Optical Coherence Elastography Method Research Articles

Anisotropic elasticity measurements of the retina using optical coherence elastography

Anisotropic elasticity measurements of the retina are essential for retinal disease diagnosis and function assessment. Optical coherence elastography (OCE) is a high-resolution imaging technique for mapping the elasticity distribution of tissues. However, previous OCE measurements quantified the tissue elasticity in a single direction, resulting in a biased estimation of the elastic properties. In this study, we propose an OCE method with acoustic radiation force (ARF) excitation to map the retinal anisotropic elasticity in the depth and lateral directions. The axial elasticity was analyzed using the natural frequency of free vibration, and the lateral elasticity was quantified using the elastic wave velocity. After evaluating the feasibility of the OCE method on the phantoms, the anisotropic elasticity of ex vivo porcine retinas was mapped. The results show that the OCE method with ARF excitation can assess the elasticity in orthogonal directions and provide a comprehensive understanding of the elasticity of the anisotropic tissues.

Static compression optical coherence elastography for the measurement of porcine corneal mechanical properties ex-vivo

SignificanceThe biomechanical properties of the cornea are important for vision and ocular health. Optical coherence elastography (OCE) has the potential to improve our capacity to measure these properties. AimThis study tested a static compression OCE method utilising a commercially available optical coherence tomography (OCT) device, to estimate the Young’s modulus of ex-vivo porcine corneal tissue.Approach: OCT was used to image corneal tissue samples before and during loading by static compression. The compressive force was measured with a piezoresistive force sensor, and tissue deformation was quantified through automated image analysis. Ten ex-vivo porcine corneas were assessed and the corneal thickness was also measured to assess the impact of corneal swelling. ResultsAn average (standard deviation) Young’s modulus of 0.271 (+/- 0.091) MPa was determined across the 10 corneas assessed. There was a mean decrease of 1.78 % in corneal thickness at the end of the compression series. These results showed that there was a moderate association between corneal thickness and the Young’s modulus recording (R2 = 0.274). ConclusionsOptical coherence elastography utilising clinical instrumentation, can reliably characterise the mechanical properties of the cornea. These results support the further investigation of the technique for in-vivo measurement of the mechanical properties of the human cornea.

Dual-channel air-pulse optical coherence elastography for frequency-response analysis

Microliter air-pulse optical coherence elastography (OCE) has recently been proposed for the characterization of soft-tissue biomechanics using transient, sub-nanometer to micrometer-scale natural frequency oscillations. However, previous studies have not been able to provide real-time air-pulse monitoring during OCE natural frequency measurement, which could lead to inaccurate measurement results due to the unknown excitation spectrum. To address this issue, we introduce a dual-channel air-pulse OCE method, with one channel stimulating the sample and the other being simultaneously measured with a pressure sensor. This allows for more accurate natural frequency characterization using the frequency response function, as proven by a comprehensive comparison under different conditions with a diverse range of excitation spectra (from broad to narrow, clean to noisy) as well as a diverse set of sample response spectra. We also demonstrate the capability of the frequency-response analysis in distinguishing samples with different stiffness levels: the dominant natural frequencies increased with agar concentrations (181–359 Hz, concentrations: 1–2%, and maximum displacements: 0.12–0.47 µm) and intraocular pressures (IOPs) for the silicone cornea (333–412 Hz, IOP: 5–40 mmHg, and maximum displacements: 0.41–0.52 µm) under a 200 Pa stimulation pressure. These frequencies remained consistent across different air-pulse durations (3 ms to 35 ms). The dual-channel OCE approach that uses transient, low-pressure stimulation and high-resolution imaging holds the potential to advance our understanding of sample frequency responses, especially when investigating delicate tissues such as the human cornea in vivo.

Optical coherence elastography and its applications for the biomechanical characterization of tissues.

The biomechanical characterization of the tissues provides significant evidence for determining the pathological status and assessing the disease treatment. Incorporating elastography with optical coherence tomography (OCT), optical coherence elastography (OCE) can map the spatial elasticity distribution of biological tissue with high resolution. After the excitation with the external or inherent force, the tissue response of the deformation or vibration is detected by OCT imaging. The elastogram is assessed by stress-strain analysis, vibration amplitude measurements, and quantification of elastic wave velocities. OCE has been used for elasticity measurements in ophthalmology, endoscopy, and oncology, improving the precision of diagnosis and treatment of disease. In this article, we review the OCE methods for biomechanical characterization and summarize current OCE applications in biomedicine. The limitations and future development of OCE are also discussed during its translation to the clinic.

