Ultrasound in Medicine and Biology

Masthead

2012-06-01

Editorial Advisory Board

2012-06-01

Atherosclerotic Risk Stratification Strategy for Carotid Arteries Using Texture-Based Features

2012-04-16

Abstract: Plaques in the carotid artery result in stenosis, which is one of the main causes for stroke. Patients have to be carefully selected for stenosis treatments as they carry some risk. Since patients with symptomatic plaques have greater risk for strokes, an objective classification technique that classifies the plaques into symptomatic and asymptomatic classes is needed. We present a computer aided diagnostic (CAD) based ultrasound characterization methodology (a class of Atheromatic systems) that classifies the patient into symptomatic and asymptomatic classes using two kinds of datasets: (1) plaque regions in ultrasound carotids segmented semi-automatically and (2) far wall gray-scale intima-media thickness (IMT) regions along the common carotid artery segmented automatically. For both kinds of datasets, the protocol consists of estimating texture-based features in frameworks of local binary patterns (LBP) and Law’s texture energy (LTE) and applying these features for obtaining the training parameters, which are then used for classification. Our database consists of 150 asymptomatic and 196 symptomatic plaque regions and 342 IMT wall regions. When using the Atheromatic-based system on semiautomatically determined plaque regions, support vector machine (SVM) classifier was adapted with highest accuracy of 83%. The accuracy registered was 89.5% on the far wall gray-scale IMT regions when using SVM, K-nearest neighbor (KNN) or radial basis probabilistic neural network (RBPNN) classifiers. LBP/LTE-based techniques on both kinds of carotid datasets are noninvasive, fast, objective and cost-effective for plaque characterization and, hence, will add more value to the existing carotid plaque diagnostics protocol. We have also proposed an index for each type of datasets: AtheromaticPi, for carotid plaque region, and AtheromaticWi, for IMT carotid wall region, based on the combination of the respective significant features. These indices show a separation between symptomatic and asymptomatic by 4.53 units and 4.42 units, respectively, thereby supporting the texture hypothesis classification.

Different Patterns of Longitudinal Displacement of the Common Carotid Artery Wall in Healthy Humans Are Stable Over a Four-Month Period

Åsa Rydén Ahlgren, Magnus Cinthio, Hans W. Persson, Kjell Lindström — 2012-04-16

Abstract: Using an in-house developed ultrasonic method, we have shown that there is distinct longitudinal multiphasic displacement of the human common carotid artery (CCA) wall during the cardiac cycle. Different subjects showed markedly different patterns of displacement. At present, it is not known if the pattern of displacement in an individual is stable over time. Therefore, in this study, we measured the longitudinal displacement of the right CCA in 10 healthy humans at two different occasions 4 months apart. The basic pattern of longitudinal displacement for an individual was highly stable, including intraclass correlation coefficient (ICC) of 0.88 for the ratio between the first antegrade and the retrograde displacement, and ICC of 0.76 for the magnitude of the first antegrade displacement. The stable basic pattern of displacement showed marked differences among subjects, also of the same age and gender. Further studies are needed to elucidate the underlying mechanisms, the physiologic, pathophysiologic and clinical implications of this phenomenon.

Spontaneous Echo Contrast in Internal Jugular Veins: A Probable Indicator for Systemic Inflammation and a Prothrombotic State

Hung-Yi Hsu, Chih-Ping Chung, Shu-Yi Chen, Yi-Ying Chiang, Han-Hwa Hu — 2012-04-04

Abstract: The hypothesis that spontaneous echo contrast (SEC) in the internal jugular vein (IJV) is a clinical indicator for systemic inflammation and thrombogenesis is investigated in this study. Fifty-two patients with cardiovascular diseases and 25 nondiseased subjects were evaluated. SEC was observed in 96 of 154 IJVs. The visual grading of SEC showed good interobserver agreement on SEC grades (κ value: 0.846, p < 0.001). Generalized estimating equations analysis was used for univariate and multivariate analysis. Univariate analysis showed that peak flow velocity in corresponding IJV (coefficient −0.001 [95% CI −0.019, −0.001], p = 0.031), jugular venous reflux (JVR, −0.010 [–0.019, −0.001], p = 0.002), plasma levels of fibrinogen (0.464 [0.208, 0.719], p < 0.001) and hs–C-reactive protein (hs-CRP) (0.479 [0.184, 0.774], p = 0.001) and previous history of ischemic stroke (0.779 [0.139, 1.417]; p = 0.017) correlated with the grades of SEC in IJV. Increased plasma levels of fibrinogen and hs-CRP, previous ischemic stroke, lower peak velocity in corresponding IJV and JVR were also independent predictors for the higher grades of SEC in IJV in multivariate regression analysis. SEC in IJV could be evaluated easily and semiquantitatively. SEC in IJVs could be a putative marker of cerebral circulation disturbance and an indicator of systemic inflammatory or prothrombotic state.

