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) 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.
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.
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.
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.
Non-invasively focusing light into strongly scattering media, such as biological tissue, is highly desirable but challenging. Recently, ultrasonically guided wavefront shaping technologies have been ...developed to address this limitation. So far, the focusing resolution of most implementations has been limited by acoustic diffraction. Here, we introduce nonlinear photoacoustically guided wavefront shaping (PAWS), which achieves optical diffraction-limited focusing in scattering media. We develop an efficient dual-pulse excitation approach to generate strong nonlinear photoacoustic (PA) signals based on the Grueneisen relaxation effect. These nonlinear PA signals are used as feedback to guide iterative wavefront optimization. As a result, light is effectively focused to a single optical speckle grain on the scale of 5-7 µm, which is ~10 times smaller than the acoustic focus with an enhancement factor of ~6,000 in peak fluence. This technology has the potential to benefit many applications that desire highly confined strong optical focus in tissue.
The field of photoacoustic tomography has experienced considerable growth in the past few years. Although several commercially available pure optical imaging modalities, including confocal ...microscopy, two-photon microscopy, and optical coherence tomography, have been highly successful, none of these technologies can provide penetration beyond ~1 mm into scattering biological tissues, because they are based on ballistic and quasi-ballistic photons. Heretofore, there has been a void in high-resolution optical imaging beyond this penetration limit. Photoacoustic tomography, which combines high ultrasonic resolution and strong optical contrast in a single modality, has broken through this limitation and filled this void. In this paper, the fundamentals of photoacoustics are first introduced. Then, scanning photoacoustic microscopy and reconstruction-based photoacoustic tomography (or photoacoustic computed tomography) are covered.
The capture of transient scenes at high imaging speed has been long sought by photographers, with early examples being the well known recording in 1878 of a horse in motion and the 1887 photograph of ...a supersonic bullet. However, not until the late twentieth century were breakthroughs achieved in demonstrating ultrahigh-speed imaging (more than 10(5) frames per second). In particular, the introduction of electronic imaging sensors based on the charge-coupled device (CCD) or complementary metal-oxide-semiconductor (CMOS) technology revolutionized high-speed photography, enabling acquisition rates of up to 10(7) frames per second. Despite these sensors' widespread impact, further increasing frame rates using CCD or CMOS technology is fundamentally limited by their on-chip storage and electronic readout speed. Here we demonstrate a two-dimensional dynamic imaging technique, compressed ultrafast photography (CUP), which can capture non-repetitive time-evolving events at up to 10(11) frames per second. Compared with existing ultrafast imaging techniques, CUP has the prominent advantage of measuring an x-y-t (x, y, spatial coordinates; t, time) scene with a single camera snapshot, thereby allowing observation of transient events with temporal resolution as tens of picoseconds. Furthermore, akin to traditional photography, CUP is receive-only, and so does not need the specialized active illumination required by other single-shot ultrafast imagers. As a result, CUP can image a variety of luminescent--such as fluorescent or bioluminescent--objects. Using CUP, we visualize four fundamental physical phenomena with single laser shots only: laser pulse reflection and refraction, photon racing in two media, and faster-than-light propagation of non-information (that is, motion that appears faster than the speed of light but cannot convey information). Given CUP's capability, we expect it to find widespread applications in both fundamental and applied sciences, including biomedical research.
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