on PA images, but its coated counterpart was clearly visualised up to depths of 35 mm. We conclude that the highly absorbing CNT/PDMS composite coating conferred excellent visibility for medical devices with the LED-based PA imaging system and that it is promising for translation in minimally invasive procedures.
Non-invasive imaging plays an important role in diagnosing and monitoring peripheral artery disease (PAD). Doppler ultrasound imaging can be used for measuring blood flow in this context. However, this technique frequently provides low contrast for flow in small vessels. Photoacoustic imaging can allow for the visualization of blood in small vessels, with direct contrast from optical absorption of hemoglobin. In this work, we investigate the potential applications of a compact LED-based photoacoustic (850 nm) and ultrasound imaging system for visualizing human peripheral blood vessels during cuff occlusion. Each measurement comprised three stages. First, a baseline measurement of a digital artery of a human finger from a volunteer without a diagnosis of PAD was performed for several seconds. Second, arterial blood flow was stopped using an occlusion cuff, with a rapid increase of pressure up to 220 mm Hg. Third, the occlusion cuff was released rapidly. Raw photoacoustic and ultrasound image data (frame rate: 70 Hz) were recorded for the entire duration of the measurement (20 s). The average photoacoustic image amplitude over an image region that enclosed the digital artery was calculated. With this value, pulsations of image amplitudes from the arteries was clearly visualized. The average photoacoustic image amplitude decreased during the increase in cuff pressure and it was followed by a rapid recovery during cuff release. With real-time non-invasive measurements of peripheral blood vessel dynamics in vivo, the compact LED-based system could be valuable for point-of-care imaging to guide treatment of PAD.
Photoacoustic imaging is a powerful and increasingly popular technique for tissue diagnostics. Suitable tissue- equivalent phantoms are in high demand for validating photoacoustic imaging methods and for clinical training. In this work, we describe a method of directly 3D printing a photoacoustic tissue-equivalent phantom of a kidney based on Gel Wax, which is a mix of polymer and mineral oil. A kidney phantom that is compatible with photoacoustic scanning will enable clinicians to evaluate a portable LED-based photoacoustic and ultrasound imaging system as a means of locating tumors and other abnormalities. This represents a significant step towards clinical translation of the compact system. Training using realistic phantoms reduces the risks associated with clinical procedures. Complications during procedures can arise due to the specific structure of the kidney under investigation. Thus the ability to create a 3D printed phantom based on detailed anatomical images of a specific patient enables clinicians to train on a phantom with exactly the same structure as the kidney to be treated. Recently we developed a novel 3D printer based on gel wax. The device combines native gel wax with glass microspheres and titanium dioxide (TiO2) particles to obtain a medium with tissue-like optical and acoustic properties. 3D models created using this printer can be given a range of values of optical absorption reduced scattering coefficients. The ability to 3D patient-specific phantoms at low cost has the potential to revolutionize the production and use of tissue-equivalent phantoms in future, and can be applied to a wide range of organs and imaging modalities.
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.
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.
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.
Endoscopic ultrasonography (EUS) is an important clinical tool for the assessment of tumours in the abdominal cavity and guiding minimally invasive surgical procedures. However, one of the drawbacks of EUS is the lack of soft tissue contrast which can compromise its ability to visualise the microvasculature and thus delineate tu mour margins. Photoacoustic endoscopy (PAE) could potentially overcome this drawback as it can visualise the microvasculature with high contrast due to the strong optical absorption of haemoglobin. Previously, we have demonstrated an all-optical laboratory demonstrator PAE probe using standard bulk optical components. We now present a miniaturized flexible PAE probe with a 6 mm outer diameter and improved acoustic sensitivity capable of high resolution volumetric imaging in the forward-viewing configuration.