A Pilot Study Evaluating Real-Time Shear Wave Ultrasound Elastography of Miscellaneous Non-Nodal Neck Masses in a Routine Head and Neck Ultrasound Clinic

2012-04-16

Abstract: A pilot study was performed to evaluate shear wave ultrasound elastography (SWE) for miscellaneous non-nodal/salivary/thyroid neck lesions. Forty-six lesions undergoing conventional sonography also underwent SWE. Elastic moduli from the stiffest areas in lesions were correlated with diagnosis. Forty lesions were benign (9 lipomas, 8 lymphatic/venous vascular malformations, 7 thyroglossal duct cysts, 4 branchial cleft cysts, 4 abscesses/phlegmons, 3 neurogenic tumors and 1 each of paraganglioma, sebaceous cyst, pseudotumor, hypertrophic scar, ranula) and 6 were malignant (1 malignant fibrous histiocytoma, 2 primary squamous cell carcinomas and 3 intramuscular metastases [2 squamous cell carcinomas, 1 malignant melanoma]).Median stiffness of malignant lesions (226.4 kPa, range 55.6 to 300.0) was higher than benign lesions (28.3 kPa, range 4.0 to 300.0) (p < 0.001). SWE cut-off with highest accuracy (174.4 kPa) achieved 83.3% sensitivity and 97.5% specificity, and the cut-off with 100% sensitivity (55.6kPa) achieved 75% specificity. All malignant lesions were suspected on conventional sonography. The preliminary data indicate that SWE is feasible for miscellaneous neck lesions. SWE would not have altered management in terms of detecting undisclosed malignancies, although as a quantitative technique, it may increase the diagnostic confidence of less experienced operators performing head and neck ultrasound.

Determination of the Augmentation Effects of Hyaluronic Acid on Different Heel Structures in Amputated Lower Limbs of Diabetic Patients Using Ultrasound Elastography

2012-04-16

Abstract: This study measured tissue properties of different anatomies of heels in amputated lower limbs of diabetic patients before and after hyaluronic acid (HA) or normal saline (NS) injections. Seven amputated lower limbs from six diabetic patients constituted the experimental group and one amputated lower limb from a diabetic patient served as the control. The limbs were placed in a fixation platform. A 5–12 MHz linear-array ultrasound transducer controlled by a stepping motor was used to load and unload tested heels. The loading-unloading velocity was 6 mm/s and the maximum loading stress was 178 kPa. Loading-unloading tests were performed before and after 1 mL HA injections into heels in the experimental group. The control limb underwent the same test before and after 1 mL NS injection. The unloaded thickness and Young‘s modulus of the macrochambers, microchambers and heel pads were determined before and after the interventions. The unloaded thickness of the macrochambers and the heel pad increased significantly (p = 0.012) after HA injection. The Young’s modulus of the macrochambers decreased nonsignificantly after HA injections. Similar thickness and tissue stiffness changes were observed in the control limb. The baseline heel-pad energy dissipation ratio (EDRhp) was 81.3 ± 1.3% and decreased significantly (p = 0.012) to 73.1 ± 1.7% after HA injections. The EDRhp in the control increased after NS injection. Histologic examinations revealed localized HA accumulation in the macrochambers with an extension into the adjacent fibrous septa. Injection of HA can increase tissue thickness and enhance heel-pad tissue resilience.

