This PDF file contains the front matter associated with SPIE Proceedings Volume 11077, including the Title Page, Copyright information, Table of Contents, Author and Conference Committee lists.

Stem cell therapies promise to allow the blind to see, the lame to walk and those enslaved to thrice weekly dialysis to be free. However, they have not yet fulfilled their potential, partly because we don’t know where stem cells go and what they do deep inside organs of real living humans. We recently identified a general limit of medical imaging which encapsulates the challenge; current technologies do not allow visualization of objects more than 200 times smaller than the depth. For example, cellular details more than c. 1 mm into typical human tissues like the skin cannot be imaged by any technology. The TOMI lab won a €6M EU H2020 grant to develop technologies to see deeper and smaller and with greater sensitivity than ever before. We go beyond the depth/resolution limit by demonstrating nanosensitive OCT to follow structural changes in cells and tissues at the nanoscale. Using a unique star-shaped gold nanoparticle made in Galway, which resonates in the low scattering and absorption window close to 1100 nm, allows us to see deeper and with greater sensitivity than ever before. The combination of long wavelength, tip field enhancement and energy transfer make this particle the brightest ever made. We combine this with photoacoustic imaging, so that we can use diffuse light to illuminate the tissue and ultrasound which is not scattered, to see where it was absorbed. The particle is magnetized by SPION conjugation so that is also visible in MRI. We will demonstrate this enhanced imaging in Cambridge during stem cell therapy for osteoarthritis of the knee. This paper will report the efforts to optimize nanostar guided optoacoustic imaging for stem cell tracking in small and large pre-clinical models.

Systemic Sclerosis (SSc) is an autoimmune disease characterized by a triad of inflammation, vasculopathy, and fibrosis of the skin and internal organs such as gastrointestinal tract, heart, lungs, and kidneys. SSc can lead to premature death especially when there is cardiopulmonary involvement. At early stages, SSc is characterized by an alteration of blood vessel network and hypoxia in the fingertip. Imaging these parameters could lead to early diagnosis of SSc patients. In this study, we investigated the feasibility to detect and diagnose SSc by imaging the oxygen saturation in the nail-bed using photoacoustics (PA) and estimating skin thickening using high-frequency ultrasound (HFUS). Thirty-one subjects (adult man and women) participated in this study: 12 patients with systemic sclerosis, 5 patients with early systemic sclerosis, 5 subjects with primary Raynaud’s phenomenon, and 9 healthy volunteers. The measurements showed that both the nail bed oxygen saturation (77.9% ±10.5 vs. 94.8% ±2.8, p < 0.0001) and the skin thickness (0.51 ±0.17 mm vs. 0.31 ±0.06 mm, p<0.005) of patients with SSc was significantly different compared to healthy volunteers. Most importantly the measurements showed a significant difference between early SSc and primary Raynaud’s phenomenon for both oxygen saturation (80.8 ± 8.1% vs. 93.9 ± 1.1%) and skin thickness (0.48 ± 0.06 mm vs. 0.27 ± 0.01 mm). The PA and HFUS data was supported by conventional capillaroscopy imaging performed on all participants. This pilot study demonstrates the possibility to use photoacoustics and high-frequency ultrasound as a diagnostic tool for early detection of systemic sclerosis.

Laser ablation (LA) represents a minimally invasive intervention that is gaining acceptance for the treatment of different types of cancer, leading to important advantages such as less pain and shorter recovery time. Accurate monitoring of ablation progression is crucial to prevent damage of non-cancerous tissues and optimize the outcome of the intervention. To this end, imaging techniques such as ultrasound, computed tomography or magnetic resonance imaging have been used for monitoring LA. However, these techniques feature important drawbacks such as the need of contrast agents, poor spatio-temporal resolution or high cost. Optoacoustics (OA, photoacoustic) has recently been shown to provide unique properties to monitor thermal treatments. Herein, we demonstrate the feasibility of optoacoustic laser-ablation (OLA) monitoring in a murine breast tumor model using a single short-pulsed 1064 nm laser source. The effect of irradiation was volumetrically tracked with the OA images acquired with a 256-element spherical array. Structural damage of the tissue was clearly seen during the LA procedure.

