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MR versus fluoroscopic guidance of a catheter/guidewire system: in vitro comparison of steerability.

Our purpose in this study was to evaluate the steerability of a combined catheter guidewire system with MR tracking in an open-configuration .5T MR system and compare it with fluoroscopic guidance. Experiments were performed with an aorta-shaped glass phantom with different-size branches connected to a roller flow pump to simulate pulsatile flow. A .035" guidewire was used in conjunction with a 5F Cobra 2-shaped catheter. For active MR guidance, a small RF coil was incorporated into the tips of all devices. In addition to fluoroscopic guidance, we used MR tracking devices to selectively catheterize all branches in the .5T open magnet (Signa SP, GEMS). Time requirements for the latter were compared with those needed under conventional angiographic conditions using standard catheters and guidewires. Active MR tracking permitted the simultaneous real time (4 updates/sec) guidance of both guidewire and catheter. Under MR guidance, all branch vessels were successfully catheterized. We found no significant differences in time requirements between guidance with the MR tracking device and fluoroscopic guidance. However, cannulation under fluoroscopic guidance with standard angiography devices required significantly less time (P < .05). Selective catheterization of small branch vessels is possible with active MR tracking of a combined catheter/guidewire system. Limitations of MR tracking device material and design result in a considerable lengthening of the cannulation procedures.

Aorta↗

Effects of pulsatile and nonpulsatile perfusion on vital organ recovery in pediatric heart surgery: a pilot clinical study.

The use of pulsatile flow during cardiopulmonary bypass (CPB) with regard to improved patient outcomes is controversial. We evaluated pulsatile perfusion in pediatric patients undergoing CPB in a clinical setting. Fifty consecutive pediatric patients undergoing open heart surgery for repair of congenital heart disease were prospectively entered into the study and randomly assigned to either the pulsatile perfusion group (group P, n = 25) or the nonpulsatile perfusion group (group NP, n = 25). Study parameters included intubation time, duration of intensive care unit (ICU) stay and hospital stay, need for inotropic support, preoperative and postoperative enzymes, creatinine, C-reactive protein, blood count, mean urine output, and total drainage. Group P, compared with group NP, had significantly less inotropic support (number of agents, 1.48 +/- 1.05 versus 2.44 +/- 1.03, p = 0.0015; dopamine, 6.48 +/- 3.27 versus 10.3 +/- 4.8 microg/kg per minute, p = 0.0023; dobutamine, 3.12 +/- 6.55 versus 8.03 +/- 9.1 microg/kg per minute, p = 0.034), shorter intubation period (20.36 +/- 17.02 versus 35.44 +/- 30.72 hours, p = 0.038), and shorter duration of ICU stay (2.16 +/- 1.07 versus 4.32 +/- 4.21 days, p = 0.028) and hospital stay (7.64 +/- 2.48 versus 11.84 +/- 6.82 days, p = 0.007). There were no significant differences in creatinine, enzyme levels, or drainage amounts between the two groups. Higher urine output during CPB (553.6 +/- 150.89 versus 465.8 +/- 151.23 ml/d, p = 0.045) and during the ICU period (658.8 +/- 210.99 versus 528,2 +/- 224.71 ml/d, p = 0.039) was observed in group P compared with group NP. We concluded that the use of pulsatile flow resulted in improved patient outcome in preserving cardiac function and maintaining better renal and pulmonic function (shorter intubation period) in the early postbypass period.

Cardiopulmonary Bypass↗

The measurement of blood flow waveforms from X-ray angiography. Part 1: Principles of the method and preliminary validation.

The principles and implementation of a method for measurement of blood flow waveforms from X-ray angiography are described. Contrast medium mass values are obtained at multitudinous positions along individual vessels and from numerous images in a time sequence. These values are represented as a matrix of grey levels in a parametric image. This image is normalized to represent contrast medium concentration, and the movement over time of isoconcentration portions of the contrast bolus is recovered to determine blood flow. Preliminary validation has been undertaken using parametric images generated in two ways: synthesis from a computer model of vascular pulsatile flow and analysis of cine-angiograms of physical models (plastic and perspex tubes) carrying known pulsatile flows. Two distinct methods for interrogation of parametric images by digital image processing were employed; both provided accurate flow measurements.

Blood Flow Velocity↗

A microcomputer-based data acquisition system for a prosthetic heart valve test apparatus.