Assessment of resection margins during breast-conserving surgery using multimodal optical coherence tomography

Background. Breast cancer (BC) has been ranked first in morbidity and mortality among the female population in Russian Federation for several years. Rapid and accurate intraoperative examination of the cleanliness of resection margins is the main condition for breast-conserving surgery (BCS) to reduce the risks of local recurrence.Aim. To examine the tumor margins and assess the cleanliness of the resection margins in BCS in patients diagnosed with BC using multimodal optical coherence tomography (MM OCT) with comparative planned histological and additional molecular genetic analysis.Materials and methods. The study was carried out on postoperative samples of tumor and non-tumor breast tissue obtained from 115 patients with BC T1–2N0M0G2–3 stage IA–IIA, after BCS in the volume of radical resection or lumpectomy with histological control of the resection margins. A spectral domain MM OCT device (OCT 1300-E, BioMedTech LLC, Russia) was used, which provides structural OCT images to study the backscattering properties of tissue and allows performing a quantitative assessment of the elastic properties of the tissue by compression optical coherence elastography (OCE).Results. The MM OCT method was able to determine the exact margins between the tumor and non-tumor breast tissue. The main signs of the tumor were a decrease in the level and depth of penetration of the OCT signal in the structural OCT images, as well as an increase in the stiffness values (>200 kPa) in the OCE images with the highest stiffness values (>600 kPa) in the area of tumor cell accumulations. The use of compression OCE made it possible to detect clusters of tumor cells in the margins of resection at a distance of 5 mm from the visible border of the tumor. Among the 132 studied resection margins in 6 cases, the positive resection margin was determined by the OCE method, which was subsequently confirmed histologically. The negative resection margins were characterized by the lowest stiffness values (<200 kPa) in the OCE images and were confirmed by both histological analysis and molecular genetic analysis. ROC-analysis established a threshold stiffness value of 159.8 kPa, which indicates the presence of tumor tissue at the resection margins in the presence of a high stiffness area larger than 500 µm. The high diagnostic accuracy of the OCE method (98.5 %) was determined to distinguish between the negative and positive resection margins during BCS.Conclusion. The use of MM OCT with OCE modality makes it possible to clearly distinguish different types of breast tissue in BC (adipose tissue, connective tissue, accumulation of tumor cells). MM OCT can be used as an additional intraoperative tool for visualizing tumor cells boundaries and assessing the cleanliness of resection margins in real time during BCS.

In situ assessment of lens elasticity with noncontact optical coherence elastography.

Lens biomechanics has great potential for application in clinical diagnostics and treatment monitoring of presbyopia and cataracts. However, current approaches to lens elastography do not meet the desired safety or sensitivity for clinical application. In this regard, we propose a noncontact optical coherence elastography (OCE) method to facilitate quantitative in situ imaging of lens elasticity. Elastic waves induced by air-pulse stimulation on the limbus propagate to the lens and are then imaged using custom-built swept-source optical coherence tomography to obtain the elastic wave velocity and Young's modulus. The proposed OCE method was first validated by comparing the results of in situ and in vitro measurements of porcine lenses. The results demonstrate that the Young's modulus measured in situ was highly consistent with that measured in vitro and had an intraclass correlation coefficient of 0.988. We further investigated the elastic changes induced by cold storage and microwave heating. During 36-hour cold storage, the mean Young's modulus gradually increased (from 5.62 ± 1.24 kPa to 11.40 ± 2.68 kPa, P < 0.0001, n = 9) along with the formation of nuclear opacities. 15-second microwave heating caused a greater increase in the mean Young's modulus (from 6.86 ± 1.21 kPa to 25.96 ± 8.64 kPa, P < 0.0025, n = 6) without apparent cataract formation. Accordingly, this study reports the first air-pulse OCE measurements of in situ lenses, which quantified the loss of lens elasticity during simulated cataract development with good repeatability and sensitivity, thus enhancing the potential for adoption of lens biomechanics in the clinic.

Optical coherence elastography based on inverse compositional Gauss-Newton digital volume correlation with second-order shape function.

A digital volume correlation (DVC)-based optical coherence elastography (OCE) method with inverse compositional Gauss-Newton (IC-GN) algorithm and second-order shape function is presented in this study. The systematic measurement errors of displacement and strain from our OCE method were less than 0.2 voxel and 4 × 10-4, respectively. Second-order shape function could better match complex deformation and decrease speckle rigidity-induced error. Compared to conventional methods, our OCE method could track a larger strain range up to 0.095 and reduce relative error by 30-50%. This OCE method has the potential to become an effective tool in characterising mechanical properties of biological tissue.

Study of Laser-Induced Microdeformations of the Cornea Using Phase-Sensitive Optical Coherent Elastography

In many clinical cases, knowledge of the biomechanical properties of the cornea will allow for early diagnosis and also contribute to the success of treatment. The methods existing in the clinic characterize the biomechanical properties of the cornea as a whole, but do not give an idea of its local properties. One of the promising approaches to measure local changes in biomechanics is optical coherence elastography (OCE) based on phase-sensitive optical coherence tomography (OCT). In this work, the OCE method, based on the registration of small tissue deformations under an applied load, showed that the appearance and propagation of mechanical waves due to laser exposure depend on the loading of the studied biological tissue due to its tension with the application of various intraocular pressures (IOP). An analysis of inter-frame differential OCT images showed that the width of the laser impact zone on the tissue increases with increasing of IOP. An analysis of the strain amplitudes depending on the IOP at a given point revealed a correlation with the IOP value and made it possible to fix the fluidity threshold for the sample under consideration in the given experimental geometry .

