Salavat R. Aglyamov

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.

AN OVERVIEW OF ELASTOGRAPHY – AN EMERGING BRANCH OF MEDICAL IMAGING

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.

Intravascular photoacoustic imaging using an IVUS imaging catheter

Catheter-based imaging of atherosclerosis with high resolution, albeit invasive, is extremely important for screening and characterization of vulnerable plaques. Currently, there is a need for an imaging technique capable of providing comprehensive morphological and functional information of plaques. In this paper, we present an intravascular photoacoustic imaging technique to characterize vulnerable plaques by using optical absorption contrast between normal tissue and atherosclerotic lesions. Specifically, we investigate the feasibility of obtaining intravascular photoacoustic (IVPA) images using a high-frequency intravascular ultrasound (IVUS) imaging catheter. Indeed, the combination of IVPA imaging with clinically available IVUS imaging may provide desired functional and morphological assessment of the plaque. The imaging studies were performed with tissue-mimicking arterial vessel phantoms and excised samples of rabbit artery. The results of our study suggest that catheter-based intravascular photoacoustic imaging is possible, and the combination of IVPA with IVUS has the potential to detect and differentiate atherosclerosis based on both the structure and composition of the plaque

A focused air-pulse system for optical-coherence-tomography-based measurements of tissue elasticity

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 Youngs 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.

Sonographic elasticity imaging of acute and chronic deep venous thrombosis in humans.

Objective. The purpose of this study was to assess the ability of sonographic elasticity imaging to distinguish acute from chronic deep venous thrombosis (DVT). Methods. Fifty‐four patients, 26 with acute DVT and 28 with chronic DVT, were studied, and we analyzed the data in 46 patients, 23 with acute (mean age, 5.7 days) and 23 with chronic (>8 months) DVT. Scanning was performed with a 5‐MHz linear array transducer during continuous freehand external deformation of each thrombus using the ultrasound scan head. The strains in the thrombi were normalized to the average strain between the skin surface and the back wall of the vein. Relative thrombus echogenicity was measured by comparing the echogenicity of the thrombus with that of the adjacent arterial lumen. Statistical analyses were performed with the Mann‐Whitney U test and receiver operating characteristic analysis. Results. The median normalized strain magnitude for the acute cases was 2.75, with an interquartile range of 2.4 to 3.71, whereas the median normalized strain magnitude for the chronic cases was 0.94, with interquartile range of 0.48 to 1.36. The difference was highly significant (P < 10−7). The area under the receiver operating characteristic curve (Az) was 0.97 ± 0.02 (SE). The echogenicity difference between the populations was highly significant (P < 10−5), with Az of 0.92 ± 0.04. The difference between the Az values was not significant (P > .05). Conclusions. In this population, sonographic elasticity imaging performs at least as well as thrombus echogenicity. Thrombus aging using elasticity imaging would be particularly helpful in evaluating symptoms in patients with post‐thrombotic syndrome.

Environment-Dependent Generation of Photoacoustic Waves from Plasmonic Nanoparticles

Nanoparticle-augmented photoacoustics is an emerging technique for molecular imaging. This study investigates the fundamental process of the photoacoustic signal generation by plasmonic nanoparticles suspended in a weakly absorbing fluid. The photoacoustic signal of gold nanospheres with varying silica shell thicknesses is shown to be dominated by the heat transfer between the nanoparticles and the surrounding environment.

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.

Air-pulse OCE for assessment of age-related changes in mouse cornea in vivo

We demonstrate the use of phase-stabilized swept source optical coherence elastography (PhS-SSOCE) to assess the relaxation rate of deformation created by a focused air-pulse in tissue-mimicking gelatin phantoms of various concentrations and mouse corneas of different ages in vivo. The results show that the relaxation rate can be quantified and is different for gels with varying concentrations of gelatin and mouse corneas of different ages. The results indicate that gel phantoms with higher concentrations of gelatin as well as older mouse corneas have faster relaxation rates indicating stiffer material. This non-contact and non-invasive measurement technique utilizes low surface displacement amplitude (in µm scale) for tissue excitation and, therefore, can be potentially used to study the biomechanical properties of ocular and other sensitive tissues.

Clinical application of sonographic elasticity imaging for aging of deep venous thrombosis: Preliminary findings

Objective. Aging of deep venous thrombosis is an important and difficult clinical problem. Because it is known that thrombi harden as they mature, we have preliminarily tested sonographic elasticity imaging, a technique that estimates tissue hardness, to age venous thrombi. Methods. Two adult patients with lower extremity thrombi were studied. One had a clinically chronic thrombus (at least 3 years old), whereas the other patients thrombus was clinically subacute (25 days old). We performed freehand compression sonographic scans using a 5‐MHz linear array transducer. Phase‐sensitive B‐scan frames were processed offline by a two‐dimensional complex correlation‐based adaptive speckle‐tracking technique. The distribution of internal strains in the wall of the vein, thrombus, and surrounding tissue was analyzed. Clot hardness was normalized to the venous wall. Results. The chronic clot was homogeneous, and the strain in the chronic clot was at least 10 times smaller than that in the vessel wall. The subacute clot was much more heterogeneous, and, on average, the strain magnitude in the clot was 3 to 4 times greater than that in the vessel wall. Conclusions. In this preliminary work, the 2 thrombi appeared very different, and these results suggest that elasticity imaging may be able to age deep venous thrombosis.

1E-5 Synergy and Applications of Combined Ultrasound, Elasticity, and Photoacoustic Imaging (Invited)

An advanced in-vivo imaging technology; namely, combined ultrasound, elasticity and photoacoustic imaging, capable of visualizing both structural and functional properties of living tissue, is presented. This hybrid imaging technology is based on the fusion of the complementary imaging modalities and takes full advantage of the many synergistic features of these systems. To highlight fundamental differences and similarities between the imaging systems and to appreciate advantages and limitations of each imaging system, the basic physics of each imaging system is described. The experimental aspects of combined imaging including hardware, signal and image processing algorithms, etc. are presented. Noise and primary artifacts associated with each imaging modality and combined imaging system are analyzed, and techniques to increase and optimize contrast-to-noise and signal-to-noise ratios in the images are discussed. Finally, biomedical and clinical applications of the combined ultrasound, elasticity and photoacoustic imaging ranging from macroscopic to microscopic imaging of pathology are demonstrated and discussed