Construction of a Tumor-Targeting Nanobubble with Multiple Scattering Interfaces and its Enhancement of Ultrasound Imaging.

Introduction: Recently, nanobubbles (NBs) have gained significant traction in the field of tumor diagnosis and treatment owing to their distinctive advantages. However, the application of NBs is limited due to their restricted size and singular reflection section, resulting in low ultrasonic reflection. Methods: We synthesized a nano-scale ultrasound contrast agent (IR783-SiO2NPs@NB) by encapsulating SiO2 nanoparticles in an IR783-labeled lipid shell using an improved film hydration method. We characterized its physicochemical properties, examined its microscopic morphology, evaluated its stability and cytotoxicity, and assessed its contrast-enhanced ultrasound imaging capability both in vitro and in vivo. Results: The results show that IR783-SiO2NPs@NB had a "donut-type" composite microstructure, exhibited uniform particle size distribution (637.2 ± 86.4 nm), demonstrated excellent stability (30 min), high biocompatibility, remarkable tumor specific binding efficiency (99.78%), and an exceptional contrast-enhanced ultrasound imaging capability. Conclusion: Our newly developed multiple scattering NBs with tumor targeting capacity have excellent contrast-enhanced imaging capability, and they show relatively long contrast enhancement duration in solid tumors, thus providing a new approach to the structural design of NBs.

Preliminary study of carotid variables under ultrasound analysis as predictors for the risk of coronary arterial atherosclerosis.

BACKGROUND: Carotid atherosclerosis by ultrasound scanning can be considered as an ideal window to reflect systemic artery atherosclerosis, which has aroused wide concern for predicting the severity of coronary artery atherosclerosis clinically. Ultrasound radio frequency (RF) data technology has enabled us to evaluate the carotid structure and elastic function precisely, for predicting the severity of coronary artery atherosclerosis. METHODS: Patients with suspected coronary artery disease (CAD) underwent coronary angiography and were assigned to four groups according to whether atherosclerotic plaque was found or not and it caused stenosis. Carotid artery intima-media thickness (IMT) and arterial stiffness were investigated by quality intima-media thickness (QIMT) and quality arterial stiffness (QAS) techniques during ultrasound scanning. Univariable and multivariable modeling were used to investigate correlations of carotid parameters to coronary artery atherosclerosis. Receive operating characteristic (ROC) curves were used to evaluate diagnostic performance of these ultrasound variables. RESULTS: Carotid IMT and stiffness variables pulse wave velocity (PWV), α, ß and compliance coefficient (CC) were statistically different between every two-group's comparisons. IMT correlated with stiffness variables significantly with r = 0.70, 0.77, 0.63, and -0.39, respectively. All variables correlated with the severity of coronary atherosclerosis with the odd ratio (OR) of 1.73, 1.67, 1.19, 1.23, and 0.56 accordingly as IMT, PWV, α, ß and CC were concerned. The AUC of IMT, PWV, α, ß and CC were 0.9257, 0.8910, 0.8016, 0.9383, 0.8581 with correctly classified rate of 88.16%, 83.77%, 78.07%, 86.84%, and 81.58%, respectively. CONCLUSIONS: Carotid artery IMT and stiffness variable PWV, α, ß and CC presented favorable predicting and differentiating values for patients with coronary atherosclerosis of different severity.

The severity of portal hypertension by a non-invasive assessment: acoustic structure quantification analysis of liver parenchyma.

BACKGROUND: Acoustic structure quantification (ASQ) has been applied to evaluate liver histologic changes by analyzing the speckle pattern seen on B-mode ultrasound. We aimed to assess the severity of portal hypertension (PHT) through hepatic ultrasonography. METHODS: Sixty patients diagnosed with PHT and underwent surgical treatment with portosystemic shunts were enrolled. Portal pressure (PP) was measured intraoperatively. Patients were divided into subgroups according to the severity of gastroesophageal varices and Child-Pugh class. Three difference ratio (Cm2) values on ASQ histogram mode were analyzed for their relationships with PP, degree of gastroesophageal varices and Child-Pugh liver function. Thirty healthy volunteers matched with the patients for gender and age were enrolled as controls. Comparisons among groups and correlation of the parameters with PP were analyzed. Area under the receive operating characteristic curve was used to evaluate the predicting value of ASQ parameters. RESULTS: In the patients, the ASQ parameters peak Cm2 (Cm2max), mean Cm2 (Cm2mean) and the highest occurred Cm2 value of the obtained red curve (RmaxCm2) were all greatly increased (P < 0.0001, P < 0.0001, P = 0.027). Multiple comparisons indicated that, regardless of Child-Pugh class and degree of gastroesophageal varices, the patients had significantly increased Cm2max and Cm2mean compared with the controls (all P < 0.0001). No differences among subgroups were observed. Cm2max was significantly statistically correlated with PP (r = 0.3505, P < 0.01), degree of varices (r = 0.4998, P < 0.0001). Youden's index for Cm2max with a cut-off value of 140.3 for predicting the presence of PHT, gastroesophageal varices and liver function equal to or worse than Child-Pugh class B were 0.8, 0.91 and 0.84, respectively. CONCLUSIONS: ASQ analysis of ultrasonographic images may have a role in the evaluation of the severity of PHT by detecting liver histologic changes in the speckle pattern caused by cirrhosis.

