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We have previously found that spectral analysis of ultrasound (US) can discriminate in vitro plaques from asymptomatic and symptomatic (transient ischemic attack within previous 4 weeks) patients. That study found no differences in percentages of lipid or thrombus between the two groups by optical microscopy/planimetry. The present study was to find out if another feature from the microscopy could show a difference. The number and size of spaces resulting from cell death or new blood vessels were measured to see if they related to symptoms or could help explain US differentiation. Twelve plaques from each group were examined by optical microscopy. The sizes and concentrations of two kinds of spaces, endothelial lined (vessel spaces) and unlined (tissue spaces), were correlated both with symptoms and also with the US tissue characterization scores from the previous study. Symptomatic vs. asymptomatic plaques showed a higher concentration and a larger size: 0.87 vs. 0.21 per mm(2) (p < 0.005) and 154 vs. 110 microm (p < 0.02). A discriminant function of spaces with symptoms as dependent variables correctly identified 91.7% of the plaques (p < 0.001). The concentration in plaques previously designated by US as true positive plaques or true negative was 1.21 vs. 0.22 per mm(2) (p < 0.005). spaces were increased in plaques of symptomatic patients and were related to UTC scores. Both the lined and unlined spaces were useful as predictors.

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.

The history of Doppler ultrasound in peripheral vascular diagnosis is considered in terms of basic developments, clinical applications and impact on medical practice. Many early developments occurred at Osaka University in Japan and the University of Washington in the United States. Through progressive steps, Doppler ultrasound technology has provided clinical applications in blood-flow sensing, waveform analysis, localizing blood flow and two-dimensional (2-D) mapping of blood flow. An important advance was the development of duplex and color Doppler scanning. Real time velocity measurements and flow mapping have led to many clinical applications. Two important applications have been detection and grading of atherosclerotic plaques in the internal carotid artery and the diagnosis of deep venous thrombosis. Doppler ultrasound is the preferred noninvasive imaging method for each of these clinical problems. The recent reaffirmation of carotid endarterectomy as the appropriate management for certain categories of carotid atherosclerotic occlusive disease has led to guidelines for selecting patients for carotid endarterectomy. New Doppler ultrasound criteria are being developed to identify categories of stenosis that relate to these guidelines. The establishment of Doppler ultrasound has led to training programs for technologists and physicians, certification of technologists and establishment of standards and quality control measures for vascular laboratories.

We evaluated the ability of ultrasonic tissue characterization (UTC), based on backscattered echo signals, to distinguish among the components of advanced carotid plaques. We performed spectral analysis of echo signals acquired from human carotid endarterectomy specimens in vitro to calculate three parameters of the calibrated power spectrum: slope, intercept and total power for fibrous, lipid pool and thrombus constituents of plaque. Plaque constituents were identified histologically. We evaluated classification efficacy by discriminant function analysis. Slope and intercept parameters alone provided correct classification in 92.5%, 57.6% and 72.4% of fibrous, lipid pool and thrombus plaque components, respectively. Slope, intercept and total power used in combination improved classification of the three tissue types to 93.0%, 69.7% and 81.0%. The overall proportion of correctly classified tissue regions increased from 84.5% to 88.0% by the combined use of the three parameters. The improvement in classification that occurred when we included total power as a third parameter suggests that ultrasound plaque components may not consist solely of small, randomly distributed isotropic scatterers. Our ability to identify plaque thrombi provides motivation for future studies of parameter-based imaging methods for identifying such plaque that presents an increased risk of embolic neurologic ischemic events.

Parameters of the power spectrum of backscattered echoes were applied to quantitatively evaluate red cell aggregation in vitro. Human red cell suspensions were circulated in a closed loop of tubing, and ultrasonic, radiofrequency, echo-signal data were obtained using a 10-MHz transducer. Data acquisition was performed at 30-s to 1-min intervals for 5 min after flow stoppage. Two parameters of the normalized power spectrum of the echo signals, spectral slope and Y-intercept, were computed, and estimates of two scattering properties, the scatterer size and acoustic concentration were calculated from these parameters using equations based on scattering theory. Size and acoustic concentration were observed as they changed over time after the stoppage of flow. The key findings were that hematocrit affected the rate of cell aggregation while fibrinogen controlled aggregate size and acoustic concentration.

