Mqwrrc Resonance Imaging. Vol. 9, pp. M-552, Printed in the USA. All rights reserved.

l

0730-725X/91 $3.00 + .oO Copyright 0 1991 Pergamon Press plc

1991

Original Contribution ESTIMATION OF MYOCARDIAL PERFUSION USING DEUTERIUM NUCLEAR MAGNETIC RESONANCE MATTHEW D. MITCHELL* MARY OSBAKKEN*?$ Departments of *Biochemistry/Biophysics, tMedicine, and $Anesthesia,

School of Medicine,

University

of Pennsylvania,

Philadelphia,

Pennsylvania,

USA

A technique to estimate regional and/or global myocardial perfusion in-vivo was developed using deuterium nuclear magnetic resonance measurement of perdeuterated saline washout from the myocardium of 9 dogs. Washout data were fitted to a one-component plus baseline Kety-Schmidt exponential model. To assess the ability of this technique to reliably measure changes in perfusion during change in myocardial workload, nonepinephrine (1 pg/kg/min) was infused and hypoxia was induced (by increasing the inspired ratio of Nz/02 to obtain a P,O, of 20-30 mmHg) in separate interventions. Myocardial work, as determined by heart rate x systolic blood pressure, increased during both interventions. To support this increased workload, myocardial perfusion increased during both physiological interventions. These data indicate that myocardial perfusion can now be reliably estimated with a non-radioactive, non-toxic (in the concentrations used) tracer, perdeuterated saline. The technique can be used for repeated real-time measurements of perfusion during sequential physiological interventions. Keywords: Deuterium NMR; Heart; Mechanical function; Perfusion.

tained with radiotracer techniques like these, repeated real time measurements are not possible. Positron emission tomography (PET) has also been used in preliminary studies for imaging of radiotracer distribution and subsequent quantitation of myocardial perfusion. The short haIf-life of positron-emitting nuclei makes repeated measurement possible, but this technique has numerous limitations.6 While the tracer used in fluorine-19 NMR perfusion imaging7 is not radioactive, this technique has not yet been successfully applied to the heart, due to technical limitations partially related to the need to gate cardiac studies. In addition the fluorine labeled compounds used for imaging can be toxic. Digital contrast angiography (DCA) has developed to the point where highly quantitative measurements of defects in coronary flow are possible,8 but measurements of tissue perfusion have not generally been

INTRODUCTION

A wide variety of techniques have been used to measure and/or estimate myocardial perfusion. ‘-I2 Absolute measurements can be made with radioactive microspheres. f-3 However, although the microsphere technique can be used to measure changes in perfusion during repeated physiological interventions (up to 7 different radiolabeled microspheres can be used and successfully counted later), it does not allow real-time measurements during changes in physiological state, nor does it allow chronic longitudinal studies. Regional and/or global perfusion deficits can be evaluated with images of thallium4 or technetium5 labeled indicator using conventional gamma cameras or single photon emission computerized tomography (SPECT). Even though much relevant information concerning in vivo myocardial perfusion can be obRECEIVED1 l/20/90;

ACCEPTED 2/21/91.

Fund, Buffalo, NY. Dr. Osbakken was an Established Investigator of the American Heart Association during the performance of this work. Address reprint requests to Mary Osbakken, M.D., Ph.D., 913 Gates, Cardiovascular Section, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USA.

