Cardiac Wolfgang Auffermann, Nuno J. Tavares, MD2 Kanu Chatterjee, MD

MD2

#{149} Wilbert

#{149} William #{149} Charles

M. Chew, PhD #{149} Christopher L Wolfe, W. Parmley, MD #{149} Richard C. Semelka, MD B. Higgins, MD

Radiology

MD #{149} Tom

Donnelly,

MD

.

Normal and Diffusely Abnormal Myocardium in Humans: Functional and Metabolic Characterization with P-31 MR Spectroscopy and Cine MR Imaging’ The current study tested the concept that cine magnetic resonance (MR) imaging and phosphorus-31 MR spectroscopy might be used to provide a comprehensive evaluation of the functional and metabolic status of the myocardium in humans. Thirteen patients with congestive cardiomyopathy and eight healthy volunteers were imaged at 1.5 T with the one-dimensional chemical shift imaging technique for localization of P-31 MR spectroscopy and an electrocardiographically referenced gradient refocused sequence for imaging of the heart. Prominent peaks in the PDE and PME regions were observed in cardiomyopathic patients, but only the former peak was measured. The PCr/fl-ATP peak ratio was not significantly lower in cardiomyopathic patients compared with healthy subjects (1.51 ± 0.08 vs 1.54 ± 0.04). The ratios of PDE/PCr (0.80 ± 0.07 vs 0.54 ± 0.10) (P .01) and PDE/ATP (1.19 ± 0.10 vs 0.84 ± 0.08) (P .05) were significantly higher in patients with dilated cardiomyopathy compared with healthy volunteers. Left ventricular systolic wall thickening was significantly lower and left ventricular peak and end-systolic wall stress and mass were significantly higher in cardiomyopathic patients compared with healthy volunteers. Thus, localized, gated P-31 MR spectroscopy combined with cine MR imaging allowed identification of both abnormal myocardial phosphate metabolism and abnormal ventricular function. While this study suggests that increased myocardial PDES may be a marker for abnormal myocardium, the sensitivity and specificity of this marker need to be further evaluated.

M

resonance (MR) imaging has been shown to be effective in the evaluation of cardiac anatomy and function in a variety of disease states (i-4), including cardiomyopathies (3,4). Cine MR imaging has been used to quantify global left ventricular function (2) and myocardial wall thickening dynamics (4). AGNETIC

Phosphorus-3i

MR

spectmoscopy

of

the human heart has been shown be feasible (5-iO). Abnormalities the P-3i MR spectrum have been served in experimental models of cardiomyopathy (1 i,i2), and P-3i spectroscopy

in two

patients

to of obMR

with

primary myocardial disease has shown differences compared with healthy subjects (5,7). Because of the less stringent requirement for localization for P-31 MR spectroscopy in diffuse myocardial disease compared

Index terms: Magnetic resonance (MR), dine study, 51 1.1214 #{149} Magnetic resonance (MR), phosphorus studies, 511.1214, 511.1299 #{149} Magnetic resonance (MR), spectroscopy, 511.1214 Myocardium, um, radionuclide Radiology

I

From

W.M.C.,

MR studies, studies,

1991;

the

511.1214 511.1299

179:253-259

Departments

C.L.W.,

#{149} Myocardi-

N.J.T.,

of Radiology

R.C.S.,

C.B.H.)

(WA.,

and

Medicine (Cardiology) (C.L.W., W.W.P., ID., K.C.), Box 0628, C309, University of California, 505 Parnassus St. San Francisco, CA 94143. Received February 19, 1990; revision requested

April

17; final

revision

received

November

9;

accepted scientific George

November 26. From the 1988 RSNA assembly. Supported in part by The D. Smith Fund, National Institutes of

Health

grant

AA 07413-01,

and National

Insti-

tutes of Health Research Training Grant HL07570-04. WA. supported by Individual Grant Au-70/2-2 from Deutsche Forschungsgemeinschaft, Bonn, Germany. Address reprint requests to C.B.H. 2 Current addresses: Department of Radiology. University of M#{252}nster, M#{252}nsten, Germany (WA.), and Department of Radiology, Hospital Santa Marta, Lisbon, Portugal (N.J.T.). RSNA, 1991

