Ultrasound in Medicine & Biology

Evidence of acoustic cavitation was identified in the form of transient echoes in ultrasound B-scan images of patients receiving extracorporeal shock-wave lithotripsy treatment on a Storz Modulith SL20. This lithotripter generates 10-microseconds duration pulses with a centre frequency of 0.2 MHz at a pulse repetition frequency of 1 Hz. The visual appearance of B-scan images was examined in a total of 30 patients and a quantitative analysis of echogenicity changes was carried out in six cases involving lithotripsy treatment of stones in the renal pelvis. In these patients new echoes were identified in images unaffected by movement artefacts and were found to occur in perinephric fat and adjacent muscle and kidney tissue at positions close to the axis of the shock-wave field between 1 and 2 cm in advance of the indicated beam focus of the lithotripter. The echogenicity within each region increased significantly above the background level when the output of the lithotripter was increased above a threshold value. The acoustic pressures corresponding to this threshold were measured in water using a calibrated PVDF membrane hydrophone. After correction for attenuation in tissue the cavitation thresholds, in terms of the temporal peak negative pressure, are found to lie between 1.5 MPa and 3.5 MPa in all six cases. Interpretation of the measured values in terms of the likely threshold at the higher frequencies used in diagnostic ultrasound is considered using a theoretical model.

Frequency responses of different PVDF polymer hydrophones, including membrane and needle designs, were measured and are presented in terms of end-of-cable voltage sensitivity vs. frequency over a wide, 4.5-octave bandwidth ranging from 0.25-2.5 MHz. The experimental data indicate that the membrane PVDF hydrophones can exhibit uniform, to within +/- 0.75 dB, responses. However, a widely used bilaminar membrane hydrophone-preamplifier combination may display sensitivity variations of +/- 2 dB. Also, even well-designed needle-type hydrophones show a more distinct sensitivity variation below 1 MHz that is on the order of 3-4 dB. The overall uncertainty of the calibration technique was estimated to be better than +/- 2 dB in the frequency range considered. The technique, which uses a combination of swept frequency chirp and reciprocity so that both the relative and absolute plots of sensitivity vs. frequency can be obtained, is also briefly described. The results of this work are important to implement procedures for adequate determination of the mechanical index of ultrasound (US) imaging devices. Mechanical index is widely accepted as a predictor of potential bioeffects associated with cavitation phenomena. Also, absolute calibration data are essential in development of therapeutic procedures based on the use of high-intensity focused ultrasound (HIFU), and in characterization of conventional therapeutic US applicators operating at frequencies below 1 MHz.

Leaves of the aquatic plant Elodea were sonicated continuously for 100 sec at ten frequencies in the range 0.45–10 MHz. Cell death thresholds were determined for three cell populations in the leaves for each frequency. The intensity thresholds were strongly dependent on frequency, and the minimum threshold for each population generally occurred near the expected resonance frequency of the gas bodies associated with each population. The thresholds were as low as 75 mW/cm2 at 0.65 MHz and 180 mW/cm2 at 5 MHz.

Free radicals, detected as light emissions (sonoluminescence), can be produced in both simple aqueous systems and agar gels by irradiation with 0.75 MHz continuous-wave (CW) ultrasound using acoustic pressures as low as 200 KPa. Although the acoustic pressures necessary for free radical formation in tap water gels (200 KPa), are considerably higher than those required for the formation of macroscopic visible bubbles (26 KPa), the sonoluminescence threshold (0.5 W/cm-2 SATA equivalent) falls at the lower end of the intensity range (0.5-3 W/cm-2) commonly used by ultrasonic physiotherapy equipment. In respect of the overall features of cavitation processes, agar gels appear to be suitable simple systems in which to model cavitation in vivo. However, cavitation processes leading to sonoluminescence are themselves complex as illustrated by the findings that small changes in ionic composition or pH have a significant effect on both the acoustic pressure threshold and the extent of sonoluminescence above this threshold.