The hydrodynamic testing of prosthetic heart valves in the laboratory under pulsatile flow conditions remains the only way of obtaining detailed information about valve function. Test procedures have become increasingly sophisticated, with a variety of different test conditions and detailed analysis of the pressure and flow signals. A computerized data acquisition system has been developed for use with the Glasgow pulsatile flow test apparatus. The computer collects seven signals from the test rig over a period of 20 s, and calculates the average waveform for each signal. Standard parameters, such as mean pressure differences, mean flows, regurgitant volumes and energy losses, are calculated automatically. The complexity of the analysis and the need for standardized documentation makes computerization essential. The system has been used extensively for function tests on over 160 prosthetic heart valves.

Biomedical Engineering↗

[Application of oligo-microarray in an in vitro study of the effects of pulsatile fluid shear stress on gene expression of human smooth muscle cells].

We assessed the effects of pulsatile flow shear stress on the gene expression profiles of human umbilical artery smooth muscle cells (HUASMCs) in vitro using the Express Chip DNA microarray method and investigated the difference between pulsatile and steady shear stress on differentially expressed genes of HUASMCs. In a modified pulsatile flow chamber system, HUASMCs were exposed to pulsatile and steady fluid shear stress (5.52 dyne/cm2) for 6 h respectively, and normal static cultured HUASMCs were selected as a control. The total cellular RNA was extracted by TRIzol Reagent (Life Technologies, Inc) according to the manufacturer's manual. Conversion of mRNA to single strand cDNA and double strand cDNA template was synthesized by Reverse Transcription from the total RNA. cRNA probe was transcribed with biotin labeling. After hybridization of probe with microarray, the binding of streptavidin to biotin was performed and amplified with the first antibody and further amplified with Cy3-conjugated second antibody. Then detection of Cy3 dye was carried out with ScanArray 5000. The results showed that a total of 1,330 genes revealed differential expression in HUASMCs exposed on pulsatile shear stress (5.52 dyne/cm2, 6 h); however, 2,676 genes revealed differential expression in HUASMCs exposed on steady shear stress. Comparsion of HUASMCs exposed to pulsatile with the HUASMCs exposed to steady shear stress showed there were 2,297 genes revealing differential expression. The transcriptional profile of fluidally induced genes in HUASMCs suggested a different response to pulsatile and steady shear stress.

Cells, Cultured↗

Computation of flow fields and shear rates in an aortic bifurcation.

A finite volume method in a boundary-fitted coordinate system together with a zonal grid method is employed to compute the flow fields and shear stresses in a two-dimensional aortic bifurcation. Eddy is found distal to plaques during pulsatile flow, whereas permanent eddies are observed only during steady flow. The computed flow fields are consistent with those visualized experimentally by other authors. It is also found that although the time averaged shear rates in a pulsatile flow are similar to those of a steady flow with mean Reynolds number in most regions, they are different in recirculation zones. This result implies that care should be taken if a steady flow shear rate were to be used in modeling shear-dependent physiological processes. The non-Newtonian viscosity has only a minor effect on the flows.

Aorta, Abdominal↗

Flow studies in a model carotid bifurcation.

Boundary layer separation in a plexiglass model carotid bifurcation was investigated in relation to the origin of atherosclerotic plaque clinically found in this region. Our model was comparable to a human carotid in both dimensions and geometry. Water flowed through the model at Reynolds numbers from 200 to 1200 under steady and pulsatile flow conditions, with outflow through the external and internal branches varied. The near-wall flow was visualized by slow injection of dye through ports machined in the model. Under steady flow at a physiological Reynolds number of 500 and a flow split at the bifurcation similar to that of a human carotid at rest, boundary layer separation was found to occur in a carotid sinus across from the external carotid origin, forming a shell of slowly moving fluid around the bifurcation. The rapidly moving mainstream impinged directly on the flow divider. The location of atherosclerotic plaque correlates best with the low shear region of separation and not with the region of high shear at the flow divider. Preliminary studies with pulsatile flow demonstrated little change from the steady flow results.

Arteriosclerosis↗

Evaluation of pulsatile and nonpulsatile flow in capillaries of goat skeletal muscle using intravital microscopy.

