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(Circulation. 1996;93:1502-1508.)
© 1996 American Heart Association, Inc.
Articles |
From the Departments of Internal Medicine (Cardiovascular Division) (W.G.H., R.A.L., C.L., D.E.S., D.L.W., J.E.W., L.D.H., R.M.P.) and Radiology (G.D.C., J.P., R.M., R.M.P.), The University of Texas Southwestern Medical Center, Dallas.
Correspondence to Ronald M. Peshock, MD, Mary Nell and Ralph B. Rogers Magnetic Resonance Center, The University of Texas Southwestern Medical Center, 5801 Forest Park, Dallas, TX 75235-9085. E-mail peshock@rad-rogers.swmed.edu.
| Abstract |
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Methods and Results Twelve subjects (7 men, 5 women; age, 44 to 67 years) underwent PC-MRI measurements of flow in the left anterior descending coronary artery or one of its diagonal branches at rest and after administration of adenosine (140 µg·kg-1·min-1 IV). Immediately thereafter, intracoronary Doppler velocity (IDV) and flow measurements were made during cardiac catheterization at rest and after intravenous administration of adenosine. For the 12 patients, the correlation between MRI and invasive measurements of coronary arterial flow and coronary arterial flow reserve was excellent: coronary flowMRI (mL/min)= 0.85xcoronary flowIDV (mL/min)+17 (mL/min), r=.89, and coronary flow reserveMRI=0.79xcoronary velocity reserveIDV+0.34, r=.89. For the range of coronary arterial flows (18 to 161 mL/min) measured by MRI, the limit of agreement between MRI and catheterization measurements of flow was -13±30 mL/min; for the range of coronary reserves (0.7 to 3.7) measured by MRI, the limit of agreement between the two techniques was 0.1±0.4.
Conclusions Cine velocity-encoded PC-MRI can noninvasively measure absolute coronary arterial flow in the left anterior descending artery in humans. PC-MRI can detect pharmacologically induced changes in coronary arterial flow and can reliably distinguish between those subjects with normal and abnormal coronary artery flow reserve.
Key Words: magnetic resonance imaging coronary disease regional blood flow
| Introduction |
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PC-MRI flow measurements are noninvasive and do not require intravascular injections or the use of ionizing radiation. Hydrogen nuclei in blood moving through a magnetic field gradient accumulate a phase shift proportional to their velocity,10 and flow is calculated by integration of blood velocity over the cross-sectional area of the vascular structure of interest. PC-MRI accurately quantifies flow in the aorta11 12 and carotid arteries13 in humans. Previous investigators measured diastolic coronary arterial velocity in normal volunteers during periods of breath holding using k-space segmentation or PEG.14 However, absolute coronary flow was not measured, the results were not validated, and the utility of PC-MRI to discriminate normal from abnormal velocity reserve was not assessed. Recently, Clarke et al15 used cine PC-MRI with PEG to measure coronary flow and flow reserve in closed-chest animals with partial coronary artery occlusion and to discriminate between vessels with and without significant epicardial stenoses. Because the accuracy and applicability of this technique are unproved in humans, we performed this blinded, prospective study to assess the accuracy of cine breath-hold PC-MRI for measuring coronary arterial flow and flow reserve in humans.
| Methods |
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Study Design
Each subject underwent MRI scanning followed immediately by
cardiac catheterization, so that both measurements were
separated by <2 hours. During both studies, coronary
arterial velocity and cross-sectional area were
measured under resting conditions and after administration of
adenosine 140
µg·kg-1·min-1
IV. This dose is commonly used during pharmacological coronary
vasodilation myocardial scintigraphy with thallium or
technetium sestamibi16 and is known to cause
coronary vasodilation similar in magnitude to that caused by
intracoronary injection of papaverine in normal
subjects.17 Heart rate and systemic arterial
pressure were monitored and recorded during both studies. All data,
including heart rate, systemic arterial pressure,
coronary velocity, and area determinations, were compiled,
analyzed, and stored without knowledge of the findings obtained
during the other procedure.
