Photoacoustic (PA) tomography imaging is an emerging, versatile, and noninvasive imaging modality, which combines the advantages of both optical imaging and ultrasound imaging. It opens up opportunities for noninvasive imaging of angiogenesis, a feature of skin pathologies including cancers and psoriasis. In this study, high-density copper oleate encapsulated within a phospholipid surfactant (CuNPs) generated a soft nanoparticle with PA contrast comparable to gold. Within the near-infrared window, the copper nanoparticles can provide a signal more than 7 times higher that of blood. ανβ3-targeted of CuNPs in a Matrigel mouse model demonstrated prominent PA contrast enhancement of the neovasculature compared to mice given nontargeted or competitively inhibited CuNPs. Incorporation of a sn-2 lipase-labile fumagillin prodrug into the CuNPs produced marked antiangiogenesis in the same model, demonstrating the theranostic potential of a PA agent for the first time in vivo. With a PA signal comparable to gold-based nanoparticles yet a lower cost and demonstrated drug delivery potential, ανβ3-targeted CuNPs hold great promise for the management of skin pathologies with neovascular features.
It is a challenge to non-invasively visualize in vivo the neovascularization in a three-dimensional (3D) scaffold with high
spatial resolution and deep penetration depth. Here we used photoacoustic microscopy (PAM) to chronically monitor
neovascularization in an inverse opal scaffold implanted in a mouse model for up to six weeks. The neovasculature was
observed to develop gradually in the same mouse. These blood vessels not only grew on top of the implanted scaffold
but also penetrated into the scaffold. The PAM system offered a lateral resolution of ~45 μm and a penetration depth of ~3 mm into the scaffold/tissue construct. By using the 3D PAM data, we further quantified the vessel area as a function
of time.
We demonstrated the potential of carbon nanoparticles (CNPs) as exogenous contrast agents for both thermoacoustic
(TA) tomography (TAT) and photoacoustic (PA) tomography (PAT). In comparison to deionized water, the CNPs
provided a four times stronger signal in TAT at 3 GHz. In comparison to blood, The CNPs provided a much stronger
signal in PAT over a broad wavelength range of 450-850 nm. Specifically, the maximum signal enhancement in PAT
was 9.4 times stronger in the near-infrared window of 635-670 nm. In vivo blood-vessel PA imaging was performed
non-invasively on a mouse femoral area. The images, captured after the tail vein injection of CNPs, show a gradual
enhancement of the optical absorption in the vessels by up to 230%. The results indicate that CNPs can be potentially
used as contrast agents for TAT and PAT to monitor the intravascular or extravascular pathways in clinical applications.
Like ultrasound endoscopy, photoacoustic endoscopy (PAE) could become a valuable addition to clinical practice due
to its deep imaging capability. Results from our recent in vivo transesophageal endoscopic imaging study on rabbits
demonstrate the technique’s capability to image major organs in the mediastinal region, such as the lung, trachea, and
cardiovascular systems. Here, we present various features from photoacoustic images from the mediastinal region of
several rabbits and discuss possible clinical contributions of this technique and directions of future technology
development.
Achieving real-time photoacoustic (PA) tomography typically requires massive ultrasound transducer arrays and data
acquisition (DAQ) electronics to receive PA waves simultaneously. In this paper, we report the first demonstration of a
photoacoustic tomography (PAT) system using optical fiber-based parallel acoustic delay lines (PADLs). By employing
PADLs to introduce specific time delays, the PA signals (on the order of a few micro seconds) can be forced to arrive at
the ultrasonic transducers at different times. As a result, time-delayed PA signals in multiple channels can be ultimately
received and processed in a serial manner with a single-element transducer, followed by single‐channel DAQ electronics. Our results show that an optically absorbing target in an optically scattering medium can be photoacoustically imaged using the newly developed PADL-based PAT system. Potentially, this approach could be adopted to significantly reduce the complexity and cost of ultrasonic array receiver systems.
Achieving real-time photoacoustic (PA) tomography typically requires multi-element ultrasound transducer arrays and their associated multiple data acquisition (DAQ) electronics to receive PA waves simultaneously. We report the first demonstration of a photoacoustic tomography (PAT) system using optical fiber-based parallel acoustic delay lines (PADLs). By employing PADLs to introduce specific time delays, the PA signals (on the order of a few micro seconds) can be forced to arrive at the ultrasonic transducers at different times. As a result, time-delayed PA signals in multiple channels can be ultimately received and processed in a serial manner with a single-element transducer, followed by single-channel DAQ electronics. Our results show that an optically absorbing target in an optically scattering medium can be photoacoustically imaged using the newly developed PADL-based PAT system. Potentially, this approach could be adopted to significantly reduce the complexity and cost of ultrasonic array receiver systems.