The probe comprises a 1.5 mm diameter flexible coherent fibre bundle consisting of 18,000 fibre-optic cores with a transparent 80MHz Fabry-Pérot ultrasound sensor at its distal end. The FP sensor thus acts as a high density 2D array composed of 18,000 individually addressable ultrasound detectors, each with a bandwidth of 80MHz and an element size and centre-to-centre spacing of 40 µm and 44 µm, respectively. The pulsed excitation light is coupled through all of the fibre-optic cores from the proximal end, and the generated photoacoustic waves are detected in backward mode by sequentially interrogating the FP sensor through individual fibre optic cores. This configuration allows for very fine sampling of the photoacoustic waves and thus high lateral spatial resolution and image fidelity. This new approach to photoacoustic endoscopy offers significant advantages over previous piezoelectric based distal-end scanning probes. These include a forward viewing capability and a wider detection bandwidth and finer spatial sampling than achievable with piezoelectric receivers, a high degree of miniaturisation, no moving parts at the distal end and relatively simple and inexpensive fabrication.
We have characterized the PAE probe in terms of its field of view, noise-equivalent pressure (NEP), and lateral and axial PSF. The lateral field of view is 5 mm and the NEP is 500 Pa over 20MHz bandwidth. The lateral spatial resolution is 50 µm at a depth of 1 mm decreasing to 150µm at a depth of 3 mm. The axial resolution is 33 µm over this depth range. The probe have also been evaluated using a variety of tissue phantoms and ex vivo tissues and shown to provide excellent high resolution 3D images of the vasculature. It is anticipated that this novel forward-viewing probe will provide new opportunities for the photoacoustic assessment of tumours in the liver and other abdominal organs, cancer in the GI tract and guiding minimally invasive procedures in abdominal surgery and foetal medicine.
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 (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.
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.
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.
Minimally invasive fetal interventions, such as those used for therapy of twin-to-twin transfusion syndrome (TTTS), require accurate image guidance to optimise patient outcomes. Currently, TTTS can be treated fetoscopically by identifying anastomosing vessels on the chorionic (fetal) placental surface, and then performing photocoagulation. Incomplete photocoagulation increases the risk of procedure failure. Photoacoustic imaging can provide contrast for both haemoglobin concentration and oxygenation, and in this study, it was hypothesised that it can resolve chorionic placental vessels. We imaged a term human placenta that was collected after caesarean section delivery using a photoacoustic/ultrasound system (AcousticX) that included light emitting diode (LED) arrays for excitation light and a linear-array ultrasound imaging probe. Two-dimensional (2D) co-registered photoacoustic and B-mode pulse-echo ultrasound images were acquired and displayed in real-time. Translation of the imaging probe enabled 3D imaging. This feasibility study demonstrated that photoacoustic imaging can be used to visualise chorionic placental vasculature, and that it has strong potential to guide minimally invasive fetal interventions.
In high-grade glioma surgery, tumor resection is often guided by intraoperative fluorescence imaging. 5-aminolevulinic acid-induced protoporphyrin IX (PpIX) provides fluorescent contrast between normal brain tissue and glioma tissue, thus achieving improved tumor delineation and prolonged patient survival compared with conventional white-light-guided resection. However, commercially available fluorescence imaging systems rely solely on visual assessment of fluorescence patterns by the surgeon, which makes the resection more subjective than necessary. We developed a wide-field spectrally resolved fluorescence imaging system utilizing a Generation II scientific CMOS camera and an improved computational model for the precise reconstruction of the PpIX concentration map. In our model, the tissue’s optical properties and illumination geometry, which distort the fluorescent emission spectra, are considered. We demonstrate that the CMOS-based system can detect low PpIX concentration at short camera exposure times, while providing high-pixel resolution wide-field images. We show that total variation regularization improves the contrast-to-noise ratio of the reconstructed quantitative concentration map by approximately twofold. Quantitative comparison between the estimated PpIX concentration and tumor histopathology was also investigated to further evaluate the system.
