Comparative safety analysis of mRNA and adenoviral vector COVID-19 vaccines: a nationwide cohort study using an emulated target trial approach.

OBJECTIVE: This nationwide cohort study compared the incidence of adverse events of special interest (AESIs) between adenoviral vector-based (ChAdOx1) and mRNA-based (BNT162b2 or mRNA-1273) coronavirus disease 2019 (COVID-19) vaccines. METHODS: A targeted trial emulation study was conducted using data from the National Health Insurance Service database. Vaccinees aged 18-85 years who had received at least one dose of ChAdOx1 or an mRNA-based vaccine were identified. The 42-day risks of AESIs were calculated. RESULTS: A total of 1 767 539 ChAdOx1 vaccinees were matched exactly with mRNA vaccinees according to their risk factors. The 42-day risks of adverse events were low (∼0 to 176 events per 100 000 persons in both vaccine groups), and the incidence rates of AESIs were comparable between the two platforms, except for a higher occurrence of acute cardiac injury (incidence rate ratio [IRR], 1.22; 95% CI, 1.10-1.35), myocarditis or pericarditis (IRR, 2.14; 95% CI, 1.14-4.04), and arrhythmia (IRR, 1.46; 95% CI, 1.24-1.71) in mRNA vaccinees. The incidence of Guillain-Barré syndrome (IRR, 0.20; 95% CI, 0.06-0.69), vasovagal syncope (IRR, 0.77; 95% CI, 0.62-0.97), radiculopathy (IRR = 0.59, 95% CI, 0.41-0.84), and aseptic arthritis (IRR, 0.81; 95% CI, 0.70-0.93) was significantly lower in mRNA-based vaccinees compared with ChAdOx1 vaccinees. DISCUSSION: A remarkable platform-dependent difference was observed in the safety profiles of COVID-19 vaccines, particularly for myocarditis or pericarditis and Guillain-Barré syndrome. However, the overall risk of AESIs was low for both vaccine platforms.

Herpes Zoster Reactivation After mRNA and Adenovirus-Vectored Coronavirus Disease 2019 Vaccination: Analysis of National Health Insurance Database.

BACKGROUND: Our study aimed to determine the risk of herpes zoster reactivation and coronavirus disease 2019 (COVID-19) vaccination (mRNA vaccine [BNT162b2] and adenovirus-vectored vaccine [ChAdOx1 nCoV-19]). METHODS: This retrospective study analyzed herpes zoster cases diagnosed between 26 February 2021 and 30 June 2021 and registered in the National Health Insurance Service database. A matched case-control study with a 1:3 matching ratio and a propensity score matching (PSM) study with a 1:1 ratio of vaccinated and unvaccinated individuals were performed. RESULTS: In the matched case control analysis, BNT162b2 was associated with an increased risk of herpes zoster reactivation (first dose adjusted odds ratio [aOR], 1.11; 95% confidence interval [CI], 1.06-1.15; second dose aOR, 1.17; 95% CI, 1.12-1.23). PSM analysis revealed a statistically significant increase in risk within 18 days following any vaccination (adjusted hazard ratio [aHR], 1.09; 95% CI, 1.02-1.16). BNT162b2 was associated with an increased risk at 18 days postvaccination (aHR, 1.65; 95% CI, 1.35-2.02) and second dose (aHR, 1.10; 95% CI, 1.02-1.19). However, the risk did not increase in both analyses of ChAdOx1 vaccination. CONCLUSIONS: mRNA COVID-19 vaccination possibly increases the risk of herpes zoster reactivation, and thus close follow-up for herpes zoster reactivation is required.

A Cost-Effective Reusable Tissue Mimicking Phantom for High Intensity Focused Ultrasonic Liver Surgery.

