A novel in vivo procedure for volumetric flow measurements

We report on a novel procedure for invasive volumetric blood flow measurements using a commercially available Doppler flow wire system, which could, until now, only measure flow velocity. We here describe a method applicable in vivo to generate both velocity and cross-sectional area information from the same pulsed-wave Doppler signal for volumetric flow assessment. We demonstrate its feasibility and validation in vivo in pig coronary arteries. Our Doppler-derived volumetric flow measurements were compared with the respective transit-time flow and showed an excellent correlation (r = 0.969; p < 0.0001). Agreement between transit-time and Doppler-derived flow measurements could be observed for flow conditions ranging from 30 to 180 mL/min. The mean values for the two methods were 71.4 +/- 43.7 mL/min and 71.3 +/- 42.2 mL/min, respectively. We conclude that this technique might possibly be introduced into future clinical practice as an invasive procedure of choice for the assessment of volumetric blood flow.     

Power M-mode Doppler (PMD) for observing cerebral blood flow and tracking emboli

Difficulties in location of transcranial ultrasound (US) windows and blood flow in cerebral vessels, and unambiguous detection of microemboli, have limited expansion of transcranial Doppler US. We developed a new transcranial Doppler modality, power M-mode Doppler (PMD), for addressing these issues. A 2-MHz digital Doppler (Spencer Technologies TCD100M) having 33 sample gates placed with 2-mm spacing was configured to display Doppler signal power, colored red and blue for directionality, in an M-mode format. The spectrogram from a user-selected depth was displayed simultaneously. This system was then explored on healthy subjects and patients presenting with varying cerebrovascular pathology. PMD facilitated window location and alignment of the US beam to view blood flow from multiple vessels simultaneously, without sound or spectral clues. Microemboli appeared as characteristic sloping high-power tracks in the PMD image. Power M-mode Doppler is a new paradigm facilitating vessel location, diagnosis, monitoring and microembolus detection.     

Assessment of the effect of vessel curvature on Doppler measurements in steady flow

Blood vessel curvature is responsible for the appearance of nonaxial velocity components and for minor changes in the pattern of the axial flow. All the velocity components are expected to contribute to the Doppler signal produced by the ultrasound (US) backscattered by the insonated blood cells, the axial velocity, contributing to the actual volumetric blood flow, and the transverse velocity, causing the recirculating vortices. A detailed, separate analysis of the velocity components is, therefore, mandatory to quantify how vessel curvature can affect results and clinical diagnosis. Both experimental in vitro measures and numerical simulations were performed on a curved tube and the Doppler power spectra so obtained were compared. The satisfactorily agreement of the above spectra shows that the nonaxial velocity components are easily detectable with clinical equipment and that their amplitude, as expected, is not negligible and can bias Doppler measurements and resulting clinical diagnosis.     

Implementation of spectral width Doppler in pulsatile flow measurements

In this paper, we present an automatic beam-vector (Doppler) angle and flow velocity measurement method and implement it in pulsatile flow measurements using a clinical Doppler ultrasound system. In current clinical Doppler ultrasound flow velocity measurements, the axis of the blood vessel needs to be set manually on the B-scan image to enable the estimation of the beam-vector angle and the beam-vector angle corrected flow velocity (the actual flow velocity). In this study, an annular array transducer was used to generate a conical-shaped and symmetrically focused ultrasound beam to measure the flow velocity vectors parallel and perpendicular to the ultrasound beam axis. The beam-vector angle and flow velocity is calculated from the mode frequency (f(d)) and the maximum Doppler frequency (f(max)) of the Doppler spectrum. We develop a spectrum normalization algorithm to enable the Doppler spectrum averaging using the spectra obtained within a single cardiac cycle. The Doppler spectrum averaging process reduces the noise level in the Doppler spectrum and also enables the calculation of the beam-vector angle and flow velocity for pulsatile flows to be measured. We have verified the measurement method in vivo over a wide range of angles, from 52 degrees to 80 degrees, and the standard deviations of the measured beam-vector angles and flow velocities in the carotid artery are lower than 2.2 degrees and 12 cm/s (about 13.3%), respectively.     

