Red cell aggregation and the echogenicity of whole blood.

To study the relationship between red cell aggregation and whole blood echogenicity, red cell aggregation was quantitated by a photometric method, whole blood echogenicity was quantitated by videodensitometry and sedimentation rate was quantitated by a modified Westergren method. Changes in red cell aggregation were produced by alterations in the hematocrit. The results showed that red cell aggregation increased in a linear fashion with increases in hematocrit. The sedimentation rate decreased in a linear manner with increases in hematocrit. Whole blood echogenicity showed a biphasic response, with an initial increase in echogenicity, peaking at hematocrits varying from 14-24% and decreasing thereafter. Over the physiologic range of hematocrits, an increase in the formation of red cell aggregates is associated with a decrease in the echogenicity of whole blood. Thus, red cell aggregates were not visible using our ultrasound equipment at physiologic hematocrits, and the echo contrast in blood under our experimental conditions at these hematocrits must represent either plasma spaces, platelet aggregates or possibly white cell aggregates. The association between spontaneous contrast and a propensity for thromboembolism imply that platelet aggregates are the most likely origin of in vivo echo contrast in flowing blood.     

High Spatial and Temporal Resolution Observations of Pulsatile Changes in Blood Echogenicity in the Common Carotid Artery of Rats

Previous studies have found that ultrasound backscatter from blood in vascular flow systems varies under pulsatile flow, with the maximum values occurring during the systolic period. This phenomenon is of particular interest in hemorheology because it is contrary to the well-known fact that red blood cell (RBC) aggregation, which determines the intensity of ultrasound backscatter from blood, decreases at a high systolic shear rate. In the present study, a rat model was used to provide basic information on the characteristics of blood echogenicity in arterial blood flow to investigate the phenomenon of RBC aggregation under pulsatile flow. Blood echogenicity in the common carotid arteries of rats was measured using a high-frequency ultrasound imaging system with a 40-MHz probe. The electrocardiography-based kilohertz visualization reconstruction technique was employed to obtain high-temporal-resolution and high-spatial-resolution time-course B-mode cross-sectional and longitudinal images of the vessel. The experimental results indicate that blood echogenicity in rat carotid arteries varies during a cardiac cycle. Blood echogenicity tends to decrease during early systole and reaches its peak during late systole, followed by a slow decline thereafter. The time delay of the echogenicity peak from peak systole in the present results is the main difference from previous in vitro and in vivo observations of backscattering peaks during early systole, which may be caused by the very rapid heart rates and low RBC aggregation tendency of rats compared with humans and other mammalian species. The present study may provide useful information elucidating the characteristics of RBC aggregation in arterial blood flow.     

Cyclic changes in blood echogenicity under pulsatile flow are frequency dependent

Previous in vivo and in vitro studies have demonstrated that blood echogenicity varies under pulsatile flow, but such changes could not always be measured at physiological stroke rates. The apparent contradiction between these studies could be a result of the use of different ultrasound frequencies. Backscattered signals from porcine blood were measured in a pulsatile Couette flow apparatus. Cyclic changes in shear rate for stroke rates of 20 to 70 beats per minute (BPM) were applied to the Couette system, and different blood samples were analyzed (normal blood and blood with hyperaggregating erythrocytes promoted with dextran). To confirm that cyclic echogenicity variations were observable, spectral analysis was performed to verify if changes in echo-amplitude corresponded to the stroke rate applied to the flow. Echogenicity was measured with two single-element transducers at 10 and 35 MHz. At 35 MHz, cyclic variations in backscatter were observed from 20 to 70 BPM. However at 10 MHz, they were detected only at 20 BPM. For all cases except for hyperaggregating red blood cells (RBCs) at 20 BPM, the magnitude of the cyclic variations were higher at 35 MHz. We conclude that cyclic variations in RBC aggregation exist at physiological stroke rates, unlike what has been demonstrated in previous in-vitro studies at frequencies of 10 MHz. The increased sensitivity at 35 MHz to small changes in aggregate size might be the explanation for the better characterization of RBC aggregation at high stroke rates. Our results corroborate in-vivo observations of cyclic blood echogenicity variations in patients using a 30-MHz intravascular ultrasound catheter.     

