Download Clinical use of ultrashort-lived radionuclide krypton-81m for

687
JACC Vol. 5, No.3
March 1985:687-98
METHODS
Clinical Use of Ultrashort-Lived Radionuclide Krypton-81m for
Noninvasive Analysis of Right Ventricular Performance in Normal
Subjects and Patients With Right Ventricular Dysfunction
CHRISTOPH A. NIENABER, MD, ROLF P. SPIELMANN, MD,* GERD WASMUS, PHD,*
DETLEF G. MATHEY, MD, RICARDO MONTZ, MD,* WALTER H. BLEIFELD, MD, FACC
Hamburg, West Germany
The ultrashort-lived radionuclide krypton-81m, eluted
in 5% dextrose from a bedside rubidium-81m generator,
was intravenously infused for rapid imaging of the rightsided heart chambers in the right anterior oblique projection adjusted for optimal right atrioventricular separation. Left-sided heart and lung background was minimized by rapid decay and efficient exhalation of krypton.
81m, requiring no algorithm for background correction.
A double region of interest method decreased the variability in the assessment of ejection fraction to 5 % .
In 10 normal subjects, 11 patients with pulmonary
hypertension, 4 patients with right ventricular outflow
tract obstruction and 4 patients with right ventricular
infarction, right ventricular ejection fraction determined
by krypton-81m equilibrium blood pool imaging ranged
from 14 to 76%. The correlation between these values
and those determined by cineangiography according to
Simpson's rule was close: r = 0.93 for all data points
In 1968, the ultrashort-lived radionuclide krypton-81m was
introduced as an imaging agent by Yano and Anger (1).
Krypton-81m minigenerators were designed (2) to provide
elution of this noble gas from rubidium-81 m for the assessment of lung ventilation and perfusion (3,4), cerebral
blood flow (3,5) and regional myocardial perfusion in animals and human patients (6-8). Recently, krypton-81m was
used to assess right ventricular function in human beings
(9). This study describes the clinical application of krypton81m to image the right ventricular blood pool and determine
right ventricular ejection fraction, both in normal subjects
and patients with right ventricular dysfunction at rest and
From the Department of Cardiology and Department of Nuclear Medicine,* University Hospital Eppendorf, Hamburg. West Germany. Manuscript received February 29, 1984; revised manuscript received September
24, 1984, accepted October 15, 1984.
Address for reprints: Christoph A. Nienaber, MD, University Hospital
Eppendorf, Department of Cardiology, 2. Med. Clinic, Martinistr. 52.
2000 Hamburg 20, West Germany.
© 1985 by the American College of Cardiology
(p < 0.001), r = 0.92 for studies at rest (p < 0.001)
and r = 0.93 for exercise studies (p < 0.(01). Exerciserelated changes in right ventricular function revealed a
disturbed functional reserve with pulmonary hypertension and right ventricular infarction, whereas in compensated right ventricular outflowtract obstruction there
was a physiologic increase in ejection fraction with exercise (p < 0.001).
Thus, equilibrium-gated right ventricular imaging
using ultrashort-lived krypton-81m is a simple, accurate
and reproducible method with potential for serial assessment of right ventricular ejection fraction in a variety of right ventricular anatomic and functional abnormalities, both at rest and during exercise. Advantages
of this method include an extremely low radiation dose
to patients and clear right atrioventricular separation
without the need to correct for background activity.
(J Am Coli CardioI1985;5.·687-98)
during exercise. The method was validated by cineangiography and tested for reproducibility.
Other noninvasive methods have been proposed to measure right ventricular ejection fraction using technetium-99m
(half-life of 5.6 hours) in first pass acquisition mode independent of right ventricular geometry. These techniques
compare well with biplane cineangiography (10-19). However, since only the first transit of technetium-99m is recorded, the technique does not provide serial measurements
without repeated injections of technetium-99m for each data
acquisition point. The number of repeat first pass studies,
however, is limited by increasing radiation exposure to the
patient and by residual blood pool background from previous
injections. To eliminate problems associated with first pass
technetium-99m angiography, multiple gated equilibrium
blood pool imaging in left anterior oblique projection had
been introduced and validated to measure right ventricular
ejection fraction assuming counts to be proportional to volume (18-21). Problems remain , however, in defining right
0735-1097/85/$3.30
688
NIENABER ET AL.
RIGHT VENTRICULAR IMAGING WITH KRYPTON-81m
ventricular background and managing right atrial overlap.