Acknowledgment-The

authors would like to thank Jeannette Forte for her excellent secretarial assistance and Christopher Duska and Ihor Ponomarenko for their technical assistance. This work was supported by NIH ROl HL39208-02, the Council for Tobacco Research, New York, NY, the WW Smith Foundation, Philadelphia, PA, and the Sklarow 545

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Magnetic Resonance Imaging 0 Volume 9, Number 4, 1991

made, mainly because approximately 5 to 10 set after tracer injection the contrast medium appears in overlying vessels and obscures the perfusion measurements.9 Subselective infusion of hydrogen-saturated saline (HZ gas agitated with saline solution) into specific coronary vessels with subsequent electrochemical measurement (voltage differences relative to a platinum electrode placed in the pulmonary artery) of washout can be used to evaluate regional perfusion defects in real time lo; but this technique suffers from its necessity for intracoronary injection of indicator and pulmonary placement of the detection electrode. Two other techniques, intracoronary Doppler flow measurement” and coronary sinus thermodilution” require invasion of the cardiac vasculature, which can be technically difficult and potentially harmful. While each method has its advantages and can potentially measure real-time changes in myocardial flow, neither can measure perfusion per mass unit of myocardium. The present study was designed to evaluate the use of a nonradioactive tracer in conjunction with deuterium nuclear magnetic resonance (*H NMR) to measure myocardial perfusion. The washout of perdeuterated saline solution (0.9% w/v NaCl in D20 injected into the left ventricle) from the left ventricular myocardium was measured with *H NMR.r3-16 This technique has the advantage that the tracer is quickly redistributed, so that intravascular deuterium contributes only minimally to the myocardial signal obtained during washout from the myocardium. Therefore, repeated sequential injections and washout measurements can be made so that real time sequential perfusion measurements can be reliably made using this relatively nontoxic tracer. If this technique can be demonstrated to reliably measure perfusion changes under different physiological conditions, it could be developed into a useful clinical tool. METHODS Animal Model Nine mongrel dogs of either sex were prepared for *H NMR studies in a protocol approved by and following the guidelines of the Institutional Animal Care and Use Committee of the University of Pennsylvania. Anesthesia was induced with 2 ml Innovar-Vet (fentanyl 0.04 mg/kg plus droperidol 20 mg/kg IM, Jennsen) and maintained with Nembutal (sodium pentobarbitol lo-40 mg/kg IV, Abbott) as needed. The trachea was intubated for maintenance of positive pressure ventilation (Harvard model 613 ventilator). Placement of a femoral artery cannula provided a means for monitoring of systemic blood pressure and arterial blood gases. A thermodilution catheter placed into the pulmonary artery (via an external jugular vein) was used

to monitor right sided pressures and cardiac output. A left ventricular catheter, placed through an external carotid artery, was used for injection of perdeuterated saline and for measurement of left ventricular pressure. A left lateral thoracotomy was made to expose the heart. After creation of a pericardial cradle, the NMR surface coil was secured to the heart with cyanoacrylate. Visible vessels on the surface of the myocardium were avoided in the placement of the surface coil. This procedure has been more fully described elsewhere. I5 NMR Experiment A 2-cm diameter double-tuned surface coil (‘H = 116 MHz, *H = 17.8 MHz) made of two turns of 14 AWG copper wire, was used for NMR pulsing and acquisition. After each dog was instrumented with the catheters and surface coil, it was placed in a plexiglass cradle for introduction into a 2.7 Tesla, 31 cm bore, horizontal magnet (Magnex Scientific Ltd). Since a partial saturation NMR pulse sequence (pulse, acquire, wait for TR) was used, the pulse duration yielding maximum signal was determined empirically for each animal. After the magnetic field was shimmed using the ‘H NMR signal, *H pulse width was titrated using the natural abundance deuterium signal. Durations (PW) of the optimized *H pulses ranged from 60-200 psec. The interpulse time (TR) was 450 msec. Deuterium NMR acquisition was not gated. The isotonic D20 solution used as a tracer was prepared by dissolving 0.81 g sodium chloride (Sigma Chemical Corp., St. Louis) in 100 g D20 (99.9 atom percent, Cambridge Isotope Labs; Woburn, MA), yielding a NaCl concentration of 0.9% (w/v). A typical NMR spectrum of natural abundance deuterium from the in vivo dog heart is presented in Fig. l(A). It is the sum of 100 FIDs, using single pulses with pulse width of 100 psec and TR of 500 msec (total acquisition time was 50 set). A sample *H NMR spectrum following intracardiac injection of 2 cc deuterated saline is presented in Fig. l(B). It is the sum of 14 FIDs acquired in 6.9 set, using the procedure described above. The width of each spectrum is 3000 Hz. An exponential line broadening of 10 Hz has been applied to each spectrum. Measurement of Perfusion with Deuterium NMR To obtain *H perfusion data, a 2-ml bolus (injected over a 5-set period) of perdeuterated saline was introduced into the left ventricle (LV) through a 5 French pigtail catheter, and flushed in by injection of an equal volume of nondeuterated saline. The catheter has multiple ports, ensuring good mixing of tracer with ventricular blood. Even at modest ejection fraction, tracer clears rapidly from the LV. The overall