Measurement of the Doppler Power of Flowing Blood Using Ultrasound Doppler Devices

Measurement of the Doppler power of signals backscattered from flowing blood (henceforth referred to as the Doppler power of flowing blood) and the echogenicity of flowing blood have been used widely to assess the degree of red blood cell (RBC) aggregation for more than 20 y. Many studies have used Doppler flowmeters based on an analogue circuit design to obtain the Doppler shifts in the signals backscattered from flowing blood; however, some recent studies have mentioned that the analogue Doppler flowmeter exhibits a frequency-response problem whereby the backscattered energy is lost at higher Doppler shift frequencies. Therefore, the measured Doppler power of flowing blood and evaluations of RBC aggregation obtained using an analogue Doppler device may be inaccurate. To overcome this problem, the present study implemented a field-programmable gate array-based digital pulsed-wave Doppler flowmeter to measure the Doppler power of flowing blood, in the aim of providing more accurate assessments of RBC aggregation. A clinical duplex ultrasound imaging system that can acquire pulsed-wave Doppler spectrograms is now available, but its usefulness for estimating the ultrasound scattering properties of blood is still in doubt. Therefore, the echogenicity and Doppler power of flowing blood under the same flow conditions were measured using a laboratory pulser–receiver system and a clinical ultrasound system, respectively, for comparisons. The experiments were carried out using porcine blood under steady laminar flow with both RBC suspensions and whole blood. The experimental results indicated that a clinical ultrasound system used to measure the Doppler spectrograms is not suitable for quantifying Doppler power. However, the Doppler power measured using a digital Doppler flowmeter can reveal the relationship between backscattering signals and the properties of blood cells because the effects of frequency response are eliminated. The measurements of the Doppler power and echogenicity of flowing blood were compared with those obtained in several previous studies.     

Ultrasonic observation of blood disturbance in a stenosed tube: effects of flow acceleration and turbulence downstream

Red blood cell (RBC) aggregation is known to be highly dependent on hemodynamic parameters such as shear rate, flow turbulence and flow acceleration under pulsatile flow. The effects of all three hemodynamic parameters on RBC aggregation and echogenicity of porcine whole blood were investigated downstream of an eccentric stenosis in a mock flow loop using B-mode images with Doppler spectrograms of a commercial ultrasonic system. A hyperechoic parabolic profile appeared downstream during flow acceleration, yielding another piece of evidence suggesting that the enhancement of rouleaux formation may be caused by flow acceleration. It was also found that echogenicity increased locally at a distance of three tube diameters downstream from the stenosis. The local increase of echogenicity is thought to be mainly due to flow turbulence. The hypoechoic "black hole" was also seen at the center of the tube downstream of the stenosis where blood flow was disturbed, and this may be caused by the compound effect of flow turbulence and shear rate.     

Simultaneous assessment of red blood cell aggregation and oxygen saturation under pulsatile flow using high-frequency photoacoustics

We investigate the feasibility of photoacoustic (PA) imaging for assessing the correlation between red blood cell (RBC) aggregation and the oxygen saturation (sO₂) in a simulated pulsatile blood flow system. For the 750 and 850 nm illuminations, the PA amplitude (PAA) increased and decreased as the mean blood flow velocity decreased and increased, respectively, at all beat rates (60, 120 and 180 bpm). The sO₂ also cyclically varied, in phase with the PAA for all beat rates. However, the linear correlation between the sO₂ and the PAA at 850 nm was stronger than that at 750 nm. These results suggest that the sO₂ can be correlated with RBC aggregation induced by decreased mean shear rate in pulsatile flow, and that the correlation is dependent on the optical wavelength. The hemodynamic properties of blood flow assessed by PA imaging may be used to provide a new biomarker for simultaneous monitoring blood viscosity related to RBC aggregation, oxygen delivery related to the sO₂ and their clinical correlation.OCIS codes: (110.5125) Photoacoustics, (170.1470) Blood or tissue constituent monitoring     

On the relation between aggregation, packing and the backscattered ultrasound signal for whole blood

Previous studies have shown that the backscattered ultrasound (US) power from blood depends on the manner in which red blood cells (RBCs) are packed and, in particular, on spatial variations in the red blood cell number density (i.e., the RBC concentration variance). Experimental measurements have also shown that the backscattered US power depends on the degree of RBC aggregation, and it has been hypothesized that this is primarily due to the effect of RBC aggregation on the concentration variance. An initial simulation study of the relationship between RBC aggregation and packing statistics is presented, in which the effects of hematocrit, aggregate size, shape and size distribution on concentration variance are investigated. Both two-dimensional (2-D) and 3-D samples of aggregated and disaggregated RBCs were simulated; these enabled the concentration variance to be calculated. In agreement with theoretical predictions and experimental US results, the concentration variance for disaggregated RBCs is shown to be lowest at low and high hematocrits, and to peak at intermediate hematocrits. The concentration variance is shown to be particularly sensitive to changes in aggregate size and size distribution, and less sensitive to the shape of small aggregates. The results of this study provide a foundation for relating the state of aggregation in a blood sample to the manner in which RBCs are packed and, therefore, to the backscattered US power.     

