OBJECTIVES:To assess whether 3D photoacoustic tomography (PAT) using the Fabry-Perot (FP) scanner can (1) reliably detect synovitis in participants with rheumatoid arthritis (RA), and (2) assess the severity of active inflammation. METHODS:A total of 247 3D-PAT images of the finger and wrist joint from 11 healthy volunteers and 9 patients with RA were obtained using the FP scanner. Patients underwent power doppler ultrasound (PDUS) assessment of RA disease activity. The 3D-PAT images were acquired over a 15 × 15 × 10 mm3 volume in <15 s. The images were assessed quantitatively by segmentation of the vasculature using k-means clustering followed by skeletonization to measure vascular path length (PAT-VPL). Patient and volunteer PAT-VPL were compared using t-tests and area under the receiver operating characteristic curve (ROC-AUC). RESULTS:The 3D-PAT differentiates between unaffected and affected joints in patients with RA, showing a statistically significant difference in PAT-VPL (unaffected joint: 11.88 mm, affected joints: 45.7 mm, P < .001). The ROC-AUC was 0.91 (95% confidence interval [CI]: 0.81-0.96), with sensitivity and specificity of 86% (95% CI: 72%-95%) and 78% (95% CI: 60%-90%), respectively. PAT-VPL was associated with PDUS-based clinical severity grade, with a correlation coefficient of 0.74 (95% CI: 0.67-0.8). Significant differences in PAT-VPL were observed between each clinical severity group. CONCLUSIONS:The FP scanner generates rapid high-resolution quantitative 3D-PAT images of the synovial microvasculature that can be used to distinguish between inflamed and non-inflamed joints, and assess the severity of active inflammation. ADVANCES IN KNOWLEDGE:The 3D-PAT FP scanner reliably distinguishes between affected and unaffected finger and wrist joints in patients with rheumatoid arthritis. Compared to previous 2D PAT scanners used to image joint inflammation, it offers superior image quality and the prospect of mitigating operator-dependent variations in probe positioning by virtue of its 3D imaging capability.

Photoacoustic imaging (PAI) technique works by delivering pulsed-laser light to the skin surface. The light penetrates deeply into the joint where it is absorbed by the synovial-blood vessels produced by inflammation. This generates high-frequency sound waves which are detected and used to form a 3D image of the blood vessels. PAI is highly sensitive to blood, it is potentially more sensitive to inflammation than ultrasound imaging. At University College London (UCL), we have developed a novel PAI scanner prototype and conducted a pilot-study on a small number of patients with rheumatoid arthritis (RA) to assess if the scanner can differentiate between diseased and healthy finger-joints a well as correlation with doppler ultrasound for severity of inflammation. A total of 13 patients with rheumatoid arthritis (age 33-74, 9 females and 4 males) were recruited from University College London Hospital (UCLH) outpatient clinics. 13 healthy volunteers (age 25-45, 8 females and 5 males) were also recruited. Twenty joints (MCPs: metacarpophalangeal joints and PIPs: proximal interphalangeal joints) were scanned for each participant. The region of interest was identified for the PAI images and then quantitatively analysed to determine the degree of joint inflammation. The results were correlated with grayscale and Power Doppler US. Two-sample tests of proportions was used for statistical analysis between multiple sample groups, i.e. healthy volunteers vs patients, inactive vs active joints, were employed, taking probability values of < 0.05 as significant. To predict the diagnostic performance of the method, a Receiver Operating Characteristic (ROC) was employed. In addition, acceptability of PAI imaging was evaluated. Participants found the use of the scanner highly acceptable, both in degree of comfort and the duration of the scan procedure. High-quality, 3D images were successfully acquired in all cases. In active joints, high contrast vessel-like structures within the synovium were detected in PAI images. By comparison, the same region in the healthy joint did not demonstrate vasculature. Statistical analysis shows there are significant differences between (i) joints from healthy subjects compared to patients, (ii) inactive and active joints from patients. The PAI image analysis correlates well with clinical severity grade (CSG) assessed by Power Doppler US. Finally, the ROC curve analysis shows the AUC of 0.9 with 95% confidence interval range of 0.80-0.96. The Fabry-Perot interferometer-based photoacoustic system generates rapid three-dimensional high-resolution images of the micro-vessels in patients with active synovitis. By quantifying the vascular signal, we have provided an additional physiological biomarker of joint inflammation, which may in time replace the need for operator-dependent ultrasound evaluation of targeted joints. Photoacoustic tomography could therefore be utilised as a safe and easy-to-use handheld tool in the diagnosis of active inflammation and monitoring of patients with RA M. Castelino: None. N. Huynh: None. J. Zhu: None. P. Beard: Other; co-founder of spin out company DeepColor Imaging SAS.