Some aspects of the relationship between instantaneous volumetric blood flow and continuous wave doppler ultrasound recordings—III. The calculation of doppler power spectra from mean velocity waveforms, and the results of processing these spectra with maximum, mean, and rms frequency processors

A method of predicting velocity profiles and hence Doppler relative power spectra (RPS) from mean volumetric flow waveforms using an extension of Womersley's theory is described. The effect on the RPS of using an ultrasound beam which is smaller than the blood vessel is calculated, and comparisons are made between RPS found in this way and experimental RPS measured in a dog model. Finally the effect of making ultrasonic Doppler measurements on complex velocity profiles with different combinations of processing technique and ultrasonic beam size are considered.     

Doppler ultrasound compatible plastic material for use in rigid flow models

A technique for the rapid but accurate fabrication of multiple flow phantoms with variations in vascular geometry would be desirable in the investigation of carotid atherosclerosis. This study demonstrates the feasibility and efficacy of implementing numerically controlled direct-machining of vascular geometries into Doppler ultrasound (DUS)-compatible plastic for the easy fabrication of DUS flow phantoms. Candidate plastics were tested for longitudinal speed of sound (SoS) and acoustic attenuation at the diagnostic frequency of 5 MHz. Teflon was found to have the most appropriate SoS (1376 +/- 40 m s(-1) compared with 1540 m s(-1) in soft tissue) and thus was selected to construct a carotid bifurcation flow model with moderate eccentric stenosis. The vessel geometry was machined directly into Teflon using a numerically controlled milling technique. Geometric accuracy of the phantom lumen was verified using nondestructive micro-computed tomography. Although Teflon displayed a higher attenuation coefficient than other tested materials, Doppler data acquired in the Teflon flow model indicated that sufficient signal power was delivered throughout the depth of the vessel and provided comparable velocity profiles to that obtained in the tissue-mimicking phantom. Our results indicate that Teflon provides the best combination of machinability and DUS compatibility, making it an appropriate choice for the fabrication of rigid DUS flow models using a direct-machining method.     

Orientation-independent rapid pulsatile flow measurement using dual-angle Doppler OCT

Doppler OCT (DOCT) can provide blood flow velocity information which is valuable for investigation of microvascular structure and function. However, DOCT is only sensitive to motion parallel with the imaging beam, so that knowledge of flow direction is needed for absolute velocity determination. Here, absolute volumetric flow is calculated by integrating velocity components perpendicular to the B-scan plane. These components are acquired using two illumination beams with a predetermined angular separation, produced by a delay encoded technique. This technology enables rapid pulsatile flow measurement from single B-scans without the need for 3-D volumetric data or knowledge of blood vessel orientation.OCIS codes: (110.4500) Optical coherence tomography, (170.3880) Medical and biological imaging     

Adenosine induces dilation of epicardial coronary arteries in mice: relationship between coronary flow velocity reserve and coronary flow reserve in vivo using transthoracic echocardiography

For an accurate estimate of volumetric coronary flow reserve (CFR) using Doppler-assessed flow velocity measurement, it is important to take into consideration potential diameter change during coronary hyperemia. Using ultrasound techniques, left coronary artery (LCA) flow velocity and LCA lumen diameter (LCA(D)) were measured simultaneously for the first time to measure coronary flow during baseline and adenosine-induced hyperemic condition in isoflurane-anesthetized C57BL/6 (n = 38) and in old apolipoprotein E-gene deficient (ApoE(-/-)) mice (n = 44) mice. LCA(D) increased significantly and to a similar extent during adenosine infusion in both groups (3.7 +/- 1.1 %, p < 0.003 for C57BL/6; 4.2 +/- 0.9 %, p < 0.00003 for ApoE(-/-)). Yet, a positive correlation was still found between velocity-based coronary flow velocity reserve (CFVR) and volumetric CFR in both strains (R(2) = 0.77, p < 0.001 for C57BL/6; R(2) = 0.80, p < 0.001 for ApoE(-/-)). Coronary reserve was higher in C57BL/6 mice than in ApoE(-/-) mice (CFR 1.93 +/- 0.17 vs. 1.47 +/- 0.07, p < 0.05; CFVR 1.73 +/- 0.13 vs. 1.28 +/- 0.07, p < 0.01). Thus, ultrasound techniques can be used to measure volumetric flow in the LCA and flow-based CFR measurements of intact, living mice. The positive correlation between CFR and CFVR, together with the lower method variability of the latter, makes CFVR a more robust protocol for assessing mouse in-vivo coronary artery function. Therefore, the CFVR protocol will probably work well in most settings.     