The proposed methods thus differ largely in their approach
to solving these problems (20,22).
In this study, the ultrashort-lived radionuclide krypton81m is continuously infused intravenously to image exclusively the right-sided cardiac blood pool since rapid decay
and low water solubility of krypton-81 m result in complete
clearance of activity from the alveolar membrane. Thus, the
technique provides serial measurements of right ventricular
ejection fraction in a gated equilibrium acquisition mode
using the right anterior oblique projection for optimal separation of the right atrium from the right ventricle, with no
need to correct for lung background and minimal radiation
burden to the patients.
Methods
Krypton-81m generator. The generator consists of
rubidium-81, produced in a cyclotron by alpha bombardment of bromine-79. Rubidium-81 decays with a half-life
of 4.7 hours to ultrashort-lived krypton-81m, which has a
half-life of 13 seconds; this process emits monoenergetic
photons with an energy of 190 keV suitable for standard
scintillation cameras and collimators (23,24). Krypton-81m
is eluted by passing a solution of nonionic 5% dextrose in
water through a cation exchange column in which the parent
nuclide rubidium-81 is bound (25-27).
The aqueous krypton-81 m solution is continuously recovered from the minigenerator and intravenously infused
by a high precision pump (LKB HPLC 2150) providing a
steady flow of 4 mllmin through a millipore filter system
(Miller, Millipore SA) connected to an 18 gauge polyethylene cannula. Sterility of the eluate was proven by negative broth cultures.
Rubidium-81 m breakthrough measured with gamma ray
spectroscopy using a solid state detector system is insignificant (25). The charged generator is shielded by 9.5 em
lead bricks completely surrounding the system. The activity
level in the shielding surface is several milliroentgens/hour,
causing no interference with imaging krypton-81 m when
positioned 20 cm lateral to the collimator. This krypton81m minigenerator is not yet commercially available. Provided by the Deutsche Kemforschungszentrum Karlsruhe,
its use is limited to about 18 hours, including transport time,
because of the 4.7 hour half-life of the 25 mCi rubidium81m parent nuclide.
Study patients (Table 1). Both krypton-81 m radionuclide and cineangiographic right ventricular ejection fraction studies were performed in 28 patients. Group 1consisted
of 10 normal subjects, 7 men and 3 women, aged 25 to 56
years (mean 38), with no clinical or hemodynamic evidence
of cardiopulmonary disease by physical and electrocardiographic examination, chest X-ray film and right heart catheterization. These 10 subjects were considered controls since
JACC Vol. 5, No.3
March 1985:687-98
results of both right heart catheterization and exercise radionuclide imaging studies for diagnostic evaluation of suspected cardiac disease were normal.
Group II consisted of 18 patients (13 men and 5 women),
aged 24 to 66 years (mean 45), with predominantly right
ventricular abnormalities, and included 9 patients with secondary pulmonary hypertension (6 of whom had mild tricuspid valve regurgitation). One patient had primary pulmonary hypertension, three patients had partial correction
of tetralogy of Fallot and residual pulmonary valve stenosis,
one patient had isolated subvalvular pulmonary stenosis and
four patients had complete occlusion of the right coronary
artery and inferior myocardial infarction partly involving
the right ventricle. Eight of the nine patients with secondary
pulmonary hypertension had previous mitral valve replacement; four of these underwent both aortic and mitral valve
replacement. Three patients in this subset had evidence of
chronic obstructive pulmonary disease.
Written informed consent according to the Helsinki declaration on human experimentation was obtained from all
subjects undergoing either the angiographic or the radionuclide studies. Both studies were completed within 72 hours
without changes in ongoing medication. There were no severe complications associated with either diagnostic study
in any subject with the exception of Patient 4, who suffered
from exhaustion and dizziness after stress cineangiography;
Patients 9 and 10 could not perform dynamic exercise because of dyspnea in the supine position.
Radionuclide angiography. Equilibrium radionuclide
right ventricular angiography at rest and during submaximal
exercise was performed with the patient in the supine position using a variable right anterior oblique view adjusted
by 5 to 10° caudal tilt for best separation between the right
atrium and the right ventricle. A mobile single crystal gamma
scintillation camera (LEM, Searle) equipped with a low
energy, all purpose, parallel-hole collimator was used for
image acquisition, with the pulse-height analyzer set at 190
keY and a 20% acoustical window. Multiple gated acquisition was controlled by a PDP 11/34 minicomputer using
GAMMA-II software. Thirty frames per cycle were acquired in frame mode by use of a zoom device that expanded
the data 1.7 times and recorded it on 64 x 64 matrix.
