| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Experimental Studies |
1 From the Department of Radiology, University of California San Francisco, 505 Parnassus Ave, Rm L-308, Box 0628, San Francisco, CA 94143-0628 (G.K.L., M.F.W., C.B.H., M.S.); GE Medical Systems, Milwaukee, Wis (A.S.); and the Departments of Clinical Physiology (H.A.) and Radiation Physics (F.S.), Lund University Hospital, Lund, Sweden. Received October 28, 1999; revision requested December 15; revision received January 27, 2000; accepted February 1. G.K.L. supported in part by a scholarship from the University Hospital Eppendorf, Hamburg, Germany. Address correspondence to M.S. (e-mail: Maythem.Saeed@radiology.ucsf.edu).
 |
ABSTRACT |
|---|
 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
MATERIALS AND METHODS: Measurements of coronary sinus flow were performed in seven dogs by using VEC MR imaging at baseline, single coronary arterial stenosis, dipyridamole stress, and reactive hyperemia. These measurements were compared with flow probe measurements of coronary blood flow (CBF) in the left anterior descending coronary (LAD) and circumflex (CFX) arteries (CBFLAD+CFX) and coronary sinus. LV blood perfusion was calculated in milliliters per minute per gram from coronary sinus flow, and LV mass was obtained by using VEC and cine MR imaging. LV mass was validated at autopsy.
RESULTS: CBFLAD+CFX and coronary sinus flow at VEC MR imaging showed close correlation (r = 0.98, P < .001). The difference between CBFLAD+CFX and MR coronary sinus flow was 3.1 mL/min ± 8.5 (SD). LV mass at cine MR imaging was not significantly different from that at autopsy (73.2 g ± 12.8 vs 69.4 g ± 12.8). At baseline, myocardial perfusion was 0.40 mL/min/g ± 0.09 at VEC MR imaging, and CBFLAD+CFX was 0.44 mL/min/g ± 0.08 (not significant). Reactive hyperemia resulted in 2.7- and 2.3-fold increases in coronary sinus flow at VEC MR imaging and flow probe CBFLAD+CFX, respectively.
CONCLUSION: VEC MR imaging has the potential to measure coronary sinus flow during different physiologic conditions and can serve as a noninvasive modality to quantify global LV perfusion in patients.
Index terms: Coronary vessels, flow dynamics, 543.12144, 544.12144 • Coronary vessels, MR, 543.12144, 544.12144 • Coronary vessels, stenosis or obstruction, 543.764, 544.764 • Magnetic resonance (MR), cine studies, 543.12144, 544.12144, 547.12144 • Magnetic resonance (MR), experimental studies, 543.12144, 544.12144, 547.12144 • Magnetic resonance (MR), vascular studies, 543.12144, 544.12144 • Myocardium, blood supply, 511.12144
|
INTRODUCTION |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
Results of recent studies have shown the potential of velocity-encoded cine (VEC) magnetic resonance (MR) imaging in quantifying blood flow in the aorta (10), pulmonary arteries (11), and coronary arteries (12,13). Measurement of coronary sinus flow at VEC MR imaging was reported by van Rossum et al (14), who found a mean coronary sinus blood flow volume of 144 mL/min ± 62 (SD) in healthy subjects. Schwitter et al (15) found a good correlation of coronary sinus flow measured at VEC MR imaging and measurements of myocardial perfusion at positron emission tomography (PET) in healthy volunteers and in orthotopic heart transplant recipients. More recently, Kawada et al (16) applied VEC MR imaging in the measurement of coronary sinus flow in patients with hypertrophic cardiomyopathy. They found a severely depressed coronary flow reserve in patients with hypertrophic cardiomyopathy compared with that in healthy subjects.
