The life sciences can benefit greatly from imaging technologies that connect microscopic discoveries with macroscopic observations. One technology uniquely positioned to provide such benefits is ...photoacoustic tomography (PAT), a sensitive modality for imaging optical absorption contrast over a range of spatial scales at high speed. In PAT, endogenous contrast reveals a tissue's anatomical, functional, metabolic, and histologic properties, and exogenous contrast provides molecular and cellular specificity. The spatial scale of PAT covers organelles, cells, tissues, organs, and small animals. Consequently, PAT is complementary to other imaging modalities in contrast mechanism, penetration, spatial resolution, and temporal resolution. We review the fundamentals of PAT and provide practical guidelines for matching PAT systems with research needs. We also summarize the most promising biomedical applications of PAT, discuss related challenges, and envision PAT's potential to lead to further breakthroughs.
Photoacoustic tomography (PAT) is probably the fastest growing biomedical imaging technology owing to its capability of high-resolution sensing of rich optical contrast in vivo at depths beyond the ...optical transport mean free path (~1 mm in the skin). Existing high-resolution optical imaging technologies, such as confocal microscopy and two-photon microscopy, have fundamentally impacted biomedicine but cannot reach such depths. Taking advantage of low ultrasonic scattering, PAT indirectly improves tissue transparency by 100 to 1000 fold and consequently enables deeply penetrating functional and molecular imaging at high spatial resolution. Further, PAT holds the promise of in vivo imaging at multiple length scales ranging from subcellular organelles to organs with the same contrast origin, an important application in multiscale systems biology research.
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Real-time imaging of countless femtosecond dynamics requires extreme speeds orders of magnitude beyond the limits of electronic sensors. Existing femtosecond imaging modalities either require event ...repetition or provide single-shot acquisition with no more than 10
frames per second (fps) and 3 × 10
frames. Here, we report compressed ultrafast spectral photography (CUSP), which attains several new records in single-shot multi-dimensional imaging speeds. In active mode, CUSP achieves both 7 × 10
fps and 10
frames simultaneously by synergizing spectral encoding, pulse splitting, temporal shearing, and compressed sensing-enabling unprecedented quantitative imaging of rapid nonlinear light-matter interaction. In passive mode, CUSP provides four-dimensional (4D) spectral imaging at 0.5 × 10
fps, allowing the first single-shot spectrally resolved fluorescence lifetime imaging microscopy (SR-FLIM). As a real-time multi-dimensional imaging technology with the highest speeds and most frames, CUSP is envisioned to play instrumental roles in numerous pivotal scientific studies without the need for event repetition.
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.
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Tutorial on photoacoustic tomography Zhou, Yong; Yao, Junjie; Wang, Lihong V
Journal of biomedical optics,
06/2016, Volume:
21, Issue:
6
Journal Article
Peer reviewed
Open access
Photoacoustic tomography (PAT) has become one of the fastest growing fields in biomedical optics. Unlike pure optical imaging, such as confocal microscopy and two-photon microscopy, PAT employs ...acoustic detection to image optical absorption contrast with high-resolution deep into scattering tissue. So far, PAT has been widely used for multiscale anatomical, functional, and molecular imaging of biological tissues. We focus on PAT's basic principles, major implementations, imaging contrasts, and recent applications.
Significance: Acoustically detecting the rich optical absorption contrast in biological tissues, photoacoustic tomography (PAT) seamlessly bridges the functional and molecular sensitivity of optical ...excitation with the deep penetration and high scalability of ultrasound detection. As a result of continuous technological innovations and commercial development, PAT has been playing an increasingly important role in life sciences and patient care, including functional brain imaging, smart drug delivery, early cancer diagnosis, and interventional therapy guidance.
Aim: Built on our 2016 tutorial article that focused on the principles and implementations of PAT, this perspective aims to provide an update on the exciting technical advances in PAT.