#{149}

with regional ischemic disease, the initial attempts to detect abnormalities in myocardial phosphorus metabolism might be more effective in patients with a diffuse myocardial disease, such as dilated cardiomyopathy. Recognition of abnormalities in the P-3i MR spectrum in myocardial diseases could be useful for detection of either primary or secondary cardiomyopathies in humans. However, the evaluation of the human myocamdium with MR spectroscopy presents a number of problems, including the low sensitivity of the P-31 nucleus and the low concentration of P-3i-containing metabolites (on the order of millimoles per liter), contamination of signal intensity from the overlying chest wall for camdiac MR spectroscopic studies, and ambiguous localization at any instant due to cardiac and respiratory motion despite the use of cardiac gating because the position of the heart is not constant and precisely identical between beats. Because of these problems associated with MR spectroscopic studies of the heart, it is important to determine whether measurements of P-3i MR spectra of the normal myocardium in humans are reproducible from one study to the next. Interstudy reproducibility is the minimum requirement for the use of this modality in monitoring severity, progression of myocardial disease, and response to therapy. Accordingly, the aims of this study were (a) to investigate the reliability and reproducibility of P-3i MR spectra in healthy subjects examined on two separate occasions, (b) to compare the characteristics of the P-3i MR spectra of healthy subjects and

Abbreviations: AlP adenosine triphosphate, ECG = electrocardiography, PCr phosphocreatine, PDE phosphodiester, PME phosphomonoester, SD standard deviation, TE = echo time, TR repetition time.

253

patients

with

ease

global

to identify

myocardial

dis-

a signature

in the

3i MR spectrum that is associated with dilated cardiomyopathies,

(c) to combine and

cine

P-31 imaging

MR

integrated

and

Heart

an

of myocardial

metabolism.

SUBJECTS Study

and

spectnoscopy to provide

assessment

function

AND

METHODS

Muscle

Population

A total

of i3 patients

diomyopathy

less

MR

P-

with

than

aged

with

an

45% (11 men

24-84

years

dilated

ejection

and

of

women

two

[mean,

car-

fraction

54 years])

Figure

1. (a) Series of P-31 spectra obtained from healthy volunteer with gated one-dimensional spectroscopic imaging technique. Each spectrum represents a 1-cm-thick disk-shaped coronal section. Spatially, spectra are displayed from anterior to posterior or from bottom to top. Spectra extending from the anterior chest wall to the heart are displayed from bottom to top. PME = phosphomonoesters. (b) Localized gradient-echo image (TR/TE = 25/ 12, 128 X 256 matrix) of a healthy volunteer obtained with the double-tuned surface coil for both transmission and reception of radio-frequency signals. The coil was subsequently positioned more to the subject’s right to decrease signal contamination from the left chest wall. The patient was not moved between the imaging and spectroscopy acquisitions.

and

eight healthy volunteers with no clinical evidence of cardiac disease with an ejection

fraction

at two-dimensional

diography

of greater

ejection fraction, men aged 27-50

were

was

55% (mean

63% ± 2) (all subjects years [mean, 34 years]) in the study. Informed

included

consent

echocar-

than

obtained

from

all

subjects.

Patients were selected according to a dinical diagnosis of idiopathic dilated cardiomyopathy. The patients were classified according to the New York Heart Association as grade I (n = 5), II (n = 5), or III

3).

(n

Initial

achieved

functional

with

diography,

assessment

was

two-dimensional

which

echocar-

showed

an

ejection

fraction of less than 45% (mean ejection fraction, 26% ± 4) in all but one patient with dilated cardiomyopathy. This patient had an ejection fraction of slightly less

than

45%

on

the

initial

dine

MR

the

of

coronary three

remaining

P-31

MR

P-3i 13 patients

1.5-1, system

1-rn-bore, (Signa;

waukee).

imag-

disease

in

acquired

dilated

in the

cardiomyopathy

and in eight healthy volseparate occasions with a whole-body GE Medical

Patients

supine

MR imaging Systems, Mil-

were

position.

examined

in the

A home-built,

wall

of the

spectively,

(ECG) 25/

[TR] 12;

was

128

to confirm

ment

of the

pical

region

in

of the

marked.

254

and

two

P-3i coil

surface

coil

place-

over the anteroaof the left ventricle. The poThe

patient

position

MR imaging acquisitions,

signal

active

nance.

on

was on

the

the

chest

wall

maintained table

from

under

shimming

Typical

were

the

of the

line

surface

coil

water

widths

were

reso-

MR Localization

in

the

y direction

was

cm-thick surface

section coil was

thus

for

500

square

pulse

cm,

nuclei

during

and P-3i MR specand the table was

received

angle. The deviation

which myocardium MR spectroscopy 3.82

cm

± 0.62,

previously sensitive tissue

of a 1-

of 400-zsec

du-

have

was sampled were 2.85-4.56 respectively.