The purposes of the current study were as follows: (a) To measure coronary sinus flow by using VEC MR imaging and to validate these measurements by using ultrasonic (US) flow probes as a reference standard. Coronary sinus flow measurements were conducted at baseline, single coronary arterial stenosis, vasodilated state (dipyridamole stress test), and reactive hyperemia; (b) to calculate LV perfusion per gram of myocardial mass. Therefore, LV mass was estimated by using cine MR imaging and was validated by the true mass measured at autopsy.
|
MATERIALS AND METHODS |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
Coronary sinus and coronary arterial blood flow volumes were measured in milliliters per minute by using flow probes as a reference standard with an absolute accuracy of plus or minus 15% and a zero offset of plus or minus 3.0 mL/min (18). Proximal segments of the left anterior descending coronary (LAD) and circumflex (CFX) arteries were isolated from surrounding epicardial tissue. The size of the flow probe (2–3 mm) was selected so that the vessel filled the probe’s acoustic window. All flow probes were secured by means of epicardial suture to prevent movement and dislocation during myocardial contraction. Jelly (Signa Jel; Parker Laboratories, Orange, NJ) was applied repeatedly as an acoustic couplant to supplant the air between the vessel and the flow probe to complete the acoustic pathway during the study.
The flow probes were connected to a volume flowmeter (Transonic T208; Transonic Systems, Ithaca, NY) by using an MR-compatible cable with a 10-MHz low-pass filter. An inflatable silicone occluder was placed around the CFX 2–3 mm distal to the flow probe. The occluder was connected to an angioplasty balloon inflator (Monarch; Merit Medical, Salt Lake City, Utah) and was secured by means of an epicardial suture without altering the basal level of CFX flow. Coronary arterial stenosis was established by slowly inflating the occluder, and the degree of stenosis was adjusted to reduce blood flow gradually. The animal was placed in the imager head first with the open chest held in the right lateral decubitus position by using a Plexiglas holder.
Cine MR Imaging for the LV Mass
All images were acquired with a 1.5-T MR imager (Signa; GE Medical Systems, Milwaukee, Wis) by using system software version 5.6 and a standard head receiver coil. A four-lead electrocardiographic apparatus and bellows were attached to the animal for cardiac and respiratory gating. Double oblique short-axis images of the left ventricle were acquired during 32 successive cardiac cycles during a breath hold at expiration. A fast cine MR sequence (FASTCARD; GE Medical Systems) was used with a k-space segmentation of eight lines per segment. Typical imaging parameters were as follows: 17/2.8 (repetition time msec/echo time msec); section thickness, 10 mm; field of view, 22 x 22 cm; and image matrix, 256 x 256. During one breath hold, five to seven data sets were acquired, and view sharing (19) was used to obtain nine to 13 images representing the cardiac cycle. Imaging was repeated in eight to nine contiguous short-axis sections to cover the entire left ventricle from apex to base.
VEC MR Imaging for Coronary Sinus Flow
The coronary sinus was localized on a basal short-axis image depicting the left and right atria and the root of the ascending aorta. Coronary sinus flow measurements were performed on a plane orthogonal to the short-axis view and dissected the coronary sinus perpendicularly approximately 2 cm proximal to the coronary sinus ostium at the right atrium. Blood flow measurements were obtained by using a non–breath-hold VEC gradient-echo sequence without segmentation (Cine PC; GE Medical Systems).
A retrospective cardiac gating strategy was used, which enabled ongoing data acquisition throughout the cardiac cycle, and frames at the end of the cycle were as well time resolved as those at the beginning (20). The image data were phase reordered according to their occurrence during the respiratory cycle to reduce respiratory motion artifacts. The imaging parameters were as follows: 27/7.9; flip angle, 30°; section thickness, 5 mm; field of view, 16 x 16 cm; and image matrix, 256 x 256, which resulted in an in-plane resolution of 0.625 x 0.625 mm2.