A polyacrylamide polysaccharide hydrogel (PASG) containing a nonionic surfactant of the polyoxyethylene nonylphenyl ethers series (NP14) has been adapted to the fabrication of a reusable cost-effective ultrasonic tissue-mimicking phantom for real-time visualization of the thermal lesions by high intensity focused ultrasound (HIFU) irradiation. The constructed NP14 (40% in w/v) PASG is optically transparent at room temperatures, and it turns out to be opaque white as heated over the clouding points of about 55 °C and returns to its original transparent state after cooling. The acoustic property of the proposed phantom is similar to those of human liver tissues, which includes the acoustic impedance of 1.68 Mrayls, the speed of sound of 1595 ± 5 m/s, the attenuation coefficient of 0.52 ± 0.05 dB cm-1 (at 1 MHz), the backscatter coefficient of 0.21 ± 0.09 × 10-3 sr-1 cm-1 (at 1 MHz), and the nonlinear parameter B/A of 6.4 ± 0.2. The NP14-PASG was tested to assess the characteristic information (sizes, shapes, and locations) of the thermal lesions visualized when exposed to typical HIFU fields (1.1 MHz, focal pressure up to 20.1 MPa, focal intensity 4075 W/cm2). The proposed NP14-PASG is expected to replace the existing costly BSA-PASG used for more effective testing of the performance of therapeutic ultrasonic devices based on thermal mechanisms.

Pattern Analysis of Laser Fiber Degradation According to the Laser Setting: In Vitro Study of the Double-Firing Phenomenon.

BACKGROUND: It is essential to understand the mechanism of the various causes of laser fiber damage and an ideal method of reducing endoscope damage induced by laser emission in multiple sites. This study classified the different patterns of laser fiber degradation according to laser settings and analyzed the role of cavitation bubbles to find a desirable way of minimizing endoscope damage. METHODS: A total of 118 laser fibers were analyzed after 1-,3-, and 5-min laser emission to artificial stones under the settings of 1 J-10 Hz, 1 J-20 Hz, 1 J-30 Hz, and 2 J-10 Hz. Every 3 cm from the fiber tip was marked and examined with a digital microscope and a high-speed camera. The images of the fibers and the movement of cavitation bubbles were taken with a distance of 1 to 5 mm from the gel. RESULTS: Seven types of fiber damage (charring, limited and extensive peeled-off, bumpy, whitish plaque, crack, and break-off) coincided during laser emission. Damages rapidly increased with emission time > 3 minutes regardless of the laser settings. The damaged lengths covered 5 mm on average, and the fibers at 5-min emission were significantly shorter than others. The fiber durability of 1J-10Hz setting was better than other settings after 3-min laser emission. Backward movement of the cavitation bubbles was found at the 1-mm distance from the gel, and the damaged lengths were longer than the diameters of the cavitation bubbles because of their proximal movement. CONCLUSION: The damage patterns of the laser fiber tips were classified into seven types. The heat damage around the surface of the laser fiber can be increased according to the high-energy or high-frequency laser setting, a short distance to the stone, a short distance from the tips of flexible ureteroscopes, no cutting laser fiber procedures, and the inappropriate use of irrigation fluid or laser fiber jacket.

Immunogenicity and Reactogenicity of Ad26.COV2.S in Korean Adults: A Prospective Cohort Study.

BACKGROUND: As the coronavirus disease 2019 (COVID-19) pandemic continues, there are concerns regarding waning immunity and the emergence of viral variants. The immunogenicity of Ad26.COV2.S against wild-type (WT) and variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) needs to be evaluated. METHOD: This prospective cohort study was conducted between June 2021 and January 2022 at two university hospitals in South Korea. Healthy adults who were scheduled to be vaccinated with Ad26.COV2.S were enrolled in this study. The main outcomes included anti-spike (S) IgG antibody and neutralizing antibody responses, S-specific T-cell responses (interferon-γ enzyme-linked immunospot assay), solicited adverse events (AEs), and serious AEs. RESULTS: Fifty participants aged ≥ 19 years were included in the study. Geometric mean titers (GMTs) of anti-S IgG were 0.4 U/mL at baseline, 5.2 ± 3.0 U/mL at 3-4 weeks, 55.7 ± 2.4 U/mL at 5-8 weeks, and 81.3 ± 2.5 U/mL at 10-12 weeks after vaccination. GMTs of 50% neutralizing dilution (ND50) against WT SARS-CoV-2 were 164.6 ± 4.6 at 3-4 weeks, 313.9 ± 3.6 at 5-8 weeks, and 124.4 ± 2.6 at 10-12 weeks after vaccination. As for the S-specific T-cell responses, the median number of spot-forming units/106 peripheral blood mononuclear cell was 25.0 (5.0-29.2) at baseline, 60.0 (23.3-178.3) at 5-8 weeks, and 35.0 (13.3-71.7) at 10-12 weeks after vaccination. Compared to WT SARS-CoV-2, ND50 against Delta and Omicron variants was attenuated by 3.6-fold and 8.2-fold, respectively. The most frequent AE was injection site pain (82%), followed by myalgia (80%), fatigue (70%), and fever (50%). Most AEs were grade 1-2, and resolved within two days. CONCLUSION: Single-dose Ad26.COV2.S was safe and immunogenic. NAb titer and S-specific T-cell immunity peak at 5-8 weeks and rather decrease at 10-12 weeks after vaccination. Cross-reactive neutralizing activity against the Omicron variant was negligible.

