Optical coherence micro-elastography: mechanical-contrast imaging of tissue microstructure

Abstract

We present optical coherence micro-elastography, an improved form of compression optical coherence elastography. We demonstrate the capacity of this technique to produce en face images, closely corresponding with histology, that reveal micro-scale mechanical contrast in human breast and lymph node tissues. We use phase-sensitive, three-dimensional optical coherence tomography (OCT) to probe the nanometer-to-micrometer-scale axial displacements in tissues induced by compressive loading. Optical coherence micro-elastography incorporates common-path interferometry, weighted averaging of the complex OCT signal and weighted least-squares regression. Using three-dimensional phase unwrapping, we have increased the maximum detectable strain eleven-fold over no unwrapping and the minimum detectable strain is 2.6 με. We demonstrate the potential of mechanical over optical contrast for visualizing micro-scale tissue structures in human breast cancer pathology and lymph node morphology.

Investigation of Optical Coherence Microelastography as a Method to Visualize Cancers in Human Breast Tissue

“…However, the relatively low spatial resolution of existing elastography techniques may limit their suitability for intraoperative tumor margin assessment. OCME achieves microscale resolution by using OCT as the imaging modality (21)(22)(23)(24). OCT may be described as the optical analog to ultrasonography (25).…”

“…The contrast in OCME images (microelastograms), alternatively, is provided by differences in tissue mechanical properties. As the stiffness variations in breast tissue are correlated with both anatomical structures and pathologic state (35), OCME has the potential to be used to more accurately identify tumor and complement the contrast provided by OCT (24).…”

In vivo volumetric quantitative micro-elastography of human skin

“…The common-path configuration was chosen for this study as it minimizes phase noise in phase-sensitive detection, as we have previously demonstrated [30]. As the sample and reference signals traverse largely common paths, any phase noise caused by, for example, motion or vibration is common to both signals and, therefore, does not affect the phase difference measurement used to estimate displacement.…”

“…Depth-resolved (i.e., local) axial strain in the sample, ( , , ) sample x y z ε , is estimated from the axial gradient of displacement in depth using a weighted least-squares fitting algorithm over an axial range of 200 μm [27], which sets the minimum axial spatial resolution of the technique. To extend the range of measurable displacements, a phase unwrapping algorithm, described previously, was employed [27,30]. The strain in the compliant layer produced by the actuator, ( , ) layer x y ε , is determined by dividing the displacement determined using phase-sensitive detection at the interface of the layer and the sample, ( , ) l d x y , by the preloaded thickness of the layer, ( , ), l x y determined from the OCT image [25], i.e.,…”

Real-time and non-invasive measurements of cell mechanical behaviour with optical coherence phase microscopy

“…Imaging techniques, such as ultrasound and Magnetic Resonance Imaging (MRI) elastography have been introduced, however both lack the spatial resolution to be used on the cellular scale. The measurement of mechanical behaviour on the nano-and microscopic scale has used techniques such as atomic force microscopy (AFM), optical tweezers, and optical coherence elastography (OCE) (Kennedy et al, 2014b). AFM uses a cantilever and tip to determine quantitative cell mechanical properties, achieving high resolution and mechanical sensitivity.…”