The velocity encoding was set to a maximum velocity of 50 cm/sec for baseline and stenosis and 150 cm/sec for dipyridamole administration and release of stenosis. The temporal resolution was 54 msec for obtaining a pair of data lines for the magnitude and phasic images. Twelve to 14 views were acquired per cardiac cycle, depending on the heart rate. The adjacent data lines were interpolated linearly to produce 16 images per cardiac cycle, regardless of the heart rate, with the magnitude and phasic images representing the same time point. A complete set of images was obtained in 3 minutes. LV blood perfusion was calculated in milliliters per minute per gram from coronary sinus flow and LV mass obtained by using VEC and cine MR imaging.
Experiment Protocol
Coronary blood flow (CBF) in the LAD and CFX (CBFLAD+CFX) was measured continuously, except during VEC MR imaging of the coronary sinus. The flow probe transducers were disconnected from the flowmeter during MR data acquisition to prevent damage of the probe calibration chips by MR pulses. Heart rate and oxygen saturation were registered continuously by using an MR pulse oximeter (Invivo 4500; Invivo Research, Orlando, Fla). After baseline data were acquired, the occluder was inflated to achieve a reduction in CFX blood flow, and measurements were repeated. Subsequently, 0.56 mg/kg dipyridamole (I.V. Persantine; Boehringer Ingelheim, Ridgefield, Conn) was injected over 5 minutes to induce vasodilation. Blood flow measurements were performed 3 minutes after completion of dipyridamole injection. Finally, the CFX stenosis was released, and blood flow was measured during reactive hyperemia. MR studies were completed in six dogs; one dog died because of ventricular fibrillation during stenosis of the CFX.
At the conclusion of the imaging protocol, a third flow probe was placed around the coronary sinus, and measurements of the CBFLAD+CFX and coronary sinus flow were performed. Phasic and mean flow from the three flow probes and electrocardiographic results were recorded simultaneously on a recorder (TA 4000; Gould, Cleveland, Ohio) at a paper speed of 50–100 mm/sec. Blood flow was measured at baseline, stenosis of CFX, dipyridamole injection (0.56 mg/kg over 5 minutes), and reactive hyperemia to evaluate CBF during hemodynamic conditions similar to those produced during the MR experiment. Complete sets of coronary sinus flow measurements by using flow probes were obtained in three animals. After completion of the flow measurements, all animals were killed by means of an injection of a lethal dose of pentobarbital sodium (10 mL of 250 mg/mL). The hearts were excised and blood washed from the chambers. The right ventricle and both atria were removed to determine LV mass.
Data Analysis
All images were transferred via Ethernet to a computer (Macintosh G3; Apple Computers, Cupertino, Calif), and all analysis was performed by using a public-domain program (NIH IMAGE 1.59; National Institutes of Health, Bethesda, Md; available at: http://rsb.info.nih.gov/nih-image/). For evaluation of LV masses, the epicardial and endocardial borders were traced manually by one observer (G.K.L.) on end-diastolic images, with inclusion of the papillary muscles at each anatomic level encompassing the left ventricle. The LV mass was calculated as the sum of myocardial volume areas multiplied by the density (1.05 mg/mL) of myocardial tissue (21).
For measurement of coronary sinus flow from VEC MR images, the contour of the coronary sinus was traced on each magnitude image throughout the cardiac cycle. Care was taken to closely follow the boundary of the vessel identified by means of a falloff in signal intensity on the magnitude image owing to surrounding epicardial fat or myocardium. The area of the coronary sinus was recorded, and the traced region of interest was applied to the corresponding phasic image to measure mean velocity (Fig 1). The tracing of the coronary sinus and the flow measurements were performed independently by two observers (G.K.L. and M.S.) to define the interobserver variability. Phasic flow was calculated as the product of area and velocity. The mean flow was derived by integration of phasic flow over time. Systole and diastole were determined from opening and closure of the aortic and mitral valves shown on the magnitude MR images, whereas in flow probe measurements the electrocardiographic recording was used.