Accuracy of chest radiography for evaluating significantly abnormal pulmonary vascularity in children with congenital heart disease

This study aims to investigate the blood flow around the perivalvular area in a human superficial vein using high-frequency ultrasound (HFUS) speckle image velocimetry. HFUS B-mode images were captured from the superficial veins of human lower extremity with a 35-MHz transducer. To measure the instantaneous velocity fields of blood flow, a cross-correlation particle image velocimetry (PIV) algorithm was applied to two B-mode images that were captured consecutively. The echo speckles of red blood cells (RBCs) were used as flow tracers. In the vicinity of the venous valve, the opening and closing motions of valve cusps were simultaneously visualized with the phasic variation of velocity fields. Large-scale vortices were observed behind the sinus pockets while the main bloodstream was directed proximally. This measurement technique combining PIV algorithm and HFUS B-mode imaging was found to be unique and useful for investigating the hemodynamic characteristics of blood flow in the perivalvular area and for diagnosing venous insufficiency and valve abnormality in superficial blood vessels.     

Cyclic changes of blood echogenicity in high-frequency ultrasound.

Ultrasound images from human arteries obtained in vivo with an intravascular 30 MHz ultrasound imaging device show that blood echogenicity changes during the cardiac cycle. Quantitative measurements of blood echogenicity during the cardiac cycle suggest that these variations may be related to changes in the state of erythrocyte aggregation, which are induced by varying shear rate.     

The acute effects of smoking on the cyclic variations in blood echogenicity of carotid artery

The objective of this research is to study the cyclic variations in echogenicity (CVE) as an acute response to smoking. CVEs, caused by the aggregation of red blood cells (RBC) were measured from the cross-sectional images of the common carotid artery using coded harmonic imaging of a commercial ultrasound system. The amplitude of the CVE (A_cve) was analyzed among 28 smokers before and after smoking. A_cve was increased in 22 smokers and decreased in six smokers after 1-2 cigarettes were smoked. Heart rate (HR) was also estimated from the ultrasonic images before and after smoking. The smokers were optimally divided into two clusters with respect to the change in A_cve and the intrinsic characteristics of smokers (i.e., daily consumed cigarettes and smoking years) through a two-step cluster analysis (TSCA). The increase in A_cve after smoking was significantly higher in the heavy smoker cluster compared with the light smoker cluster. The results suggest that the acute changes in A_cve in response to smoking are different between heavy smokers and light smokers. This preliminary study demonstrates the potential application of coded harmonic ultrasound imaging to detect or characterize RBC aggregation. In addition, the results may be useful for understanding the acute physiologic changes caused by smoking. (E-mail: paeng@jejunu.ac.kr)     

Doppler power variation from porcine blood under steady and pulsatile flow

Although a number of recent studies have demonstrated that the echogenicity of blood varies as a function of time under pulsatile flow, the fundamental mechanisms responsible for it are still uncertain. To better understand this phenomenon, the Doppler power from porcine blood and polystyrene microsphere suspensions was measured at the center of the tube as functions of two crucial parameters, flow velocity and stroke rate (for pulsatile flow), under steady and pulsatile flow in a mock flow loop. In the present study, the experimental results were obtained with a 10-MHz pulsed Doppler system with a frequency response estimated more accurately by electronic injection, and validated by comparing to the radiofrequency (RF) signal acquired from the same Doppler instrument. The results show that the Doppler power from microspheres and porcine red blood cell (RBC) suspensions did not vary appreciably (< 2 dB), with either the speed or stroke rate (for pulsatile flow only) under steady and pulsatile flow. It was found that the Doppler power from porcine whole blood under steady flow decreased with the speed by approximately 13 dB from 3 to 33 cm/s and was only 3 dB higher than that from RBC suspension at 33 cm/s, suggesting minimal RBC aggregation in whole blood at this speed. The apparent cyclic variation from whole blood was observed at 20 and 40 beats/min (BPM). The cyclic variation became more obvious as the speed and stroke rate decreased. The mean Doppler power over a cycle increased as the peak speed decreased. The Doppler power reached a maximum near peak systole and a minimum at late diastole at the center of the tube. This pattern cannot be explained by RBC aggregation due to the shear rate alone, and may be attributed to acceleration and deceleration along with aggregation. The cyclic variation was not observed at 60 BPM, probably because of a lack of time for aggregation to occur.     

