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

Single-breath-hold photoacoustic computed tomography of the breast

We have developed a single-breath-hold photoacoustic computed tomography (SBH-PACT) system to reveal detailed angiographic structures in human breasts. SBH-PACT features a deep penetration depth (4 cm in vivo) with high spatial and temporal resolutions (255 µm in-plane resolution and a 10 Hz 2D frame rate). By scanning the entire breast within a single breath hold (~15 s), a volumetric image can be acquired and subsequently reconstructed utilizing 3D back-projection with negligible breathing-induced motion artifacts. SBH-PACT clearly reveals tumors by observing higher blood vessel densities associated with tumors at high spatial resolution, showing early promise for high sensitivity in radiographically dense breasts. In addition to blood vessel imaging, the high imaging speed enables dynamic studies, such as photoacoustic elastography, which identifies tumors by showing less compliance. We imaged breast cancer patients with breast sizes ranging from B cup to DD cup, and skin pigmentations ranging from light to dark. SBH-PACT identified all the tumors without resorting to ionizing radiation or exogenous contrast, posing no health risks

Emerging technologies for the non-invasive characterization of physical-mechanical properties of tablets

The density, porosity, breaking force, viscoelastic properties, and the presence or absence of any structural defects or irregularities are important physical-mechanical quality attributes of popular solid dosage forms like tablets. The irregularities associated with these attributes may influence the drug product functionality. Thus, an accurate and efficient characterization of these properties is critical for successful development and manufacturing of a robust tablets. These properties are mainly analyzed and monitored with traditional pharmacopeial and non-pharmacopeial methods. Such methods are associated with several challenges such as lack of spatial resolution, efficiency, or sample-sparing attributes. Recent advances in technology, design, instrumentation, and software have led to the emergence of newer techniques for non-invasive characterization of physical-mechanical properties of tablets. These techniques include near infrared spectroscopy, Raman spectroscopy, X-ray microtomography, nuclear magnetic resonance (NMR) imaging, terahertz pulsed imaging, laser-induced breakdown spectroscopy, and various acoustic- and thermal-based techniques. Such state-of-the-art techniques are currently applied at various stages of development and manufacturing of tablets at industrial scale. Each technique has specific advantages or challenges with respect to operational efficiency and cost, compared to traditional analytical methods. Currently, most of these techniques are used as secondary analytical tools to support the traditional methods in characterizing or monitoring tablet quality attributes. Therefore, further development in the instrumentation and software, and studies on the applications are necessary for their adoption in routine analysis and monitoring of tablet physical-mechanical properties

Photoacoustic Microscopy and Computed Tomography: From Bench to Bedside

Photoacoustic imaging (PAI) of biological tissue has seen immense growth in the past decade, providing unprecedented spatial resolution and functional information at depths in the optical diffusive regime. PAI uniquely combines the advantages of optical excitation and those of acoustic detection. The hybrid imaging modality features high sensitivity to optical absorption and wide scalability of spatial resolution with the desired imaging depth. Here we first summarize the fundamental principles underpinning the technology, then highlight its practical implementation, and finally discuss recent advances toward clinical translation

Transcranial photoacoustic computed tomography based on a layered back-projection method

A major challenge of transcranial human brain photoacoustic computed tomography (PACT) is correcting for the acoustic aberration induced by the skull. Here, we present a modified universal back-projection (UBP) method, termed layered UBP (L-UBP), that can de-aberrate the transcranial PA signals by accommodating the skull heterogeneity into conventional UBP. In L-UBP, the acoustic medium is divided into multiple layers: the acoustic coupling fluid layer between the skull and detectors, the skull layer, and the brain tissue layer, which are assigned different acoustic properties. The transmission coefficients and wave conversion are considered at the fluid–skull and skull–tissue interfaces. Simulations of transcranial PACT using L-UBP were conducted to validate the method. Ex vivo experiments with a newly developed three-dimensional PACT system with 1-MHz center frequency demonstrated that L-UBP can substantially improve the image quality compared to conventional UBP