Myocardial

perfusion

measured

with

deuterium

NMR

0 M.D.

541

MITCHELL AND M. OSBAKKEN

D20

WASHOUT

CURVES Control

(A)

Noreplnephrlne

Frequency

0

SO

I60 240 Tlme(sec)

320

400

@I

Fig. 1. (A) Natural abundance deuterium spectrum. Typical spectrum of natural abundance deuterium from the in vivo dog heart. This spectrum is the sum of 100 FIDs, pulse width of 100 psec and delay time (TR) of 500 msec. Exponential line broadening of 10 Hz has been applied. (B) Deuterium-enriched spectrum. A typical 2H NMR spectrum from an in vivo dog heart following injection of 2 cc D20. Spectral width is 3000 Hz with 256 points collected, so the acquisition time of each FID is 85.3 msec. Pulse width was 100 psec; TR was 450 msec. This spectrum is the sum of 14 FIDs acquired in 6.9 sec. Exponential line broadening of 10 Hz has been applied. The signal-to-noise ratio of this spectrum is over 20 to 1. In subsequent spectra, the signal declines as tracer washes out, but noise remains constant; signal-to-noise ratios ultimately fall to about 2.5 to 1 after 5 min. After the first 50 spectra, when time resolution is not so important to characterization of the washout curve, 37 FIDs are summed in each spectrum, increasing signal-tonoise to approximately 4 to 1.

perfusion measurement should be minimally affected by injection site. As long as most of the tracer gets to the coronary arteries at approximately the same time, the means of its getting there is irrelevant. In similar

studies using injections into the LA or a peripheral vein (unpublished results using a different group of dogs), the perfusion measurement results were similar to those obtained with LV injection. Sequential deuterium spectra were collected for a IO-min period after injection of tracer as demonstrated in Fig. 2; for the first 5 min, one spectrum (summing 14 FIDs) was collected every 6 to 7 set; in the last 5 min, one spectrum (summing 37 FIDs) was collected every 15 sec. It is possible that the sensitive volume of the surface coil would include some signal from intracavitary

Fig. 2. Example of deuterium (D,O) washout curves (superposition of offset spectra) after injection of 2 ml of perdeuterated saline into the left ventricle during control and NE infusion. Note that the initial decrease of DzO peak intensity is more rapid during NE infusion than during control conditions. Previous D20 injections have left a large baseline (residual) D,O level.

blood. However, assuming good mixing within the LV, the concentration of tracer within the ventricular chamber is the same as the arterial concentration of tracer C,. The latter is demonstrated to clear within lo-15 set after bolus injection by the studies mentioned below. Therefore, the myocardial signal would only be minimally contaminated by intracavitary blood signal during the time of in vivo washout measurements. The area under the DzO peak of each spectrum was determined by integration and plotted against time. A partial derivative technique was used to fit these washout data to a decaying exponential plus baseline as described in the following equation: C(t) =Ae-B’+K.

