Photoacoustic (PA) imaging combines optical spectroscopic contrast with deep tissue penetration, offering valuable functional, molecular, and structural information about tissue. However, a long-standing challenge with PA imaging has been that the quantification accuracy of tissue chromophores concentrations remains limited due to the spectral colouring effect. Monte Carlo (MC) simulation is regarded as the gold standard to model light transportation in tissue but can be computationally demanding, thus not suitable for real-time applications. We propose a time-efficiency solution using conditional generative adversarial networks (cGANs) to generate light fluence distributions within tissue towards real-time spectral decolouring in PA imaging. The networks were trained to predict light fluence distribution from realistic tissue anatomy and optical properties using MC simulation as ground truth. We achieved high-quality light fluence synthesis, with a peak signal-to-noise ratio of 31.9 dB using in vivo segmentation. We also demonstrated the validity of spectral decolouring for PA quantification, with an error of absorption efficient estimation around 0.05 using numerical phantoms. Thus, this approach holds promise for enhancing the quantification performance of PA imaging in real-time.
An all-optical, forward-viewing, optical-resolution photoacoustic endomicroscopy probe was developed for guiding minimally invasive procedures. The probe comprises a multimode fibre for the delivery of excitation laser via wavefront shaping, and a fibre-optic ultrasound sensor based on a plane-concave microresonator at the tip of a single-mode fibre. High-resolution photoacoustic microscopy images of mouse red blood cells and mouse ear vasculature were acquired, and the high scalability of the probe in terms of field-of-view and spatial resolution was demonstrated. The ultrathin photoacoustic endomicroscopy probe promises to guide minimally invasive surgery by providing both molecular and microstructural information.
Photoacoustic (PA) imaging has demonstrated tremendous potential for various clinical and pre-clinical applications in the past two decades. Laser diodes and light-emitting diodes can be used as substitutes for solid-state lasers with the benefits of low cost and compact size. However, PA signals generated by such light sources have relatively low signal-to-noise ratios due to the low output energy. Here, we proposed a spatiotemporal singular value decomposition denoising method for PA radiofrequency data acquired at high frame rates. Within silico and in vivo experiments, it outperformed frame averaging and could be used for real-time in vivo applications.
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.
High-speed photoacoustic (PA) endomicroscopy imaging is desired for real-time guidance of minimally invasive surgery. However, the imaging speed of wavefront shaping-based endomicroscopy has been limited by the speed of spatial light modulators. In this work, a deep convolutional neural network was used to improve the imaging speed of a newly developed PA endomicroscopy system by enhancing sparsely sampled PA images. With a carbon fibre phantom, this method increased the imaging speed by 16 times without significantly affecting the image quality. With further validation on more complex datasets, this approach is promising to achieve real-time PA endomicroscopy imaging via wavefront shaping.
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.
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.
Photoacoustic (PA) endoscopy promises to be useful in a variety of clinical contexts including intravascular imaging, gastrointestinal tracts imaging and surgical guidance. Recent advancements of optical wavefront shaping allow the development of ultrathin endoscopy probes based on multimode optical fibres, which can provide higher spatial resolution than previously reported fibre bundle-based endoscopes. In this work, we developed a forward-viewing PA endomicroscopy imaging system and further improved its performance with a deep image prior (DIP) neural network. Laser was focused and scanned through a multimode fibre via wavefront shaping, in which a real-valued intensity transmission matrix approach was used for fibre characterisation, and a digital micromirror device (DMD) was used for light modulation. The excited ultrasound waves at the distal fibre tip were detected by an ultrasound transducer. High fidelity images of ex vivo mouse red blood cells were acquired. A DIP neural network was then used to improve the spatial resolution with unsupervised learning. Convolutional filters were used to learn features of low-level images as priors and reconstruct high-resolution images accordingly. The performance of the DIP approach was evaluated using a structural similarity index measure (SSIM) at a level of 0.85 with 25% effective pixels, which outperformed the bicubic method. The use of DIP allows reducing scanning positions by several times, and thus improves the speed of pixel-wise PA microscopy imaging. With further miniaturisation of the ultrasound detector, we anticipate that this system could be used for real-time guidance of minimally invasive surgeries by providing micro-structural, molecular, and functional information of tissue.
