Relaxation time constant based optical coherence elastography

This study aimed at visualizing relative relaxation time constant (RTC) in soft tissue by using optical coherence elastography (OCE). We proposed a forced vibration model as a theoretical base to express RTC using axial gradient of periodic vibration phase captured by phase sensitive optical coherence tomography (PhS‐OCT). Validation of the model had been accomplished by experiments with isotropic and double‐layered phantoms. A fresh chicken breast sample treated with focused ultrasound was prepared to test performance of the RTC‐OCE in real tissue. All results were cross‐validated with indentation test and traditional strain‐based elastography. This study first utilized RTC mapping in 2D and 3D that covers the information of both elasticity and viscosity. The generated RTC mapping revealed the same mechanical difference internal sample which is correlated with conventional strain mapping. RTC mapping is potentially to be served as new biomarker for disease diagnosis in the future.     

Interplay of temperature,thermal‐stresses and strains in laser‐assisted modification of collagenous tissues: Speckle‐contrast and OCT‐based studies

Moderate heating of collagenous tissues such as cartilage and cornea by infrared laser irradiation can produce biologically nondestructive structural rearrangements and relaxation of internal stresses resulting in the tissue reshaping. The reshaping results and eventual changes in optical and biological properties of the tissue strongly depend on the laser‐irradiation regime. Here, a speckle‐contrast technique based on monochromatic illumination of the tissue in combination with strain mapping by means of optical coherence elastography (OCE) is applied to reveal the interplay between the temperature and thermal stress fields producing tissue modifications. The speckle‐based technique ensured en face visualization of cross correlation and contrast of speckle images, with evolving proportions between contributions of temperature increase and thermal‐stresses determined by temperature gradients. The speckle‐technique findings are corroborated by quantitative OCE‐based depth‐resolved imaging of irradiation‐induced strain‐evolution. The revealed relationships can be used for real‐time control of the reshaping procedures (e.g., for laser shaping of cartilaginous implants in otolaryngology and maxillofacial surgery) and optimization of the laser‐irradiation regimes to ensure the desired reshaping using lower and biologically safer temperatures. The figure of waterfall OCE‐image demonstrates how the strain‐rate maximum arising in the heating‐beam center gradually splits and drifts towards the zones of maximal thermal stresses located at the temperature‐profile slopes.     

Strain and elasticity imaging in compression optical coherence elastography: The two-decade perspective and recent advances

Quantitative mapping of deformation and elasticity in optical coherence tomography has attracted much attention of researchers during the last two decades. However, despite intense effort it took ~15 years to demonstrate optical coherence elastography (OCE) as a practically useful technique. Similarly to medical ultrasound, where elastography was first realized using the quasi-static compression principle and later shear-wave-based systems were developed, in OCE these two approaches also developed in parallel. However, although the compression OCE (C-OCE) was proposed historically earlier in the seminal paper by J. Schmitt in 1998, breakthroughs in quantitative mapping of genuine local strains and the Young's modulus in C-OCE have been reported only recently and have not yet obtained sufficient attention in reviews. In this overview, we focus on underlying principles of C-OCE; discuss various practical challenges in its realization and present examples of biomedical applications of C-OCE. The figure demonstrates OCE-visualization of complex transient strains in a corneal sample heated by an infrared laser beam.     

Handheld volumetric manual compression‐based quantitative microelastography

Compression optical coherence elastography (OCE) typically requires a mechanical actuator to impart a controlled uniform strain to the sample. However, for handheld scanning, this adds complexity to the design of the probe and the actuator stroke limits the amount of strain that can be applied. In this work, we present a new volumetric imaging approach that utilizes bidirectional manual compression via the natural motion of the user's hand to induce strain to the sample, realizing compact, actuator‐free, handheld compression OCE. In this way, we are able to demonstrate rapid acquisition of three‐dimensional quantitative microelastography (QME) datasets of a tissue volume (6 × 6 × 1 mm³) in 3.4 seconds. We characterize the elasticity sensitivity of this freehand manual compression approach using a homogeneous silicone phantom and demonstrate comparable performance to a benchtop mounted, actuator‐based approach. In addition, we demonstrate handheld volumetric manual compression‐based QME on a tissue‐mimicking phantom with an embedded stiff inclusion and on freshly excised human breast specimens from both mastectomy and wide local excision (WLE) surgeries. Tissue results are coregistered with postoperative histology, verifying the capability of our approach to measure the elasticity of tissue and to distinguish stiff tumor from surrounding soft benign tissue.     

