Combined intravascular ultrasound and intravascular photoacoustic (IVUS/IVPA) imaging has been previously established as a viable means for assessing atherosclerotic plaque morphological and compositional characteristics using both endogenous and exogenous contrast. In this study, IVUS/IVPA imaging of atherosclerotic rabbit aortas following systemic injection of gold nanorods (AUNRs) with peak absorbance within the tissue optical window is performed. Ex vivo imaging results reveal a high photoacoustic signal from localized AUNRs in regions with atherosclerotic plaques. Corresponding histological staining further confirms the preferential extravasation of AUNRs in atherosclerotic regions with compromised luminal endothelium and acute inflammation. The ability to detect AUNRs using combined IVUS and photoacoustic imaging in the presence of luminal saline and luminal blood is evaluated using both spectroscopic and single wavelength IVPA imaging techniques. Results demonstrate that AUNR detection within the arterial wall can be achieved using both methods, even in the case of imaging through luminal blood.
Pilot studies of in vivo combined intravascular ultrasound (IVUS) and intravascular photoacoustic (IVPA) imaging are reported. A recently introduced prototype of an integrated IVUS/IVPA imaging catheter consisting of a single-element ultrasound transducer and a light delivery system based on a single optical fiber was adapted and used for in vivo imaging of a coronary stent deployed in a rabbit's thoracic aorta in the presence of luminal blood. The results suggest that in vivo IVUS/IVPA imaging is feasible using the integrated IVUS/IVPA imaging catheter. The challenges of in vivo combined IVUS/IVPA imaging are discussed, and further improvements on the design of the catheter and the clinical imaging system are proposed.
Combined intravascular photoacoustic (IVPA) and intravascular ultrasound (IVUS) imaging has been previously
established as a viable means for imaging atherosclerotic plaques using both endogenous and exogenous contrast. In this
study, IVUS/IVPA imaging of an atherosclerotic rabbit aorta following injection of gold nanorods (AuNR) with peak
absorbance within the tissue optical window was performed. Ex-vivo imaging results revealed high photoacoustic signal
from localized AuNR. Corresponding histological cross-sections and digital photographs of the artery lumen confirmed
the presence of AuNR preferentially located at atherosclerotic regions and in agreement with IVPA signal. Furthermore,
an integrated IVUS/IVPA imaging catheter was used to image the AuNR in the presence of luminal blood. The results
suggest that AuNR allow for IVPA imaging of exogenously labeled atherosclerotic plaques with a comparatively low
background signal and without the need for arterial flushing.
The ability to visualize and track temporarily or permanently implanted metal devices is important in many applications ranging from diagnosis to therapy. Specifically, reliable imaging of metal needles is required in today's clinical settings. Currently, ultrasound is utilized to image a needle inserted into tissue in real time. However, the diagnostic value and tracking ability of these images depends highly on the orientation of the needle, and also its proximity to regions of interest in the tissue. We examine the use of photoacoustic imaging combined with current ultrasound imaging methods to obtain high-contrast images of commonly used needles in the body. Experiments were performed using 21 G and 30 G needles inserted into ex vivo porcine tissue and tissue-mimicking phantoms. The needles and surrounding tissue were imaged using an ultrasound imaging system interfaced with the pulsed laser source necessary for photoacoustic imaging. The results suggest that photoacoustic imaging, combined with ultrasound imaging, is capable of real-time, high-contrast, and high-spatial-resolution visualization of metal implants within anatomical landmarks of the background tissue.
The vulnerability of atherosclerotic plaques that are formed in the arterial walls due to atherosclerosis depends on both
their distribution and composition. The distribution of the plaques can be imaged using an intravascular ultrasound
(IVUS) imaging which is a clinically approved minimally-invasive method. The recently introduced intravascular
photoacoustic (IVPA) imaging may be used to obtain the necessary information about the composition of the plaques.
Previous studies using excised rabbit arteries have demonstrated that the combined IVUS/IVPA imaging may
simultaneously provide the morphology and functional information of plaques. However, for in-vivo IVUS/IVPA
imaging, an integrated IVUS/IVPA imaging catheter capable both of delivering light into a vessel lumen with
consequent detection of photoacoustic transients and of probing the arterial walls in pulse-echo mode is required. In the
current study, an advanced prototype of the integrated IVUS/IVPA imaging catheter based on a 40-MHz single-element
ultrasound transducer and a 600-μm-core single optical fiber is introduced. Unlike previously reported prototypes, the
current integrated IVUS/IVPA imaging catheter is capable of
cross-sectional imaging of vessel walls via mechanical
rotation of the catheter. The performance of the integrated IVUS/IVPA catheter was evaluated in tissue-mimicking
phantoms with and without the presence of blood in a lumen. The results of our study suggest that the approach used to
develop integrated IVUS/IVPA imaging catheter can be successfully translated to the clinical environment for in-vivo
combined IVUS/IVPA imaging.