Ultrasonic assessment of liver stiffness and carotid artery elasticity in patients with chronic viral hepatitis.

BACKGROUND: This study investigated the relationship between liver stiffness and carotid artery elasticity in patients with chronic viral hepatitis. We used an acoustic radiation force impulse (ARFI) technique to measure stiffness, and a radio frequency (RF) vascular quantitative ultrasound technique to measure changes in common carotid artery elasticity and vascular function. METHODS: Two-hundred seventeen patients with chronic viral hepatitis caused by either hepatitis B virus (HBV) or hepatitis C virus (HCV) were enrolled. We divided the patients into two groups, one comprising 147 patients with chronic hepatitis B (CHB) (98 men and 49 women, average age 46.5 ± 12.2 years) and another comprising 70 patients with chronic hepatitis C (CHC) (47 men and 23 women, average age 47.6 ± 12.1 years). Additionally, 64 healthy age- and sex-matched participants (43 men and 21 women, average age 47.8 ± 5.1 years) were selected as the control group. The ARFI technique was used to measure liver stiffness and the RF ultrasound technique was used to measure carotid artery elasticity parameters including intima-media thickness (IMT), pulse wave velocity (PWV), arterial wall dilation coefficient (DC), compliance coefficient (CC), sclerosis indices α and ß, and augmentation index (Aix). Clinical indicators, liver stiffness, and carotid artery elasticity parameters were observed and compared between the different age groups to investigate the correlation between carotid artery elasticity parameters and liver stiffness. RESULTS: The ARFI values for the CHB and CHC groups were significantly higher than those for the control group (1.84 ± 0.52 vs. 1.04 ± 0.11 m/s; 1.86 ± 0.37 vs. 1.04 ± 0.11 m/s, respectively; P < 0.001). When compared to the control group, both CHB and CHC groups showed an IMT of the same order, but had significantly higher elasticity parameters, such as α and ß, as well as lower DC and CC values (P < 0.001). The PWV of the CHC group was significantly higher than that of the control group (7.98 ± 1.42 vs. 6.09 ± 0.90 m/s, P < 0.001). In the CHB group, all parameters including ARFI, IMT, PWV, DC, CC, α and ß, were significantly different between the two age groups (P < 0.05). Within the CHC group, all parameters including IMT, PWV, DC, α and ß, were significantly different between the two age groups (P < 0.05), except for ARFI, wherein the difference was not statistically significant. The correlation analysis and stepwise multiple linear regression analysis indicated that for patients with CHB, age was an independent predictor of common carotid artery IMT (R2 = 0.468, F = 54.635, and P < 0.001). For patients with CHC, age and blood sugar were independent predictors of common carotid artery IMT (R2 = 0.465, F = 29.118, and P < 0.001). CONCLUSION: Although based on ARFI and RF ultrasound, the carotid artery IMT in patients with CHB and CHC was not significantly higher than that in the control group, their functional elasticity parameters had already changed. This finding serves as a useful reference for the clinical diagnosis of vascular diseases in patients with viral hepatitis. TRIAL REGISTRATION: ClinicalTrials: ChiCTR1800015859 25/04/2018.

Aortic stiffness evaluated by echocardiography in female patients with Takayasu's arteritis.