Doppler color flow imaging

By simultaneous processing of frequency, phase, and amplitude information in the backscattered ultrasound signal, new instruments now permit the real-time display of high-resolution grey scale images of tissue combined with the simultaneous display of flow data from vessels within the scan plane. Doppler Color Flow Imaging, or DCFI, using such processing, permits blood flow direction and relative velocity to be detected and displayed in a color encoded display from throughout the ultrasound image. We have tested a new Doppler color flow imaging system over a period of two years to evaluate the carotid arteries, peripheral arteries and veins, and dialysis fistulas. In the abdomen and pelvis we have imaged blood flow to the liver, spleen, kidneys, uterus and renal transplants. Our experience in over 500 patients leads us to conclude that DCFI has significant advantages over conventional duplex Doppler sonography for blood flow evaluation. For examination of carotid and peripheral vessels, we have found DCFI to permit more rapid assessment in both normal and abnormal states. Areas of vessel narrowing or turbulent flow may be identified rapidly and accurately, and vessel orientation may be determined precisely, allowing accurate calculation of blood flow velocity from Doppler frequency shifts. The system we have used has adequate penetration and sensitivity to allow imaging of hepatic and renal blood flow and is extremely promising as a method of imaging organ perfusion and in the detection of abnormalities of perfusion that accompany disease, such as transplant rejection. Tumor vascularity may also be identified with DCFI, opening the possibility of additional clinical applications.     

Assessment of coronary stenoses by Doppler wires: a validation study using in vitro modeling and computer simulations.

The present study evaluates the use of intracoronary velocity measurements by Doppler guidewires for assessing coronary obstructions. In vitro experiments were performed in a flow model using acrylic phantoms of coronary stenoses with different configurations (stenosis area: 56%, 75% and 89%; stenosis length: 1 and 5 mm; stenosis border: tapering or abrupt). Nonpulsatile laminar flow conditions of a test fluid were established at flow rates ranging from 0.5 to 2.0 mL/s to simulate baseline flow and flow after vasodilation. Peak Doppler velocity was measured proximal to, within and distal to the model stenoses. Computer simulations were employed to calculate radial flow profiles with and without a Doppler wire aligned with the vessel center. In 84 in vitro flow experiments, peak Doppler velocity correlated well with the average flow velocity as calculated from the actual flow rate and the vessel's cross-sectional area proximal to (r = 0.98, SEE = 1.4, p < 0.001) and within (r = 0.97, SEE = 16.4, p < 0.001) the stenosis. However, the ratio of calculated average velocity to Doppler-measured peak velocity was significantly different from 0.5, the expected value for a parabolic flow profile (0.76+/-0.08, 0.81+/-0.14; p < 0.001). Acceptable accuracy was found for the Doppler estimation of stenosis severity using the continuity equation (error: 0.9+/-1.2% and -4.6+/-3.5% for stenosis with a length of 5 mm and 1 mm, respectively). Doppler velocity reserve significantly underestimated the true flow reserve for the 56% and 75% stenoses (p < 0.01). Computer simulations demonstrated significant alterations of flow profiles by the wire, which explained the observed underestimation of the true flow reserve by the Doppler velocity reserve. Thus, Doppler guidewire measurements of intracoronary flow velocities are useful to assess the severity of coronary stenoses. However, the in vitro results and computer simulations indicate that guidewires alter the flow profile, so that Doppler velocity reserve may underestimate the true flow reserve.     