Transparent phantoms, made of bovine hide gelatine, have been constructed in order to study the consequences of the occurrence of cavitation in tissues. Gas pockets of about resonant size, physically introduced into the gel, lead to a mean temperature rise of 41 +/- 15 degrees C in 1 min, when the gel of concentration 11.4% (w/v) is sonicated in the continuous-wave (cw) mode at 1 W cm-2 (spatial average) and 0.75 MHz. Nyborg (1965) has shown that gas bubbles in a sound field can act as acoustic amplifiers and the observations reported here may be connected with this feature. A layer of gelatine foam was also used to introduce gas into the gel and in this case the temperature rise was about 12 +/- 5 degrees C under similar conditions. Without gaseous inclusions, the mean temperature rise in gel in 1 min was 2.3 +/- 0.2 degree C. At a gel/air interface, the rise per unit intensity per minute was 4.4 degrees C. It is concluded that in clinical situations, cavitation (or degassing due to supersaturation), when it does occur, is likely to be an undesirable consequence of ultrasound treatment. This finding, of large temperature rises in proximity to gas bubbles, is in broad agreement with the report by Hynynen (1991) of an excess temperature elevation of 60 degrees C in dogs' muscle in vivo during a 1 s pulse at 250 W cm-2 and 0.56 MHz. Other studies, by ter Haar and Daniels (1981) and Daniels and ter Haar (1986), of sonicated animal tissues in vivo, have found thresholds for bubble inception but no consequent temperature rise greater than 0.3 degrees C was observed.

It has been shown that low-intensity pulsed ultrasound (US) accelerates fracture healing in animal models and in clinical studies. However, the mechanism by which US accelerates fracture healing remains unclear. Systemic factors and several growth factors, such as platelet-derived growth factor (PDGF), are thought to be involved in the process of fracture healing. In the present study, we examined the effects of US and 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] on growth factor secretion in a co-culture system of human osteoblastic cells (SaOS-2) and endothelial cells (HUVEC). US was applied to cultured cells for 20 min daily for four consecutive days. US treatment increased the PDGF-AB level in the conditioned media. 1,25-(OH)2D3 (1 x 10(-8) M) also enhanced PDGF-AB secretion. The secretion of PDGF-AB was synergistically increased by the combination of US and 1,25-(OH)2D3. These results suggest that the stimulation of growth factor secretion from cells by US and 1,25-(OH)2D3 treatment may be involved in the acceleration of fracture healing.

Anesthetized hairless mice were exposed to continuous or pulsed 1.09-MHz ultrasound with or without prior injection of a gas-body-based ultrasound contrast agent. Albunex at a dose of 10 mL/kg increased the production of intestinal hyperemia, petechia and hemorrhages by continuous ultrasound. For pulsed ultrasound, with 10 micros pulses and 0.01 duty cycle, petechiae were produced for exposures as low as 1 MPa spatial peak pressure amplitude with added gas bodies. The enhancement of petechiae production was robust for pulsed exposure; for example, at 2.8 MPa, an average of 227 petechiae was obtained with added gas bodies, which was 30 times more than without the agent. The production of petechia was roughly proportional to the dosage of Albunex for pulsed exposure. Results did not appear to be strongly dependent on pulsing parameters, but long bursts (0.1 s) were somewhat more effective than pulses (10 micros). The observed vascular bioeffects appeared to involve both thermal and nonthermal mechanisms for continuous exposure, but to result primarily from gas-body activation for pulsed exposure.

Cultured mouse L cells attached to circular plates were exposed to continuous wave 1.2 MHz ultrasound and the amount of 14C-thymidine (TdR) incorporated into cellular DNA was measured. Enhanced 14C-TdR incorporation per cell in attached cells was observed at ultrasonic intensities above 0.5, ISATA (0.8, ISPTA) W/cm2, although the total amount of incorporated 14C-TdR per sample decreased with increasing exposure energy at intensities above 1.5 (2.8) W/cm2. The presence of cavitation was evidenced by three kinds of physicochemical dosimeters; the liberation of iodine from KI-starch solution, a decrease in DNA molecular weight and sucrose hydrolysis. Collapse cavitation was detected at intensities above 1.5 (2.8) W/cm2 and stable cavitation was observed at 0.5 (0.8) W/cm2. These results suggest that the change in DNA synthesis of irradiated mouse L cells takes place independently of collapse cavitation, and may be due to stable cavitation.