Acquisition at rest was terminated when 3,000,000 counts
were reached in the total field of view (10 minutes). Exercise
acquisition time was limited to a maximal period of 300
seconds, yielding 1,500,000 counts at a count rate of 5,000
counts/s ± 10%. Approximately 500,000 counts were routinely obtained in the end-diastolic region of interest. Data
were processed using a semiautomated computer algorithm
that involved definition of separate end-systolic and enddiastolic right ventricular regions of interest. Nine point
spatial and three point time-smoothing was performed on
each frame of a composite cycle.
Operator intervention was permitted to define the tricus-
689
NIENABER ET AL.
RIGHT VENTRICULAR IMAGING WITH KRYPTON-81m
JACC Vol. 5, No.3
March 1985:687-98
Table 1. Mean and Individual Hemodynamic Results in 10 Normal Subjects and 18 Patients With Right Ventricular Abnormalities
Group I: 10 Normal Subjects OM, 3F; mean age 38 years)
CO
(liters/min)
Ex
Re
Ex
Re
4
6
±3
±3
P < 0.05
5
±3
8
±4
NS
RAP
(mm Hg)
Re
Re
Ex
13
19
±4
±5
p < 0.05
Mean value
± SO
p
RAV
wave
(mmHg)
PAP
(mm Hg)
Ex
Simpson's
RVEF
Kr-8lm
RVEF
(%)
(%)
Re
Ex
Re
Ex
6.0
I\.4
± \.0
± \.9
P < 0.01
49
60
±7
±7
P < 0.001
52
63
±8
±7
P < 0.001
CO
Simpson's
RVEF
Kr-8lm
RVEF
(liters/min)
(%)
(%)
Group II: 18 Patients With Right Ventricular Abnormalities
Case Age (yr)
(no.) & Sex
Diagnosis
I 30/M
2 29/M
3 61/M
4 6O/M
5 64/F
6 52/F
7 42/M
8 53/M
9 61/F
10 311M
Mean value
± SO
P (Re vs. Ex)
AVR, MVR, PH, TR
MVR, PH
MVR, capo, TR, AVR
MVR, capo, PH, TR
MVR, PH, TR
MVR, PH, TR, AVR
AVR, MVR, PH, TR
PH,PE
MVR, capo
PPH
37/M
II
12 24/M
13 24/M
14 31/F
Mean Value
± SO
p (Re vs. Ex)
15 45/M
16 60/M
17 54/F
18 66/M
Mean value
± SO
p (Re vs. Ex)
TOF, PS
TOF, PS, PI
TOF, PS
PS
INF
INF
INF
INF
+
+
+
+
aP:Re Ex
36 37
55 80
92 89
40 44
56 62
±25 ±26
NS
RVMI
RVMI
RVMI
RVMI
NYHA
Class
III
III
III
lll/IV
IV
II
III111
II
IV
IV
0
0
0
0
0
0
III
II
PCWP
(mm Hg)
PAP
(mm Hg)
RAP
(mm Hg)
Re
Re
Re
Ex
Ex
22
25
52
55
40
48
14
19
II
34
22
36
22
30
39
49
17
19
45
55
20
32
53
18
15
50
12
16
22
15
42
6
18
26
76
15
49§
36*
16* 23:j:
±5
±6 ±19 ±7
p < 0.05
P < 0.01
7
8
8
II
7
7
±I
10
10
±2
NS
10
13
12
12
15
18
14
16
13* 15*
±2
±3
NS
II
20
15
20
19
22
18
26
16
22
±4
±3
P < 0.05
18
22
13
18
16
29
14
30
IS
26
±2
±6
P < 0.05
Ex
RAV Wave
(mm Hg)
Re
Ex
Re
Ex
Re
Ex
Re
Ex
IS
16
II
13
7
15
16
20
15
19
10
21
9
20
I
8
9
13
II * 17t
±5
±4
P < 0.01
20
23
3.2
4.9
12
16
3.4
5.4
15
24
4.6
9.4
19
34
3.9
4.9
18
26
5.4
6.9
13
29
12
38
6.5
8.1
3
17
4.4
6.4
IS
4.8
16
2.1
6.5§
14t 26:j:
4.4*
±5
±8 ±1.3
± \.6
P < 0.01
P < 0.01
32
28
37
30
35
34
37
38
43
47
45
50
42
29
44
33
44
32
45
48
41
42
37
52
42
36
40
32
45
50
41
52
34
43
12
14
4!:j:
37*
37+ 40
±IO ±8 ± 10 ±9
NS
NS
5
12
9
10
8
II
10
13
8* 12t
±2
±2
P < 0.05
6
9
10
12
12
14
10
II
lOt
12t
±3
±2
P < 0.02
6
12
13
II
10
±3
43
56
45
62
50
56
53
69
50
65
51
69
42
49
46
54
46
56
49
64
±4
±7
±4
±7
P < 0.02
P < 0.01
40
51
43
48
41
36
36
39
29
33
30
28
36
40
38
38
35:j:
40:j: 38t 39§
±5
±8
±6
±9
NS
NS
16
4.1
14
5.3
15
4.8
IS
4.7
15:j:
4.7
±I
±0.5
NS
P<
9
II
5.7
13
14
4.5
4.9
13
16
12
13
5.0
12t 14t
5.0
±2
±2 ±0.5
P < 0.05
P<
7.4
12.9
9.9
8.3
9.6
±2.4
0.02
9.2
8.8
6.8
8.6
8.5:j:
± \.0
0.01
*p < 0.05; tp < 0.02; :j:p < 0.01; §p < 0.001 versus normal subjects. AVR = aortic valve replacement; CAD = coronary artery disease; CO =