In situ temperature monitoring with photoacoustic measurements is introduced in an integrated setup, specifically designed for photothermotherapy treatmentof the glioblastoma, aided by nanoparticles and HIFU blood-brain barrier opening.

We present the comparison of two approaches of blood oxygen saturation determination from multispectral optoacoustic measurements: a calibration-free approach based on evaluation of the effective optical attenuation coefficient derived from in-depth OA signal decay, and an approach based on determination of optical absorption coefficient from OA signal amplitudes. Both approaches were tested in in vitro and in vivo experiments. The results of in vitro and in vivo experiments demonstrated the large difference between experimentally obtained μ_eff spectra and the literature data, that indicates much lower potential of the OA signal decay approach as compared to OA amplitudes approach. In vivo measurements of the μ_a spectrum experimentally obtained from OA signal amplitudes give the saturation values of 0.57±0.08 and 0.50±0.07 for two veins of the thoracic spine that agree well with physiological values for venous blood oxygenation in rat. Instead of multiple wavelengths measurements, a pair of wavelengths can be employed for OA measurements. In this case, the saturation maps were obtained at all wavelength pairs from the 658‒1069 nm range. The results demonstrated that the most accurate oxygenation values can be achieved at wavelength pairs of 700 nm and a wavelength from the range 850-1069 nm.

Photoacoustic imaging relies on diffused photons for optical contrast, and diffracted ultrasound for high resolution. As a tomographic imaging modality, often times an inverse problem of acoustic diffraction needs to be solved to reconstruct a photoacoustic image. The inverse problem is complicated by the fact that the acoustic properties, including the speed of sound distribution, in the image field of view are unknown. During reconstruction, subtle changes of the speed of sound in the acoustic ray path may accumulate and give rise to noticeable blurring in the image. Thus, in addition to the ultrasound detection bandwidth, inaccurate acoustic modeling, especially the unawareness of the speed of sound, defines the image resolution and influences image quantification. Here, we proposed a method termed feature coupling to jointly reconstruct the speed of sound distribution and a photoacoustic image with improved sharpness, at no additional hardware cost. In vivo experiments demonstrated the effectiveness and reliability of our method.

A method to quantify morphological parameters of photoacoustic (PA) source from its angular distribution of differential photoacoustic cross-section (DPACS) is discussed. The DPACS for spheroidal particles with varying aspect ratio (AR) and the Chebyshev particles with different waviness and deformation parameters has been calculated using Green’s function approach. The DPACS as a function of measurement angle of those particles has been fitted with tri-axes ellipsoid form factor model to estimate the shape parameters. It is found that an enhancement of the DPACS occurs as the surface area of the source normal to the direction of measurement is increased. It decreases as the thickness of the source along the direction of measurement increases. For example, the DPACS in case of a spheroid for AR = 1:6 is 1.7 times greater than that of a particle with AR = 1:3 along θ=0°. The tri-axes ellipsoid model determines the size information of the spheroids accurately (error ≤10%). Estimated volumes for Chebyshev particles differ within ±10% with respect to the nominal values for most of the cases. The approach reported here may find application in practice to assess cellular morphology.

The Fabry-Perot interferometer (FPI) is widely used in photoacoustic imaging (PAI) as an ultrasound (US) sensor due to its high sensitivity to weak US waves. Such high sensitivity is important as it allows for increasing the depth in tissue at which PAI can access, thus strongly influencing its clinical applicability. FPI sensitivity is impacted by many factors including the FPI mirror reflectivity, focussed beam spot size, FPI cavity thickness and aberrations introduced by the optical readout system. Improving FPI sensitivity requires a mathematical model of its optical response which takes all of these factors into account. Previous attempts to construct such a model have been critically limited by unrealistic assumptions. In this work we have developed a general model of FPI optical readout which based upon electromagnetic theory. By making very few assumptions, the model is able to replicate experimental results and allows insight to be gained into the operating principles of the sensor.