(1)

To determine the robustness of the fitting technique, washout curves were fitted to most data sets from multiple sets of initial parameters chosen arbitrarily by the investigators. The fitted curves obtained with this fitting process approached the same final fitted parameters from multiple starting sets of parameters chosen arbitrarily by the investigators. The exponential time constant of washout was converted to a perfusion rate by the Kety-Schmidt method. ‘%I7

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Magnetic Resonance Imaging 0 Volume 9, Number 4, 1991

Data Analysis The Kety-Schmidt method” principle, which states that

is based on the Fick

where C, and CA are myocardial tissue and arterial concentrations of tracer, t is time (seconds), V, is the volume of the myocardial compartment, and F is the flow between the two compartments. Since perfusion (P) is defined as flow per unit volume of tissue, it can be substituted for the terms F and V,, leaving

G,

-

dt

= P(C,

- C,)

where P is the myocardial perfusion rate expressed as ml/100 g/min. If it is assumed that the arterial concentration of tracer is no higher than the natural abundance level of deuterium after the initial passage of the tracer bolus, the equation becomes dC, dt

~

= -P.C,

.

(4)

This equation can be integrated to yield CM(t) = C,(O)e-”

+K

(where t > 0 and K is a constant)

.

(9

The constant K includes both the natural abundance of deuterium and the residual deuterium from previous perfusion measurements, so the solution of the equations of washout is unaffected by repeated tracer injection. The perfusion rate in ml/100 g/min can be obtained directly from the exponential time constant (7 in set) of washout using the following equation:

p =

60 sec/min x 100

ml/gm 7

tissue x 0.9

(6a)

or P = 5400 ml/100 g/min 7

(6b)

where 60 sec/min is the conversion from time constant (7) measured in seconds to perfusion in reciprocal minutes, 100 ml/gm converts to the conventional expression of perfusion per 100 g tissue, and 0.9 is the tissue/blood partition coefficient (A), of DzO. Be-

cause of the chemical similarity of D20 and HzO, the value for the partition coefficient of Hz0 is substituted for that of D20. The coefficient is simply the ratio of water content in tissue to water content in blood. The accepted value for this coefficient is 0.9.r6 Validation of Input Function Our exponential interpretation of tracer washout depends on the assumption that after passage of the input bolus, CA is no higher than the residual abundance of deuterium [Kin Eq. (5)], so efflux of tracer from the myocardium varies only as C,. This assumption was verified in our experimental system by two methods. First, the NMR surface coil was placed over an isolated carotid artery of the experimental animal. The standard bolus of perdeuterated saline was injected into the left ventricle (LV) and deuterium NMR spectra collected from blood passing through the carotid. Relaxation delay (TR) was reduced to 0.1 set, to both increase the signal to noise (S/N) ratio in the carotid and to provide additional suppression of signal from surrounding tissue whose spins were saturated by the rapid pulses. Rapid vascular flow prevented saturation of spins in the carotid. To further eliminate the possibility of obtaining signal from surrounding tissue, the carotid was lifted out of the neck and isolated on a bed of gauze. Summation of spectra was done every 1 second for 50 sec. The tracer input function fell to natural abundance levels in less than 10 set, even in the left carotid artery, downstream from the origin of the coronary arteries (Fig. 3). The possibility of surface coil and rapid acquisition artifacts in this experiment were controlled for in a second experiment where 1 ml samples of femoral arterial blood were withdrawn (into plastic syringes, gas evacuated, and refrigerated until the time that in vitro spectra were measured) every 15 set for 2.5 min following the standard tracer injection, and then at 4, 8, and 12 min. The deuterium concentration of each sample was measured by deuterium NMR using a small solenoidal coil (2 min acquisition). Deuterium signal levels were referenced to proton (‘H) signals measured simultaneously in the same samples to normalize for sample size. Deuterium levels remained very low after the first 15 second sample, thus verifying the bolus nature of the tracer input function. (Fig. 3). Physiological Intervention and Monitoring Norepinephrine (NE) infusion (1 pg/kg/min) was begun and increased to maintain heart rate x systolic blood pressure (HR x SBP) product at 50 to 100% above baseline. Hypoxia was induced by increasing the ratio of inspired N2/02 to obtain a PA02 of be-

