Cho Chiang Shih

Assessing the viscoelastic properties of thrombus using a solid-sphere-based instantaneous force approach.

The viscoelastic properties of thrombus play a significant role when the clot closes a leak in a vessel of the blood circulation. The common method used to measure the viscoelastic properties of a clot employs a rheometer but this might be unsuitable due to the clot fiber network being broken up by excessive deformation. This study assessed the feasibility of using a novel acoustic method to assess the viscoelastic properties of blood clots. This method is based on monitoring the motion of a solid sphere in a blood clot induced by an applied instantaneous force. Experiments were performed in which a solid sphere was displaced by a 1 MHz single-element focused transducer, with a 20 MHz single-element focused transducer used to track this displacement. The spatiotemporal behavior of the sphere displacement was used to determine the viscoelastic properties of the clot. The experimental system was calibrated by measuring the viscoelastic modulus of gelatin using different types of solid spheres embedded in the phantoms and, then, the shear modulus and viscosity of porcine blood clots with hematocrits of 0% (plasma), 20% and 40% were assessed. The viscoelastic modulus of each clot sample was also measured directly by a rheometer for comparison. The results showed that the shear modulus increased from 173 ± 52 (mean ± SD) Pa for 40%-hematocrit blood clots to 619.5 ± 80.5 Pa for plasma blood clots, while the viscosity decreased from 0.32 ± 0.07 Pa∙s to 0.16 ± 0.06 Pa∙s, respectively, which indicated that the concentration of red blood cells and the amount of fibrinogen are the main determinants of the clot viscoelastic properties.

Estimating the viscoelastic modulus of a thrombus using an ultrasonic shear-wave approach.

PURPOSE Measurements of the viscoelastic properties of a thrombus can be used to assess whether blood clots are likely to become occlusive or to break apart and leak into the blood circulation and block smaller vessels. An accurate method for estimating both the shear elasticity and viscosity of a blood clot in vivo is still lacking, which prompted us to use a novel shear-wave approach to measure the viscoelastic modulus of blood clots. METHODS The shear-wave dispersion ultrasound vibrometry was used to measure both the elasticity and viscosity of blood clots. The experimental system was verified by measuring the viscoelastic modulus of phantoms containing gelatin at different concentrations. Blood-clot experiments were carried out using porcine whole blood with hematocrits ranging from 3% to 40%. The measured values for both clots and gelatin phantoms were compared to those obtained using an embedded-sphere method in order to validate the accuracy of the viscoelastic modulus estimations. RESULTS The shear elastic modulus increased from 406.9 ± 15.8 (mean ± SD) Pa for 3% gelatin to 1587.2 ± 28.9 Pa for 7% gelatin, while the viscosity increased from 0.12 ± 0.02 Pa s to 0.86 ± 0.05 Pa s, respectively. The shear modulus increased from 196.8 ± 58.4 Pa for 40%-hematocrit clots to 641.4 ± 76.3 Pa for 3%-hematocrit clots, while the viscosity increased from 0.29 ± 0.02 Pa s to 0.42 ± 0.01 Pa s, respectively. CONCLUSIONS The results from the statistical analysis indicated that both the embedded-sphere and shear-wave approaches can provide accurate estimations of the shear elasticity for clots and gelatin phantoms. In contrast, the shear-wave approach as well as other methods of rheological measurements does not provide accurate viscosity estimations for blood clots. However, the measured viscosity range of 0.29-0.42 Pa s is reasonable for blood clots.

High-Resolution Acoustic-Radiation-Force-Impulse Imaging for Assessing Corneal Sclerosis

In ophthalmology, detecting the biomechanical properties of the cornea can provide valuable information about various corneal pathologies, including keratoconus and the phototoxic effects of ultraviolet radiation on the cornea. Also, the mechanical properties of the cornea can be used to evaluate the recovery from corneal refractive surgeries. Therefore, noninvasive and high-resolution estimation of the stiffness distribution in the cornea is important in ophthalmic diagnosis. The present study established a method for high-resolution acoustic-radiation-force-impulse (ARFI) imaging based on a dual-frequency confocal transducer in order to obtain a relative stiffness map, which was used to assess corneal sclerosis. An 11-MHz pushing element was used to induce localized displacements of tissue, which were monitored by a 48-MHz imaging element. Since the tissue displacements are directly correlated with the tissue elastic properties, the stiffness distribution in a tiny region of the cornea can be found by a mechanical B/D scan. The experimental system was verified using tissue-mimicking phantoms that included different geometric structures. Ex vivo cornea experiments were carried out using fresh porcine eyeballs. Corneas with localized sclerosis were created artificially by the injection of a formalin solution. The phantom experiments showed that the distributions of stiffness within different phantoms can be recognized clearly using ARFI imaging, and the measured lateral and axial resolutions of this imaging system were 177 and 153 μm, respectively. The ex vivo experimental results from ARFI imaging showed that a tiny region of localized sclerosis in the cornea could be distinguished. All of the obtained results demonstrate that high-resolution ARFI imaging has considerable potential for the clinical diagnosis of corneal sclerosis.