Clinical application of the therapeutic ultrasound in urologic disease: Part II of therapeutic ultrasound in urology.

This article aimed to review the clinical application and evidence of the therapeutic ultrasound in detail for urological diseases such as prostate cancer, kidney tumor, erectile dysfunction, and urolithiasis. We searched for articles about high-intensity focused ultrasound (HIFU), extracorporeal shock wave therapy, ultrasound lithotripsy, and extracorporeal shockwave lithotripsy (ESWL) in the MEDLINE and Embase. HIFU may be indicated as a primary treatment for low- or intermediate-risk prostate cancer, and salvage therapy for local recurrence as a promising way to address the limitations of current standard therapies. The application of HIFU in treating kidney tumors has scarcely been reported with unsatisfactory results. Evidence indicates that low-intensity shockwave therapy improves subjective and objective erectile function in patients with erectile dysfunction. Regarding the application of ultrasound in stone management, the novel combination of ultrasound lithotripsy and other energy sources in a single probe promises to be a game-changer in efficiently disintegrating large kidney stones in percutaneous nephrolithotomy. ESWL is losing its role in managing upper urinary tract calculi worldwide. The burst-wave lithotripsy and ultrasound propulsion could be the new hope to regain its position in the lithotripsy field. According to our investigations and reviews, cavitation bubbles of the therapeutic ultrasound are actively being used in the field of urology. Although clinical evidence has been accumulated in urological diseases such as prostate cancer, kidney tumor, erectile dysfunction, and lithotripsy, further development is needed to be a game-changer in treating these diseases.

Comparison of antiviral effect for mild-to-moderate COVID-19 cases between lopinavir/ritonavir versus hydroxychloroquine: A nationwide propensity score-matched cohort study.

OBJECTIVES: We aimed to compare the antiviral effect of hydroxychloroquine (HCQ) and lopinavir/ritonavir (LPV/r) in patients with COVID-19. METHODS: Nationwide retrospective case-control study was conducted to compare the effect of HCQ and LPV/r on viral shedding duration among patients with mild-to-moderate COVID-19 using the reimbursement data of National Health Insurance Service. After propensity score matching (PSM), multivariate analysis was conducted to determine statistically significant risk factors associated with prolonged viral shedding. RESULTS: Overall, 4197 patients with mild-to-moderate COVID-19 were included. Patients were categorized into three groups: LPV/r (n = 1268), HCQ (n = 801), and standard care without HCQ or LPV/r (controls, n = 2128). The median viral shedding duration was 23 (IQR 17-32), 23 (IQR 16-32), and 18 (IQR 12-25) days in the LPV/r, HCQ, and control groups, respectively. Even after PSM, the viral shedding duration was not significantly different between LPV/r and HCQ groups: 23 (IQR, 17-32) days versus 23 (IQR, 16-32) days. On multivariate analysis, old age, malignancy, steroid use, and concomitant pneumonia were statistically significant risk factors for prolonged viral shedding. CONCLUSION: The viral shedding duration was similar between HCQ and LPV/r treatment groups. There was no benefit in improving viral clearance compared to the control group.

