KEYWORDS: Ultrasonography, Photoacoustic imaging, Microscopy, Data acquisition, Photoacoustic spectroscopy, In vivo imaging, Algorithm development, Temporal resolution, Super resolution, Oncology
Photoacoustic (PA) imaging can map the physiological conditions of tissue and track the biodistribution of contrast agents; ultrasound localization microscopy (ULM) with microbubbles provides deep-tissue super-resolution blood vessel images and blood velocity maps. When combined, the dual imaging technique will become a powerful tool with diverse applications. However, longer acquisition time of ULM poses a challenge. To address this, we propose sparsity constraint optimization to accelerate ULM and develop an interleaved PA/fast ULM imaging sequences for the dual imaging. We demonstrate 3D and time-lapse dual imaging with a commonly used linear array imaging system in a mouse model.
Scanning probe technology is advantageous in visualizing nanoscale light-matter interactions, however, this technology is limited by the slow raster scanning speed. In this talk, I will discuss how to visualize these ultrafast interactions beyond the conventional scanning speed. We develop a technique called decoupled optical force nanoscopy that can differentiate optical forces with different origins.
KEYWORDS: Plasmonics, Super resolution microscopy, Atomic force microscopy, Molecules, Visualization, Macromolecules, Proteins, Optical tweezers, Resonance energy transfer, Fluorescence resonance energy transfer
In this talk, I will discuss how light can be sculpted with engineered nanostructures to enhance chiral light-matter interactions. With these nanostructures, we have developed optical force nanoscopes to visualize and quantify molecular chirality with high sensitivity and resolution. Specifically, we have designed and developed a cavity-enhanced atomic force microscope to image chiral optical forces with nanometer spatial resolution and piconewton force sensitivity. We use this technique to measure the chirality of DNA molecules, on the order of few tens of molecules. These studies provide a foundation for new sensing and imaging techniques at the single molecular to cellular level in-situ and in real time.
The ability to image metallic implants is important for medical applications ranging from diagnosis to therapy. Photoacoustic (PA) imaging has been recently pursued as a means to localize metallic implants in soft tissue. The work presented herein investigates different mechanisms to modulate the PA signal generated by macroscopic metallic surfaces. Wires of five different metals are tested to simulate medical implants/tools, while surface roughness is altered or physical vapor deposition (PVD) coatings are added to change the wires’ overall optical absorption. PA imaging data of the wires are acquired at 970 nm. Results indicate that PA signal generation predominately occurs in a wire’s metallic surface and not its aqueous surroundings. PA signal generation is similar for all metals tested, while addition of PVD coatings offers significant modulations (i.e., 4-dB enhancement and 26-dB reduction achieved) in PA signal generation. Results also suggest that PA signal increases with increasing surface roughness. Different coating and roughness schemes are then successfully utilized to generate spatial PA signal patterns. This work demonstrates the potential of surface modifications to enhance or reduce PA signal generation to permit improved PA imaging of implants/tools (i.e., providing location/orientation information) or to allow PA imaging of surrounding tissue.
Photoacoustic imaging, using targeted plasmonic metallic nanoparticles, is a promising noninvasive molecular imaging method. Analysis of the photoacoustic signal generated by plasmonic metallic nanoparticles is complex because of the dependence upon physical properties of both the nanoparticle and the surrounding environment. We studied the effect of the aggregation of gold nanoparticles on the photoacoustic signal amplitude. We found that the photoacoustic signal from aggregated silica-coated gold nanoparticles is greatly enhanced in comparison to disperse silica-coated gold nanoparticles. Because cellular uptake and endocytosis of nanoparticles results in their aggregation, these results have important implications for the application of plasmonic metallic nanoparticles towards quantitative molecular imaging.
Metal needles are commonly used for drug delivery or biopsy collection in clinical settings. Needle deflection and
deformation can occur when inserting needles into soft,
non-homogeneous tissues which can affect the location accuracy
of insertion. Therefore, the ability to visualize both anatomical surrounding structures and the advancing needle is
required. Ultrasound is commonly used for image-guidance of needles; however, specular reflections from the metal
surface can deflect the acoustic beam away from the transducer when the needle is even slightly angled from the US
transducer thereby rendering the needle invisible in the image.