Human erythrocytes and Optison contrast agent have been exposed to ultrasound, both alone and in combination, in a single-half-wavelength chamber driven at its resonance frequency (fo) of 1.5 MHz. Cell movements were recorded by video microscopy at speeds up to 500 frames/s. The hypothesis that cells near a standing wave pressure node might be stressed by the microbubble products of sonicated contrast agent was examined. In the absence of contrast agent, cells moved rapidly to form an aggregate in the standing wave pressure node plane. First subharmonic and second harmonic emissions were detected from cell-contrast agent suspensions immediately on exposure to a threshold peak pressure amplitude of 0.98 MPa. Emissions at 3fo/2 occurred at 1.47 MPa, whereas white noise and lower-order subharmonic emissions coincided with the appearance of visible bubbles at a threshold of approximately 1.96 MPa. Cells exposed together with contrast agent at a pressure of 0.98 MPa precessed very rapidly about the pressure node plane. This behavior was discussed in the context of a recent analysis predicting that, in contrast to the situation for lower-pressure amplitudes, subresonant size bubbles translate about pressure node plane if the driving pressure amplitude is sufficiently high. Many precessing erythrocytes were clearly spiculated and this morphology persisted after the cells had left the area of precession. Hemoglobin release was significant under conditions inducing precession with first subharmonic and first harmonic emissions. Protein release increased discontinuously near the pressure thresholds, where more complex categories of frequency emission were detected. The potential of this system, which induces erythrocyte morphology changes and some protein release at the first emission threshold, to provide some control on the membrane-permeabilizing stress experienced by cells in a cavitation field is discussed.

Uptake of fluorescein isothiocynate-dextran (FITC-dextran) by Chinese hamster ovary cells was studied after exposure to ultrasonic standing wave (USW) in presence of Optison, an ultrasound contrast agent. Confluent Chinese hamster ovary cells were harvested and suspended in phosphate-buffered saline + 0.1% bovine serum albumin containing FITC-dextran (10, 40, and 500 kDa) at 10 microM final concentration. The suspension was seeded with contrast agent (75 microL/mL) and exposed to a 1.5 MHz USW system at acoustic pressures ranging from 0.98 to 4.2 MPa. Macromolecular uptake was assessed by fluorescent microscopy and quantified by flow cytometry 10 min after exposure. FITC-dextran positive cells, as assessed by flow cytometry, were 1 +/- 0.05% and 2.58 +/- 0.27% for acoustic pressures of 1.96 and 4.2 MPa, respectively (p = 0.006). Fluorescent microscopy indicated a degree of macromolecular loading at 0.98 MPa with 46% of peripherally FITC-dextran- and/or propidium iodide-stained cells coincident with the appearance of significant frequency (f0/2 and 2 f0) emission signals. At higher pressures, high macromolecular loading with 6% peripherally stained cells at 1.96 MPa was associated with lower order emission signals and white noise. The study conclusively demonstrates macromolecular loading in an USW, a significantly higher macromolecular loading at higher pressures and indicates potential of emission signals for a feedback loop to control the acoustic power outputs and fine-tune the biologic effects associated with sonoporation.

The purpose of this study was to investigate the diagnostic value of color Doppler twinkling artifacts (CDTAs) in the evaluation of gallbladder adenomyomatosis with differently colored Doppler frequencies. An ultrasound was performed by an experienced radiologist in 17 patients with typical gallbladder adenomyomatosis. Two abdominal radiologists retrospectively evaluated the anatomic locations, the intensity of 69 CDTAs on 1.8 MHz and 4.0 MHz Doppler frequencies, and the intensity of the corresponding comet-tail artifacts. Statistical analysis was performed using the Friedman and Kruskal-Wallis test. The intensity of the CDTAs was significantly greater than that of the comet-tail artifacts, regardless of the color Doppler frequency and anatomic location (p < 0.001). The intensity of the CDTAs on 1.8 MHz was significantly higher than that on 4.0 MHz color Doppler frequency (p < 0.05). In conclusion, CDTAs may be useful in recognizing gallbladder adenomyomatosis, and 1.8 MHz color Doppler frequency is more highly recommended than 4.0 MHz for the visualization of CDTAs.