Volumetric and quantitative imaging of retinal blood flow in rats with optical microangiography

In this paper, we present methods for 3D visualization and quantitative measurements of retinal blood flow in rats by the use of optical microangiography imaging technique (OMAG). We use ultrahigh sensitive OMAG to provide high-quality 3D RBF perfusion maps in the rat eye, from which the Doppler angle, as well as the diameters of blood vessels, are evaluated. Estimation of flow velocity (i.e. axial flow velocity) is achieved by the use of Doppler OMAG, which has its origins in phase-resolved Doppler optical coherence tomography. The measurements of the Doppler angle, vessel size, and the axial velocity lead to the quantitative assessment of the absolute flow velocity and the blood flow rate in selected retinal vessels. We demonstrate the feasibility of OMAG to provide 3D microangiograms and quantitative assessment of retinal blood flow in a rat model subjected to raised intra-ocular pressure (IOP). We show that OMAG is capable of monitoring the longitudinal response of absolute blood velocity and flow rate of retinal blood vessels to increased IOP in the rat, demonstrating its usefulness for ophthalmological research.     

Evaluation of descending aortic flow volumes and effective orifice area through aortic coarctation by spatiotemporal integration of color Doppler data: An in vitro study.

Flow volumes in an in vitro model of the aorta with 3 different degrees of stiffness (stiff, moderately stiff, and compliant) proximal to a coarctation were calculated by using a digital color Doppler echocardiography flow calculation method that semiautomatically integrates spatial and temporal color flow velocity data. These flow volumes were compared with those obtained by the conventional pulsed Doppler method with reference to ultrasonic flowmeter. Flow volumes determined by the automated method agreed well with those obtained by ultrasonic flowmeter, even in this compliant aorta model with vessel size changing with pulsation, whereas the pulsed Doppler method overestimated the reference data, especially for more compliant descending aortic segments. The combination of flow data with continuous wave Doppler allows definition of effective orifice area for coarctation.     

Intraluminal ultrasound intensity distribution and backscattered Doppler power

Ultrasound (US) incident obliquely on a cylindrical vessel is redistributed in space when the propagation path includes walls with acoustic impedance different from that of the surrounding media. We investigated this using low-density polyethylene (PE) as the vessel wall material. Both simulations and experiments were carried out. Direct hydrophone measurements of the acoustic field were made within a half section of the PE tube, and the distribution of backscattered Doppler power along a scan line was obtained using a range-Doppler instrument. Both simulation and hydrophone results demonstrate lateral shadow regions within the lumen. In every one of various Doppler flow experiments conducted, the backscattered Doppler power, compensated for on-axis transducer behaviour, increased with depth. Simulation results for an incident continuous-wave (CW) plane wave show that it tends to be focused by the curvature of the PE tube walls. The wall interactions are, however, angle-dependent and so the behaviour of a focused US beam depends on the beam as well as the walls. This study demonstrates alterations in the spatial distribution of US within a cylindrical vessel as a result of known vessel wall properties. It also provides evidence that local intensity variations within the lumen affect the relative Doppler power backscattered from small sample volumes.     

A wall-less vessel phantom for Doppler ultrasound studies

Doppler ultrasound flow measurement techniques are often validated using phantoms that simulate the vasculature, surrounding tissue and blood. Many researchers use rubber tubing to mimic blood vessels because of the realistic acoustic impedance, robust physical properties and wide range of available sizes. However, rubber tubing has a very high acoustic attenuation, which may introduce artefacts into the Doppler measurements. We describe the construction of a wall-less vessel phantom that eliminates the highly attenuating wall and reduces impedance mismatches between the vessel lumen and tissue mimic. An agar-based tissue mimic and a blood mimic are described and their acoustic attenuation coefficients and velocities are characterised. The high attenuation of the latex rubber tubing resulted in pronounced shadowing in B-mode images; however, an image of a wall-less vessel phantom did not show any shadowing. We show that the effects of the highly attenuating latex rubber vessels on Doppler amplitude spectra depend on the vessel diameter and ultrasound beam width. In this study, only small differences were observed in spectra obtained from 0.6 cm inside diameter thin-wall latex, thick-wall latex and wall-less vessel phantoms. However, a computer model predicted that the spectrum obtained from a 0.3-cm inside diameter latex-wall vessel would be significantly different than the spectrum obtained from a wall-less vessel phantom, thus resulting in an overestimation of the average fluid velocity. These results suggest that care must be taken to ensure that the Doppler measurements are not distorted by the highly attenuating wall material. In addition, the results show that a wall-less vessel phantom is preferable when measuring flow in small vessels.     