Assessing blood coagulation status with laser speckle rheology

We have developed and investigated a novel optical approach, Laser Speckle Rheology (LSR), to evaluate a patient’s coagulation status by measuring the viscoelastic properties of blood during coagulation. In LSR, a blood sample is illuminated with laser light and temporal speckle intensity fluctuations are measured using a high-speed CMOS camera. During blood coagulation, changes in the viscoelastic properties of the clot restrict Brownian displacements of light scattering centers within the sample, altering the rate of speckle intensity fluctuations. As a result, blood coagulation status can be measured by relating the time scale of speckle intensity fluctuations with clinically relevant coagulation metrics including clotting time and fibrinogen content. Our results report a close correlation between coagulation metrics measured using LSR and conventional coagulation results of activated partial thromboplastin time, prothrombin time and functional fibrinogen levels, creating the unique opportunity to evaluate a patient’s coagulation status in real-time at the point of care.OCIS codes: (170.1610) Clinical applications, (290.4210) Multiple scattering, (120.4820) Optical systems, (170.4580) Optical diagnostics for medicine, (030.6140) Speckle     

Statistical variations of ultrasound signals backscattered from flowing blood

The statistical distributions of ultrasonic signals backscattered from blood have recently been used to characterize hemodynamic properties, such as red blood cell (RBC) aggregation and blood coagulation. However, a thorough understanding of the relationship between blood properties and the statistical behavior of signals backscattered from flowing blood is still lacking. This prompted us to use the statistical parameter to characterize signals backscattered from both whole blood and RBC suspensions at different flow velocities (from 10 to 60 cm/s) and hematocrits (from 20% to 50%) under a steady laminar flow condition. The Nakagami parameter, scaling parameter, backscatter amplitude profile and flow velocity profile across a flow tube were acquired using a 10 MHz focused ultrasonic transducer. The backscattered signal peaked approximately at the centerline of the flow tube due to the effects of RBC aggregation, with the peak value increasing as the flow velocity of whole blood decreased. The Nakagami parameter increased from 0.45 to 0.78 as the flow velocity increased from 10 to 60 cm/s. The probability density function (PDF) of signals backscattered from flowing whole blood conformed with a pre-Rayleigh distribution. The Nakagami parameter was close to 1 for signals backscattered from RBC suspensions at all the flow velocities and hematocrits tested, for which the PDF was Rayleigh distributed. These differences in the statistical distributions of backscattered signals between whole blood and RBC suspensions suggest that variations in the size of dynamic scatterers in the flow affect the shape of the backscattered signal envelope, which should be considered in future statistical models used to characterize blood properties. (E-mail: j648816n@ms23.hinet.net and shyhhau@cycu.edu.tw)     

妊娠高血压综合征的血液流变学观察及机制探讨

作者对２０例妊娠高血压综合征患者血液流变学十四项指标进行了观察，发现全血高切粘度，高切还原粘度，全血低切粘度，低切还原粘度，血浆纤维蛋白原含量，红细胞聚集指数，红细胞刚性指数较正常人明显升高（Ｐ＜０．０１），提示妊娠高血压综合征红细胞变形能力下降，血液的凝固性增加，血细胞的聚集性增强，血液的粘滞性升高．并对其变化机理作了初步探讨。     

高频超声及能量多普勒超声在类风湿关节炎中的应用

近几年,高频超声(HFUS)及能量多普勒超声(PDUS)技术在类风湿关节炎(RA)的诊疗中发挥重要作用,本文就HFUS及PDUS的成像特点、疗效评价,不同关节间HFUS检查的相关性,PDUS与RA滑膜病理学相关性及PDUS在RA达标治疗中的价值等方面的研究做一综述。     

Decorrelation characteristics of transverse blood flow along an intravascular array catheter: effects of aggregation of red blood cells

