Measurement of pulsatile total blood flow in the human and rat retina with ultrahigh speed spectral/Fourier domain OCT

We present an approach to measure pulsatile total retinal arterial blood flow in humans and rats using ultrahigh speed Doppler OCT. The axial blood velocity is measured in an en face plane by raster scanning and the flow is calculated by integrating over the vessel area, without the need to measure the Doppler angle. By measuring flow at the central retinal artery, the scan area can be very small. Combined with ultrahigh speed, this approach enables high volume acquisition rates necessary for pulsatile total flow measurement without modification in the OCT system optics. A spectral domain OCT system at 840nm with an axial scan rate of 244kHz was used for this study. At 244kHz the nominal axial velocity range that could be measured without phase wrapping was ±37.7mm/s. By repeatedly scanning a small area centered at the central retinal artery with high volume acquisition rates, pulsatile flow characteristics, such as systolic, diastolic, and mean total flow values, were measured. Real-time Doppler C-scan preview is proposed as a guidance tool to enable quick and easy alignment necessary for large scale studies. Data processing for flow calculation can be entirely automatic using this approach because of the simple and robust algorithm. Due to the rapid volume acquisition rate and the fact that the measurement is independent of Doppler angle, this approach is inherently less sensitive to involuntary eye motion. This method should be useful for investigation of small animal models of ocular diseases as well as total blood flow measurements in human patients in the clinic.     

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     

Errors in measuring blood flow velocity behind hepatic mass lesions using color doppler sonography

The authors designed microcomputer simulation models to investigate the combined effect of a distorted grayscale ultrasound image and an inaccurately measured Doppler angle on the accuracy of measurement of blood-flow velocity in vessels located behind mass lesions in the liver. Error decreased when flow was measured at the midpoint of the posttumoral segment of the vessel and increased with distance between the mass and the vessel, with inclination of the vessel, and with decrease in the diameter of the mass. Error was least with the sector probe, intermediate with the convex probe, and greatest with the linear probe. These findings suggest that the error can be minimized when measuring blood flow velocity in a vessel located behind a mass, if the Doppler images are acquired using a sector probe from the midpoint of the posttumoral segment of the vessel.     

A feasability study of color flow doppler vectorization for automated blood flow monitoring

An ongoing issue in vascular medicine is the measure of the blood flow. Catheterization remains the gold standard measurement method, although non-invasive techniques are an area of intense research. We hereby present a computational method for real-time measurement of the blood flow from color flow Doppler data, with a focus on simplicity and monitoring instead of diagnostics. We then analyze the performance of a proof-of-principle software implementation. We imagined a geometrical model geared towards blood flow computation from a color flow Doppler signal, and we developed a software implementation requiring only a standard diagnostic ultrasound device. Detection performance was evaluated by computing flow and its determinants (flow speed, vessel area, and ultrasound beam angle of incidence) on purposely designed synthetic and phantom-based arterial flow simulations. Flow was appropriately detected in all cases. Errors on synthetic images ranged from nonexistent to substantial depending on experimental conditions. Mean errors on measurements from our phantom flow simulation ranged from 1.2 to 40.2% for angle estimation, and from 3.2 to 25.3% for real-time flow estimation. This study is a proof of concept showing that accurate measurement can be done from automated color flow Doppler signal extraction, providing the industry the opportunity for further optimization using raw ultrasound data.     

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.     

A double beam doppler ultrasound method for quantitative blood flow velocity measurement

A method for measuring the absolute blood flow velocity waveform is reported. Two independent beams of ultrasound illuminate a vessel simultaneously, producing complementary Doppler signals. The two Doppler frequency shift signals are processed by subtraction and addition at the receiver. The optimum probe position where blood flow velocity is detected can be found as the position where the subtractor output reaches zero. At this position the blood flow velocity is the output from the adder. By this means the influence of the angle between the probe and blood flow is eliminated so that a quantitative measurement is obtained. Both in vitro and clinical results are reported.     