We report an optical fiber ultrasound transmitter with electrospun MWCNT-polymer composite, generating high-amplitude broadband ultrasound. They produced pressures in the range of conventional intravascular imaging transducers, and can be incorporated into catheters/needles for keyhole surgery
Ultrasound (US) imaging is widely used to guide vascular access procedures such as arterial and venous cannulation. As needle visualisation with US imaging can be very challenging, it is easy to misplace the needle in the patient and it can be life threating. Photoacoustic (PA) imaging is well suited to image medical needles and catheters that are commonly used for vascular access. To improve the success rate, a certain level of proficiency is required that can be gained through extensive practice on phantoms. Unfortunately, commercial training phantoms are expensive and custom-made phantoms usually do not replicate the anatomy very well. Thus, there is a great demand for more realistic and affordable ultrasound and photoacoustic imaging phantoms for vasculature access procedures training. Three-dimensional (3D) printing can help create models that replicate complex anatomical geometries. However, the available 3D printed materials do not possess realistic tissue properties. Alternatively, tissue-mimicking materials can be employed using casting and 3D printed moulds but this approach is limited to the creation of realistic outer shapes with no replication of complex internal structures. In this study, we developed a realistic vasculature access phantom using a combination of mineral oil based materials as background tissue and a non-toxic, water dissolvable filament material to create complex vascular structure using 3D printing. US and PA images of the phantoms comprising the complex vasculature network were acquired. The results show that 3D printing can facilitate the fabrication of anatomically realistic training phantoms, with designs that can be customized and shared electronically.
5-ALA-PpIX fluorescence-guided brain tumour resection can increase the accuracy at which cancerous tissue is removed and thereby improve patient outcomes, as compared with standard white light imaging. Novel optical devices that aim to increase the specificity and sensitivity of PpIX detection are typically assessed by measurements in tissue-mimicking optical phantoms of which all optical properties are defined. Current existing optical phantoms specified for PpIX lack consistency in their optical properties, and stability with respect to photobleaching, thus yielding an unstable correspondence between PpIX concentration and the fluorescence intensity.
In this study, we developed a set of aqueous-based phantoms with different compositions, using deionised water or PBS buffer as background medium, intralipid as scattering material, bovine haemoglobin as background absorber, and either PpIX dissolved in DMSO or a novel nanoparticle with similar absorption and emission spectrum to PpIX as the fluorophore. We investigated the phantom stability in terms of aggregation and photobleaching by comparing with different background medium and fluorophores, respectively. We characterised the fluorescence intensity of the fluorescent nanoparticle in different concentration of intralipid and haemoglobin and its time-dependent stability, as compared to the PpIX-induced fluorescence. We corroborated that the background medium was essential to prepare a stable aqueous phantom. The novel fluorescent nanoparticle used as surrogate fluorophore of PpIX presented an improved temporal stability and a reliable correspondence between concentration and emission intensity. We proposed an optimised phantom composition and recipe to produce reliable and repeatable phantom for validation of imaging device.
A novel all-optical forward-viewing photoacoustic probe using a flexible coherent fibre-optic bundle and a Fabry- Perot (FP) ultrasound sensor has been developed. The fibre bundle, along with the FP sensor at its distal end, synthesizes a high density 2D array of wideband ultrasound detectors. Photoacoustic waves arriving at the sensor are spatially mapped by optically scanning the proximal end face of the bundle in 2D with a CW wavelength-tunable interrogation laser. 3D images are formed from the detected signals using a time-reversal image reconstruction algorithm. The system has been characterized in terms of its PSF, noise-equivalent pressure and field of view. Finally, the high resolution 3D imaging capability has been demonstrated using arbitrary shaped phantoms and duck embryo.
In glioma resection surgery, the detection of tumour is often guided by using intraoperative fluorescence imaging notably with 5-ALA-PpIX, providing fluorescent contrast between normal brain tissue and the gliomas tissue to achieve improved tumour delineation and prolonged patient survival compared with the conventional white-light guided resection. However, the commercially available fluorescence imaging system relies on surgeon’s eyes to visualise and distinguish the fluorescence signals, which unfortunately makes the resection subjective. In this study, we developed a novel multi-scale spectrally-resolved fluorescence imaging system and a computational model for quantification of PpIX concentration. The system consisted of a wide-field spectrally-resolved quantitative imaging device and a fluorescence endomicroscopic imaging system enabling optical biopsy. Ex vivo animal tissue experiments as well as human tumour sample studies demonstrated that the system was capable of specifically detecting the PpIX fluorescent signal and estimate the true concentration of PpIX in brain specimen.