In vivo noninvasive measurement of spatially resolved corneal elasticity in human eyes using Lamb wave optical coherence elastography

Current elastography techniques are limited in application to accurately assess spatially resolved corneal elasticity in vivo for human eyes. The air‐puff optical coherence elastography (OCE) with an eye motion artifacts correction algorithm is developed to distinguish the in vivo cornea vibration from the eye motion and visualize the Lamb wave propagation clearly in healthy subjects. Based on the Lamb wave model, the phase velocity dispersion curve in the high‐frequency is calculated to obtain spatially resolved corneal elasticity accurately with high repeatability. It is found that the corneal elasticity has regional variations and is correlated with intraocular pressure, which suggests that the method has the potential to provide noninvasive measurement of spatially resolved corneal elasticity in clinical practice.     

Translational optical coherence elastography for assessment of systemic sclerosis

Systemic sclerosis (SSc‐scleroderma) is an autoimmune disorder with high mortality rate that results in excessive accumulation of collagen in the skin and internal organs. Currently, the modified Rodnan Skin Score (mRSS) is the gold standard for evaluating the dermal thickening due to SSc. However, mRSS has noticeable inter‐ and intra‐observer variabilities as quantified by the interclass correlation coefficient (ICC: 0.6‐0.75). In this work, optical coherence elastography (OCE) combined with structural optical coherence tomography (OCT) image analysis was used to assess skin thickness in 12 SSc patients and healthy volunteers. Inter‐ (ICC: 0.62‐0.99) and intra‐observer (ICC > 0.90) assessment of OCT/OCE showed excellent reliability. Clinical assessments, including histologically assessed dermal thickness (DT), mRSS, and site‐specific mRSS (SMRSS) were also performed for further validation. The OCE and OCT results from the forearm demonstrated the highest correlation (OCE: 0.78, OCT: 0.65) with SMRSS. Importantly, OCE and OCT had stronger correlations with the histological DT (OCT: r = .78 and OCE: r = .74) than SMRSS (r = .57), indicating the OCT/OCE could outperform semi‐quantitative clinical assessments such as SMRSS. Overall, these results demonstrate that OCT/OCE could be useful for rapid, noninvasive and objective assessments of SSc onset and monitoring skin disease progression and treatment response.     

In vivo non-contact measurement of human iris elasticity by optical coherence elastography

Quantifying the mechanical properties of the iris can offer valuable insights into the pathophysiology of primary angle closure glaucoma. However, current techniques for iris elastography remain ex vivo with limited clinical applications. This article describes a proposition for a non-contact and non-invasive air-puff optical coherence elastography (OCE) system that can evaluate iris elasticity in vivo. Ten eyes recruited from seven subjects underwent OCE imaging acquisition under three different illumination conditions. The Young's modulus of each eye was detected and shown to be inversely proportional to the iris length, indicating a relationship between mechanical properties and morphology of the iris. With its noninvasive and high-resolution features, this air-puff system shows great potential for applications in clinical ophthalmology.     

Acoustic radiation force optical coherence elastography for evaluating mechanical properties of soft condensed matters and its biological applications

Evaluating mechanical properties of biological soft tissues and viscous mucus is challenging because of complicated dynamic behaviors. Soft condensed matter models have been successfully used to explain a number of dynamical behaviors. Here, we reported that optical coherence elastography (OCE) is capable of quantifying mechanical properties of soft condensed matters, micellar fluids. A 7.5 MHz focused transducer was utilized to generate acoustic radiation force exerted on the surface of soft condensed matters in order to produce Rayleigh waves. The waves were recorded by optical coherence tomography (OCT). The Kelvin‐Voigt model was adopted to evaluate shear modulus and loss modulus of soft condensed matters. The results reported that various concentrations of micellar fluids can provide reasonable ranges of elasticity from 65.71 to 428.78 Pa and viscosity from 0.035 to 0.283 Pa·s, which are close to ranges for actual biological samples, like mucus. OCE might be a promising tool to differentiate pathologic mucus samples from healthy cases as advanced applications in the future.     