In optical detection of ultrasound, resonators with high Q-factors are frequently used to maximize sensitivity. However, in order to perform parallel interrogation, conventional interferometric techniques require an overlap between the resonator spectra, which is difficult to achieve with high Q-factor resonators. In this work, a new method is developed for simultaneous interrogation of optical resonators with non-overlapping spectra. The method is based on a phase modulation scheme for pulse interferometry (PM-PI) and requires only a single photodetector and sampling channel per ultrasound detector. Using PM-PI, parallel ultrasound detection is demonstrated with four high Q-factor resonators.

We present a ultra-thin system that combines optical resolution photoacoustic microscopy and fluorescence imaging based on a multimode fiber and a fiber optical hydrophone with only 250μm cross section.

During percutaneous medical interventions, accurate needle placement and advancing to the target of interest is required to avoid complications and to improve clinical outcomes. Therefore, we present a novel photoacoustic (PA) imaging-based approach as a complement to conventional ultrasound (US) imaging for visualization and guidance of interventional needles. To overcome the limitations associated with light penetration with the conventional extracorporeal illumination, we propose an interstitial light delivery to the target of interest by use of a custom-made annular illumination probe (AIP). This probe accommodates an interventional needle (14 gauge) within its lumen, allowing to advance both tools and acquire real-time PAUS images simultaneously. The light is delivered utilizing 72 multimode optical fibers arranged around the circumference of the hollow center of the AIP. Preliminary results show that PA images obtained with the AIP provide with good complementary contrast to the US imaging for visualization of the interventional needles and its guidance to an absorbing target within chicken breast tissue.

We present the investigation of in vivo small model organisms, which are well established in biological and biomedical research, using a hybrid multiphoton and optoacoustic microscope (HyMPOM). The unique capabilities of HyMPOM for multimodal and potentially label-free signal acquisition, high resolution, as well as deep and fast imaging allow extraction of detailed information across large areas of living tissue on the microscale. Applying HyMPOM to living zebrafish-like fish larvae allowed exploration of the structural composition of the entire brain, including the brain vasculature and the neuronal network. Applying HyMPOM to the ears of living mice enabled accurate imaging of vasculature, connective tissue, keratinocytes, and sebaceous glands. The hybrid microscope proposed here constitutes a novel approach to explore small model organisms in vivo in great detail by revealing the spatial distribution and interplay of various tissue compartments on the microscale.

We report on further progress made on enhancing the capabilities of a multi-imaging modality instrument capable of producing high resolution images of biological tissues. At the core of the instrument is a supercontinuum (SC) source. Two SC sources commercialized by NKT Photonics were employed for our experiments: SuperK COMPACT and SuperK Extreme (EXR9). Using these two sources, we assembled an instrument capable to simultaneously provide in real-time cross-section high-resolution Optical Coherence Tomography (OCT) and Photo-acoustic (PA) images in various spectral ranges. Currently, the OCT channel is operating in the IR range around 1300 nm to allow better penetration into the tissue using either the COMPACT or the EXR9. The measured optical power on the sample is in both cases above 9.5 mW. An in-house spectrometer equipped with a sensitive InGaAs camera capable of operating at 47 kHz and sampling data over a spectral range from 1205 to 1395 nm was developed. A constant axial resolution provided by the instrument in the OCT channel over a range of 1.5 mm was experimentally measured (4.96 μm), matching the theoretical prediction. The spectral range 500-800 nm was used for PA channel. The COMPACT, used in the PA channel, can select the central wavelength and the spectral bandwidth of operations. Typically, the optical energy per pulse on the sample is superior to 60 nJ when a bandwidth superior to 50 nm is employed. This make the instrument usable for PA imaging of tissues.

