Variable ultrasound echogenicity in flowing blood.

Real-time ultrasound imaging of large abdominal veins revealed bloodstream echogenicity of variable intensity. This variability is largely due to the entrance and persistance of tributary blood currents that show different echogenicity. Red cell aggregation is probably an important cause of bloodstream echoes and their variable intensity.

Ultrasonic detection of red cell aggregation immediately preceding blood clotting.

High-resolution ultrasonic imaging of circulating blood was used to study the relation between red cell aggregation and blood clotting in vitro. A reversible increase in echogenicity produced by red cell aggregation occurred in moving heparinized blood as shear rate was decreased. We induced clotting of the heparinized blood by administration of protamine. At both low (1.6 sec-1) and moderate (22.6 sec-1) mean shear rates, transient homogenous increased echogenicity indicative of red cell aggregation preceded blood clotting. In separate experiments, we established that protamine can cause increased echogenicity due to red cell aggregation which can be reversed by adding heparin to circulating suspended red cells in the absence of clotting factors. Presumably, these effects of protamine and heparin are due to electrostatic bonding involving red cell surfaces. We conclude from these studies that red cell aggregation precedes clotting of heparinized blood by protamine at low and moderate shear rates.

Risk assessment of pulmonary embolism by multivariate analysis.

A prospective study of 6,527 hospitalized patients was performed to evaluate the effectiveness of multivariate analysis of risk factors to correctly designate risk for pulmonary embolism. History of previous pulmonary embolism was the single most important factor. In patients without prior history, five factors emerged: inactivity, congestive heart failure, Doppler ultrasound evidence of deep-vein occlusion, female sex, and black race. Used together, these factors permitted a discrimination of risk such that 68.7% of pulmonary embolization was found to occur in 32.2% of the population designated as showing increased risk. Multivariate analysis of clinical factors improved assessment of risk, compared to the use of lower extremity findings alone, and proved to be useful in identifying individuals at increased risk for pulmonary embolism.

Role of red cells in preventing the growth of platelet aggregation.

Using high-resolution real-time two-dimensional ultrasound, we have investigated the role of red cells in the growth of already established platelet aggregates under controlled flow conditions. Platelet rich plasma (PRP) was circulated in vitro in horizontally and vertically arranged tubing at mean shear rate ranging from 60 to 0 sec-1, and adenosine diphosphate (ADP) was used to induce platelet aggregation. ADP-induced platelet aggregates grew in size and tended to sediment as shear rate decreased, in particular, below 10 sec-1. At 0 sec-1 (stasis), large clusters of platelet aggregates formed. The addition of washed red cells to produce a hematocrit of only 2% significantly interfered with the growth and sedimentation of platelet aggregates as shear rate was reduced. Formaldehyde-hardened erythrocytes had a similar effect in preventing the growth of platelet aggregates, suggesting that mechanical collision of red cells with platelet aggregates may be the cause of growth inhibition. Therefore, the thrombotic process may be enhanced in red cell poor zones in circulation resulting from flow disturbances associated with vascular stenosis or within artificial organs and extracorporeal systems. The present study also suggested that red cell free PRP should be carefully administered therapeutically.

Experimental assessment of spectrum analysis of ultrasonic echoes as a method for estimating scatterer properties.

In vitro experiments using weak scatterers ranging in size from mean longest diameter of 26.9 to 83.0 microns were performed to test the validity of theoretical predictions for scatterer size and concentration derived from normalized power spectrum parameters of ultrasonic backscatterer echoes. Scatterers consisting of cell clusters were suspended in collagen gel and scanned by a 10 MHz transducer system. Optical measurements validated theoretical predictions that (1) slope value is a function solely of scatterer size; (2) intercept value is a function of scatterer size and concentration; and (3) midband fit value increases as scatterer concentration increases, and, to a lesser extent, as size increases. These results were obtained under relatively ideal conditions of minimal attenuation and scatterer spacing (not closer than two scatterer diameters) and were consistent with the assumptions underlying the scattering theory.