Myocardial perfusion measured with deuterium NMR 0 M.D.

normalized \Ignnl

0 -

IO 20

myocardium

30

40 50 60 70 time (seconds)

- - carotid

80

90

100

MITCHELL AND M. OSBAKKEN

549

using arterial blood gas measurements and systemic and pulmonary artery pressures. Arterial blood gases were maintained within physiological ranges by changing inspired gases and/or administration of NaHCO, as needed, except when hypoxia was initiated as a controlled physiological intervention. Systemic and pulmonary pressures were maintained within physiological ranges by fluid administration, except when they were increased in a controlled manner with NE infusion.

- - - - arterial sample

Fig. 3. Typical deuterium (2H) input functions compared to myocardial washout curve after injection of 2-ml boluses of deuterated saline into the left ventricle. The input function is characterized using two methods: (i) washout of a 2-ml bolus of deuterated saline from the carotid artery (carotid) measured in situ (spectra collected each second for 50 set); (ii) washout of 2-ml bolus of deuterated saline from withdrawn samples of femoral arterial blood (arterial). This curve was generated by collecting spectra from 1 ml blood samples taken every 15 set for 2.5 min and then at 4, 8, and 12 min after the initial left ventricular bolus injection of the tracer. These data were compared to the first 100 set of washout of a 2-ml bolus of perdeuterated saline measured in the myocardium (myocardium). Note that falloff of carotid signal is faster than that of arterial signal, probably due to splay of data obtained from spectra of 1S-set blood aliquots obtained in method 2 when compared to I-set in situ data acquisition in method I. Normalized signal is defined as follows: the maximum and minimum points for each curve were determined for each experimental run; each curve was linearly scaled between these maximum and minimum points to normalize the data so that curves can be compared from run to run and animal to animal.

tween 20-30 mmHg. All animals received both types of physiological intervention (NE infusion and hypoxia). The order of the interventions was randomized from animal to animal. Effects from NE infusion dissipate after 5-15 min. I8 To be certain that no residual effects of NE infusion remained at time of initiation of hypoxia, 30 min were allowed to elapse between interventions (i.e., between NE infusion and hypoxia). The residual effects of hypoxia on the heart also dissipate quickly after return to normoxia (5-15 min).‘* At least 30 minutes were allowed to elapse after hypoxia, before NE infusion was begun. Mechanical function was monitored with the following parameters: heart rate x systolic blood pressure product (HR x SBP), systolic blood pressure x stroke volume (P x V), and oxygen consumption (MV02). Oxygen consumption was determined using an algorithm designed and validated by Rooke and Fiegl, I8 which uses HR, SBP, diastolic blood pressure, and stroke volume data to estimate MV02. Physiological status of each dog was monitored

Statistical Analysis Analysis of variance (ANOVA) was used to analyze the data. Numerical data are presented as mean + SD. Statistical significance is measured at the p < 0.05 level. RESULTS Typical myocardial *H input functions after left ventricular injection (in vivo NMR measurement and in vitro NMR measurement of sequentially-acquired femoral arterial blood samples) are presented in Fig. 3. D20 washout curves obtained with a myocardial surface coil during control, NE infusion and hypoxic states are presented in Fig. 4. Perfusion and mechanical function responses during NE infusion and hypoxia are presented in Table 1. Both NE infusion and hypoxia were associated with increases in mechanical function, as determined by HR x SBP, P x V and MV02. Both hypoxia and NE are associated with significant increases in myocardial

Fig. 4. Typical myocardial D,O washout curves during control conditions, norepinephrine (NE) infusion, and hypoxia. Myocardial clearance of perdeuterated saline after NE infusion is intermediate between control and hypoxia, which indicates that perfusion during NE infusion is greater than during control, but less than during hypoxia. Each myocardial washout curve was acquired, with a surface coil placed over the left ventricle, after a 2-ml bolus of perdeuterated saline was injected into the left ventricle. The technique is described in the text. Normalized signal is defined in the legend of Fig. 2.