With

representing

shown

of

approximately

a

range and mean (SD) of the depth

50%

± at

for P-31 cm and use

that

adjacent

expect between

sec-

the signal healthy

msec)

for

a total

minutes,

scanning

depending

on

the

less

than

the

of the

10%

effedtive

i,500

msec

Analysis

TR varied for

all

of P-31 were

between

subjects

MR

processed

Spectra a two-dimen-

transform in the chemical

with

sion

apodization

in

and

no

were use

dimension. in both

analyzed of only

corrections. deconvoluted, vidual

in the

and

the

phased

and

The

15-Hz line shift dimensecond

Raw data dimensions.

first-

resonances

were All

areas

also data

mode

second-order

resulting the

900

studied.

with

sional Fourier broadening (spatial) zero-filled

ra-

with phase

spectra were of the mdi-

of phosphodiesters

(PDEs), phosphocreatine three peaks of adenosine

(PCr), and triphosphate

a, and

/3-ATP)

tegration system mont,

routine available (GEN 1280; General Calif). PCr/$-ATP,

were

and PDE/PCr peak lated, and standard

quantified

with with the Electric, PDE//3-ATP,

area ratios errors were

the (‘y, an

in-

Signa Fre-

were calcudeter-

mined.

of

of the (13), the

tal signal at a depth of 4 cm from the was calculated to be 60 cm3. Phantom studies

800 i5-25

Data

plane. The and reRadio-frewith a

reported calculations volume of surface coils

volume

TR, of

and

sec,

a representation

in the coronal used to transmit

ceive radio-frequency signals. quency excitation was achieved nonselective

from

not

subjects and patients. The TR for healthy subjects was 1,152 msec ± 186 (mean ± SD), while that for patients was 1,351 msec ± 224. Sixteen to 20 averages were collected per phase-encoding step (mini-

cause

32 phase-encoding views acquired a 32-cm field of view. Each resulting

spectrum

occurs

One would to be different

patient’s heart rate. Because these were gated, some variations in the peak area tio will be due to the variability of the heart rates of the different patients be-

Signal localization to myocardial tissue was achieved with a gated (to systole) one-dimensional spectroscopic imaging sequence. Phase-encoding gradients were with over

bleed”

tions. bleed

time

Spectroscopy Technique

P-31

“signal

mum

0.4-0.7

ppm.

60#{176} flip standard

excitations)

further

posi-

images

acquired in the transverse plane. The P-31 MR spectra were acquired in the systolic phase of the cardiac tycle. Magnetic field homogeneity in the region of interest was optimized by observation of the

3.5

msec

MR spectros-

guide

surface

Radiology

#{149}

(repetition

[TE]

matrix;

before

a constant

the dine troscopy

time

X 256

copy

was

Retro-

dine MR imaging msec/echo

performed

sition

subject.

center

tients because coil loading was constant between subjects, and phantom studies demonstrated that at an average depth

electrocardiographically

gated

time

supine

The

ration, and pulse power was kept constant between patients. The power of the surface coil was not adjusted between pa-

9-cm-di-

ameter, circular, double-tuned (hydrogen-1--P-3i) surface coil was initially placed over the anterior portion of the chest

acquisitions.

during

applied

were

with

occasion on two

at an established

tion

and

Spectroscopy

MR spectra

on one unteers

arterial patients.

maintained

proton

ing study. Coronary artery disease had been excluded from the diagnosis with use of coronary cineangiography in nine of 13 patients. One patient underwent an exercise thallium study that revealed no ischemic disease. There was no history

suggestive

b.

a.

to-

coil of

Cine Cine

MR MR

Imaging imaging

was

performed

in

12

of the 13 patients and in the eight volunteers. In one cardiomyopathic patient, a domplete dine MR study could not be ob-

April

1991

tnix was 128 X 256 in a field of view of 32 cm interpolated to 256 X 256 for display. Two data acquisitions were aver-

aged to improve ATP

PME

the signal-to-noise

ratio;

thus, images were acquired during RR intervals. The total time required the P-3i MR spectroscopy and cine imaging studies was approximately hours.