Current research has been extensively focusing on translating photoacoustic imaging into clinics using ultrasound handheld probes. However, a major drawback of these probes is the occurrence of artifacts which might lead to critical image misinterpretation. In-plane and out-of-plane artifacts are the two types of the artifacts in photoacoustic imaging. Recently we have reported a method for identifying reflection artifacts (in-plane artifacts). In this work, we propose a new method for removing out-of-plane artifacts by displacing the transducer array. Using transducer array displacement, out-of-plane artifacts can be de-correlated with in-plane image features and thus removed. We experimentally demonstrated this method with experiments in phantoms as well as in vivo. Results show that this is a promising approach for correcting out-of-plane artifacts.

Photoacoustic tomography (PAT) is a hybrid imaging modality that combines optical contrast with ultrasound resolution. Most of the PAT configurations are based on high-energy solid-state lasers such as Nd:YAG laser. In this work, a PAT system that uses light-emitting diode (LED) as a light source is introduced. The system is designed so that the imaged target can be stationary. The target is illuminated by a LED light source from one side and the pressure wave is measured using an acoustic transducer that is rotated around the target. Image reconstruction is based on Bayesian approach to illposed inverse problems. The system was tested with light absorbing targets also in limited-view and sparse angle measurement situations. The results show that LED-based instrumentation and advanced reconstruction methods can form a potential PAT system that can also be applied in limited-view and sparse angle photoacoustic tomography.

An optical resolution photoacoustic microscopy (OR-PAM) setup was used to generate transient cavitation on a strongly absorbing target. The cavitation bubble dynamics were monitored with an optical probe beam, which was guided collinearly and confocally with the excitation laser pulses. Simultaneously, the acoustic transients occurring during initiation and collapse of the bubbles were measured with a probe beam deflection method. With 25 nJ pulse energy, cavitation bubbles of 15 to 20 μm maximum diameter were generated around a carbon fiber. Bubble properties, such as its expansion speed and lifetime were observed with the optical signal, which showed oscillations caused by interference after reflection at the bubble walls. The acoustic signal provided additional measurements of the bubble lifetime. The proposed method can be used to investigate the influence of cavitation on the acoustic OR-PAM signal and to monitor theranostic applications of cavitation bubbles.

We present a dual-wavelength laser using stimulated Raman scattering (SRS) effect which have high pulse repetition rate for fast functional photoacoustic (PA) imaging. This laser has a high pulse repetition rate of 300 kHz and high pulse energy more than 200 nJ. We periodically modulated the electro-optic modulator voltage from 0 to 168 V to switch the polarization of the output light. Two different pulse lights separated by polarization switching were used to generate different SRS peaks using Raman fibers with lengths of 5 and 20 m. The operating wavelength of this laser was switched to 545 nm and 603 nm using SRS effect and polarization switching. Wavelength dependent fast functional PA images of blood vessels and gold nanorods were obtained using a dual-wavelength switchable SRS pulsed-laser.

Raster-scan optoacoustic angiography at 532 nm wavelength with 50 μm lateral resolution at 2 mm diagnostic depth was used for quantitative characterization of neoangiogenesis in colon cancer models. Vessels of subcutaneously growing murine colon carcinoma (СT26) was imaged from 5th to 13th day of growth. The values of vascular density were calculated from the optoacoustic data. Inhomogeneous distribution of areas with high and low vascularization was demonstrated in the tumors. During tumor development vessel growth from the periphery to the center of the tumor was shown. Increase of vascular density precedes the increase of tumor volume. The obtained results may be important for the investigation of tumor development and for improvement of cancer treatment strategies.