There is considerable interest in the development of photoacoustic endoscopy (PAE) probes for the clinical assessment of pathologies in the gastrointestinal (GI) tract, guiding minimally invasive laparoscopic surgeries and applications in foetal medicine. However, most previous PAE probes integrate mechanical scanners and piezoelectric transducers at the distal end which can be technically complex, expensive and pose challenges in achieving the necessary level of miniaturisation. We present two novel all-optical forward-viewing endoscopic probes operating in widefield tomography mode that have the potential to overcome these limitations. In one configuration, the probe comprises a transparent 40 MHz Fabry-Pérot ultrasound sensor deposited at the tip of a rigid, 3 mm diameter coherent fibre-optic bundle. In this way, the distal end of coherent fibre bundle acts as a 2D array of wideband ultrasound detectors. In another configuration, an optical relay is used between the distal end face of flexible fibre bundle and the Fabry-Pérot sensor to enlarge the lateral field of view to 6 mm x 6 mm. In both configurations, the pulsed excitation laser beam is full-field coupled into the fibre bundle at the proximal end for uniform backward-mode illumination of the tissue at the probe tip. In order to record the photoacoustic waves arriving at the probe tip, the proximal end of the fibre bundle is optically scanned in 2D with a CW wavelength-tunable interrogation laser beam thereby interrogating different spatial points on the sensor. A time-reversal image reconstruction algorithm was used to reconstruct a 3D image from the detected signals. The 3D field of view of the flexible PAE probe is 6 mm x 6 mm x 6 mm and the axial and lateral spatial resolution is 30 µm and 90 µm, respectively. 3D imaging capability is demonstrated using tissue phantoms, ex vivo tissues and in vivo. To the best of our knowledge, this is the first forward-viewing implementation of a photoacoustic endoscopy probe, and it offers several advantages over previous distal-end scanning probes. These include a high degree of miniaturisation, no moving parts at the distal end and simple and inexpensive fabrication with the potential to realise disposable probes for clinical imaging of the GI tract and other minimally invasive applications.
High frequency ultrasound probes such as intravascular ultrasound (IVUS) and intracardiac echocardiography (ICE) catheters can be invaluable for guiding minimally invasive medical procedures in cardiology such as coronary stent placement and ablation. With current-generation ultrasound probes, ultrasound is generated and received electrically. The complexities involved with fabricating these electrical probes can result in high costs that limit their clinical applicability. Additionally, it can be challenging to achieve wide transmission bandwidths and adequate wideband reception sensitivity with small piezoelectric elements. Optical methods for transmitting and receiving ultrasound are emerging as alternatives to their electrical counterparts. They offer several distinguishing advantages, including the potential to generate and detect the broadband ultrasound fields (tens of MHz) required for high resolution imaging. In this study, we developed a miniature, side-looking, pulse-echo ultrasound probe for intravascular imaging, with fibre-optic transmission and reception. The axial resolution was better than 70 microns, and the imaging depth in tissue was greater than 1 cm. Ultrasound transmission was performed by photoacoustic excitation of a carbon nanotube/polydimethylsiloxane composite material; ultrasound reception, with a fibre-optic Fabry-Perot cavity. Ex vivo tissue studies, which included healthy swine tissue and diseased human tissue, demonstrated the strong potential of this technique. To our knowledge, this is the first study to achieve an all-optical pulse-echo ultrasound probe for intravascular imaging. The potential for performing all-optical B-mode imaging (2D and 3D) with virtual arrays of transmit/receive elements, and hybrid imaging with pulse-echo ultrasound and photoacoustic sensing are discussed.