In vitro validation of volumetric blood flow measurement using Doppler flow wire

Determination of any volumetric blood flow requires assessment of mean blood flow velocity and vessel cross-sectional area. For evaluation of coronary blood flow and flow reserve, however, assessment of average peak velocity alone is widely used, but changes in velocity profile and vessel area are not taken into account. We studied the feasibility of a new method for calculation of volumetric blood flow by Doppler power using a Doppler flow wire. An in vitro model with serially connected silicone tubes of known lumen diameters (1.5, 2.0, 2.5, 3.0, 3.5 and 4.0 mm) and pulsatile blood flow ranging from 10 to 200 mL/min was used. A Doppler flow wire was connected to a commercially available Doppler system (FloMap(R), Cardiometrics) for online calculation of the zeroth (M(0)) and the first (M(1)) Doppler moment, as well as mean flow velocity (V(m)). Two different groups of sample volumes (at different gate depths) were used: 1. two proximal sample volumes lying completely within the vessel were required to evaluate the effect of scattering and attenuation on Doppler power, and 2. distal sample volumes intersecting completely the vessel lumen to assess the vessel cross-sectional area. Area (using M(0)) and V(m) (using M(1)/M(0)) obtained from the distal gates were corrected for scattering and attenuation by the data obtained from the proximal gates, allowing calculation of absolute volumetric flow. These results were compared to the respective time collected flow. Correlation between time collected and Doppler-derived flow measurements was 0.98 (p < 0.0001), with a regression line close to the line of equality indicating an excellent agreement of the two measurements in each individual tube. The mean paired flow difference between the two techniques was 1.5 +/- 9.0 mL/min (ns). Direct volumetric blood flow measurement from received Doppler power using a Doppler flow wire system is feasible. This technique may potentially be of great clinical value because it allows an accurate assessment of coronary flow and flow reserve with a commercially available flow wire system.     

Performance of the mean frequency Doppler modulator.

The mean frequency Doppler demodulator is of interest for quantitative measurement of blood flow, particularly in small or deep-lying vessels. It is thus desirable that the various potential sources of error be considered, and that their effects on its performance be quantified where possible. This paper analyzes the effects of interfering noise, more than one vessel falling within the Doppler sample volume, Doppler filtering, frequency aliasing, and double-sidebanding of the Doppler signal. The analysis applies to either frequency offset or non-offset Doppler systems, and a variety of blood velocity distributions is considered. It is shown that, in a number of instances, the errors can be predicted and therefore corrected. Experimental results are presented confirming the theoretical analysis.     

Rapid volume flow rate estimation using transverse colour Doppler imaging

A system is described in which the volume flow rate of blood in a vessel is determined using transverse colour Doppler ultrasound imaging. The system measures rapidly the two-dimensional velocity profile of blood flowing through a vessel. By integration of the measured velocity profiles the volume flow rate of blood in the vessel is obtained. The Doppler angle is obtained from the included angle between two imaging planes, and their respective average measured flows. This technique yields instantaneous and average flow rate in real time, and permits long flow recordings to be made and stored digitally. The error is less than 5% over a 8:1 flow rate range.     

Methodology and basic problems related to blood flow studies in the human fetus

A method was developed for non-invasive measurement of human fetal blood flow. The method combines real-time ultrasonography with 2 MHz pulsed Doppler technique. The blood flow is calculated from the blood velocity, estimated from the Doppler spectrum, and the vessel diameter, measured in the real-time image. Time-distance recording was applied for measurements of the pulsatile diameter changes in the fetal aorta. The method proved to possess a good accuracy and reproducibility when tested in vitro experiments and in a comparison with electromagnetic flow measurements in animals. Possible sources of error were analysed and recommendations for minimizing the risk of errors are presented.     

Quantification of Ultrasound Correlation‐Based Flow Velocity Mapping and Edge Velocity Gradient Measurement

This study investigated the use of ultrasound speckle decorrelation‐ and correlation‐based lateral speckle‐tracking methods for transverse and longitudinal blood velocity profile measurement, respectively. By studying the blood velocity gradient at the vessel wall, vascular wall shear stress, which is important in vascular physiology as well as the pathophysiologic mechanisms of vascular diseases, can be obtained. Decorrelation‐based blood velocity profile measurement transverse to the flow direction is a novel approach, which provides advantages for vascular wall shear stress measurement over longitudinal blood velocity measurement methods. Blood flow velocity profiles are obtained from measurements of frame‐to‐frame decorrelation. In this research, both decorrelation and lateral speckle‐tracking flow estimation methods were compared with Poiseuille theory over physiologic flows ranging from 50 to 1000 mm/s. The decorrelation flow velocity measurement method demonstrated more accurate prediction of the flow velocity gradient at the wall edge than the correlation‐based lateral speckle‐tracking method. The novelty of this study is that speckle decorrelation‐based flow velocity measurements determine the blood velocity across a vessel. In addition, speckle decor‐relation‐based flow velocity measurements have higher axial spatial resolution than Doppler ultrasound measurements to enable more accurate measurement of blood velocity near a vessel wall and determine the physiologically important wall shear.     