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Table 1. Mechanical and metabolic function responses to norepinephrine infusion and hypoxia (N = 9) Name Con NE 5’ Ret Hypoxia 5’ Ret

HR x10-1 1.4 * 1.5 f 1.7 * 1.8 + 1.7 f

0.3 0.3 0.2 0.2* 0.2

SBP

HR x SBP

x 10-2

x 10-4

1.4 * 2.4 + 1.3 f 2.1 f 1.4 +

0.2 0.7* 0.1 0.5 0.3

1.9 f 3.5 + 2.3 + 3.7 + 2.3 f

0.5 1.2* 0.5 0.4* 0.6

co 1.6 * 2.5 + 1.6 + 2.0 + 1.6 +

0.5 0.4* 0.1 0.4 0.5

PXV

MVOz

x 10-3

x10-1

1.4 +-0.3 3.8 +-0.6* 1.1 t- 0.3 2.1 Z!Z 0.5* 1.3 t- 0.3

0.9 * 1.9 f 1.2 f 1.4 + 1.1 +

0.2 0.5* 0.3* 0.5 0.3

MP 87 + 162 + lOOk 200 f 70 +

10 42* 42* 6

*p < 0.05 compared to CON. HR = Heart rate (beatslmin); SBP = Systolic Blood Pressure (mm Hg); CO = Cardiac Output (Urnin); PxV = Systolic pressure x stroke volume; MV02 = O2 Consumption (ml/min/lOO g); MP = Myocardial perfusion (ml/min/lOO g); CON = Control; REC = Recovery.

perfusion. Hypoxia generally produced slightly larger increases in myocardial perfusion than NE administration, but these differences were not statistically significant. These data demonstrate that under both conditions, myocardial mechanical function is maintained at increased absolute levels associated with increased myocardial perfusion. DISCUSSION

Stable myocardial mechanical function is dependent on adequate perfusion, so both are closely regulated, Many potential mechanisms of regulation of myocardial perfusion have been proposed” and are beyond the scope of this paper. Our method, using perdeuterated saline (nontoxic in the doses used in these experiments) as a tracer, has the potential to provide similar real time perfusion data with intravenous injection of tracer which is safer and much less technically demanding than the other techniques. The present study evaluates the use of 2H NMR techniques to measure myocardial perfusion. The use of 2H NMR to measure perfusion is relatively new. While several investigators have used this technique to measure perfusion in different organ systems, 13-16*20 this is one of the first applications of the technique to the physiology of the heart. Also, this is the first study which experimentally verifies the tracer input function on which exponential models of perfusion are based. Deuterium tracer concentration data collected from samples of withdrawn arterial blood and of blood in the isolated carotid artery indicate that the characterization of the input function as a narrow bolus with little recirculation is appropriate, even for well-perfused organs such as the beating heart (Figs. 3,4). This answers one of the more significant questions of the general validity of using a deuterated tracer (in this case perdeuterated saline) washout technique.