Determination of carotid plaque risk by ultrasonic tissue characterization.

This in vitro study investigated the ability of ultrasonic tissue characterization (UTC) to discriminate between plaques from asymptomatic and symptomatic patients and to compare UTC findings with quantitative measurements of plaque morphology. A total of 34 plaque specimens removed at carotid endarterectomy were scanned transversely at intervals of 1 mm, and compared to tissue cross-sections examined by optical microscopy employing computer-assisted planimetry. UTC was performed by spectral analysis of backscattered radiofrequency signals. The slope, intercept and total power parameters of the spectrum were evaluated. Discriminant analysis was used to compare the ability of the UTC spectral parameters and morphological constituents to correctly classify plaques according to their symptom group membership. UTC correctly classified 88.2% of the plaques. Thrombus was present in 93.9% of the plaques, and there was little difference in the morphological constituents of plaques from asymptomatic and symptomatic patients. Morphological constituents correctly classified 60.7% of the plaques. We conclude, in this preliminary study, that UTC can discriminate between carotid plaques from asymptomatic and symptomatic patients with moderate accuracy, despite a similarity in their morphological composition. UTC discrimination is not related to differences in the type or amount of morphological constituents in the plaques.

Relation of in vivo blood flow to ultrasound echogenicity.

The mechanism of echogenicity of flowing blood during real-time ultrasonography was investigated experimentally in vivo by scanning venous and arterial blood and venous blood subjected to varying degrees of obstruction. Luminal echoes were more intense in flowing blood of the vena cava than in aortic blood of dogs. Vena cava and portal echoes increased in intensity as flow was decreased progressively by obstruction. We believe that an important cause of echogenicity of flowing blood is red cell aggregation which is greatest at low shear rates (low flow velocity). Echogenicity decreases with increase in shear rate (higher flow velocity) which causes red cell disaggregation.

The effects of temperature on blood flow ultrasonic echogenicity in vitro.

An explanation of the mechanism of ultrasonic echogenicity in flowing blood is proposed based upon an in vitro study that indicates a causal relation between red cell aggregation and these echoes. Echogenicity was measured in vitro at 37 degrees, 24 degrees, and 0 degree C as blood flow shear rates were varied. Echogenicity increased at higher temperatures and lower shear rates. The directions of changes in blood echogenicity exactly paralleled previously known changes in red cell aggregation resulting from changes in temperature. The authors consider this to be further evidence that red cell aggregation is an important cause of low-intensity echoes observed in clinical ultrasonography of the heart and circulation.

Experimental assessment of imaging variables associated with operative ultrasonic and radiographic cholangiography.

The comparative accuracies of operative ultrasonic and radiographic cholangiography to detect biliary calculi 1 mm in diameter inside tubes of different calibers were assessed. One hundred eighty tubes were prepared to provide ten tubes each for the following variables: three sizes of tubes (6, 13, 20 mm), three concentrations of contrast material (15, 30, 60 per cent), and presence or absence of calculi. Real-time B-mode ultrasound scans with a single gain and time gain compensation (TGC) setting were performed and contrast radiographs were also made at a single optimal exposure. Sixty ultrasonic and 180 radiographic examinations were studied. All ultrasonic interpretations were correct regardless of size of tube. Under optimal conditions, radiographic interpretations were also correct. However, whereas a single gain and TGC setting was applicable for all ultrasound examinations, variable contrast concentrations were required for the best radiographic imaging. Optimal radiographic contrast concentrations differed with tube diameters. The authors conclude that both ultrasonic and radiographic contrast imaging are highly accurate for the detection of small biliary calculi. However, contrast radiography requires stricter optimization of variables needed to provide the high accuracy. Thus, operative ultrasonography may be a more practical and reliable diagnostic procedure because of high sensitivity and greater ease of performance and interpretation.

Critical factors in the image clarity of operative cholangiography.

