Li-Ke Wang

Effects of optical beam angle on quantitative optical coherence tomography (OCT) in normal and surface degenerated bovine articular cartilage

Quantitative measurement of articular cartilage using optical coherence tomography (OCT) is a potential approach for diagnosing the early degeneration of cartilage and assessing the quality of its repair. However, a non-perpendicular angle of the incident optical beam with respect to the tissue surface may cause uncertainty to the quantitative analysis, and therefore, significantly affect the reliability of measurement. This non-perpendicularity was systematically investigated in the current study using bovine articular cartilage with and without mechanical degradation. Ten fresh osteochondral disks were quantitatively measured before and after artificially induced surface degradation by mechanical grinding. The following quantitative OCT parameters were determined with a precise control of the surface inclination up to an angle of 10° using a step of 2°: optical reflection coefficient (ORC), variation of surface reflection (VSR) along the surface profile, optical roughness index (ORI) and optical backscattering (OBS). It was found that non-perpendicularity caused systematic changes to all of the parameters. ORC was the most sensitive and OBS the most insensitive to the inclination angle. At the optimal perpendicular angle, all parameters could detect significant changes after surface degradation (p < 0.01), except OBS (p > 0.05). Nonsignificant change of OBS after surface degradation was expected since OBS reflected properties of the internal cartilage tissue and was not affected by the superficial mechanical degradation. As a conclusion, quantitative OCT parameters are diagnostically potential for characterizing the cartilage degeneration. However, efforts through a better controlled operation or corrections based on computational compensation mechanism should be made to minimize the effects of non-perpendicularity of the incident optical beam when clinical use of quantitative OCT is considered for assessing the articular cartilage.

In Vivo and ex Vivo Approaches to Studying the Biomechanical Properties of Healing Wounds in Rat Skin

An evaluation of wound mechanics is crucial in reflecting the wound healing status. The present study examined the biomechanical properties of healing rat skin wounds in vivo and ex vivo. Thirty male Sprague-Dawley rats, each with a 6 mm full-thickness circular punch biopsied wound at both posterior hind limbs were used. The mechanical stiffness at both the central and margins of the wound was measured repeatedly in five rats over the same wound sites to monitor the longitudinal changes over time of before wounding, and on days 0, 3, 7, 10, 14, and 21 after wounding in vivo by using an optical coherence tomography-based air-jet indentation system. Five rats were euthanized at each time point, and the biomechanical properties of the wound tissues were assessed ex vivo using a tensiometer. At the central wound bed region, the stiffness measured by the air-jet system increased significantly from day 0 (17.2%), peaked at day 7 (208.3%), and then decreased progressively until day 21 (40.2%) as compared with baseline prewounding status. The biomechanical parameters of the skin wound samples measured by the tensiometer showed a marked reduction upon wounding, then increased with time (all p < 0.05). On day 21, the ultimate tensile strength of the skin wound tissue approached 50% of the normal skin; while the stiffness of tissue recovered at a faster rate, reaching 97% of its prewounded state. Our results suggested that it took less time for healing wound tissues to recover their stiffness than their maximal strength in rat skin. The stiffness of wound tissues measured by air-jet could be an indicator for monitoring wound healing and contraction.

Correction on the distortion of Scheimpflug imaging for dynamic central corneal thickness

Abstract. 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.

Three-dimensional high frequency power Doppler ultrasonography for the assessment of microvasculature during fracture healing in a rat model

We aimed to establish a novel approach with 3D high frequency power Doppler ultrasonography (3D‐HF‐PDU) to assess microvasculature at the fracture site in rat femurs by comparing with microCT‐based microangiography. Twenty‐four 9‐month‐old ovariectomized (OVX) osteoporotic rats and age‐matched sham‐ovariectomized (Sham) rats were used for establishing closed fracture models on right femora. At 2, 4, and 8 weeks post‐operatively, four rats in each group underwent in vivo 3D‐HF‐PDU scanning for evaluation of vascularization and blood flow at the fracture site. Then the fractured femora were harvested for ex vivo microangiography, and neovasculatures within the callus were reconstructed for vascular volume analysis. Correlation between the vascular volumes of the two methodologies was examined. Both 3D‐HF‐PDU and microangiography showed a decline of vascular volume at the fracture site from 2 to 8 weeks and a significantly larger volume in the Sham group than the OVX group. A significant linear positive correlation (r = 0.87, p < 0.001) was detected between the volumes measured by the two methodologies. Osteoporotic rats had a diminished angiogenic response and lower blood perfusion than Shams. We believe 3D‐HF‐PDU is feasible and reproducible for in vivo assessment of microvasculature during femoral fracture healing in rats.