MRI Technique
MRI was performed with a 1.5-T Picker Vista HPQ whole-body
imaging system (Picker International, Inc). A standard quadrature spine
coil (20x26 cm) was used as a radiofrequency receiver. Each subject
was imaged in the supine position after placement of ECG monitoring
leads, a respiratory gating belt (to monitor the breath holds), and the
surface coil on the chest. Imaging parameters for coronal
and long-axis scout images of the heart were the same as for
previously published techniques18 incorporating breath
hold, fast-field echo sequences with first moment compensation in
the readout and slice-select directions, a repetition time of 20
ms, and an echo time of 9.4 ms. PEG was used to obtain multiple
phase-encoding steps for each frame during a cardiac
cycle.19 20
After obtaining scout views, we imaged the artery of interest in short-axis, tangential, and longitudinal planes. The purpose of these scans was to visualize the coronary vessel and to obtain a cross-sectional view perpendicular to the direction of flow throughout the cardiac cycle. The extra time spent in proper slice positioning was important to ensure that through-plane motion and partial volume effects would be minimal when vessel images were analyzed.15 In subjects in whom a signal void was detected proximally in the vessel of interest (indicating a potential arterial stenosis), cross-sectional images of the vessel were obtained along a straight segment distal to the area of dropout. Images were obtained with the same number of frames and PEG sizes as those of the scout images with two modifications: the field of view was decreased to 21 to 23 cm, thereby decreasing pixel sizes to 0.82 to 1.00 mm in the phase-encoding and readout directions, and an in-plane presaturation pulse was applied at the first frame of each cardiac cycle. The presaturation pulse was used to suppress signal from tissue in the slice so that in-flowing blood appeared bright and of different contrast relative to stationary tissue; no fat saturation pulses were used.
To measure flow, cine breath-hold PEG acquisitions with velocity compensation and encoding interleaved were positioned perpendicularly across vessel segments in the optimal slice positions determined from the cine scout images. A PEG size of 3 to 7 was selected for each subject studied to yield four to five frames per cardiac cycle. Other imaging parameters included a 7-mm slice thickness with a 256x256 to 256x224 matrix, a field of view of 21 to 23 cm (yielding pixel sizes of 0.82x0.82 to 0.89x1.00 mm), a flip angle of 40°, a repetition time of 19.5 ms, and an echo time of 11 ms. The total number of views was limited to keep the duration of the breath hold at 15 to 25 seconds. Resting coronary arterial flow was measured twice with the breath-hold technique, after which adenosine 140 µg·kg-1·min-1 IV was infused for 6 minutes. During the last 3 minutes of the infusion, coronary flow measurements were repeated twice (at 3 and 5 minutes into the infusion), each during periods of breath holding.
Velocity maps were generated by pixel-to-pixel subtraction of the velocity-sensitized and velocity-compensated phase images and the application of a correction algorithm designed to remove background phase error.11 21
Flow was calculated by summing the flow per frame over the cardiac cycle and multiplying by the mean heart rate during the measurement:
![]() | (1) |
where HR is heart rate (cardiac cycles per minute), n is number of frames in the cycle, Fi is flow in frame i of the cardiac cycle (cubic centimeters per frame), which is equal to the mean velocity over the vessel area (centimeters per second)xvessel area (square centimeters)x(2xPEG sizexrepetition time of the sequence) (seconds per frame). Vessel area was determined from
![]() | (2) |
![]() |
x Number of Pixels Within the Lumen of the Coronary Artery on the Magnitude Image
where FOV is the field of view.
With prospective gating, images were not acquired during the last 30 to 80 ms of diastole. For this terminal portion of the cardiac cycle, we estimated flow to be equivalent to flow in the last imaged diastolic frame.