cardiac output; capo = chronic obstructive pulmonary disease; Ex = exercise; F = female; INF = inferior; M = male; MVR = mitral valve
replacement; NS = not significant; ap = systolic pressure gradient of pulmonary stenosis; PAP = mean pulmonary artery pressure; PCWP = pulmonary
capillary wedge pressure; PE = pulmonary embolism; PH = pulmonary hypertension; PI = pulmonary insufficiency; PPH = primary pulmonary
hypertension; PS = pulmonary stenosis; RAP = mean right atrial pressure; Re = rest; RVEF = right ventricular ejection fraction; RVMI = right
ventricular myocardial infarction; RVOT = right ventricular outflow tract; SO = standard deviation; TOF = tetralogy of Fallot; TR = tricuspid
regurgitation.
pid and the pulmonary valve plane. If the right atrioventricular border could not be defined visually from original
images, it was determined from phase images by first temperol Fourier transformation of time-activity curves (28,29)
to compensate for systolic tricuspid valve plane motion. The
pulmonary valve plane was defined as the junction between
the contracting and the noncontracting regions of the right
ventricular outflow tract or the region of the outflow tract
between a systolic increase in counts superiorly (pulmonary
artery) and a systolic decrease in counts inferiorly.
Right ventricular septal and free wall contours were aligned
by a semi automated edge detection program; right ventric-
690
NIENABER ET AL.
RIGHT VENTRICULAR IMAGING WITH KRYPTON-81m
ular end-diastolic and end-systolic regions of interest were
defined by isocountlines of 50% of the right ventricular
count maximum in the end-diastolic image. Right ventricular ejection fraction was calculated by subtracting endsystolic from end-diastolic counts divided by end-diastolic
counts x 100. No background correction was performed.
To test both methods (krypton-81 m ventriculography and
contrast cineangiography) for inter- and intraobserver variability, two experienced observers (R.P.S. and C.A.N.),
both blinded to the clinical diagnosis, independently evaluated ejection fraction in all subjects. In addition, for the
assessment of intraobserver variability of each method, one
observer blinded to his previous reading repeated the analysis I week after his first evaluation.
Cineangiography (Table 2). Both rest and exercise biplane contrast ventriculography was performed in 16 of the
18 patients of Group II (Patients 9 and 10 were studied only
at rest) and all 10 subjects in Group I in the anteroposterior
and lateral views with power injection of 45 ml of meglumine diatrizoate (Urografin-76) at a rate of 15 mils and a
pressure of 400 lb/in? (60 kg/em"). Stress right ventricular
cineangiograms were performed at a level of submaximal
exercise that was identical to the work load during the radionuclide study. Cine frames were obtained at a rate of 50
frames/so A I cnf grid was used for magnification correction. Maximal outward displacement of the right ventricle
was determined in the end-diastolic frame, whereas the endsystolic frame was taken as the point of maximal inward
motion. Simpson's rule was applied in the evaluation of
both frames as described previously (12, 13) and used to
calculate ejection fraction by subtracting the end-systolic
volume from the end-diastolic volume divided by the enddiastolic volume x 100.