Role of sensor sensitivity in photoacoustic tomography (PAT) imaging is discussed. In this study, sensitivity profile (apodization) of finite size sensors was considered as axisymmetric and modelled by using a Gaussian function. The full width at half maximum (FWHM) of the Gaussian function was varied in order to investigate its effect on PAT image reconstruction. The images were reconstructed using conventional delay-and-sum (CDAS) and modified delay-and-sum (MDAS) algorithms. In case of the CDAS, a Gaussian function was used to weight the PA signals detected by different parts of the sensor and the resultant signal was computed by summing those signals. However, in case of the MDAS, the Gaussian weight was applied in both directions (signal acquisition and redistribution of the pressure values at different point locations on the aperture of the finite sensor). The performance of these algorithms was investigated with respect to ideal point detectors by conducting numerical experiments in the k-Wave toolbox. The results for the CDAS and the MDAS algorithms are found to be very close to that of ideal point detectors when FWHM is small. The MDAS technique appears to be much superior to the CDAS approach when FWHM is large. The MDAS method can be employed in practice for apodized transducers as well if the Gaussian weight is applied in both directions (signal acquisition and redistribution).

Coherence-restored pulse interferometry (CRPI) is a recently developed method for optical detection of ultrasound that achieves shot-noise-limited sensitivity and high dynamic range. In principle, the wideband source employed in CRPI may enable the interrogation of multiple detectors by using wavelength multiplexing. However, the noisereduction scheme in CRPI has not been shown to be compatible with wideband operation. In this work, we introduce a new scheme for CRPI that relies on a free-space Fabry-Perot filter for noise reduction and a pulse stretcher for reducing nonlinear effects. Using our scheme, we demonstrate that shot-noise-limited detection may be achieved for a spectral band of 80 nm and powers of up to 5 mW.

Radiofrequency ablation (RFA) is a widely used treatment method for unresectable malignant tumors. In percutaneous RFA, the tumor recurrence rate is high due to incomplete ablation. Feedback from the imaging system during the RFA procedure is vital in reducing the tumor recurrence. We propose the use of photoacoustic (PA) imaging, integrated with an ultrasound (US) system to monitor the RFA procedure. The imaging system consists of a US system with a linear array and a pulsed laser illumination. We study the PA assisted RFA device guidance to an anomalous target embedded inside a chicken breast tissue. We compare both US and PA images to highlight the advantage of using the proposed method. Further, we image an ablated ex vivo bovine liver sample using the system. The result shows a drop in PA intensity from the ablated region compared to normal tissue. Our preliminary study shows that PA imaging is a potential modality for RFA procedures.

We present a 3D photoacoustic and ultrasound tomographic system intended for imaging of breast phantoms with the capacity to detect millimetric objects. The speciality of the ultrasound imaging part is that transmitters based on laser-induce ultrasound (LIUS) are used for acoustic generation. We describe the design and development of transmitters including an absorbing layer for photoacoustic generation.

Photoacoustic imaging can show the distribution of vessels and the degree of oxygen saturation, reliably supporting diagnoses of complaints such as cancer and articular rheumatism. Our handheld imaging system for percutaneous photoacoustic imaging and ultrasound imaging can take measurements easily. However, an important difficulty remains: reflection artifacts degrade the image quality. Reflection artifacts arise when photoacoustic waves from signal source reflect at the tissue boundary and are detected using a handheld probe. To address this difficulty, methods for identifying and eliminating reflection artifacts using single wavelength light have been developed.however, the detection accuracy of these methods is insufficient. On the other hand, tissue specificity of optical properties can achieve higher image quality when taking multi-wavelength measurements. We propose a method for identifying and eliminating reflection artifacts using the photoacoustic spectrum in multi-wavelength measurements. The photoacoustic signal intensity is wavelength-dependent and fluence-dependent. Reflection artifacts’ spectra are similar to that of the upper signal source. The spectrum of the signal source at the same depth as reflection artifact differs from the upper signal source. We took multi-wavelength measurements of a phantom mimicking vessels using piano wire in deaerated water including black ink or Intralipid of various consistencies. We then compared the photoacoustic spectra of piano wire and reflection artifacts by calculating root mean square (RMS). Results show that the reflection artifact spectrum and the upper signal source spectrum are more similar than the lower photoacoustic signal source spectrum. These analyses underscore the potential of this method for identifying and eliminating reflection artifacts.