MRI data were stored on optical disks for subsequent recall and analysis. To determine the interobserver variability of analyzing the PC-MRI images, images were analyzed by two investigators blinded to the results of the other investigator and catheterization. To evaluate the reproducibility of PC-MRI flow measurements, they were performed twice at baseline resting conditions and twice after the administration of adenosine. After completing the MRI scanning procedure, subjects were transferred immediately to the catheterization laboratory. The location within the coronary artery in which the PC-MRI flow measurements were made (with landmarks such as the branch points of septal and diagonal branches, the approximate distance in centimeters from the measurement point in the artery to the ostium of the left main coronary artery, and the distance distal to a potential stenosis)18 was given to the catheterization laboratory investigators. Other than the MRI measurement location in the coronary arterial segment, no results from the MRI study were given to the investigators in the catheterization laboratory.
Cardiac Catheterization
In each subject, a 7F or an 8F sheath was inserted
percutaneously into the femoral artery.
Intra-arterial and brachial cuff pressures, along with
heart rate and rhythm, were monitored and recorded. A 7F
diagnostic catheter was positioned in the left
coronary ostium, and a single arteriogram was performed with
nonionic contrast to exclude disease of the left main coronary
artery. A 0.014-in Doppler velocity wire (FloWire, Cardiometrics
Inc) was advanced into the vessel of interest to the same area of the
PC-MRI flow measurements and positioned to obtain a high-quality
phasic velocity and an APV during normal respiration and a 25-second
breath hold.22 23 In subjects with coronary
stenoses, the wire was positioned distal to the
stenosis at a location derived from the landmarks supplied by
the MRI investigators. After these baseline measurements were obtained,
a cineangiogram was obtained with nonionic contrast to
determine coronary arterial diameter.
Coronary velocities were allowed to return to baseline; then
the subject was given adenosine 140
µg·kg-1·min-1
IV over 6 minutes. Repeated coronary APV measurements were made
3 and 5 minutes into the infusion during breath hold and normal
respiration. During the last minute of the infusion, coronary
arterial diameter was reassessed angiographically.
Coronary velocity reserve was defined as the ratio of peak to resting APV after maximal dilation of the vascular territory with adenosine.24 Time-averaged coronary flow was determined with the following equation:
![]() | (3) |
where FlowD is Doppler-derived time-averaged flow (milliliters per minute) and d is vessel diameter.24 Mean velocity was estimated by assuming a parabolic velocity profile across the vessel, and vessel area was estimated by assuming a circular lumen. Cross-sectional diameter of the vessel 5 mm distal to the steel silhouette of the velocity wire seen on the cineangiograms (location of the sample volume reported by the manufacturer) was determined by use of computer-assisted quantitative coronary angiography (CAAS system, PIE Medical) according to previously published techniques.25 Coronary flow reserve was defined as the ratio of peak to resting flow velocity.
Data Analysis
To be included in the analysis, each subject was
required to complete both the MRI and catheterization
portions of the study with heart rates that did not vary by >15% and
mean systemic arterial pressures that did not vary by
>20%. All data are expressed as mean±SD. The values for
coronary arterial flow and coronary reserve
obtained invasively were compared with those measured by MRI with a
two-variable linear regression analysis. An
analysis of the limits of agreement between the
catheterization and MRI measurement methods as
described by Bland and Altman26 was performed.
| Results |
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Coronary arterial diameters by quantitative coronary arteriography ranged from 2.0 to 4.0 mm. The pixel sizes used to calculate coronary area by MRI ranged from 0.82x0.82 to 0.89x1.0 mm2, and the number of pixels seen within the vessel lumen on all the frames sampled in this study ranged from 4 to 18. The difference between catheterization measurements of coronary flow and flow reserve in subjects with normal respiration and during 20 to 25 seconds of breath holding was -5±12 mL/min (-9±12%) and 0.1±0.2 (1±6%), respectively.