Evaluation of hemodynamics. Systemic arterial blood
pressure and heart rate were monitored conventionally at
rest and during submaximal bicycle exercise. All patients
who underwent cineangiography were studied simultaneously with invasive hemodynamic monitoring. Intracardiac pressures including pulmonary wedge pressure, mean
pulmonary artery pressure and phasic right ventricular as
well as phasic and mean right atrial pressures were obtained
by right heart catheterization with a Swan-Ganz thermodilution catheter inserted through an antecubital or femoral
vein using the Seldinger technique and advanced into the
pulmonary artery. Cardiac output was determined by the
thermodilution method. The pulmonary artery wedge pressure was measured as an index of left ventricular filling
pressure. In four patients, the systolic pressure gradient
between the right ventricle and pulmonary artery was used
as an index for residual pulmonary stenosis.
Exercise protocol. In each subject who underwent exercise studies, data were acquired at an identical work load.
The patients pedaled at a constant speed, usually at a load
lACC Vol. 5, No, 3
March 1985:687-98
of 300 kpmlmin. Radionuclide imaging was started after 2
to 3 minutes or when a stable heart rate during exercise was
reached. Hemodynamic measurements and cineangiography
were also undertaken at this time. Patients 4 and 5 exercised
to a work load of only 150 and 60 kpmlmin, respectively,
for a period of 6 minutes; Patients 9 and 10 had no exercise
studies (Table 2).
Statistical methods. Ejection fraction values are reported as mean values ± standard deviation. Linear regression analysis was applied for statistical correlation between
right ventricular ejection fraction by both methods. Student's t test was used to assess statistically significant differences. Rest and exercise data were compared by use of
the paired t test. Intra- and interobserver variability of radionuclide and cineangiographic determinations of right ventricular ejection fraction is given as the residual error of a
two-way analysis of variance. A probability (p) level of less
than 0.05 was considered statistically significant.
Results
Correlation between krypton-81m and angiographic
right ventricular ejection fraction measurements. The
correlation between the gated equilibrium technique using
krypton-81m and biplane right ventricular contrast cineangiography for calculating right ventricular ejection fraction
was good when all data points (n = 54) in all 28 subjects
were compared (r = 0.93, standard error of the estimate
[SEE] = 4.58 [p < 0.001], y = 1.0 X + 3.05). A comparison of resting and ejection fraction values determined
at rest and during exercise revealed similar results (r =
0.91, SEE = 4.01 [p < 0.001], Y = 0.95 x + 4.8 for
rest studies; r = 0.93, SEE = 5.23 [p < 0.001], Y =
1.01 x + 2.95 for exercise studies) (Fig. 1).
Similar results were also observed when rest and exercise
ejection fraction measurements were analyzed separately in
normal subjects and patients. In normal subjects, the correlation obtained at rest was r = 0.74, SEE = 5.31 (p <
0.02), whereas during exercise the correlation wasr = 0.75,
SEE = 4.7 (p < 0.02) (Fig. 2A). When rest and exercise
data in normal subjects are considered together, the regression line is described by r = 0.84, SEE = 4.85 (p < 0.001),
y = 0.95 x + 5.63 (Fig. 2A). When both imaging methods
were compared in patients in Group II (Fig. 2B), the correlation coefficient of right ventricular ejection fraction was
higher in the studies at rest (r = 0.92, SEE = 3.45 [p <
0.001]) than in the exercise studies (r = 0.9, SEE = 5.72
[p < 0.00 I]). Comparison of both methods with respect to
combined rest and exercise data points (n = 34) resulted
in values of r = 0.91, SEE = 4.56 (p < 0.001). The
related linear regression equation is y = 1.02 x + 2.1 I .
The correlation in Group II was better than that in Group I
NIENABER ET AL.
