Photoacoustic Microscopy and Photoacoustic Computed Tomography Using High-frequency Linear Array Ultrasonic Transducers

Photoacoustic tomography (PAT) is a highly promising imaging technology which forms images by detecting the induced pressure waves resulting from pulsed light absorption in biological tissues. Because the excitation source is light, PAT is a very safe, non-ionizing, and non-carcinogenic imaging technology. In biomedicine, PAT has the unique advantage of probing endogenous optical absorbers at different length scales with 100% relative sensitivity. With such scalability, PAT can image anatomical, functional, metabolic, molecular, and genetic contrasts of vasculature, hemodynamics, oxygen metabolism, biomarkers, and gene expression. Among several implementations of PAT, optical-resolution photoacoustic microscopy (OR-PAM) and photoacoustic computed tomography (PACT) are two of the most widely used. OR-PAM can achieve optical diffraction limited spatial resolution with maximum imaging depths up to one transport mean free path (~1 mm in biological tissue). PACT can achieve several centimeters imaging depth in tissue by employing ultrasonic array detectors and inverse algorithms. This dissertation aims to improve the functionality of OR-PAM using a high-frequency linear ultrasonic array, and to advance the performance of linear-array PACT to full view angle capability and higher resolution. The first part of this dissertation describes the technological advancement of multifocal optical-resolution photoacoustic microscopy (MFOR-PAM). Compared with single-focus OR-PAM, 1D multifocal OR-PAM utilizes both multifocal optical illumination and an ultrasonic transducer array, significantly increasing the imaging speed. We present a reflection-mode 1D multifocal OR-PAM system based on a 1D microlens array that provides multiple foci as well as an ultrasonic transducer array that receives the excited photoacoustic waves from all foci simultaneously. Using a customized microprism to reflect the incident laser beam to the microlens array, the multiple optical foci are aligned confocally with the focal zone of the ultrasonic transducer array. Experiments show the reflection-mode 1D multifocal OR-PAM is capable of imaging microvessels in vivo, and it can image a 6 × 5 × 2.5 mm3 volume at 16 μm lateral resolution in ∼2.5 min, limited by the signal multiplexing ratio and laser pulse repetition rate. While 1D-MFOR-PAM accelerates the scan in only one direction, a two-dimensional MFOR-PAM (2D-MFOR-PAM) fully explores the advantage of a 2D microlens array. By scanning a small range of 250 mm × 250 mm, we eventually obtained a large field of view of 10 mm × 10 mm in ~50 seconds, with a spatial resolution of 15.2 mm. The second part of this dissertation describes methods of increasing the view angle of linear-array PACT, which suffers from a limited view. While rotating either the transducer array or the imaging objects circularly enables full-view linear-array PACT, this process is time consuming. Here we propose two innovative methods to increase the view angle. The first method is to triple the detection view angle by using two planar acoustic reflectors placed at 120 degrees to each other. Without sacrificing the imaging speed, we form two virtual linear transducer arrays, adding two vantage points. Experimental results show the detection view angle of the linear-array PACT was increased from 80 to 240 degrees. The second method is an ultrasonic thermal encoding approach that is universally applicable to achieve full-view imaging with linear-array PACT. We demonstrate full-view in vivo vascular imaging and compare it to the original linear-array PACT images, showing dramatically enhanced imaging of arbitrarily oriented blood vessels. The last part of the dissertation describes the development of algorithms for linear-array PACT. The first proposed algorithm is a multi-view Hilbert transformation, which provides accurate optical absorption for full-view linear-array PACT. A multi-view high-frequency PACT imaging system was implemented with a commercial 40-MHz central frequency linear transducer array. By rotating the object through multiple angles with respect to the linear transducer array, we acquired full-view photoacoustic pressure measurements. The in-plane spatial resolution of this full-view linear-array PACT was quantified to be isotropically 60 mm within a 10×10 mm2 field of view. The system was demonstrated by imaging both a leaf skeleton and a zebrafish in vivo. The second algorithm is an inverse linear Radon transformation (ILRT), which allows linear-PACT to achieve isotropic resolution at all depth planes. Images of microspheres acquired by inverse linear Radon transformation PACT (ILRT-PACT) demonstrate that our technique improves the elevational resolution by up to 9.4 times over that of a single linear scan. The technique is further demonstrated through in vivo imaging of the mouse brain through an intact scalp