Vascular elasticity measurement of the great saphenous vein based on optical coherence elastography

Vascular elasticity is important in physiological and clinical problems. The mechanical properties of the great saphenous vein (GSV) deserve attention. This research aims to measure the radial elasticity of ex vivo GSV using the optical coherence elasticity (OCE). The finite element model of the phantom is established, the displacement field is calculated, the radial mechanical characteristics of the simulation body are obtained. Furthermore, we performed OCE on seven isolated GSVs. The strain field is obtained by combining the relationship between strain and displacement to obtain the radial elastic modulus of GSVs. In the phantom experiment, the strain of the experimental region of interest is mainly between 0.1 and 0.4, while the simulation result is between 0.06 and 0.40. The radial elastic modulus of GSVs ranged from 3.83 kPa to 7.74 kPa. This study verifies the feasibility of the OCE method for measuring the radial elastic modulus of blood vessels.     

Three‐dimensional static optical coherence elastography based on inverse compositional Gauss‐Newton digital volume correlation

The three‐dimensional (3D) mechanical properties characterization of tissue is essential for physiological and pathological studies, as biological tissue is mostly heterogeneous and anisotropic. A digital volume correlation (DVC)‐based 3D optical coherence elastography (OCE) method is developed to measure the 3D displacement and strain tensors. The DVC algorithm includes a zero‐mean normalized cross‐correlation criterion‐based coarse search regime, an inverse compositional Gauss‐Newton fine search algorithm and a local ternary quadratic polynomial fitting strain calculation method. A 3D optical coherence tomography (OCT) scanning protocol is proposed through theoretical analysis and experimental verification. Measurement errors of the DVC‐based 3D OCE method are evaluated to be less than 2.0 μm for displacements and 0.30% for strains by rigid body motion experiments. The 3D displacements and strains of a phantom and a specimen of chicken breast tissue under compression are measured. Results of the phantom show a good agreement with theoretical analysis and tensile testing. The strains of the chicken breast tissue indicate anisotropic biomechanical properties. This study provides an effective method for 3D biomechanical property studies of soft tissue and improves the development of 3D OCE techniques.     

Buzz-pollination in Neotropical bees:genus-dependent frequencies and lack of optimal frequency for pollen release

Over 50 genera of bees release pollen from flower anthers using thoracic vibrations,a phenomenon known as buzz-pollination.The efficiency of this process is directly affected by the mechanical properties of the buzzes,namely the duration,amplitude,and frequency.Nonetheless,although the effects of the former two properties are well described,the role of buzz frequency on pollen release remains unclear.Furthermore,nearly all of the existing studies describing vibrational properties of natural buzz-pollination are limited to bumblebees(Bombus)and carpenter bees(Xvlocopa)constraining our current understanding of this behavior and its evolution.Therefore,we attempted to minimize this shortcoming by testing whether flower anthers exhibit optimal frequency for pollen release and whether bees tune their buzzes to match these(optimal)frequencies.If true,certain frequencies will trigger more pollen release and lighter bees will reach buzz frequencies closer to this optimum to compensate their smaller buzz amplitudes.Two strategies were used to test these hypotheses:(i)the use of(artificial)vibrational playbacks in a broad range of buzz frequencies and amplitudes to assess pollen release by tomato plants(Solarium Ivcopersicum L.)and(ii)the recording of natural buzzes of Neotropical bees visiting tomato plants during pollination.The playback experiment indicates that although buzz frequency does affect pollen release,no optimal frequency exists for that.In addition,the recorded results of natural buzz-pollination reveal that buzz frequencies vary with bee genera and are not correlated with body size.Therefore,neither bees nor plants are tuned to optimal pollen release frequencies.Bee frequency of buzz-pollination is a likely consequence of the insect flight machinery adapted to reach higher accelerations,while flower plant response to buzz-pollination is the likely result of its pollen granular properties.     

