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(Circulation. 1995;92:1151-1158.)
© 1995 American Heart Association, Inc.

Articles

Magnetic Resonance Imaging Assessment of the Severity of Mitral Regurgitation

Comparison With Invasive Techniques

W. Gregory Hundley, MD; Hong F. Li, BS; John E. Willard, MD; Charles Landau, MD; Richard A. Lange, MD; Benjamin M. Meshack; L. David Hillis, MD; Ronald M. Peshock, MD

From the Departments of Internal Medicine, Cardiovascular Division (W.G.H., J.E.W., C.L., R.A.L., B.M.M., L.D.H., R.M.P.), and Radiology (H.F.L., R.M.P.), University of Texas Southwestern Medical Center, Dallas.

Correspondence to Ronald M. Peshock, MD, Mary Nell and Ralph B. Rogers Magnetic Resonance Center, 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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Background In the patient with mitral regurgitation who is being considered for valvular surgery, cardiac catheterization is usually performed to quantify the severity of regurgitation and to determine its influence on left ventricular volumes and systolic function. Magnetic resonance imaging (MRI) potentially provides a rapid, noninvasive method of acquiring these data. Thus, this study was done to determine whether MRI can reliably measure the magnitude of mitral regurgitation and evaluate the effect of regurgitation on left ventricular volumes and systolic function.

Methods and Results Twenty-three subjects (14 women and 9 men 15 to 72 years of age) with (n=17) or without (n=6) mitral regurgitation underwent MRI scanning followed immediately by cardiac catheterization. The presence (or absence) of valvular regurgitation was determined, and left ventricular volumes and regurgitant fraction were quantified during each procedure. There was excellent correlation between invasive and MRI assessments of left ventricular end-diastolic (r=.95) and end-systolic (r=.95) volumes and regurgitant fraction (r=.96). All MRI examinations were completed in <28 minutes.

Conclusions In the patient with mitral regurgitation, MRI compares favorably with cardiac catheterization for assessment of the magnitude of regurgitation and its influence on left ventricular volumes and systolic function.

Key Words: regurgitation • magnetic resonance imaging • mitral valve • cardiovascular images • blood flow

	Introduction

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In the patient with chronic mitral insufficiency, regurgitation of a portion of the left ventricular stroke volume into the left atrium results in left ventricular diastolic volume overload.^{1 2 3} This, in turn, often leads to left ventricular systolic dysfunction and increased end-systolic volume.^{4 5} In general, surgical intervention is warranted if symptoms of pulmonary congestion persist despite appropriate medical therapy or left ventricular systolic dysfunction develops, even without symptoms.^{6 7} Therefore, evaluation of the patient with mitral regurgitation requires confirmation of its presence, assessment of its magnitude, and determination of its influence on left ventricular contractile function.⁸ An accurate, rapid, noninvasive, and widely available technique for quantitative assessment of the severity and physiological importance of mitral regurgitation is highly desirable.

Magnetic resonance imaging (MRI) is a noninvasive modality that is well suited for evaluating the cardiovascular system with high spatial and temporal resolution.⁹ It has been used to assess cardiac structure,^{10 11} quantify ventricular volumes¹² and ejection fraction,¹³ measure flow in the great vessels,^{14 15} and estimate flow through regurgitant valves.^{16 17} However, no previous study has rigorously examined the accuracy and expense of assessing mitral valvular regurgitation by MRI. Accordingly, this study was performed for these purposes.

	Methods

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Study Population
The study was approved by the Institutional Review Board for Human Experimentation at the University of Texas Southwestern Medical Center at Dallas, and all participants gave written, informed consent. The study population consisted of 23 subjects (14 women and 9 men 15 to 72 years of age) referred for cardiac catheterization for hemodynamic evaluation. Patients were ineligible for enrollment if they had an in-dwelling pacemaker, intracranial clips, intra-auricular or intraocular implant, a history of metal fragments in the eye, claustrophobia, marked ventricular ectopy (bigeminy, trigeminy, or >20 premature ventricular contractions per minute), or aortic or pulmonic stenosis.