Correlation and Agreement Between Contrast-Enhanced Ultrasonography and Perfusion Computed Tomography for Assessment of Liver Metastases from Endocrine Tumors: Normalization Enhances Correlation

2012-04-04

Abstract: We studied correlation and agreement between perfusion parameters derived from contrast-enhanced ultrasonography (CEUS) and computed tomography (CT). Both techniques were performed in 16 patients with proven liver metastases from endocrine tumor. Replenishment study after ultrasound-induced destruction of microbubbles was used for CEUS quantification. CEUS-derived relative values of blood flow, blood volume and mean transit time were compared with perfusion CT–derived parameters measured in the same tumors. Significant correlation was observed between CEUS normalized values and CT absolute tumor values for blood flow (r = 0.58; p = 0.018), blood volume (r = 0.61; p = 0.012) and mean transit time (r = 0.52; p = 0.037). Correlation was not significant for non-normalized values. Agreement between CEUS normalized values and perfusion CT relative values was significant (p < 0.04). Estimated bias between CEUS and CT for relative perfusion values was −1.38 (−5.02; 2.27) for blood flow, +0.26 (−0.79; 1.31) for blood volume and +0.21 (−0.46; 0.87) for mean transit time. We conclude that normalization markedly increased correlation between CEUS- and CT-derived perfusion values and allowed agreement assessment.

Phalangeal Quantitative Ultrasound Measurements in Chronic Hemodialysis Patients: A 4-Year Follow-Up

2012-04-16

Abstract: In the course of chronic kidney disease, bone metabolism disturbances occur and become aggravated simultaneously with the progression of renal disorder, worsening patients’ quality of life. We conducted a 4-year follow-up to assess phalangeal quantitative ultrasound (QUS) measurements in 32 patients undergoing chronic hemodialysis (17 males and 15 females) whose mean ages were 56.3 ± 15.2 years. The QUSs of hand phalanges were performed using DBM 1200 (IGEA, Carpi, Italy) and are expressed as amplitude-dependent speed of sound (Ad-SoS), Z-scores, and T-scores. In comparison with the age-, sex-, and body mass index–adjusted control group, QUS parameters were significantly decreased in all patients undergoing dialysis. During the 4-year follow-up, Ad-SoS and T-scores in all study groups sloped significantly with time. The significant negative relationships between follow-up Ad-SoS results and both baseline and follow-up parathormone values were demonstrated. Our results confirm a high prevalence of bone disturbances in patients undergoing chronic hemodialysis, and they do not improve during renal replacement therapy. The parathormone level seems to be an important agent in influencing bone status, but further studies are needed to understand the other risk factors in kidney-related bone disease.

Using the Gradient of Human Cortical Bone Properties to Determine Age-Related Bone Changes Via Ultrasonic Guided Waves

Cécile Baron — 2012-04-16

Abstract: Bone fragility depends not only on bone mass but also on bone quality (structure and material). To accurately evaluate fracture risk or propose therapeutic treatment, clinicians need a criterion, which reflects the determinants of bone strength: geometry, structure and material. In human long bone, the changes due to aging, accentuated by osteoporosis are often revealed through the trabecularization of cortical bone, i.e., increased porosity of endosteal bone inducing a thinning of the cortex. Consequently, the intracortical porosity gradient corresponding to the spatial variation in porosity across the cortical thickness is representative of loss of mass, changes in geometry (thinning) and variations in structure (porosity). This article examines the gradient of material properties and its age-related evolution as a relevant parameter to assess bone geometry, structure and material. By applying a homogenization process, cortical bone can be considered as an anisotropic functionally graded material with variations in material properties. A semi-analytical method based on the sextic Stroh formalism is proposed to solve the wave equation in an anisotropic functionally graded waveguide for two geometries, a plate and a tube, without using a multilayered model to represent the structure. This method provides an analytical solution called the matricant and explicitly expressed under the Peano series expansion form. Our findings indicate that ultrasonic guided waves are sensitive to the age-related evolution of realistic gradients in human bone properties across the cortical thickness and have their place in a multimodal clinical protocol.

Ultrasound Assessment of Transverse Carpal Ligament Thickness: A Validity and Reliability Study

Zhilei Liu Shen, Zong-Ming Li — 2012-04-16

Abstract: The transverse carpal ligament (TCL) forms the palmar boundary of the carpal tunnel and plays an important role in carpal tunnel mechanics. TCL hypertrophy has been observed for individuals with carpal tunnel syndrome (CTS) and postulated as a potential etiologic factor. Ultrasound is particularly advantageous for TCL imaging because of its capability of detecting the interfaces between the TCL and other tissues. The purposes of this study were to develop an ultrasound based method to measure the TCL thickness and to test the validity and reliability of this method. Three operators conducted two sessions of ultrasound examination on eight cadaveric specimens and eight healthy volunteers. A custom script was used to calculate TCL thickness along the TCL length from the ultrasound images. The ultrasound based TCL thickness of the cadaveric specimens was compared with the dissection based TCL thickness for validation. The results showed Pearson’s correlation coefficients of 0.867–0.928, intraclass correlation coefficient (ICC) values of 0.726–0.865, a standard error of measurement of 0.02–0.07 mm and a minimal detectable difference of 0.05–0.15 mm. The high correlation coefficients and small errors indicate that the ultrasound based method is valid for measuring TCL thickness. Furthermore, ultrasound measurements showed excellent intraoperator and interoperator reliability with ICC values as 0.826–0.933 and 0.840–0.882, respectively. The ultrasound based TCL thickness was in the range of 0.93–2.34 (1.54 ± 0.33) mm and agreed well with previous studies. The ultrasound method developed in this study is a valuable tool to examine morphologic properties of healthy and pathologic TCLs.