|
|
|
RESULTS |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
|
|
|
|
|
|
|
|
|
|
DISCUSSION |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
Measurement of LV blood flow and coronary flow reserve is important to quantify the severity of cardiac diseases with macro- and microvascular perfusion abnormalities (1,2). Quantification of coronary flow reserve allows early detection of perfusion deficits, which is important in situations in which the coronary angiogram is difficult to interpret. In patients with global coronary diseases, such as LV hypertrophy or dilated cardiomyopathy, coronary flow reserve is impaired due to functional and structural alterations at the level of the coronary microvasculature, which requires sophisticated approaches to assess myocardial perfusion (3,4,23). VEC MR imaging has been used to quantify blood flow in selective coronary arteries (12,13,24). However, measurement of regional blood flow from single vessels will not provide information regarding global LV flow. Therefore, measuring blood flow in the coronary sinus by means of VEC MR imaging represents a novel approach for noninvasive quantification of total myocardial perfusion and coronary flow reserve.
Results of experimental studies (7,25) have indicated that the coronary arterial flow of the LAD and CFX approximates coronary sinus flow. Nakazawa et al (25) recovered 88% of dye selectively injected into the LAD or CFX in the coronary sinuses in dogs. Mathey et al (7) also found a good correlation between CBFLAD+CFX and coronary sinus flow by using thermodilution in dogs. However, to our knowledge, until now no simultaneous flow probe measurements of coronary arterial flow and coronary sinus flow during various physiologic conditions have been reported.
In previous clinical studies, coronary sinus flow was measured by means of thermodilution (8,9,26), transesophageal echocardiography (27), or Doppler flow wires (28). The widespread use of the available techniques is restricted by methodologic limitations or invasiveness. Thermodilution requires invasive catheter placement in the coronary sinus, which affects blood flow measurements (29,30). Coronary sinus flow may be underestimated because of deep placement of the thermodilution catheter into the coronary sinus (29) or overestimated owing to backflow into the coronary sinus during conditions with increased right arterial pressure, such as pulmonary hypertension, tricuspid valve insufficiency, or respiratory fluctuation in right atrial pressure (7). Transesophageal echocardiography and Doppler flow wire studies provide only coronary sinus blood flow velocity but not flow volume, because the flow-sensitive cross-sectional area of the vessel cannot be provided simultaneously by the currently available systems (27,28). This is a severe limitation of these techniques, since the area of the coronary sinus changes continuously during the cardiac cycle, as seen on the MR images in the current study.
Measurement of coronary sinus flow at VEC MR imaging has considerable advantages over the modalities currently used. This technique is independent of catheter placement and injection of contrast materials or nuclear tracer. VEC MR imaging simultaneously provides the blood flow velocity and the dimension of the coronary sinus, which are both necessary for quantification of coronary sinus flow. Overestimation of flow because of backflow into the coronary sinus is not relevant for VEC MR imaging, because the direction of flow is encoded, and any retrograde coronary sinus flow that passes the section of measurement twice in opposite directions cancels out in the absolute measurement.
Phasic Coronary Sinus Flow
At baseline, a biphasic pattern of coronary sinus flow was found at VEC MR imaging, with a first peak during midsystole and a second peak during early diastole. A similar pattern of phasic flow has been found by using flow probes in conscious dogs (31). During reactive hyperemia, a predominantly systolic increase in coronary sinus flow was observed, with peak flow during the end of systole and beginning of diastole. The phasic flow pattern was confirmed at subsequent flow probe measurements of coronary sinus flow. Furthermore, the phasic flow pattern of coronary sinus flow described in the current study is in agreement with that found in a previous study (15) in which VEC MR imaging was used in humans. However, van Rossum et al (14) and Kawada et al (16) reported a different phasic flow pattern of coronary sinus flow.
