An in vitro phantom study on the influence of tear size and configuration on the hemodynamics of the lumina in chronic type B aortic dissections.

OBJECTIVE: Management and follow-up of chronic aortic dissections continue to be a clinical challenge due to progressive dilatation and subsequent rupture. To predict complications, guidelines suggest follow-up of aortic diameter. However, dilatation is triggered by hemodynamic parameters (pressures/wall shear stresses) and geometry of false (FL) and true lumen (TL), information not captured by diameter alone. Therefore, we aimed at better understanding the influence of dissection anatomy on TL and FL hemodynamics. METHODS: In vitro studies were performed using pulsatile flow in realistic dissected latex/silicone geometries with varying tear number, size, and location. We assessed three different conformations: (1) proximal tear only; (2) distal tear only; (3) both proximal and distal tears. All possible combinations (n = 8) of small (10% of aortic diameter) and large (25% of aortic diameter) tears were considered. Pressure, velocity, and flow patterns were analyzed within the lumina (at proximal and distal sections) and at the tears. We also computed the FL mean pressure index (FPI(mean)%) as a percentage of the TL mean pressure, to compare pressures among models. RESULTS: The presence of large tears equalized FL/TL pressures compared with models with only small tears (proximal FPI(mean)% 99.85 ± 0.45 vs 92.73 ± 3.63; distal FPI(mean)% 99.51 ± 0.80 vs 96.35 ± 1.96; P < .001). Thus, large tears resulted in slower velocities through the tears (systolic velocity <180 cm/s) and complex flows within the FL, whereas small tears resulted in lower FL pressures, higher tear velocities (systolic velocity >290 cm/s), and a well-defined flow. Additionally, both proximal and distal tears act as entry and exit. During systole, flow enters the FL through all tears simultaneously, while during diastole, flow leaves through all communications. Flow through the FL, from proximal to distal tears or vice versa, is minimal. CONCLUSIONS: Our results suggest that FL hemodynamics heavily depends on cumulative tear size, and thus, it is an important parameter to take into account when clinically assessing chronic aortic dissections.

Accurate guidance of a catheter by ultrasound imaging and identification of a catheter tip by pulsed-wave Doppler.

BACKGROUND: With the advent of numerous minimally invasive medical procedures, accurate catheter guidance has become imperative. We introduce and test an approach for catheter guidance by ultrasound imaging and pulsed-wave (PW) Doppler. METHODS: A steerable catheter is fitted with a small piezoelectric crystal at its tip that actively transmits signals driven by a function generator. We call this an active-tip (AT) catheter. In a water tank, we immersed a "target" crystal and a rectangular matrix of four "reference" crystals. Two-dimensional (2D) ultrasound imaging was used for initial guidance and visualization of the catheter shaft, and then PW Doppler mode was used to identify the AT catheter tip and guide it to the simulated target that was also visible in the 2D ultrasound image. Ten guiding trials were performed from random initial positions of the AT catheter, each starting at approximately 8 cm from the target. RESULTS: After the ten navigational trials, the average final distance of the catheter tip from the target was 2.4 ± 1.2 mm, and the range of distances from the trials was from a minimum of 1.0 mm to a maximum of 4.5 mm. CONCLUSIONS: Although early in the development process, these quantitative in vitro results show promise for catheter guidance with ultrasound imaging and tip identification by PW Doppler.

A critical review of the ability of continuous cardiac output monitors to measure trends in cardiac output.