Methodological Aspects of Functional Transcranial Doppler Sonography and Recommendations for Simultaneous EEG Recording

Bernhard Rosengarten, Michael Deppe, Manfred Kaps, Jürgen Klingelhöfer — 2012-04-16

Abstract: The neurovascular coupling describes a vasoregulative principle of the brain that adapts local cerebral blood flow in accordance with the underlying neuronal activity. It is the basis of modern indirect brain imaging techniques. Because of its wide availability and high tolerability the functional transcranial Doppler has been often used to assess brain function in clinical conditions. In the present paper we will give an overview of the current understanding of the coupling, explain basic principles of the Doppler technique and summarize relevant findings of functional Doppler tests in the different vascular territories of the brain. Finally, the concept of a combined functional electroencephalogram and transcranial Doppler technique will be outlined, which allows simultaneous investigation of the neuronal and vascular responses of neurovascular coupling.

Effects of Active, Passive and Motor Imagery Paradigms on Cerebral and Peripheral Hemodynamics in Older Volunteers: A Functional TCD Study

Angela S.M. Salinet, Ronney B. Panerai, Thompson G. Robinson — 2012-04-16

Abstract: This study aimed to compare the response of metabolic-induced cerebral hemodynamic changes measured using transcranial Doppler (TCD) ultrasonography during passive, active and motor imagery paradigms, and associated peripheral hemodynamic responses. Continuous recordings of bilateral cerebral blood flow velocity (CBFv), blood pressure, heart rate and end-tidal CO2 were performed in 12 right-handed subjects (aged ≥45 y) before, during and after 60 s of active, passive and mental-imagined paradigms. The results revealed no significant difference in CBFv responses between the paradigms and, furthermore, the temporal patterns of the hemodynamic responses showed some degree of similarity. Moreover, significant changes were seen in cerebral and peripheral hemodynamic responses for all paradigms. Our results suggest that active, passive and motor imagery paradigms can be used interchangeably to assess hemodynamic responses. This will enable more detailed noninvasive assessment in patients, where voluntary movement is not possible, but where abnormalities of cerebral hemodynamic control mechanisms can be anticipated.

A Practical Method for Ultrasonographically Monitoring the Day-to-Day Growth of Individual Ovarian Follicles in Women Undergoing Assisted Reproduction

Desiree Rouleau, Allison Case, Adrian Gamelin, Hyun Lim, Angela Baerwald — 2012-04-16

Abstract: The objective of this study was to validate the use of the nonidentity (NonID) method compared with the identity (ID) method for tracking the day-to-day growth of individual follicles in women undergoing ovarian stimulation for assisted reproduction. A retrospective observational study was conducted in 20 women during ovarian stimulation. Conventional 2-D transvaginal ultrasonography was used to monitor follicle growth every 2–3 days throughout stimulation. Video clips of both ovaries were obtained in sagittal and coronal planes at each visit. Standardized diameter measurements of all follicles ≥4 mm were made retrospectively from video clips. The growth profiles of all follicles that developed to ≥10 mm were determined using the ID and NonID methods. Using Lin’s concordance statistics, we documented that agreement between methods was 91% for follicles <10 mm, 96% for follicles 10–15 mm and 99% for follicles >15 mm. Lin’s concordance correlation coefficient between the two methods was 0.96 (standard error = 0.003). We concluded that the NonID method is a practical, effective tool for monitoring the day-to-day growth of individual ovarian follicles in women undergoing assisted reproduction.