It is commonly believed that pulsatile flow generated by the pumping action of the heart is dampened out by the time it reaches the microcirculation. In clinical practice, most of the cardiopulmonary bypass pumps and ventricular assist devices are nonpulsatile. To test the hypothesis that pulsatile flow generated by the heart does exist at the microvascular level, intravital microscopy of a large animal model (goat) was developed to visualize and to videorecord the surface microcirculation of the flexor carpi ulnaris muscle from the right forelimb. Density of perfused capillaries and red blood cell velocity in capillaries were measured in five goats during pulsatile perfusion provided by the heart and during a subsequent 3-hr period of nonpulsatile perfusion provided by a centrifugal ventricular assist device (Centrimed, Sarns 3M) that bypassed the heart. Throughout the experiment, the heart rate, innominate artery mean blood pressure, and flow remained unchanged. During the pulsatile regimen, velocities showed regular fluctuations that coincided with the period of the cardiac cycle (range of periods: 0.5-0.8 sec). The peak velocity amplitudes (range: 0.25-0.55 mm/sec) correlated directly with the amplitude of the pulse pressure. During the nonpulsatile regimen, no such correlations were seen. During pulsatile flow and during the 3-hr nonpulsatile period, capillary density remained stable at 24 capillaries/mm of test line but there were significant increases in red cell velocity, from 0.8 to 1.2 mm/sec (P < 0.05), and in coefficient of variation of velocity (used as an index of flow heterogeneity), from 19 to 34% (P < 0.05). We conclude that (1) pulsatility exists in the capillary bed and that it directly correlates with the pumping action of the heart and (2) nonpulsatile flow produced by the ventricular assist device does not cause an acute deterioration in microvascular perfusion. We interpret the increase in heterogeneity of flow as an early sign of microvascular dysfunction. Prolonged use of the nonpulsatile device may, therefore, lead to deterioration in perfusion that could compromize the function of the organ.

Animals↗

The reversibility of impaired prostacyclin production of the vein graft.

The effects of changes in shear stress (shear stress variation) on production of prostacyclin (PGI2) were examined in canine autologous vein grafts, which were implanted in the poor or normal distal runoff limbs. Four weeks after grafting, the vein grafts were perfused ex vivo and PGI2 was assayed as 6-ketoprostaglandin F1 alpha. The vein grafts were perfused under constant flow for the first 30 min and then under pulsatile flow simulating an abnormal flow with a low shear stress variation or a normal flow with a high shear stress variation for the next 30 min. Basal production rates (30-min cumulative PGI2 production) of vein grafts implanted in the poor runoff and normal runoff limbs were 1.97 +/- 0.71 and 2.19 +/- 0.40 ng/cm2, respectively, with no significant difference. Pulsatile flow effects (increased PGI2 production between 30 and 60 min) of simulated abnormal versus normal flow were 0.50 +/- 0.50 ng/cm2 versus 2.31 +/- 1.87 ng/cm2 in vein grafts implanted in poor runoff limbs (P < 0.05) and 0.48 +/- 0.41 ng/cm2 versus 3.48 +/- 1.08 ng/cm2 in vein grafts implanted in normal runoff limbs (P < 0.01), respectively. There were no significant differences in simulated normal flow effects between poor runoff limbs and normal runoff limbs. The results indicate that the release of PGI2 in vein grafts may decrease in the presence of an abnormal blood flow with a low shear stress variation. In addition, it is suggested that even vein grafts implanted in the poor runoff could increase PGI2 production once the grafts were placed into normal arterial circulation.

Animals↗

Measurement of absolute flow rate in vessels using a stereoscopic DSA system.

We used a stereoscopic digital subtraction angiography (DSA) system to measure absolute blood flow rates in vessels. The magnification factor and the three-dimensional orientation of a selected vessel are obtained from automated analysis of stereoscopic DSA images. The cross-sectional area of the vessel is determined from the vessel diameter, which is measured with an iterative deconvolution technique. The time required for fluid to flow through a selected segment of a vessel is determined from the automated analysis of contrast medium 'time-density' curves. The effectiveness of these combined techniques was demonstrated in measurement of rates of both continuous and pulsatile flow in a vessel phantom, with the actual flow rate calibrated volumetrically or by an electromagnetic flowmeter. We have obtained accuracies in measured flow rates of approximately 5% and 18% for continuous and pulsatile flow respectively.

Angiography↗

Precise quantification of pressure flow waveforms of a pulsatile ventricular assist device.