The use of a planar detection geometry in photoacoustic tomography results in the so- called limited-view problem due to the finite extent of the acoustic detection aperture. When images are reconstructed using one-step reconstruction algorithms, image quality is compromised by the presence of streaking artefacts, reduced contrast, image distortion and reduced signal-to-noise ratio. To mitigate this, model-based iterative reconstruction approaches based on least squares minimisation with and without total variation regularization were evaluated using in-silico, experimental phantom, ex vivo and in vivo data. Compared to one-step reconstruction methods, it has been shown that iterative methods provide better image quality in terms of enhanced signal-to-artefact ratio, signal-to-noise ratio, amplitude accuracy and spatial fidelity. For the total variation approaches, the impact of the regularization parameter on image feature scale and amplitude distribution was evaluated. In addition, the extent to which the use of Bregman iterations can compensate for the systematic amplitude bias introduced by total variation was studied. This investigation is expected to inform the practical application of model-based iterative image reconstruction approaches for improving photoacoustic image quality when using finite aperture planar detection geometries.

We demonstrate increasing the sensitivity of interferometric ultrasound sensors by boosting the probe laser power then averaging over many detectors to reduce noise while avoiding saturation. The method could enable order-of-magnitude sensitivity increases, enhancing the capabilities of photoacoustic imaging and other optical ultrasound systems.

A Fabry Perot photoacoustic scanner has been developed for clinical use. The scanner has been evaluated by conducting an exploratory healthy volunteer and patient study to assess its applicability to the assessment of inflammatory arthritis.

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.

A 3D convolutional neural network which was trained using simulated data only has been assessed for the purpose of estimating surrogate sO2 from multiwavelength photoacoustic images of experimental phantoms with well-defined ground truths.

Curvelet frame is of special significance for photoacoustic tomography (PAT) due to its sparsifying and microlocalisation properties. We derive a one-to-one map between wavefront directions in image and data spaces in PAT which suggests near equivalence between the recovery of the initial pressure and PAT data from compressed/subsampled measurements when assuming sparsity in Curvelet frame. As the latter is computationally more tractable, investigation to which extent this equivalence holds conducted in this paper is of immediate practical significance. To this end we formulate and compare DR, a two step approach based on the recovery of the complete volume of the photoacoustic data from the subsampled data followed by the acoustic inversion, and p 0 R , a one step approach where the photoacoustic image (the initial pressure, p 0 ) is directly recovered from the subsampled data. Effective representation of the photoacoustic data requires basis defined on the range of the photoacoustic forward operator. To this end we propose a novel wedge-restriction of Curvelet transform which enables us to construct such basis. Both recovery problems are formulated in a variational framework. As the Curvelet frame is heavily overdetermined, we use reweighted l 1 norm penalties to enhance the sparsity of the solution. The data reconstruction problem DR is a standard compressed sensing recovery problem, which we solve using an ADMM-type algorithm, SALSA. Subsequently, the initial pressure is recovered using time reversal as implemented in the k-Wave Toolbox. The p 0 reconstruction problem, p 0 R , aims to recover the photoacoustic image directly via FISTA, or ADMM when in addition including a non-negativity constraint. We compare and discuss the relative merits of the two approaches and illustrate them on 2D simulated and 3D real data in a fair and rigorous manner.

The limited view of a planar detector array results in artefacts in the reconstructed images. To address this, iterative image reconstruction methods have been proposed. However, there remains a need for a rigorous assessment of their performance in terms of artefact reduction, small structure detection, spatial resolution and robustness to noise. Additionally, an understanding of the impact of regularisation parameters on image fidelity and SNR as a function of the target geometry and instrument noise is required. The aim of this study is to explore these factors and advance the practical application of iterative reconstruction methods for in vivo images acquired using a planar detection geometry.

