Due to their optical absorption properties, metallic nanoparticles are excellent photoacoustic imaging contrast agents. A silver nanosystem is presented here as a potential contrast agent for photoacoustic imaging and image-guided therapy. Currently, the nanosystem consists of a porous silver layer deposited on the surface of spherical silica cores ranging in diameter from 180 to 520 nm. The porous nature of the silver layer will allow for release of drugs or other therapeutic agents encapsulated in the core in future applications. In their current PEGylated form, the silver nanosystem is shown to be nontoxic in vitro at concentrations of silver up to 2 mg/ml. Furthermore, the near-infrared absorbance properties of the nanosystem are demonstrated by measuring strong, concentration-dependent photoacoustic signal from the silver nanosystem embedded in an ex vivo tissue sample. Our study suggests that silver nanosystems can be used as multifunctional agents capable of augmenting image-guided therapy techniques.
We have developed a multifunctional nanoagent, termed the combined imaging and therapy
nanocage system (CIT-NS). This nanosystem platform consists of a poly(lactic-co-glycolic) acid polymer
core and outer silver cage network. The inner core of CIT-NS is capable of carrying drugs, such as the
chemotherapeutic agent doxorubicin, or imaging contrast agents, such as dyes or fluorescent compounds.
The outer silver cage is specifically designed to enhance contrast in photoacoustic imaging, i.e., acoustic
imaging of optical absorption. In this paper, methods to create the CIT-NS are described. Initial
characterization indicates that the developed CIT-NS will significantly increase contrast in photoacoustic
imaging while retaining the potential to deliver large payloads of drug simultaneously. Therefore, the CITNS
may enable multi-modal imaging approaches or simultaneous imaging and therapy strategies to
improve treatment and detection of cancer and other pathologies.
A new metallodielectric nanoparticle consisting of a silica core and silver outer cage was
developed for the purpose of enhancing photoacoustic imaging contrast in pancreatic tissue. These
nanocages were injected into an ex vivo porcine pancreas and imaged using a combined photoacoustic and
ultrasound (PAUS) assembly. This custom-designed PAUS assembly delivered 800 nm light through a
fiber optical light delivery system integrated with 128 element linear array transducer operating at 7.5 MHz
center frequency. Imaging results prove that the nanocage contrast agents have the ability to enhance
photoacoustic imaging contrast. Furthermore, the value of the combined PAUS imaging modality was
demonstrated as the location of nanocages against background native tissue was evident. Future
applications of these nanocage contrast agents could include targeting them to pancreatic cancer for
enhancement of photoacoustic imaging for diagnosis and therapy.
Treatment of deep venous thrombosis (DVT)—a primary cause of potentially fatal pulmonary embolism (PE)—depends on the age of the thrombus. The existing clinical imaging methods are capable of visualizing a thrombus but cannot determine the age of the blood clot. Therefore, there is a need for an imaging technique to reliably diagnose and adequately stage DVT. To stage DVT (i.e., to determine the age of the thrombus, and therefore, to differentiate acute from chronic DVT), we explored photoacoustic imaging, a technique capable of noninvasive measurements of the optical absorption in tissue. Indeed, optical absorption of the blood clot changes with age, since maturation of DVT is associated with significant cellular and molecular reorganization. The ultrasound and photoacoustic imaging studies were performed using DVT-mimicking phantoms and phantoms with embedded acute and chronic thrombi obtained from an animal model of DVT. The location and structure of the clots were visualized using ultrasound imaging, while the composition, and therefore age, of thrombi were related to the magnitude and spatiotemporal characteristics of the photoacoustic signal. Overall, the results of our study suggest that combined ultrasound and photoacoustic imaging of thrombi may be capable of simultaneous detection and staging of DVT.