OBJECTIVES: The aim of this study was to evaluate the aortic stiffness (AS) in young female patients with Takayasu's arteritis (TAK) and comparable controls by measuring carotid-femoral PWV (PWVcf) using echocardiography with pulse wave Doppler. The clinical feasibility and reproducibility of this echocardiographic method were also investigated. METHODS: Twenty-five TAK female patients (mean age 28.3±6.2 years) and 25 strictly matched healthy controls were included according to rigorous inclusion and exclusion criteria. The PWVcf of all subjects were measured by echocardiography based on the principle that PWVcf could be calculated by pulse wave spreading distance divided by the transmit time. Reproducibility of the echocardiographic measured PWVcf were performed randomly in 15 TAK patients and 15 healthy controls. RESULTS: The patients with TAK had a higher PWVcf value measured by echocardiography, compared with healthy controls (8.37±2.23 vs. 6.46±1.15 m/s; p<0.001). The echocardiographic measured PWVcf was significantly dependent on the TAK (p=0.003), age (p=0.032) and pulse pressure (p=0.025). PWVcf did not correlate with the echocardiographic measured cardiac systolic and diastolic parameters and the laboratory variables in TAK patients (p>0.05 for all). The intra- and inter-observer coefficients of variation were low and the Bland-Altman plots indicated a satisfactory reproducibility. CONCLUSIONS: Our results indicated that AS in female patients with TAK is increased, which may predict a higher cardiovascular risk. This manifestation is prior to the impairment of cardiac diastolic function. This elevated AS can be detected by echocardiographic measured PWVcf with a good reproducibility.

Ultrasound-guided imaging of junctional adhesion molecule-A-targeted microbubbles identifies vulnerable plaque in rabbits.

Identification of vulnerable atherosclerotic plaques by imaging the molecular characteristics is intensively studied recently, in which verification of specific markers is the critical step. JAM-A, a junctional membrane protein, is involved in the plaque formation, while it is unknown whether it can serve as a marker for vulnerable plaques. Vulnerable and stable plaques were created in rabbits with high cholesterol diet with or without partial ligation of carotid artery respectively. Significant higher JAM-A expression was found in vulnerable plaques than that in stable plaques. Furthermore, JAM-A was not only expressed in the endothelium, but also abundantly expressed in CD68-positive area. Next, JAM-A antibody conjugated microbubbles (MBJAM-A) or control IgG-conjugated microbubbles (MBC) were developed by conjugating the biotinylated antibodies to the streptavidin modified microbubbles, and visualization by contrast-enhance ultrasound (CEUS). Signal intensity of MBJAM-A was substantially enhanced and prolonged in the vulnerable plaque and some of the MBJAM-A was found colocalized with CD68 positive macrophages. In addition, cell model revealed that MBJAM-A were able to be phagocytized by activated macrophages. Taken together, we have found that increase of JAM-A serves as a marker for vulnerable plaques and targeted CEUS would be possibly a novel non-invasive molecular imaging method for plaque vulnerability.

OXIDATIVE STRESS IN A RAT MODEL OF COTTON SMOKE INHALATION-INDUCED PULMONARY INJURY.

BACKGROUND: Smoke inhalation injury refers to airway and lung parenchyma injury and general chemical damage caused by inhaling toxic gases and substances. The aim of this study was to explore the oxidative stress mechanism of cotton smoke inhalation-induced pulmonary injury in a rat model. MATERIALS AND METHODS: Eighteen male Sprague-Dawley rats were randomly divided into control group, 6 h group, and 24 h group (six rats in each group), which duplicated previous rat cotton smoke-inhalation injury models. Rats in 6 h and 24 h groups were euthanised at 6 h and 24 h after smoke inhalation, respectively. ELISA method was used to detect indicators in the rats' lung tissue. Quantitative iNOS mRNA and γ-GCS mRNA measurements were performed using a fluorescence PCR method. RESULTS: The concentrations of MDA, NO, iNOS, γ-GCS, iNOS mRNA, and the relative expression of γ-GCS mRNA in the rats' lung tissues in 6 h and 24 h groups were higher than control group (P < 0.05), and the concentration of NO and relative expressions of iNOS mRNA and γ-GCS mRNA in 24 h group were significantly higher than 6 h group (P < 0.05). The concentrations of GSH in 24 h and 6 h groups were significantly lower than control group (P < 0.05), and that in 24 h group was even significantly lower than 6 h group (P < 0.05). CONCLUSION: In rats with cotton smoke inhalation-induced pulmonary injury, the increased iNOS mRNA transcription can cause increase of iNOS synthesis and promotion of NO synthesis. The increased γ-GCS mRNA transcription can cause increase of γ-GCS synthesis and but decrease of GSH concentration. The activation of the antioxidant system is insufficient to combat oxidative stress damage. So the oxidant/antioxidant system is imbalanced, leading to gradual aggravation of lung injury.