Micromachined Scanning Devices for 3D Acoustic Imaging

Acoustic imaging (including ultrasound and photoacoustic imaging) refers to a class of imaging methods that use high-frequency sound (ultrasound) waves to generate contrast images for the interrogated media. It provides 3D spatial distribution of structural, mechanical, and even compositional properties in different materials. To conduct 3D ultrasound imaging, 2D ultrasound transducer arrays followed by multi-channel high-frequency data acquisition (DAQ) systems are frequently used. However, as the quantity and density of the transducer elements and also the DAQ channels increase, the acoustic imaging system becomes complex, bulky, expensive, and also power consuming. This situation is especially true for 3D imaging systems, where a 2D transducer array with hundreds or even thousands of elements could be involved. To address this issue, the objective of this research is to achieve new micromachined scanning devices to enable fast and versatile 2D ultrasound signal acquisition for 3D image reconstruction without involving complex physical transducer arrays and DAQ electronics. The new micromachined scanning devices studied in this research include 1) a water-immersible scanning mirror microsystem, 2) a micromechanical scanning transducer, and 3) a multi-layer linear transducer array. Especially, the water-immersible scanning mirror microsystem is capable of scanning focused ultrasound beam (from a single-element transducer) in two dimensions for 3D high-resolution acoustic microscopy. The micromechanical scanning transducer is capable of sending and receiving ultrasound signal from a single-element transducer to a 2D array of locations for 3D acoustic tomography. The multi-layer linear transducer array allows a unique electronic scanning scheme to simulate the functioning of a much larger 2D transducer array for 3D acoustic tomography. The design, fabrication and testing of the above three devices have been successfully accomplished and their applications in 3D acoustic microscopy and tomography have been demonstrated

Micromachined Scanning Devices for 3D Acoustic Imaging

Acoustic imaging (including ultrasound and photoacoustic imaging) refers to a class of imaging methods that use high-frequency sound (ultrasound) waves to generate contrast images for the interrogated media. It provides 3D spatial distribution of structural, mechanical, and even compositional properties in different materials. To conduct 3D ultrasound imaging, 2D ultrasound transducer arrays followed by multi-channel high-frequency data acquisition (DAQ) systems are frequently used. However, as the quantity and density of the transducer elements and also the DAQ channels increase, the acoustic imaging system becomes complex, bulky, expensive, and also power consuming. This situation is especially true for 3D imaging systems, where a 2D transducer array with hundreds or even thousands of elements could be involved. To address this issue, the objective of this research is to achieve new micromachined scanning devices to enable fast and versatile 2D ultrasound signal acquisition for 3D image reconstruction without involving complex physical transducer arrays and DAQ electronics. The new micromachined scanning devices studied in this research include 1) a water-immersible scanning mirror microsystem, 2) a micromechanical scanning transducer, and 3) a multi-layer linear transducer array. Especially, the water-immersible scanning mirror microsystem is capable of scanning focused ultrasound beam (from a single-element transducer) in two dimensions for 3D high-resolution acoustic microscopy. The micromechanical scanning transducer is capable of sending and receiving ultrasound signal from a single-element transducer to a 2D array of locations for 3D acoustic tomography. The multi-layer linear transducer array allows a unique electronic scanning scheme to simulate the functioning of a much larger 2D transducer array for 3D acoustic tomography. The design, fabrication and testing of the above three devices have been successfully accomplished and their applications in 3D acoustic microscopy and tomography have been demonstrated

High Resolution Imaging and Digital Characterization of Skin Pathology By Scanning Acoustic Microscopy

Skin cancer represents the most common worldwide malignancy with a widely varying prognosis. Most of the diagnostic tools used for skin imaging are still limited to provide a definite diagnosis of skin cancer, especially melanoma. Easy access to the skin to biopsy and excision made skin underexplored using ultrasonic diagnostic imaging. Given the fact that speed of sound and acoustic impedance are related to elastic modulus, quantitative acoustic microscopy shows great potential as a useful tool for skin cancer diagnosis. The high-frequency acoustic microscopy method was used to evaluate properties of the cancer lesions for melanoma, basal cell carcinoma, and squamous cell carcinoma. The algorithm for quantitative characterization of individual cells in the histological slices has been developed. All cancer cells regardless of the cancer type have lower sound speed comparing to healthy skin cells. The melanoma cells have the lowest values of sound speed (1360 ± 50 m/s) comparing to basal cell carcinoma and squamous cell carcinoma. It was demonstrated on thickly cut skin specimens that melanoma lesions have lower acoustic impedance compared to healthy skin. These findings may become the basis for a new ultrasonic method for melanoma diagnosis or for margin status verification during the surgery helting to reduce the mortality rate from melanoma and improve healthcare in Canada and worldwide