A miniature (175 μm) all-optical photoacoustic probe has been developed for minimally invasive sensing and imaging applications. The probe comprises a single optical fibre which delivers the excitation light and a broadband 50 MHz Fabry-Pérot (F-P) ultrasound sensor at the distal end for detecting the photoacoustic waves. A graded index lens proximal to the F-P sensor is used to reduce beam walk-off and thus increase sensitivity as well as confine the excitation beam in order to increase lateral spatial resolution. The probe was evaluated in non-scattering media and found to provide lateral and axial resolutions of < 100 μm and < 150 μm respectively for distances up to 1 cm from the tip of the probe. The ability of the probe to detect a blood vessel mimicking phantom at distances up to 7 mm from the tip was demonstrated in order to illustrate its potential suitability for needle guidance applications.
Laparoscopic procedures can be an attractive treatment option for liver resection, with a shortened hospital stay and reduced morbidity compared to open surgery. One of the central challenges of this technique is visualisation of concealed structures within the liver, particularly the vasculature and tumourous tissue. As photoacoustic (PA) imaging can provide contrast for haemoglobin in real time, it may be well suited to guiding laparoscopic procedures in order to avoid inadvertent trauma to vascular structures. In this study, a clinical laparoscopic ultrasound probe was used to receive ultrasound for PA imaging and to obtain co-registered B-mode ultrasound (US) images. Pulsed excitation light was delivered to the tissue via a fibre bundle in dark-field mode. Monte Carlo simulations were performed to optimise the light delivery geometry for imaging targets at depths of 1 cm, 2 cm and 3 cm, and 3D-printed mounts were used to position the fibre bundle relative to the transducer according to the simulation results. The performance of the photoacoustic laparoscope system was evaluated with phantoms and tissue models. The clinical potential of hybrid PA/US imaging to improve the guidance of laparoscopic surgery is discussed.
Accurate identification of tissue structures such as nerves and blood vessels is critically important for interventional procedures such as nerve blocks. Ultrasound imaging is widely used as a guidance modality to visualize anatomical structures in real-time. However, identification of nerves and small blood vessels can be very challenging, and accidental intra-neural or intra-vascular injections can result in significant complications. Multi-spectral photoacoustic imaging can provide high sensitivity and specificity for discriminating hemoglobin- and lipid-rich tissues. However, conventional surface-illumination-based photoacoustic systems suffer from limited sensitivity at large depths. In this study, for the first time, an interventional multispectral photoacoustic imaging (IMPA) system was used to image nerves in a swine model in vivo. Pulsed excitation light with wavelengths in the ranges of 750 - 900 nm and 1150 - 1300 nm was delivered inside the body through an optical fiber positioned within the cannula of an injection needle. Ultrasound waves were received at the tissue surface using a clinical linear array imaging probe. Co-registered B-mode ultrasound images were acquired using the same imaging probe. Nerve identification was performed using a combination of B-mode ultrasound imaging and electrical stimulation. Using a linear model, spectral-unmixing of the photoacoustic data was performed to provide image contrast for oxygenated and de-oxygenated hemoglobin, water and lipids. Good correspondence between a known nerve location and a lipid-rich region in the photoacoustic images was observed. The results indicate that IMPA is a promising modality for guiding nerve blocks and other interventional procedures. Challenges involved with clinical translation are discussed.
Accurate and efficient identification of nerves is an essential component of peripheral nerve blocks. While ultrasound (US) imaging is increasingly used as a guidance modality, it often provides insufficient contrast for identifying nerves from surrounding tissues such as tendons. Electrical nerve stimulators can be used in conjunction with US imaging for discriminating nerves from surrounding tissues, but they are insufficient to reliably prevent neural punctures, so that alternative methods are highly desirable. In this study, an interventional multispectral photoacoustic (PA) imaging system was used to directly compare the signal amplitudes and spectra acquired from nerves and tendons ex vivo, for the first time. The results indicate that the system can provide significantly higher image contrast for discriminating nerves and tendons than that provided by US imaging. As such, photoacoustic imaging could be valuable as an adjunct to US for guiding peripheral nerve blocks.
