The term "elastography" covers a dynamic and expanding set of diagnostic imaging techniques which probe the biomechanical properties of tissues. This overview covers some of the major approaches that have evolved and their role in improving clinical diagnoses. A deeper level of study is also emerging linking our estimates of viscoelasticity to the multiscale structure and composition of living tissue in normal and diseased states. These studies can be undertaken at the highest spatial resolution with optical techniques, and examples in cornea, brain, and skin will be covered.
A recent theoretical framework using power-law functions was proposed to model scattering from biological tissues in ultrasound and optical coherence tomography. Multi-scale scattering sites such as the fractal branching vasculature will then contribute to power-law based probability distributions of speckle statistics. These distributions are the Burr type XII distribution, the Lomax distribution, and the generalized logistic distribution for speckle amplitude, intensity, and log amplitude, respectively. Previous experiments with ultrasound and optical coherence tomography demonstrate that these distributions are better fits to image histogram data of various biological tissues when compared with classical models (e.g., Rayleigh, K, and gamma distributions). Of critical importance is that this framework provides novel parameters, most notably the power-law exponent parameter, for characterizing the physics of scattering from soft tissue. The typical range for the exponent parameter in other normal tissues is approximately 3 to 6. The aim is for this parameter to be used as a new biomarker for diagnostic imaging, sensitive to changes in tissue structures. Here, we demonstrate a specific application to mouse brain tissue, in which the exponent parameter is used to characterize mouse cortical brain under various conditions including ex vivo and in vivo using optical coherence tomography.
Significance: Corneal cross-linking (CXL) is a well-known procedure for treating certain eye disorders such as keratoconus. However, characterization of the biomechanical changes in the cornea as a result of this procedure is still under active research. Specifically, there is a clinical need for high-resolution characterization of individual corneal layers.
Aim: A high-resolution elastography method in conjunction with a custom optical coherence tomography system is used to track these biomechanical changes in individual corneal layers. Pre- and post-treatment analysis for both low-dose and high-dose CXL experiments are performed.
Approach: A recently developed elastography technique that utilizes the theory of reverberant shear wave fields, with optical coherence tomography as the modality, is applied to pig corneas ex vivo to evaluate elasticity changes associated with corneal CXL. Sets of low-dose and high-dose CXL treatments are evaluated before and after treatments with three pairs of pig corneas per experiment.
Results: The reverberant three-dimensional (3D) optical coherence elastography (OCE) technique can identify increases in elasticity associated with both low-dose and high-dose CXL treatments. There is a notable graphical difference between low-dose and high-dose treatments. In addition, the technique is able to identify which layers of the cornea are potentially affected by the CXL procedure and provides insight into the nonlinearity of the elasticity changes.
Conclusions: The reverberant 3D OCE technique can identify depth-resolved changes in elasticity of the cornea associated with CXL procedures. This method could be translated to assess and monitor CXL efficacy in various clinical settings.
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.
In medicine, both pathological (e.g. cirrhosis) and non-pathological states (e.g. aging) can be characterized by changes in the mechanical properties of biological tissue. The use of optical techniques to measure and map the elastic properties of soft tissue, known as optical elastography, is an emergent field with applications in various clinical disciplines, including ophthalmology and dermatology. In this paper, a brief overview of optical elastography will be provided with a short taxonomy. Categories include appropriate types of tissue models (semi-infinite, single thin layer, composite stacks), clinical tasks (classification or estimation), and excitation modes (transient, continuous, quasi-static, or molecular shift). We will then discuss examples of current advances, including optical coherence elastography using reverberant shear wave fields and Brillouin microscopy. The examples will demonstrate how current and future techniques may address clinical needs. Advantages and disadvantages of these techniques will be presented, augmenting the framework of the categorization system. With emerging applications, the taxonomy may be expanded providing a roadmap to future techniques.
A number of approaches employ optical coherence tomography (OCT) to obtain the mechanical properties of biological tissue. These are generally referred to as optical coherence elastography (OCE), and have demonstrated promising applications with studies in cornea, breast, muscle, skin, and other soft tissues. A particular application of interest is the brain, in which changes in local and global elastic properties may correlate with the onset and progression of degenerative brain diseases. In this preliminary study, mice brains are studied ex vivo and in situ with preservation of the brain/skull anatomical architecture. A small 6 mm diameter portion of the skull is replaced with a glass cap to allow for OCT imaging. Various permutations of source placement for generating shear waves and modes of excitation are evaluated to optimize the experimental setup. The use of reverberant shear wave fields, which takes advantage of inevitable reflections from boundaries and tissue inhomogeneities, allow for estimation of the shear wave speed, which is directly related to the elastic modulus of soft tissues. Preliminary estimates for the shear wave speed in brains of recently deceased mice are obtained. This study demonstrates potential applications in brain OCE ex vivo and in vivo.
The H-scan analysis of ultrasound images is a matched-filter approach derived from analysis of scattering from incident pulses in the form of Gaussian-weighted Hermite polynomial functions. This framework is applied in a preliminary study of thyroid lesions to examine the H-scan outputs for three categories: normal thyroid, benign lesions, and cancerous lesions within a total group size of 46 patients. In addition, phantoms comprised of spherical scatterers are analyzed to establish independent reference values for comparison. The results demonstrate a small but significant difference in some measures of the H-scan channel outputs between the different groups.
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