Development of a Flexible Implantable Sensor for Postoperative Monitoring of Blood Flow

We have developed a blood flow measurement system using Doppler ultrasound flow sensors fabricated of thin and flexible piezoelectric‐polymer films. These flow sensors can be wrapped around a blood vessel and accurately measure flow. The innovation that makes this flow sensor possible is the diffraction‐grating transducer. A conventional transducer produces a sound beam perpendicular to its face; therefore, when placed on the wall of a blood vessel, the Doppler shift in the backscattered ultrasound from blood theoretically would be 0. The diffraction‐grating transducer produces a beam at a known angle to its face; therefore, backscattered ultrasound from the vessel will contain a Doppler signal. Flow sensors were fabricated by spin coating a poly(vinylidene fluoride–trifluoroethylene) copolymer film onto a flexible substrate with patterned gold electrodes. Custom‐designed battery‐operated continuous wave Doppler electronics along with a laptop computer completed the system. A prototype flow sensor was evaluated experimentally by measuring blood flow in a flow phantom and the infrarenal aorta of an adult New Zealand White rabbit. The flow phantom experiment demonstrated that the error in average velocity and volume blood flow was less than 6% for 30 measurements taken over a 2.5‐hour period. The peak blood velocity through the rabbit infrarenal aorta measured by the flow sensor was 118 cm/s, within 1.7% of the measurement obtained using a duplex ultrasound system. The flow sensor and electronics operated continuously during the course of the 5‐hour experiment after the incision on the animal was closed.     

Jugular Venous Flow Quantification Using Doppler Sonography

A consensus on venous flow quantification using echo spectral Doppler sonography is lacking. Doppler sonography data from 83 healthy individuals were examined using manually traced transverse cross-sectional area and diameter-derived cross-sectional area obtained in longitudinal view measurements of the internal jugular vein. Time-averaged velocity over a 4-s interval was obtained in the longitudinal plane using manual tracing of the waveform. Manual and computer-generated blood flow volume calculations were also obtained for the common carotid artery, for accuracy purposes. No differences were detected between semi-automated and manual blood flow volume calculations for the common carotid artery. The manual calculation method resulted in almost twofold larger venous internal jugular vein flow measurements compared with the semi-automated method. Doppler sonography equipment does not provide accurate automated calculation of venous size and blood flow. Until further technological development occurs, manual calculation of venous blood flow is warranted.     

Reproducibility of ultrasonic fetal volume blood flow measurements

The intraobserver reproducibility of ultrasonic volume blood flow measurements in the human fetus was evaluated in this study. A new approach, simultaneous measurement of the vessel diameter and the flow velocity with a pulsed-wave Doppler ultrasound synchronized with a real-time ultrasound phase-locked echo-tracking system, was used to estimate volume blood flow (VBF) in the fetal descending aorta. Measurements were performed in a longitudinal study on 20 normally grown fetuses. Intraobserver reproducibility of repeated estimations of mean blood flow velocities throughout gestation was very good, with high values of intraclass correlation coefficient (IntraCC 0·80–0·91) and low values of coefficient of variation (CV 4–11%). The IntraCC of repeated vessel diameter measurements throughout gestation was low (0·30–0·68), whereas the values of CV were acceptable (< 12%), with the exception of the period between 140 and 167 gestational days (CV > 12%). The lower reproducibility of vessel diameter measurement contributed directly to the relatively low reproducibility of VBF estimations overall (IntraCC 0·25–0·70; CV 17–28%), as these are calculated from a formula using both flow velocity and vessel diameter. Nevertheless, the synchronized approach gives absolute values of vessel diameter, flow velocity and VBF comparable with values reported in the human fetus previously. The new method provides, by taking the vessel wall pulsations into consideration and by measuring diameter and velocity simultaneously, a more complete information on fetal haemodynamics and fetal physiology.     

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.     

In Vivo Validation of Volume Flow Measurements of Pulsatile Flow Using a Clinical Ultrasound System and Matrix Array Transducer

The goal of this study was to evaluate the accuracy of a non-invasive C-plane Doppler estimation of pulsatile blood flow in the lower abdominal vessels of a porcine model. Doppler ultrasound measurements from a matrix array transducer system were compared with invasive volume flow measurements made on the same vessels with a surgically implanted ultrasonic transit-time flow probe. For volume flow rates ranging from 60 to 750 mL/min, agreement was very good, with a Pearson correlation coefficient of 0.97 (p < 0.0001) and a mean bias of ?4.2%. The combination of 2-D matrix array technology and fast processing gives this Doppler method clinical potential, as many of the user- and system-dependent parameters of previous methods, including explicit vessel angle and diameter measurements, are eliminated.     