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.

The purpose of this study was to determine the effect of blood flow perfusion and red cell content on ultrasonic scattering by liver tissue. Data acquisition for ultrasonic tissue characterization (UTC) employing analysis of the backscattered echoes from the power spectrum was obtained from the same region of pig liver tissue under four conditions: 1) normal perfusion in situ, 2) ischemia in situ in the living pig, 3) ischemia in situ immediately postmortem, and 4) immediately after excision of the liver. Discriminant function analysis was used to evaluate differences in the two basic parameters from the normalized power spectrum: slope and intercept. Normal perfused liver had significantly higher intercept values and lower slope values than liver under the other three conditions. Excised liver showed the lowest intercept and highest slope values (p < 0.01). These experiments indicate that differences in perfusion produce significant differences in ultrasonic scattering by liver tissue (ischemia caused a 3 dB drop in intercept amplitude). Normal or ischemic in vivo and in vitro liver tissue is associated with different patterns of ultrasonic scattering, and scattering data under these various circumstances are not equivalent.

Ultrasonic tissue characterization (UTC) employing slope and Y-intercept parameters from the normalized power spectrum of backscattered echoes was employed in vivo to study compositional changes in the walls of pig jugular veins in which thrombi were experimentally induced. Light microscopy revealed these changes to be intimal hyperplasia with an early predominance of smooth muscle cells and a later mixture of smooth muscle cells and collagen deposits. UTC distinguished intimal hyperplasia from previously reported data from luminal thrombosis UTC. Furthermore, UTC was able to discriminate between early (predominantly smooth muscle cells) and older (smooth muscle cells plus collagen deposits) intimal hyperplasia. The study suggests that intimal hyperplasia in the experimental model used may be organized thrombus and that UTC may be able to follow both the development of wall changes as well as luminal changes occurring in venous thrombosis.

This in vitro study was designed to evaluate the ability of ultrasonic tissue characterization (UTC) based on power spectrum analysis of backscattered radio-frequency echo signals to distinguish two prominent variables of thrombi: cellularity (primarily red cell content) and fibrin-mesh density. Six types of clots simulating thrombus components were prepared by varying red-cell and platelet concentrations and shear forces during clotting. Data were acquired with a linear-array transducer, digitized, and analyzed in terms of slope and intercept parameters obtained from normalized power spectra of radio-frequency echo signals. Increased cellularity and fibrin-mesh density both produced lower slope and higher intercept values, which permitted statistically significant discrimination of cellularity and mesh density in the six types of clots analyzed. Shearing forces and (to a lesser degree) platelet concentrations increased fibrin-mesh density. This study suggests that UTC based upon the power spectrum of echo signals may be used to detect and follow compositional differences that have clinical relevance in the diagnosis and follow-up of thrombi.

Although percutaneous ultrasound-guided technique is currently a common practice, the use of ultrasound for the purpose of guidance during surgery has not been widely practiced. Over a period of 10 years, we performed operative ultrasonography in 2,314 operations. In 321 of these operations, operative ultrasound guidance was performed for direct assistance of various surgical procedures, particularly during operations on the brain and spinal cord, liver, pancreas, and kidney. Procedures guided by operative ultrasound were classified into the following categories: intraoperative needle placement for fluid aspiration (n = 38), agent injection (n = 14), catheter introduction (n = 27), biopsy (n = 57), surgical tissue dissection for incision (n = 48), resection (n = 82) of organs, and extraction (n = 55) of stones or foreign bodies. Operative ultrasound guidance facilitates various surgical procedures and is considered a useful modality for reducing operative complications, shortening operating time, performing otherwise impossible procedures, and, at times, developing new surgical operations.

Real-time ultrasound B-mode scanning was used during vascular operations to detect defects produced by reconstructive surgery. Ultrasound detection of defects was more accurate than arteriography. Use of operative imaging led to re-exploration and correction of defects in 8% of patients undergoing vascular reconstruction.

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.