Clinical studies of acute stroke patients have shown that the use of high frequency, low energy transcranial "diagnostic" ultrasound (US) enhances thrombolysis (sonothrombolysis). In contrast, a previous in vitro study using a clot preparation with coagulation induced by recalcification failed to reproduce an effect of "diagnostic" transcranial US on thrombolysis. We sought to evaluate this contradiction in an in vitro model with modified clot preparation. The efficacy of 1.8-MHz pulsed-wave (PW) ultrasound (US) emitted by a commercial probe on thrombolysis was tested. Whole blood clots from 0.5-mL venous blood samples were insonated for 1 h through a human temporal bone, using 1.8-MHz PW US emitted by a diagnostic device. The experiment was performed with or without recombinant tissue-type plasminogen activator (rt-PA) at a concentration of 10 μg/mL. Thrombolysis was measured by means of clot weight loss after 1 h of insonation. A reduction in thrombus weight occurred when US was used in combination with rt-PA, compared with rt-PA alone (78.7% ± 2.1% versus 70.8% ± 4.1%, p ≤ 0.0001). Repetition of the experiment produced identical results (76.9% ± 2.5%, compared with control, p = 0.001). Even without rt-PA, US was effective (41.0% ± 1.7% versus 36.7% ± 3.7%, p = 0.04). The results of this in vitro study support the clinical observation that diagnostic transcranial US, with or without rt-PA, enhances thrombolysis. (E-mail: [email protected] /* */).

The study objective was to gain insight into ultrasound-induced, sub-lytic cell surface modifications. Two primary hypotheses were tested by flow cytometric methods; viz., sonication will: 1. remove all or part of a specific cell surface marker in lymphocytes surviving insonation, and 2. induce transient pores in the cell membranes of some surviving cells. RPMI 1788 human lymphocytes were exposed in vitro to 1-MHz, continuous-wave ultrasound (approximately 8 W/cm2 ISP) for 30 s, which lysed approximately 50% of the cells. Insonation: 1. altered cell morphology, increasing the population of cells of reduced size but high structure (designated as population R2), many of which were nonviable, and diminishing the population of cells of large size and high structure (designated as population R1), most of which were viable, 2. diminished the fluorescence signal from the pan B lymphocyte marker CD19 in populations R1 and R2 to equivalent extents, and 3. increased by approximately 7-fold the number of transiently permeabilized cells in R1, as evidenced by simultaneous uptake of propidium iodide and fluorescein diacetate. The results indicate that ultrasound-induced CD19 removal from R1 cells can occur without accompanying gross membrane loss. The cell morphology/mortality shifts indicate that the ultrasound-induced morphological change is associated with lethal membrane poration, suggesting that the diminished CD19 fluorescence signal from insonated R2 cells arises partly by simultaneous loss of membrane fragments, CD19 and cytoplasm.

The feasibility of blood-brain barrier (BBB) opening in the hippocampus of wild-type mice using focused ultrasound (FUS) through the intact skull and skin was investigated. Needle hydrophone measurements through ex vivo skulls revealed minimal attenuation (∼18% of the pressure amplitude), a well-focused beam pattern and minute focus displacement through the parietal bone. In experiments in vivo, the brains of three mice were sonicated transcranially. Pulsed ultrasound sonications at 1.5 MHz and acoustic pressures ranging from 0.8 to 2.7 MPa were used at 20% duty cycle. Before sonication, a bolus of 10 μL of an ultrasound contrast agents (Optison) was injected intravenously. Contrast-enhanced high-resolution magnetic resonance imaging (9.4 T) revealed BBB opening and allowed for the monitoring of the slow permeation of gadolinium in the hippocampus. The region of the brain where BBB opening occurred increased with the pressure amplitude. These findings thus demonstrated the feasibility of locally opening the BBB in mice using FUS through intact skull and skin and serve as the first step in determining and assessing feasibility of drug delivery to specific regions in the mouse brain using FUS. (E-mail: [email protected] /* */).