Photoacoustic imaging has been proposed for guidance of metal needles and other metal objects in-vivo. The high
optical absorption coefficient of stainless steel can provide high photoacoustic imaging contrast. The photoacoustic
signal is produced omni-directionally from the metal surface allowing for greater detection of needles at increasing
injection angles compared to ultrasound imaging. In the current work, needles were inserted into excised tissue and
imaged using an ultrasound array transducer and a pulsed 800 nm laser. The results showed that at a shallow 10°
insertion angle, the photoacoustic ratio of needle signal to background was four-times higher compared to ultrasound.
Furthermore, the surrounding tissue composition was observed to have an effect on photoacoustic signal enhancement
which correlated with the change of the Grüneisen coefficient of the surrounding tissue environment, suggesting that the
photoacoustic signal amplitude could be used to ascertain surrounding tissue composition. Photoacoustic imaging
provides sufficient depth penetration for this application and offers excellent image contrast.
Ultrasound imaging can provide excellent resolution at reasonable depths while retaining the advantages of being nonionizing,
cost-effective and portable. However, the contrast in ultrasound imaging is limited, and various ultrasoundbased
techniques such as photoacoustic (PA) and magneto-motive ultrasound (MMUS) imaging have been developed to
augment ultrasound imaging. Photoacoustic imaging enhances imaging contrast by visualizing the optical absorption of
either tissue or injected contrast agents (e.g., gold or silver nanoparticles). MMUS imaging enhances the sensitivity and
specificity of ultrasound based on the detection of magnetic nanoparticles perturbed by an external magnetic field. This
paper presents integrated magneto-photo-acoustic (MPA) imaging - a fusion of complementary ultrasound-based
imaging techniques. To demonstrate the feasibility of MPA imaging, porcine ex-vivo tissue experiments were performed
using a dual contrast (magnetic/plasmonic) agent. Spatially
co-registered and temporally consecutive ultrasound,
photoacoustic, and magneto-motive ultrasound images of the same
cross-section of tissue were obtained. Our ex-vivo
results indicate that magneto-photo-acoustic imaging can be used to detect magnetic/plasmonic nanoparticles with high
resolution, sensitivity and contrast. Therefore, our study suggests that magneto-photo-acoustic images can identify the
morphological properties, molecular information and complementary functional information of the tissue.
Image-guided molecular photothermal therapy using targeted gold nanoparticles acting as photoabsorbers can be used to
noninvasively treat various medical conditions including cancer. Among different types of gold nanoparticles, gold
nanorods are an attractive candidate for both photothermal therapy and photoacoustic imaging due to their high and
tunable optical absorption cross-section. However, nanorods are not thermodynamically stable; under laser exposure, the
nanorods can easily transform to spheres, thus changing their desired optical properties. In this study, gold-silica coreshell
nanorods were prepared by coating silica directly onto the surface of PEGylated gold nanorods using a modified
Stöber method. The nanorods were exposed to 800 nm wavelength, 7 ns pulses of light at a 10 Hz pulse repetition rate.
For different fluences ranging from 0 to 8 mJ/cm2, the optical extinction spectrum was measured before and after the
exposure to investigate their photothermal stability. Finally, the effectiveness of gold-silica core-shell nanoparticles as a
photoacoustic contrast agent and photothermal nanoabsorber was tested using inclusion-embedded phantoms and a
combined ultrasound and photoacoustic imaging system. The results of our study suggest that gold-silica core-shell
nanorods are excellent candidates for image-guided molecular photothermal therapy.
Photothermal therapy is a laser-based non-invasive technique for cancer treatment. Photothermal therapy can be
enhanced by employing metal nanoparticles that absorb the radiant energy from the laser leading to localized thermal
damages. Targeting of nanoparticles leads to more efficient uptake and localization of photoabsorbers thus increasing the
effectiveness of the treatment. Moreover, efficient targeting can reduce the required dosage of photoabsorbers; thereby
reducing the side effects associated with general systematic administration of nanoparticles. Magnetic nanoparticles, due
to their small size and response to an external magnetic field gradient have been proposed for targeted drug delivery. In
this study, we investigate the applicability of multifunctional nanoparticles (e.g., magneto-plasmonic nanoparticles) and
magneto-motive ultrasound imaging for image-guided photothermal therapy. Magneto-motive ultrasound imaging is an
ultrasound based imaging technique capable of detecting magnetic nanoparticles indirectly by utilizing a high strength
magnetic field to induce motion within the magnetically labeled tissue. The ultrasound imaging is used to detect the
internal tissue motion. Due to presence of the magnetic component, the proposed multifunctional nanoparticles along
with magneto-motive ultrasound imaging can be used to detect the presence of the photo absorbers. Clearly the higher
concentration of magnetic carriers leads to a monotonic increase in magneto-motive ultrasound signal. Thus, magnetomotive
ultrasound can determine the presence of the hybrid agents and provide information about their location and
concentration. Furthermore, the magneto-motive ultrasound signal can indicate the change in tissue elasticity - a
parameter that is expected to change significantly during the photothermal therapy. Therefore, a comprehensive guidance
and assessment of the photothermal therapy may be feasible through magneto-motive ultrasound imaging and magnetoplasmonic
nanoparticles.