A broadband all-optical plane-wave ultrasound imaging system for high-resolution 3-D imaging of biological tissues is presented. The system is based on a planar Fabry-Perot (FP) scanner for ultrasound detection and the photoacoustic generation of ultrasound in a carbon-nanotube-polydimethylsiloxane (CNT-PDMS) composite film. The FP sensor head was coated with the CNT-PDMS film which acts as an ultrasound transmitting layer for pulse-echo imaging. Exciting the CNT-PDMS coating with nanosecond laser pulses generated monopolar plane-wave ultrasound pulses with MPa-range peak pressures and a -6-dB bandwidth of 22 MHz, which were transmitted into the target. The resulting scattered acoustic field was detected across a 15 mm ×15 mm scan area with a step size of 100 [Formula: see text] and an optically defined element size of [Formula: see text]. The -3-dB bandwidth of the sensor was 30 MHz. A 3-D image of the scatterer distribution was then recovered using a k -space reconstruction algorithm. To obtain a measure of spatial resolution, the instrument line-spread function (LSF) was measured as a function of position. At the center of the scan area, the depth-dependent lateral LSF ranged from 46 to 65 [Formula: see text] for depths between 1 and 12 mm. The vertical LSF was independent of position and measured to be [Formula: see text] over the entire field of view. To demonstrate the ability of the system to provide high-resolution 3-D images, phantoms with well-defined scattering structures of arbitrary geometry were imaged. To demonstrate its suitability for imaging biological tissues, phantoms with similar impedance mismatches, sound speed and scattering properties to those present in the tissue, and ex vivo tissue samples were imaged. Compared with conventional piezoelectric-based ultrasound scanners, this approach offers the potential for improved image quality and higher resolution for superficial tissue imaging. Since the FP scanner is capable of high-resolution 3-D photoacoustic imaging of in vivo biological tissues, the system could ultimately be developed into an instrument for dual-mode all-optical ultrasound and photoacoustic imaging.

Minimally invasive procedures are increasingly being preferred over the conventional open procedures as it offers range of benefits to the patients such as quick recovery time, reduced infection rates, minimal tissue damage and scarring. However, in situ assessment of malignancies and identification of tumour margins remains a challenge with existing intraoperative imaging techniques. We present a novel 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.

AbstractSuccessful therapy of twin‐to‐twin transfusion syndrome requires accurate imaging to guide laser photocoagulation of the anastomosing placental vessels. Photoacoustic (PA) imaging is an alternative imaging method that provides contrast for hemoglobin, and in this study, it was used to visualize chorionic superficial and subsurface vasculature in human placentas. The strong potential of PA imaging to guide minimally invasive fetal therapies was demonstrated.Further details can be found in the article by Efthymios Maneas, Rosalind Aughwane, Nam Huynh, et al. (e201900167). image

A custom fibre laser designed as an excitation source for biomedical photoacoustic tomography has been developed. It is based on a custom-drawn large core diameter fibre (200 µm) that enables high pulse energies (∼10 mJ) to be achieved. The system can provide variable pulse durations (10 - 500 ns) and pulse repetition frequencies (100 Hz - 1 kHz), as well as arbitrary pulse bursts according to specific user defined sequences. The system is also compact and does not require external water cooling. This, along with the flexibility in the temporal characteristics of its output that it offers, will aid the translation of photoacoustic imaging to practical application in medicine and biology.

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.

Non-GPS localization has gained much interest from researchers and industries recently because GPS might fail to meet the accuracy requirements in shadowing environments. The two most common range-based non-GPS localization methods, namely Received Signal Strength Indicator (RSSI) and Angle-of-Arrival (AOA), have been intensively mentioned in the literature over the last decade. However, an in-depth analysis of the weighted combination methods of AOA and RSSI in shadowing environments is still missing in the state-of-the-art. This paper proposes several weighted combinations of the two RSSI and AOA components in the form of pAOA + qRSSI, devises the mathematical model for analyzing shadowing effects, and evaluates these weighted combination localization methods from both accuracy and precision perspectives. Our simulations show that increasing the number of anchors does not necessarily improve the precision and accuracy, that the AOA component is less susceptible to shadowing than the RSSI one, and that increasing the weight of the AOA component and reducing that of the RSSI component help improve the accuracy and precision at high Signal-to-Noise Ratios (SNRs). This observation suggests that some power control algorithm could be used to increase automatically the transmitted power when the channel experiences large shadowing to maintain a high SNR, thus guaranteeing both accuracy and precision of the weighted combination localization techniques.