Fetal growth restriction is one of the greatest risk factors for stillbirth. This pilot cohort study examined whether rapid placental volume (PlaV) calculation at 11 to 13 + 6 weeks can predict the small for gestational age (cSGA) baby. Women with singleton pregnancies were recruited (N = 145), a static three-dimensional (3-D) volume was captured, and the placental volume was computed using a semi-automated technique. Regression analysis explored the relationships between customized birth weight, placental quotient (PQ), standardized placental volume (sPlaV), and other predictors of SGA (including pregnancy-associated protein and uterine artery pulsatility index (PI). The results were examined using receiver-operating characteristic (ROC) curve analysis in the total population and then in the 2 subgroups whose members were classified as low risk or high risk at booking. Both PQ and sPlaV were significantly different for cSGA pregnancies compared to appropriate for gestational age (AGA) babies (p = 0.003 and <0.001, respectively) but only sPlaV was normally distributed. The independent predictors of birth weight (sPlaV, pregnancy associated protein, and nuchal translucency) were combined to produce a predictive model for cSGA. The ROC curves for prediction of cSGA in all 143 women gave areas under the curve of 0.77 (0.66 to 0.87) for sPlaV alone and 0.80 (0.69 to 0.92) for the combined model. When this was applied to the low-risk group, the areas under the curve were 0.82 (0.69 to 0.94) and 0.84 (0.72 to 0.95), respectively. For the high-risk group, the areas under the curve were 0.67 (0.45 to 0.86) for sPlaV alone and 0.76 (0.55 to 0.96) for the combined model. The use of this rapid-image analysis technique and dimensionless index to correct for gestation brings the possibility of an early combined screening test for the cSGA baby a step closer.

This study was designed to establish a fetal spine nomogram for age 11 through 14 weeks of gestation and to document relations among fetal spine length, distance and angle. These parameters were prospectively measured during the first trimester of singleton pregnancies, along with nuchal translucency, over a 3-year period. A total of 430 fetuses were included in the study. The regression equations among fetal spine parameters and gestational age were as follows: Spine length (mm) = 1.116 × gestational age (days) - 59.169; spine distance (mm) = 1.079 × gestational age (days) - 59.038; head-spine angle = 0.740 × gestational age (days) + 4.735; spine length:spine distance ratio = -0.002 × gestational age (days) + 1.234. Prenatal age-specific reference intervals for fetal spine biometry between 11 and 14 weeks of gestation may assist in evaluation of fetuses investigated for genetic abnormalities that can be expressed by deviation in spine length, distance, or angle. (E-mail: [email protected] /* */).

Targeted microbubble imaging at ultrasound frequencies above 5 MHz has applications in both a preclinical context for a range of disease processes and clinically for the assessment of atherosclerosis and superficial tumors. Although the feasibility of ultrasound molecular imaging has been well demonstrated for a range of target molecules, little work has examined the effects of binding on microbubble oscillations, which is of potential relevance to improving the sensitivity, specificity, and quantification of bound-bubble detection. In this study we investigated the influence of binding on the subharmonic response of bubbles at transmit frequencies of 11 and 25 MHz. Individual bubbles were situated adjacent to a boundary in either a bound or an unbound state, optically sized and acoustically interrogated with pressures ranging from 0.02 to 1.2 MPa. At 11 MHz, unbound bubbles (n = 53) were found to have strong subharmonic activity for sizes between 2.4 and 2.6 μm, whereas bound bubbles (n = 50) were most active from 2.6 to 3.0 μm. Destruction thresholds were found to be lower for bound bubbles. At 25 MHz, bound-bubble (n = 57) activity was found to peak at 1.9 μm as compared to 2.1 μm in the unbound cases (n = 53), with a 20% increase in amplitude. Comparison with simulations indicates that both unbound and bound bubbles undergo compression-only behavior at 11 MHz, and expansion-dominated behavior at 25 MHz. Subharmonic emissions elicited from 0 radian transmit pulses were found to be π/2 radians out of phase with those elicited from a π radian transmit pulse, suggesting inefficient subharmonic preservation from pulse inversion schemes. With the appropriate postprocessed phase correction, an increase in the subharmonic amplitude of up to 60% was shown, depending on the bubble size and transmit frequency.