Metallo-dielectric photonic crystals (MDPCs) can exhibit intriguing and potentially useful optical properties, including
ultra-wide photonic bandgaps, engineered thermal emission, and negative refractive index. But access to such materials
has been limited by the lack of suitable methods for their preparation. We have developed a route to three-dimensional
(3D) MDPCs that involves fabricating a polymeric pre-form by multi-photon direct laser writing and then conformally
depositing metal onto the pre-form by electroless metallization. We use the approach to prepare silver- and copper-plated
"woodpile" PCs having face-centered tetragonal symmetry and unit-cell period of several micrometers. The
resulting 3D metallized structures exhibit mid-infrared reflectance that is consistent with theory and experimental
observations obtained for MDPCs prepared by other routes. These data indicate that multi-photon direct laser writing
coupled with electroless metallization is a viable route to complex 3D MDPCs of many symmetries and basis sets and
provides a path for integrating such structures with other micron-scale optical elements.
Interest in three-dimensional (3D) metallo-dielectric photonic crystals (MDPCs) has grown considerably given their
potential applications in optics and photonics. MDPCs can exhibit intriguing and potentially useful optical properties,
including ultra-wide photonic bandgaps, engineered thermal emission, and negative refractive index. Yet experimental
studies of such materials remain few because of the difficulties associated with fabricating 3D micron- and sub-micron-scale
metallic structures. We report a route to MDPCs based on metallization of a 3D polymeric photonic crystal (PC)
fabricated by multi-photon microfabrication (MPM). Polymeric PCs having face-centered tetragonal symmetry and
micrometer-scale periodicity were created using a cross-linkable acrylate or epoxide pre-polymer. The resulting PCs
were metallized by electroless deposition of silver or copper. Analysis of the metallized structures in cross-section by
scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy shows that silver deposited conformally
onto the entire micro-porous lattice. The dielectric and metallized PCs were characterized by Fourier transform infrared
(FTIR) spectroscopy. The polymer photonic crystals exhibit a stop band with strong reflectance near 4 to 6 microns,
depending upon the lattice period. In contrast, FTIR spectra of the metallized PCs show widened stop bands of nearly
6 microns and greater and maximum reflectance exceeding 90%. The appreciable broadening of the stop band due to the
presence of the deposited metal is a result consistent with previously reported theoretical and experimental data for all-metallic
3D PCs. Thus, the approach reported here appears suitable for fabricating 3D MDPCs of many symmetries and
basis sets and provides a path for integrating such structures with other micron-scale optical elements.
Interest in three-dimensional (3D) metal photonic crystals (MPCs) has grown considerably given their potential applications in optics and photonics. Yet, experimental studies of such materials remain few because of the difficulties associated with fabricating 3D micron- and sub-micron-scale metallic structures. We report a route to MPCs based on metallization of 3D polymeric photonic crystals fabricated by multi-photon direct laser writing. Polymeric photonic crystals (PCs) having simple-cubic symmetry with periodicities varying from 1.6 to 3.2 microns were created using a cross-linkable acrylate pre-polymer. The resulting dielectric PCs were metallized by electroless deposition of silver. Analysis of the metallized structures in cross-section by scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy shows that silver deposited conformally onto the entire micro-porous lattice. The dielectric and metallized PCs were characterized by Fourier transform infrared (FTIR) spectroscopy in the (001) direction. The polymer photonic crystals exhibit a stop band resulting in circa 60% reflectance centered at 3.2 to 6.4 microns, depending upon the lattice period, with a full-width at half-maximum (FWHM) of 500 nm. Interestingly, FTIR spectra of the metallized PCs show widened stop bands of nearly 6 microns FWHM, while the center wavelengths were red shifted and ranged from 6 to 7 microns. The appreciable broadening of the stop band due to the presence of the deposited silver is a result consistent with previously reported theoretical and experimental data for all-metallic 3D PCs. Thus, the approach described here appears suitable for fabricating 3D MPCs of many symmetries and basis sets and provides a path for integrating such structures with other micron-scale optical elements.
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