Ultrahigh resolution spectral-domain optical coherence tomography using the 1000-1600†nm spectral band.

Ultrahigh resolution optical coherence tomography (UHR-OCT) can image microscopic features that are not visible with the standard OCT resolution of 5-15 µm. In previous studies, high-speed UHR-OCT has been accomplished within the visible (VIS) and near-infrared (NIR-I) spectral ranges, specifically within 550-950 nm. Here, we present a spectral domain UHR-OCT system operating in a short-wavelength infrared (SWIR) range from 1000 to 1600 nm using a supercontinuum light source and an InGaAs-based spectrometer. We obtained an axial resolution of 2.6 µm in air, the highest ever recorded in the SWIR window to our knowledge, with deeper penetration into tissues than VIS or NIR-I light. We demonstrate imaging of conduction fibers of the left bundle branch in freshly excised porcine hearts. These results suggest a potential for deep-penetration, ultrahigh resolution OCT in intraoperative applications.

In vivo stiffness measurement of epidermis, dermis, and hypodermis using broadband Rayleigh-wave optical coherence elastography.

Traveling-wave optical coherence elastography (OCE) is a promising technique to measure the stiffness of biological tissues. While OCE has been applied to relatively homogeneous samples, tissues with significantly varying elasticity through depth pose a challenge, requiring depth-resolved measurement with sufficient resolution and accuracy. Here, we develop a broadband Rayleigh-wave OCE technique capable of measuring the elastic moduli of the 3 major skin layers (epidermis, dermis, and hypodermis) reliably by analyzing the dispersion of leaky Rayleigh surface waves over a wide frequency range of 0.1-10 kHz. We show that a previously unexplored, high frequency range of 4-10 kHz is critical to resolve the thin epidermis, while a low frequency range of 0.2-1 kHz is adequate to probe the dermis and deeper hypodermis. We develop a dual bilayer-based inverse model to determine the elastic moduli in all 3 layers and verify its high accuracy with finite element analysis and skin-mimicking phantoms. Finally, the technique is applied to measure the forearm skin of healthy volunteers. The Young's modulus of the epidermis (including the stratum corneum) is measured to be ∼ 4 MPa at 4-10 kHz, whereas Young's moduli of the dermis and hypodermis are about 40 and 15 kPa, respectively, at 0.2-1 kHz. Besides dermatologic applications, this method may be useful for the mechanical analysis of various other layered tissues with sub-mm depth resolution. STATEMENT OF SIGNIFICANCE: To our knowledge, this is the first study that resolves the stiffness of the thin epidermis from the dermis and hypodermis, made possible by using high-frequency (4 - 10 kHz) elastic waves and optical coherence elastography. Beyond the skin, this technique may be useful for mechanical characterizations of various layered biomaterials and tissues.

Supershear surface waves reveal prestress and anisotropy of soft materials.

Surface waves play important roles in many fundamental and applied areas from seismic detection to material characterizations. Supershear surface waves with propagation speeds greater than bulk shear waves have recently been reported, but their properties are not well understood. Here we describe theoretical and experimental results on supershear surface waves in rubbery materials. We find that supershear surface waves can be supported in viscoelastic materials with no restriction on the shear quality factor. Interestingly, the effect of prestress on the speed of the supershear surface wave is opposite to that of the Rayleigh surface wave. Furthermore, anisotropy of material affects the supershear wave much more strongly than the Rayleigh surface wave. We offer heuristic interpretation as well as theoretical verification of our experimental observations. Our work points to the potential applications of supershear waves for characterizing the bulk mechanical properties of soft solid from the free surface.

In vivo measurement of shear modulus of the human cornea using optical coherence elastography.

Corneal stiffness plays a critical role in shaping the cornea with respect to intraocular pressure and physical interventions. However, it remains difficult to measure the mechanical properties noninvasively. Here, we report the first measurement of shear modulus in human corneas in vivo using optical coherence elastography (OCE) based on surface elastic waves. In a pilot study of 12 healthy subjects aged between 25 and 67, the Rayleigh-wave speed was 7.86 ± 0.75 m/s, corresponding to a shear modulus of 72 ± 14 kPa. Our data reveal two unexpected trends: no correlation was found between the wave speed and IOP between 13-18 mmHg, and shear modulus decreases with age (- 0.32 ± 0.17 m/s per decade). We propose that shear stiffness is governed by the interfibrillar matrix, whereas tensile strength is dominated by collagen fibrils. Rayleigh-wave OCE may prove useful for clinical diagnosis, refractive surgeries, and treatment monitoring.

Optical coherence tomographic measurements of the sound-induced motion of the ossicular chain in chinchillas: Additional modes of ossicular motion enhance the mechanical response of the chinchilla middle ear at higher frequencies.