Numerous cardiac output (CO) monitors have been produced that provide continuous rather than intermittent readings. Bland and Altman has become the standard method for validating their performance against older standards. However, the Bland and Altman method only assesses precision and does not assess how well a device detects serial changes in CO (trending ability). Currently, there is no consensus on how trending ability, or trend analysis, should be performed. Therefore, we performed a literature review to identify articles published between 1997 and 2009 that compared methods of continuous CO measurement. Identified articles were grouped according to measurement technique and statistical methodology. Articles that analyzed trending ability were reviewed with the aim of finding an acceptable statistical method. Two hundred two articles were identified. The most popular methods were pulse contour (69 articles), Doppler (54), bioimpedance (38), and transpulmonary or continuous thermodilution (27). Forty-one articles addressed trending, and of these only 23 provided an in-depth analysis. Several common statistical themes were identified: time plots, regression analysis, Bland and Altman using change in CO (ΔCO), and the 4-quadrant plot, which used direction of change of ΔCO to determine the concordance. This plot was further refined by exclusion of data when values were small. Receiver operating characteristic curves were used to define the exclusion zone. In animal studies, a reliable reference standard such as an aortic flowprobe was frequently used, and regression or time plots could be used to show trending. Clinical studies were more problematic because data collection points were fewer (8-10 per subject). The consensus was to use the 4-quadrant plot with exclusion zones and apply concordance analysis. A concordance rate of >92% when using a 15% zone indicated good trending. A new method of presenting trend data (ΔCO) on a polar plot is proposed. Agreement was shown by the angle with the horizontal axis and ΔCO by the distance from the center. Trending can be assessed by the vertical limits of the data, similar to the Bland and Altman method.

Ultrasonic Doppler measurements of blood flow velocity of rabbit retinal vessels using a 45-MHz needle transducer.

BACKGROUND: The purpose of this study is to measure blood flow velocity of rabbit retinal vessels using a 45-MHz ultrasonic Doppler system with a needle transducer. METHODS: A high-frequency pulsed Doppler system that utilizes a 45-MHz PMN-PT needle transducer was developed to measure retinal blood flow velocity in situ. The pulsed Doppler allowed the differentiation of retinal from choroidal blood flow velocity. The needle transducer was inserted into the vitreous cavity through a 20-gauge incision port to access the retinal vessels. The first phase of the experiment evaluated the reproducibility of the measurements. The second phase measured velocities at four positions from the optic disc edge to the distal part of each vessel in nine eyes for the temporal and six eyes for the nasal portions. The angle between the transducer and the retinal vessel at each site was measured in enucleated rabbit eyes to estimate and compensate for measurement errors. RESULTS: In the first phase, the average measurement error was 5.97 +/- 1.34%. There was no significant difference comparing all eyes. In the second phase, the velocities gradually slowed from the disc edge to the distal part, and temporal velocities were faster than nasal velocities at all measurement sites. CONCLUSION: This study demonstrated the feasibility of reliably measuring retinal blood flow velocity using a 45-MHz ultrasonic Doppler system with a needle transducer.

Convolutional modeling of diffraction effects in pulse-echo ultrasound imaging.

A model is presented for pulse-echo imaging of three-dimensional, linear, weakly-scattering continuum media by ultrasound array transducers. The model accounts for the diffracted fields of focused array subapertures in both transmit and receive modes, multiple transmit and receive focal zones, frequency-dependent attenuation, and aberration caused by mismatched medium and beamformer sound speeds. For a given medium reflectivity function, computation of a B-scan requires evaluation of a depth-dependent transmit/receive beam product, followed by two one-dimensional convolutions and a one-dimensional summation. Numerical results obtained using analytic expressions for transmit and receive beams agree favorably with measured B-scan images and speckle statistics.

Computer vision approach for ultrasound Doppler angle estimation.

Doppler ultrasound is an important noninvasive diagnostic tool for cardiovascular diseases. Modern ultrasound imaging systems utilize spectral Doppler techniques for quantitative evaluation of blood flow velocities, and these measurements play a crucial rule in the diagnosis and grading of arterial stenosis. One drawback of Doppler-based blood flow quantification is that the operator has to manually specify the angle between the Doppler ultrasound beam and the vessel orientation, which is called the Doppler angle, in order to calculate flow velocities. In this paper, we will describe a computer vision approach to automate the Doppler angle estimation. Our approach starts with the segmentation of blood vessels in ultrasound color Doppler images. The segmentation step is followed by an estimation technique for the Doppler angle based on a skeleton representation of the segmented vessel. We conducted preliminary clinical experiments to evaluate the agreement between the expert operator's angle specification and the new automated method. Statistical regression analysis showed strong agreement between the manual and automated methods. We hypothesize that the automation of the Doppler angle will enhance the workflow of the ultrasound Doppler exam and achieve more standardized clinical outcome.