Cine

MR

Image

256 for MR 2

Analysis

Images were first displayed on the computer monitor in a cinematic fashion to evaluate cardiac function. Measurements were made on short-axis images of the heart. End-systolic and end-diastolic images were chosen as those showing the largest

and

smallest

area

tnicular chamber. The tolic and end-diastolic fied by the movement

and mitral

valves

of the

timing images of the

when

these

left

yen-

Calculation Wall Stress

of end-syswas veritricuspid were

in-

on the image. End-systole was deas the last image showing closed atnioventnicular valves and end-diastole as the last image showing these valves open. Left ventricular volumes were calcluded fined

10 Figure

0 2

-10

Myocardial

-20

P-31

spectra

PPM obtained

from the same healthy volunteer on two separate occasions. PCr/-ATP peak area ratios were 1.76 and 1.62, while PDE/PCr peak area ratios were 0.39 and 0.52 for the top and bottom spectra, respectively. Note the presence of a large resonance at 8-10 ppm, attnibutable to 2,3-diphosphoglycerate phosphomonoesters (PMEs). The split peak labeled PME probably

represent

PME alone

composed

of inorganic

bly contaminated ate.

or broad

and

does not but is also partially phosphate

and

possi-

by 2,3-diphosphoglycer-

tamed. An initial multisection gradientrefocused sequence was acquired in the coronal plane to locate the inferior and superior cardiac borders. Then an oblique gradient-refocused image was acquired along the true long axis of the heart, calculated from the coronal localizer. The cardiac short-axis images were acquired perpendicular to the long-axis image, which contained the mitral valve and apex of the left ventricle. Short-axis images were obtained at the apex of the heart and continued for 2 cm above the aortic valve, thereby encompassing both the right and left ventricular chambers. The heart was usually encompassed in 12 to 16 imaging planes of 10-mm section thickness. Cine MR imaging was performed with a flip angle of 30#{176}, a TE of 17 msec, and a pulse TR of 31 msec. The ECG signal was recorded simultaneously to retrospectively reference the imaging data to the multiple segments of the cardiac cycle. To limit total imaging time, two levels were imaged simultaneously in an interleaved fashion, resulting in a temporal resolution of 62 msec per image. The number of time frames acquired per cardiac cycle was inversely related to the subject’s heart rate (number of time frames RR interval of 62 msec). The acquisition ma-

Volume

179

#{149} Number

1

culated

by

outlining

the

area

of the

of the 1-cm sections encompassing the entire ventricle. The areas from each section were summed to produce the left-ventricular volumes. Wall thickening was measured from only the midventnicular (equatorial) section. The

of thickening

from

thickness

measurements, were

analyzed blindly dent observer.

Blood While

Pressure resting

the

randomly

selected

by a second

and

of

scribed

Measurements

in a supine position, the patients and volunteers were given at least 10 minutes to reach a steady state. With use of a sphygmomanometric digital recorder (Dinamap; Critikon, Tampa, Fla), systolic and diastolic blood pressure were measured every 2 minutes over a 10-mmute interval. ECG and carotid pulse tmacings from the common carotid artery were recorded simultaneously to estimate the point of end-systole, so that it could be referenced to continuous digital blood pressure measurements as shown by the sphygmomanometnic recorder. Peak systolic and diastolic blood pressures were assigned to the peak and nadir of the carotid pulse tracing, respectively. To deter. mine the mean ratio of dicrotic notch pressure to peak systolic blood pressure for each subject, the ratio of dicrotic notch

de-

. (ESP

1.35

where end-systolic, meridional and h mean

D

ES

meridional

wall

diamemidven-

thickness

in

cen-

ESP is given

in millimeters of and multiplying by 1.35 convalue into grams per square

mercury, verts this

indepen-

WSm

+ (hm/Drs)],

=

timeters.

10

to a previously

(6,14):

Drs)/4hrs[1

tricular

re-

Ventricular

according

formula

wall stress, mean midventricular ter in centimeters,

end-dias-

images

MR images

WS

tole to end-systole was measured for the anterior, posterior, septal, and lateral walls of the left ventricle. This midventricular plane was chosen as the section midway between the apex and the aortic valve. The average of these four measurements was calculated for each patient. The left ventricular diameters were measured at two sites perpendicular to each other; these were the anteroposterior and septolateral diameters. To assess interobserver reproducibility of volume and wall subjects

of Left

Left ventricular end-systolic meridional wall stress was calculated from pressure tracings and meridional left ventnicular wall thickness and diameter measurements obtained from short-axis cine

x

blood

pool on each

percentage

pressure to peak systolic blood pressure was calculated separately in each of the tracings for 10 individual cardiac cycles and then averaged for each of the tracings. End-systolic pressure was estimated by linear interpolation to the height of the dicrotic notch. This method has been used by others (14) and has been validated for systolic, diastolic, and mean arterial pressures against an intraarterial standard (14,15). End-systolic pressure was calculated according to the following formula: ESP = (SBP/DNP) X (SBP - DBP) + DBP, where ESP end-systolic pressure, SBP = systolic blood pressure, DNP = dicrotic notch pressure, and DBP = diastolic blood pressure.

centimeter.