Optical clearing, in combination with recently developed optical imaging techniques, enables visualization and acquisition of high-resolution, three-dimensional images of biological structures deep within the tissue. Many different approaches can be used to reduce light absorption and scattering within the tissue, but there is a paucity of research on the quantification of clearing efficacy. With the use of a custom-made spectroscopy system, we developed a way to quantify the quality of clearing in biological tissue and applied it to the mouse brain. Three clearing techniques were compared: BABB (1:2 mixture of benzyl alcohol and benzyl benzoate, also known as Murray’s clear), pBABB (peroxide BABB, a modification of BABB which includes the use of hydrogen peroxide), and passive CLARITY. We found that BABB and pBABB produced the highest degree of optical clearing. Furthermore, the approach allows regional measurement of light attenuation to be performed, and our results show that light is most attenuated in regions with high lipid content. We provide a way to choose between the multiple clearing protocols available, and it could prove useful for evaluating images that are acquired with cleared tissues.
Precise device guidance is important for interventional procedures in many different clinical fields including fetal medicine, regional anesthesia, interventional pain management, and interventional oncology. While ultrasound is widely used in clinical practice for real-time guidance, the image contrast that it provides can be insufficient for visualizing tissue structures such as blood vessels, nerves, and tumors. This study was centered on the development of a photoacoustic imaging system for interventional procedures that delivered excitation light in the ranges of 750 to 900 nm and 1150 to 1300 nm, with an optical fiber positioned in a needle cannula. Coregistered B-mode ultrasound images were obtained. The system, which was based on a commercial ultrasound imaging scanner, has an axial resolution in the vicinity of 100 μm and a submillimeter, depth-dependent lateral resolution. Using a tissue phantom and 800 nm excitation light, a simulated blood vessel could be visualized at a maximum distance of 15 mm from the needle tip. Spectroscopic contrast for hemoglobin and lipids was observed with ex vivo tissue samples, with photoacoustic signal maxima consistent with the respective optical absorption spectra. The potential for further optimization of the system is discussed.
There is considerable interest in the development of photoacoustic endoscopy probes (PAE) for applications in foetal medicine, interventional surgery and gastroenterology. However, most previous PAE probes employ a combination of mechanical scanning and piezoelectric transducers at the distal end which can be technically complex and pose challenges in achieving the required level of miniaturisation and acoustic performance. To overcome these limitations, we present two novel all-optical forward-viewing endoscopic probes that use coherent fibre bundles to address a Fabry-Perot polymer film ultrasound sensor.
In a wide range of clinical procedures, accurate placement of medical devices such as needles and catheters is critical to optimize patient outcomes. Ultrasound imaging is often used to guide minimally invasive procedures, as it can provide real-time visualization of patient anatomy and medical devices. However, this modality can provide low image contrast for soft tissues, and poor visualization of medical devices that are steeply angled with respect to the incoming ultrasound beams. Photoacoustic sensors can provide information about the spatial distributions of tissue chromophores that could be valuable for guiding minimally invasive procedures. In this study, a system for guiding minimally invasive procedures using photoacoustic sensing was developed. This system included a miniature photoacoustic probe with three optical fibers: one with a bare end for photoacoustic excitation of tissue, a second for photoacoustic excitation of an optically absorbing coating at the distal end to transmit ultrasound, and a third with a Fabry-Perot cavity at the distal end for receiving ultrasound. The position of the photoacoustic probe was determined with ultrasonic tracking, which involved transmitting pulses from a linear-array ultrasound imaging probe at the tissue surface, and receiving them with the fiber-optic ultrasound receiver in the photoacoustic probe. The axial resolution of photoacoustic sensing was better than 70 μm, and the tracking accuracy was better than 1 mm in both axial and lateral dimensions. By translating the photoacoustic probe, depth scans were obtained from different spatial positions, and two-dimensional images were reconstructed using a frequency-domain algorithm.