Clinical Application of Superior Vena Cava Spectra in Evaluation of Pulmonary Hypertension: A Comparative Echocardiography and Catheterization Study.

This study was designed to assess whether superior vena cava (SVC) Doppler flow velocities are associated with invasive measures of pulmonary arterial pressure. Eighty patients with unrepaired congenital heart disease who underwent cardiac catheterization were included (31 men, 49 women; mean age: 37.3 ± 14.7 y). Compared with the non-pulmonary hypertension group, the moderate and severe pulmonary hypertension groups had decreased SVC ventricular reserve flow velocity and a significantly increased ratio of atrial reverse flow to systolic flow (AR/S). AR/S correlated significantly with invasive pulmonary arterial systolic pressure (r = 0.426, p < 0.0001). A cutoff of 0.45 had a sensitivity and specificity of 74% and 80%, respectively, for prediction of pulmonary hypertension. Good correlation also existed between SVC AR/S and pulmonary arterial systolic pressure in cases without tricuspid regurgitation (r = 0.706, p = 0.034). These results indicate that SVC AR/S may be an alternative method for assessing pulmonary hypertension.

The Optimized Fabrication of Nanobubbles as Ultrasound Contrast Agents for Tumor Imaging.

Nanobubbles, which have the potential for ultrasonic targeted imaging and treatment in tumors, have been a research focus in recent years. With the current methods, however, the prepared uniformly sized nanobubbles either undergo post-formulation manipulation, such as centrifugation, after the mixture of microbubbles and nanobubbles, or require the addition of amphiphilic surfactants. These processes influence the nanobubble stability, possibly create material waste, and complicate the preparation process. In the present work, we directly prepared uniformly sized nanobubbles by modulating the thickness of a phospholipid film without the purification processes or the addition of amphiphilic surfactants. The fabricated nanobubbles from the optimal phospholipid film thickness exhibited optimal physical characteristics, such as uniform bubble size, good stability, and low toxicity. We also evaluated the enhanced imaging ability of the nanobubbles both in vitro and in vivo. The in vivo enhancement intensity in the tumor was stronger than that of SonoVue after injection (UCA; 2 min: 162.47 ± 8.94 dB vs. 132.11 ± 5.16 dB, P < 0.01; 5 min: 128.38.47 ± 5.06 dB vs. 68.24 ± 2.07 dB, P < 0.01). Thus, the optimal phospholipid film thickness can lead to nanobubbles that are effective for tumor imaging.

N-Acetyl Cysteine improves the diabetic cardiac function: possible role of fibrosis inhibition.

BACKGROUND: Diabetic cardiomyopathy is one of the leading causes of death in diabetes mellitus (DM) patients. This study aimed to explore the therapeutic implication of N-acetyl-L-cysteine (NAC, an antioxidant and glutathione precursor) and the possible underlying mechanism. METHODS: Thirty five 12-week-old male C57BL/6 mice were included. Twenty-five diabetic mice were induced by intraperitoneal injection of streptozocin (STZ, 150 mg/kg, Sigma-Aldrich) dissolved in a mix of citrate buffer after overnight fast. Mice with a blood glucose level above 13.5 mmol/L were considered diabetic. As a non-DM (diabetic) control, mice were injected with equal volume of citrate buffer. The 25 diabetic mice were divided into 5 groups with 5 animals in each group: including DM (diabetes without NAC treatment), and 4 different NAC treatment groups, namely NAC1, NAC3, NAC5 and NAC7, with the number defining the start time point of NAC treatment. In the 10 non-DM mice, mice were either untreated (Ctrl) or treated with NAC for 5 weeks (NAC only). Echocardiography was performed 12 weeks after STZ injection. Heart tissue were collected after echocardiography for Hematoxylin Eosin (HE) and Trichrome staining and ROS staining. Cardiac fibroblast cells were isolated, cultured and treated with high glucose plus NAC or the vehicle. qPCR analysis and CCK-8 assay were performed to observe fibrotic gene expression and cell proliferation. RESULTS: We found that both cardiac systolic function and diastolic function were impaired, coupled with excessive reactive oxygen stress and cardiac fibrosis 12 weeks after STZ induction. NAC significantly reduced ROS generation and fibrosis, together with improved cardiac systolic function and diastolic function. Strikingly, NAC1 treatment, which had the earlier and longer treatment, produced significant improvement of cardiac function and less fibrosis. In the cardiac fibroblasts, NAC blocked cardiac fibroblast proliferation and collagen synthesis induced by hyperglycemia. CONCLUSIONS: Our study indicates that NAC treatment in diabetes effectively protects from diabetic cardiomyopathy, possibly through inhibiting the ROS production and fibrosis, which warrants further clarification.