Supersonic shear imaging (SSI) has recently been demonstrated to be a repeatable and reproducible transient bidimensional elastography technique. We report a prospective clinical evaluation of the performances of SSI for liver fibrosis evaluation in 113 patients with hepatitis C virus (HCV) and a comparison with FibroScan (FS). Liver elasticity values using SSI and FS ranged from 4.50 kPa to 33.96 kPa and from 2.60 kPa to 46.50 kPa, respectively. Analysis of variance (ANOVA) shows a good agreement between fibrosis staging and elasticity assessment using SSI and FS (p < 10(-5)). The areas under receiver operating characteristic (ROC) curves for elasticity values assessed from SSI were 0.948, 0.962 and 0.968 for patients with predicted fibrosis levels F ≥ 2, F ≥ 3 and F = 4, respectively. These values are compared with FS area under the receiver operating characteristic curve (AUROC) of 0.846, 0.857 and 0.940, respectively. This comparison between ROC curves is particularly significant for mild and intermediate fibrosis levels. SSI appears to be a fast, simple and reliable method for noninvasive liver fibrosis evaluation.

Papillary thyroid microcarcinoma (PTMC) is a malignant thyroid tumor of less than 1 cm in size. Ultrasound (US) is the preferred imaging modality for PTMC. This study retrospectively evaluated the US results from 113 consecutive cases of PTMC with 127 nodules and correlated the results with the histopathologic findings. The results showed none of the PTMC nodules had a cystic element. Half of the PTMC nodules had a well-defined boundary and the remaining half had an ill-defined boundary. A percent (6.3%) of the nodules had a halo sign. Microcalcification was present in approximately half of the PTMC nodules. The cancerous tissue with a papillary structure was hypoechogenic and the amount of fibrous stroma determined whether the nodule echogenicity was heterogeneous or homogeneous. Heterogeneous echogenicity was associated with a fibrous stroma proportion of >20%. Only PTMC nodules with predominantly follicular structures containing a large proportion of colloid demonstrated isoechogenicity. Well-defined boundaries on US were associated with well-defined histologic margins, with or without the presence of an intact fibrous pseudo-capsule. A halo sign with a well-defined boundary detected by US was associated with the presence of an intact fibrous pseudo-capsule. Half of the PTMC nodules with ill-defined boundaries exhibited infiltration into the surrounding thyroid tissue, while the remaining half of the PTMC nodules with ill-defined boundaries on US presented irregular nodule margins by histology, rather than nodule infiltration. Psammoma bodies detected at a frequency ≥5 per ×200 microscopic field of view were detectable on US as microcalcifications.

This selective review of the biological effects of ultrasound presents a synopsis of our current understanding of how cells insonated in vitro are affected by inertial cavitation from the standpoint of physical and chemical mechanisms. The focus of this review is on the physical and chemical mechanisms of action of inertial cavitation which appear to be effective in causing biological effects. There are several fundamental conditions which must be satisfied before cavitation-related bioeffects may arise. First, bubbles must be created and then brought into proximity to cells. Exposure methods are critical in this regard, and simple procedures such as rotation of a vessel containing the cells during exposure can drastically alter the results. Second, once association is achieved between bubbles and cells, the former must interact with the latter to produce a bioeffect. It is not certain that the inertial event is the prime mechanism by which cells are lysed; there is evidence that the turbulence associated with bubble translation may cause lysis. Additionally, there appear to be chemical and other physical mechanisms by which inertial cavitation may affect cells; these include the generation of biologically effective sonochemicals and the apparent emission of ultraviolet (UV) and soft X-rays. The evidence for inertial cavitation occurring within cells is critically reviewed.