Fully distributed absolute blood flow velocity measurement for middle cerebral arteries using Doppler optical coherence tomography

Doppler optical coherence tomography (DOCT) is considered one of the most promising functional imaging modalities for neuro biology research and has demonstrated the ability to quantify cerebral blood flow velocity at a high accuracy. However, the measurement of total absolute blood flow velocity (BFV) of major cerebral arteries is still a difficult problem since it is related to vessel geometry. In this paper, we present a volumetric vessel reconstruction approach that is capable of measuring the absolute BFV distributed along the entire middle cerebral artery (MCA) within a large field-of-view. The Doppler angle at each point of the MCA, representing the vessel geometry, is derived analytically by localizing the artery from pure DOCT images through vessel segmentation and skeletonization. Our approach could achieve automatic quantification of the fully distributed absolute BFV across different vessel branches. Experiments on rodents using swept-source optical coherence tomography showed that our approach was able to reveal the consequences of permanent MCA occlusion with absolute BFV measurement.OCIS codes: (110.4500) Optical coherence tomography, (170.2655) Functional monitoring and imaging, (100.2960) Image analysis     

Numerical assessment of the impact of a flow wire on its velocity measurements

Blood flow velocities can be measured using a Doppler flow wire. This numerical study evaluates the impact of a 0.014" flow wire on the measured frequencies in a straight artery with diameters of 3 mm and 4 mm, under steady and pulsatile flow conditions. Simulations were performed with the wires positioned differently in the artery (perfectly centred and at an offset of 0.5 mm from the wall) and with different types of wire (tilted and straight). Measurements were taken at range gates from 4 mm to 10 mm. During simulations using a 3-mm vessel under pulsatile flow conditions, the relative error between the measured and reference maximum frequency (occurring in absence of the wire) decreased from 17.7% to 11.6% (with a mean value of 14.9%). During simulations using an off-centre 1.5 degree tilted wire, the mean error was approximately 5%. Therefore, our study suggests that that a centrally positioned flow wire is unfavourable for measuring flow velocities.     

Blood flow velocity profiles in the aortic annulus: a 3-dimensional freehand color flow Doppler imaging study.

BACKGROUND: The use of a single sample volume in Doppler measurements of the velocity time integral (VTI) in the aortic annulus may introduce errors in calculations of stroke volumes, shunts, regurgitant fractions, and aortic valve area. To study the blood flow velocity distribution and assess this potential error, we used a dynamic 3-dimensional color flow Doppler imaging method. METHODS AND RESULTS: Seventeen healthy volunteers were studied. The ultrasound data were captured from 10 to 20 heartbeats at a high frame rate (mean 57 frames per second) while freely tilting the transducer in the apical position. A magnetic position-sensor system recorded the spatial position and orientation of the probe. The raw digital ultrasound data were analyzed off-line with no loss of temporal resolution. Blood flow velocities were integrated across a spherical surface that tracked the aortic annulus during systole. The ratios of the systolic maximum to the systolic mean VTI ranged from 1.2 to 1.5 (mean 1.4). At the time of systolic peak flow, the ratios of the maximum to the mean velocity ranged from 1.1 to 2.0 (mean 1.5). The location of the maximum velocities and VTI showed individual variation. CONCLUSION: The blood flow velocity profile was nonuniform. By using a single sample volume in Doppler measurements of the VTI in the aortic annulus, errors ranging from 20% to 50% may be introduced in calculations of stroke volumes.     