High-Resolution Tissue Doppler Imaging of the Zebrafish Heart During Its Regeneration

The human heart cannot regenerate after injury, whereas the adult zebrafish can fully regenerate its heart even after 20% of the ventricle is amputated. Many studies have begun to reveal the cellular and molecular mechanisms underlying this regenerative process, which have exciting implications for human cardiac diseases. However, the dynamic functions of the zebrafish heart during regeneration are not yet understood. This study established a high-resolution echocardiography for tissue Doppler imaging (TDI) of the zebrafish heart to explore the cardiac functions during different regeneration phases. Experiments were performed on AB-line adult zebrafish (n=40) in which 15% of the ventricle was surgically removed. An 80-MHz ultrasound TDI based on color M-mode imaging technology was employed. The cardiac flow velocities and patterns from both the ventricular chamber and myocardium were measured at different regeneration phases relative to the day of amputation. The peak velocities of early diastolic inflow, early diastolic myocardial motion, late diastolic myocardial motion, early diastolic deceleration slope, and heart rate were increased at 3 days after the myocardium amputation, but these parameters gradually returned to close to their baseline values for the normal heart at 7 days after amputation. The peak velocities of late diastolic inflow, ventricular systolic outflow, and systolic myocardial motion did not significantly differ during the heart regeneration.

Application of a novel Kalman filter based block matching method to ultrasound images for hand tendon displacement estimation

PURPOSE Information about tendon displacement is important for allowing clinicians to not only quantify preoperative tendon injuries but also to identify any adhesive scaring between tendon and adjacent tissue. The Fisher-Tippett (FT) similarity measure has recently been shown to be more accurate than the Laplacian sum of absolute differences (SAD) and Gaussian sum of squared differences (SSD) similarity measures for tracking tendon displacement in ultrasound B-mode images. However, all of these similarity measures can easily be influenced by the quality of the ultrasound image, particularly its signal-to-noise ratio. Ultrasound images of injured hands are unfortunately often of poor quality due to the presence of adhesive scars. The present study investigated a novel Kalman-filter scheme for overcoming this problem. METHODS Three state-of-the-art tracking methods (FT, SAD, and SSD) were used to track the displacements of phantom and cadaver tendons, while FT was used to track human tendons. These three tracking methods were combined individually with the proposed Kalman-filter (K1) scheme and another Kalman-filter scheme used in a previous study to optimize the displacement trajectories of the phantom and cadaver tendons. The motion of the human extensor digitorum communis tendon was measured in the present study using the FT-K1 scheme. RESULTS The experimental results indicated that SSD exhibited better accuracy in the phantom experiments, whereas FT exhibited better performance for tracking real tendon motion in the cadaver experiments. All three tracking methods were influenced by the signal-to-noise ratio of the images. On the other hand, the K1 scheme was able to optimize the tracking trajectory of displacement in all experiments, even from a location with a poor image quality. The human experimental data indicated that the normal tendons were displaced more than the injured tendons, and that the motion ability of the injured tendon was restored after appropriate rehabilitation sessions. CONCLUSIONS The obtained results show the potential for applying the proposed FT-K1 method in clinical applications for evaluating the tendon injury level after metacarpal fractures and assessing the recovery of an injured tendon during rehabilitation.

Evaluating the intensity of the acoustic radiation force impulse (ARFI) in intravascular ultrasound (IVUS) imaging: Preliminary in vitro results

The ability to measure the elastic properties of plaques and vessels is significant in clinical diagnosis, particularly for detecting a vulnerable plaque. A novel concept of combining intravascular ultrasound (IVUS) imaging and acoustic radiation force impulse (ARFI) imaging has recently been proposed. This method has potential in elastography for distinguishing between the stiffness of plaques and arterial vessel walls. However, the intensity of the acoustic radiation force requires calibration as a standard for the further development of an ARFI-IVUS imaging device that could be used in clinical applications. In this study, a dual-frequency transducer with 11MHz and 48MHz was used to measure the association between the biological tissue displacement and the applied acoustic radiation force. The output intensity of the acoustic radiation force generated by the pushing element ranged from 1.8 to 57.9mW/cm(2), as measured using a calibrated hydrophone. The results reveal that all of the acoustic intensities produced by the transducer in the experiments were within the limits specified by FDA regulations and could still displace the biological tissues. Furthermore, blood clots with different hematocrits, which have elastic properties similar to the lipid pool of plaques, with stiffness ranging from 0.5 to 1.9kPa could be displaced from 1 to 4μm, whereas the porcine arteries with stiffness ranging from 120 to 291kPa were displaced from 0.4 to 1.3μm when an acoustic intensity of 57.9mW/cm(2) was used. The in vitro ARFI images of the artery with a blood clot and artificial arteriosclerosis showed a clear distinction of the stiffness distributions of the vessel wall. All the results reveal that ARFI-IVUS imaging has the potential to distinguish the elastic properties of plaques and vessels. Moreover, the acoustic intensity used in ARFI imaging has been experimentally quantified. Although the size of this two-element transducer is unsuitable for IVUS imaging, the experimental results reported herein can be applied in ARFI-IVUS imaging applications.