Protective effects of hydrogen sulfide inhalation on oxidative stress in rats with cotton smoke inhalation-induced lung injury.

The aim of the present study was to investigate the mechanism by which hydrogen sulfide (H2S) inhalation protects against oxidative stress in rats with cotton smoke inhalation-induced lung injury. A total of 24 male Sprague-Dawley rats were separated randomly into four groups, which included the control, H2S, smoke and smoke + H2S groups. A rat model of cotton smoke inhalation-induced lung injury was established following inhalation of 30% oxygen for 6 h. In addition, H2S (80 ppm) was inhaled by the rats in the H2S and smoke + H2S groups for 6 h following smoke or sham-smoke inhalation. Enzyme-linked immunosorbent assays were performed to measure various indices in the rat lung homogenate, while the levels of nuclear factor (NF)-κBp65 in the lung tissue of the rats were determined and semiquantitatively analyzed using immunohistochemistry. In addition, quantitative fluorescence polymerase chain reaction was employed to detect the mRNA expression of inducible nitric oxide synthase (iNOS) in the rat lung tissue. The concentrations of malondialdehyde (MDA), nitric oxide (NO), inducible iNOS and NF-κBp65, as well as the sum-integrated optical density of NF-κBp65 and the relative mRNA expression of iNOS, in the rat lung tissue from the smoke + H2S group were significantly lower when compared with the smoke group. The concentrations of MDA, NO, iNOS and NF-κBp65 in the H2S group were comparable to that of the control group. Therefore, inhalation of 80 ppm H2S may reduce iNOS mRNA transcription and the production of iNOS and NO in rats by inhibiting NF-κBp65 activation, subsequently decreasing oxidative stress and cotton smoke inhalation-induced lung injury.

Comparative sonographic study of cerebral hemodynamic differences and changes after oxygen therapy in healthy youths of different ethnicities in Tibet.

OBJECTIVES: The purpose of this study was to sonographically assess the cerebral hemodynamic differences and changes after oxygen therapy in healthy youths of different ethnicities in Tibet. METHODS: Sixty-six healthy young Han visitors and 29 healthy young Tibetan residents were divided into 4 groups. Basic information was collected. Pulsed Doppler sonography was used to record the cerebral hemodynamic parameters for the internal carotid, vertebral, and middle cerebral arteries. The participants were then instructed to inhale oxygen, and basic information and cerebral hemodynamic parameters were recorded at 1, 2, 4, and 8 minutes, respectively. Differences in these parameters between groups were analyzed. RESULTS: In comparisons of the flow parameters between sex-matched groups, the mean resistive index values for the internal carotid, vertebral, and middle cerebral arteries in the Han groups were significantly lower than those in the Tibetan groups (P <. 05). The mean peak systolic velocity, end-diastolic velocity, and mean velocity values for the middle cerebral artery in the Han groups were significantly higher than those in the Tibetan groups (P < .05). After oxygen uptake, there were no significant differences in the mean arterial oxygen saturation, heart rate, mean velocity, and resistive index values between the male groups, and similar changes were found for the arterial oxygen saturation and peak systolic velocity values between female groups after 8 minutes of oxygen uptake (P > .05). CONCLUSIONS: Sonography is a useful modality for noninvasive and real-time detection of changes in cerebral hemodynamics and can provide reference values for the prevention and treatment of cerebrovascular diseases.

New method for noninvasive quantification of central venous pressure by ultrasound.

BACKGROUND: The central venous pressure (CVP) is essential for assessing the cardiac preload and circulating blood volume in clinic. The invasive CVP measurement by central venous catheter has been reported with various complications. The aim of this study was to develop a new noninvasive method for quantification of CVP by ultrasound. METHODS AND RESULTS: Seventy-six patients who had their CVP monitored for intraoperative or postoperative management were recruited. By accurate location of the collapse point of the internal jugular vein and the center of the right atrium using ultrasound imaging, the height of the fluid column between those 2 points was measured as the noninvasive CVP (CVPn). A total of 118 measurements were performed and compared with the invasive CVP (CVPi). Linear correlation analysis revealed a significant correlation between CVPi and CVPn (preoperative measurements, r=0.90; P<0.01 and postoperative measurements, r=0.93; P<0.01). Bland-Altman plots showed a good agreement between CVPi and CVPn with the mean difference of 0.22 mm Hg (preoperative measurements) and -0.09 mm Hg (postoperative measurements), respectively. CONCLUSIONS: The new noninvasive CVP quantification method based on the location of both the collapse point of internal jugular vein and the center of right atrium by ultrasound could be used as a reliable approach for monitoring the hemodynamic status in clinic.

