Dye-labeled protein microspheres, submicron in size and capable of producing thermoelastically generated ultrasound in response to laser stimulation, are presented as contrast agents for photoacoustic imaging. Incident laser energy absorbed by fluorescein isothiocyanate (FITC)-labeled elastin submicrospheres results in thermoelastically generated sound production. Plotted A-line graphs reveal a distinctive morphology and a greater than two orders of magnitude increase in signal amplitude subsequent to converting FITC elastin into submicrospheres (despite a four orders of magnitude decrease in concentration). Evidence of nonlinearity and enhancement of ultrasound backscatter indicate a potential use in contrast-enhanced harmonic imaging. Photoacoustic and ultrasound imaging of FITC-elastin submicrospheres in a water-filled phantom vessel shows enhanced contrast at low concentration and clear delineation of the phantom vessel wall.
In-vivo photoacoustic/ultrasound (PA/US) imaging of nude mice was investigated using a photoacoustic imaging system
based on a commercial ultrasound scanner HDI-5000. Raw per-channel data was captured and beamformed to generate
each individual photoacoustic image with a single laser shot. An ultra-broadband CL15-7 linear array with a center
frequency of 8 MHz, combined with a Schott Glass fiber bundle, was used as a compact high resolution imaging probe,
with lateral and axial PA resolutions of about 300µm and 200µm, respectively. The imaging system worked in a dual
PA-US mode, with the ultrasound outlining the tissue structure and the photoacoustic image showing the blood vessels.
PA signals were generated by exposing mice to ultra-short optical pulses from a Nd:YAG-pumped OPO laser operating
in a wavelength range of 700-950nm. The corresponding ultrasound images were generated in the regular B-mode with
standard delay-and-sum beamforming algorithm. The system resolution was sufficiently high to identify and clearly
distinguish the dorsal artery and the two lateral veins in the mouse tail. Both the saphena artery and the ischiatic vein on
the cross-section of the mouse leg were clearly outlined in the PA images and correctly overlaid on the ultrasound image
of the tissue structure. Similarly, cross-section PA images of the mouse abdomen revealed mesenteric vasculatures
located below the abdominal wall. Finally, a successful PA imaging of the mouse thoracic cavity unveiled the ascending
and descending aorta. These initial results demonstrate a great potential for a dual photoacoustic/ultrasound imaging
modality implemented on a commercial ultrasound imaging scanner.
Photoacoustic (PA) experiments were performed using a modified commercial ultrasound scanner equipped with an
array transducer and a Nd:YAG pumped OPO laser. The contrast agent SIDAG (Bayer Schering Pharma AG, Germany),
used to enhance the optical absorption, demonstrated an expected pharmacokinetic behavior of the dye in the tumor and
in the bladder of the nude mice. A typical behavior in the tumor consisted of an initial linear increase in PA signal
followed by an exponential decay. PA signal approached the pre-injection level after about one hour following the dye
injection, which was consistent with the behavior for such contrast agents when used in other imaging modalities, such
as fluorescence imaging. The in-vivo spectral PA data from the mouse bladder, conducted 1.5 hours after the dye injection, clearly demonstrated presence of the dye. The multi-spectral PA data was obtained at 760nm, 784nm and 850nm laser excitations. The PA
intensities obtained at these three wavelengths accurately matched the dye absorption spectrum.
In addition, in the kidney, a clearance organ for this contrast agent, both in-vivo and ex-vivo results demonstrated a
significant increase (~ 40%) in the ratio of PA signal at 760nm (the peak of the dye absorption) relative to the signal at
850nm (<1% absorption), indicating significant amounts of the dye in this organ.
Our initial results confirm the desired photoacoustic properties of the contrast agent, indicating its great potential to be
used for imaging with a commercial array-based ultrasound scanner.
We studied the nature of photoacoustic signals that were generated under a variety of conditions from vessel-mimicking
polyethylene tubes. The vessels, filled with a range of contrast agents, were buried in tissue-like phantoms that possessed
low to high optical absorption and scattering properties. In a photoacoustic image, we observed that either a single spot
or two distinct spots could represent a single vessel depending on the strength of the infused contrast agent and on the
size of the vessels. We typically found linear increase of the photoacoustic intensity with laser excitation power as well
as with absorption coefficient of the contrast agent. However, we found that there is an optimum excitation power for
achieving the best photoacoustic signal. If a vessel is buried in a highly absorbing background, increasing the laser
power beyond a certain limit reversibly reduces the photoacoustic signal from the vessel, eventually decreasing it to
zero. We also studied the blood-to-tissue absorption contrast requirement for observing the photoacoustic signal from a
vessel buried in an absorbing and scattering tissue. We find that, in order to distinguish the photoacoustic signal from its
background, the absorption coefficient of contrast agent in the vessel must be at least 2.5 times larger than that of the
surroundings.
Protein nanospheres capable of frequency controlled oscillation in response to laser stimulation are presented as contrast
agents for photoacoustic imaging. Incident laser energy absorbed by dye-labeled protein nanospheres causes
thermoelastically generated sound production. Plotted A-line graphs reveal a distinctive morphology and greater than 2
orders of magnitude increase in signal amplitude subsequent to converting labeled proteins into nanospheres. Evidence
of nonlinearity and enhancement of ultrasound backscatter indicate a potential use in contrast-enhanced harmonic
imaging. Photoacoustic and ultrasound imaging of protein nanospheres in phantom vessels show enhanced contrast at
low concentration and clear delineation of the phantom vessel wall.
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