Tripling the detection view of high-frequency linear-array-based photoacoustic computed tomography by using two planar acoustic reflectors

Background: Linear-array-based photoacoustic computed tomography (PACT) suffers from a limited view. Circular scanning does increase the detection view angle but is time-consuming. Therefore, it is desirable to increase the detection view angle of linear-array-based PACT without sacrificing imaging speed. Methods: Two planar acoustic reflectors placed at 120 degrees to each other were added to a linear-array-based PACT system. Each reflector redirects originally undetectable photoacoustic waves back to the transducer array elements, and together they triple the original detection view angle of the PACT system. Results: Adding two reflectors increased the detection view angle from 80 to 240 degrees. As a comparison, a single-reflector PACT has a detection view angle of only 160 degrees. A leaf skeleton phantom with a rich vascular network was imaged with the double-reflector PACT, and most of its features were recovered. Conclusions: The two acoustic reflectors triple the detection view angle of a linear-array-based PACT without compromising the original imaging speed. This nearly full-view detection capability produces higher-quality images than single-reflector PACT or conventional PACT without reflectors

Investigation of ultrasonic properties of MAGIC gels for pulse-echo gel dosimetry

This thesis describes investigations into the design and evaluation of novel ultrasonic methods for 3-dimensional ionising radiation dose verification. Pulse-echo ultrasound methods were investigated for the measurement and analysis of complex radiation therapy dose delivery.The physical properties of MAGIC (Methacrylic and Ascorbic acid in Gelatin Initiated by Copper) polymer gel dosimeters have been characterized. The variations of speed of sound, ultrasonic attenuation coefficient and density of MAGIC gel with radiation dose and temperature have been quantified. This extends work that has previously been reported for the properties of this gel to the effect of measurement temperature on the results. The facilities to perform these measurements were specified, constructed and evaluated as part of the project.The measurement of radiation dose using ultrasound back scatter from an interface between the polymer gel dosimeter and an inert reflector is demonstrated. To enable the measurement of radiation dose using pulse-echo ultrasound methods a novel inert material has been specified, manufactured and characterised. This material is matched to the acoustic impedance of MAGIC gel to produce the most dose-sensitive reflections.The reflections from the interface between the inert reflector and dose-dependent MAGIC gel have been analysed using both a single element transducer and a commercial ultrasound scanner. Both measurement systems demonstrate the same dose and temperature dependence of the ultrasonic reflection. A methodology has been developed to relate pixel values from the ultrasound scanner to the amplitude of the reflected ultrasound signal. A phantom consisting of an array of threads formed from the inert backscattering material has been designed and constructed and a method of extracting pixel data from images of the array acquired using a commercial ultrasound scanner has been developed, so that multiple imaging positions could be used to perform a 3-dimensional assessment of radiation dose distributions.It has been demonstrated that a pulse-echo technique using a commercial ultrasound scanner shows promise for radiation gel dosimetry. Further investigation and alternative polymer gel and inert reflector combinations may improve these techniques

