Synovitis is a driver of osteoarthritis. Imaging of the synovial vasculature is essential for osteoarthritis assessment, while traditional imaging techniques like contrast-enhanced MRI/CT and conventional ultrasonography have limitations such as invasive manipulation, radiation and subjective results. In this study, an emerging non-invasive ultrasound imaging technique – optoacoustic molecular imaging (OA) was applied to evaluate the synovial vasculature in a mouse model of knee joint osteoarthritis. 16 male Balb/c mice undertook destabilization of medial meniscus surgery (DMM), 8 were intact as baseline controls. Three-dimensional high-frequency ultrasonography, including B mode, Power Doppler (PD) and OA, was performed to the knees of live mice at baseline (n=8), 1 month (n=8), and 4 months (n=7) after DMM, before tissue harvest. We found that OA vascular density increased significantly at 1 month (p=0.028) and remained high at 4 months (p=0.541), indicating synovial neovascularization during osteoarthritis progression, which was consistent with uCT-based angiography and histological findings. Meanwhile, OA could also evaluate the function of the synovial vasculature by measuring blood oxygen saturation (sO2). We found OA sO2 declined significantly at 4 months compared to baseline (p=0.043) and 1 month (p=0.027), indicating vascular dysfunction at late stage osteoarthritis. Moreover, OA sO2 was found closely related with histological cartilage damage (p=0.028). In this study, we demonstrated that OA was reliable to evaluate the small vasculatures in the knee joint of DMM mouse model. Our findings provided a new technique for the non-invasive monitoring of both structure and function of the synovial vasculature during osteoarthritis progression.
The measurement of central corneal thickness (CCT) is important in ophthalmology. Most studies concerned the value at normal status, while rare ones focused on its dynamic changing. The commercial Corvis ST is the only commercial device currently available to visualize the two-dimensional image of dynamic corneal profiles during an air puff indentation. However, the directly observed CCT involves the Scheimpflug distortion, thus misleading the clinical diagnosis. This study aimed to correct the distortion for better measuring the dynamic CCTs. The optical path was first derived to consider the influence of factors on the use of Covis ST. A correction method was then proposed to estimate the CCT at any time during air puff indentation. Simulation results demonstrated the feasibility of the intuitive-feasible calibration for measuring the stationary CCT and indicated the necessity of correction when air puffed. Experiments on three contact lenses and four human corneas verified the prediction that the CCT would be underestimated when the improper calibration was conducted for air and overestimated when it was conducted on contact lenses made of polymethylmethacrylate. Using the proposed method, the CCT was finally observed to increase by 66±34 μm at highest concavity in 48 normal human corneas.
In this study, we developed a miniaturized optical coherence tomography (OCT) probe with a diameter of 4 mm. It was integrated with an air-jet indentation and air suction to induce deformation of tissue. The deforming process of tissue under suction or indentation was continuously monitored by OCT, and deformation of tissue was then derived from the transient OCT signals. Studies on phantoms with different stiffness were conducted. Results showed that the stiffness obtained by the OCT-based suction and indention well correlated with the stiffness detected using conventional mechanical testing. The probe was small enough for endoscopic use. In addition to the elasticity, the viscoelasticity of tissues can also be detected using creep indentation and suction test.
Articular cartilage (AC) is a biological weight-bearing tissue covering the ends of articulating bones within synovial joints. Its function very much depends on the unique multi-layered structure and the depth-dependent material properties, which have not been well invetigated nondestructively. In this study, transient depth-dependent material properties of bovine patella cartilage were measured using ultrasound elastomicroscopy methods. A 50 MHz focused ultrasound transducer was used to collect A-mode ultrasound echoes from the articular cartilage during the compression and subsequent force-relaxation. The transient displacements of the cartilage tissues at different depths were calculated from the ultrasound echoes using a cross-correlation technique. It was observed that the strains in the superficial zone were much larger than those in the middle and deep zones as the equilibrium state was approached. The tissues inside the AC layer continued to move during the force-relaxation phase after the compression was completed. This process has been predicted by a biphasic theory. In this study, it has been verified experimentally. It was also observed that the tissue deformations at different depths of AC were much more evenly distributed before force-relaxation. AC specimens were also investigated using a 2D ultrasound elastomicroscopy system that included a 3D translating system for moving the ultrasound transducer over the specimens. B-mode RF ultrasound signals were collected from the specimens under different loading levels applied with a specially designed compressor. Preliminary results demonstrated that the scanning was repeatable with high correlation of radio frequency signals obtained from the same site during different scans when compression level was unchanged (R<sup>2</sup> > 0.97). Strains of the AC specimens were mapped using data collected with this ultrasound elastomicroscope. This system can also be potentially used for the assessment of other biological tissues, bioengineered tissues or biomaterials with fine structures.
Articular cartilage (AC) is a biological weight-bearing tissue covering the bony ends of articulating joints. Subtle changes in structure or composition can lead to degeneration of AC such as in osteoarthritis. Currently, there is a lack of reliable diagnostic techniques for early signs of osteoarthritis. The objective of this study was to use ultrasound to probe the transient depth-dependent swelling of AC in vitro, and ultimately to develop a new approach for the early assessment of osteoarthritis. A 50 MHz ultrasound system was used to collect reflected and scattered echoes from AC specimens. The displacements of selected portions of ultrasound signals were measured using a cross-correlation tracking approach. Osteochondral cylinders prepared from fresh bovine patellae were used in this study. During a test, the AC specimen was fixed in a testing chamber filled with saline solution. AC swelling was induced by either changing the concentration of the saline solution or emerging dehydrated AC specimens into the saline solution. Our preliminary results demonstrated that ultrasound could be used to reliably monitor the transient depth-dependent swelling induced by both approaches. It was found that water was gradually absorbed by the AC, first in the superficial layer, and then deep layer. The ultrasound speeds of AC tissues bathed in different saline solutions were different.