Precise and efficient guidance of medical devices is of paramount importance for many minimally invasive procedures. These procedures include fetal interventions, tumor biopsies and treatments, central venous catheterisations and peripheral nerve blocks. Ultrasound imaging is commonly used for guidance, but it often provides insufficient contrast with which to identify soft tissue structures such as vessels, tumors, and nerves. In this study, a hybrid interventional imaging system that combines ultrasound imaging and multispectral photoacoustic imaging for guiding minimally invasive procedures was developed and characterized. The system provides both structural information from ultrasound imaging and molecular information from multispectral photoacoustic imaging. It uses a commercial linear-array ultrasound imaging probe as the ultrasound receiver, with a multimode optical fiber embedded in a needle to deliver pulsed excitation light to tissue. Co-registration of ultrasound and photoacoustic images is achieved with the use of the same ultrasound receiver for both modalities. Using tissue ex vivo, the system successfully discriminated deep-located fat tissue from the surrounding muscle tissue. The measured photoacoustic spectrum of the fat tissue had good agreement with the lipid spectrum in literature.
Optical clearing allows the reduction of light scattering in biological tissue, enabling 3D morphological information to be
obtained deep within tissue using techniques such as optical projection tomography and light sheet microscopy. However, the
extent of the clearing is dependent on the technique that is used. There is therefore a need for methods to quantify the quality
of the clearing process and thereby to compare clearing techniques. In this study, we developed such a method using a
custom spectroscopy system and applied it to compare three techniques that were applied to mouse brain: BABB (Murray’s
clear), pBABB (a modification of BABB which includes the use of hydrogen peroxide), and passive CLARITY.
Detection of tissue structures such as nerves and blood vessels is of critical importance during many needle-based minimally invasive procedures. For instance, unintentional injections into arteries can lead to strokes or cardiotoxicity during interventional pain management procedures that involve injections in the vicinity of nerves. Reliable detection with current external imaging systems remains elusive. Optical generation and reception of ultrasound allow for depth-resolved sensing and they can be performed with optical fibers that are positioned within needles used in clinical practice. The needle probe developed in this study comprised separate optical fibers for generating and receiving ultrasound. Photoacoustic generation of ultrasound was performed on the distal end face of an optical fiber by coating it with an optically absorbing material. Ultrasound reception was performed using a high-finesse Fabry-Pérot cavity. The sensor data was displayed as an M-mode image with a real-time interface. Imaging was performed on a biological tissue phantom.
Accurate and efficient identification of nerves is of great importance during many ultrasound-guided clinical procedures, including nerve blocks and prostate biopsies. It can be challenging to visualise nerves with conventional ultrasound imaging, however. One of the challenges is that nerves can have very similar appearances to nearby structures such as tendons. Several recent studies have highlighted the potential of near-infrared optical spectroscopy for differentiating nerves and adjacent tissues, as this modality can be sensitive to optical absorption of lipids that are present in intra- and extra-neural adipose tissue and in the myelin sheaths. These studies were limited to point measurements, however. In this pilot study, a custom photoacoustic system with a clinical ultrasound imaging probe was used to acquire multi-spectral photoacoustic images of nerves and tendons from swine ex vivo, across the wavelength range of 1100 to 1300 nm. Photoacoustic images were processed and overlaid in colour onto co-registered conventional ultrasound images that were acquired with the same imaging probe. A pronounced optical absorption peak centred at 1210 nm was observed in the photoacoustic signals obtained from nerves, and it was absent in those obtained from tendons. This absorption peak, which is consistent with the presence of lipids, provides a novel image contrast mechanism to significantly enhance the visualization of nerves. In particular, image contrast for nerves was up to 5.5 times greater with photoacoustic imaging (0.82 ± 0.15) than with conventional ultrasound imaging (0.148 ± 0.002), with a maximum contrast of 0.95 ± 0.02 obtained in photoacoustic mode. This pilot study demonstrates the potential of photoacoustic imaging to improve clinical outcomes in ultrasound-guided interventions in regional anaesthesia and interventional oncology.