Approach: This perspective focuses on the recent PAT innovations in volumetric deep-tissue imaging, high-speed wide-field microscopic imaging, high-sensitivity optical ultrasound detection, and machine-learning enhanced image reconstruction and data processing. Representative applications are introduced to demonstrate these enabling technical breakthroughs in biomedical research.
Conclusions: We conclude the perspective by discussing the future development of PAT technologies.
Commercially available high-resolution three-dimensional optical imaging
modalities—including confocal microscopy, two-photon microscopy, and optical coherence
tomography—have fundamentally impacted ...biomedicine. Unfortunately, such tools cannot
penetrate biological tissue deeper than the optical transport mean free path
(
∼
1
mm
in the skin). Photoacoustic
tomography, which
combines strong optical contrast and high ultrasonic resolution in a single modality, has
broken through this fundamental depth limitation and achieved superdepth high-resolution
optical
imaging. In parallel, radio frequency-or microwave-induced
thermoacoustic tomography is being actively developed to combine radio frequency or
microwave contrast
with ultrasonic resolution. In this Vision
20
∕
20
article, the prospects of photoacoustic
tomography are
envisaged in the following aspects: (1) photoacoustic microscopy of optical absorption
emerging as a mainstream technology, (2) melanoma detection using photoacoustic
microscopy, (3) photoacoustic endoscopy, (4) simultaneous functional and molecular
photoacoustic
tomography, (5)
photoacoustic
tomography of gene
expression, (6) Doppler photoacoustic
tomography for
flow measurement, (7) photoacoustic
tomography of
metabolic rate of oxygen, (8) photoacoustic mapping of sentinel lymph nodes, (9)
multiscale photoacoustic
imaging
in vivo with common signal origins, (10) simultaneous photoacoustic and
thermoacoustic tomography of the breast, (11) photoacoustic and
thermoacoustic tomography of the brain, and (12) low-background thermoacoustic
molecular imaging.
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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.
Photoacoustic microscopy Yao, Junjie; Wang, Lihong V.
Laser & photonics reviews,
September 2013, Volume:
7, Issue:
5
Journal Article
Peer reviewed
Open access
Photoacoustic microscopy (PAM) is a hybrid in vivo imaging technique that acoustically detects optical contrast via the photoacoustic effect. Unlike pure optical microscopic techniques, PAM takes ...advantage of the weak acoustic scattering in tissue and thus breaks through the optical diffusion limit (∼1 mm in soft tissue). With its excellent scalability, PAM can provide high‐resolution images at desired maximum imaging depths up to a few millimeters. Compared with backscattering‐based confocal microscopy and optical coherence tomography, PAM provides absorption contrast instead of scattering contrast. Furthermore, PAM can image more molecules, endogenous or exogenous, at their absorbing wavelengths than fluorescence‐based methods, such as wide‐field, confocal, and multi‐photon microscopy. Most importantly, PAM can simultaneously image anatomical, functional, molecular, flow dynamic and metabolic contrasts in vivo. Focusing on state‐of‐the‐art developments in PAM, this Review discusses the key features of PAM implementations and their applications in biomedical studies.
Photoacoustic microscopy (PAM) is a hybrid in vivo imaging technique that acoustically detects optical contrast via the photoacoustic effect. Unlike pure optical microscopic techniques, PAM takes advantage of the weak acoustic scattering in tissue and thus breaks through the optical diffusion limit (∼1 mm in soft tissue). With its excellent scalability, PAM can provide high‐resolution images at desired maximum imaging depths up to a few millimeters. Compared with backscattering‐based confocal microscopy and optical coherence tomography, PAM provides absorption contrast instead of scattering contrast. Furthermore, PAM can image more molecules, endogenous or exogenous, at their absorbing wavelengths than fluorescence‐based methods, such as wide‐field, confocal, and multi‐photon microscopy. Most importantly, PAM can simultaneously image anatomical, functional, molecular, flow dynamic and metabolic contrasts in vivo. Focusing on state‐of‐the‐art developments in PAM, this Review discusses the key features of PAM implementations and their applications in biomedical studies.
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