RIGHT VENTRICULAR IMAGING WITH KRYPTON-81m
l ACC Vol. 5, No. 3
March 1985:687- 98
691
Table 2. Exercise Protocol and Hemodynamic Data During Krypton-81m Radionuclide Ventriculography and Cineangiography
Cine angiograp hic Exercise Studies
Krypton-81 m Radionucl ide Exe rcise Studies
HR
(beats/min)
SBP
(mm Hg)
Re
Re
Ex
Ex
RP P
(HR x SBP
x 10")
Re
Ex
Work Load
(kpm/ min)
T ime
(min)
HR
(beats/min)
SBP
(mm Hg)
Re
Re
Gro up I: Normal Sub jects (n
Mean value
:t SD
p (Re vs . Ex )
74
117
:t 14 :t 13
p < 0 .001
125
166
:t 15 :t 16
p < 0 .001
9 .3
19 .4
:t 1.6 :t2.6
P < 0 .001
300
9
=
Ex
Ex
RPP
(HR x S BP
x 10 ' )
Re
Ex
Work Load T ime
(kpm/ rnin) (min)
10)
120
72
± 16
± 16
P < 0 .001
12 1
163
± 17 1: 17
P < 0 .01
19 .6
8.7
± 1.9 ± 2 .1
P < 0.00 1
300
9
20 . 1
6 .6
21.7
9 .4
10.4
19 .5
10.4
20 .8
8.8
2 1.8
26 .4
8 .6
10 .1
25 .5
25 .7
8 .8
10.4
11.0
22 .7
9.4
± 1.3 ± 2.8
P < 0 .00 1
9 .2
20 .7
9 .8
23.8
24 .7
8.8
24.4
11.4
9 .8
23 .4
± 1.2 :t 1.9
P < 0 .0 1
19 .4
7 .4
22 .8
8. 1
9 .9
18 .6
9 .6
19 .7
8 .8
20. 1
± 1.2 ± 1.9
P < 0 .0 1
300
300
300
150
60
300
300
300
6
6
6
4
4
6
9
8
25 1
1: 93
6 .3
± 1.8
300
300
300
300
300
9
9
9
9
9
300
300
150
300
262
9
9
9
9
9
Gro up II: 18 Patient s With Right Ventr icular Abnormalities
Case (no .)
I
62
126
118
84
84
122
138
88
148
96
78
130
134
86
72
128
100
86
13 1
83
± 11
±9
p < 0. 001
84
134
142
82
136
72
152
90
141t
82
±8
±9
±SD
P (Re vs. Ex )
p < 0 .001
114
15
60
108
16
58
17
84
130
114
18
78
Mean value
117
70
± SD
± 13
± IO
p (Re vs . Ex)
p < 0.01
2
3
4
5
6
7
8
9
10
Mean value
:tSD
p (Re vs. Ex)
II
12
13
14
Mean value
115
150
120
170
130
170
110
145
105
140
115
190
100
150
125
205
105
115
114
165
± IO ±23
P < 0 .001
110
145
125
170
130
195
130
170
124
170
:t 10 :t 2 1
P < 0 .01
130
170
140
195
115
150
120
165
126
169
±11
± 19
P < 0 .0 1
18.9
7. 1
10 .1
20 .1
20.7
10.9
9.7
20 .0
20 .7
10.1
24 .7
9 .0
20 . 1
8 .6
26 .2
9 .0
10.5
9 .9
2 1.4
9 .5
:t 1. 1 ± 2 .6
P < 0 .00 1
9 .2
19 .4
24. 1
10.3
26. 5
9 .4
11.7
25 .8
23 .9
10.1
± 1.2 ±3 .2
P < 0 .01
7 .8
19.4
21.1
8.1
19 .5
9.7
9.4
18.8
19.7
8. 8
± 1.0 ± 1.0
P < 0 .0 1
*p < 0 .05 ; t p < 0 .01 versus norm al subjects . Ex
pressure; SD = standard dev iation.
=
300
300
300
150
60
300
300
300
7
6
6
6
6
6
9
10
25 1
1: 93
6 .9
:t 1.6
300
300
300
300
300
9
9
9
9
9
300
300
150
300
262
9
9
9
9
9
exercise; HR
since it encompassed a wider range of ejection fraction
values.