Photoacoustic Reporter Gene Imaging And Optical Coherence Computed Tomography

Advances in imaging technologies have always been the major driving forces for the evolution of biomedical research. Compared with other modalities, optical imaging possesses several prominent merits. Because light interacts with tissue at the microscopic level through many distinct physical mechanisms, optical methods allow sensitive exploration of various aspects of the life down to the single-molecule level. From the technical perspective, optical systems utilize safe non-ionizing radiation, could be implemented at relatively low cost, also have the potential to be miniaturized for portable or endoscopic applications. As a result, optical imaging tools are playing an increasingly important role in both laboratorial research and clinical practice. Among them, photoacoustic imaging: PAI) and optical coherence tomography: OCT) are the two fastest growing branches. PAI measures the laser-induced acoustic wave, and produces high-resolution images of the optically absorbing features of tissue at multiple length-scales. OCT detects singly backscattered photons, and enables real-time high-resolution in vivo biopsy of tissue up to an optical transport mean-free-path. My doctoral research is focused on developing three novel optical imaging techniques based on the spirits of PAI and OCT. In the first part of this study, we established a new paradigm to visualize gene expression in vivo based on optical absorption. In the post-genomic era, we are now being challenged to develop novel molecular imaging methods to identify the functions of genes. PAI can detect specific molecules according to their characteristic absorption spectra, thus is a promising candidate for molecular imaging of gene expression. The full potential of photoacoustic molecular imaging still remains to be explored. For the first time, we demonstrated imaging gene expression by PAI in living mice and rats, using a chromogenic lacZ/X-gal reporter gene system. We demonstrated the expression of the lacZ reporter gene can be detected by PAI as deep as 5 cm inside tissue. In addition, we showcased that PAI could follow gene expression from the microscopic to the macroscopic level. This work represents one of the pioneering efforts to extend photoacoustic methods for molecular imaging. In the second part of this study, we developed a novel multimodal microscope, called the integrated photoacoustic and optical coherence microscope: iPOM), which combines PAI and OCT in a single imaging platform. PAI is predominantly sensitive to optical absorption, while OCT exploits optical scattering. By combining their naturally complementary imaging contrasts, iPOM can provide comprehensive information about biological tissue. We designed and built a reflection-mode prototype of iPOM, which fuses optical-resolution photoacoustic microscopy with spectral-domain optical coherence tomography. The potential applications of iPOM in studying cutaneous and ocular microcirculation, and tissue engineering were demonstrated. Finally, we invented a new optical tomography, named optical coherence computed tomography: optical CCT), which overcomes several major limitations of OCT. OCT relies on singly backscattered photons to obtain high-resolution images. Its image quality degrades fast with the increase of the depth, because the multiply scattered photons quickly become dominant at a penetration larger than 500 &mum. As a result, OCT can only effectively penetrate ~1 mm into highly scattering tissue like skin. In addition, OCT is mainly sensitive to optical scattering, which does not reflect the molecular content of tissue directly. Optical CCT measures both singly and multiply scattered photons using a low-coherence interferometer. We make use of both types of photons by adopting a model-based reconstruction algorithm. The light-tissue interaction model was established using the time-resolved Monte Carlo method. The optical properties of the tissue were reconstructed from measurements by solving the inverse radiative transport problem under the first Born approximation. As a result, optical CCT could image deeper than OCT, and provide extra molecule-specific contrasts, such as optical absorption. We designed and built the first optical CCT system. In experiments, absorbing inclusions of 100 &mum diameter were imaged with consistent quality through a 2.6-mm-thick: equivalent to ~3 transport mean-free-paths) tissue-mimicking phantom