One problem with washout techniques is that it can take 5 to 10 min to measure perfusion, because tracer washout must be followed until a stable low level of tracer in tissue is achieved. However, generally the majority of washout is completed in 1 to 2 min. Therefore, even though the subject must be in a reasonably stable physiological state during the measurements, 1 to 2 min of physiological stability are reasonably easy to achieve. The data obtained in these studies indicate that the increased myocardial perfusion which results from steady but elevated workloads can be accurately measured with 2H NMR measurements of deuterated tracer washout. When our perfusion data were compared to data reported by other investigators using different methods of perfusion measurement, there was good agreement. Perfusion rates obtained by D20 washout were comparable to those reported using radioactive microspheres. Under control conditions, the mean perfusion rate by the D20 method was 87 +- 10 ml/100 g/min (mean + SD, n = 9). With microspheres, perfusion rates of 108 f 28 (Grines”) and 89 f 35 (Schanzenbacher2’) ml/lOOg/min have been reported in the literature. The D20 washout rates were also comparable to results of other washout techniques. With ‘33Xe gas washout, Yoshida22 reported baseline perfusion rates of 79 + 7 ml/100 g/min. With ‘HZ gas washout, Grines” found a perfusion rate of 109 f 28 ml/100 g/min, while Schanzenbacher’s2’ was 103 f 29. All of these values are similar to (within experimental error) our baseline perfusion values determined with D20 washout. Because of the different physiological conditions under which other investigators have made myocardial perfusion measurements using other techniques, comparison of our NE and hypoxia data to their experimental results may not always be valid. Therefore, we

Myocardial perfusion measured with deuterium NMR 0 M.D.

compared our D20 perfusion results to specific coronary flow rates as measured with a Doppler flowmeter” placed around the left anterior descending (LAD) coronary artery, and divided by the mass of the heart it perfused, which was weighed at the conclusion of each experiment. While these two techniques (D20 perfusion and Doppler flow) measure different quantities, if the Doppler flow rate is divided by the mass of perfused myocardium, the two sets of values are in agreement under both control and experimental conditions. In control conditions, perfusion measured by DzO washout was 87 ? 10 ml/100 g/min; perfusion by Doppler flow was 100 + 12 ml/100 g/min. During hypoxia, D20 perfusion was 200 + 42 ml/100 g/min and Doppler perfusion was 183 f 20. During norepinephrine infusion, D20 perfusion was 162 f 5 ml/100 g/min, and Doppler perfusion was 190 + 40. These comparisons were carried out in five dogs (unpublished results). Results from these experiments demonstrate that deuterium NMR measurements of washout of a deuterated tracer can be used to measure myocardial perfusion with reasonable accuracy. These data also demonstrate that increased myocardial work loads are associated with adequately increased perfusion to maintain mechanical function, thus supporting observations made by others using other techniques, that myocardial perfusion is closely regulated by mechanical needs. To go one step further in development of *H NMR tracer washout techniques, *H NMR has been used to acquire true perfusion images of the cat brain in vivo,20 and this imaging technique is being applied to the heart in preliminary studies. In the brain studies, sequential deuterium images were acquired following arterial tracer injection. For each pixel of the series of images, an individual washout curve was plotted and the corresponding perfusion rate calculated. The rates were then displayed as a perfusion image. In the cat brain, perfusion images with resolution of 3 mm x 3 mm x 1 cm were acquired in 4 min after injection of 1 cc perdeuterated saline into the carotids. The spatial resolution was less than that of a corresponding proton MR image, but was sufficient for evaluation of regional cerebral blood flo~.~* Perfusion rates of heart and brain are similar, so a similar approach to regional myocardial blood flow should be feasible. At present, left intraventricular injection yields good tracer uptake in the heart and good NMR signal levels. However, for D20 perfusion imaging to be widely accepted, data must be acquired noninvasively after intravenous injection of tracer. As with proton MRI of the heart, cardiac gating will probably be needed.

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If the technical challenges can be met, deuterium NMR imaging may become a valuable tool for measurement of regional myocardial perfusion. REFERENCES 1. Pelt, L.R.; Gross, G.J.; Warltier, D.C. Preferential increase in subendocardial perfusion produced by endo-

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13. Ackerman, J.J.H.; Ewy, C.S.; Kim, S.G.; Shalwitz, R.A. Deuterium magnetic resonance in vivo: The measurement of blood flow and tissue perfusion. Ann. NY Acad. Sci. 508:89-98; 1986. 14. Mitchell, M.D.; Clark, B.J.; Leigh, J.S. Simultaneous

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