An exposimetry system using tissue-mimicking liquid.

Acoustic output measurements of diagnostic ultrasound scanners are currently performed in water and derated to approximate in situ values. The derating scheme ignores nonlinear propagation of sound waves and has been shown in previous numerical and experimental studies to tend to underestimate relevant pressure and intensity values in tissue mimicking media. This work describes an alternative method, which uses a tissue-mimicking liquid with attenuation coefficient slope of 0.3 dB/cm/MHz, speed of sound of 1,540 m/s and nonlinearity parameter B/A of 7.5. The acoustic properties of this liquid are stable for at least 2 y after production. Initial results using a single M-mode configuration are presented. These results confirm that derating can significantly underestimate the pulse intensity integral and peak rarefactional pressure.

High-frequency ultrasound Doppler system for biomedical applications with a 30-MHz linear array.

In this paper, we report the development of the first high-frequency (HF) pulsed-wave Doppler system using a 30-MHz linear array transducer to assess the cardiovascular functions in small animals. This array-based pulsed-wave Doppler system included a 16-channel HF analog beamformer, a HF pulsed-wave Doppler module, timing circuits, HF bipolar pulsers and analog front ends. The beamformed echoes acquired by the 16-channel analog beamformer were fed directly to the HF pulsed-wave Doppler module. Then the in-phase and quadrature-phase (IQ) audio Doppler signals were digitized by either a sound card or a Gage digitizer and stored in a personal computer. The Doppler spectrogram was displayed on a personal computer in real time. The two-way beamwidths were determined to be 160 microm to 320 microm when the array was electronically focused at different focal points at depths from 5 to 10 mm. A micro-flow phantom, consisting of a polyimide tube with an inner diameter of 127 microm and the wire phantom were used to evaluate and calibrate the system. The results show that the system is capable of detecting motion velocity of the wire phantom as low as 0.1 mm/s, and detecting blood-mimicking flow velocity in the 127-microm tube lower than 7 mm/s. The system was subsequently used to measure the blood flow in vivo in two mouse abdominal superficial vessels, with diameters of approximately 200 microm, and a mouse aorta close to the heart. These results demonstrated that this system may become an indispensable part of the current HF array-based imaging systems for small animal studies.

Role of ultrasonic shear rate estimation errors in assessing inflammatory response and vascular risk.

Atherosclerotic lesions preferentially originate in arterial regions that experience low wall shear stress (WSS) and reversing flow patterns. Therefore, routinely monitoring arterial WSS may help to identify the potential sites of early atherosclerosis. A new noninvasive ultrasonic method implemented with coded excitation techniques was utilized to improve WSS estimation accuracy and precision by providing high spatial and temporal resolution. WSS measurement errors were quantified in a model system by scanning a linearly varying WSS field (0.3 to 1.9 Pa) within a flow chamber. A 13-bit optimal code (Opt) was found to be most effective in reducing bias and standard deviation in WSS estimates down to approximately 10% and approximately 8%. The measurement errors slowly increased with input WSS for all imaging pulses. The expression of endothelial cellular adhesion molecules vascular cell adhesion molecule-1 (VCAM-1) and endothelial-leukocyte adhesion molecule-1 (E-selectin) was investigated over a similar shear range (0 to 1.6 Pa) to study the impact of relating shear-mediated cellular adhesion molecule (CAM) expression to inaccuracies in WSS measurements. We quantified this influence as the prediction error, which accounts for the ultrasonic measurement errors and the sensitivity of CAM expression within certain shear ranges. The highest prediction errors were observed at WSS <0.8 Pa, where CAM expression is most responsive to WSS. The results emphasize the importance of minimizing estimation errors, especially within low shear regions. Preliminary two-dimensional in vivo shear imaging is also presented to provide information about the spatial heterogeneity in arterial WSS distribution.

High-frequency subharmonic pulsed-wave Doppler and color flow imaging of microbubble contrast agents.