New methods for deep tissue imaging

Microscopes play vital role biological science and medicine. For single photon microscopies, the scattering of photons makes regions of interest located a few hundred microns beneath the surface inaccessible. Multi-photon microscopes are widely used for minimally invasive in vivo brain imaging due to their increased imaging depth. However, multi-photon microscopes are hampered by limited dynamic range, preventing weak sample features from being detected in the presence of strong features, or preventing the capture of unpredictable bursts in sample strength. In the first part of the thesis, I present a solution to vastly improve the dynamic range of a multi-photon microscope while limiting potential photodamage. Benefits are shown in both structural and in-vivo functional mouse brain imaging applications. In the second section of the thesis work, I explore a completely different approach towards deep tissue imaging by changing the type of radiation from light to ultrasound. Inspired by an optical phase contrast technique invented in the lab, I developed an unprecedented ultrasound imaging system that can visualize the ultrasound phase contrast in the sample. The ultrasound phase contrast technique is able to visualize local sound speed variations instead of local reflectivity. Compared with existing sound speed tomography systems, our technique eliminates the cumbersome sound speed reconstruction process. The research work in this section contains three parts. In the first part, we designed a low-cost single element scanning system as proof of concept. In the second part, we implemented the ultrasound phase contrast imaging system on a commercial linear phased transducer array and an imaging apparatus designed for samples with finite thickness. In the third part, we studied the feasibility of ultrasound phase contrast imaging in arbitrarily thick tissue. We presented a complete workflow of theoretical study, simulation, prototyping and experimental testing for all three parts.2020-02-28T00:00:00

Forward model for quantitative pulse-echo speed-of-sound imaging

Computed ultrasound tomography in echo mode (CUTE) allows determining the spatial distribution of speed-of-sound (SoS) inside tissue using handheld pulse-echo ultrasound (US). This technique is based on measuring the changing phase of beamformed echoes obtained under varying transmit (Tx) and/or receive (Rx) steering angles. The SoS is reconstructed by inverting a forward model describing how the spatial distribution of SoS is related to the spatial distribution of the echo phase shift. CUTE holds promise as a novel diagnostic modality that complements conventional US in a single, real-time handheld system. Here we demonstrate that, in order to obtain robust quantitative results, the forward model must contain two features that were not taken into account so far: a) the phase shift must be detected between pairs of Tx and Rx angles that are centred around a set of common mid-angles, and b) it must account for an additional phase shift induced by the error of the reconstructed position of echoes. In a phantom study mimicking liver imaging, this new model leads to a substantially improved quantitative SoS reconstruction compared to the model that has been used so far. The importance of the new model as a prerequisite for an accurate diagnosis is corroborated in preliminary volunteer results

Frequency-Dependent Attenuation Reconstruction with an Acoustic Reflector

Attenuation of ultrasound waves varies with tissue composition, hence its estimation offers great potential for tissue characterization and diagnosis and staging of pathology. We recently proposed a method that allows to spatially reconstruct the distribution of the overall ultrasound attenuation in tissue based on computed tomography, using reflections from a passive acoustic reflector. This requires a standard ultrasound transducer operating in pulse-echo mode and a calibration protocol using water measurements, thus it can be implemented on conventional ultrasound systems with minor adaptations. Herein, we extend this method by additionally estimating and imaging the frequency-dependent nature of local ultrasound attenuation for the first time. Spatial distributions of attenuation coefficient and exponent are reconstructed, enabling an elaborate and expressive tissue-specific characterization. With simulations, we demonstrate that our proposed method yields a low reconstruction error of 0.04dB/cm at 1MHz for attenuation coefficient and 0.08 for the frequency exponent. With tissue-mimicking phantoms and ex-vivo bovine muscle samples, a high reconstruction contrast as well as reproducibility are demonstrated. Attenuation exponents of a gelatin-cellulose mixture and an ex-vivo bovine muscle sample were found to be, respectively, 1.4 and 0.5 on average, from images of their heterogeneous compositions. Such frequency-dependent parametrization could enable novel imaging and diagnostic techniques, as well as help attenuation compensation other ultrasound-based imaging techniques

Ultrasonic Tomography of Immersion Circular Array by Hyperbola Algorithm

This paper presents a development and research of a non-invasive ultrasonic tomography for imaging gas/liquid two-phase flow. Ultrasonic transmitting and receiving are implemented using a circular array model that consists of 36 transducers. COMSOL Multiphysics® software is adopted for the simulation of the ultrasonic propagation in the detecting zone. Various two-phase flows with different gas distributions are radiated by ultrasonic waves and the reflection mode approach is utilized for detecting the scattering waves after the generation of fan-shaped beam. Ultrasonic attenuation and sound speed are both taken into consideration while reconstructing the two-phase flow images under the inhomogeneous medium conditions. The inversion procedure of the image reconstruction is realized using the hyperbola algorithm, which in return demonstrates the feasibility and validity of the proposed circular array model