Photoacoustic endoscopy (PAE) allows close visualisation of internal tissues that are challenging to be assessed from outside. It usually employs optical fibres to deliver light to optically excite ultrasound from internal tissues and detect these ultrasound signals with a detector integrated with the fibre. Conventional designs of PAE usually comprise piezoelectric transducers for photoacoustic signals detection, however, due to their opaque nature, these transducers are required to be laterally offset, leading to reduced acoustic sensitivity and increased footprint dimensions. In this work, we fabricated a miniaturized transparent ultrasound sensor using a transparent polyvinylidene fluoride (PVDF) thin film coated with indium tin oxide (ITO) electrodes for PAE. The PVDF-ITO thin film was coated at the tip of a brass tube that had an outer diameter of 2 mm and an inner diameter of 1 mm. A multimode optical fibre was inserted into the brass tube to deliver nano-second-pulsed laser through the PVDF-ITO sensor for photoacoustic signals excitation. The sensor showed an optical transmission rate of ~ 65% to 75% in the wavelength range of 450 to 700 nm, and the photoacoustic signals generated from a carbon fibre had a centre frequency of 15 MHz and a -10 dB bandwidth of 30 MHz. Raster scanning of a focused laser beam on a carbon fibre phantom was performed to obtain optical-resolution photoacoustic endomicroscopy images using a high-speed digital micromirror device via wavefront shaping. Further pre-clinical experiments (tissue samples and in vivo) are required to evaluate the potential of the imaging system for guiding minimally invasive procedures.
We present the development of a forward-viewing optical-resolution photoacoustic endo-microscopy probe based on a multimode fibre via high-speed wavefront shaping. High-resolution 3D photoacoustic microscopy images of carbon fibres and red blood cells were obtained.
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.
Photoacoustic endoscopy holds great potential for guiding minimally invasive procedures including fetal surgery, and tumour biopsy, as it can provide functional and molecular information of tissue with high spatial resolution. Multimode fibre has shown promise for the development of an ultrathin, forward-viewing photoacoustic probes. In this work, we report the development of a photoacoustic endomicroscopy system based on a multimode fibre and a new method for calibration. With a simple setup, this method exhibited high-speed calibration of MMFs, and it could be useful for the development and clinical translations of ultra-thin photoacoustic endomicroscopy probes.
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.
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.
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.
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.
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.
Intravascular (IV) imaging in percutaneous coronary interventions can be invaluable to treat coronary artery disease, to facilitate decision making and to guide stent placement. Intravascular ultrasound (IVUS) and optical coherence tomography (OCT) are both established IV imaging modalities. However, achieving contrast for specific structures such as lipid plaques can be challenging; with OCT, visualisation is typically limited to tissue depths less than 2 mm. Photoacoustic (PA) imaging provides contrast that is complementary to those of IVUS and OCT, and with previous demonstrations, visualisation of lipid plaques at depths greater than 4 mm has been achieved. In this study, we developed an intravascular PA probe that comprises a commercial OCT catheter and a high sensitivity miniature fibre optic ultrasound sensor with a Fabry-Pérot cavity. This probe, which can provide both PA imaging and OCT, had a maximum width of 1.2 mm. The PA excitation sources included both pulsed and modulated lasers at different wavelengths. The omni-directionality of the US sensor allowed for three-dimensional PA images. The PA-OCT probe was characterised using a series of resolution phantoms, including fine carbon fibres. It was found that with PA imaging, the probe can provide a lateral resolution better than 25 µm and an axial resolution better than 100 µm at the optical focus. Co-registered PA and OCT images of blood vessels ex-vivo with stents and lipid injections were acquired. We conclude that PA imaging with OCT catheters is viable and that it has strong potential to guide clinical interventions.
Phantoms are crucial for developing photoacoustic imaging systems and for training practitioners. Advances in 3D printing technology have allowed for the generation of detailed moulds for tissue-mimicking materials that represent anatomically realistic tissue structures such as blood vessels. Here, we present methods to generate phantoms for photoacoustic and ultrasound imaging based on patient-specific anatomy and mineral oil based compounds as tissue-mimicking materials. Moulds were created using a 3D printer with fused deposition modelling. Optical and acoustic properties were independently tuned to match different soft tissue types using additives: inorganic dyes for optical absorption, TiO2 particles for optical scattering, paraffin wax for acoustic attenuation, and solid glass spheres for acoustic backscattering. Melted mineral oil compounds with additives were poured into the 3D printed moulds to fabricate different anatomical structures. Optical absorption and reduced scattering coefficients across the wavelength range of 400 to 1600 nm were measured using a spectrophotometer with an integrating sphere, and inverse adding-doubling. The acoustic attenuation and speed-of-sound were measured in reflection mode using a 10 MHz transducer. Three phantoms were created to represent nerves and adjacent blood vessels, a human placenta obtained after caesarean section, and a human heart based on an MRI image volume. Co-registered multi-wavelength photoacoustic and ultrasound images were acquired with a system that comprised a clinical ultrasound imaging scanner, an optical parametric oscillator, and linear-array ultrasound imaging probes. We conclude that mineral oil based compounds can be well suited to create anatomically-realistic phantoms for photoacoustic and ultrasound imaging using 3D printed moulds.