Phasic coronary sinus flow is greatly affected by multiple factors, such as myocardial contractility, coronary arterial vascular resistance, coronary sinus compliance, pressure in the venous system, site of measurement, and the variable size and function of the thebesian valve (7,31–34). These factors may explain the variability in phasic coronary sinus flow measurements between the studies.
LV Perfusion
In humans, the normal values for LV perfusion range between 0.75 and 1.1 mL/min/g, as measured by means of PET (35). Similar results were found by using microspheres in conscious dogs with flow values of 0.75–0.79 mL/min/g (36,37). In the current study, the calculated LV perfusion measured by using VEC MR imaging and flow probes (0.40 mL/min/g ± 0.09 and 0.44 mL/min/g ± 0.08, respectively) was lower than that reported in previous studies (15,35–37). The low values for perfusion most likely are related to the open chest model, low temperature inside the magnet, pentobarbital sodium anesthesia, and mechanical ventilation. Our data are in agreement with those from a previous canine study in which pentobarbital sodium anesthesia and open chest preparation were used (38).
Another possible explanation is that a variable part of the posterior wall of the left ventricle and the interventricular septum is drained by the posterior interventricular vein, which drains variably either into the coronary sinus just before it empties into the right atrium or directly into the right atrium (35). This variable fraction of LV perfusion was not measured, since sampling of coronary sinus flow was performed approximately 2 cm before the entrance of the coronary sinus into the right atrium. Furthermore, in dogs, 80% of the venous flow from the interventricular septum drains directly into the right ventricle of the heart (39). Since the septal artery in dogs originates close to the left coronary ostium, septal flow presumably was not included in the measurement of CBFLAD+CFX, which explains the low flow measurements for both methods. In contrast to dogs, in humans most of the septal venous blood is drained directly into the coronary sinus, which most likely reduces this factor of underestimation in patient studies (6,40,41).
Limitations
Measurements of coronary sinus flow by using VEC MR imaging and flow probes were not performed simultaneously owing to technical limitations, such as the difficulty in keeping the flow probe perpendicular to the coronary sinus inside the magnet. The presence of a flow probe around a vessel produces an artifact that complicates imaging of the coronary sinus. These limitations were resolved by using CBFLAD+CFX for validation. In addition, we repeated simultaneous flow probe measurements after each MR experiment, which confirmed a close correlation of CBFLAD+CFX and coronary sinus flow and justified the use of coronary inflow measurements for validation.
Accurate flow measurements depend on precise definition of vessel size and flow velocity. The vessel size was defined by outlining the border of the vein on the magnitude image. The decision to include a pixel was based on the brightness of the pixel, which represents a simple approach to analyzing the data in a clinical setting. The accuracy of the measurements and the low interobserver variability support the reliability of this approach. Other potential problems with the technique are related to inaccuracies that result from partial volume effects of the small vessel, which result in a low number of pure pixels and through-plane motion of the coronary sinus during the cardiac cycle. In summary, the results of our study suggest that VEC and cine MR imaging have the potential to measure coronary sinus flow volume and myocardial perfusion during baseline, coronary arterial stenosis, and reactive hyperemia.
Practical application: In this canine model, VEC MR imaging provided accurate measurements of coronary sinus flow. Simultaneous measurements by using all three flow probes confirmed a close correlation between the coronary arterial flow of the LAD and CFX and coronary sinus flow. This technique has the potential to measure total LV blood flow and coronary flow reserve in patients with perfusion deficit at the macro- and microvascular levels.
|
FOOTNOTES |
|---|
Author contributions: Guarantors of integrity of entire study, M.S., G.K.L., C.B.H.; study concepts and design, M.S., C.B.H.; definition of intellectual content, M.S., G.K.L., C.B.H.; literature research, M.S., G.K.L.; experimental studies, M.S., G.K.L., M.F.W., H.A.; data acquisition, M.S., G.K.L., M.F.W., A.S.; data analysis, G.K.L., M.S.; statistical analysis, G.K.L., M.S., M.F.W.; manuscript preparation, G.K.L., M.S.; manuscript editing, G.K.L., M.S., C.B.H., H.A., F.S.; manuscript review, all authors.
