Wen-Shiang Chen

Inertial cavitation dose and hemolysis produced in vitro with or without Optison

Gas-based contrast agents (CAs) increase ultrasound (US)-induced bioeffects, presumably via an inertial cavitation (IC) mechanism. The relationship between IC dose (ICD) (cumulated root mean squared [RMS] broadband noise amplitude; frequency domain) and 1.1-MHz US-induced hemolysis in whole human blood was explored with Optison; the hypothesis was that hemolysis would correlate with ICD. Four experimental series were conducted, with variable: 1. peak negative acoustic pressure (P-), 2. Optison concentration, 3. pulse duration and 4. total exposure duration and Optison concentration. P- thresholds for hemolysis and ICD were approximately 0.5 MPa. ICD and hemolysis were detected at Optison concentrations >/= 0.01 V%, and with pulse durations as low as four or two cycles, respectively. Hemolysis and ICD evolved as functions of time and Optison concentration; final hemolysis and ICD values depended on initial Optison concentration, but initial rates of change did not. Within series, hemolysis was significantly correlated with ICD; across series, the correlation was significant at p < 0.001.

The disappearance of ultrasound contrast bubbles: Observations of bubble dissolution and cavitation nucleation

The destruction process of biSphere and Optison ultrasound (US) contrast microbubbles were studied at 1.1 MHz. High-amplitude tone bursts caused shell disruption and/or fragmentation of the microbubbles, leading to dissolution of the freed gas. The bubble destruction and subsequent dissolution process was imaged with a high pulse-repetition frequency (PRF) 10-cycle, 5-MHz bistatic transducer configuration. Three types of dissolution profiles were measured: In one case, biSphere microbubbles showed evidence of dissolution through resonance, during which a temporary increase in the scattering amplitude was observed. In another case, both biSphere and Optison microbubbles showed evidence of fragmentation, during which the scattering amplitude decreased rapidly. Finally, in some cases, we observed the impulsive growth and subsequent rapid decay of signals that appear to be due to cavitation nucleation. Simulations of bubble dissolution curves show good agreement with experiments.

Hemorrhage detection during focused-ultrasound induced blood-brain-barrier opening by using susceptibility-weighted magnetic resonance imaging.

High-intensity focused ultrasound has been discovered to be able to locally and reversibly increase the permeability of the blood-brain barrier (BBB), which can be detected using magnetic resonance imaging (MRI). However, side effects such as microhemorrhage, erythrocyte extravasations or even extensive hemorrhage may also occur. Although current contrast-enhanced T1-weighted MRI can be used to detect the changes in BBB permeability, its efficacy in detecting tissue hemorrhage after focused-ultrasound sonication remains limited. The purpose of this study is to investigate the feasibility of magnetic resonance susceptibility-weighted imaging (MR-SWI) for identifying possible tissue hemorrhage associated with disruption of the BBB induced by focused ultrasound in a rat model. The brains of 42 Sprague-Dawley rats were subjected to 107 sonications, either unilaterally or bilaterally. Localized BBB opening was achieved by delivering burst-mode focused ultrasound energy into brain tissue in the presence of microbubbles. Rats were studied by T2-weighted and contrast-enhanced T1-weighted MRI techniques, as well as by SWI. Tissue changes were analyzed histologically and the extent of apoptosis was investigated with the terminal deoxynucleotidyl transferase biotin-dUTP nick-end labeling method. The results demonstrated that SWI is more sensitive than standard T2-weighted and contrast-enhanced T1-weighted MRI techniques in detecting hemorrhages after brain sonication. Longitudinal study showed that SWI is sensitive to the recovery process of the damage and, therefore, could provide important and complementary information to the conventional MR images. Potential applications such as drug delivery in the brain might be benefited.

Thresholds for inertial cavitation in Albunex suspensions under pulsed ultrasound conditions