Photoacoustic tomography (PAT) of the human brain is challenging due to the fact that the skull strongly absorbs and scatters light, and attenuates and distorts ultrasound as well. For the first time, we demonstrated the feasibility of PAT through a whole adult human skull. A photon recycler (PR) was built to increase light transmittance through the skull. Both a graphite target and a canine brain were imaged through the skull. Use of the PR was found to improve the photoacoustic signal-to-noise ratio by a factor of 2.4. In addition, subtraction of photoacoustic signals that arise from light absorption within the skull significantly improved the contrast of the target. Our results indicate that PAT can potentially be applied to in vivo human brain imaging.
As a new class of sentinel lymph node (SLN) tracers for photoacoustic (PA) imaging, Au nanocages offer the advantages
of noninvasiveness, strong optical absorption in the near-infrared region (for deep penetration), and accumulation in
higher concentrations than the initial injected solution. By monitoring the amplitude changes of PA signals in an animal
model, we quantified the accumulations of nanocages in SLNs over time. Based on this method, we quantitatively
evaluated the kinetics of gold nanocages in SLN in terms of concentration, size, and surface modification. We could
detect the SLN at an Au nanocage injection concentration of 50 pM and a dose of 100 μL in vivo. This concentration is
about 40 times less than the previously reported value. We also investigated the influence of nanocages' size (50 nm and
30 nm in edge length), and the effects of surface modification (with positive, or neutral, or negative surface charges).
The results are helpful to develop this AuNC-based PA imaging system for noninvasive lymph node mapping, providing
valuable information about metastatic cancer staging.
Photoacoustic endoscopy (PAE) provides unique functional information with high spatial resolution at super depths.
The provision of functional information is predicated on its strong spectroscopic imaging ability, and its deep imaging
capability is derived from its ultrasonic detection of diffused photon absorption. To accurately image functional
physiological parameters, it is necessary to rapidly alternate laser pulses of sufficient energy and different wavelengths.
In this study, we developed peripheral optical systems for PAE based on two identical pulsed-laser systems to achieve
the fast laser wavelength switching that is essential for accurate functional imaging. Each laser system was comprised of
a tunable dye laser pumped by a solid-state, diode-pumped Nd:YLF laser. Both systems deliver adequate energy at the
scanning head of the endoscope for imaging biological tissue in the optically diffusive regime (~0.3-0.6 mJ per pulse
with a repetition rate of ~1 kHz). In this paper, we introduce the employed laser systems and design of the light delivery
optics, and present results from an ex vivo animal imaging experiment that validates the system's multi-wavelength
functional imaging capability.
In detecting small foreign bodies in soft biological tissue, ultrasound imaging suffers from poor sensitivity (52.6%) and specificity (47.2%). Hence, alternative imaging methods are needed. Photoacoustic (PA) imaging takes advantage of strong optical absorption contrast and high ultrasonic resolution. A PA imaging system is employed to detect foreign bodies in biological tissues. To achieve deep penetration, we use near-infrared light ranging from 750 to 800 nm and a 5-MHz spherically focused ultrasonic transducer. PA images were obtained from various targets including glass, wood, cloth, plastic, and metal embedded more than 1 cm deep in chicken tissue. The locations and sizes of the targets from the PA images agreed well with those of the actual samples. Spectroscopic PA imaging was also performed on the objects. These results suggest that PA imaging can potentially be a useful intraoperative imaging tool to identify foreign bodies.
Three-dimensional scaffolds provide physical support and an adjustable microenvironment to facilitate vascularization of
ischemic tissues; however, in vivo imaging of scaffold functioning is still challenging. Micro-CT, the current frequentlyused
imaging modality for scaffold characterization, provides poor contrast for wet scaffold, which limits its in vivo
applications. In this paper, dual modes of photoacoustic microscopy (PAM), using acoustic resolution PAM (AR-PAM)
and optical resolution PAM (OR-PAM), were employed for imaging scaffolds in blood as well as in chicken breast
tissues. By choosing different wavelengths, 570 nm and 638 nm, we spectroscopically differentiated the photoacoustic
signals generated from blood and from carbon nanotube incorporated scaffolds. The ex vivo experiments demonstrated a
lateral resolution of 45 μm and a maximum penetration of ~2 mm for AR-PAM, and a lateral resolution of 3 μm and a
maximum penetration of ~660 μm for OR-PAM. OR-PAM further quantified the average pore size of scaffolds to be
100-200 μm in diameter. Our results suggest that PAM is a promising tool for in vivo monitoring of scaffold-induced
angiogenesis as well as the degradability of scaffolds themselves.