Linear regression curves in all sets of correlations revealed slightly higher ejection fraction values with the countbased scintigraphic method as compared with the cineangiographic method based on right ventricular volume estimations determined according to Simpson' s rule (Fig. I and
2). Because the majority of studies were performed both at
rest and during exercise, we correlated the change in right
ventricular ejection fraction during exercise obtained by both
methods (Fig. 3). This correlation is r = 0.73 , SEE = 6.1
(p < 0 .001). The linear regression equation y = 0.78 x
=
130
60
82
124
80
118
90
134
88
150
132
72
150
88
61l
132
104
81l
134*
82
± 13
± II
P < 0 .00 1
84
138
140
82
130
61l
81l
148
139t
80
:t9
±8
P < 0 .00 1
58
118
62
114
120
86
80
116
71
117
± 14
±3
P < 0 .0 1
heart rate; Re
=
lID
155
105
175
130
165
liS
155
100
145
120
200
105
170
130
195
100
125
114
170
:t 12 :!:20
P < 0 .00 1
110
150
120
170
130
190
130
165
123
172
± 7 :!:20
P < 0 01
128
164
130
200
115
155
120
170
123
172
± 7 :!:20
P < 0 .0 1
rest; RPP
=
rate -pr essure produ ct ; SBP
=
systolic blood
+ ] .93 describing this relation is close to the line of identity
and separates subjects with normal and abnormal functional
right ventricular reserve . Since 9 of the IO normal subjects
had an increase in right ventricular ejection fraction greater
than 5% (ejection fraction units) during submaxirnal exercise, a decrease or no change in ejection fraction was considered a disturbed functional reserve.
Inter- and intraobse rver variability. The interobserver
variability for determination of right ventricular ejection
fraction from krypton-Sl m equilibrium blood pool images
averaged 5 .2% (ejection fraction units) for studies at rest
and 5.5% for studies during exercise . For cineangiographic
lACC Vol. 5. No.3
NIENABER ET AL.
RIGHT VENTRICULAR IMAGING WITH KRYPTON-81m
692
March 1985:687-98
GROUP 1+ 11
right ventricular ejection fraction, similar values of interobserver variability were found: 4.4% for studies at rest and
6.0% for studies during exercise. The intraobserver variability for krypton-81m studies was of comparable magnitude, averaging 5.0% for rest studies and 5.9% for exercise
studies; these values did not differ from cineangiographic
values for intraobserver variability in determining right ventricular ejection fraction at rest and exercise, that is, 4.5
and 5.8%, respectively.
Kr81m RVEF
[%)
o
• REST
70
o ExERCISE
60
50
0
.,
40
.
v'
SEE
n-
20
~
SEE · 4 01
n · 28 Cres,1
n
"
v » 1.01 . ·
I
·
SEE'
n ·
10
Right ventricular ejection fraction from gated equilibrium krypton-81m blood pool scans in normal subjects (Fig. 4A). At rest, right ventricular ejection fraction
~
v 09S •• 4 ti
, . 0 9 11p,0001l
hi
30
1 0 . · 3 0S
09 3 '0 <0 00 1'
4 !Xl
20
30
40
50
averaged 52.7 ± 7.4% and was not statistically different
from cineangiographic right ventricular ejection fraction
(50.4 ± 6.2%). With submaximal dynamic exercise, right
ventricular ejection fraction increased by 11.0% to 63.7 ±
6.7% (p < 0.001 versus rest).
2 ,9 ~
0 .93 IP< O001 1
on
26
60
( @ . pr CI ~ 1
70 [%)
Simpson's RVEF
Right ventricular function in pulmonary hypertension
(Fig. 4B). In the nine patients with secondary pulmonary
Figure I. Comparison of right ventricular ejectionfraction (RVEF)
in 28 subjects, including 10 normal subjects and 18 patients with
altered right ventricularfunction or geometry, obtained by krypton81m multiple gated equilibrium blood pool scans and biplane right
ventricular angiography (Simpson's rule). Separate linear regression lines are given a) for all data points (n = 54) from all subjects
at rest (closed circles) and during exercise (open circles), y =
1.0 x + 3.05, r = 0.93 (p < 0.001), SEE = 4.58; b) for all
measurements at rest (n = 28), y = 0.95 x + 4.8, r = 0.91 (p
< 0.(01), SEE = 4.01; and c) for exercise data in all subjects
(n = 26), Y = 1.01 x + 2.95, r = 0.93 (p < 0.(01), SEE =
5.23.
A
B
GROUP I
GROUP II
Kr81m RVEF
Kr81m RVEF
[%]
[%)
• REST
• REST
70
70
o ExERCISE
•
60
,/
60
/' .·.1
50
/ '
v · 0.9S.· S6 3
30
,,0
,,-
,/
/ '
r · 084 ID<0 .00 1'
~E ' . ~
n - 10
bl
/
n
20 ,...;/.
v · 0 ,89 .