Wavelength-swept optical coherence tomography (OCT) was used to scan the structure of cadaveric chinchilla ears in three dimensions with high spatial resolution and measure the sound-induced displacements of the entire OCT-visible lateral surfaces of the ossicles in the lateral-to-medial direction. The simultaneous measurement of structure and displacement allowed a precise match between the observed motion and its structural origin. The structure and measured displacements are consistent with previously published data. The coincident detailed structural and motion measurements demonstrate the presence of several frequency-dependent modes of ossicular motion, including: (i) rotation about an anteriorly-to-posteriorly directed axis positioned near the commonly defined anatomical axis of rotation that dominates at frequencies below 8 kHz, (ii) a lateral-to-medial translational component that is visible at frequencies from 2 to greater than 10 kHz, and (iii) a newly described rotational mode around an inferiorly-to-superiorly directed axis that parallels the manubrium of the malleus and dominates ossicular motion between 10 and 16 kHz. This new axis of rotation is located near the posterior edge of the manubrium. The onset of the second rotational mode leads to a boost in the magnitude of sound-induced stapes displacement near 14 kHz, and adds a half-cycle to the accumulating phase in middle-ear sound transmission. Similar measurements in one ear after interruption of the incudostapedial joint suggest the load of the cochlea and stapes annular ligament is important to the presence of the second rotational mode, and acts to limit simple ossicular translation.

Measuring mechanical wave speed, dispersion, and viscoelastic modulus of the cornea using optical coherence elastography.

Acoustic wave velocity measurement based on optical coherence tomography (OCT) is a promising approach to assess the mechanical properties of biological tissues and soft materials. While studies to date have demonstrated proof of concept of different ways to excite and detect mechanical waves, the quantitative performance of this modality as mechanical measurement has been underdeveloped. Here, we investigate the frequency dependent measurement of the wave propagation in viscoelastic tissues, using a piezoelectric point-contact probe driven with various waveforms. We found that a frequency range of 2-10 kHz is a good window for corneal elastography, in which the lowest-order flexural waves can be identified in post processing. We tested our system on tissue-simulating phantoms and ex vivo porcine eyes, and demonstrate reproducibility and inter-sample variability. Using the Kelvin-Voigt model of viscoelasticity, we extracted the shear-elastic modulus and viscosity of the cornea and their correlation with the corneal thickness, curvature, and eyeball mass. Our results show that our method can be a quantitative, useful tool for the mechanical analysis of the cornea.

Mapping the phase and amplitude of ossicular chain motion using sound-synchronous optical coherence vibrography.

The sound-driven vibration of the tympanic membrane and ossicular chain of middle-ear bones is fundamental to hearing. Here we show that optical coherence tomography in phase synchrony with a sound stimulus is well suited for volumetric, vibrational imaging of the ossicles and tympanic membrane. This imaging tool - OCT vibrography - provides intuitive motion pictures of the ossicular chain and how they vary with frequency. Using the chinchilla ear as a model, we investigated the vibrational snapshots and phase delays of the manubrium, incus, and stapes over 100 Hz to 15 kHz. The vibrography images reveal a previously undescribed mode of motion of the chinchilla ossicles at high frequencies.

Effects of Corneal Hydration on Brillouin Microscopy In Vivo.

Purpose: To investigate how corneal hydration affects the Brillouin frequency of corneal stroma. Methods: From a simple analytical model considering the volume fraction of water in corneal stroma, we derived the dependence of Brillouin frequency on hydration and hydration-induced corneal thickness variation. The Brillouin frequencies of fresh ex vivo porcine corneas were measured as their hydration was varied in dextran solution and water. Healthy volunteers (8 eyes) were scanned in vivo repeatedly over the course of 9 hours, and the diurnal variations of Brillouin frequency and central corneal thickness (CCT) were measured. Results: The measured dependence of Brillouin frequency on hydration, both ex vivo and in vivo, agreed well with the theoretical prediction. The Brillouin frequencies of human corneas scanned immediately after waking were on average ∼25 MHz lower than their daytime average values. For stabilized corneas, the typical variation of Brillouin frequency was ± 7.2 MHz. With respect to CCT increase or swelling, the Brillouin frequency decreased with a slope of -1.06 MHz/µm in vivo. Conclusions: The ex vivo and in vivo data agree with our theoretical model and support that the effect of corneal hydration on Brillouin frequency comes predominantly from the dependence of the tissue compressibility on the water. Corneal hydration correlates negatively with the Brillouin frequency. During daytime activities, the influence of physiological hydration changes in human corneas is < ± 10 MHz. The sensitivity to hydration may potentially be useful in detecting abnormal hydration change in patients with endothelial disorders.

Shear Brillouin light scattering microscope.

Brillouin spectroscopy has been used to characterize shear acoustic phonons in materials. However, conventional instruments had slow acquisition times over 10 min per 1 mW of input optical power, and they required two objective lenses to form a 90° scattering geometry necessary for polarization coupling by shear phonons. Here, we demonstrate a confocal Brillouin microscope capable of detecting both shear and longitudinal phonons with improved speeds and with a single objective lens. Brillouin scattering spectra were measured from polycarbonate, fused quartz, and borosilicate in 1-10 s at an optical power level of 10 mW. The elastic constants, phonon mean free path and the ratio of the Pockels coefficients were determined at microscopic resolution.

Observation of sound-induced corneal vibrational modes by optical coherence tomography.

The mechanical stability of the cornea is critical for maintaining its normal shape and refractive function. Here, we report an observation of the mechanical resonance modes of the cornea excited by sound waves and detected by using phase-sensitive optical coherence tomography. The cornea in bovine eye globes exhibited three resonance modes in a frequency range of 50-400 Hz. The vibration amplitude of the fundamental mode at 80-120 Hz was ~8 µm at a sound pressure level of 100 dB (2 Pa). Vibrography allows the visualization of the radially symmetric profiles of the resonance modes. A dynamic finite-element analysis supports our observation.