Using contrast agents with desired targeting moiety and optical absorption, intravascular photoacoustic imaging may
be used to identify various biomarkers expressed during the progression of atherosclerotic lesions. In this paper, we
present intravascular photoacoustic imaging of macrophages in the atherosclerotic lesions using bio-conjugated gold
nanoparticles as the contrast agent. Atherosclerotic lesions were created in the aorta of a New Zealand white rabbit
subjected to a high cholesterol diet and balloon injury. The rabbit was injected with 20 nm spherical gold
nanoparticles conjugated with antibodies. The macrophages with internalized gold nanoparticles were imaged by
intravascular photoacoustic imaging in the near infrared range; this was possible because of plasmon resonance
coupling between closely spaced gold nanoparticles internalized by macrophages. The multi-wavelength
intravascular photoacoustic images of the diseased aorta were analyzed to identify the presence and location of
macrophages labeled with gold nanoparticles. Spectroscopic intravascular photoacoustic image showing the
distribution of gold nanoparticles was further confirmed by the gold-specific silver staining of the tissue crosssection.
The results of our study suggest that molecular intravascular photoacoustic imaging can be used to image
macrophages in atherosclerosis.
Coronary atherosclerosis is a complex disease accompanied by the development of plaques in the arterial wall. Since the
vulnerability of the plaques depends on their composition, the appropriate treatment of the arteriosclerosis requires a
reliable characterization of the plaques' geometry and content. The intravascular ultrasound (IVUS) imaging is capable
of providing structural details of the plaques as well as some functional information. In turn, more functional information
about the same plaques can be obtained from intravascular photoacoustic (IVPA) images since the optical properties of
the plaque's components differ from that of their environment. The combined IVUS/IVPA imaging is capable of
simultaneously detecting and differentiating the plaques, thus determining their vulnerability. The potential of combined
IVUS/IVPA imaging has already been demonstrated in phantoms and ex-vivo experiments. However, for in-vivo or
clinical imaging, an integrated IVUS/IVPA catheter is required. In this paper, we introduce two prototypes of integrated
IVUS/IVPA catheters for in-vivo imaging based on a commercially available single-element IVUS imaging catheter.
The light delivery systems are developed using multimode optical fibers with custom-designed distal tips. Both
prototypes were tested and compared using an arterial mimicking phantom. The advantages and limitations of both
designs are discussed. Overall, the results of our studies suggest that both designs of integrated IVUS/IVPA catheter
have a potential for in-vivo IVPA/IVUS imaging of atherosclerotic plaques.
An acceleration of angiogenesis in the adventitial vasa-vasorum is usually associated with vulnerable, thin-cap fibroatheroma
in atherosclerotic plaques. Angiogenesis creates microvasculature too small to be detected and differentiated
using conventional imaging techniques. However, by using spectroscopic photoacoustic imaging, we take advantage of
the wavelength-dependent optical absorption properties of blood. We used a vessel-mimicking phantom with micro
blood vessels. The phantom was imaged with intravascular photoacoustic imaging across a range of wavelengths. The
image intensities were cross-correlated with the known absorption spectra of blood. The resulting cross-correlation
image was able to reveal the location of the artificial blood vessels differentiated from non-blood vessel components.
In atherosclerosis, tracking and locating the activity of macrophages that are highly involved in plaque development will
help to identify the pathology of the disease. Intravascular photoacoustic (IVPA) imaging has shown potential to detect
atherosclerosis and to determine plaque composition. Furthermore, using optical absorbers as contrast agents, IVPA can
also be used for molecular imaging. In this paper, we study the feasibility of using gold nanoparticles as contrast agent
for high sensitivity IVPA imaging of macrophages. The artery was modeled using a cylindrical tube made out of
polyvinyl alcohol. Within the vessel wall, several compartments were made to mimic plaques. After incubating murine
macrophages with 50 nm spherical gold nanoparticles overnight, macrophages loaded with particles were filled into the
compartments of the arterial phantoms. Because of the plasmon resonance coupling of aggregated nanoparticles inside
the macrophages, these macrophages can be detected by IVPA imaging using 680 nm wavelength. The sensitivity of the
molecular IVPA imaging was tested using phantoms with different concentrations of nanoparticles and macrophages.
Finally, to address the feasibility of in-vivo IVPA imaging with gold nanoparticles, the viability of the macrophages
loaded with nanoparticles exposed to laser irradiation was studied. The results show that IVPA imaging can safely image
macrophages loaded with gold nanoparticles with relatively high sensitivity.
In laser beam projection through the atmosphere under conditions where strong scintillation is present, real zeros can appear in the beacon field. Recent advances in phase reconstruction have enabled phase estimation from phase differences in the presence of branch points, or real zeros, in the beacon field. While it is not possible to perfectly fit a physically realizable deformable mirror to the resulting discontinuous phase, the errors in the deformable mirror figure can be minimized based on knowledge of the locations and general shape of the discontinuities. In this paper we review two approaches to reconstructing phase in the presence of branch points, and compare the performance of these approaches to each other and to a conventional least-squares phase reconstructor in a laser beam projection system.
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