Unreliable quantification of flow pulsatility has hampered many efforts to assess the importance of pulsatile perfusion. Generation of pulsatile flow depends upon an energy gradient. It is necessary to quantify pressure flow waveforms in terms of hemodynamic energy levels to make a valid comparison between perfusion modes during chronic support. The objective of this study was to quantify pressure flow waveforms in terms of energy equivalent pressure (EEP) and surplus hemodynamic energy (SHE) levels in an adult mock loop using a pulsatile ventricle assist system (VAD). A 70 cc Pierce-Donachy pneumatic pulsatile VAD was used with a Penn State adult mock loop. The pump flow rate was kept constant at 5 L/min with pump rates of 70 and 80 bpm and mean aortic pressures (MAP) of 80, 90, and 100 mm Hg, respectively. Pump flows were adjusted by varying the systolic pressure, systolic duration, and the diastolic vacuum of the pneumatic drive unit. The aortic pressure was adjusted by varying the systemic resistance of the mock loop EEP (mm Hg) = (integral of fpdf)/(integral of fdt) SHE (ergs/cm3) = 1,332 [((integral of fpdt)/(integral of fdt))--MAP] were calculated at each experimental stage. The difference between the EEP and the MAP is the extra energy generated by this device. This difference is approximately 10% in a normal human heart. The EEP levels were 88.3 +/- 0.9 mm Hg, 98.1 +/- 1.3 mm Hg, and 107.4 +/- 1.0 mm Hg with a pump rate of 70 bpm and an aortic pressure of 80 mm Hg, 90 mm Hg, and 100 mm Hg, respectively. Surplus hemodynamic energy in terms of ergs/cm3 was 11,039 +/- 1,236 ergs/cm3, 10,839 +/- 1,659 ergs/cm3, and 9,857 +/- 1,289 ergs/cm3, respectively. The percentage change from the mean aortic pressure to EEP was 10.4 +/- 1.2%, 9.0 +/- 1.4%, and 7.4 +/- 1.0% at the same experimental stages. Similar results were obtained when the pump rate was changed from 70 bpm to 80 bpm. The EEP and SHE formulas are adequate to quantify different levels of pulsatility for direct and meaningful comparisons. This particular pulsatile VAD system produces near physiologic hemodynamic energy levels at each experimental stage.

Adult↗

Validation of volume blood flow measurements using three-dimensional distance-concentration functions derived from digital x-ray angiograms.

RATIONALE AND OBJECTIVES: The authors present phantom validation of a method for computing pulsatile flow waveforms in arterial vessels from high-frame-rate biplane x-ray angiograms. METHODS: The three-dimensional course of a blood vessel is constructed from biplane digital x-ray angiograms. A parametric image of contrast mass versus time and true three-dimensional path length is generated. Adjacent contrast mass-distance profiles are matched to compute instantaneous velocity, which is multiplied by cross-sectional area to yield volume flow. An electromagnetic flowmeter was used to validate flow estimates in a phantom consisting of 150-mm tubes 3, 4, and 6 mm in diameter, orientated 15 degrees, 30 degrees, and 35 degrees to the imaging plane, with flow rates and waveforms expected in vivo. RESULTS: Mean and peak flows were accurate to within 9% and 10%, respectively, for velocities of less than 1 meter/second at a frame rate of 25 frames per second. CONCLUSIONS: A practical method for computing highly pulsatile flow waveforms in vivo in tortuous vessels is presented.

Algorithms↗

Flow characteristics in symmetrically branched tubes simulating the human aortic bifurcation.

The purpose of this study was to investigate the characteristics of flow in a symmetrically branched tube that had an area ratio (0.8) and angle of branching (70 deg) that were comparable to the human descending aorta. Velocity profiles were measured in steady and pulsatile flow with a laser Doppler anemometer. A region of transient flow reversal was found along the outer wall during minimal flow in the pulsatile cycle. Flow separation did not occur. For both steady and pulsatile flow, the shear rates were higher along the inner wall and lower along the outer wall in the region of the vertex of the bifurcation.

Aorta↗

Attenuation of flow disturbances in tapered arterial grafts.

Flow disturbances in tapered arterial grafts of angles of taper between 0.5 and 1.0 deg were measured in vitro using a pulsed ultrasound Doppler velocimeter. The increase in transition Reynolds numbers with angle of taper and axial distance was determined for steady flow. The instantaneous centerline velocities were measured distal to a 50 percent area stenosis (as a model of a proximal anastomosis), in steady and pulsatile flow, from which the disturbance intensities were calculated. A significant reduction in post-stenotic disturbance intensity was recorded in the tapered grafts, relative to a conventional cylindrical graft. In pulsatile flow with a large backflow component, however, there was an increase in disturbance intensity due to diverging flow during flow reversal. This was observed only in the 1.0 deg tapered graft. These findings indicate that taper is an important consideration in the design of vascular prostheses.

