Single-side access, isotropic resolution and multispectral 3D photoacoustic imaging with rotate-translate scanning of ultrasonic detector array

Photoacoustic imaging can achieve high-resolution three-dimensional visualization of optical absorbers at penetration depths ~ 1 cm in biological tissues by detecting optically-induced high ultrasound frequencies. Tomographic acquisition with ultrasound linear arrays offers an easy implementation of single-side access, parallelized and high-frequency detection, but usually comes with an image quality impaired by the directionality of the detectors. Indeed, a simple translation of the array perpendicularly to its median imaging plane is often used, but results both in a poor resolution in the translation direction and in strong limited view artifacts. To improve the spatial resolution and the visibility of complex structures while keeping a planar detection geometry, we introduce, in this paper, a novel rotate-translate scanning scheme, and investigate the performance of a scanner implemented at 15 MHz center frequency. The developed system achieved a quasi-isotropic uniform 3D resolution of ~170 um over a cubic volume of side length 8.5 mm, i.e. an improvement in the resolution in the translation direction by almost one order of magnitude. Dual wavelength imaging was also demonstrated with ultrafast wavelength shifting. The validity of our approach was shown in vitro. We discuss the ability to enable in vivo imaging for preclinical and clinical studies.Comment: 43 pages, 5 figure

Investigation of Techniques to increase the Field of View of a Staring Transducer Array for Photoacoustic Imaging

Photoacoustic imaging (PAI) is a hybrid imaging modality that takes advantage of both optical and acoustic techniques for biomedical imaging. It is believed that PAI can successfully assess the margins of lumpectomy specimens in the operating room, decreasing the number of surgeries and wait time for patients. However, current PAI systems do not have sufficient field of view (FOV) to accommodate the size of lumpectomy specimens. In this work, transducer directionality and the use of a shaped matching layer were explored as means to increase the FOV of a staring photoacoustic transducer array. The results indicated that applying a convex matching layer to the face of transducers and directing them toward the centre of the array provides optimal sensitivity throughout the imaging volume. By employing these techniques, any PAI system’s effective FOV can be increased without replacing existing transducers. The optimized system can now be investigated for lumpectomy margin assessment

Mitigating the limited view problem in photoacoustic tomography for a planar detection geometry by regularised iterative reconstruction

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 regularisation 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 regularisation 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

A method for delineation of bone surfaces in photoacoustic computed tomography of the finger

Photoacoustic imaging of interphalangeal peripheral joints is of interest in the context of using the synovial membrane as a surrogate marker of rheumatoid arthritis. Previous work has shown that ultrasound produced by absorption of light at the epidermis reflects on the bone surfaces within the finger. When the reflected signals are backprojected in the region of interest, artifacts are produced, confounding interpretation of the images. In this work, we present an approach where the photoacoustic signals known to originate from the epidermis, are treated as virtual ultrasound transmitters, and a separate reconstruction is performed as in ultrasound reflection imaging. This allows us to identify the bone surfaces. Further, the identification of the joint space is important as this provides a landmark to localize a region-of-interest in seeking the inflamed synovial membrane. The ability to delineate bone surfaces allows us not only to identify the artifacts, but also to identify the interphalangeal joint space without recourse to new US hardware or a new measurement. We test the approach on phantoms and on a healthy human finger

Photo-acoustic tomographic image reconstruction from reduced data using physically inspired regularization

We propose a model-based image reconstruction method for photoacoustic tomography(PAT) involving a novel form of regularization and demonstrate its ability to recover good quality images from significantly reduced size datasets. The regularization is constructed to suit the physical structure of typical PAT images. We construct it by combining second-order derivatives and intensity into a non-convex form to exploit a structural property of PAT images that we observe: in PAT images, high intensities and high second-order derivatives are jointly sparse. The specific form of regularization constructed here is a modification of the form proposed for fluorescence image restoration. This regularization is combined with a data fidelity cost, and the required image is obtained as the minimizer of this cost. As this regularization is non-convex, the efficiency of the minimization method is crucial in obtaining artifact-free reconstructions. We develop a custom minimization method for efficiently handling this non-convex minimization problem. Further, as non-convex minimization requires a large number of iterations and the PAT forward model in the data-fidelity term has to be applied in the iterations, we propose a computational structure for efficient implementation of the forward model with reduced memory requirements. We evaluate the proposed method on both simulated and real measured data sets and compare them with a recent reconstruction method that is based on a well-known fast iterative shrinkage threshold algorithm (FISTA).Comment: This manuscript has been published in Journal of Instrumentatio