The Role of Preterm Placental Calcification in High-Risk Pregnancy as a Predictor of Poor Uteroplacental Blood Flow and Adverse Pregnancy Outcome

Kuo-Hu Chen, Li-Ru Chen, Yu-Hsiang Lee — 2012-04-04

Abstract: This prospective cohort study aims to clarify the role of preterm placental calcification in high-risk (i.e., hypertension, diabetes, placenta previa or severe anemia) pregnant women as a predictor of poor uteroplacental blood flow (absent or reverse end-diastolic velocity [AREDV]) and adverse pregnancy outcome. Monthly ultrasound was performed starting at 28 weeks' gestation to establish the diagnosis of Grade III placental calcification, with measurement of Doppler velocimetry in the umbilical vessels at 32 weeks' gestation. The participants were classified into three groups: Group A (n = 776), a low-risk group without antenatal complication; group B (n = 42), a high-risk group with preterm (28 to 36 weeks) placental calcification; and group C (n = 71), a high-risk control group without preterm (<36 weeks) placental calcification. Analyzed by logistic regression, the risks of AREDV (OR 4.32, 95%CI 1.25 to 14.94), adverse maternal outcome including postpartum hemorrhage (OR 3.98, 95% CI 1.20 to 13.20), placental abruption (OR 4.80, 95% CI 1.19 to 19.35), maternal transfer to intensive care unit (OR 3.83, 95% CI 1.10 to 13.33) and adverse fetal outcome including preterm birth (OR 3.86, 95% CI 1.32 to 11.29), low birth weight (OR 2.99, 95% CI 1.11 to 8.03), low Apgar score (OR 5.14, 95% CI 1.64 to 16.08) and neonatal death (OR 4.52, 95% CI 1.15 to 17.73) were greater in group B compared with group C. In contrast, the risks of AREDV and adverse pregnancy outcome were significantly lower in group A than those in group C, except postpartum hemorrhage (OR 0.53, 95% CI 0.19 to 1.46). We conclude that in high-risk pregnant women, the presence of preterm placental calcification is a predictor of poor uteroplacental flow and adverse pregnancy outcome, requiring closer surveillance for maternal and fetal well-being. This finding helps identify the most dangerous population among high-risk pregnant women.

Contrast Ultrasound Imaging for Identification of Early Responder Tumor Models to Anti-Angiogenic Therapy

2012-03-19

Abstract: Agents targeting vascular endothelial growth factor (VEGF) have been validated as cancer therapeutics, yet efficacy can differ widely between tumor types and individual patients. In addition, such agents are costly and can have significant toxicities. Rapid noninvasive determination of response could provide significant benefits. We tested if response to the anti-VEGF antibody bevacizumab (BV) could be detected using contrast-enhanced ultrasound imaging (CEUS). We used two xenograft model systems with previously well-characterized responses to VEGF inhibition, a responder (SK-NEP-1) and a non-responder (NGP), and examined perfusion-related parameters. CEUS demonstrated that BV treatment arrested the increase in blood volume in the SK-NEP-1 tumor group only. Molecular imaging of αVβ3 with targeted microbubbles was a more sensitive prognostic indicator of BV efficacy. CEUS using RGD-labeled microbubbles showed a robust decrease in αVβ3 vasculature following BV treatment in SK-NEP-1 tumors. Paralleling these findings, lectin perfusion assays detected a disproportionate pruning of smaller, branch vessels. Therefore, we conclude that the response to BV can be identified soon after initiation of treatment, often within 3 days, by use of CEUS molecular imaging techniques. The use of a noninvasive ultrasound approach may allow for earlier and more effective determination of efficacy of antiangiogenic therapy.

Early Estimation of Left Ventricular Systolic Pressure and Prediction of Successful Aortic Constriction in a Mouse Model of Pressure Overload by Ultrasound Biomicroscopy

2012-03-19

Abstract: Elevation of left ventricular end-systolic pressure (LVESP) and hypertrophic response in mice varies after transverse aorta constriction (TAC). Micromanometric catheterization, conventionally used to select mice with successful TAC, is invasive and nonreusable. We aimed to establish noninvasive imaging protocols for early estimation of successful TAC by ultrasound biomicroscopy (UBM). Out of 55 C57BL/6J mice, we randomly selected 45 as TAC group and 10 as controls. UMB was performed before TAC and, at day 3 and day 14, after TAC. In all mice, LVESP was measured with a Millar conductance catheter at day 14. With LVESP ≥ 150 mm Hg set as indicator of successful TAC (TAC+) and LVESP < 150 mm Hg as unsuccessful (TAC−), receiver operating characteristic curve analysis demonstrated that postoperative inner diameter at aortic banding site (IDb), peak flow velocity at aortic banding site (PVb) and peak flow velocity of right/left common carotid artery (PVr/l) at day 3 served as most effective predictors for LVESP at day 14 (area under curve = 0.9016, 0.9143, 0.8254, respectively. p < 0.01 for all). Among all UBM parameters at day 3, IDb, PVb, right common carotid artery peak flow velocity (PVr) and PVr/l correlated best with LVESP at day 14 (R2 = 0.5740, 0.6549, 0.5208, 0.2274, respectively. p < 0.01 for all). Furthermore, IDb, PVb, and PVr/l at day 3 most effectively predict long-term cardiac hypertrophy, using the cut-off values of 0.45 mm, 2698.00 mm/s, 3.08, respectively. UBM can be a noninvasive and effective option for early prediction of successful TAC.