Stabilized microbubbles used as echo-contrast agents can be destroyed by ultrasonic irradiation. We have identified two pressure thresholds at which these microbubbles undergo inertial cavitation (here, defined as the collapse of gas bubbles followed by emission of an acoustic broadband noise). The first threshold (P1) corresponds to the pressure at which all the microbubbles in a cavitation field lose their property as an effective scatterer because of fragmentation or deflation. The second threshold (P2) is associated with the acoustic reactivation of the remnants of the contrast agents and is related to the onset of more violent inertial cavitation. P1 and P2 were measured as a function of the concentration of Albunex(R) (Molecular Biosystems Inc., San Diego, CA) contrast agent, the number of transmitting acoustic cycles, and the pulse repetition frequency (PRF). The ultrasound frequency used was 1.1 MHz, and the peak negative acoustic pressures ranged from 0 to 8 MPa. Our results, measured in Isoton(R) II (Coulter Diagnostics, Miami, FL) and whole blood solutions, showed that P1 increased with increasing Albunex(R) concentration and decreased with increasing PRF, whereas P2 decreased with increasing Albunex(R) concentration and was independent of the PRF. Both P1 and P2 decreased with increasing number of acoustic cycles N for N<10 and were independent of the number of cycles for N>10. Ultrasound images of Albunex(R) acquired by a commercial scanner showed echo enhancement not only at pressure levels below P1 but also at levels above P2. The threshold P2 was achieved at ultrasound energies above the diagnostic level. Inertial cavitation produced at P2 was associated with a higher level of hemolysis compared with P1. The results of this investigation have potential significance for both diagnostic and therapeutic ultrasound applications.

Sonoelastography of the Plantar Fascia

PURPOSE To compare the stiffness of the plantar fascia by using sonoelastography in healthy subjects of different ages, as well as patients with plantar fasciitis. MATERIALS AND METHODS The study protocol was approved by the Research Ethics Committee of the hospital, and all of the subjects gave their informed consent. Bilateral feet of 40 healthy subjects and 13 subjects with plantar fasciitis (fasciitis group) were examined by using color-coded sonoelastography. Healthy subjects were divided into younger (18-50 years) and older (> 50 years) groups. The color scheme was red (hard), green (medium stiffness), and blue (soft). The color histogram was subsequently analyzed. Each pixel of the image was separated into red, green, and blue components (color intensity range, 0-255). The color histogram then computed the mean intensity of each color component of the pixels within a standardized area. Mixed model for repeated measurements was used for comparison of the plantar fascia thickness and the intensity of the color components on sonoelastogram. RESULTS Quantitative analysis of the color histogram revealed a significantly greater intensity of blue in older healthy subjects than in younger (94.5 ± 5.6 [± standard deviation] vs 90.0 ± 4.6, P = .002) subjects. The intensity of red and green was the same between younger and older healthy subjects (P = .68 and 0.12). The intensity of red was significantly greater in older healthy subjects than in the fasciitis group (147.8 ± 10.3 vs 133.7 ± 13.4, P < .001). The intensity of green and blue was the same between older healthy subjects and those in the fasciitis group (P = .33 and .71). CONCLUSION Sonoelastography revealed that the plantar fascia softens with age and in subjects with plantar fasciitis.

Mechanisms of lesion formation in high intensity focused ultrasound therapy

The lesions generated by high intensity ultrasound were studied in transparent tissue phantoms premixed with and without ultrasound contrast agents (UCA) at 1.1- and 3.5-MHz acoustic waves. Generation of small bubbles was observed at the very beginning of exposure, whereas cigar-shaped thermal lesions began to form at the focus after a delay. After further heating, boiling occurred and changed the lesion to tadpole-shape, with advancement toward the transducer. Broadband noise was detected in phantoms with UCA initially. UCA also lowered the pressure threshold and enlarged the lesion. Although thermal and cavitation effects are believed to be both important in lesion formation, tadpole-shaped transformation results from boiling activity.

Feasibility of transrib focused ultrasound thermal ablation for liver tumors using a spherically curved 2D array: a numerical study.

The use of focused ultrasound thermal ablation to treat hepatocarcinoma and other liver tumors produces promising clinical results. However, one of the major drawbacks is the high absorption of ultrasonic energy by the rib, making partial rib removal necessary in many cases. This study numerically investigated the feasibility of using a spherical ultrasound phased array for transrib liver-tumor thermal ablation. An independently array-element activitation scheme, which switches off the transducer elements obstructed by the ribs based on feedback anatomical medical imaging, was proposed to reduce the rib-overheating problem. The numerical results showed that the proposed treatment planning strategy can effectively reduce the specific energy absorbed by the rib while maintaining the energy at the target position, which both reduces the rib-overheating problem and increases the possibility of treating a target lesion under an intact rib. The analysis also demonstrated that the target position and the ultrasound frequency play key roles in the treatment. Patients with diverse characteristics were also tested to show the generality of the proposed strategy. The proposed treatment planning strategy also provides useful information for evaluating the treatment effectiveness prior to clinically performing transrib ultrasound liver-tumor thermal ablation.

Effects of functional electrical stimulation on dysphagia caused by radiation therapy in patients with nasopharyngeal carcinoma.