We demonstrate the application of an extended field of view microscope, combining photoacoustic and fluorescence label-free contrast modalities, for the ex vivo investigation of ocular tissues including the ciliary muscle in healthy rabbit eyes and surgical biopsies of benign nevi removed from human eyes. In the case of ciliary muscle samples, the intrinsic photoacoustic and the glutaraldehyde-induced autofluorescence signals were observed to be spatially complementary, offering specific and high resolution morphological information as regards to Pars plana and Pars plicata ciliary body portions, iris, and zonule fiber strands. On the other hand, the biopsy samples presented a remarkable spatial overlap of the two signals in the nevus region, indicating a positive correlation between them. The bimodal microscopy approach presented in this work, has the potential to contribute in the understanding of the physiological function of the eye involving the detailed study of the ocular accommodation system and the elucidation of ageing effects such as presbyopia. Finally, the proposed hybrid diagnostic approach could be employed for the differentiation between benign and malignant intraocular tumors of the uvea in surgical biopsies, simplifying the relevant procedures for this purpose.

In order to combine sensitive optical detection with acoustic focusing in a compact device, we propose in this work the idea of large area optical ultrasound detection, utilizing the integrating effect of a probe laser beam propagating in a plane for enhanced interaction with the acoustic field. The key component of the setup is the sensor head consisting of an acoustic lens mounted on a glass cube. Two opposite side faces of the cube are coated with a reflective metal layer except a small stripe at the edges of the cube that enables the probe beam to enter and exit the interaction zone for ultrasound detection. An obliquely incident probe beam crosses the cube along a zigzag path, thereby increasing the interaction length compared to single-pass detection. Recorded signals are proportional to the beam deflection caused by acoustically generated pressure gradients in the glass cube. With the proposed detection approach a 5 MHz detection bandwidth, a lateral spatial resolution of 330 μm and an 8-times increased signal strength was observed compared to single pass detection without folded probe beam propagation. Although the proposed free beam detection setup cannot keep up with the performance of commonly used AR-PAM systems based on piezoelectric ultrasound detection, the idea of large area optical ultrasound detection equipped with an acoustic lens has high potential. For instance, it should be possible to transfer this idea to integrated optics equipped with an acoustic lens.

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.

In this work we developed a novel near-infrared two-path optoacoustic spectrometer (NiR-TAOS) that could sense OA intensity changes due to metabolite concentration changes in-vivo. The main aim of dividing the optical path in two is 1) perform real time correction of the laser emission profile of the laser source at different wavelengths and, 2) perform pulse to pulse correction to remove laser beam fluctuation and instability to increase signal to noise ratio. Signal to noise ratio improvement was significant not only at spectral peaks, but also at all other wavelengths. The system can be used for broad applications in biomedical measurements such as various metabolites in the SWIR.

Remote photoacoustic tomography by speckle-analysis which is based on the measurement of the surface tilt is interesting for a lot of medical applications such as endoscopy or wound imaging. In this work, a new model which is capable to simulate the resulting surface tilt after photoacoustic excitation is presented. A Monte Carlo simulation is coupled to a stress simulation which allows the determination of the temporal surface deformation and the resulting tilt. A first comparison to experimental results from literature is done and discussed. In future, this model might help to optimize the speckle-sensing technique for photoacoustic signal detection. Furthermore, it could be used to develop and test image reconstruction algorithms.

Associated with local articular rigidity, swelling and pain as well as systemic development of fever and a sense of fatigue, arthritis is a disorder causing deterioration of patients’ quality of life. Approximately 300,000 patients report rheumatoid arthritis, one of the typical chronic joint inflammation, in Japan alone: 1% of the world’s population has the disorder worldwide. Although X-ray CT, MRI, and ultrasonic Doppler method are used for examination and diagnosis, various problems exist such as radiation exposure, administration of contrast agents and difficulty in earlier diagnosis and quantitative evaluation. To resolve these difficulties, we developed a handheld photoacoustic imaging system. In this study, the feasibility of evaluating the degree of inflammation using photoacoustic imaging with multiple wavelengths was investigated with in vivo measurements of model rats. The changes in signal intensity depending on the presence or absence of the disorder was examined. It was confirmed that the signal intensity can be intensified at diseased joints. Then, the changes with different time elapsed from drug administration was examined using rats. It was clarified that the degree of inflammation can be evaluated by shapes of photoacoustic spectra, which changed along with the progress of the inflammation. Through these analyses, we verified the usefulness of photoacoustic imaging for the diagnosis and evaluation of arthritis.