Fig 2
shows the correlation between PC-MRI and
catheterization measurements of coronary
arterial flow. As Fig 3
shows, there was
good correlation between catheterization and PC-MRI
coronary reserve measurements. The limits of agreement (defined
as ±2 SD from the mean difference) between the invasive and PC-MRI
measurements of arterial flow and coronary reserve
are shown in Figs 4
and 5
. For the range
of coronary arterial flows (18 to 161 mL/min)
measured by PC-MRI, the interobserver variability was -5±19
mL/min, and the reproducibility for repeated measurements was 5±13
mL/min. For the range of coronary flow reserves (0.7 to 3.7)
measured by PC-MRI, the interobserver variability was 0±0.4
(5±14%).
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| Discussion |
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At present, absolute coronary arterial flow and flow reserve can be measured with a surgically placed flow probe, a Doppler velocity catheter or guide wire, or a coronary sinus thermodilution catheter.9 Each of these techniques is invasive and therefore impractical for repetitive assessments. The most commonly used noninvasive methods of measuring coronary flow reserve in humans can be quantitative (positron emission tomography29 and Doppler transesophageal echocardiography30 ) or qualitative (nuclear scintigraphy31 with thallium or technetium sestamibi radioisotopes). Although positron emission tomography can directly quantify myocardial perfusion, it requires the proximity of a cyclotron and is relatively expensive.29 Doppler transesophageal echocardiography has been used to estimate coronary flow reserve,30 but it is somewhat uncomfortable (because it requires esophageal intubation), and localizing the Doppler sample volume distal to a stenosis or a major side branch is difficult. Importantly, neither positron emission tomography nor Doppler transesophageal echocardiography quantifies absolute flow within a coronary vessel.32 Currently, the most widely used method for assessing myocardial perfusion is radionuclide perfusion imaging, but this process requires intravenous administration of a radioisotope and estimates regional myocardial blood flow relative to other regions of the heart, rather than quantifying absolute coronary arterial flow and flow reserve.31 32
Velocity-encoded PC-MRI measurements of flow in small-caliber
phantom models and coronary arteries in animals have proved
accurate and reproducible.15 21 They are noninvasive and
do not require the use of ionizing radiation or the administration of
radioactive isotopes. Unlike Doppler
echocardiography, which samples a velocity profile
over a limited sample volume and assumes a velocity profile within the
lumen of the vessel of interest, PC-MRI directly samples the entire
velocity profile within the vessel. Our data allow us to reach several
important conclusions. First, PC-MRI can determine absolute
coronary arterial flow in humans, and PC-MRI
measurements correlate well with those made invasively (see the Table
and Figs 2
and 4
). Second, PC-MRI can accurately assess
pharmacologically induced changes in coronary
arterial flow, thereby providing a reliable noninvasive
assessment of flow reserve (see the Table
and Figs 3
and 5
).
Additionally, with proper hemodynamic monitoring in the
MRI suite, intravenous adenosine can be
administered safely to patients undergoing an MRI examination. It is
well tolerated by patients during 20 to 25 seconds of breath holding.
As reflected by our catheterization data, 20- to
25-second periods of breath holding do not substantially alter
coronary arterial flow or flow reserve compared
with normal respiratory patterns.
Three technical differences exist between this and previous MRI
assessments of coronary flow reserve in humans. First, instead
of lying prone on the surface coil, our subjects were positioned
supine, with the surface coil resting on the chest; this technique was
well tolerated. Second, cine MRI with PEG was used to obtain flow
information throughout the cardiac cycle instead of during a single
diastolic frame. At baseline, the majority of flow occurred
during the first and last frames of our cine sequences, whereas with
adenosine infusion, the greatest percentage change in flow was
seen during the second and third frames of our sequence. The sampling
of multiple frames during the cardiac cycle appeared to be important
for accurate measurement of coronary flow reserve in our
subjects. Third, we acquired images with 0.82x0.82- to
0.89x1.00-mm2 pixel resolution. Tang et al33
showed that the error of measured volume flow rate is <10% if the
ratio of in-plane pixel dimension to vessel radius is <0.5,
thereby implying that
9 to 16 pixels would have to be sampled within
the vessel lumen to obtain accurate flow measurements. With the imaging
parameters used in this study, the data of Tang et al would
suggest that accurate flow measurements could be obtained only in
>3.5- to 4-mm-diameter vessels. However, more recently, Hofman et
al34 showed that accurate PC-MRI flow information can be
obtained in vessels in which only four pixels are sampled within the
vascular lumen. Our data suggest that accurate coronary
arterial flow and flow reserve measurements can be obtained
in vessels >2 to 2.5 mm in diameter with as few as four to eight
pixels sampled within the vascular lumen.