Photothermal therapy is a noninvasive, targeted, laser-based technique for cancer treatment. During photothermal therapy, light energy is converted to heat by tumor-specific photoabsorbers. The corresponding temperature rise causes localized cancer destruction. For effective treatment, however, the presence of photoabsorbers in the tumor must be ascertained before therapy and thermal imaging must be performed during therapy. This study investigates the feasibility of guiding photothermal therapy by using photoacoustic imaging to detect photoabsorbers and to monitor temperature elevation. Photothermal therapy is carried out by utilizing a continuous wave laser and metal nanocomposites broadly absorbing in the near-infrared optical range. A linear array-based ultrasound imaging system is interfaced with a nanosecond pulsed laser to image tissue-mimicking phantoms and ex-vivo animal tissue before and during photothermal therapy. Before commencing therapy, photoacoustic imaging identifies the presence and spatial location of nanoparticles. Thermal maps are computed by monitoring temperature-induced changes in the photoacoustic signal during the therapeutic procedure and are compared with temperature estimates obtained from ultrasound imaging. The results of our study suggest that photoacoustic imaging, augmented by ultrasound imaging, is a viable candidate to guide photoabsorber-enhanced photothermal therapy.
In photothermal therapy, a localized temperature increase is achieved by using a continuous wave laser and optically
tuned metal nanoparticles. However, the successful outcome of therapy depends on identifying the presence of
nanoparticles in the tumor before therapy and monitoring temperature rise during the photothermal procedure. In this
paper, we investigate the utility of photoacoustic and ultrasound imaging to guide photothermal therapy. Differences in
the optical properties of tissue, enhanced by the presence of nanoparticles, provide a contrast for photoacoustic imaging.
Thus, an uptake of nanoparticles in the tumor can be detected by monitoring a photoacoustic image over time. A
temperature rise causes the photoacoustic signal amplitude to increase. In addition, a temperature change also leads to
time shifts in an ultrasound signal, primarily due to the change in speed of sound. Therefore, by measuring the change in
the photoacoustic signal, and differential motion of ultrasound speckle, the temperature rise during photothermal
therapy can be computed. Combined imaging was performed with a tunable pulsed laser and an array-based ultrasound
transducer. Experiments were carried out on ex-vivo animal tissue injected with composite and broadly absorbing gold
nanoparticles. The photoacoustic imaging identified the presence of nanoparticles in tissue. In addition, a localized
temperature increase, obtained during therapy, was monitored using photoacoustic and ultrasound imaging. The
temperature profiles, obtained by both imaging techniques, were spatially and temporally co-registered. Therefore, the
experimental results suggest that photoacoustic and ultrasound imaging can be used to guide and monitor photothermal
A hybrid imaging system is proposed for cancer detection, diagnosis and therapy monitoring by integrating
three complementary imaging techniques - ultrasound, photoacoustic and elasticity imaging. Indeed, simultaneous
imaging of the anatomy (ultrasound imaging), cancer-induced angiogenesis (photoacoustic imaging) and changes in
biomechanical properties (elasticity imaging) of tissue is based on many synergistic features of these modalities and
may result in a unique and important imaging tool. To facilitate the design and development of a real-time imaging
system for clinical applications, we have investigated the core components of the imaging system using numerical
simulations. Differences and similarities between each imaging technique were considered and contrasted. The results
of our study suggest that the integration of ultrasound, photoacoustic and elasticity imaging is possible using a custom
designed imaging system.
Combination of three complementary imaging technologies - ultrasound imaging, elastography, and optoacoustic imaging - is suggested for detection and diagnostics of tissue pathology including cancer. The fusion of these ultrasound-based techniques results in a novel imaging system capable of simultaneous imaging of the anatomy (ultrasound imaging), cancer-induced angiogenesis (optoacoustic imaging) and changes in mechanical properties (elasticity imaging) of tissue to uniquely identify and differentiate pathology at various stages. To evaluate our approach, analytical and numerical studies were performed using heterogeneous phantoms where ultrasonic, optical and viscoelastic properties of the materials were chosen to closely mimic soft tissue. The results of this study suggest that combined ultrasound-based imaging is possible and can provide more accurate, reliable and earlier detection and diagnosis of tissue pathology. In addition, monitoring of cancer treatment and guidance of tissue biopsy are possible with a combined imaging system.