A new approach to the noninvasive measurement of cardiac output using an annular array Doppler technique--I. Theoretical considerations and ultrasonic fields

This paper describes the development of a Doppler flowmeter capable of measuring blood volume flow rate without the need to measure the vessel lumen area or beam-vessel angle. It requires the production of a uniform wide ultrasound beam to encompass the whole vessel and thus to produce a Doppler spectrum which corresponds to all the flowing blood, and a narrow reference beam placed within the lumen to compensate for various unknown quantities, such as tissue attenuation. The general definition of volume flow rate is described and applied to a new flowmeter, which allows an absolute value of volume flow rate to be measured independently of vessel size, beam-vessel angle, and tissue attenuation. By electronically apodising an annular array transducer in transmission and reception, a uniform wide beam and a narrow reference reception beam are produced. Theory to predict these beam patterns is developed and a computer simulation is made. The ultrasonic fields obtained from an annular array transducer in water are compared with the theoretical fields.     

Measurement of coronary flow using high-frequency intravascular ultrasound imaging and pulsed Doppler velocimetry: in vitro feasibility studies.

The recent development of intravascular ultrasound imaging offers the potential to measure blood flow as the product of vessel cross-sectional area and mean velocity derived from pulsed Doppler velocimetry. To determine the feasibility of this approach for measuring coronary artery flow, we constructed a flow model of the coronary circulation that allowed flow to be varied by adjusting downstream resistance and aortic driving pressure. Assessment of intracoronary flow velocity was accomplished using a commercially available end-mounted pulsed Doppler catheter. Cross-sectional area of the coronary artery was measured using a 20 MHz mechanical imaging transducer mounted on a 4.8 F catheter. The product of mean velocity and cross-sectional area was compared with coronary flow measured by timed collection in a graduated cylinder by linear regression analysis. Excellent correlations were obtained between coronary flow calculated by the ultrasound method and measured coronary flow at both ostial (r = 0.99, standard error of the estimate [SEE] = 13.9 ml/min) and distal (r = 0.98, SEE = 23.0 ml/min) vessel locations under steady flow conditions. During pulsatile flow, calculated and measured coronary flow also correlated well for ostial (r = 0.98, SEE = 12.7 ml/min) and downstream (r = 0.99, SEE = 9.3 ml/min) locations. That the SEE was lower for pulsatile as compared with steady flow may be explained by the blunting of the flow profile across the vessel lumen by the acceleration phase of pulsatile flow. These data establish the feasibility of measuring coronary artery blood flow using intravascular ultrasound imaging and pulsed Doppler techniques.     

Flow index evaluation of 3-D volume flow images: an in vivo and in vitro study

Three-dimensional (3-D) ultrasound imaging has improved evaluation of organ circulation and might contribute new information on maternal and fetal blood supply. Flow index (FI) of 3-D color images has been proposed as a measure of perfusion. The aim of this study was to evaluate whether the 3-D FI is a parameter of volume flow and flow velocity in a human vessel and in a flow phantom. A 1-cm-long strip of the uterine artery was recorded in 3-D power Doppler (3D-PD) mode in a cross-sectional study of 170 normal singleton pregnancies between 26 and 42 weeks' gestation. A fixed ultrasound system installation was used during the examination. The VOCAL software integrated in the ultrasound unit calculated vessel volume and FI. Reproducibility of the measurements was tested. The method was also tested on a commercially available flow phantom. Reproducibility measurements gave satisfactory results, both in terms of inter- and intraobserver variation. Unexpectedly, in normal pregnancy, the uterine artery FI decreased slightly with gestation. Uterine artery vessel volume increased, however, with gestational age. A poor correlation was found between the FI and both flow velocity and volume flow in the flow phantom. In conclusion, 3D-PD imaging can give impressive anatomical pictures of organ vascular tree. However, the new FI is poorly related to flow velocity or volume of flow.