Statistical

Analysis

Data

are presented as mean ± standard For healthy subjects who were studied on two separate occasions, the average value for the two studies was used for each subject. Differences between cardiomyopathic patients and healthy volunteers were tested for statistical significance with a single-factor analysis of variance. The Scheff#{233}test for multiple contrasts was applied to detect significant differences defined by the analysis of variance (16). Interobserver reproducibility of measurements was assessed by linear regression analysis (16). The null hy.

error.

was rejected with P

pothesis

dence level, statistically

at the 95% confi.05 considered

significant.

RESULTS P-31

MR

A typical

Spectroscopy series

of spectra

obtained

with the one-dimensional chemical shift imaging sequence (each spectrum representing a i-cm-thick comonal section) is shown in Figure ia. As seen, the first three anterior spectra

have larger PCrfl9-ATP peak area tios than the most posterior spectrum.

This

observation

well with the position of the chest wall and

ma-

correlates

and thickness the myocardiRadiology

#{149} 255

urn immediately below the surface coil (Fig ib). Measurements from the cine MR images indicated that the myocardium was situated at a depth of approximately 4 cm below the coil. The spectra with larger PCr/-ATP peak area ratios emanated from the skeletal muscle in the chest wall, while the myocardial tissue exhibited lower PCr//3-ATP peak area ratios. Figure 2 shows the case of worst agreement for the P-3i spectra obtamed on two separate occasions from one volunteer. Qualitatively, the spectra are similar; the PCrfl9ATP peak area ratios were 1 .76 and i.62 and the PDE/PCr peak area matios were 0.39 and 0.52 for the spectra obtained on two separate days. The Table shows the interstudy meproducibility of the P-3i MR spectral peaks in the healthy subjects. PDE/ PCr peak area ratios were in the mange of 0.4-0.6, while PCn/9-ATP ratios were in the range of 1.5-1.6. None of the groups of data (PCrfl9ATP and PDE/PCm peak area ratios) were significantly different between studies i and 2. Representative P-31 MR spectra from a healthy volunteer and from a cardiomyopathic patient are shown in Figure 3. A prominent peak in the region of PDE is clearly visible in the cardiomyopathic patient. Another prominent peak is visible in the megion of the phosphornonoesters (PMEs). However, the PME peak was not measured because of concern megamding overlap of PME resonances with those of inorganic phosphate and 2,3-diphosphoglycemate. The PCm/f3-ATP ratio was not significantly changed in patients with cardiomyopathy compared with healthy volunteers (Fig 4). The PCm/ inorganic phosphate ratio was not measured because of concern regarding overlap of the inorganic phosphate resonance with PME and 2,3diphosphoglycemate. The PDE/PCn ratio was significantly increased in cardiomyopathic patients compared with healthy volunteers (P < .05). The PDE/3-ATP ratio was also significantly increased in cardiomyopathic patients compared with healthy volunteems (P < .05) (Fig 4).

Cine MR Parameters

Imaging:

Functional

Representative cine MR images in the true short axis of the heart are shown in Figure 5. Ejection fraction (24% ± 3 vs 59% ± 3; P < .01) and mean wall thickening (20% ± 3 vs 50% ± 4; P < .01) were significantly 256

#{149} Radiology

PMEPOE

F

10

0

-10

-20

i’o

PPM

a.

,-1-

0

-10

-20

PPM

b.

Figure

3.

Representative

P-31

MR

spectra

obtained

from

healthy

volunteer

(a) and

with dilated cardiomyopathy (b). The broad and split peak labeled PME represent PME alone but is also partially composed of inorganic phosphate contaminated by 2,3-diphosphoglycerate from the blood pool.

patient

probably

does

and

possibly

not

PCr/B-ATP

P-31 MR Spectroscopic Peak for Two Studies in Healthy

Ratios

Volunteers Study (n7) PCn/-ATP peakratio PDE/PCr peakratio Heartrate Note-Values

1

Study (n7)

1111/

2

1.591±0.110

1.482±0.221

0.516±0.202 73±5

0.584±0.142 81±7

PDEIPCr

are mean

± SD.

0.8 2 0.6 0.4 0.2

1.0

lower in cardiomyopathic patients compared with healthy subjects. The left ventricular end-systolic wall stress was significantly greater (143 dynes/cm2 ± i4 vs 42 dynes/cm2 ± 4; P < .Oi) in the patients with camdiomyopathy than in healthy volunteers. Intemobsemver reproducibility for left ventricular end-systolic and end-diastolic mean wall thicknesses was r = .94, and for left ventricular end-systolic and end-diastolic diametersitwasr

0.8

!

NORMAL

Figure fl-ATP

8) and in patients with dilated athy (ii = 13). Data are presented standard error. * = P < .05.