Carotid Arterial Stiffness in Patients with Congenital Heart Disease-Related Pulmonary Hypertension Assessed with Radio Frequency Data Technique.

BACKGROUND: It has been well known that pulmonary hypertension (PH) caused by congenital heart disease (CHD) leads to reduced flexibility of the small pulmonary arteries, due to hemodynamic changes in the pulmonary circulation and alterations of the vasoactive profile. However, whether CHD-related PH affects the elasticity of the systemic arteries, such as the common carotid artery (CCA), has not been fully investigated. The purpose of this study was to explore the CCA stiffness in patients with CHD-related PH using the radio frequency data technique. METHODS: Forty patients with CHD were included. They were divided into PH and non-PH (NPH) groups by the right heart catheter-determined or regurgitation velocity-determined mean pulmonary arterial pressure (mPAP). MyLabTwice (Esaote, Genoa, Italy) ultrasound machine equipped with automatic quality intima-media thickness (QIMT) and quality arterial stiffness (QAS) capabilities was used to measure the left common carotid arterial (CCA) intima-media thickness and arterial stiffness parameters. RESULTS: The results have shown that the left CCA internal diameter, pulse wave velocity, arterial wall tension, and local diastolic pressure were increased in the CHD-related PH group compared with the CHD-related NPH group (all P < 0.05). The left CCA internal diameter negatively and significantly correlated with the mean PAP. CONCLUSIONS: Common carotid artery diameter and stiffness increase in patients with CHD-related pulmonary hypertension. QIMT and QAS ultrasound techniques may provide a comprehensive assessment of the CCA remodeling.

Noninvasive method for measuring local pulse wave velocity by dual pulse wave Doppler: in vitro and in vivo studies.

OBJECTIVES: To evaluate the validity and reproducibility of a noninvasive dual pulse wave Doppler (DPWD) method, which involves simultaneous recording of flow velocity of two independent sample volumes with a measurable distance, for measuring the local arterial pulse wave velocity (PWV) through in vitro and in vivo studies. METHODS: The DPWD mode of Hitachi HI Vision Preirus ultrasound system with a 5-13MHz transducer was used. An in vitro model was designed to compare the PWV of a homogeneous rubber tubing with the local PWV of its middle part measured by DPWD method. In the in vivo study, local PWV of 45 hypertensive patients (25 male, 49.8±3.1 years) and 45 matched healthy subjects (25 male, 49.3±3.0 years) were investigated at the left common carotid artery (LCCA) by DPWD method. RESULTS: In the in vitro study, the local PWV measured by DPWP method and the PWV of the homogeneous rubber tubing did not show statistical difference (5.16 ± 0.28 m/s vs 5.03 ± 0.15 m/s, p = 0.075). The coefficient of variation (CV) of the intra- and inter- measurements for local PWV were 3.46% and 4.96%, for the PWV of the homogeneous rubber tubing were 0.99% and 1.98%. In the in vivo study, a significantly higher local PWV of LCCA was found in the hypertensive patients as compared to that in healthy subjects (6.29±1.04 m/s vs. 5.31±0.72 m/s, P = 0.019). The CV of the intra- and inter- measurements in hypertensive patients were 2.22% and 3.94%, in healthy subjects were 2.07% and 4.14%. CONCLUSIONS: This study demonstrated the feasibility of the noninvasive DPWD method to determine the local PWV, which was accurate and reproducible not only in vitro but also in vivo studies. This noninvasive echocardiographic method may be illuminating to clinical use.

Hemodynamic changes of the middle hepatic vein in patients with pulmonary hypertension using echocardiography.