A recent study has shown the feasibility of subharmonic (SH) flow imaging at a transmit frequency of 20 MHz. This paper builds on these results by examining the performance of SH flow imaging as a function of transmit pressure. Further, we also investigate the feasibility of SH pulsed-wave Doppler (PWD) imaging. In vitro flow experiments were performed with a 1-mm-diameter wall-less vessel cryogel phantom using the ultrasound contrast agent Definity and an imaging frequency of 20 MHz. The phantom results show that there is an identifiable pressure range where accurate flow velocity and power estimates can be made with SH imaging at 10 MHz (SH10), above which velocity estimates are biased by radiation force effects and unstable bubble behavior, and below which velocity and power estimates are degraded by poor SNR. In vivo validation of SH PWD was performed in an arteriole of a rabbit ear, and blood velocity estimates compared well with fundamental (F20) mode PWD. The ability to suppress tissue signals using SH signals may enable the use of higher frame rates and improve sensitivity to microvascular flow or slow velocities near large vessel walls by reducing or eliminating the need for clutter filters.

"Compression-only" behavior of phospholipid-coated contrast bubbles.

Ultrasound contrast agents oscillate approximately linearly up to a certain pressure range where nonlinearity sets in. Nonlinear microbubble oscillations are exploited in ultrasound pulse-echo imaging as this improves the contrast-to-tissue ratio. Here we report the observation of a highly nonlinear response of phospholipid-coated contrast agents at pressures as low as 50 kPa, termed "compression-only" behavior, where the microbubbles only compress, yet hardly expand. Time-resolved bubble dynamics recorded through ultra high-speed imaging revealed that nearly 40% of the coated bubbles show "compression-only" behavior.

PMN-PT single crystal, high-frequency ultrasonic needle transducers for pulsed-wave Doppler application.

High-frequency needle ultrasound transducers with an aperture size of 0.4 mm were fabricated using lead magnesium niobate-lead titanate (PMN-33% PT) as the active piezoelectric material. The active element was bonded to a conductive silver particle matching layer and a conductive epoxy backing through direct contact curing. An outer matching layer of parylene was formed by vapor deposition. The active element was housed within a polyimide tube and a 20-gauge needle housing. The magnitude and phase of the electrical impedance of the transducer were 47 omega and -38 degrees, respectively. The measured center frequency and -6 dB fractional bandwidth of the PMN-PT needle transducer were 44 MHz and 45%, respectively. The two-way insertion loss was approximately 15 dB. In vivo high-frequency, pulsed-wave Doppler patterns of blood flow in the posterior portion and in vitro ultrasonic backscatter microscope (UBM) images of the rabbit eye were obtained with the 44-MHz needle transducer.

[Innovative Ultrasound: Contrast-Enhanced Ultrasound of the Kidneys]. / Innovativer Ultraschall: Kontrastverstärkter Ultraschall der Nieren.

Ultrasound examination of the kidneys with grey-scale imaging and colour Doppler ultrasound is the most common renal imaging modality. A few years ago, contrast-enhanced ultrasound (CEUS) emerged as a non-invasive perfusion imaging modality to evaluate the renal vessels and microvascularisation. These contrast media contain intravenous microbubbles (sulfur hexafluoride), which have no deleterious effect on renal function. Being free of iodine, they also pose no risk for the thyroid gland. CEUS of the kidneys is mainly used for the evaluation of renal cysts and the analysis of renal lesions suspicious for malignancy. Also this method is used to visualise inflammation as well as renal perfusion after trauma or infarction.

Measurement of the ultrasonic attenuation coefficient of human blood plasma during clotting in the frequency range of 8 to 22 MHz.

The blood coagulation mechanism consists of a series of concatenated chemical reactions, governed by the coagulation factors present in the blood plasma, after the activation of the clot mechanism. The last reaction corresponds to the fibrinogen conversion into fibrin, followed by the fibrin polymerisation and production of a stable fibrin network. During the clotting process, there is a sol-gel transformation of the medium. The subject of the present paper is the measurement of the ultrasonic attenuation coefficient for human blood plasma during the coagulation process, in the frequency range of 8 to 22 MHz. The clot was obtained after the procedure to measure the prothrombin time (approximately 12 s): mixing 150 microL of reconstituted lyophilised normal plasma with 300 microL of reconstituted lyophilised thromboplastin immersed in a water bath with the temperature controlled at 36.5 degrees C. The attenuation coefficient for pure plasma remained constant within the measurement period of 10 s and at frequencies of 8, 9, 10, 15, 20, 21 and 22 MHz. On the other hand, there is a detectable time-decay of the attenuation coefficient for samples of plasma going through the coagulation process and at frequencies of 8, 9, 10 and 15 MHz. The time-decay becomes less and less detectable as the frequency increases and it becomes completely undetectable at 20, 21 and 22 MHz.