.99.

In Figures 6 and 7, the mean and individual values of PDE/PCm and PDE/fi-ATP ratios are shown in relation to ejection fraction, systolic wall thickening, and end-systolic wall stress for healthy subjects and patients with cardiomyopathy. The PDE/PCr ratio was the P-3i MR spectmoscopy parameter that provided the best discrimination between healthy subjects and cardiomyopathic patients. However, this parameter did not allow differentiation of three of the 12 patients with cardiomyopathy from the healthy group. These three patients had the highest ejection fractions and lowest systolic wall stress among the cardiomyopathic group.

MYOPATHIC

PCn/fl-ATP, PDE/PCr, and peak ratios in healthy volunteers

PDE/

4.

(n

cardiomyopas mean

±

DISCUSSION The is that

first observation reproducible

can be obtained the next with ical

shift

ization of the

P-3i

in our study MR spectra

from one one-dimensional

imaging

surface

techniques. important

study coil

to chemlocal-

The average peaks did not

ratio differ

significantly in the group between studies. From the spectra collected at vanous depths from the body surface, the spectrum attributed to cardiac tissue

was in the

identified

by an abrupt

PCrfl3-ATP

cause the PCn/fl-ATP muscle is substantially that of myocardium,

peak

area

decrease ratio.

Be-

ratio of skeletal greater than this decrease in-

April

1991

I 0 I 0 !

60

2

40

a

20

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PDE/8-ATP

7.

Figures

6, 7. Plots of PDE/PCr (6) and PDEfl5-ATP (7) ratios versus left ventricular ejection fraction, mean systolic wall thickening, and end-systolic wall stress in healthy volunteers (n = 8) and patients with dilated cardiomyopathy (n 12). The data points with the error bars

Figure

5.

Sample

dine MR images obtained parallel to the true short axis of the heart from a healthy volunteer. These images were obtained at the midportion of the left ventridle. The intracavitary blood pool shows high signal intensity compared with the myocardium. The extent of wall thickening from end-diastole to end-systole was measured on dine MR images (TR/TE 31/ 17).

dicates mates diurn.

that this spectrum likely onigpredominantly from myocanAlso, because one-dimensional

chemical

shift

imaging

corresponding

over

yields

spectra

to i-cm-thick

a 32-cm

position referenced images.

field

sections

of view,

of the spectra can to the transverse Such cross-referencing

the be

spatial

crosslocalizem be-

tween the spatial dial spectra and the heart showed This supposition the observations

position of myocamthe actual position of good agreement. is consistent with from previous stud-

ies that

muscle

skeletal

en PCn/fl-ATP peak observed for cardiac ly, PCr/f3-ATP peak skeletal muscle are with only 1-2:1 for

The

selected

in vivo

chemical

spectroscopy

surface

The

advantages

coil

signal intensity, very little distortion (due to the very phase-encoding time [500 absence of spatial chemical set effects for the different

Volume

179

Number

#{149}

1

and

spectnos-

include

nances. The this technique definition

good

baseline short .isecJ), and shift offreso-

values

major are of the

and the placement

resulting of the

for each

of the two

disadvantages of the lack of precise localized

volume

imaging

techniques,

and reliability of the averarea ratios reported in this that this factor.

the one-dimensional imaging technique, chest wall muscle causing

some

myocardial

chemical sampling is unavoidable,

contamination

MR

repro-

problem With use

is of

shift of some of the

spectra.

This

be equivalent for and cardiomyopathic and therefore does

effect

healthy not

volpavitiate

of i.69

between

wall

in the

These

crease

the

a PCm/ATP the image setechnique

tech-

coil

et al (6)

variations

between

studies

coil).

(6,8,i7,i8).

the

surface

to either

Table,

py

subjects

with

with variations rates (see mean

or differences

in healthy

± 0.07

MR spectra. a PCm//3-ATP

Blackledge

due

associated ual heart

muscle signal intensity. The PCm/f3ATP (1.54 ± 0.04) and PDE/PCr (0.54 :1: 0.10) peak area ratios in this study are similar to those reported in the few prior reports on MR spectroscoSchaefer et al (i7) found ratio of 1.33 ± 0.19 with lected in vivo spectroscopy

of P-3i reported

for sev-

found this ratio to be i.55 ± 0.20 in six healthy subjects. Thus, the values reported in this study for PCr//3-ATP ratios are similar to those reported in prior studies, with the exception of the report by Schaefer et al (17), in which the ‘y-ATP rather than the f3ATP peak was measured. No attempt was made to draw conclusions megarding PME/PCm or inorganic phosphate/PCm peak area ratios. This was due to the uncontrolled and, perhaps, unquantifiable contamination of signal in the PME-inomganic phosphate region (5-6.5 ppm from PCm) from 2,3-diphosphoglycemate contained in blood. Some of the deviations in the peak area ratios may be due to changes in saturation factors from study to

sampling

chest

are shown

of depth-resolved

study,

and

values

for localization Grist et al (i8)

our findings. During the severalminute acquisition period, mespimatony thomacic wall excursion causes some cyclic variation in the relative of heart

stress

spectroscopy.