The Practice Guideline for Vaccinating Korean Patients with Autoimmune Inflammatory Rheumatic Disease.

To develop a clinical practice guideline for vaccination in patients with autoimmune inflammatory rheumatic disease (AIIRD), the Korean College of Rheumatology and the Korean Society of Infectious Diseases developed a clinical practice guideline according to the clinical practice guideline development manual. Since vaccination is unlikely to cause AIIRD or worsen disease activities, required vaccinations are recommended. Once patients are diagnosed with AIIRD, treatment strategies should be established and, at the same time, monitor their vaccination history. It is recommended to administer vaccines when the disease enters the stabilized stage. Administering live attenuated vaccines in patients with AIIRD who are taking immunosuppressants should be avoided. Vaccination should be considered in patients with AIIRD, prior to initiating immunosuppressants. It is recommended to administer influenza, Streptococcus pneumoniae, hepatitis A, hepatitis B, herpes zoster, measles-mumps-rubella virus, human papillomavirus, and tetanus-diphtheria-pertussis vaccines in patients with AIIRD; such patients who planned to travel are generally recommended to be vaccinated at the recommended vaccine level of healthy adults. Those who live in a household with patients with AIIRD and their caregivers should also be vaccinated at levels that are generally recommended for healthy adults.

Temperature Dependence of Tissue Thermal Parameters Should Be Considered in the Thermal Lesion Prediction in High-Intensity Focused Ultrasound Surgery.

This study considers the temperature-dependent thermal parameters (specific heat capacity, thermal diffusivity and thermal conductivity) used when predicting the temperature rise of tissue exposed to high-intensity focused ultrasound (HIFU). Numerical analysis was performed using the Khokhlov-Zabolotskaya-Kuznetsov equation coupled with a bioheat transfer function. The thermal parameters were set as the functions of temperature using experimental data. The results revealed that, for liver tissue exposed to HIFU with a focal intensity of 3000 W/cm2 for 10 s, the predicted focal temperature rise was 23% lower and the thermal lesion area 41% smaller than those predicted without considering the temperature dependence. The prediction was validated by experimental observations on thermal lesions visualized in a tissue-mimicking phantom. The present results suggest that temperature-dependent thermal parameters should be considered in the prediction of HIFU-induced temperature rise to avoid lowering ultrasonic output settings for HIFU surgery. The aim of the present study was to investigate how significantly the temperature dependence of the thermal parameters affects the thermal dose imposed on the tissue by a typical clinical HIFU device. A numerical simulation was performed using a thermo-acoustic algorithm coupling the non-linear Khokhlov-Zabolotskaya-Kuznetsov (KZK) equation (Meaney et al. 1998; Filonenko and Khokhlova 2001) and a bio-heat transfer (BHT) equation (Pennes 1948). Thermal parameters of liver tissue were modeled in the present study as functions of temperature and were incorporated into the BHT equation to compensate for the variations in thermal parameters with temperature. Experimental validation was achieved by comparing the predictions with the thermal lesions formed in the tissue-mimicking phantoms.

Pneumonitis and concomitant bacterial pneumonia in patients receiving pembrolizumab treatment: Three case reports and literature review.

RATIONALE: Pembrolizumab, a monoclonal antibody against the programmed cell death 1 (PD-1) protein, can induce a stable regression of some malignancies refractory to conventional chemotherapy. Despite such therapeutic benefits, pembrolizumab can induce immune-related adverse events, with pneumonitis being the most critical problem. PATIENT CONCERNS: All 3 patients complained of fever, cough, and dyspnea after a variable time interval (1-21 days) from pembrolizumab treatment. DIAGNOSES: Chest computed tomography invariably showed ground glass opacity. All tests for possible infectious agents were negative. Based on high procalcitonin level, one of 3 patients was diagnosed to have accompanying bacterial pneumonia. INTERVENTIONS: All patients received antibiotics and steroid treatments (methylprednisolone, 1 mg/kg). OUTCOMES: The 3 patients showed different clinical courses ranging from mild pneumonitis to rapidly progressing respiratory failure. Among the 3 patients, 2 fully recovered with steroid treatment; 1 died from superimposed bacterial pneumonia. LESSONS: The prognosis of pembrolizumab-induced pneumonitis with a superimposed bacterial pneumonia would be poor. It is important to distinguish pure pneumonitis from that with a superimposed bacterial pneumonia.