Visualizing cells in three-dimensional (3D) scaffolds has been one of the major challenges in tissue
engineering. Current imaging modalities have limitations. Microscopy, including confocal microscopy,
cannot penetrate deeply (> 300 μm) into the scaffolds; X-ray micro-computed tomography (micro-CT)
requires staining of the structure with a toxic agent such as osmium tetroxide. Here, we demonstrate
photoacoustic microscopy (PAM) of the spatial distribution and temporal proliferation of melanoma cells
inside three-dimensionally porous scaffolds with thicknesses over 1 mm. Melanoma cells have a strong
intrinsic contrast which is easily imaged by label-free PAM with high sensitivity. Spatial distributions of
the cells in the scaffold were well-resolved in PAM images. Moreover, we chronically imaged the same
cell/scaffold constructs at different time points over 2 weeks. The number of cells in the scaffold was
quantitatively measured from the PAM volumetric information. The cell proliferation profile obtained from
PAM correlated well with that obtained using the traditional
3-(4,5-dimethylthiazol-2-yl)-2,
5-diphenyltetrazolium bromide (MTT) assay. We believe that PAM will become a useful imaging modality
for tissue engineering applications, especially when thick scaffold constructs are involved, and that this
modality can also be extended to image other cell types labeled with contrast agents.
We have successfully implemented a focused ultrasonic transducer for photoacoustic endoscopy. The photoacoustic
endoscopic probe's ultrasound transducer determines the lateral resolution of the system. By using a focused ultrasonic
transducer, we significantly improved the endoscope's spatial resolution and signal-to-noise ratio. This paper describes
the technical details of the ultrasonic transducer incorporated into the photoacoustic endoscopic probe and the
experimental results from which the transducer's resolution is quantified and the image improvement is validated.
Photoacoustic microscopy (PAM) utilizes short laser pulses to deposit energy into light
absorbers and sensitively detects the ultrasonic waves the absorbers generate in response.
PAM directly renders a three-dimensional spatial distribution of sub-surface optical absorbers.
Unlike other optical imaging technologies, PAM features label-free optical absorption contrast
and excellent imaging depths. Standard dental imaging instruments are limited to X-ray and
CCD cameras. Subsurface optical dental imaging is difficult due to the highly-scattering enamel
and dentin tissue. Thus, very few imaging methods can detect dental decay or diagnose dental
pulp, which is the innermost part of the tooth, containing the nerves, blood vessels, and other
cells. Here, we conducted a feasibility study on imaging dental decay and dental pulp with PAM.
Our results showed that PAM is sensitive to the color change associated with dental decay.
Although the relative PA signal distribution may be affected by surface contours and subsurface
reflections from deeper dental tissue, monitoring changes in the PA signals (at the same site)
over time is necessary to identify the progress of dental decay. Our results also showed that
deep-imaging, near-infrared (NIR) PAM can sensitively image blood in the dental pulp of an in
vitro tooth. In conclusion, PAM is a promising tool for imaging both dental decay and dental
pulp.
Ultrasound imaging suffers from poor sensitivity (~50%) and specificity in detecting small foreign bodies
in tissue. Hence, alternative imaging methods are needed. Photoacoustic (PA) imaging takes advantage of
strong optical absorption contrast and high ultrasonic resolution. This work employed a PA imaging system
to detect foreign bodies in biological tissues. To achieve deep penetration, we used near-infrared light and a
5-MHz spherically focused ultrasonic transducer. PA images were obtained from objects (glass, wood,
cloth, plastic, and metal) embedded in chicken tissue. The location and size of the targets from the PA
images agreed well with those of the actual samples. Objects were imaged more than 1 cm deep.
Spectroscopic PA imaging was also performed on the objects. These results suggest PA imaging can
potentially be a useful intraoperative imaging tool to identify foreign bodies and discriminate viable tissues
in wounded patients.
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