This PDF file contains the front matter associated with SPIE Proceedings Volume 11242, including the Title Page, Copyright information, Table of Contents, Author and Conference Committee lists.

We consider application of optical coherence elastography (OCE) to problems of laser-assisted structural modification/reshaping of avascular collagenous tissues used for fabrication of cartilaginous implants and corneal tissue reshaping for perspective technologies of vision-correction. The developed OCE technique allows one to quantitatively visualize aperiodic strains during the IR-laser irradiation of the tissue samples and evaluate cumulative strains produced by the laser irradiations. OCE can assess stability of laser-modeled implants via monitoring of post-irradiation slow strains and to study the interplay of temperature and thermal stresses to optimize tissue reshaping. Irradiation-induced micro-porosity in the tissue can be assessed via combination of strain mapping with compressional optical elastography.

Photonic force optical coherence elastography (PF-OCE) is a new approach for volumetric characterization of microscopic mechanical properties of soft materials. PF-OCE utilizes harmonically modulated optical radiation pressure to exert localized mechanical excitation on individual microbeads embedded in viscoelastic media. We present microrheological quantification of complex shear modulus in polyacrylamide gels with PF OCE. Spectroscopic measurements over a frequency range spanning 1 Hz to 7 kHz revealed rich frequency-dependent microstructural dynamics of entangled polymer networks across multiple microrheological regimes. PF-OCE provides an all-optical approach to quantitative three-dimensional mechanical microscopy and broadband spectroscopic microrheological studies of soft materials.

The biomechanical properties of the cornea can be an important biomarker for assessing tissue health. In this work, we evaluated cornea biomechanical properties during intraocular pressure fluctuation simulating heartbeat induced corneal pulse. This method results in a more physiologically relevant assessment of tissue mechanics, and thus diverges from typical elastography techniques that rely on externally induced deformation. Optical coherence tomography is used to detect displacements in the cornea as IOP is cycled. The axial strains within the cornea are calculated from these displacements, so that dynamic changes in stiffness can be determined. The results indicate a gradient in axial displacement within the cornea and illustrate a distinct difference in strain between the untreated and crosslinked tissues. This suggests that heartbeat OCE may be a useful technique in assessing stiffness of the cornea.

Silk graft biomaterials are proposed to improve the surgical repair of ruptured eardrums. The correct mechanical properties of these silk membranes are critical to ensure optimum patient outcomes. In this study, we use quantitative micro-elastography to characterize the elasticity of three dimensionally printed silk membrane scaffolds. To achieve this, we present a novel sample preparation technique that improves image quality. Using this approach we are able to characterize changes in silk membrane elasticity and study microscale elasticity gradients. We believe this approach will become an important tool to image biomaterials previously thought to be unsuitable for optical elastography.

We recently proposed an alternative elasticity measurement technique based on elastic wave propagation within a single cell. Waves are capture using an ultrafast camera and a microscope. This technique is based on the local measurement of the speed vs of a shear wave, a type of elastic wave. By assuming an infinite and homogeneous elastic medium with respect to the wavelength, the shear modulus μ (elasticity) is estimated. These latter assumptions are discussed through experiments conducted in controlled elastic solids. The conclusion is that wave guide effects as well as viscosity are crucial for quantitative mapping of elasticity.

In the last 10 years, Shear Wave Elastography became a very successful technique that is now widely used in medical diagnosis and is now commercialized by several companies. It is based on a multi-wave approach combining ultrasound and low frequency shear waves. We will give a historical perspective on all this field and we will show how these ideas has emerged in the ultrasound imaging community. We will describe the different approaches that were proposed and the limitations of each of them. We will show why some techniques have disappeared and we will discussed future perspectives of this field.

Breast neoplasia is accompanied by a heterogeneous micromechanical remodeling of the tumor landscape. Nevertheless, the role of these micromechanical heterogeneities in the progression of invasive breast carcinoma remains unclear. We have developed a novel optical tool, termed laser speckle microrheology (LSM) for micro-mechanical mapping of the tissue to investigate mechano-pathological features of breast cancer progression. Results reveal distinct micromechanical properties both between tumor of different diagnosis and within various regions of each tumor. Additionally, distinct stiffness gradients are observed at the interface of tumors with different invasive potential. Taken together, these findings identify key micromechanical features involved in breast cancer progression.