Dengue-associated hemophagocytic lymphohistiocytosis in an adult: A case report and literature review.

BACKGROUND: Infection-associated hemophagocytic syndrome (IAHS) is potentially a fatal disease caused by systemic infection complicated by hemophagocyticlymphohistiocytosis (HLH). Here, we report a case of HLH associated with dengue hemorrhagic fever (DHF) after a trip to Thailand. CASE SUMMARY: A 33-year-old healthy female patient presented with 3 days of fever, myalgia, and skin rash. Serotype 3 dengue virus was isolated. Clinical and laboratory findings fulfilled the criteria of HLH. After the initiation of corticosteroid therapy, the patient recovered and laboratory findings were normalized. CONCLUSION: It would be important to differentially diagnose dengue-associated HLH from severe DHF. Early recognition and initiation of steroid treatment would be crucial for the successful treatment of dengue fever complicated by HLH.

A typical case of L-transposition of the great arteries initially presented as complete atrioventricular block in middle-aged man.

L-transposition of the great arteries (L-TGA) is a rare congenital anomaly and could cause complete atrioventricular (AV) block at relatively younger age. We present a case of 43-year-old male who complained of dizziness due to complete AV block. We confirmed L-TGA using transthoracic echocardiography and cardiac computed tomography. Permanent pacemaker was inserted without complications. No invasive treatment including corrective surgery was performed because patient's cardiac function was almost normal and the symptom was completely resolved after pacemaker insertion.

The role of the acoustic radiation force in color Doppler twinkling artifacts.

PURPOSE: The aim of this experimental study was to evaluate whether the acoustic radiation force (ARF) is a potential source of twinkling artifacts in color Doppler images. METHODS: Color Doppler images were obtained using a clinical ultrasonic scanner (Voluson e, GE Healthcare) for a high contrast (+15 dB) circular scattering phantom at pulse repetition frequencies (PRFs) ranging from 0.1 to 13 kHz. Ultrasound transmissions resulting in ARF were measured using a hydrophone at the various PRFs considered. The influence of ARF on the appearance of twinkling colors was examined via the common parameter PRF. This methodology is based on the fact that alternating positive and negative Doppler shifts induced by the ARF are centered at a PRF twice the maximum Doppler frequency on the color scale bar, whereas the twinkling color aliasing is expected to remain similar regardless of PRF. RESULTS: Color twinkling artifacts were observed to be most conspicuous at the lowest PRF of 0.1 kHz. The extent of twinkling rapidly decreased as the PRF increased, eventually disappearing when the PRF ≥0.6 kHz. The measured ultrasound transmissions, however, were found to be insensitive to the PRF, and therefore it can be inferred that the PRF was insensitive to the ARF. CONCLUSION: Based on our experimental observations, the ARF may not be a source of color Doppler twinkling artifacts.

Effects of low-intensity ultrasound on oxidative damage in retinal pigment epithelial cells in vitro.