A method to measure transverse blood flow, based on the correlation between consecutive radiofrequency (RF) signals, has been introduced. This method was validated for an intravascular (IVUS) rotating single element catheter. Currently, we are implementing the method for an IVUS array transducer catheter. The decorrelation characteristics during transverse blood flow using the IVUS array catheter were investigated using computer modeling. Before this, blood was simulated as a collection of randomly located point scatterers and, by moving this scattering medium transversely across the acoustical beam, blood flow was simulated. This paper presents a more realistic scattering media by simulating aggregates of red blood cells (RBCs) as strings of point scatterers. Three configurations of aggregates of RBCs were simulated. First, aggregates of RBCs were strings with different lengths and parallel to the catheter axis. Second, the strings were with a fixed length and angles of plus or minus 45 degrees with respect to the catheter axis. Third, the strings were with different lengths and random angles ranging from -45 degrees to + 45 degrees. The decorrelation characteristics for these configurations of aggregates of RBCs were investigated and compared with point scatterers. For the aggregates of RBCs parallel to the catheter axis, the decorrelation rate became slower when the aggregate length was increased. RBC aggregations with fixed and random lengths and angles resulted in a decorrelation rate that approaches the decorrelation pattern from point scatterers. Results suggests that the presence of aggregates of RBCs will probably not affect the measurements of transverse blood flow using a decorrelation-based method and an IVUS array catheter.     

Lower limb vein enlargement and spontaneous blood flow echogenicity are normal sonographic findings during pregnancy

PURPOSE: We studied pregnancy-induced changes in lower limb venous function. METHODS: We used plethysmography and sonography to assess the changes in venous wall distensibility, saphenous vein diameters, and spontaneous blood flow echogenicity in the common femoral veins in 190 consecutive women during and after uncomplicated pregnancies (total of 409 examinations). RESULTS: The percentage of women with clinical symptoms and signs of venous insufficiency increased significantly during pregnancy. The mean diameters of the great and small saphenous veins also increased significantly, while occlusive venous plethysmography showed a decrease in parameters indicating vein distensibility. Spontaneous blood flow echogenicity in the common femoral veins was clearly visible or marked in 6% of cases during the first trimester of pregnancy, 63% during the second trimester, and 96% during the third trimester, versus 6% after delivery (p < 0.0001). The mean hematocrit decreased and the mean fibrinogen concentration increased during pregnancy. CONCLUSIONS: The increase in lower limb venous pressure seen during pregnancy leads to venous overdistention and worsens blood stasis. Decreased venous flow velocity and rheological alterations result in increased red cell aggregation, giving rise to spontaneous blood flow echogenicity. Spontaneous blood flow echogenicity is therefore a normal finding during pregnancy and should not be mistaken for venous thrombosis.     

High frequency ultrasound device to investigate the acoustic properties of whole blood during coagulation

This study was designed to investigate the changes in acoustic properties of whole blood during the coagulation process. High frequency (from 20 to 40 MHz) ultrasound parameters were measured both in double transmission (DT) and backscattering (BS) mode to assess sound velocity and backscatter coefficient, respectively. The integrated backscatter coefficient (IBC) and the effective scatterer size (ESS) were deducted from the backscatter coefficient. Measurements were performed on whole blood samples collected from 12 healthy volunteers. During the blood clotting process (2 h observation), acoustic parameters were measured with 15 s time resolution for the transmission parameter and 5 s (for the 5 first min) and 30 s (for the end of the observation time) for the backscattering parameters. The results obtained clearly showed that simultaneous measurements of parameters in DT and BS modes are able to identify several stages during the in vitro blood clotting process. In particular, red blood cell (RBC) aggregation can be described from the backscattering parameters and liquid-gel transition phase of blood from the sound velocity. Intra- and inter-individual dispersion of these parameters were also measured and discussed.     

Analysis of blood clot echogenicity

The ability of B-mode ultrasound to follow effectively blood clot echogenicity changes over time under conditions of red cell preservation and lysis was evaluated. Blood clots were produced in cellulose dialysis tubing and then placed into appropriate baths of either saline or water. The echogenicity changes were then followed quantitatively using A-mode and qualitatively using B-mode imaging. Blood clots in saline showed an initial decrease followed by a leveling off in echogenicity. Blood clots in water showed a decline in echogenicity throughout the experiment. The A-mode imaging was effectively able to follow blood clot echogenicity changes under these controlled conditions.