Three-dimensional Photoacoustic Tomography System Design Analysis and Optimization

Photoacoustic tomography (PAT) is an emerging imaging modality capable of mapping optical absorption in tissues. It is a hybrid technique that combines the high spatial resolution of ultrasound imaging with the high contrast of optical imaging, and has demonstrated much potential in biomedical applications. Conventional PAT systems employ raster scanning to capture a large number of projections, thus improving image reconstruction at the cost of temporal resolution. Arising from the desire for real-time 3D PA imaging, several groups have begun to design PAT systems with staring arrays, where image acquisition is only limited by the repetition rate of the laser. However, there has been little emphasis on staring array design analysis and optimization. We have developed objective figures of merit for PAT system performance and applied these metrics to improve system design. The results suggested that the developed approach could be used to objectively characterize and improve any PAT system design

Review of photoacoustic imaging plus X

Photoacoustic imaging (PAI) is a novel modality in biomedical imaging technology that combines the rich optical contrast with the deep penetration of ultrasound. To date, PAI technology has found applications in various biomedical fields. In this review, we present an overview of the emerging research frontiers on PAI plus other advanced technologies, named as PAI plus X, which includes but not limited to PAI plus treatment, PAI plus new circuits design, PAI plus accurate positioning system, PAI plus fast scanning systems, PAI plus novel ultrasound sensors, PAI plus advanced laser sources, PAI plus deep learning, and PAI plus other imaging modalities. We will discuss each technology's current state, technical advantages, and prospects for application, reported mostly in recent three years. Lastly, we discuss and summarize the challenges and potential future work in PAI plus X area

Handheld optoacoustic probe facilitating nearfield investigations through a transparent detector

Modern medicine relies strongly on measurement devices, enabling the physician to investigate the human body in ever greater detail. In addition to established techniques of optical microscopy, ultrasound, x-ray and magnetic resonance imaging, optoacoustic (OA) imaging is on its path to enter the clinics. The research field of optoacoustics already produced a variety of remarkable setups, from high resolution microscopy to deep penetrating tomography. Through the broad range of wavelengths available for this technique, it is capable of detecting the concentration of endogenous as well as exogenous contrast agents, even blood oxygenation levels can be determined in real time. Depending on the application, different OA setups can be created, customized to best address the specific task. This thesis is concerned with the development of a handheld optoacoustic setup to determine the thickness of melanoma. Penetration depth is the most important factor in staging of skin tumors. To facilitate near field measurements the detector is designed to be transparent, which allows illumination through the detector. Indium tin oxide electrodes are sputtered on a piezoelectric polymer film to create a circular detector area. Transparency was confirmed using spectrophotometric measurements in the visible and near infrared light spectrum. To characterize the capabilities of the transparent detector, far field measurements on hydrogel samples with layers containing different concentrations of melanin were performed. An OA measurement series on a mole under laboratory conditions showcased the possibility using wavelengths in the range from 432-652 nm with this detector. For logistical reasons, only 532 nm were used in the other measurements. Near field measurements on a coated glass plate are compared with simulation, confirming the validity of the data processing algorithm to remove the pyroelectric signal and deconvolve the instrument response function from the OA signal. In a small clinical study, suspicious nevi were investigated using the setup developed here. The obtained OA signals are discussed in relation with the histology of the respective nevus. Even though their thicknesses could not yet be determined reliably, the results are promising that further improvements with regards to noise reduction will allow real time measurements of the absorption depth profile