Biological matter is usually structurally anisotropic. As such the speed of acoustic phonons, which can be probed using Brillouin spectroscopy, depends on the angular-direction. Using a novel spectrometer-setup, which simultaneously probes the acoustic-velocity from different azimuthal angles, we quantify this anisotropy in different biological structures. By point-scanning the sample we render spatial-maps of parts of the phonon dispersion relation and find different regions in live cells have distinct anisotropic properties in their phonon velocity, with variations related to cell-health and phase. I will discuss the physical/biological interpretation of our results, their relevance for understanding/modelling cellular mechanics, and potential diagnostic applications.

One challenge of common confocal Brillouin microscopy is the relatively slow mapping speed, which is due to both the intrinsically weak signal of spontaneous Brillouin scattering and the point-by-point mapping strategy. We previously have proposed a multiplex mapping idea called line-scanning Brillouin microscopy and demonstrated its capability for fast imaging. In this work, we adapt this idea into a new setup for biological application by redesigning the whole optical configuration. We will evaluate the performance of the new setup and show the feasibility for rapid biomechanical mapping.

Brillouin microscopy is an emerging imaging modality in a broad area of biomedical research and clinical applications. Over the past decade, a significance progress has been achieved in developing better, more accurate and more user-friendly instrumentation for Brillouin microscopy and in fundamental understanding of the imaging contrast affordable in Brillouin microscopy. In this report, we report on our progress on developing advanced Brillouin microscopy imaging for imaging of dynamic biological processes.

Biological tissues have complex structures, dynamics and interactions between their constituents. When probing mechanical properties, differences are observed across spatial and temporal scales owing to the tissue viscoelastic response. Quasistatic mechanical testing, ultrasound and AFM-based techniques provide the traditional approach to measure stiffness based on the Young’s modulus. A novel technique in the fields of biophotonics and biomechanics is Brillouin spectroscopy, which is a contactless optical method to detect viscoelastic properties from the propagation of thermally-driven acoustic waves or phonons at high frequencies, GHz. A longitudinal elastic modulus is detected, whose significance in mechanobiology and clinical settings is currently emerging.

In Brillouin microscopy, absorption-induced photodamage of incident light is the primary limitation on signal-to-noise ratio in many practical scenarios. 660 nm may represent an optimal wavelength for Brillouin microscopy as it offers minimal absorption-mediated photodamage at high Brillouin scattering efficiency. We demonstrate that live cells are ~80 times less susceptible to the 660 nm incident light compared to 532 nm light, which overall allows Brillouin imaging with more than 30 times higher signal intensity. We apply this improved Brillouin microscope to analyze the response of human glioblastoma cells to a range of in vitro biomimetic environments.

Knowledge of corneal and ocular biomechanics is important in understanding the development and progression in many disease processes, as well as in screening for pathologic conditions and monitoring response to treatment. However, measuring classic properties such as modulus of elasticity is challenging in the living eye, where destructive testing is not appropriate. Many technologies are under development, but are years away from translation to the clinic. Two clinical devices are available commercially, and both use an air puff as the applied load on the cornea. The spatial and temporal profiles of the air puffs are distinct, as are the responses.

In assuming an isotropic model for soft-tissue, dynamic OCE can produce order of magnitude errors in Young’s modulus estimates relative to static mechanical tests. Considering corneal fiber arrangement, we propose a simplified transverse isotropic (TI) model of the cornea, which depends on moduli λ and μ and the independent modulus G (which affects the propagation of vertically polarized surface waves, such as those measured in OCE). Early theoretical and experimental studies suggest that this TI model of the cornea may greatly improve quantitative estimates of corneal mechanics obtained using dynamic OCE.

The exquisite phase sensitivity of Optical Coherence Tomography (OCT) has enabled the development of sensitive spatially resolved vibrometers. Using this technology, it is possible to measure vibratory response in live animals and humans down to a few picometers in amplitude. We are employing this technology in animal models to probe the mechanics of the cochlea, the part of the inner ear responsible for hearing. OCT based Vibrometry (OCTV) can image through the bone to capture morphological and functional images of the soft tissues within the cochlea. These measurements have led to new understandings of the mechanical processing of sound. Through recent advances it is now possible to make completely noninvasive OCTV measurements in awake mice. This has enabled studies including feedback from the efferent nerves that are shutdown in an anesthetized animal. These and related optical technologies are making a significant impact on our understanding of the mechanics of hearing.