Oxidative stress in retinal pigment epithelium (RPE) is one of the key causative factors of RPE injury in age-related macular degeneration (AMD). Low-intensity ultrasound (LIUS) less than 1 W/cm(2) in intensity has been found to have cytoprotective and anti-inflammatory effects in many cell types and diseases. In this study, we investigated for the first time the feasibility of using LIUS to protect RPE cells from oxidative damage. ARPE-19 cells were treated with H2O2 (an exogenous source of reactive oxygen species) or L-buthionine-(S,R)-sulfoximine (BSO), a glutathione synthase inhibitor, and exposed immediately to LIUS at intensities of 50, 100 and 200 mW/cm(2) and a frequency of 1 MHz for 20 min. Both H2O2 and BSO increased the percentage of cells positive for mitochondrial reactive oxygen species at 1 h, but not at 24 h. Co-treatment with LIUS clearly repressed these cells similarly at all intensities by approximately 34%-43% for H2O2 and 24%-25% for BSO (p < 0.05). The percentage of cells with mitochondrial membrane depolarization also increased with H2O2 and BSO treatment, particularly at 1 h, and decreased by approximately 60% with LIUS at 100 mW/cm(2) (p < 0.05). The amount of intracellular calcium ion ([Ca(2+)]i) was elevated only by BSO at 24 h and was also significantly diminished, by approximately 45%, by LIUS at 100 mW/cm(2) (p < 0.05). Both H2O2 and BSO significantly hampered cell viability at 24 h, but LIUS at 100 mW/cm(2) restored only BSO-induced cell viability by approximately 2.7-fold (p < 0.05). This study illustrated that LIUS has a protective effect on RPE cells against oxidative damage caused by BSO, an endogenous mitochondrial reactive oxygen species generator. We speculate that LIUS has the potential to treat oxidative damage and related pathologic changes in RPE.

Influence of temperature-dependent thermal parameters on temperature elevation of tissue exposed to high-intensity focused ultrasound: numerical simulation.

High-intensity focused ultrasound (HIFU) has been used successfully as a non-invasive modality in treating solid tumors. The temperature rise HIFU irradiation causes in a tissue depends on the thermal properties of the tissue. This study was motivated by our observation that the thermal properties of a tissue vary significantly with temperature (Guntur SR, Lee KI, Paeng DG, Coleman AJ, Choi MJ. Ultrasound Med Biol 2013;39:1771-1784). This research investigated how significantly the alteration of tissue thermal parameters, in the ranges of values measured at 25°C-90°C, affects prediction of the temperature elevation of tissue under the same HIFU exposure. The numerical simulation was performed by coupling a non-linear Khokhlov-Zabolotskaya-Kuznetsov equation with a bio-heat transfer function. In the conventional method of prediction, the thermal parameters were set as constants measured at room temperature (25°C). This study compared the conventional prediction with those predicted with different thermal parameters measured at the various temperatures up to 90°C. The results indicated that the conventional method significantly overestimated the rise in focal temperature in the liver tissue exposed to a clinical HIFU field, compared with the prediction made using thermal parameters measured at temperatures that cause thermal denaturation. This finding suggests that temperature-dependent thermal parameters should be considered in predicting the temperature rise in a tissue to avoid use of an insufficient thermal dose in treatment planning for HIFU surgery.

Histological correlates of optical coherence tomography in non-melanoma skin cancer.

BACKGROUND: Non-melanoma skin cancer (NMSC) is rarely fatal but is now the most common malignancy occurring in white populations, accounting for 70% of the cost of managing skin cancer. Optical coherence tomography (OCT) has the potential to improve diagnostic accuracy and help delineate pre-surgical margins in NMSC. Its widespread clinical acceptance awaits the accumulation of evidence from studies of direct histological comparisons. METHOD: In this study, seventy-eight subjects presenting with skin lesions, including 28 NMSCs, were imaged using the VivoSight OCT scanner and a biopsy taken. Haemotoxylin and eosin stained histology sections were compared with the OCT images. RESULTS: The depth of superficial basal cell carcinoma (BCC) lesions (<1 mm) can be measured accurately using OCT. A low-strength OCT signal at the periphery of the cell nests seen in superficial and nodular BCC is identified as corresponding to cellular palisading. A weak inverse linear correlation (r(2) = 0.3) is found between the optical attenuation coefficient measured on OCT and the nuclear-cytoplasmic ratio (N/C) of cells determined from histology. CONCLUSIONS: OCT has clinical value in providing accurate dimensional measurement of superficial BCC and in identifying the presence of peripheral palisading in nodular BCC.

Changes in ultrasonic properties of liver tissue in vitro during heating-cooling cycle concomitant with thermal coagulation.

