Photoacoustic tomography (PAT) can create multiscale multicontrast images of living biological structures ranging from organelles to organs. This emerging technology overcomes the high degree of scattering of optical photons in biological tissue by making use of the photoacoustic effect. Light absorption by molecules creates a thermally induced pressure jump that launches ultrasonic waves, which are received by acoustic detectors to form images. Different implementations of PAT allow the spatial resolution to be scaled with the desired imaging depth in tissue while a high depth-to-resolution ratio is maintained. As a rule of thumb, the achievable spatial resolution is on the order of 1/200 of the desired imaging depth, which can reach up to 7 centimeters. PAT provides anatomical, functional, metabolic, molecular, and genetic contrasts of vasculature, hemodynamics, oxygen metabolism, biomarkers, and gene expression. We review the state of the art of PAT for both biological and clinical studies and discuss future prospects.

Photoacoustic Tomography: In Vivo Imaging from Organelles to Organs

Gold nanoparticles have been used in biomedical applications since their first colloidal syntheses more than three centuries ago. However, over the past two decades, their beautiful colors and unique electronic properties have also attracted tremendous attention due to their historical applications in art and ancient medicine and current applications in enhanced optoelectronics and photovoltaics. In spite of their modest alchemical beginnings, gold nanoparticles exhibit physical properties that are truly different from both small molecules and bulk materials, as well as from other nanoscale particles. Their unique combination of properties is just beginning to be fully realized in range of medical diagnostic and therapeutic applications. This critical review will provide insights into the design, synthesis, functionalization, and applications of these artificial molecules in biomedicine and discuss their tailored interactions with biological systems to achieve improved patient health. Further, we provide a survey of the rapidly expanding body of literature on this topic and argue that gold nanotechnology-enabled biomedicine is not simply an act of ‘gilding the (nanomedicinal) lily’, but that a new ‘Golden Age’ of biomedical nanotechnology is truly upon us. Moving forward, the most challenging nanoscience ahead of us will be to find new chemical and physical methods of functionalizing gold nanoparticles with compounds that can promote efficient binding, clearance, and biocompatibility and to assess their safety to other biological systems and their long-term term effects on human health and reproduction (472 references).

The golden age: gold nanoparticles for biomedicine

Photoacoustic imaging (also called optoacoustic or thermoacoustic imaging) has the potential to image animal or human organs, such as the breast and the brain, with simultaneous high contrast and high spatial resolution. This article provides an overview of the rapidly expanding field of photoacoustic imaging for biomedical applications. Imaging techniques, including depth profiling in layered media, scanning tomography with focused ultrasonic transducers, image forming with an acoustic lens, and computed tomography with unfocused transducers, are introduced. Special emphasis is placed on computed tomography, including reconstruction algorithms, spatial resolution, and related recent experiments. Promising biomedical applications are discussed throughout the text, including (1) tomographic imaging of the skin and other superficial organs by laser-induced photoacoustic microscopy, which offers the critical advantages, over current high-resolution optical imaging modalities, of deeper imaging depth and higher absorptioncontrasts, (2) breast cancerdetection by near-infrared light or radio-frequency–wave-induced photoacoustic imaging, which has important potential for early detection, and (3) small animal imaging by laser-induced photoacoustic imaging, which measures unique optical absorptioncontrasts related to important biochemical information and provides better resolution in deep tissues than optical imaging.

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Photoacoustic imaging in biomedicine

Photoacoustic (PA) imaging, also called optoacoustic imaging, is a new biomedical imaging modality based on the use of laser-generated ultrasound that has emerged over the last decade. It is a hybrid modality, combining the high-contrast and spectroscopic-based specificity of optical imaging with the high spatial resolution of ultrasound imaging. In essence, a PA image can be regarded as an ultrasound image in which the contrast depends not on the mechanical and elastic properties of the tissue, but its optical properties, specifically optical absorption. As a consequence, it offers greater specificity than conventional ultrasound imaging with the ability to detect haemoglobin, lipids, water and other light-absorbing chomophores, but with greater penetration depth than purely optical imaging modalities that rely on ballistic photons. As well as visualizing anatomical structures such as the microvasculature, it can also provide functional information in the form of blood oxygenation, blood flow and temperature. All of this can be achieved over a wide range of length scales from micrometres to centimetres with scalable spatial resolution. These attributes lend PA imaging to a wide variety of applications in clinical medicine, preclinical research and basic biology for studying cancer, cardiovascular disease, abnormalities of the microcirculation and other conditions. With the emergence of a variety of truly compelling in vivo images obtained by a number of groups around the world in the last 2–3 years, the technique has come of age and the promise of PA imaging is now beginning to be realized. Recent highlights include the demonstration of whole-body small-animal imaging, the first demonstrations of molecular imaging, the introduction of new microscopy modes and the first steps towards clinical breast imaging being taken as well as a myriad of in vivo preclinical imaging studies. In this article, the underlying physical principles of the technique, its practical implementation, and a range of clinical and preclinical applications are reviewed.