A multiphysics model was developed to model the increase in temperature during phototherapy treatment (PTT) in mouse brain. The model includes also a numerical model for Photoacoustic thermometer during the hyper- thermia therapy. The coupling of different physics was investigated.

The Er:YAG laser has gained significant interest in the field of oral surgery due to its high water absorptivity, precision and patient acceptance. However, its application is limited by the lack of a contact-free feedback system which would enable safe laser guidance. In this work, a potential new, robust feedback modality based on speckle-analysis is presented which detects the acoustic signals produced during laser surgery. Oral soft- and hard tissue samples are investigated ex-vivo for its differentiation capability using the speckle modality. This technique might help to broaden the clinical application of Er:YAG lasers.

The rupture of a vulnerable carotid plaque featuring a lipid-rich necrotic core and intra-plaque haemorrhages is the major cause of stroke. Photoacoustic imaging (PAI) is a promising technique for assessing plaque vulnerability in the carotid artery due to its ability to assess the chemical composition in addition to its anatomy. However, assessment of chemical composition is usually based on the absorption differences of chromophores between multiple wavelengths, which heavily increase the complexity and cost of the imaging system. In this study, a new method based on single-wavelength PAI to detect intra-plaque haemorrhages, an important indicator of plaque vulnerability, is developed. The method uses wall filtering based on singular value decomposition. To test the method, a carotid plaque phantom mimicking intra-plaque haemorrhages, lumen and vasa vasorum is designed and imaged at 808nm in vitro. The phantom experiment shows wall filtering using singular value decomposition to be a viable method capable of discriminating signals originating from the lumen, vasa vasorum and intraplaque haemorrhages, allowing for the detection of intra-plaque haemorrhages with single wavelength PAI. This enables new opportunities for PAI of vulnerable carotid plaques with more cost effective and diverse laser sources.

Photoacoustic measurements are tested as a possible tool for non invasive quantification of Water/Collagen relative content in InterVertebral Discs (IVDs).

Lasers have become a generally accepted tool for surgery due to their advantages compared to traditional approaches like the scalpel. However, lasers lack a feedback system for safe laser guidance. This problem prevents the potential laser application for a lot of medical cases in the clinical environment. In this work, a new tissue differentiation modality which might be implemented as a feedback system using remote speckle-sensing is presented. This modality is tested on three tissue types and the results are discussed.

Photoacoustic remote sensing microscopy is a recently developed optical non-contact imaging method that provides optical absorption contrast in reflection mode. Previously, this was performed by co-scanning of tightly co-focused excitation and interrogation beams. We have demonstrated the proof of principle that superficial optical absorption information can be measured from a scattering sample by a camera in reflection mode using a pulsed excitation and interrogation beams. This allows wide field-of-view absorption imaging in scattering samples in real-time. Using a wirebonding wire embedded in a phantom, the photoacoustic effect is first induced by a 532-nm pulsed excitation beam which alters the optical property of the wire that is illuminated with a 1064-nm pulsed interrogation beam with 80 ns delay. The scattering of the interrogation beam with and without the excitation beam is captured by the camera and the difference is calculated. Increasing contrast in difference images can be observed as the fluence rate of the excitation beam is set to 5.28 mJ/cm², 12.8 mJ/cm², 19.5 mJ/cm² and 26.0 mJ/cm². The mean relative difference is increased from 0.92 %, 2.10 %, 2.64 % and 3.27%, respectively.