Age-related cataract is one of the most prevalent causes of visual impairment worldwide. Early detection of cataracts can be immensely helpful for preserving visual acuity by ensuring that the appropriate therapeutic procedures are performed at earlier stages of the disease. In this work, we investigated the relationship between the progression of oxidative cataract and the biomechanical properties of the crystalline lens. We assessed the changes in the stiffness induced by cataracts in porcine lenses in vitro with dynamic optical coherence elastography. The efficacy of α-lipoic acid to minimize the stiffening of the lens was also quantified. The results showed a significant increase in Young’s modulus of the lens due to the formation of the oxidative cataract (from ~ 8 kPa to ~123 kPa). Young’s moduli of the lenses decreased after incubation in α-Lipoic Acid (~123 kPa vs ~45 kPa). These results show that the lens stiffness increased during oxidative cataract formation and that α-lipoic acid has the potential to reduce the stiffening of the lens caused by the oxidative damage.

Longitudinal shear waves (LSW) are waves with longitudinally polarized displacement that travel at the shear wave speed through depth when generated at the surface of tissues. In this study, we explore LSW generated by a circular glass plate in contact with the sample. Results demonstrated the potential of LSW in detecting an elasticity gradient along axial (resolution < 0.13 mm) and lateral (resolution < 0.78 mm) directions simultaneously. Finally, LSWs are used for the elastography of ex vivo mouse brain and demonstrated differentiated LSW speed values between the cerebral cortex (2.91 m/s) and cerebellum/midbrain (1.18 m/s) regions.

The changes in biomechanical properties of lens and cornea are closely correlated with presbyopia and cataract. We developed an optical coherence elastography system utilizing acoustic radiation force excitation to simultaneously assess the elasticities of the crystalline lens and the cornea in vivo. A swept light source was integrated into the system to provide an enhanced imaging range that covers both the lens and the cornea. Additionally, the oblique imaging approach combined with orthogonal excitation also improved the image quality. Simultaneous elasticity measurements of lens and cornea were performed in anesthetized rabbits to demonstrate the capability of ARF-OCE to characterize in vivo elasticity in the anterior eye.

This presentation reports a comparison between two handheld quantitative micro elastography (QME) methods: PZT actuated compression QME and manual compression QME. PZT actuated compression QME utilizes a PZT actuator to provide a periodic compression against the scanned sample, whilst manual compression QME utilizes the continuous motion of the user’s hand holding the probe to create compression against the sample. From our results, each method has its own advantages, and both methods are capable of measuring elasticity of the sample and distinguishing stiff tumor from regions of soft benign tissue on excised human breast specimens.

This paper summarizes the latest results on acoustic micro-tapping (AμT) -based OCE and provides answers to several important questions related to dynamic elastography, including: what is the maximum spatial resolution that can be achieved in dynamic OCE? How should propagation speed be measured in soft tissue, especially in layered or bounded media? How can tissue elastic properties be properly reconstructed from experimental data? What is the potential for clinical translation, and what barriers remain?

Polarization-sensitive optical coherence elastography was developed. It integrates Jones matrix-based polarization-sensitive optical coherence tomography with compression OCE. The method simultaneously measures OCT, attenuation coefficient, birefringence, and tissue mechanical properties. Ex-vivo porcine esophagus was measured by PS-OCE. Evident alteration caused by heat-induced denaturation was obtained in almost all of the optical and mechanical properties including attenuation coefficient, birefringence, in-plane lateral displacement, and microstructural deformation.

We develop a spatial coordinate corrected (SCC) motion tracking method for optical coherence elastography. SCC motion tracking refers the instantaneous velocity field extracted from optical coherence tomography (OCT) data to the laboratory coordinate system and accurately reconstructs the displacement field established during the mechanical excitation (compression) process. We acquired image data from compression OCE experiments on human breast tissue specimens, and reconstructed the displacement field through Doppler analysis of OCT data. Our results suggested that SCC tracking enables accurate reconstruction of displacement field, and enables effective identification mechanical heterogeneity that can be used as a biomarker for cancer diagnosis and tumor margin assessment.