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.
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.
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.
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.
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.
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.
The ultrasound detector is the heart of a photoacoustic imaging system. In photoacoustic imaging of the breast
there is a requirement to detect tumors located a few centimeters deep in tissue, where the light is heavily attenuated.
Thus a sensitive ultrasound transducer is of crucial importance. As the frequency content of photoacoustic
waves are inversely proportional to the dimensions of the absorbing structures, and in tissue can range from hundreds
of kHz to tens of MHz, a broadband ultrasound transducer is required centered on an optimum frequency.
A single element piezoelectric transducer structurally consists of the active piezoelectric material, front- and
back-matching layers and a backing layer. To have both high sensitivity and broad bandwidth, the materials,
their acoustic characteristics and their dimensions should be carefully chosen. In this paper, we present design
considerations of an ultrasound transducer for imaging the breast such as the detector sensitivity and frequency
response, which guides the selection of active material, matching layers and their geometries. We iterate between
simulation of detector performance and experimental characterization of functional models to arrive at an
optimized implementation. For computer simulation, we use 1D KLM and 3D finite-element based models. The
optimized detector has a large-aperture possessing a center frequency of 1 MHz with fractional bandwidth of
more than 80%. The measured minimum detectable pressure is 0.5 Pa, which is two orders of magnitude lower
than the detector used in the Twente photoacoustic mammoscope.
Current imaging modalities are often not able to detect early stages of breast cancer with high imaging contrast.
Visualizing malignancy-associated increased hemoglobin concentrations might improve breast cancer diagnosis.
Photoacoustic imaging can visualize hemoglobin in tissue with optical contrast and ultrasound resolution, which makes it
potentially ideal for breast imaging. The Twente Photoacoustic Mammoscope (PAM) has been designed specifically for
this purpose. Based on a successful pilot study in 2007, a large clinical study using PAM has been started in December
2010. PAM uses a pulsed Q-switched Nd:YAG laser at 1064 nm to illuminate a region of interest on the breast.
Photoacoustic signals are detected with a 1MHz, unfocused ultrasound detector array. Three dimensional data are
reconstructed using an acoustic backprojection algorithm. Those reconstructed images are compared with conventional
imaging and histopathology. In the first phase of the study, the goal was to optimize the visualization of malignancies.
We performed sixteen technically acceptable measurements on confined breast malignancies. In the reconstructed
volumes of all malignancies, a confined high contrast region could be identified at the expected lesion depth. After ten
successful measurements, the illumination area was increased and the fluence was substantially decreased. This caused a
further significant increase in PAM lesion contrast.
A custom-made first prototype of a linear array ultrasound transducer for breast imaging is presented. Large active area
transducer elements (5 mm × 5 mm) with 1 MHz resonance frequency are chosen to obtain a relatively high sensitivity.
Acoustic lenses are used to enlarge the narrow acceptance angle of such transducer elements. The minimum detectable
pressure, frequency bandwidth and electrical impedance of the transducer elements are characterized. The results show
the transducer has a minimum detectable pressure of 0.8 Pa, which is superior than the transducers used in the Twente
Photoacoustic Mammoscope system previously developed in our group. The bandwidth of the transducer is relative
small, however it can be improved when using optimized matching layer thickness in future. We also observed a strong
lateral resonance at 330 kHz, which may cause problems in various aspects for a photoacoustic imaging system. We
discuss the future improvement and plans for the transducer optimizations.
In photoacoustic imaging, upon short laser pulse irradiation, absorbers generate N-shaped pulses which can be detected
by ultrasound transducers. Radio frequency signals from different spatial locations are then reconstructed taking into
account the ultrasound transducer angular response. Usually, the directivity is part of the "a priori" characterization of the
transducer and it is assumed to be constant in the reconstruction algorithm.
This approach is valid in both transmission and reflection ultrasound imaging, where any echo resembles the transducer
frequency response. Center frequency and bandwidth of any echo are almost the same, and the ultrasound transducer
collect signals with the same "fixed" acceptance angle. In photoacoustics, instead, absorbers generate echoes whose time
duration is proportional to the absorber size. Large absorbers generate low frequency echoes, whereas small absorber
echoes are centered at higher frequencies. Thus for different absorber sizes, different pulse frequencies are obtained and
different directivities need to be applied.