Dual-axis illumination for virtually augmenting the detection view of optical-resolution photoacoustic microscopy

Optical-resolution photoacoustic microscopy (OR-PAM) has demonstrated fast, label-free volumetric imaging of optical-absorption contrast within the quasiballistic regime of photon scattering. However, the limited numerical aperture of the ultrasonic transducer restricts the detectability of the photoacoustic waves, thus resulting in incomplete reconstructed features. To tackle the limited-view problem, we added an oblique illumination beam to the original coaxial optical-acoustic scheme to provide a complementary detection view. The virtual augmentation of the detection view was validated through numerical simulations and tissue-phantom experiments. More importantly, the combination of top and oblique illumination successfully imaged a mouse brain in vivo down to 1 mm in depth, showing detailed brain vasculature. Of special note, it clearly revealed the diving vessels that were long missing in images from original OR-PAM

Imaging of Structural Timber Based on in Situ Radar and Ultrasonic Wave Measurements: A Review of the State-Of-The-Art

With the rapidly growing interest in using structural timber, a need exists to inspect and assess these structures using non-destructive testing (NDT). This review article summarizes NDT methods for wood inspection. After an overview of the most important NDT methods currently used, a detailed review of Ground Penetrating Radar (GPR) and Ultrasonic Testing (UST) is presented. These two techniques can be applied in situ and produce useful visual representations for quantitative assessments and damage detection. With its commercial availability and portability, GPR can help rapidly identify critical features such as moisture, voids, and metal connectors in wood structures. UST, which effectively detects deep cracks, delaminations, and variations in ultrasonic wave velocity related to moisture content, complements GPR’s capabilities. The non-destructive nature of both techniques preserves the structural integrity of timber, enabling thorough assessments without compromising integrity and durability. Techniques such as the Synthetic Aperture Focusing Technique (SAFT) and Total Focusing Method (TFM) allow for reconstructing images that an inspector can readily interpret for quantitative assessment. The development of new sensors, instruments, and analysis techniques has continued to improve the application of GPR and UST on wood. However, due to the hon-homogeneous anisotropic properties of this complex material, challenges remain to quantify defects and characterize inclusions reliably and accurately. By integrating advanced imaging algorithms that consider the material’s complex properties, combining measurements with simulations, and employing machine learning techniques, the implementation and application of GPR and UST imaging and damage detection for wood structures can be further advanced

A Characterization of Ultrasonic Full Angle Spatial Compounding as a Possible Alternative for Breast Cancer Screening

10 páginas, 10 figuras, 1 tabla.Breast cancer screening is based on X-ray mammography, while ultrasound is considered a comple- mentary technique with improved detection in dense tissue. However, breast cancer screening requires a technique that provides repeatable results at the inspection interval which cannot be achieved with manual breast exploration. During the last years there have appeared several approaches to overcome this limitation by means of automated ultrasonic tomography performed with motorized probes or with a large set of array trans- ducers. This work addresses these problems by considering a quite simple and low-cost arrangement, formed with a ring of conventional medical-grade array probes which are multiplexed to the electronics to build Full Angle Spatially Compounded (FASC) images. The work analyzes the performance of such arrange- ment in terms of resolution and isotropy, showing by numerical modelling and experimentally that it provides high resolution and homogeneity in the whole imaged region. The implementation of this technique would provide more than one circular FASC per second and a whole breast volume image in 1–2 minutes with conventional technology, a process fast enough to be clinically useful. Moreover, the automated technique is repeatable and can be used by the clinician to perform immediately the diagnosis without requiring additional data processingThis work has been supported by the project DPI2013-42236-R founded by the Spanish Ministry of Economy and Competitiveness and the project S2013/MIT-3024 funded by the Madrid Community and the EUPeer reviewe