Ravi Kiran Manapuram

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.

Noncontact measurement of elasticity for the detection of soft-tissue tumors using phase-sensitive optical coherence tomography combined with a focused air-puff system

We report on an optical noncontact method for the detection of soft-tissue tumors based on the measurement of their elasticity. A focused air-puff system is used to excite surface waves (SWs) on soft tissues with transient static pressure. A high-speed phase-sensitive optical coherence tomography system is used to measure the SWs as they propagate from the point of excitation. To evaluate the stiffness of soft tissues, the Youngs modulus is quantified based on the group velocity of SWs. Pilot experiments were performed on ex vivo human myxoma and normal fat. Results demonstrate the feasibility of the proposed method to measure elasticity and differentiate soft-tissue tumors from normal tissues.

Development of Phase-Stabilized Swept-Source OCT for the Ultrasensitive Quantification of Microbubbles

This paper describes the development of a novel-phase resolved system based on swept-source optical-coherence tomography (SSOCT) for the ultrasensitive imaging and monitoring of gas microbubbles in aqueous media. The developed phase-stabilized SSOCT (PhS-SSOCT) system has an axial resolution of 10 μm, a phase sensitivity of 0.03 rad, an imaging depth of up to 6 mm in air, and a scanning speed of 20 kHz for a single A line. The performance of the sensing system was evaluated in water-containing gas microbubbles with a different diameter. The obtained results demonstrate that bubbles with a diameter greater than 10 μm could be detected by both structural imaging and phase response, whereas bubbles with diameters of less than 10 μm could be detected by the phase response of the SSOCT with a high sensitivity. The accuracy for the measurement of the diameter of gas microbubbles is limited to 10 μm in structural imaging and 0.01 μm in phase-sensitive monitoring. The results from this study indicate that PhS-SSOCT could be used to detect fast-moving microbubbles in aqueous solutions and ultimately could be applied for rapid assessment in biofluids (e.g., blood) and tissues (e.g., skin) in vivo.

Dynamic optical coherence tomography measurements of elastic wave propagation in tissue-mimicking phantoms and mouse cornea in vivo

Abstract. We demonstrate the use of phase-stabilized swept-source optical coherence tomography to assess the propagation of low-amplitude (micron-level) waves induced by a focused air-pulse system in tissue-mimicking phantoms, a contact lens, a silicone eye model, and the mouse cornea in vivo. The results show that the wave velocity can be quantified from the analysis of wave propagation, thereby enabling the estimation of the sample elasticity using the model of surface wave propagation for the tissue-mimicking phantoms. This noninvasive, noncontact measurement technique involves low-force methods of tissue excitation that can be potentially used to assess the biomechanical properties of ocular and other delicate tissues in vivo.

Estimation of shear wave velocity in gelatin phantoms utilizing PhS-SSOCT

We report a method for measuring shear wave velocity in soft materials using phase stabilized swept source optical coherence tomography (PhS-SSOCT). Wave velocity was measured in phantoms with various concentrations of gelatin and therefore different stiffness. Mechanical waves of small amplitudes (∼10 μm) were induced by applying local mechanical excitation at the surface of the phantom. Using the phase-resolved method for displacement measurement described here, the wave velocity was measured at various spatially distributed points on the surface of the tissue-mimicking gelatin-based phantom. The measurements confirmed an anticipated increase in the shear wave velocity with an increase in the gelatin concentrations. Therefore, by combining the velocity measurements with previously reported measurements of the wave amplitude, viscoelastic mechanical properties of the tissue such as cornea and lens could potentially be measured.

In vivo estimation of elastic wave parameters using phase-stabilized swept source optical coherence elastography

Abstract. We report a highly sensitive method based on phase-stabilized swept source optical coherence elastography (PhS-SSOCE) to measure elastic wave propagation in soft tissues in vivo. The waves were introduced using a mechanical stimulus and were assessed using the phase response of the swept source optical coherence tomography signal. The technique was utilized to measure age-related changes in elastic flexural wave velocity and attenuation in mice cornea in vivo. Results demonstrate that the wave velocity increases with animal age, supporting previous observations that stiffness of mice cornea gradually increases with age. Our studies suggest that the PhS-SSOCE technique could potentially be used to obtain biomechanical properties of ocular tissues in vivo.

Phase-sensitive swept source optical coherence tomography for imaging and quantifying of microbubbles in clear and scattering media

A phase resolved system based on swept source optical coherence tomography (SSOCT) called as phase-sensitive SSOCT to detect and quantify gas microbubbles in aqueous and tissue simulated media is developed. The structural images of gas microbubbles are obtained using conventional SSOCT, while common path SSOCT was used to perform the phase-sensitive measurements. The system shows an axial resolution of 10μm, a phase sensitivity of 0.03rad, an imaging depth of up to 6mm in air, and a scanning speed of 20kHz for a single A-line. The structural images of the bubbles show an accuracy of 10μm, whereas the temporal phase response show an accuracy of 0.01μm. Images of rapidly moving bubbles are also presented which indicate that the SSOCT could be ultimately applied for the rapid assessment of microbubbles in biofluids and tissues.

Detection and Monitoring of Microparticles Under Skin by Optical Coherence Tomography as an Approach to Continuous Glucose Sensing Using Implanted Retroreflectors

We demonstrate the feasibility of using optical coherence tomography (OCT) to image and detect 2.8 μm diameter microparticles (stationary and moving) on a highly-reflective gold surface both in clear media and under skin in vitro. The OCT intensity signal can clearly report the microparticle count, and the OCT response to the number of microparticles shows a good linearity. The detect ability of the intensity change (2.9%±0.5%) caused by an individual microparticle shows the high sensitivity of monitoring multiple particles using OCT. An optical sensing method based on this feasibility study is described for continuously measuring blood sugar levels in the subcutaneous tissue, and a molecular recognition unit is designed using competitive binding to modulate the number of bound microparticles as a function of glucose concentration. With further development, an ultra-small, implantable sensor might provide high specificity and sensitivity for long-term continuous monitoring of blood glucose concentration.

Dynamic OCE measurement of the biomechanical properties of gelatin phantom and mouse cornea in vivo

Here we demonstrate our use of phase stabilized swept-source optical coherence elastography (PhS-SSOCE) to assess elastic wave propagation in gelatin phantoms. From these measurements, Young’s moduli of the samples were determined. Low-amplitude (<10μm) mechanical waves were introduced using a focused air pulse on gelatin of different concentrations. Elastic wave amplitude and velocity were measured at multiple points on the phantom surface using a phase-resolved method. The results demonstrate that this method is capable of resolving very small changes in wave amplitude (~ 10 nm) as well as differences in wave velocity due to material stiffness. We further demonstrate use of this method for measurements with a contact lens, a silicone eye model and with the eye of an 18-month-old mouse in vivo. This non-destructive, non-invasive measurement system produces minimal tissue excitation and has high measurement sensitivity. These traits make this make this method useful for in vivo study of the biomechanical properties of ocular and other tissues.

3D assessment of mechanical wave propagation in the crystalline eye lens using PhS-SSOCT

The stiffness of biological tissues could be assessed by measuring the propagation of mechanically induced waves on its surfaces that could help identifying various tissue pathologies. Here we present results for the volumetric assessment of mechanical waves propagating on both surfaces of the crystalline lens measured with the Phase-Sensitive Swept Source Optical Coherence Tomography (PhS-SSOCT) technique. The results indicate that the system could detect vibrations of as small as 0.03 μm in amplitude induced on the surface of crystalline lens, and hence, PhS-SSOCT could potentially be used to assess stiffness of a crystalline lens.