The present work considers the ultrasonic properties of porcine liver tissue in vitro measured during heating concomitant with thermal coagulation followed by natural cooling, so as to provide information about changes in the ultrasonic properties of the tissue after thermal coagulation. The excised liver samples were heated in a degassed water bath up to 75°C and naturally cooled down to 30°C. The tissue was observed to begin thermally coagulating at temperatures lower than 75°C. The ultrasonic parameters considered include the speed of sound, the attenuation coefficient, the backscatter coefficient and the nonlinear parameter of B/A. They were more sensitive to temperature when heating than during natural cooling. All of the parameters were shown to rise significantly on completion of the heating-cooling cycle. At 35°C after thermal coagulation, the B/A value was increased by 96%, the attenuation and backscatter coefficients were increased by 50%∼68% and 33%∼37%, respectively, in the typical frequency ranges of 3 MHz∼5 MHz used for ultrasonic imaging and the speed of sound was increased by 1.4%. The results of this study added to the evidence that tissue characterization, in particular, based on the B/A could be valuable for ultrasonically imaging the thermal lesions following high-intensity focused ultrasound (HIFU) surgery.

The acute effects of smoking on the cyclic variations in blood echogenicity of carotid artery.

The objective of this research is to study the cyclic variations in echogenicity (CVE) as an acute response to smoking. CVEs, caused by the aggregation of red blood cells (RBC) were measured from the cross-sectional images of the common carotid artery using coded harmonic imaging of a commercial ultrasound system. The amplitude of the CVE (A(cve)) was analyzed among 28 smokers before and after smoking. A(cve) was increased in 22 smokers and decreased in six smokers after 1-2 cigarettes were smoked. Heart rate (HR) was also estimated from the ultrasonic images before and after smoking. The smokers were optimally divided into two clusters with respect to the change in A(cve) and the intrinsic characteristics of smokers (i.e., daily consumed cigarettes and smoking years) through a two-step cluster analysis (TSCA). The increase in A(cve) after smoking was significantly higher in the heavy smoker cluster compared with the light smoker cluster. The results suggest that the acute changes in A(cve) in response to smoking are different between heavy smokers and light smokers. This preliminary study demonstrates the potential application of coded harmonic ultrasound imaging to detect or characterize RBC aggregation. In addition, the results may be useful for understanding the acute physiologic changes caused by smoking.

Influence of cell packing by centrifugation on 40-MHz ultrasound backscatter.

High-frequency ultrasound (HFUS) signals backscattered from RBL-2H3 cell pellets prepared under different centrifugal forces were analyzed to investigate the packing effect of cell aggregates. The measurements were performed in a pulse-echo setup with a 40-MHz transducer. The changes of ultrasound signals from cell pellet in backscattered power, statistical parameter, and pellet thickness were monitored after centrifugation at between 100g and 1600g. Experimental results showed that the HFUS backscattered power from cell pellets was inversely proportional to centrifugal force and increased to a plateau within 1-2h after centrifugation. The initial thickness of cell pellets decreased with higher centrifugal force, but the changes in thickness and time that took to reach a plateau increased at higher centrifugal force. The envelope statistics of backscattered signals with Nakagami distribution indicates that the centrifugal force and elapsed time after centrifugation affected the backscattering characteristics. The present study suggests that centrifugal force and data acquisition time after cell pellet formation should be considered in in vitro cell packing method with centrifugation to emulate the tissue in vivo.

Ultrasonic backscatter from rat blood in aggregating media under in vitro rotational flow.

Ultrasonic backscatter from flowing and static rat red blood cells (RBCs) in autologous plasma and in 360 kDa polyvinylpyrrolidone (PVP 360) solution was measured as a function of hematocrit. The flow speed was varied by a stirring magnet in a cylindrical chamber. The radio-frequency (RF) signals backscattered by RBC samples were measured over 5 min in a pulse-echo setup with a 5 MHz focused transducer. Although the intact rat blood has poor RBC aggregability, RBC aggregation of rat blood was enhanced by replacing its plasma with a higher molecular weight polymer solution. The experimental results showed that the nonlinear relationship between hematocrit and ultrasonic backscatter from rat RBCs in plasma and aggregating media is affected by flow speed, which may provide a unified insight into hematocrit dependence of RBC aggregation under flowing and static conditions.