Study Design
In each of the 23 subjects, we attempted to visualize the regurgitant jet with MRI and contrast ventriculography and then compare MRI measurements of left ventricular and regurgitant volumes with those made during cardiac catheterization. Left ventricular stroke volume index (LVSVI) was calculated as the difference between left ventricular end-diastolic volume index (LVEDVI) and end-systolic volume index (LVESVI), and the left ventricular cardiac index (LVCI) was calculated as the product of LVSVI and heart rate. The regurgitant volume index (RVI) was calculated by subtracting forward cardiac index (FCI) from LVCI, and regurgitant fraction (RF) was measured by dividing RVI by LVCI.

Each subject underwent MRI scanning followed immediately by cardiac catheterization, so MRI and catheterization volume and flow measurements were made within 1 to 2 hours. Heart rate and systemic arterial pressure were monitored and recorded during both studies. All data, including heart rate, blood pressure, forward cardiac output, and left ventricular volume 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). Each patient was positioned supine on the MRI table after placement of ECG monitoring leads, a respiratory gating belt, and a brachial blood pressure cuff. All MRI scans used prospective ECG and respiratory gating. MRI signal acquisition was performed with a method of k-space segmentation called phase encoding grouping (PEG), which acquires multiple phase encoding steps for each cardiac frame during each cardiac cycle.¹⁸ Multislice gradient-echo PEG sequences were used to obtain coronal and long-axis images of the left ventricle for viewing the presence of regurgitant jets and positioning later acquisitions.

Interleaved, velocity-encoded, phase-difference PEG sequences were used to measure forward cardiac output. The imaging plane was positioned perpendicular to the proximal aorta, 2 to 4 cm above the aortic valve and distal to the coronary ostia. A PEG size of two (yielding 8 to 12 frames per cardiac cycle) was used for all patients. These scans were 10-mm-thick slices with 256x256 matrices, a field of view ranging from 30 to 35 cm (yielding voxel sizes of approximately 1x1.3x10 mm), a flip angle of 40°, a repetition time of 19.5 ms, and an echo time of 11 ms. After Fourier transformation of the first-order, motion-compensated reference scan and the velocity sensitized scan into two sets of images (magnitude and corresponding phase image), velocity maps were generated by pixel-to-pixel subtraction of the velocity-sensitized and velocity-compensated phase images and application of a correction algorithm designed to remove background phase error:F_i=Flow in Frame i of the Cardiac Cycle (cm³/frame)=Mean Velocity (cm/s)xArea (cm²)x(2xPEG SizexRepetition Time of the sequence) (s/frame), where:

where FOV is the field of view, and Mean Velocity=Average Pixel Intensity Within the Vessel Lumen on the Velocity Map for Each Frame in the Sequence. Thus,

where F_i is the flow in frame i and n is the number of frames in the cycle plus the last interval of the cycle. Patients 11 and 17 had mild to moderate aortic regurgitation. In these subjects, only the frames with forward flow were included in the forward flow determination.¹⁹

Multiframe short-axis, gradient-echo sequences with a PEG size of two (temporal resolution of 40 ms) were used to calculate left ventricular volumes. These sequences were positioned perpendicular to the long axis of the ventricle spanning apex to base. They were 8-mm slices separated by a 2-mm gap with 256x200 to 256x256 matrices with a field of view ranging from 28 to 39 cm (yielding voxel sizes of approximately 1x1.1x8 mm to 1x2.0x8 mm), flip angle of 60°, repetition time of 19.5 ms, and echo time of 9.4 ms. For left ventricular volume determinations, the endocardial border of each slice was identified by use of a contour-following, gradient-based, semiautomated drawing program,²⁰ and volumes were calculated by summation (Simpson's rule).²¹ Basal slices were reviewed in cine format to resolve structures for inclusion (the aortic outflow tract) or exclusion (left atrium and mitral leaflets) from the volume measurements. Because subject 17 had a mitral valve prosthesis, volumetric determinations were also acquired with a multislice spin-echo sequence to reduce the artifact from the metal struts of the prosthesis.

MRIs were stored on optical disks for subsequent recall and analysis. To determine the interobserver variability of analyzing the phase-difference forward flow, gradient-echo volumetric images, and determinations of RF, images were analyzed by two investigators blinded to the other's results and to the results of catheterization. Upon completion of the MRI scanning procedure, patients were transferred immediately to the catheterization laboratory.

