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

Photoacoustic imaging in biomedicine and life sciences

Photo-acoustic imaging, also known as opto-acoustic imaging, has become a widely popular modality for biomedical applications. This hybrid technique possesses the advantages of high optical contrast and high ultrasonic resolution. Due to the distinct optical absorption properties of tissue compartments and main chromophores, photo-acoustics is able to non-invasively observe structural and functional variations within biological tissues including oxygenation and deoxygenation, blood vessels and spatial melanin distribution. The detection of acoustic waves produced by a pulsed laser source yields a high scaling range, from organ level photo-acoustic tomography to sub-cellular or even molecular imaging. This review discusses significant novel technical solutions utilising photo-acoustics and their applications in the fields of biomedicine and life sciences

Real-time delay-multiply-and-sum beamforming with coherence factor for in vivo clinical photoacoustic imaging of humans

In the clinical photoacoustic (PA) imaging, ultrasound (US) array transducers are typically used to provide B-mode images in real-time. To form a B-mode image, delay-and-sum (DAS) beamforming algorithm is the most commonly used algorithm because of its ease of implementation. However, this algorithm suffers from low image resolution and low contrast drawbacks. To address this issue, delay-multiply-and-sum (DMAS) beamforming algorithm has been developed to provide enhanced image quality with higher contrast, and narrower main lobe compared but has limitations on the imaging speed for clinical applications. In this paper, we present an enhanced real-time DMAS algorithm with modified coherence factor (CF) for clinical PA imaging of humans in vivo. Our algorithm improves the lateral resolution and signal-to-noise ratio (SNR) of original DMAS beam-former by suppressing the background noise and side lobes using the coherence of received signals. We optimized the computations of the proposed DMAS with CF (DMAS-CF) to achieve real-time frame rate imaging on a graphics processing unit (GPU). To evaluate the proposed algorithm, we implemented DAS and DMAS with/without CF on a clinical US/PA imaging system and quantitatively assessed their processing speed and image quality. The processing time to reconstruct one B-mode image using DAS, DAS with CF (DAS-CF), DMAS, and DMAS-CF algorithms was 7.5, 7.6, 11.1, and 11.3 ms, respectively, all achieving the real-time imaging frame rate. In terms of the image quality, the proposed DMAS-CF algorithm improved the lateral resolution and SNR by 55.4% and 93.6 dB, respectively, compared to the DAS algorithm in the phantom imaging experiments. We believe the proposed DMAS-CF algorithm and its real-time implementation contributes significantly to the improvement of imaging quality of clinical US/PA imaging system.11Ysciescopu

MEMS Technology for Biomedical Imaging Applications

Biomedical imaging is the key technique and process to create informative images of the human body or other organic structures for clinical purposes or medical science. Micro-electro-mechanical systems (MEMS) technology has demonstrated enormous potential in biomedical imaging applications due to its outstanding advantages of, for instance, miniaturization, high speed, higher resolution, and convenience of batch fabrication. There are many advancements and breakthroughs developing in the academic community, and there are a few challenges raised accordingly upon the designs, structures, fabrication, integration, and applications of MEMS for all kinds of biomedical imaging. This Special Issue aims to collate and showcase research papers, short commutations, perspectives, and insightful review articles from esteemed colleagues that demonstrate: (1) original works on the topic of MEMS components or devices based on various kinds of mechanisms for biomedical imaging; and (2) new developments and potentials of applying MEMS technology of any kind in biomedical imaging. The objective of this special session is to provide insightful information regarding the technological advancements for the researchers in the community

High-Speed Photoacoustic Microscopy In Vivo

The overarching goal of this research is to develop a novel photoacoustic microscopy: PAM) technology capable of high-speed, high-resolution 3D imaging in vivo. PAM combines the advantages of optical absorption contrast and ultrasonic resolution for deep imaging beyond the quasi-ballistic regime. Its high sensitivity to optical absorption enables the imaging of important physiological parameters, such as hemoglobin concentration and oxygen saturation, which closely correlate with angiogenesis and hypermetabolism--two hallmarks of cancer. To translate PAM to the clinic, both high imaging speed and high spatial resolution are desired. With high spatial resolution, PAM can detect small structural and functional changes early; whereas, high-speed image acquisition helps reduce motion artifacts, patient discomfort, cost, and potentially the risks associated with minimally invasive procedures such as endoscopy and intravascular imaging. To achieve high imaging speed, we have constructed a PAM system using a linear ultrasound array and a kHz-repetition-rate tunable laser. The system has achieved a 249-Hz B-scan rate and a 0.5-Hz 3D imaging rate: over ~6 mm × 10 mm × 3 mm), over 200 times faster than existing mechanical scanning PAM using a single ultrasonic transducer. In addition, high-speed optical-resolution photoacoustic microscopy: OR-PAM) technology has been developed, in which the spatial resolution in one or two dimension(s) is defined by the diffraction-limited optical focus. Using section illumination, the elevational resolution of the system has been improved from ~300 micron to ~28 micron, resulting in a significant improvement in the 3D image quality. Furthermore, multiple optical foci with a microlens array have been used to provide finer than 10-micron lateral resolution--enabling the system to image capillary-level microvessels in vivo--while offering a speed potentially 20 times faster than previously existing single-focus OR-PAM. Finally, potential biomedical applications of the developed technology have been demonstrated through in vivo imaging of murine sentinel lymph nodes, microcirculation dynamics, and human pulsatile dynamics. In the future, this high-speed PAM technology may be adapted for clinical imaging of diabetes-induced vascular complications or tumor angiogenesis, or miniaturized for gastrointestinal or intravascular applications

Super-resolution photoacoustic and ultrasound imaging with sparse arrays

It has previously been demonstrated that model-based reconstruction methods relying on a priori knowledge of the imaging point spread function (PSF) coupled to sparsity priors on the object to image can provide super-resolution in photoacoustic (PA) or in ultrasound (US) imaging. Here, we experimentally show that such reconstruction also leads to super-resolution in both PA and US imaging with arrays having much less elements than used conventionally (sparse arrays). As a proof of concept, we obtained super-resolution PA and US cross-sectional images of microfluidic channels with only 8 elements of a 128-elements linear array using a reconstruction approach based on a linear propagation forward model and assuming sparsity of the imaged structure. Although the microchannels appear indistinguishable in the conventional delay-and-sum images obtained with all the 128 transducer elements, the applied sparsity-constrained model-based reconstruction provides super-resolution with down to only 8 elements. We also report simulation results showing that the minimal number of transducer elements required to obtain a correct reconstruction is fundamentally limited by the signal-to-noise ratio. The proposed method can be straigthforwardly applied to any transducer geometry, including 2D sparse arrays for 3D super-resolution PA and US imaging