Blood Flow Velocity↗

Hemodynamics alter arterial low-density lipoprotein metabolism.

We have investigated the role of hemodynamic factors on low-density lipoprotein transport and metabolism in the intact arterial wall. Freshly excised canine carotid blood vessels were exposed to well-defined pulsatile flow in vitro for continuous periods up to 20 hours. We chose to impose the following hemodynamic conditions on our test carotid arteries: normotension, hypertension (at physiologic flow conditions), and hypertension coupled with elevated flow of canine serum perfusate. In several experiments the effect of endothelial denudation was examined in carotid arteries exposed to normotensive pulsatile flow. A trapped ligand method was used for quantitating low-density lipoprotein uptake and metabolism in the arterial wall. The distribution of both intact and degraded low-density lipoprotein fractions was determined from measurements of radiolabelled low-density lipoprotein activity within thin radial sections of perfused arteries. Our results suggest that both hypertensive hemodynamic simulations exacerbate the uptake of low-density lipoprotein within the arterial wall (by a factor of three to nine). The percentage of low-density lipoprotein that undergoes irreversible degradation falls from 41% under normotensive conditions to below 30% when hypertensive conditions are imposed, indicating that degradative processes are not proportionally elevated with the accelerated influx. A similar pattern is observed for deendothelialized vessels.

Animals↗

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.

Arteries↗

In vitro and in vivo comparison of three MR measurement methods for calculating vascular shear stress in the internal carotid artery.

BACKGROUND AND PURPOSE: Vascular abnormalities, such as atherosclerosis and the growth and rupture of cerebral aneurysms, result from a derangement in tissue metabolism and injury that are, in part, regulated by hemodynamic stress. The purpose of this study was to establish the feasibility and accuracy of determining wall shear rate in the internal carotid artery from phase-contrast MR data. METHODS: Three algorithms were used to generate shear rate estimates from both ungated and cardiac-gated 2D phase-contrast data. These algorithms were linear extrapolation (LE), linear estimation with correction for wall position (LE*), and quadratic extrapolation (QE). In vitro experiments were conducted by using a phantom under conditions of both nonpulsatile and pulsatile flow. The findings from five healthy volunteers were also studied. MR imaging-derived shear rates were compared with values calculated by solving the fluid flow equations. RESULTS: Findings of in vitro constant-flow experiments indicated that at one or two excitations, QE has the advantage of good accuracy and low variance. Results of in vitro pulsatile flow experiments showed that neither LE* nor QE differed significantly from the predicted value of wall shear stress, despite errors of 17% and 22%, respectively. In vivo data showed that QE did not differ significantly from the predicted value, whereas LE and LE* did. The percentages of errors for QE, LE, and LE* in vivo measurements were 98.5%, 28.5%, and 36.1%, respectively. The average residual of QE was low because the residuals were both above and below baseline whereas, on average, LE* tended to be a more biased overestimator of the shear rate in volunteers. The average and peak wall shear force in five volunteers was approximately 8.10 dyne/cm2 and 13.2 dyne/cm2, respectively. CONCLUSION: Our findings show that LE consistently underestimates the shear rate. Although LE* and QE may be used to estimate shear rate, errors of up to 36% should be expected because of variance above and below the true value for individual measurements.

Biomechanical Phenomena↗

Cerebrospinal fluid flow. III. Pathological cerebrospinal fluid pulsations.

Cardiac- and respiration-related movements of the cerebrospinal fluid (CSF) were investigated by MRI in 71 patients. In most patients with arteriosclerotic occlusive vascular disease CSF pulsations are normal. Decreased pulsatile flow is detectable in those with arteriovenous malformations, intracranial air and following lumbar puncture and withdrawal of CSF. Increased pulsatile flow in the cerebral aqueduct was found in 2 patients with large aneurysms, idiopathic communicating syringomyelia and in most cases of normal pressure hydrocephalus (NPH). CSF flow in the cervical spinal canal is, however, reduced or normal in NPH, indicating reduction of the unfolding ability of the surface of the brain and/or inhibition of rapid CSF movements in the subarachnoid space over its convexity.

Adult↗