Ultrasound Safety with Midfrequency Transcranial Sonothrombolysis: Preliminary Study on Normal Macaca Monkey Brain

2012-04-04

Abstract: We investigated the safety of transcranial-targeting midfrequency (0.1 to 1 MHz) ultrasonic thrombolysis for acute ischemic stroke. We applied a new therapeutic and imaging transducer to healthy Macaca monkey brains via sonication of the ipsilateral middle cerebral artery through an acoustic temporal window. Young adult cynomolgus monkeys (Macaca fascicularis) were assigned to a group without sonication (control), a group maintained for 1 d after sonication (C1) and a group maintained for 7 d after sonication (C7; n = 3 for each). Two elder rhesus monkeys (Macaca mulatta) were ultrasonicated under transvenous injection of the recombinant tissue plasminogen activator alteplase (0.9 mg/kg), and maintained for 7 d (R). An automatic switching circuit alternately operated a therapeutic ultrasound beam (T-beam) generator for thrombolysis (frequency = 490 kHz; intensity = 0.72 W/cm2) and a diagnostic color-flow imaging ultrasound beam (D-beam; frequency = 2.5 MHz; intensity = 0.20 W/cm2). A 15-min protocol, comprising four repeats of a sequence of 120-s T-beam activation followed by 30-s D-beam activation and then 5-min T-beam deactivation together with D-beam activation, was repeated four times over 60 min. After confirmation of neurologic deficits, the brains were removed and investigated histologically and immunohistochemically. Three skull samples were subjected to 494-kHz continuous waveform ultrasound, the transcranial intensity was measured and the mechanical index was calculated. None of the monkeys showed neurologic deficits after ultrasonication. The transskull ultrasound intensity rate was 48 ± 12%. The intracranial mechanical index value was 0.15. The novel system did not cause tissue damage in the primate brain and no cavitation effect was detected intracranially.

Prenatal Exposure to Diagnostic Ultrasound Impacts Blood-Brain Barrier Permeability in Rats

Feng-Yi Yang, Guan-Liang Lin, Shih-Cheng Horng, Ran-Chou Chen — 2012-03-19

Abstract: The central nervous system vasculature consists of a tightly sealed endothelium that forms the blood-brain barrier (BBB); these blood vessels are impermeable to large-molecular-size agents. The aim of this study was to determine the influence of prenatal ultrasound exposure on blood-brain barrier (BBB) integrity as measured by the permeation of Evans blue (EB) through the BBB during the postnatal development of the rat. Diagnostic levels of ultrasound (2.89 MHz, mechanical index = 1.1, acoustic output power = 70.5 mW) for 1 h and 2 h per day, for 9 consecutive days were used on Sprague-Dawley rats. Offspring were assessed postnatally on days 10, 17, 24 and 38. Our analysis of over 139 animals reveals that, when exposed to diagnostic levels of ultrasound during embryonic development, a statistically significant amount of EB extravasation into the cerebrum and cerebellum could be detected on postnatal day 10 but not later. In addition, small changes in pup body weight, cerebrum weight and cerebellum weight were observed after relatively prolonged ultrasound exposure on all postnatal days. Taken together, these results emphasize the need for further investigation of the effects of ultrasound exposure during the potentially vulnerable period of intense BBB development in the human fetus.