For this purpose once a radio-frequency signal is aquired, it is pre-processed with a sliding window: every segment is
Fourier transformed to extract the central frequency. Then, a proper directivity can be estimated for each segment.
Finally signals can be reconstructed via a backprojection algorithm, according to the system's geometry. Echoes are
backprojected over spheres with the angular extension being adapted to the frequency content of the photoacoustic
sources.
Simulation and experimental validation of this approach are discussed showing promising results in terms of image
contrast and resolution.
A popular phantom in photoacoustic imaging is poly(vinyl alcohol) (PVA) hydrogel fabricated by freezing and thawing (F-T) aqueous solutions of PVA. The material possesses acoustic and optical properties similar to those of tissue. Earlier work characterized PVA gels in small test specimens where temperature distributions during F-T are relatively homogeneous. In this work, in breast-sized samples we observed substantial temperature differences between the shallow regions and the interior during the F-T procedure. We investigated whether spatial variations were also present in the acoustic and optical properties. The speed of sound, acoustic attenuation, and optical reduced scattering coefficients were measured on specimens sampled at various locations in a large phantom. In general, the properties matched values quoted for breast tissue. But while acoustic properties were relatively homogeneous, the reduced scattering was substantially different at the surface compared with the interior. We correlated these variations with gel microstructure inspected using scanning electron microscopy. Interestingly, the phantom's reduced scattering spatial distribution matches the optical properties of the standard two-layer breast model used in x ray dosimetry. We conclude that large PVA samples prepared using the standard recipe make excellent breast tissue phantoms.
A large surface area transducer is preferable to be used to detect extremely weak photoacoustic signals in
mammography due to its high sensitivity. The lateral resolution is limited by the small acceptance angle of such
a transducer. We introduce an excellent material for an acoustic lens used to enlarge the transducer's acceptance
angle. Our acoustic characterizations showed that this material has tissue-like acoustic impedance, large speed
of sound and low acoustic attenuation. These acoustic properties ensures an excellent acoustic lens material.
We further investigated the acoustic irradiation pattern of a 1 MHz, 5 mm x 5 mm single element transducer.
Transducer irradiation pattern with and without acoustic lens made from our proposed material and common
used lens material are simulated using the Field II program and also the k-wave package. Good agreement has
been achieved comparing the simulation results from two different methods. Both simulations show that the
proposed material not only enlarged the acceptance angle of the transducer but also minimized the signal loss
compared to the common used lens material. We conclude that the proposed material can be used as an excellent
acoustic lens for photoacoustic tomography.
Worldwide, yearly about 450,000 women die from the consequences of breast cancer. Current imaging modalities are
not optimal in discriminating benign from malignant tissue. Visualizing the malignancy-associated increased
hemoglobin concentration might significantly improve early diagnosis of breast cancer. Since photoacoustic imaging
can visualize hemoglobin in tissue with optical contrast and ultrasound-like resolution, it is potentially an ideal method
for early breast cancer imaging.
The Twente Photoacoustic Mammoscope (PAM) has been developed specifically for breast imaging. Recently, a
large clinical study has been started in the Medisch Spectrum Twente in Oldenzaal using PAM. In PAM, the breast is
slightly compressed between a window for laser light illumination and a flat array ultrasound detector. The
measurements are performed using a Q-switched Nd:YAG laser, pulsed at 1064 nm and a 1 MHz unfocused ultrasound
detector array. Three-dimensional data are reconstructed using a delay and sum reconstruction algorithm. Those
reconstructed images are compared with conventional imaging and histopathology. In the first phase of the study 12
patients with a malignant lesion and 2 patients with a benign cyst have been measured. The results are used to guide
developments in photoacoustic mammography in order to pave the way towards an optimal technique for early diagnosis
of breast cancer.
Tissue mimicking phantoms are important for performance evaluation of imaging systems: in photoacoustics they need
to accomplish both soft tissue optical and acoustic properties. PVA gels by freezing-thawing (F-T) have been used to
simulate tissue properties. The microstructure, dependent on rate and extent of temperature cycling, is responsible for
optical and acoustic properties. In F-T of larger phantoms, temperature differences in the mass are expected, resulting in
a likely inhomogeneous distribution of properties in the phantom. We investigated speed of sound, acoustic attenuation,
reduced optical scattering coefficient and microstructure: their variations are correlated with thermal differences between
phantom surface and bulk.
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