|
REFERENCES |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
This article has been cited by other articles:
|
|
 |
|
  S. M. Kim, M. J. Chung, K. S. Lee, Y. H. Choe, C. A. Yi, and B.-K. Choe Coronary Calcium Screening Using Low-Dose Lung Cancer Screening: Effectiveness of MDCT with Retrospective Reconstruction Am. J. Roentgenol., April 1, 2008; 190(4): 917 - 922. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Herzog, S. A. Nguyen, G. Savino, P. L. Zwerner, J. Doll, C. D. Nielsen, T. G. Flohr, T. J. Vogl, P. Costello, and U. J. Schoepf Does Two-Segment Image Reconstruction at 64-Section CT Coronary Angiography Improve Image Quality and Diagnostic Accuracy? Radiology, July 1, 2007; 244(1): 121 - 129. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Shemesh, R. Evron, N. Koren-Morag, S. Apter, J. Rozenman, D. Shaham, Y. Itzchak, and M. Motro Coronary Artery Calcium Measurement with Multi-Detector Row CT and Low Radiation Dose: Comparison between 55 and 165 mAs Radiology, September 1, 2005; 236(3): 810 - 814. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. K. Lund, N. Watzinger, M. Saeed, G. P. Reddy, M. Yang, P. A. Araoz, D. Curatola, M. Bedigian, and C. B. Higgins Chronic Heart Failure: Global Left Ventricular Perfusion and Coronary Flow Reserve with Velocity-encoded Cine MR Imaging: Initial Results Radiology, April 1, 2003; 227(1): 209 - 215. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Hunold, F. M. Vogt, A. Schmermund, J. F. Debatin, G. Kerkhoff, T. Budde, R. Erbel, K. Ewen, and J. Barkhausen Radiation Exposure during Cardiac CT: Effective Doses at Multi-Detector Row CT and Electron-Beam CT Radiology, January 1, 2003; 226(1): 145 - 152. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Hong, K. T. Bae, T. K. Pilgram, J. Suh, and D. Bradley Coronary Artery Calcium Measurement with Multi-Detector Row CT: In Vitro Assessment of Effect of Radiation Dose Radiology, December 1, 2002; 225(3): 901 - 906. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A.F. Kopp, S. Schroeder, A. Kuettner, A. Baumbach, C. Georg, R. Kuzo, M. Heuschmid, B. Ohnesorge, K.R. Karsch, and C.D. Claussen Non-invasive coronary angiography with high resolution multidetector-row computed tomography. Results in 102 patients Eur. Heart J., November 1, 2002; 23(21): 1714 - 1725. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. K. Willmann, D. Weishaupt, M. Lachat, R. Kobza, J. E. Roos, B. Seifert, T. F. Luscher, B. Marincek, and P. R. Hilfiker Electrocardiographically Gated Multi-Detector Row CT for Assessment of Valvular Morphology and Calcification in Aortic Stenosis Radiology, October 1, 2002; 225(1): 120 - 128. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. F. Kopp, S. Schroeder, A. Kuettner, M. Heuschmid, C. Georg, B. Ohnesorge, R. Kuzo, and C. D. Claussen Coronary Arteries: Retrospectively ECG-gated Multi-Detector Row CT Angiography with Selective Optimization of the Image Reconstruction Window Radiology, December 1, 2001; 221(3): 683 - 688. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
), CFX stenosis (
), and reactive hyperemia (
). At baseline, a biphasic flow pattern is observed, with a first peak during midsystole and a second peak during early diastole. CFX stenosis results in a slight delay in systolic peak flow. During reactive hyperemia, peak flow occurs during late systole and early diastole. A similar pattern is found at flow probe measurement of coronary sinus flow as shown in b.