Simplifying the assessment of human breast cancer by mapping a micro‐scale heterogeneity index in optical coherence elastography

Surgical treatment of breast cancer aims to identify and remove all malignant tissue. Intraoperative assessment of tumor margins is, however, not exact; thus, re‐excision is frequently needed, or excess normal tissue is removed. Imaging methods applicable intraoperatively could help to reduce re‐excision rates whilst minimizing removal of excess healthy tissue. Optical coherence elastography (OCE) has been proposed for use in breast‐conserving surgery; however, intraoperative interpretation of complex OCE images may prove challenging. Observations of breast cancer on multiple length scales, by OCE, ultrasound elastography, and atomic force microscopy, have shown an increase in the mechanical heterogeneity of malignant breast tumors compared to normal breast tissue. In this study, a micro‐scale mechanical heterogeneity index is introduced and used to form heterogeneity maps from OCE scans of 10 ex vivo human breast tissue samples. Through comparison of OCE, optical coherence tomography images, and corresponding histology, malignant tissue is shown to possess a higher heterogeneity index than benign tissue. The heterogeneity map simplifies the contrast between tumor and normal stroma in breast tissue, facilitating the rapid identification of possible areas of malignancy, which is an important step towards intraoperative margin assessment using OCE.

     

Functional assessment of moisture influenced cadaveric tympanic membrane using phase shift‐resolved optical Doppler vibrography

An elevated relative moisture in the external ear canal and middle ear cavity may predispose to chronic otorrhea and related infections along with abnormal tympanic membrane (TM) vibration patterns. Therefore, phase shift‐resolved optical Doppler vibrography (ODV) was used for vibration assessments of moisture influenced cadaveric TM. ODV was applied to generate time resolved cross‐sectional and volumetric vibrographs of a cadaveric TM, driven acoustically at several frequencies. In order to analyze the effect of moisture on TM, homogenous moisture conditions were provided by soaking the cadaveric TM specimens in 1× phosphate buffer saline with a pH of 7.4. The TM specimen was exposed to a rapidly switchable frequency generator during the ODV image acquisition. The experiment was conducted for 3 hours and the cadaveric TM was exposed to each frequency with an interval of 30 minutes. Acquired phase shift‐resolved ODV assessments revealed a depth dependent vibration tendency between the applied frequencies, along with a decline in the moisture level of the cadaveric TM specimen. Thus, the ODV method can aid our understanding of sound conduction in the middle ear, thus supporting the diagnosis of TM diseases.     

Measurement of small mechanical vibrations of brain tissue exposed to extremely-low-frequency electric fields

Electromagnetic fields can interact with biological tissue both electrically and mechanically. This study investigated the mechanical interaction between brain tissue and an extremely-low-frequency (ELF) electric field by measuring the resultant vibrational amplitude. The exposure cell is a section of X-band waveguide that was modified by the addition of a center conductor to form a small TEM cell within the waveguide structure. The ELF signal is applied to the center conductor of the TEM cell. The applied ELF electric field generates an electrostrictive force on the surface of the brain tissue. This force causes the tissue to vibrate at a frequency equal to twice the frequency of the applied sinusoidal signal. An X-band signal is fed through the waveguide, scattered by the vibrating sample, and detected by a phase-sensitive receiver. Using a time-averaging spectrum analyzer, a vibration sensitivity of approximately 0.2 nmp-p can be achieved. The amplitude of the brain tissue vibrational response is constant for vibrational frequencies below 50 Hz; between 50 and 200 Hz resonant phenomena were observed; and above 200 Hz the amplitude fall-off is rapid.     