Determination of an ultrasonic transducer's sensitivity and impedance in a pulse-echo setup.

The role that an ultrasonic piezoelectric transducer plays in an ultrasonic measurement system can be described in terms of the transducer's input electrical impedance and its sensitivity. Here, a new model-based approach is proposed to determine both the transducer impedance and sensitivity in a pulse-echo setup. This new method is much simpler to apply than previous "self-reciprocity" calibration methods for determining sensitivity and generalizes those methods. It is demonstrated that sensitivities obtained with this new method agree well with the sensitivities obtained by a three-transducer method commonly used in calibration studies. It is demonstrated that at the megahertz frequencies at which ultrasonic transducers operate it is important to compensate for cabling effects in these measurements. The influence of the pulser/receiver settings on the results obtained also will be discussed.

Efficiency of U.S. Tissue Perfusion Estimators.

We measure the detection and discrimination efficiencies of conventional power-Doppler estimation of perfusion without contrast enhancement. The measurements are made in a phantom with known blood-mimicking fluid flow rates in the presence of clutter and noise. Efficiency is measured by comparing functions of the areas under the receiver operating characteristic curve for Doppler estimators with those of the ideal discriminator, for which we estimate the temporal covariance matrix from echo data. Principal-component analysis is examined as a technique for increasing the accuracy of covariance matrices estimated from echo data. We find that Doppler estimators are <50% efficient at directed perfusion detection between 0.1 and 2.0 mL/min per 2 cm(2) flow area. The efficiency was 20%-40% for the task of discriminating between two perfusion rates in the same range. We conclude that there are reasons to search for more efficient perfusion estimators, one that incorporates covariance matrix information that could significantly enhance the utility of Doppler ultrasound without contrast enhancement.

Evolution of Hemodynamic and Functional Human Kidney Graft Dose Response to Dopamine Using an Implantable Doppler Device.

OBJECTIVES: The relation between dopamine infusion and renal hemodynamics and function has not been studied in renal allografts during early recovery. We analyzed the dose response of dopamine infusion on renal blood flow and function in human kidney transplant recipients at reperfusion and during early graft recovery. MATERIALS AND METHODS: Phasic and mean renal blood flow was measured by the pulsed Doppler technique using implantable Doppler microprobes in contact with the graft artery. Systemic and renal parameters were recorded on dopamine infusion (0, 3, 5, and 10 µg·kg⁻¹·min⁻¹) immediately after transplant (day 0) in 13 patients and at day 6 in 7/13 patients with early graft recovery. Results are expressed as median and interquartile range between the 25th and 75th percentiles. RESULTS: At day 0, 3 µg·kg⁻¹·min⁻¹) dopamine did not increase mean renal blood flow over baseline (580 mL/min [219-663 mL/min] vs 542 mL/min [207-686 mL/min]; P = .84). There was an absence of effect with higher dopamine doses, whereas cardiac output, heart rate, and systolic and mean arterial pressure were significantly increased. Urinary sodium excretion, creatinine clearance, and urine output increased dose dependently, with a positive correlation between the increase in urine output and mean arterial pressure (r = 0.48, P < .001). At day 6, 3 µg·kg⁻¹·min⁻¹ dopamine increased mean renal blood flow over baseline (318 mL/min [234-897 mL/min] vs 191 mL/min [173-706 mL/min]; P = .016), with no further increase at higher doses. CONCLUSIONS: Immediately after transplant, kidney grafts with ischemic-reperfusion injury are fully dilated and do not respond to dopamine. The specific renal effects observed are due to systemic hemodynamic status. Vascular responsiveness to a "renal dopamine dose" returns on graft recovery.

