Nanoparticles as Contrast Agents for Optoacoustic Imaging - Nanotechnology for Biomedical Imaging and Diagnostics - page 108

OA imaging utilizes absorption of short laser pulses in tissue and effective
conversion of the deposited energy into heat. Rapid deposition of thermal energy
in tissues results in an immediate pressure increase, which propagates out of the
heated voxels in the form of transient ultrasonic waves. OA imaging combines the
most compelling properties of light and sound in a hybrid modality, simulta-
neously avoiding limitations of light and sound when utilized separately. While
scattering of optical photons is an obstacle for resolution and sensitivity of pure
optical imaging in the depth of tissue beyond 1 mm, it only helps to deliver homog-
enized distribution of the optical energy. Hence, every photon within the tissue is
utilized in OAs. OA imaging system detects acoustic waves generated at the loca-
tion of absorbed photons. Acoustic waves propagate in a well-defined manner as
expanding spheres, so that the distance between acoustic sources and ultrasonic
transducers (detectors) can be accurately determined as the product of propagation
time and the speed of sound. Therefore, OA imaging has much higher spatial res-
olution and deeper imaging depth when compared with other optical imaging
methods (such as those based on fluorescence or optical scattering) limited by
scattering in tissues.
currently, two OA imaging techniques are being actively developed: optoacoustic
tomography (OAT) in deep tissues [8-10] and OA microscopy of thin tissue layers
[11, 12]. Typically, tomography utilizes either an array of ultrasound transducers
scanned around/along the tissue surface and an inverse algorithm to reconstruct
cross-sectional or three-dimensional (3D) images of biological tissue [13-15]. In
contrast, microscopy uses a raster-scanned single-focused ultrasonic detector cou-
pled with confocal optical illumination and requires no reconstruction algorithm.
The advantage of tomography techniques is rapid acquisition of large-volume tissue
images with relatively low resolution measured in hundreds of microns, while
microscopy permits high-resolution (1-50µm) imaging of thin tissue slices with
relatively small total volume. Both imaging modalities demonstrate an excellent ratio
of depth to resolution (about 100-200), high sensitivity resulting in their capability
to resolve the optical absorption contrast of about Δ μ a = 0.5/cm, and the ability to
quantify the signal in terms of the optical absorption coefficient, which is propor-
tional to the concentration of chromophores.
ultrasound imaging contrast is defined by the mechanical properties (density and
speed of sound), which have no resonances in biological tissues. Optical contrast of
OA imaging is defined by the spectral resonances in molecules, which can be
exploited by tuning the laser illumination wavelength to a desirable resonance.
Administration of exogenous contrast agents with strong resonance absorption in the
spectral range of weak endogenous optical absorption creates a unique opportunity
to visualize biological tissues with molecular specificity and greater contrast com-
pared with ultrasonic imaging. Nanotechnology-based methods that further enhance
the realization of this opportunity are the subject of the present review. We demon-
strate that OA imaging techniques with contrast agents based on strongly absorbing
nanoparticles have the capability to bring greater value and safety to biomedical
diagnostics and angiography, compared with methods based on more traditional
small molecule-based imaging.