Jignesh Shah

Photoacoustic imaging and temperature measurement for photothermal cancer therapy.

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.

Combined ultrasound and photoacoustic imaging to detect and stage deep vein thrombosis: phantom and ex vivo studies.

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.

Silver nanosystems for photoacoustic imaging and image-guided therapy

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 mgml. 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.

Ultrasound imaging to monitor photothermal therapy – Feasibility study

This study investigates the feasibility of ultrasound imaging to monitor temperature changes during photothermal treatment. Experiments were performed on tissue-mimicking phantoms and ex-vivo animal tissue samples. Gold nanoparticles were utilized as photoabsorbers. Prior to laser irradiation, structural features of the phantoms and tissue were visualized by ultrasound imaging. Ultrasound thermal imaging, performed during laser heating, showed that the temperature elevation was localized to the region of embedded or injected nanoparticles. The results of our study suggest that ultrasound imaging is a candidate approach to remotely guide photothermal therapy.

Combined ultrasound, optoacoustic, and elasticity imaging

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.

Combined ultrasound and photoacoustic imaging of pancreatic cancer using nanocage contrast agents

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.

Integrated system for ultrasonic, photoacoustic and elasticity imaging

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.

An instrument to measure the heat convection coefficient on the endocardial surface

This work describes the fundamentals and calibration procedure of an instrument for in vivo evaluation of the heat convection coefficient between the endocardium and the circulating blood flow. The instrument is to be used immediately before radio-frequency cardiac ablation is performed. Thus, this instrument provides researchers with a valuable parameter to predict lesion size to be achieved by the procedure. The probe is a thermistor mounted in a Swan-Ganz catheter, and it is driven by a constant-temperature anemometer circuit. A 1D model of the sensor behaviour in a convective medium, the calibration procedure and the apparatus are explained in detail. Finally, a performance analysis of the instrument in the range of 200-3500 W m(-2) K(-1) shows that the average absolute error of full scale is 7.4%.

Molecular therapeutic agents for noninvasive photoacoustic image-guided photothermal therapy

Gold nanop articles are attracting increasing attention in nanomedicine due to their inherently low toxicity and unique optical properties. In particular, gold nanorods have been used in the thermal therapy due to their tunable strong longitudinal plasmon resonance in the near infra-red region and high conversion efficiency from optical to thermal energy. In this study we explore the potential of gold nanorods for photoacoustic image-guided photothermal therapy to treat cancers. We synthesize the gold nanorods and make them biocompatible by replacing the cytotoxic surfactant used in the synthesis (cetyl trimethyl ammonium bromide) with a biocompatible molecule and then demonstrate the targeting to the cancer cells by bioconjugation of the modified nanorods.

Instrument to measure the heat convection coefficient on the endothelial surface of arteries and veins.

The primary objective of the paper was to present the design and analysis of an instrument to measure the heat convection coefficient h on the endothelial surfaces of arteries and veins. An invasive thermistor probe was designed to be inserted through the vessel wall and positioned on the endothelial surface. Electrical power was supplied to the thermistor by a constant temperature anemometry circuit. Empirical calibrations were used to relate electrical measurements in the thermistor to the h at the endothelial surface. As the thermal processes are strongly dependent on baseline blood temperature, the instrument was calibrated at multiple temperatures to minimise this potentially significant source of error. Three different sizes of thermistor were evaluated to optimise accuracy and invasiveness, and the smallest thermistors provided the best results. The sensitivity to thermistor position was evaluated by testing the device at multiple locations, varying both depth of thermistor penetration and position along the vessel. Finally, the measurement accuracy of the instrument was determined for the range of h from 430 to 4200 W m−2K, and the average error of the reading was 4.9% for the smallest thermistor. Although the instrument was designed specifically for measurements in the portal vein to obtain useful data for current numerical modelling, the device can be used in any large vessel.