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Biomedical photoacoustic imaging

Imaging techniques based on optical contrast analysis can be used to visualize dynamic and functional properties of the nervous system via optical signals resulting from changes in blood volume, oxygen consumption and cellular swelling associated with brain physiology and pathology. Here we report in vivo noninvasive transdermal and transcranial imaging of the structure and function of rat brains by means of laser-induced photoacoustic tomography (PAT). The advantage of PAT over pure optical imaging is that it retains intrinsic optical contrast characteristics while taking advantage of the diffraction-limited high spatial resolution of ultrasound. We accurately mapped rat brain structures, with and without lesions, and functional cerebral hemodynamic changes in cortical blood vessels around the whisker-barrel cortex in response to whisker stimulation. We also imaged hyperoxia- and hypoxia-induced cerebral hemodynamic changes. This neuroimaging modality holds promise for applications in neurophysiology, neuropathology and neurotherapy.

Noninvasive laser-induced photoacoustic tomography for structural and functional in vivo imaging of the brain

We report results of a reconstruction algorithm for three-dimensional photoacoustic computed tomography. A universal back-projection formula is presented for three types of imaging geometries: planar, spherical, and cylindrical surfaces. A solid-angle weighting factor is introduced in the back-projection formula to compensate for the variations of detection views. A method for implementing this algorithm is described. Numerical simulation is used to demonstrate the performance of the algorithm.

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Universal back-projection algorithm for photoacoustic computed tomography.

Reconstruction-based microwave-induced thermoacoustic tomography in a spherical configuration is presented. Thermoacoustic waves from biological tissue samples excited by microwave pulses are measured by a wide-band unfocused ultrasonic transducer, which is set on a spherical surface enclosing the sample. Sufficient data are acquired from different directions to reconstruct the microwave absorption distribution. An exact reconstruction solution is derived and approximated to a modified backprojection algorithm. Experiments demonstrate that the reconstructed images agree well with the original samples. The spatial resolution of the system reaches 0.5 mm.

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Time-domain reconstruction for thermoacoustic tomography in a spherical geometry

We report a universal back-projection formula for three-dimensional photoacoustic computed tomography in three types of imaging geometries: planar, spherical, and cylindrical surfaces. A solid-angle weighting factor is introduced in the back-projection formula to compensate for the variations of detection views. Numerical simulation demonstrates the performance of the algorithm.

/pdf/universal-back-projection-algorithm-for-photoacoustic-436sb7bdzw.pdf

Universal back-projection algorithm for photoacoustic computed tomography

An analytic explanation of the spatial resolution in thermoacoustic or photoacoustic reconstruction is presented. Three types of specific recording geometries, including spherical, planar, and cylindrical surface, as well as other general cases, are investigated. Analytic expressions of the point-spread functions (PSF's), as a function of the bandwidth of the measurement system and the finite size of the detector aperture, are derived based on rigorous reconstruction formulas. The analyses clearly reveal that the dependence of the PSF's on the bandwidth of all recording geometries shares the same space-invariant expression while the dependence on the aperture size of the detector differs. The bandwidth affects both axial and lateral resolutions; in contrast, the detector aperture blurs the lateral resolution greatly but the axial resolution only slightly.

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Minghua Xu

Papers

Photoacoustic imaging in biomedicine

Universal back-projection algorithm for photoacoustic computed tomography.

Time-domain reconstruction for thermoacoustic tomography in a spherical geometry

Universal back-projection algorithm for photoacoustic computed tomography

Analytic explanation of spatial resolution related to bandwidth and detector aperture size in thermoacoustic or photoacoustic reconstruction.