Cardiac Catheterization
In each subject, 8F sheaths were inserted percutaneously into the femoral vein and artery. A 7.5F flow-directed, balloon-tipped thermodilution catheter was advanced to the pulmonary artery. Forward cardiac output was measured by the Fick principle (using a timed collection of expired air to measure oxygen consumption) and the thermodilution technique according to methods described previously.^{22 23} In previous studies from our laboratory, results of the Fick principle and thermodilution are within 20% of one another in 90% of subjects^{23 24} ; therefore, the catheterization measurement of forward cardiac output was reported as the mean of the Fick and thermodilution values for each patient.

Immediately thereafter, single-plane (30° right anterior oblique) or biplane (30° right and 60° left anterior oblique) left ventriculography was performed according to previously described methods.^{25 26} Left ventricular volumes were calculated by the area-length method of Dodge et al²⁷ and corrected with the regression equation of Kennedy et al²⁸ or Wynne et al²⁹ for single or biplane left ventriculography, respectively. Left ventricular volumes were quantified from a well-opacified sinus beat not preceded by an extrasystole for patients in sinus rhythm; for those with atrial fibrillation, volumes were quantified from the average of 3 to 5 consecutive beats not preceded by an extrasystole. Additionally, for each patient, the angiographic severity of mitral regurgitation (0 to 4+) was agreed on by three observers according to previously published criteria.³⁰ To determine the interobserver variability of measuring left ventricular volumes and RF, studies were analyzed by two investigators blinded to the other's results and to the results of MRI.

Data Analysis
To be included in the analysis, each patient was required to complete both the MRI and catheterization portions of the two studies 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 LVEDVI and LVESVI, LVSVI, FCI, RVI, and RF obtained invasively were compared with those measured by MRI with a two-variable linear regression analysis. An analysis of the differences of the measurements was performed according to the technique of Bland and Altman.³¹

Procedure Expenses
To estimate the expense of catheterization, regional outpatient Medicare reimbursement for catheterization and ventriculography (with and without selective coronary angiography) of the right and left sides of the heart, physician fees associated with catheterization, and a 23-hour observation period in a non–telemetry-monitored hospital bed were used (current procedural terminology [CPT] codes 93526, 93555, 93556, 99217, and 99218).³² Because transthoracic echocardiography (TTE) is sometimes used to evaluate these patients, Medicare reimbursements for color Doppler TTE and physician's interpretation also were obtained (CPT codes 93307 and 93325).³² To estimate the expense of the MRI scan, Medicare reimbursement for obtaining the scan and physician reimbursement for interpreting a functional cardiac imaging procedure (CPT code 75554) were used.³²

	Results

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MRI studies were well tolerated and completed in all subjects. Nineteen patients underwent single-plane contrast left ventriculography, and 4 (patients 18, 20, 21, and 23) had biplane ventriculography. Twenty-one patients were in sinus rhythm, and 2 (patients 17 and 20) had atrial fibrillation. The duration of the MRI procedure (actual time spent in the magnet) was <28 minutes for all subjects. Table 1 gives detailed data on the 23 subjects.

View this table: [in this window] [in a new window]   Table 1. Summary of Patient Data

All 17 patients with angiographic evidence of mitral regurgitation (5 with 1+, 6 with 2+, and 6 with 3+ or 4+) had visible regurgitant jets on the MRI long-axis view of the left ventricle. As Fig 1 shows, the MRI measurements of LVEDVI, LVESVI, and LVSVI correlated well with those obtained by catheterization, although the MRI measurements of LVEDVI and LVESVI were consistently somewhat smaller (11±11 and 13±11 mL/m², respectively, as shown in Fig 2). For both RVI and RF, there was excellent correlation (Fig 3) and agreement (Fig 4) between the invasive and MRI measurements. The interobserver variabilities for the MRI measurements of flow in the aorta, left ventricular volumes, and RF were 3±3%, 9±7%, and 10±9%, respectively. For the catheterization measurements of ventricular volumes and RF, the interobserver variabilities were 11±12% and 7±8%, respectively.

View larger version (12K): [in this window] [in a new window]   Figure 1. Scatterplots showing catheterization (horizontal axes) and magnetic resonance imaging (MRI, vertical axes) measurements of (A) end-diastolic, (B) end-systolic, and (C) stroke volumes indexed for body surface for 23 patients. Each symbol represents data from 1 patient. Shown are the regression lines (solid lines), 95% CIs (dashed lines), and regression equations.