ducibility age peak

study indicate not a hindering

the

(Wall

nique

tive disk from which each spectrum can be attributed. This problem may be alleviated through the use of twoand three-dimensional chemical shift but

groups.

ratio

need for precise surface coil. This

stems from the use of the physical properties of the surface coil to define the circumference of the sensi-

should unteens tients

technique offers some and disadvantages comother techniques (ie, im-

depth-resolved

copy).

lang-

area ratios than muscle (typicalarea ratios for 5-7:i compared cardiac tissue).

one-dimensional

shift imaging advantages pared with

age

exhibits

represent the mean en volunteers.)

in TR

of individheart mates

patients

in the

and

same

in chest

patient)

wall

thickness

between individuals (changes in thickness would mean different effective flip angles that tissues expenience depending on depth from the

tios

calculated

weighting

factors

spread

would

of the because

of the

spectra

tend

to in-

peak

area

of the

Ti

due Radiology

ma-

to the #{149} 257

long Ti of P-3i nuclei and the relatively variable, short TRs used for these examinations (900-i,500 msec). The second observation in this study is that impaired left ventricular systolic function in dilated cardiomyopathy in humans is associated with disproportionately high levels of PDES relafive to high-energy phosphate compounds (PCr and ATP). However, the three patients with the least depression in left ventricular ejection fraction as assessed with cine MR imaging yielded normal PDE/PCr ratios. It should be noted that a relationship between functional and metabolic parameters was not sought in this study because prior case reports have mdicated that PDE peaks were elevated in two patients with hypertrophic cardiomyopathy, a disease in which functional parameters are usually increased rather than depressed (5,7). MR spectroscopy has been used to detect changes in high-energy phosphate metabolism in isolated perfused cardiomyopath.ic rodent hearts (ii) and in surgically exposed hearts of animals in situ (i2). In contrast to the animal studies, the levels of highenergy phosphate metabolites in cardiomyopathic hearts were found to be similar to those of healthy subjects. Prior reports involving the cardiomyopathic hamster have shown alterations in ATP and PCr values. These abnormalities in high-energy phosphate compounds have been ob-

arterial sumably

obstructive ischemic

disease necrosis

and was

preex-

athy, when myocardial necrosis and evidence of ischemia are present. The current study in humans did not indicate alterations in the PCn/ATP ratio; from this, it is inferred that ATP and PCr are not substantially depressed in the cardiomyopathic patient at rest. The few anecdotal meports on P-3i MR spectroscopy in humans with cardiomyopathy have also suggested that the PCr/ATP ratio and PCr and ATP values are not decreased at rest. The discrepancy in the results in the isolated hearts of rodents with myopathy and humans may be related to a variety of differences, including the experimental conditions, as the isolated heart may be borderline ischemic at rest, especially in the form of hypertrophic

cluded in these patients. The P-31 MR spectra of human myocardiu.m have been found to have a prominent peak at i.5-3.5 ppm (vs 0 ppm for PCr), which represents mainly PDES (19). It has been shown in two patients with hypertrophic cardiomyopathy that the PDE peak was increased (5,7). There is much speculation about the biochemical relevance of the PDE peak in myocardial disease states. The PDE peak seen in normal and myopathic human hearts has been assigned to membrane cornpounds, such as glycerophosphoryl choline and glycerophosphoryl ethanolamine. PDES are closely related to the pathogenesis of certain muscular dystrophies in rodents (20) and humans (2i). An increase in the myocardial PDE peak may be related to an increase in the synthesis and/or degradation of cell membranes. It might be proposed as a speculation for further investigation that the parallel progression of abnormal phosphorus spectra and impaired systolic function is mediated by membrane damage meflected in the PDE peak. A limitation of the current study and of previous P-3i MR spectroscopic studies in humans is the need for evaluation of the myocardium with a surface coil, which causes the region for sampling to be large. In the early days of MR spectroscopy of humans, the position of the organ was approximated by surface landmarks and spectra were accumulated from a spherical region of interest with the technique of topical MR (22). These approaches had been limited by lack of depth localization and imaging control of the region of interest. Now, an imaging technique has been described that uses field gradients to acquire depth-localized P-3i spectra from the human heart (iO). In this study, we also used a depth-localized technique in which the region of interest was a disk 60 cm3 in volume. The technique was applied to diffuse myocardial disease because of recognition of the uncertainty entailed with resolving spectra from any region of the left ventricle. Prior reports have demonstrated ab-