Experimental Research of RB94 Gene Transfection Into Retinoblastoma Cells Using Ultrasound-Targeted Microbubble Destruction

Min-Ming Zheng, Xi-Yuan Zhou, Li-Ping Wang, Zhi-Gang Wang — 2012-04-16

Abstract: The purpose of this study was to explore the transfection of the recombinant expression plasmid pEGFP-C1/RB94 into human retinoblastoma cells (HXO-Rb44) using ultrasound-targeted microbubble destruction (UTMD). pEGFP-C1/RB94 was transfected into HXO-Rb44 in vitro by UTMD, with liposome as the positive control. After 24 to 72 h, the expression of the reporter gene enhanced green fluorescent protein (EGFP) was observed using fluorescent microscopy and flow cytometry. The cell viability of HXO-Rb44 was measured by a MTT assay. The mRNA and proteins of RB94, caspase-3 and Bax were analyzed by reverse transcription polymerase chain reaction (RT-PCR) and Western blot. Moreover, the apoptosis rate and cell cycle progression of the cells were detected by flow cytometry. This study demonstrated that UTMD can enhance the transfection efficiency of RB94, which has an obvious impact on the inhibition of the growth process of retinoblastoma cells, suggesting that the combination of UTMD and RB94 compounds might be a useful tool for use in the gene therapy of retinoblastoma.

Effect of Albumin and Dextrose Concentration on Ultrasound and Microbubble Mediated Gene Transfection In Vivo

2012-04-16

Abstract: Ultrasound and microbubble mediated gene transfection has great potential for site-selective, safe gene delivery. Albumin-based microbubbles have shown the greatest transfection efficiency but have not been optimised specifically for this purpose. Additionally, few studies have highlighted desirable properties for transfection specific microbubbles. In this article, microbubbles were made with 2% or 5% (w/v) albumin and 20% or 40% (w/v) dextrose solutions, yielding four distinct bubble types. These were acoustically characterised and their efficiency in transfecting a luciferase plasmid (pGL4.13) into female, CD1 mice myocardia was measured. For either albumin concentration, increasing the dextrose concentration increased scattering, attenuation and resistance to ultrasound, resulting in significantly increased transfection. A significant interaction was noted between albumin and dextrose; 2% albumin bubbles made with 20% dextrose showed the least transfection but the most transfection with 40% dextrose. This trend was seen for both nonlinear scattering and attenuation behaviour but not for resistance to ultrasound or total scatter. We have determined that the attenuation behaviour is an important microbubble characteristic for effective gene transfection using ultrasound. Microbubble behaviour can also be simply controlled by altering the initial ingredients used during manufacture.

Relationship Between Plasmid Size and Shock Wave-Mediated Bacterial Transformation

Juan Campos-Guillén, Francisco Fernández, Xóchitl Pastrana, Achim M. Loske — 2012-04-16

Abstract: Bacterial transformation is a fundamental tool in molecular biology; nevertheless, there is still a lack of efficient methods for gene delivery. The use of shock waves has been proposed as an alternative. Recently, our group demonstrated that shock wave-induced transfer of deoxyribonucleic acid (DNA) into bacteria can be increased by enhancing acoustic cavitation; however, so far, little information exists about the effects of shock waves on DNA. The objective of this study was to identify the size regimes of plasmids (DNA molecules that are separate from the chromosomal DNA), which promote shock wave-induced transformation. The transformation efficiency of shock waves and the integrity of DNA were studied for six different plasmid sizes, using the parameters that led to the best results in our previous study.

Ultrasound-Microbubble Mediated Cavitation of Plant Cells: Effects on Morphology and Viability

Peng Qin, Lin Xu, Wenjing Zhong, Alfred C.H. Yu — 2012-04-16

Abstract: The interaction between ultrasound pulses and microbubbles is known to generate acoustic cavitation that may puncture biological cells. This work presents new experimental findings on the bioeffects of ultrasound-microbubble mediated cavitation in plant cells with emphasis on direct observations of morphological impact and analysis of viability trends in tobacco BY-2 cells that are widely studied in higher plant physiology. The tobacco cell suspensions were exposed to 1 MHz ultrasound pulses in the presence of 1% v/v microbubbles (10% duty cycle; 1 kHz pulse repetition frequency; 70 mm between probe and cells; 1-min exposure time). Few bioeffects were observed at low peak negative pressures (<0.4 MPa) where stable cavitation presumably occurred. In contrast, at 0.9 MPa peak negative pressure (with more inertial cavitation activities according to our passive cavitation detection results), random pores were found on tobacco cell wall (observed via scanning electron microscopy) and enhanced exogenous uptake into the cytoplasm was evident (noted in our fluorescein isothiocyanate dextran uptake analysis). Also, instant lysis was observed in 23.4% of cells (found using trypan blue staining) and programmed cell death was seen in 23.3% of population after 12 h (determined by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling [TUNEL]). These bioeffects generally correspond in trend with those for mammalian cells. This raises the possibility of developing ultrasound-microbubble mediated cavitation into a targeted gene transfection paradigm for plant cells and, conversely, adopting plant cells as experimental test-beds for sonoporation-based gene therapy in mammalian cells.