The aim of this study was to analyze the changes of the middle hepatic vein (MHV) spectra in patients with pulmonary hypertension (PH) caused by congenital heart disease (CHD) and determine the proper parameters of MHV to predict PH. Eighty patients with CHD were included, whose pulmonary artery pressure was measured via right heart catheterization, and the MHV spectra were detected via echocardiography. The peak value of velocity (V) and velocity time integral (VTI) of the waves, including S wave, D wave and A wave, were measured at the end of inspiration. The values of the MHV parameters that were predictive of PH were evaluated and their cut-off points were determined. Compared with the control group, V of S wave (S), VTI of S wave (SVTI), V of D wave (D), VTI of D wave (DVTI) decreased and V of A wave (A), VTI of A wave (AVTI), A/S, AVTI/SVTI, A/(S+D), AVTI/ (SVTI+DVTI) increased in the PH group. These differences were statistically significant (P<0.05). A correlation analysis determined that the ratios of A/S, A/(S+D), AVTI/(SVTI+DVTI) were positively correlated with pulmonary artery mean pressure (r=0.529,0.575,0.438,P<0.001). An ROC curve analysis determined that the diagnostic effect of A/(S+D) was superior to the other two parameters. On the ROC curve, when the ratio of A/(S+D) was 0.30, the sensitivity was 85.37% and specificity was 75.00% for predicting PH. The spectral parameters of MHV, including the ratios of A/S, A/(S+D) and AVTI/(SVTI+DVTI), increased with increasing pulmonary pressure in CHD patients. When the ratio of A/(S+D) was 0.30 in MHV spectra, it had sufficient sensitivity and specificity for diagnosing PH, and this method could be used as a new non-invasive complementary echocardiographic parameter for predicting PH.

Middle cerebral arterial flow changes on transcranial color and spectral Doppler sonography in patients with increased intracranial pressure.

OBJECTIVES: Intracranial pressure usually increases after severe brain injury. However, a method for noninvasive evaluation of intracranial pressure is still lacking. The purpose of this study was to explore the potential role of transcranial color Doppler sonography in assessing intracranial pressure by observing the middle cerebral artery blood flow parameters in patients with increased intracranial pressure of varying etiology. METHODS: The hemodynamic changes in the middle cerebral artery in patients with varying degrees of increased intracranial pressure were investigated by transcranial color Doppler sonography in 93 patients who had emergency surgery for brain injury. RESULTS: Middle cerebral artery Doppler flow spectra changed regularly as intracranial pressure increased. The pulsatility index (PI) and resistive index (RI) had a significantly positive correlation with intracranial pressure (r = 0.90 and 0.89, respectively; P< .001), whereas the middle cerebral artery diastolic velocity showed a significant negative correlation with intracranial pressure (r = -0.52; P< .01). A receiver operating characteristic curve showed that the RI and PI cutoff values were 0.705 and 1.335, respectively, for predicting increased intracranial pressure, with sensitivity of 0.885 and specificity of 0.970. CONCLUSIONS: In addition to the PI and RI, middle cerebral artery diastolic flow velocity measurement by transcranial color Doppler sonography may also be a useful variable for evaluating intracranial pressure in patients with acute brain injury.

A new method of measurement of cerebral circulation time: contrast-enhanced ultrasonography in healthy adults and patients with intracranial shunts.

Alterations in the cerebral circulation time (CCT) are observed in several cerebrovascular diseases. We designed a new method of global CCT measurement using gray-scale contrast-enhanced ultrasound and studied healthy Chinese adults and patients with intracranial shunts. Eighty-one healthy volunteers and eight patients with intracranial shunt disease were enrolled. The contrast agent Sonovue was used. Perfusion in the carotid artery and internal jugular vein bilaterally was recorded. Start and peak filling CCTs were calculated and analyzed. Imaging of carotid vessels was uncomplicated in all patients. The bilateral start CCT was 6.23 ± 1.39 s in healthy patients. There were no significant differences within subgroups and contrast-dosage groups. In the patient group, the mean start CCT was 3.0 ± 0.56 s. There was a significant difference between the control and patient groups (p < 0.001). This new method using gray-scale contrast imaging can measure CCT and cerebral blood volume accurately. It can be used to visualize blood flow differences in real time and is less dependent on the training of the operator.

Ultrasound study of carotid and cardiac remodeling and cardiac-arterial coupling in normal pregnancy and preeclampsia: a case control study.