Novel ultrasound transducers were created with a composite of carbon nanotubes (CNTs) and polydimethylsiloxane (PDMS) that was dip coated onto the end faces of optical fibers. The CNTs were functionalized with oleylamine to allow for their dissolution in xylene, a solvent of PDMS. Ultrasound pulses were generated by illuminating the composite coating with pulsed laser light. At distances of 2 to 16 mm from the end faces, ultrasound pressures ranged from 0.81 to 0.07 MPa and from 0.27 to 0.03 MPa with 105 and 200 μm core fibers, respectively. Using an optical fiber hydrophone positioned adjacent to the coated 200 µm core optical fiber, ultrasound reflectance measurements were obtained from the outer surface of a sheep heart ventricle. The results of this study suggest that ultrasound transducers that comprise optical fibers with CNT-PDMS composite coatings may be suitable for miniature medical imaging probes.
Ultrasound imaging is frequently used for guiding needles during minimally invasive procedures, but accurate
identification of the needle tips can be challenging, even for experienced practitioners. In this study, a novel method for
tracking needles inside the human body was developed. This method, called ultrasonic device tracking (UDT), involved
the detection of ultrasound pulses from the external imaging probe with an optical fibre hydrophone integrated into the
needle cannula. Two methods for estimating the needle tip position that were based on the maximum and the centroid of
the optical fibre hydrophone signal were tested. The variability of the position estimates is measured at different
distances to the electronic focus. The maximum longitudinal variability was less than 80 μm for all distances. The lateral
variability remains below 500 μm in a 20 mm region around the focus, but increases up to several mm away from the
electronic focus. In the close proximity of the electronic focus, the lateral and longitudinal variability lower down to 22
μm and less. This study suggests that UDT allows for safer and more efficient procedures in a manner that is compatible
with the current clinical workflow.
The effectiveness of peripheral nerve blocks is highly dependent on the accuracy at which the needle tip is navigated to the target injection site. Even when electrical stimulation is utilized in combination with ultrasound guidance, determining the proximity of the needle tip to the target region close to the nerve can be challenging. Optical reflectance spectroscopy could provide additional information about tissues that is complementary to these navigation methods. We demonstrate a novel needle stylet for acquiring spectra from tissue at the tip of a commercial 20-gauge needle. The stylet has integrated optical fibers that deliver broadband light to tissue and receive scattered light. Two spectrometers resolve the light that is received from tissue across the wavelength range of 500-1600 nm. In our pilot study, measurements are acquired from a postmortem dissection of the brachial plexus of a swine. Clear differences are observed between spectra acquired from nerves and those acquired from adjacent tissue structures. We conclude that spectra acquired with the stylet have the potential to increase the accuracy with which peripheral nerve blocks are performed.
We present a novel, hand-held microscope probe for acquiring confocal images of biological tissue. This probe generates images by scanning a fiber-lens combination with a miniature electromagnetic actuator, which allows it to be operated in resonant and nonresonant scanning modes. In the resonant scanning mode, a circular field of view with a diameter of 190 μm and an angular frequency of 127 Hz can be achieved. In the nonresonant scanning mode, a maximum field of view with a width of 69 μm can be achieved. The measured transverse and axial resolutions are 0.60 and 7.4 μm, respectively. Images of biological tissue acquired in the resonant mode are presented, which demonstrate its potential for real-time tissue differentiation. With an outer diameter of 3 mm, the microscope probe could be utilized to visualize cellular microstructures in vivo across a broad range of minimally-invasive procedures.
We demonstrate a method to estimate the concentrations of water and lipid in scattering media such as biological tissues with diffuse optical spectra acquired over the range of 900 to 1600 nm. Estimations were performed by fitting the spectra to a model of light propagation in scattering media derived from diffusion theory. To validate the method, spectra were acquired from tissue phantoms consisting of lipid and water emulsions and swine tissues ex vivo with a two-fiber probe.
Diffuse reflectance spectroscopy is one of the different optical techniques that are used to extract optical properties of
tissues such as the scattering and the absorption coefficients. These properties can in turn be linked to physiological
parameters. Therefore optical probes are of interest to extract physiological parameters from tissue that derive from
diffuse reflectance spectroscopy. Investigating to which extend theses models are valid is of importance in order to
assess the reliability of the estimated parameters. We present different models that are used to extract optical parameters
from spatially resolved diffuse reflectance measurement.
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