Optical microangiography of retina and choroid and measurement of total retinal blood flow in mice

We present a novel application of optical microangiography (OMAG) imaging technique for visualization of depth-resolved vascular network within retina and choroid as well as measurement of total retinal blood flow in mice. A fast speed spectral domain OCT imaging system at 820nm with a line scan rate of 140 kHz was developed to image the posterior segment of eyes in mice. By applying an OMAG algorithm to extract the moving blood flow signals out of the background tissue, we are able to provide true capillary level imaging of the retinal and choroidal vasculature. The microvascular patterns within different retinal layers are presented. An en face Doppler OCT approach [Srinivasan et al., Opt Express 18, 2477 (2010)] was adopted for retinal blood flow measurement. The flow is calculated by integrating the axial blood flow velocity over the vessel area measured in an en face plane without knowing the blood vessel angle. Total retinal blood flow can be measured from both retinal arteries and veins. The results indicate that OMAG has the potential for qualitative and quantitative evaluation of the microcirculation in posterior eye compartments in mouse models of retinopathy and neovascularization.OCIS codes: (170.4500) Optical coherence tomography, (170.3880) Medical and biological imaging     

能量多普勒显像与彩色多普勒显像显示血管内径准确性的实验比较

目的：比较能量多普勒显像（ＰＤＩ）和彩色多普勒血流显像（ＣＤＦＩ）显示离体模拟血流血管内边界的准确性。方法：在０．４ｍｍ、３ｍｍ和８ｍｍ内径的硅胶管中模拟低速血流,分别用二维超声（２ＤＵＳ）、ＣＤＦＩ及ＰＤＩ进行显像,准确测量各显像模式中各血管的血管内径或彩色血流直径。结果：①、２ＤＵＳ测量的各种血管内径与实际内径均无明显差别（Ｐ＞０．０５）;②、ＰＤＩ在０．４ｍｍ内径血管的血流显示中,ＰＤＩ血流直径比２ＤＵＳ的血管内径大２．４倍（Ｐ＜０．０１）;在３ｍｍ和８ｍｍ内径血管,ＰＤＩ血流直径与２ＤＵＳ的血管内径无明显差异（Ｐ＞０．０５）;③、在三种内径血管显示中,ＣＤＦＩ血流直径均明显大小ＰＤＩ血流直径（Ｐ＜０．０１）,且血流前后径明显大于血流横径（Ｐ＜０．０１）。结论：ＰＤＩ用血流直径代表血管内径的准确性明显高于ＣＤＦＩ,尤其在较粗的血管中,ＰＤＩ血流直径能准确反映血管内径。     

Imaging flow dynamics in murine coronary arteries with spectral domain optical Doppler tomography

Blood flow in murine epicardial and intra-myocardial coronary arteries was measured in vivo with spectral domain optical Doppler tomography (SD-ODT). Videos at frame rates up to 180 fps were collected and processed to extract phase shifts associated with moving erythrocytes in the coronary arteries. Radial averaging centered on the vessel lumen provided spatial smoothing of phase noise in a single cross-sectional frame for instantaneous peak velocity measurement without distortion of the flow profile. Temporal averaging synchronized to the cardiac cycle (i.e., gating) was also performed to reduce phase noise, although resulting in lower flow profiles. The vessel angle with respect to incident imaging beam was measured with three-dimensional raster scans collected from the same region as the high speed cross-sectional scans. The variability in peak phase measurement was 10-15% from cycle to cycle on a single animal but larger for measurements among animals. The inter-subject variability is attributed to factors related to real physiological and anatomical differences, instrumentation variables, and measurement error. The measured peak instantaneous flow velocity in a ~40-μm diameter vessel was 23.5 mm/s (28 kHz Doppler phase shift). In addition to measurement of the flow velocity, we observed several dynamic features of the vessel and surrounding myocardium in the intensity and phase sequences, including asymmetric vessel deformation and rapid flow reversal immediately following maximum flow, in confirmation of known coronary artery flow dynamics. SD-ODT is an optical imaging tool that can provide in vivo measures of structural and functional information on cardiac function in small animals.