Using PC-MRI to obtain routine clinical measurements of coronary arterial flow and flow reserve in humans is appealing for several reasons. First, it is safe and easy to perform in an outpatient setting without an intravenous contrast agent. Second, it directly visualizes the coronary vessel of interest and provides quantitative epicardial flow information in a single procedure. Third, MRI is widely available. Fourth, because MRI is noninvasive, serial quantitative assessments are performed easily, a helpful feature when patients are followed long term and therapeutic interventions are monitored. Fifth, the technique described can be combined with other cardiovascular MRI examinations, such as determination of myocardial mass and ventricular volumes, ejection fraction, or systolic function. Finally, the use of accessory materials is minimal. MRI is not associated with the procurement, handling, and administration of radioactive isotopes or the one-time use of intracoronary Doppler guide wires.
Our study has limitations. First, all our subjects were in sinus
rhythm. None had frequent ventricular ectopy or atrial
fibrillation. We are uncertain whether this technique provides reliable
results in subjects with irregular rhythms. Second, we used
intravenous adenosine to induce coronary
vasodilation. Although it is widely used clinically and causes
coronary artery vasodilation similar in magnitude to that
caused by intracoronary injection of papaverine in normal
subjects, its effects in subjects with disease processes affecting the
coronary microcirculation (ie, diabetes mellitus, concentric
hypertrophy, or
hypercholesterolemia) are not well described.
Third, although MRI data are acquired rapidly, processing and
analysis may be time-consuming when performed manually.
However, with automated analysis programs, these times are
reduced substantially (<1 minute for flow
measurements).35 Fourth, we measured coronary
arterial flow only in the LAD or its diagonal branches.
Previous MRI coronary angiographic studies36 noted
decreased sensitivity and specificity for detecting vessels on the
lateral wall of the left ventricle; however, special coils or phased
array units that improve signals from the lateral and posterior walls
may improve these results.37 Fifth, in three subjects
(subjects 9 through 11, the Table
), MRI flow measurements tended to be
larger than invasive measurements. In these subjects, the matrix size
was decreased (pixel sizes were
0.95 mm2), and
undersampling was used to decrease the duration of the breath hold.
Partial volume effects (causing overestimation of coronary
arterial area) or wraparound noise artifact may have
introduced errors into the MRI flow calculations. Finally, while
Doppler-derived assessments of coronary velocity and
flow reserve are used widely, they are not a perfect gold-standard
measurement technique. Doppler wire velocity measurements assume a
parabolic velocity profile within the vascular lumen, and
coronary area determinations are derived from formulas that
assume a circular vessel lumen.
In conclusion, cine velocity-encoded PC-MRI can noninvasively measure absolute coronary arterial flow in the LAD in humans. PC-MRI can detect pharmacologically induced changes in coronary arterial flow and reliably distinguish between those subjects with normal and abnormal coronary arterial flow reserve. Without the use of ionizing radiation or intravenous contrast agents, it provides a unique, widely available, well-tolerated method in humans for directly visualizing coronary arteries and assessing the physiological response of the coronary circulation to pharmacological stimuli.
| Selected Abbreviations and Acronyms |
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| Acknowledgments |
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Received September 20, 1995; revision received November 1, 1995; accepted November 5, 1995.
| References |
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