View larger version (12K): [in this window] [in a new window]   Figure 2. Scatterplots showing mean (A) end-diastolic, (B) end-systolic, and (C) stroke volumes indexed for body surface area by catheterization and magnetic resonance imaging (MRI, horizontal axes) and the difference between catheterization and MRI measurements (vertical axes) for 23 patients. Each symbol represents data from 1 patient. The mean difference (solid lines) ±2 SD (dashed lines) is shown. MRI consistently underestimated left ventricular end-diastolic and end-systolic volume measurements compared with catheterization (A and B). However, MRI and catheterization left ventricular stroke volume measurements were in good agreement (C).

View larger version (11K): [in this window] [in a new window]   Figure 3. Scatterplots showing catheterization (horizontal axes) and magnetic resonance imaging (MRI, vertical axes) measurements of (A) cardiac index, (B) regurgitant volume index, and (C) regurgitant fraction for 23 patients. Each symbol represents data from 1 patient. Shown are the regression lines (solid lines) and equations; the dashed lines represent the ±95% CIs for the regression equations.

View larger version (11K): [in this window] [in a new window]   Figure 4. Scatterplots showing mean (A) cardiac index, (B) regurgitant volume, and (C) regurgitant fraction indexed for body surface area by catheterization and magnetic resonance imaging (MRI, horizontal axes) and the difference between catheterization and MRI measurements (vertical axes) for 23 patients. Each symbol represents data from 1 patient. The mean difference (solid lines) ±2 SD (dashed lines) is shown. There is excellent agreement between MRI and catheterization measurements of regurgitant volume index and regurgitant fraction.

Table 2 gives the Medicare reimbursements for a color Doppler TTE, catheterization of the right and left sides of the heart (with and without selective contrast coronary angiography), and an MRI functional cardiac examination.

View this table: [in this window] [in a new window]   Table 2. Medicare Reimbursement for Outpatient Procedures1

	Discussion

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Evaluation of the patient with mitral regurgitation should include confirming the presence of regurgitation, quantifying it, and determining its influence on left ventricular volumes and systolic function. Mitral regurgitation is usually confirmed qualitatively with contrast ventriculography or color Doppler echocardiography.^{33 34} Although these techniques allow one to establish the presence of mitral regurgitation, they imprecisely quantify it.^{34 35} Valvular regurgitation is quantified by cardiac catheterization, during which the regurgitant flow is calculated by subtracting the forward cardiac output (measured by the Fick principle or indicator dilution) from the left ventricular output (measured by contrast ventriculography). Although this provides a more accurate assessment of regurgitation than angiographic grading or color Doppler estimates, it is invasive, not risk-free, time-consuming, subject to inaccuracies in some patients, and not well suited for repetitive measurements.^{8 36}

Left ventricular volume measurements provide insight into the severity of regurgitation and its effect on left ventricular systolic function. These assessments help to determine the patient's suitability for surgical correction^{37 38} and his or her perioperative mortality.^{6 7} Although noninvasive estimates of left ventricular volumes can be obtained with TTE, several factors may limit the echocardiographic acquisition of these data, including obtaining adequate acoustic windows, particularly of the cardiac apex; foreshortening of the left ventricle (because the transducer is not positioned at the true cardiac apex); and obtaining adequate endocardial definition because of limited lateral resolution of the transducer.³⁹ Because of these difficulties, contrast left ventriculography is usually performed to measure left ventricular volumes in the patient with mitral regurgitation,⁸ but it is invasive, and the area-length equation used to quantify volumes is based on certain assumptions about left ventricular shape that, in certain circumstances, may be invalid.^{25 26 27 28 29}

MRI is well suited for depicting cardiac anatomy, determining left ventricular function, and measuring flow. With it, cardiovascular anatomy can be tomographically imaged in virtually any plane, and unlike TTE, it has no acoustic window limitations. When the image acquisition is synchronized to the onset of the QRS complex (cardiac gating) and diaphragmatic excursion (respiratory gating), gradient-echo sequences can acquire images with superb clarity and well-defined blood-tissue interfaces. By viewing these images in cine format, one can obtain high-temporal-resolution information concerning left ventricular volumes, ejection fraction, and wall motion.^{12 13} In addition, the ability to acquire this information in three dimensions with MRI provides an advantage over conventional imaging techniques, particularly in assessments of patients with distorted ventricular shapes.

