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.
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.
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.
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.
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.
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.
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.
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