Optical coherence elastography of bilayer soft tissue based on harmonic surface wave spectroscopy

Diseases often initiate from a certain layer of the biological tissue, thus simultaneous measurement of the elastic modulus of each layer is important for early diagnosis and treatment of various diseases. A surface wave spectroscopy (SWS) optical coherence elastography (OCE) technique based on harmonic wave excitation was proposed. An actuator consisting of a piezoelectric stack with a pin was designed to generate harmonic surface waves. A B-mode OCT data acquisition and phase analysis method was proposed to image the wave forms, and calculate the surface wave velocity. By exciting the sample with different frequencies, the surface wave dispersion curves were obtained. A total variation (TV) regularization iterative algorithm was proposed to obtain the elastic modulus distribution along the depth. Effectiveness of the proposed method was evaluated by both finite element simulation and experimental measurement of a bi-layer phantom. The mechanically driven harmonic wave actuation based OCE method is simple and cost-effective in experimental setup. Based on B-mode OCT scans, data analysis can be very fast, which is possible to realize real-time elastography imaging. This study provides an effective method for biomechanical properties study of layered tissue.

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.

Compression optical coherence elastography with two-dimensional displacement measurement and local deformation visualization.

Current compression-based optical coherence elastography (OCE) only measures the axial displacement of a tissue, although the tissue also undergoes lateral displacement and microstructural alteration by the compression. In this Letter, we demonstrate a new compression-based OCE method that visualizes not only axial displacement, but also lateral displacement and microstructural decorrelation (MSD). This method employs complex correlation-based displacement and MSD measurements. It is implemented in a swept-source optical coherence tomography system with an active submicrometer compression. The performance of the method was demonstrated by measuring the porcine carotid artery and esophagus. The results showed significant axial and lateral displacements in the tissues by compression. An MSD map demonstrates high-contrast mechanical-property imaging.

Biomechanical assessment of myocardial infarction using optical coherence elastography.

Myocardial infarction (MI) leads to cardiomyocyte loss, impaired cardiac function, and heart failure. Molecular genetic analyses of myocardium in mouse models of ischemic heart disease have provided great insight into the mechanisms of heart regeneration, which is promising for novel therapies after MI. Although biomechanical factors are considered an important aspect in cardiomyocyte proliferation, there are limited methods for mechanical assessment of the heart in the mouse MI model. This prevents further understanding the role of tissue biomechanics in cardiac regeneration. Here we report optical coherence elastography (OCE) of the mouse heart after MI. Surgical ligation of the left anterior descending coronary artery was performed to induce an infarction in the heart. Two OCE methods with assessment of the direction-dependent elastic wave propagation and the spatially resolved displacement damping provide complementary analyses of the left ventricle. In comparison with sham, the infarcted heart features a fibrotic scar region with reduced elastic wave velocity, decreased natural frequency, and less mechanical anisotropy at the tissue level at the sixth week post-MI, suggesting lower and more isotropic stiffness. Our results indicate that OCE can be utilized for nondestructive biomechanical characterization of MI in the mouse model, which could serve as a useful tool in the study of heart repair.

Investigating Elastic Anisotropy of the Porcine Cornea as a Function of Intraocular Pressure With Optical Coherence Elastography

To evaluate the elastic anisotropy of porcine corneas at different intraocular pressures (IOPs) using a noncontact optical coherence elastography (OCE) technique. A focused air-pulse induced low amplitude (≤ 10 µm) elastic waves in fresh porcine corneas (n = 7) in situ in the whole eye globe configuration. A home-built phase-stabilized swept source optical coherence elastography (PhS-SSOCE) system imaged the elastic wave propagation at different stepped radial directions. A closed-loop feedback system was used to artificially control the IOP and the OCE measurements were repeated as the IOP was incrementally increased from 15 to 30 mm Hg in 5-mm Hg increments. The OCE measurements demonstrated that the stiffness of the cornea increased as a function of IOP and elastic anisotropy of the cornea became more pronounced at higher IOPs. The standard deviation of the modified planar anisotropy coefficient increased from 0.72 ± 0.42 at an IOP of 15 mm Hg to 1.58 ± 0.40 at 30 mm Hg. The presented noncontact OCE method was capable of detecting and assessing the corneal elastic anisotropy as a function of IOP. Due to the noninvasive nature and small amplitude of the elastic wave, this method may be able to provide further information about corneal health and integrity in vivo. [J Refract Surg. 2016;32(8):562-567.].