The Influence of Gas Saturation on Microbubble Stability

Helen Mulvana, Eleanor Stride, Meng-Xing Tang, Jo V. Hajnal, Robert J. Eckersley — 2012-04-04

Abstract: Accurate acoustic characterisation is an essential component of any experimental investigation concerning the use and development of microbubble contrast agents. It is of increasing importance as applications such as therapy and molecular and quantitative imaging are investigated. Such characterisation is generally conducted in the laboratory in the form of bulk acoustic studies or optical observation of single bubbles using high speed photography in a water tank containing “out-gassed” water. The approach is widely used in acoustics to prevent inaccurate measurements being made due to the presence of gas bubbles settling on instrumentation, however, the term is often used to cover a range of water preparation techniques and the final gas content of the water is not usually stated. This technical note demonstrates the influence of gas content on the stability of microbubble contrast agents and concludes that characterisation should always be conducted in equilibrated, gas-saturated water to ensure accurate and repeatable measurements are made.

Calendar

2012-06-01

Ultrasound in Medicine and Biology

Masthead

Editorial Advisory Board

Contents

Atherosclerotic Risk Stratification Strategy for Carotid Arteries Using Texture-Based Features

Different Patterns of Longitudinal Displacement of the Common Carotid Artery Wall in Healthy Humans Are Stable Over a Four-Month Period

Spontaneous Echo Contrast in Internal Jugular Veins: A Probable Indicator for Systemic Inflammation and a Prothrombotic State

A Pilot Study Evaluating Real-Time Shear Wave Ultrasound Elastography of Miscellaneous Non-Nodal Neck Masses in a Routine Head and Neck Ultrasound Clinic

Determination of the Augmentation Effects of Hyaluronic Acid on Different Heel Structures in Amputated Lower Limbs of Diabetic Patients Using Ultrasound Elastography

Correlation and Agreement Between Contrast-Enhanced Ultrasonography and Perfusion Computed Tomography for Assessment of Liver Metastases from Endocrine Tumors: Normalization Enhances Correlation

Phalangeal Quantitative Ultrasound Measurements in Chronic Hemodialysis Patients: A 4-Year Follow-Up

Using the Gradient of Human Cortical Bone Properties to Determine Age-Related Bone Changes Via Ultrasonic Guided Waves

Ultrasound Assessment of Transverse Carpal Ligament Thickness: A Validity and Reliability Study

Methodological Aspects of Functional Transcranial Doppler Sonography and Recommendations for Simultaneous EEG Recording

Effects of Active, Passive and Motor Imagery Paradigms on Cerebral and Peripheral Hemodynamics in Older Volunteers: A Functional TCD Study

A Practical Method for Ultrasonographically Monitoring the Day-to-Day Growth of Individual Ovarian Follicles in Women Undergoing Assisted Reproduction

The Role of Preterm Placental Calcification in High-Risk Pregnancy as a Predictor of Poor Uteroplacental Blood Flow and Adverse Pregnancy Outcome

Contrast Ultrasound Imaging for Identification of Early Responder Tumor Models to Anti-Angiogenic Therapy

Early Estimation of Left Ventricular Systolic Pressure and Prediction of Successful Aortic Constriction in a Mouse Model of Pressure Overload by Ultrasound Biomicroscopy

Ultrasound Safety with Midfrequency Transcranial Sonothrombolysis: Preliminary Study on Normal Macaca Monkey Brain

Prenatal Exposure to Diagnostic Ultrasound Impacts Blood-Brain Barrier Permeability in Rats

Experimental Research of RB94 Gene Transfection Into Retinoblastoma Cells Using Ultrasound-Targeted Microbubble Destruction

Effect of Albumin and Dextrose Concentration on Ultrasound and Microbubble Mediated Gene Transfection In Vivo

Relationship Between Plasmid Size and Shock Wave-Mediated Bacterial Transformation

Ultrasound-Microbubble Mediated Cavitation of Plant Cells: Effects on Morphology and Viability

The Influence of Gas Saturation on Microbubble Stability

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