cardiomyopathy

normalities

served

in the

late

stage

in the

of this

Syrian

myop-

ham-

stem. In prior studies, the alterations in P-3i MR spectra were detected in the advanced stage of myopathy in the Syrian hamster when myocardial necrosis was evident. Such widespread necrosis is not a characteristic of idiopathic dilated cardiomyopathy in patients. The presence of coronary 258

#{149} Radiology

of the

P-3i

spectra

of the

left ventricle in humans with ischemic heart disease (8,9); thus, our goal of detecting diffuse myocardial disease was less ambitious than that already accomplished with depth-bcalized surface coil P-31 MR spectroscopy in humans. Uncontrollable variaMes in this study that could have in-

fluenced the results are variations in the distance from the surface coil to the myocardium and variations in RR interval (TR interval for ECG-gated acquisition) among the subjects. Both of these factors might have variable influences on the amplitude of the spectra among the subjects. End-systolic wall stress is related to myocardial oxygen consumption (23,24). It is influenced substantially by the diameter of the left ventricubar chamber rather than by cardiac output (25,26). This may explain why the cardiomyopathic heart consumes more oxygen (27) than the normal heart even though systolic function is reduced.

End-systolic

wall

stress

is

another parameter, along with global (ejection fraction) and regional (wall thickening) parameters of left yentriculam function, that can be derived with cine MR imaging. These parameters might be used to characterize the severity of the hemodynamic dysfunction and to monitor the progmession of such dysfunction in cardiomyopathy. The PDE/PCr ratio was the best discriminator between healthy volunteers and patients with cardiomyopathy. Whether this index is compamable with hemodynamic measurements cannot be determined from this study because the patients were selected based on the presence of the hemodynamic abnormality. We conclude that localized, gated P31 MR spectroscopy, combined with cine MR imaging, identifies both abnormalities in the level of PDES in the myocardium and depressed ventricubar function, which might be useful in the characterization of patients with dilated cardiomyopathy. Our conclusion about the alterations in the P-3i MR spectra associated with cardiomyopathy must be considered with recognition of the possible contamination of the myocardial spectra by signal from skeletal

muscle

of the

chest

wall

when

the one-dimensional chemical shift imaging acquisition technique is used. The pathogenetic significance of the increase in POE is unknown but may be related to a breakdown in components of myocardial membranes. These observations indicate the feasibility of integrating MR imaging and MR spectroscopy in the evaluation of the functional and metabolic states of the left ventricle in humans. U References 1.

2.

Higgins CB. MR of the heart: anatomy, physiology, and metabolism. AJR 1988; 151:239-248. Higgins CB, Holt WW, Pflugfelder P, Sechtem U. Functional evaluation of the

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Markiewicz W, Wu S. Parmley WW, et al. Evaluation of the hereditary Syrian hamster cardiomyopathy by P-31 nuclear magnetic resonance spectroscopy: improvement after acute verapamil therapy. Circ Res 1986; 59:597-604. Kobayashi A, Yamashita T, Kaneko M, Nishiyama T, Hayashi H, Yamazaki N. Effects of verapamil on experimental cardiomyopathy in the Bio 14.6 Syrian hamster. J Am CoIl Cardiol 1987; 10:1128-1134. Bottomley PA. Spatial localization in NMR spectroscopy in vivo. Ann N Y Acad Sci 1987; 508:333-348. Marsh JD, Green LH, Wynne JW, Cohn PF, Grossman W. Left ventricular endsystolic pressure-dimension and stresslength relations in normal human subjects. Am J Cardiol 1979; 44:1311-1317. Stefadouros MA, Dougherty MJ, Gross-

man W, Craige E. Determination of systemic vascular resistance by a noninvasive 16. 17.

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technic. Circulation 1973; 47:101-107. Zar JH. Biostatistical analysis. 2nd ed. Englewood Cliffs, NJ: Prentice-Hall, 1984. Schaefer S. Gober J, Valenza M, et al. Nuclear magnetic resonance imaging guided phosphorus-3l spectroscopy of the human heart. J Am CoIl Cardiol 1988; 12:14491455. Grist TM, Kneeland JB, Rilling WR, Jesmanowicz A, Frondisz W, Hyde JS. Gated

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