High intensity, low frequency catheter-delivered ultrasound dissolution of occlusive coronary artery thrombi: an in vitro and in vivo study.

OBJECTIVES: This study assessed the efficacy of a new high intensity, low frequency therapeutic coronary ultrasound catheter for thrombus dissolution in vitro and in vivo in canine coronary arteries. BACKGROUND: Therapeutic ultrasound has been shown to dissolve thrombi in vitro and in peripheral arteries in vivo. There have been no previous studies on in vivo coronary thrombus dissolution by ultrasound. METHODS: In vitro, we exposed 1- to 4-h old human blood clots for 3 min to pulsed-wave ultrasound. Clot dissolution under various conditions was evaluated. In vivo occlusive coronary thrombi were induced in 18 dogs. RESULTS: In vitro irrigation alone (10 ml/min of normal saline solution) and ultrasound alone each contributed to a reduction of clot weight by 47.1 +/- 11.4 mg and 84.6 +/- 25.6 mg, respectively, after 3 min (p < 0.001). Ultrasound plus irrigation resulted in a reduction of clot weight by 216.5 +/- 31.5 mg after 3 min (p < 0.001). The magnitude of clot dissolution was considerably amplified when ultrasound energy was combined with irrigation, probably because of cavitational effects. In vivo, in three dogs mechanical passage of the unactivated probe failed to recanalize the artery, and the arteries remained thrombotically occluded. After passage of the activated ultrasound probe, angiography revealed widely patent coronary arteries in 13 of 15 dogs and partial recanalization with filling defects indicative of residual thrombus in 2 of 15 dogs. Three of 15 coronary arteries were histologically free of residual thrombi. Mural thrombi extending to < or = 10% of the vessel circumference were seen in 10 of 15 dogs. Residual thrombi > or = 50% of the vessel circumference were found in two cases. There was no histologic evidence of ultrasound-mediated vessel damage. CONCLUSIONS: Catheter-delivered therapeutic ultrasound effectively dissolves clots in vitro and in canine coronary arteries in vivo. Thus, therapeutic catheter-delivered ultrasound has the potential to serve as an adjunct or alternative treatment for thrombus-mediated coronary ischemic syndromes or myocardial infarction.

Investigation of intensity thresholds for ultrasound tissue erosion.

Our previous studies have shown that short intense pulses delivered at certain pulse repetition frequencies (PRF) can achieve localized, clean erosion in soft tissue. In this paper, the intensity thresholds for ultrasound induced erosion and the effects of pulse intensity on erosion characterized by axial erosion rate, perforation area and volume erosion rate were investigated on in vitro porcine atrial wall tissue. Ultrasound pulses with a 3-cycle pulse duration and a 20-kHz PRF were delivered by a 788-kHz single element focused transducer. I(SPPA) values of 1000 to 9000 W/cm2 were tested. Results show the following: (1) the estimated intensity threshold for generating erosion was at I(SPPA) of 3220 W/cm2; (2) the axial erosion rate increased with higher intensity at I(SPPA) < or = 5000 W/cm2, while decreased with higher intensity at I(SPPA) > or = 5000 W/cm2; and (3) the perforation area and the volume erosion rate increased with higher intensity.

Design and initial evaluation of an implantable sonomicrometer and CW Doppler flowmeter for simultaneous recordings with a multichannel telemetry system.

We have developed a sonomicrometer and continuous wavelength (CW) Doppler flowmeter for a multichannel telemetry system. These developments will enable us to measure ventricular dimension and coronary artery blood velocity, which are valuable parameters to characterize sudden cardiac death (SCD) in ambulatory animal models of ventricular arrhythmias. The design goals for the sensors were accuracy, low power consumption, small size and compatibility with each other. The circuits were designed successfully and tested simultaneously in vivo. The CW Doppler flowmeter draws 9 mA and the sonomicrometer draws 28 mA on a 5-V supply. The ability to measure heart dimension and blood velocity will add significantly to our understanding of the sequence of events leading up to spontaneous sudden cardiac death.