Quantitative photoacoustic tomography: experimental phantom studies

Photoacoustic tomography (PAT) is a promising non-invasive imaging modality exhibiting high resolution, good contrast and specificity to light-absorbing molecules (chromophores). One of the outstanding challenges the technique faces is that PAT images, though dependent on optical absorption, are not its direct representation because they are coloured by the unknown light fluence. Theoretical studies have succeeded in quantifying optical absorption and chromophore concentration by employing model-based inversions (MBI) that can deal with the non-linearity of the problem and the fluence-related distortion. However, experimental translation has been scarce. The aim was to perform quantitative PAT (qPAT) in a rigorous experimental phantom study to show that highly-resolved 3D estimation of chromophore distributions can be achieved. The first consideration was finding a tissue-relevant and stable matrix material and chromophores. Thermoplastic PVCP was fully assessed. Its stability, intrinsic optical properties, thermoelastic efficiency and low-frequency acoustic properties were suitable. The limitation was the lack of photostability of embedded pigments. Separately, we fully characterised aqueous solutions of sulphate salts and found them to be suitable chromophores for qPAT and potential surrogates for oxy- and deoxyhemoglobin. For a phantom made of sub-mm tubes filled with sulphate solutions in an intralipid-rich background, 3D high resolution estimates of chromophore concentrations were obtained through an efficient diffusion-approximation MBI. Uncertainties in optical inputs of the MBI were tackled by assessing in silico their effect on quantification accuracy and then mitigated in the designed experiment through careful measurements. A faithful representation of the multiwavelength photoacoustic tomography images was sought by employing broadband, near-omnidirectional and high-sensitivity sensors and a detection configuration and reconstruction that overcame the limited-view problem. Estimation of the chromophore ratio, analogous to the much sought-after blood oxygenation, gave a mean absolute error of 3.4 p.p., whilst normalised estimates of the two main chromophore distributions gave errors of 13.2% and 17.2%

Limited Angle Ultrasound Tomography of the Compressed Breast

X-ray mammography is widely accepted as the clinical standard for breast cancer screening and diagnosis. However, reflection mode ultrasound has been known to outperform x-ray in screening performance in dense breasts. With newer modes of ultrasound, acoustic properties of breast tissue, such as the speed of sound and attenuation coefficient distributions, can be extracted from captured ultrasound signals and used to characterize breast tissue types and contribute to detection and diagnosis of malignancy. The same is possibly true for optical absorption via photoacoustic imaging. Recently, we have developed a dual-sided ultrasound scanner that can be integrated with existing x-ray mammographic systems and acquire images in the mammographic view and compression. Transmission imaging for speed of sound and attenuation coefficient in this geometry is termed limited angle tomography, as the beams at frequencies yielding high resolution cannot transit the long axis of the compressed breast. This approach, ideally, should facilitate the co-registration and comparisons between images from three modalities discussed here (x-ray, ultrasound and photoacoustic) and increase diagnostic detection confidence. However, potential limitations inherent in limited angle tomography have received minimal exploration up to this study, and existing imaging techniques developed for this approach are based on overly optimistic assumptions that hinder achievement of the desired image quality. This investigation of these problems should contribute valuable information to the validation and translation of the mammographically-configured, dual-sided ultrasound, or ultrasound and photoacoustic, scanner to the clinic. This dissertation first aims to extensively identify possible sources of error resulting from imaging in the limited angle tomography approach. Simulation findings mapping parametric conditions reveal that image artifacts arising in reflection mode (B-mode) can be modulated or mitigated by ultrasound gels with adequate acoustic properties. In addition, sound speed imaging was performed determining the level of significance for several key sources of error. Results suggest that imaging in transmission mode is the most sensitive to transducer misplacement in the signal propagation direction. This misplacement, however, could be minimized easily by routinely calibrating transducer positions. Next, this dissertation aims to advance speed of sound, attenuation, and photoacoustic image reconstruction algorithms for the limited angle tomography approach. This was done by utilizing both structural information of the imaged objects/tissues by means of the corresponding reflection mode images taken from the same imaging location, and a full acoustic modeling framework to account for complex acoustic interactions within the field of view. We have shown through simulations that both a priori information from reflection mode images and full acoustic modeling contribute to a noticeable improvement in the reconstructed images. Work done throughout the course of this dissertation should provide a foundation and insight necessary for improvements upon the existing dual-sided ultrasound scanner towards breast imaging in the clinic.PHDBiomedical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/143944/1/rungroj_1.pd