A retrospective study of 117 normal and pathologic pancreatic ducts by endoscopic retrograde cholangiopancreatography (ERCP), with ultrasonic correlation in 80 cases, confirmed the value of ultrasound in the diagnosis of ductal dilatation. The specificity of ultrasound is good: the ultrasonic discovery of a dilatation constitutes a relevant feature. Sensitivity is however poor, particularly in moderate and localized dilatations: a suggestive clinical picture requires ERCP even if sonography is in favor of a normal pancreatic duct. Correlative measurements show discrepancies, with higher ERCP values in normal subjects. The average ERCP diameter in the corporeal ductal segment is 2.6 mm. Until correlative results arising from a prospective study are available, the ultrasonic diagnosis of ductal dilatation must take into account the high normal values demonstrated by ERCP.

It has been known for some time that the application of ultrasound can enhance the efficacy of thrombolytic medications such as recombinant tissue plasminogen activator (rt-PA). Potential clinical applications of this ultrasound-enhanced thrombolysis (UET) include the treatment of myocardial infarction, acute ischemic stroke, deep venous thrombosis and other thrombotic disorders. It may be possible to reduce the dose of rt-PA while maintaining lytic efficacy; however there is little data on the rt-PA concentration dependence of UET. In this work, the rt-PA concentration dependence of clot lysis resulting from 120 kHz UET exposure was measured in an in vitro human clot model. Clots were exposed to rt-PA for 30 min, with (UET treated) or without 120 kHz ultrasound (rt-PA treated) at 37°C, and the clot width measured as a function of time. The rt-PA concentration ranged from 0-10 μg/mL. The initial lytic rate for the UET-treated group was greater than that of the rt-PA group at almost all rt-PA concentrations, and exhibited a maximum over concentration values of 1-3 μg/mL. (E-mail: [email protected] /* */).

Primary Fallopian tube carcinoma is rarely diagnosed preoperatively. We present the case of a 69-year-old woman with primary tubal carcinoma, which was diagnosed preoperatively on the basis of the cytological finding, characteristic features on transvaginal sonography, transvaginal color flow imaging and elevated CA-125. Transvaginal color Doppler imaging demonstrated the tumor revealed areas of neovascularization with characteristic low impedance (resistance index, 0.34 and pulsatility index, 0.62). Pathohistologic confirmation of the clearcell carcinoma has been done.

A total of 1175 umbilical venous Doppler flow velocity waveforms were acquired from 449 normal pregnant women whose fetuses were delivered at term without neonatal asphyxia or anomalies. Arterial and venous flow velocity waveforms were acquired from a free loop of the umbilical cord. The incidence of umbilical venous pulsation decreased from 30.4% at 13-14 weeks of gestation to 14.8% at 21-22 weeks of gestation. After 23 weeks, this incidence was settled within 5.0-7.8%. There was no difference between the umbilical arterial resistance index of the fetuses with venous pulsation and without pulsation before 22 weeks. But the resistance index was lower in the pulsatile fetuses than in the nonpulsatile fetuses after 23 weeks of gestation. The origin of venous pulsations before early second trimester was suspected to be different from that after late second trimester.

Abdominal ultrasonographic (US) screening of 219,640 persons has been performed in the past 13 y, and 723 (0.33%) cases of malignant neoplasm were detected. Renal cell carcinoma (RCC) was detected in 192 cases (0.09% of the examinees). In almost all cases of RCC, no symptoms were evident and no abnormalities were detected in the blood chemistry tests or urinalyses. A total of 189 cases (98%) were resected curatively, and 38% of the tumors were less than 25 mm in size (T1). With respect to pTNM classification, 35% were pT1 and 52% were pT2. No metastasis to the lymph nodes or other organs was found in any case. The cumulative survival rate for cases resected was 97% at 5 y, and 95% at 10 y. Regarding US features of RCC, the internal echo pattern of half of T1 tumors showed homogeneous and hyperechoic, and became heterogeneous as they grew. Other notable US findings in cases of RCC were marginal hypoechoic zone (29%), anechoic component in the tumor (23%), and protrusion from the kidney (85%, 71% of the T1 tumors). US screening is useful for detection of RCC in the early stage. However, to detect small tumors, it is very important to know well the US features of RCC. For cost-effectiveness analysis, it is more effective to examine, not only the kidney, but other abdominal organs. It is expected that many other abdominal cancers, such as hepatocellular carcinoma, gallbladder cancer, pancreatic cancer, and so on, could be found in the early stage by broad implementation of US screening.