Spatiotemporal frequency responses of cat retinal ganglion cells

Spatiotemporal frequency responses were measured at different levels of light adaptation for cat X and Y retinal ganglion cells. Stationary sinusoidal luminance gratings whose contrast was modulated sinusoidally in time or drifting gratings were used as stimuli. Under photopic illumination, when the spatial frequency was held constant at or above its optimum value, an X cell's responsivity was essentially constant as the temporal frequency was changed from 1.5 to 30 Hz. At lower temporal frequencies, responsivity rolled off gradually, and at higher ones it rolled off rapidly. In contrast, when the spatial frequency was held constant at a low value, an X cell's responsivity increased continuously with temporal frequency from a very low value at 0.1 Hz to substantial values at temporal frequencies higher than 30 Hz, from which responsivity rolled off again. Thus, 0 cycles X deg-1 became the optimal spatial frequency above 30 Hz. For Y cells under photopic illumination, the spatiotemporal interaction was even more complex. When the spatial frequency was held constant at or above its optimal value, the temporal frequency range over which responsivity was constant was shorter than that of X cells. At lower spatial frequencies, this range was not appreciably different. As for X cells, 0 cycles X deg-1 was the optimal spatial frequency above 30 Hz. Temporal resolution (defined as the high temporal frequency at which responsivity had fallen to 10 impulses X s-1) for a uniform field was approximately 95 Hz for X cells and approximately 120 Hz for Y cells under photopic illumination. Temporal resolution was lower at lower adaptation levels. The results were interpreted in terms of a Gaussian center-surround model. For X cells, the surround and center strengths were nearly equal at low and moderate temporal frequencies, but the surround strength exceeded the center strength above 30 Hz. Thus, the response to a spatially uniform stimulus at high temporal frequencies was dominated by the surround. In addition, at temporal frequencies above 30 Hz, the center radius increased.     

Application of compression optical coherence elastography for characterization of human pericardium: A pilot study

The recent impressive progress in Compression Optical Coherence Elastography (C-OCE) demonstrated diverse biomedical applications, comprising ophthalmology, oncology, etc. High resolution of C-OCE enables spatially resolved characterization of elasticity of rather thin (thickness < 1 mm) samples, which previously was impossible. Besides Young's modulus, C-OCE enables obtaining of nonlinear stress–strain dependences for various tissues. Here, we report the first application of C-OCE to nondestructively characterize biomechanics of human pericardium, for which data of conventional tensile tests are very limited and controversial. C-OCE revealed pronounced differences among differently prepared pericardium samples. Ample understanding of the influence of chemo-mechanical treatment on pericardium biomechanics is very important because of rapidly growing usage of own patients' pericardium for replacement of aortic valve leaflets in cardio-surgery. The figure demonstrates differences in the tangent Young's modulus after glutaraldehyde-induced cross-linking for two pericardium samples. One sample was over-stretched during the preparation, which caused some damage to the tissue.     

Mechanical properties of the dorsal fin muscle of seahorse (Hippocampus) and pipefish (Syngnathus)

The dorsal and pectoral fins are the primary locomotor organs in seahorses (Hippocampus) and pipefish (Syngnathus). The small dorsal fins beat at high oscillatory frequencies against the viscous medium of water. Both species are able to oscillate their fins at frequencies likely exceeding the point of flicker fusion for their predators, thus enhancing their ability to remain cryptic. High-speed video demonstrated that seahorse dorsal fins beat at 30-42 Hz, while pipefish dorsal fins oscillate at 13-26 Hz. In both species, the movement of the fin is a sinusoidal wave that travels down the fin from anterior to posterior. Mechanical properties of seahorse and pipefish dorsal fin muscles were tested in vitro by the work loop method. Maximum isometric stress was 176.1 kN/m(2) in seahorse and 111.5 kN/m(2) in pipefish. Work and power output were examined at a series of frequencies encompassing the range observed in vivo, and at a number of strains (percent length change during a contractile cycle) within each frequency. At a given strain, work per cycle declined with increasing frequency, while power output rose to a maximum at an intermediate frequency and then declined. Frequency and strain interacted in a complex fashion; optimal strain was inversely related to cycle frequency over most of the frequency range tested. Seahorse dorsal fin muscle was able to generate positive work at higher cycling frequencies than pipefish. Both species produced positive work at higher frequencies than have been reported for axial and fin muscles from other fish.     