BACKGROUND: Cardiovascular adaptions, such as cardiac and uterine spiral arterial remodeling, and aortic arterial stiffening during pregnancy have been extensively investigated, while the interactions between the elastic artery and the left ventricle are poorly understood. This study was to evaluate the cardiac-arterial coupling in both normal pregnancy and preeclampsia using ultrasound techniques. METHODS: Twenty-three preeclamptic women with no antihypertensive treatment prior to admission, and 40 age- (27.2 ± 3.0 y vs. 29.1 ± 5.7 y, p = 0.0805) and gestational week- (35.6 ± 3.4 wk vs. 34.8 ± 3.6 wk, p = 0.3573) matched normotensive pregnant women were included. All women signed informed consent. All were nulliparas, had singleton pregnancies, and had no other risk factors for arterial stiffening. Carotid and cardiac ultrasound was performed using a MylabTwice ultrasound unit (Esaote, Italy). Cardiac and carotid remodeling and their associations were analyzed. Left ventriculo-carotid coupling was characterized by the ratio between the arterial elastance (Ea) and the left ventricular systolic elastance (Ees). Follow-up study was performed 16-20 months after parturition. RESULTS: Left ventricular and carotid arterial remodeling was seen more frequently in preeclamptic women than in normal pregnant controls (96% vs. 40%, 82% vs. 48%, both p < 0.0001). The relative carotid arterial wall thickness showed no significant difference between the two groups. However, the carotid cross-sectional area, a surrogate for carotid arterial mass, was significantly greater in preeclampsia than that in normal controls (11.23 ± 0.17 mm2 vs. 8.58 ± 1.88 mm2, p < 0.00001). Carotid arterial stiffness and intima-media thickness correlated significantly with cardiac diastolic function parameters and blood pressures (p < 0.05). Both Ea and Ees were significantly greater in preeclampsia, compared with values in normal pregnant controls (Ea: 2.41 ± 0.57 mmHg/ml vs. 1.98 ± 0.46 mmHg/ml, p = 0.0005; Ees: 11.68 ± 9.51 m/s2 vs. 6.91 ± 6.13 m/s2, p = 0.002). However, there was no significant difference in the left ventriculo-carotid coupling index, Ea/Ees, between the two groups. Carotid remodeling persisted in both preeclamptic women and normal pregnant controls 16-20 months after parturition. CONCLUSIONS: Significant cardiac and carotid remodeling and similar left ventriculo-carotid coupling were observed in both preeclampsia and normal pregnancy. Carotid remodeling may persist postpartum. Further studies with larger populations are needed to confirm these findings.

Evaluation of carotid artery elasticity changes in patients with type 2 diabetes.

BACKGROUND: Type 2 diabetes is one of the most common causes of cardiovascular disease as it causes arterial stiffness changes. The purpose of this study is to characterize, in vivo, carotid arterial structural and functional changes by applying radio frequency and X-strain ultrasound techniques. METHODS: Ninety-one subjects were assigned into two groups; a diabetes group and a control group. Structural and functional changes in the common carotid arterial wall were investigated by quality intima-media thickness (QIMT), quality arterial stiffness (QAS), and X-strain analysis with a Mylab Twice ultrasound instrument. The relationships among variables between the two groups were analyzed in this study. RESULTS: There was no significant difference in carotid IMT (626.5 ± 169.1 µm vs. 568.5 ± 122.6 µm, P = 0.1506) between two groups. Pulse wave velocity (PWV) and stiffness index (ß) were remarkably greater (8.388 ± 3.254 m/s vs. 7.269 ± 1.332 m/s; 12.51 ± 14.16 vs.9.279 ± 2.871), while compliance coefficient (CC) decreased significantly in the diabetes group (0.802 ± 0.3094 mm2/Kpa vs. 0.968 ± 0.3992 mm2/Kpa) (P < 0.05). The displacement difference of radial (RD-D), longitudinal (LD-D) and rotation (ROT-D) directions were significantly different between two groups' comparison (P = 0.0212, P = 0.0235 and P = 0.0072, respectively). The time of circumferential peak strain difference (CS-DT) and the time of radial peak strain rate (RSR-T) were found to be significantly different between the two groups (341.9 ± 77.56 ms vs. 369.0 ± 78.26 ms, P = 0.0494; 142.7 ± 22.43 ms vs. 136.2 ± 30.70 ms, P = 0.0474). CS-TD and RSR-T were also found to be positively correlated with CC value (r = 0.3908, P < 0.005 and r = 0.3027, P = 0.0326, respectively). Finally, PWV was negatively correlated with CC with (r = -0.6177, P < 0.001). CONCLUSIONS: In type 2 diabetes, the functional changes in CCA can be identified using the methods presented in this article earlier than the structural changes. Arterial stiffness values provided by QAS and X-strain analysis can be used as indicators of CCA functional lesions in patients with type 2 diabetes.