Determining in vivo elasticity and viscosity with dynamic Scheimpflug imaging analysis in keratoconic and healthy eyes

The paper presents a novel analysis method of corneal elasticity and viscosity based on corneal visualization Scheimpflug technology (CorVis ST) for keratoconus diagnosis. Methods for air puff force measurement and corneal imaging boundary extraction were proposed. Corneal biomechanical properties, described as tangent stiffness coefficient (STSC ) and energy absorbed area (Aabsorbed ), were assessed using the curves of the applied air puff force with corneal displacement to form a loading-unloading cycle. Twenty-five patients with keratoconus and 34 healthy control subjects, matched for intraocular pressure (IOP), were enrolled in this prospective study. The results showed that the intraclass correlation coefficients (ICC) of the STSC and Aabsorbed were 0.941 and 0.878 in Healthy group; and were 0.891 and 0.809 in Keratoconus group, respectively. Both STSC and Aabsorbed of keratoconus patients were significantly different from that of controls (both probability value P < 0.001). ROC curve analysis showed that the area under curve for STSC was 0.918 and for Aabsorbed was 0.894, which reached a good level of predictive accuracy for detecting keratoconus. Our results demonstrated that this new analysis method could be used to characterize the biomechanical properties of corneas. (a) The air puff force of CorVis ST was measured by a custom-designed force detection system. (b) Corneal displacement was extracted from CorVis ST using a proposed imaging analysis. (c) With the utilization of the air puff force and corneal dynamic displacement, an analysis method was developed to introduce new corneal biomechanical parameters - STSC and Aabsorbed .

A piezoresistive normal and shear force sensor using liquid metal alloy as gauge material

We present a novel normal and shear force sensor by using liquid metal alloy (Ga-In-Sn) as piezoresistive gauge material encapsulated in a polydimethylsiloxane (PDMS) substrate. By using liquid metal alloy as gauge material, it can detect large forces without breaking the sensor wires. Since the liquid-metal piezoresistors deform with the elastomeric substrate, shear and normal forces can be detected with resistance changes of the piezoresistors. Each force sensor comprises a pair of symmetric piezoresistors, which is screen-printed on the cavity of PDMS substrate with tilt angle around 30° to be sensitive to both normal and shear forces. Normal force will compress both piezoresistors as common mode while shear force will shorten one piezoresistor but elongate the other as differential mode. The testing results demonstrate the sensitivity of the force sensor in both normal and shear directions. The hysteresis of the force sensor was also measured.

Measurement of corneal tangent modulus using ultrasound indentation.

Biomechanical properties are potential information for the diagnosis of corneal pathologies. An ultrasound indentation probe consisting of a load cell and a miniature ultrasound transducer as indenter was developed to detect the force-indentation relationship of the cornea. The key idea was to utilize the ultrasound transducer to compress the cornea and to ultrasonically measure the corneal deformation with the eyeball overall displacement compensated. Twelve corneal silicone phantoms were fabricated with different stiffness for the validation of measurement with reference to an extension test. In addition, fifteen fresh porcine eyes were measured by the developed system in vitro. The tangent moduli of the corneal phantoms calculated using the ultrasound indentation data agreed well with the results from the tensile test of the corresponding phantom strips (R(2)=0.96). The mean tangent moduli of the porcine corneas measured by the proposed method were 0.089±0.026MPa at intraocular pressure (IOP) of 15mmHg and 0.220±0.053MPa at IOP of 30mmHg, respectively. The coefficient of variation (CV) and intraclass correlation coefficient (ICC) of tangent modulus were 14.4% and 0.765 at 15mmHg, and 8.6% and 0.870 at 30mmHg, respectively. The preliminary study showed that ultrasound indentation could be applied to the measurement of corneal tangent modulus with good repeatability and improved measurement accuracy compared to conventional surface displacement-based measurement method. The ultrasound indentation can be a potential tool for the corneal biomechanical properties measurement in vivo.

Ultrasound biomicroscopy measurement of skin thickness change induced by cosmetic treatment with ultrasound stimulation

Moisturizing creams and lotions are commonly used in daily life for beauty and treatment of different skin conditions such as dryness and wrinkling, and ultrasound stimulation has been used to enhance the delivery of ingredients into skin. However, there is a lack of convenient methods to study the effect of ultrasound stimulation on lotion absorption by skin in vivo. Ultrasound biomicroscopy was adopted as a viable tool in this study to investigate the effectiveness of ultrasound stimulation on the enhancement of lotion delivery into skin. The forearm skin of 10 male and 10 female young subjects was tested at three different sites, including two lotion treatment sites with (Ultrasound Equipment - UE ON) and without (UE OFF) ultrasound stimulation and a control site without any lotion treatment. 1 MHz ultrasound with a duty cycle of 1.7%, a spatial peak temporal peak pressure of 195 kPa and an average power of 0.43 W was used for the stimulation. The skin thickness before, immediately after (0 min), and 15 and 30 min after the treatment was measured by an ultrasound biomicroscopic system (55 MHz). It was found that the skin thickness significantly increased immediately after the lotion treatment for both UE ON (from 1.379 ± 0.187 mm to 1.466 ± 0.182 mm, p<0.001) and UE OFF (from 1.396 ± 0.193 mm to 1.430 ± 0.194 mm, p<0.001) groups. Further comparison between the two groups revealed that the skin thickness increase of UE ON group was significantly larger than that of UE OFF group (6.5 ± 2.4% vs. 2.5 ± 1.3%, p<0.001). Furthermore, it was disclosed that the enhancement of lotion delivery by ultrasound stimulation was more effective for the female subjects than the male subjects (7.6 ± 2.3% vs. 5.4 ± 2.0% immediately after treatment, p=0.017). In conclusion, this study demonstrated that ultrasound biomicroscopy was a feasible method for studying the effectiveness of lotion treatment in vivo, and ultrasound stimulation was effective to enhance the rate of lotion absorption into skin.

An OCT-based air suction-indentation probe for tissue elasticity measurement

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.