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

From times immemorial manual palpation served as a source of information on the state of soft tissues and allowed detection of various diseases accompanied by changes in tissue elasticity. During the last two decades, the ancient art of palpation gained new life due to numerous emerging elasticity imaging (EI) methods. Areas of applications of EI in medical diagnostics and treatment monitoring are steadily expanding. Elasticity imaging methods are emerging as commercial applications, a true testament to the progress and importance of the field. In this paper we present a brief history and theoretical basis of EI, describe various techniques of EI and, analyze their advantages and limitations, and overview main clinical applications. We present a classification of elasticity measurement and imaging techniques based on the methods used for generating a stress in the tissue (external mechanical force, internal ultrasound radiation force, or an internal endogenous force), and measurement of the tissue response. The measurement method can be performed using differing physical principles including magnetic resonance imaging (MRI), ultrasound imaging, X-ray imaging, optical and acoustic signals. Until recently, EI was largely a research method used by a few select institutions having the special equipment needed to perform the studies. Since 2005 however, increasing numbers of mainstream manufacturers have added EI to their ultrasound systems so that today the majority of manufacturers offer some sort of Elastography or tissue stiffness imaging on their clinical systems. Now it is safe to say that some sort of elasticity imaging may be performed on virtually all types of focal and diffuse disease. Most of the new applications are still in the early stages of research, but a few are becoming common applications in clinical practice.

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Accurate non-invasive assessment of tissue elasticity in vivo is required for early diagnostics of many tissue abnormalities. We have developed a focused air-pulse system that produces a low-pressure and short-duration air stream, which can be used to excite transient surface waves (SWs) in soft tissues. System characteristics were studied using a high-resolution analog pressure transducer to describe the excitation pressure. Results indicate that the excitation pressure provided by the air-pulse system can be easily controlled by the air source pressure, the angle of delivery, and the distance between the tissue surface and the port of the air-pulse system. Furthermore, we integrated this focused air-pulse system with phase-sensitive optical coherence tomography (PhS-OCT) to make non-contact measurements of tissue elasticity. The PhS-OCT system is used to assess the group velocity of SW propagation, which can be used to determine Young’s modulus. Pilot experiments were performed on gelatin phantoms with different concentrations (10%, 12% and 14% w/w). The results demonstrate the feasibility of using this focused air-pulse system combined with PhS-OCT to estimate tissue elasticity. This easily controlled non-contact technique is potentially useful to study the biomechanical properties of ocular and other tissues in vivo.

The biomechanical properties of the cornea play a critical role in forming vision. Diseases such as keratoconus can structurally degenerate the cornea causing a pathological loss in visual acuity. UV-A/riboflavin corneal collagen crosslinking (CXL) is a clinically available treatment to stiffen the cornea and restore its healthy shape and function. However, current CXL techniques do not account for pre-existing biomechanical properties of the cornea nor the effects of the CXL treatment itself. In addition to the inherent corneal structure, the intraocular pressure (IOP) can also dramatically affect the measured biomechanical properties of the cornea. In this work, we present the details and development of a modified Rayleigh-Lamb frequency equation model for quantifying corneal biomechanical properties. After comparison with finite element modeling, the model was utilized to quantify the viscoelasticity of in situ porcine corneas in the whole eye-globe configuration before and after CXL based on noncontact optical coherence elastography measurements. Moreover, the viscoelasticity of the untreated and CXL-treated eyes was quantified at various IOPs. The results showed that the stiffness of the cornea increased after CXL and that corneal stiffness is close to linear as a function of IOP. These results show that the modified Rayleigh-Lamb wave model can provide an accurate assessment of corneal viscoelasticity, which could be used for customized CXL therapies.

The motion of a rigid sphere in a viscoelastic medium in response to an acoustic radiation force of short duration was investigated. Theoretical and numerical studies were carried out first. To verify the developed model, experiments were performed using rigid spheres of various diameters and densities embedded into tissue-like, gel-based phantoms of varying mechanical properties. A 1.5 MHz, single-element, focused transducer was used to apply the desired radiation force. Another single-element, focused transducer operating at 25 MHz was used to track the displacements of the sphere. The results of this study demonstrate good agreement between theoretical predictions and experimental measurements. The developed theoretical model accurately describes the displacement of the solid spheres in a viscoelastic medium in response to the acoustic radiation force.

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.