PurposeThis study aimed to assess the effectiveness of functional electrical stimulation on the swallowing function of irradiated nasopharyngeal carcinoma patients with dysphagia.Materials and methodsTwenty nasopharyngeal carcinoma subjects with dysphagia were divided into a functional electrical stimulation (FES) and a home rehabilitation program (HRP) group. Each subject completed a quality of life questionnaire on swallowing and a videofluoroscopic study at the commencement and the end of the procedures. The FES group received functional electrical stimulation of the supra-hyoid muscles over 15 sessions. The HRP group performed self-swallowing exercises at home. The evaluation parameters included the quality of life questionnaire scores, the penetration–aspiration scale (PAS), the movement of the hyoid bone, and the amount of pyriform sinuses stasis.ResultsMost swallowing outcomes of the FES group improved after FES. The quality of life score (p = 0.003), the duration of the movement of thin barium through the hyoid (p = 0.001), the moving speed of paste barium through the hyoid (p = 0.028), and the pyriform sinus stasis area of the paste barium (p = 0.026) reached significant difference in the FES group. Most swallowing outcomes did not improve in the HRP group. The degree of improvement in the movement speed of the hyoid bone in the thin barium (p = 0.018) and the PAS of the paste barium (p = 0.016) were statistically significantly greater in the FES group than in the HRP group.ConclusionFES will improve the swallowing function of NPC patients with dysphagia and bring about better quality of life.

Thinner plantar fascia predicts decreased pain after extracorporeal shock wave therapy

Increased plantar fascia thickness is common with chronic plantar fasciitis, and reduction of the thickness after extracorporeal shock wave therapy or steroid injection has been reported. We hypothesized a decrease of plantar fascia thickness was associated with pain reduction after extracorporeal shock wave therapy. Fifty-three eligible patients with 78 symptomatic feet were randomly treated with piezoelectric-type extracorporeal shock wave therapy of two intensity levels (0.12 and 0.56 mJ/mm2). Two thousand shock waves for three consecutive sessions were applied at weekly intervals. A visual analog scale for pain, the Foot Function Index, the Short Form-36 Health Survey, and ultrasonographic measurement of plantar fascia thickness were evaluated at baseline and 3 and 6 months after treatment. We analyzed the association between pain level and plantar fascia thickness with generalized estimating equation analysis and adjusted for demographic and treatment-related variables. Patients with thinner plantar fascia experienced less pain after treatment; high-intensity treatment and regular exercise were associated with lower pain level. The overall success rates were 63% and 60% at the 3- and 6-month followups. High- and low-intensity treatments were associated with similar improvements in pain and function. Receiving high-intensity treatment, although associated with less pain at followup, did not provide a higher success rate.Level of Evidence: Level I, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.

Early Versus Delayed Passive Range of Motion Exercise for Arthroscopic Rotator Cuff Repair: A Meta-analysis of Randomized Controlled Trials.

Background: Postoperative shoulder stiffness complicates functional recovery after arthroscopic rotator cuff repair. Purpose: To compare early passive range of motion (ROM) exercise with a delayed rehabilitation protocol with regard to the effectiveness of stiffness reduction and functional improvements and rates of improper healing in patients undergoing arthroscopic repair for torn rotator cuffs. Study Design: Systematic review and meta-analysis. Methods: Randomized controlled trials (RCTs) comparing both rehabilitation approaches were identified in PubMed and Scopus. Between-group differences in shoulder function were transformed to effect sizes for comparisons, whereas the effectiveness against stiffness and the risk of tendon failure were reported using standardized mean differences of ROM degrees and odds ratios (ORs) of recurrent tears, respectively. Results: Six RCTs were included, consisting of 482 patients. No significant difference in shoulder function existed across both protocols. The early ROM group demonstrated more improvement in shoulder forward flexion than the delayed rehabilitation group, with a standardized mean difference of 7.45° (95% CI, 3.20°-11.70°) at 6 months and 3.51° (95% CI, 0.31°-6.71°) at 12 months. Early ROM exercise tended to cause a higher rate of recurrent tendon tears (OR, 1.43; 95% CI, 0.90-2.28), and the effect became statistically significant (OR, 1.93; 95% CI, 1.04-3.60) after excluding 2 RCTs that recruited only those patients with small to medium-sized tears. Conclusion: Early ROM exercise accelerated recovery from postoperative stiffness for patients after arthroscopic rotator cuff repair but was likely to result in improper tendon healing in shoulders with large-sized tears. The choice of either protocol should be based on an accommodation of the risks of recurrent tears and postoperative shoulder stiffness.