Estimating fish swimming metrics and metabolic rates with accelerometers: the influence of sampling frequency

Accelerometry is growing in popularity for remotely measuring fish swimming metrics, but appropriate sampling frequencies for accurately measuring these metrics are not well studied. This research examined the influence of sampling frequency (1–25 Hz) with tri‐axial accelerometer biologgers on estimates of overall dynamic body acceleration (ODBA), tail‐beat frequency, swimming speed and metabolic rate of bonefish Albula vulpes in a swim‐tunnel respirometer and free‐swimming in a wetland mesocosm. In the swim tunnel, sampling frequencies of ≥ 5 Hz were sufficient to establish strong relationships between ODBA, swimming speed and metabolic rate. However, in free‐swimming bonefish, estimates of metabolic rate were more variable below 10 Hz. Sampling frequencies should be at least twice the maximum tail‐beat frequency to estimate this metric effectively, which is generally higher than those required to estimate ODBA, swimming speed and metabolic rate. While optimal sampling frequency probably varies among species due to tail‐beat frequency and swimming style, this study provides a reference point with a medium body‐sized sub‐carangiform teleost fish, enabling researchers to measure these metrics effectively and maximize study duration.     

On the Quantification of SSVEP Frequency Responses in Human EEG in Realistic BCI Conditions

This article concerns one of the most important problems of brain-computer interfaces (BCI) based on Steady State Visual Evoked Potentials (SSVEP), that is the selection of the a-priori most suitable frequencies for stimulation. Previous works related to this problem were done either with measuring systems that have little in common with actual BCI systems (e.g., single flashing LED) or were presented on a small number of subjects, or the tested frequency range did not cover a broad spectrum. Their results indicate a strong SSVEP response around 10 Hz, in the range 13–25 Hz, and at high frequencies in the band of 40–60 Hz. In the case of BCI interfaces, stimulation with frequencies from various ranges are used. The frequencies are often adapted for each user separately. The selection of these frequencies, however, was not yet justified in quantitative group-level study with proper statistical account for inter-subject variability. The aim of this study is to determine the SSVEP response curve, that is, the magnitude of the evoked signal as a function of frequency. The SSVEP response was induced in conditions as close as possible to the actual BCI system, using a wide range of frequencies (5–30 Hz, in step of 1 Hz). The data were obtained for 10 subjects. SSVEP curves for individual subjects and the population curve was determined. Statistical analysis were conducted both on the level of individual subjects and for the group. The main result of the study is the identification of the optimal range of frequencies, which is 12–18 Hz, for the registration of SSVEP phenomena. The applied criterion of optimality was: to find the largest contiguous range of frequencies yielding the strong and constant-level SSVEP response.     

Transmission of Podisus maculiventris tremulatory signals through plants

Males of the predaceous stink bug Podisus maculiventris (Say) (Heteroptera: Pentatomidae: Asopinae) emit low frequency tremulatory signals. Laser vibrometry was used to record and analyze naturally emitted signals, focusing on variation in signal velocity and frequency during transmission through plants (Phaseolus vulgaris L. and Plumbago auriculata Lam.) as a function of distance from the vibrational source. Signal velocity varied individually between 2 and 15 mm/s recorded on a plant close to the calling male and decreased by 0.3 to 1.5 dB/cm on bean and 0.3 to 0.9 dB/cm on plumbago. The dominant frequency of signals was variable at frequencies below 50 Hz. On bean frequencies centered around 10 Hz or 20 Hz were dominant for signals recorded at the source. Transmission through bean resulted in an increase in the 20 Hz peak relative to other frequencies in the signal. Variation of the dominant frequencies of signals transmitted through plumbago stems were more predictable, showing typical changes in amplitude relative to the distance from the source. The regular variation of the dominant frequency along the stem with linear increase of signal velocity at decreasing distance from the source may provide plant-dwelling insects with information about the distance to the calling individual.