To evaluate image clarity in operative cholangiography with changing radiographic variables, in vitro experiments were performed in which 1-mm radiographically nonopaque biliary calculi in tubes were examined. Variables changed in these studies were tube caliber (6, 13 and 20 mm), contrast concentration (15, 30, and 60%), X-ray exposures (1, 2, 4, 8, 16, 32, 64, and 128 mAs) and location of calculi (central or peripheral). Sensitivity for the detection of calculi and the clarity of contrast radiographic images depended upon these variables. Reduced contrast concentration or increased radiographic exposure were needed for large caliber tubes. Central small calculi required more exposure than peripheral calculi. Practical inferences from these studies can be summarized as guidelines for performing operative cholangiography: (1) Surgeons should become aware of exposure settings used on the radiographic equipment in the operating room. In particular, the milliampere-seconds-setting is an important variable. (2) Normal size and slightly enlarged ducts should be injected with 30% radiographic contrast. (3) Ducts which are 20 mm or more in diameter should be injected with 15% contrast. (4) Variable radiographic exposures may be necessary to demonstrate centrally and peripherally located calculi, especially for small calculi in large ducts.

Red cell aggregation as a cause of blood-flow echogenicity.

The role of red cell aggregation as a cause of ultrasonic echogenicity in flowing blood was evaluated by in vitro experiments using fresh human blood. Blood was circulated in tubes of varying diameter (12 mm to 6 mm). In all experiments, echogenicity increased as blood approached static conditions. Echogenicity was greater in tubes with a larger diameter over the same range of blood velocity. However, echogenicity in tubes of various diameters was the same when evaluated in terms of shear rate. Thus, shear rate and not velocity is the flow condition that determines echogenicity. Since shear rate determines the degree of red cell aggregation, while other conditions affecting red cell aggregation (hematocrit, erythrocyte membrane conditions, and plasma macromolecules) are held constant, we conclude that these results provide additional evidence that red cell aggregation is a cause of echogenicity in flowing blood. Furthermore, a red cell aggregation mechanism for blood-flow echogenicity would explain the increased prominence of internal echoes in lower shear rate venous blood flow compared with those of higher shear rate arterial blood flow.

Ultrasonic detection of platelet aggregation at variable shear rates.

We have observed that high-resolution ultrasonic imaging can be used to detect and measure the size and sedimentation of large human platelet aggregates formed in vitro. At progressively lower shear rates, individual platelet aggregates grew in cross-sectional area from the limit of ultrasonic detectability of less than 1 mm2 at moderate shear rates to an approximate mean area of 25 mm2 at zero shear. Platelet aggregates tended to sediment at mean shear rates higher than zero shear. At a shear rate of 5.5 s-1, 70% of platelet aggregates had settled, and at 1.6 s-1, 90% had settled to the dependent half of horizontal tubes in less than 15 s. Ultrasonic aggregometry of platelets may be a valuable technique for investigation of platelet dynamics under controlled flow conditions in vitro.

Pulsed Doppler ultrasound detection of flow disturbances in arteriosclerosis.

Pulsed Doppler ultrasound blood flow detection has been used in a noninvasive manner to detect arterial abnormalities associated with arteriosclerosis. Sound spectrograms of ultrasound signals obtained from in vitro and animal studies in which flow was disturbed by obstacles placed in the flow stream showed a different distribution of energy over frequency than signals obtained from studies with no flow disturbances. Similar findings were seen clinically. A technique has been developed which can detect disturbed flow patterns resulting from partial occlusion in important superficial arteries (e.g. femoral and carotid) up to 15 cm distal to localized arterial wall abnormalities. Thirty-five arterial examinations of normal and arteriographically abnormal arteries in 12 patients revealed a sensitivity of 83 percent and a specificity of 61 percent. This study suggests that pulsed Doppler ultrasound may be useful as a screening technique for detection of arteriosclerotic lesions in major superficial arteries.