A Novel Adhesion Index for Verifying the Extent of Adhesion for the Extensor Digitorum Communis in Patients with Metacarpal Fractures

This study aims to determine if the relative displacement between the extensor digitorum communis (EDC) tendon and its surrounding tissues can be used as an adhesion index (AI) for assessing adhesion in metacarpal fractures by comparing two clinical measures, namely single-digit-force and extensor lag (i.e., the difference between passive extension and full active extension). The Fisher–Tippett block-matching method and a Kalman-filter algorithm were used to determine the relative displacements in 39 healthy subjects and 8 patients with metacarpal fractures. A goniometer was used to measure the extensor lag, and a force sensor was used to measure the single-digit-force. Measurements were obtained twice for each patient to evaluate the performance of the AI in assessing the progress of rehabilitation. The Pearson correlation coefficient was calculated to quantify the various correlations between the AI, extensor lag, and single-digit-force. The results showed strong correlations between the AI and the extensor lag, the AI and the single-digit-force, and the extensor lag and the single-digit-force (r = 0.718, −0.849, and −0.741; P = 0.002, P < 0.001, and P = 0.001, respectively). The AI in the patients gradually decreased after continuous rehabilitation, but remained higher than that of healthy participants.

Assessing the viscoelastic properties of thrombus using shear wave dispersion ultrasound vibrometry

The viscoelastic properties of thrombus play a significant role when the clot closes a leak in a vessel of the blood circulation. Therefore, it is important to evaluate the viscoelastic properties of blood clots in clinical applications. In this study, we perform the shear wave dispersion ultrasound vibrometry (SDUV) technique to characterize the thrombus at two different hematocrits. In thrombus experiments, two different hematocrits blood clots (hematocrit concentration 20% and 40%) were measured. The shear modulus is 422.7±66.2 for 20% hematocrit blood clot and 200.8±58.4 for 40% hematocrit blood clot. The viscosity is 0.37±0.02 for 20% hematocrit blood clot and 0.27±0.02 for 40% hematocrit blood clot.

High frequency ultrasound computed tomography for small animal imaging applications

This study developed a high frequency ultrasound computed tomography (UCT) imaging system for small animal imaging. Both attenuation and sound velocity UCT were used to recognize the tissue properties with a high image contrast. The center frequencies of transducers ranging from 25 to 40 MHz were used in this system. The high frequency transducer was mounted on a three axes step motor system for linear scan, and the object was fixed on a rotational stage which was controlled by another step motor. The projections of object at different angles were obtained by measuring the sound speed and relative attenuation passed through the object. The filtered backprojection algorithm was used to reconstruct the two dimensional UCT image. The resolution of the system was verified by scanning a 200 μm diameter micro-tube. The system verification was performed by imaging the gelatin phantoms and zebrafish. In phantom experiments, the phantom was composed of two different gelatins (gelatin concentration for 4% and 6%). In contrast to ultrasound B-mode image, the slight difference in different concentration gelatins can be recognized easily by using the UCT system. For small animal experiments, most organs of zebrafish can be observed by high frequency UCT images. All the results indicate that the UCT has great potential applications in imaging small animal, such as zebrafish liver tumor and rat testicle.

Three dimension high frequency ultrasound computed tomography for detecting the testicular tumor in vitro

The aim of this study was to establish three dimension high frequency ultrasound computed tomography (HFUCT) for detecting the testicular tumor in vitro. Currently, the UCT has been applied for diagnosing the breast cancer for females. This study is the first report for applying this modality for testicular tumor applications. Experiments were carried out by artificial testicular tumor from rat. Two 25 MHz transducers were used in this research. The transmitting transducer and receiving transducer were both fitted on the three-axes step motor platform by two brackets, and the testicle was fixed on a rotational stage which was controlled by a rotating motor. The projection data of UCT were obtained by measuring the ultrasonic attenuation. A filtered backprojection algorithm was used to reconstruct the HFUCT images. In the results of healthy testicle, the transmission attenuation HFUCT image and the B-mode imaging both showed that the testicular tissue had a homogeneous property because the distribution of ultrasonic attenuation seems uniform within whole testis. In the results of testicular tumor samples, it was difficult to detect the tumor by using B-mode image, however, the size and location of tumor was observed clearly by the HFUCT image. Moreover, the three dimensional HFUCT image was reconstructed in this study, and the volume of tumor can be measured accordingly.