Changes in the phase of the MRI signal can be used to measure velocity and subsequently to derive flow measurements. Velocity-encoded, phase-difference measurements of flow in phantom models, animals, and humans have proved reliable and do not have the limitations of conventional techniques.^{14 15} Unlike Doppler echocardiography, which samples a velocity profile over a limited sample volume, MRI samples the entire velocity profile within the vessel. Compared with catheterization, MRI flow measurements are noninvasive and do not require the use of ionizing radiation. As the results of our study indicate, a single MRI examination can provide reliable measurements of left ventricular volumes, forward cardiac output, regurgitant volumes, and RF compared with those made by catheterization under similar hemodynamic conditions (Table 1 and Figs 1 through 4).

Numerous features make MRI attractive for evaluation of patients with mitral regurgitation. First, it is safe and easily performed in an outpatient setting without the need for intravenous injections. Second, it provides quantitative ventricular volume and cardiovascular flow information rapidly and efficiently with a single examination. The incorporation of PEG allows the completion of multislice short-axis ventricular volume determinations in <15 minutes and velocity-encoded, phase-difference flow sequences in <3 minutes; therefore, a complete examination (the entire time a patient is on the MRI table) requires <30 minutes. Third, MRI is widely available. This study was performed on a conventional 1.5-T MRI scanner without special modifications of the system hardware. Fourth, because MRI is noninvasive, serial quantitative assessments are easily performed. This is helpful when one is following patients long term and choosing the optimal time for surgical intervention. Finally, from Medicare reimbursement guidelines, the results of this study indicate that MRI can accurately measure left ventricular volumes, forward cardiac output, regurgitant volume, and RF at an expense competitive with Doppler TTE and substantially lower than cardiac catheterization (Table 2).

Our study has limitations. First, most of our patients were in sinus rhythm. None had frequent ventricular ectopy, and only 2 had atrial fibrillation. We are uncertain whether this technique provides reliable results in subjects with irregular rhythms. Second, we excluded patients with aortic stenosis because they have turbulent, high-velocity flow jets in the proximal great vessels. Third, compared with the results of catheterization, the MRI-derived assessments of left ventricular volumes and forward flow were consistently somewhat smaller (Figs 1 and 2). As opposed to contrast ventriculography, the left ventricular papillary muscles and trabeculae are well visualized with MRI, so MRI assessments of the left ventricular cavity are potentially more accurate than those of contrast ventriculography.^{12 13} Fourth, although MRI data are acquired rapidly, processing and analysis may be time-consuming when performed manually (20 minutes for volume and 50 minutes for flow data). However, with automated analysis programs, these times are reduced substantially (<1 minute for flow and <5 minutes for volume measurements).^{40 41} Fifth, MRI currently cannot reliably assess coronary anatomy. In patients in whom the determination of coronary anatomy is deemed necessary, contrast coronary angiography is required. Finally, it was not the intent of this study to measure pulmonary arterial pressures by MRI. When this information is required, it must be obtained by catheterization of the right side of the heart or estimated by TTE by sampling the velocity jet through a regurgitant tricuspid valve.

In conclusion, when considering surgical intervention in the patient with mitral regurgitation, cine gradient-echo and velocity-encoded, phase-difference MRI can accurately assess the magnitude of regurgitation and help to determine the patient's suitability for surgical correction and estimate perioperative mortality by determining left ventricular systolic function. MRI is safe, efficient, and widely available, and it does not require intravascular injections or the use of ionizing radiation. Because it inexpensively and noninvasively allows one to make left ventricular and regurgitant volume measurements, it is well suited to repetitive evaluations in attempts to determine the optimal time for surgical intervention.

	Acknowledgments

 
This research was supported in part by grants from the NIH Special Center of Research (Ischemic SCOR grant HL-17669), the Moss Heart Fund, the Society of Cardiac Angiography and Intervention, Squibb Diagnostics, and Picker International, Inc.

Received December 14, 1994; revision received March 2, 1995; accepted March 5, 1995.

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