8 04
SEE· S 3 1
n -
cl
20
30
40
50
v » 079 .. • 16,0
60
o
v » 1.02. · 2J 1
• • 0.91 10<0.0011
40
SEE' ' .$6
n ' 34
bl
30
• • 0.92 '0 <0.0011
20
n·
10 (@.e'f CI1le)
70 [%]
Simpson's RVEF
v . 0 .94 ... 4 .8
SEE' 3.4S
n · 18 h Mt l
cI
v · 1.06 1 · 0 .71
r · 0 .9 lp <0 00 1)
SEE' S.12
IOlrnll
, . 0 .7510...0 .021
SEE' 4.1
n -
10
+
, . 0 .7410< 0 .02)
/ " b
0 EXERCISE
o
/.
"..,/(/
50
40
hypertension and the one patient with primary pulmonary
hypertension, the average right ventricular ejection fraction
at rest was 42.5 ± 5.0%, which differs from that in control
subjects at rest (p < 0.05). In this subgroup of patients,
however, no significant change in ejection fraction was found
with dynamic exercise (40.6 ± 8.7%, P = NS). In four
patients (Patients 1, 4, 6 and 7), ejection fraction even
decreased with exercise in association with a marked in-
10
20
30
40
50
60
16 le lHCI1.e1
70 [%]
Simpson's RVEF
Figure 2. Comparison of right ventricular ejection fraction (RVEF)
measurements obtained by krypton81m multiple gated equilibrium scintigraphy and biplane angiography
using Simpson's rule. A, Separate
regression lines are calculated a) for
all data points (n = 20) from IO
normal subjects at rest (closed circles) and during exercise (open circles), y = 0.95 x + 5.63, r = 0.84
(p < 0.(01), SEE = 4.85; b) for all
measurements at rest (n = 10), Y =
0.89 x + 8.04, r = 0.74 (p < 0.02),
SEE = 5.31; and c) for exercise data
(n = 10), Y = 0.79x + 16.0, r =
0.75 (p < 0.02), SEE = 4.7. B,
Eighteen patients with functional or
geometric right ventricular abnormalities. Separate linear regression
lines are given a) for both rest and
exercise right ventricular ejection
fraction (n = 34), y = 1.02 x +
2.11, r = 0.91 (p < 0.001), SEE
= 4.56; b) for all measurements at
rest (n = 18), Y = 0.94x + 4.8,
r = 0.92 (p < 0.(01), SEE = 3.45
16),
and c) for exercise data (n
y = 1.06x + 0.71, r = 0.9
(p < 0.(01), SEE = 5.72.
NIENABER ET AL.
RIGHT VENTRICULAR IMAGING WITH KRYPTON-81m
JACC Vol. 5. No.3
March 1985:687-98
ventricular ejection fraction at rest was 14%. Patients 9 and
10 did not perform exercise since both were symptomatic
at rest (New York Heart Association functional class IV).
Kr81m ~RVEF
[%]
25
+ 1.9
y = 0.78 x
Right ventricular function in right ventricular outflow
tract obstruction (Fig. 4C). Average ejection fraction in
= 0.73 Ip < O.OOli
r
SEE = 6.1
n =
.. /
">"
20
26
15
10 -
-15
four patients with altered right ventricular anatomy as a
consequence of chronic right ventricular outflow tract obstruction (tetralogy of Fallot and pulmonary stenosis) was
found to be normal (48.25 ± 4.6%) . During exercise . there
was a physiologic increase to 63.5 ± 7.1% (p < 0.01 versus
rest). No patient in this subset was symptomatic; however,
all four patients revealed marked right ventricular hypertrophy, right heart dilation and highly elevated systolic right
ventricular pressure resulting in a mean valvulopulmonary
pressure gradient of 55.7 ± 22.1 mm Hg (range 36 to 92)
at rest and 62.5 ± 22.3 mm Hg (range 37 to 89) during
exercise. Pulmonary artery pressure both at rest (16 ± 3.6
mm Hg) and during exercise (22 ± 3 mm Hg) did not differ
from that in normal subjects (Table I). However, in patients
with pulmonary hypertension during exercise pulmonary
artery pressure was 49 ± 7 mm Hg (p < 0.001). Pulmonary
capillary wedge pressure both at rest and during exercise
was normal (7.3 ± I and 9.7 ± 2 mm Hg, respectively),
but right atrial pressure increased from 8 ± 2 mm Hg at
rest to 12 ± 2 mm Hg during exercise (p < 0.05), which
was higher than normal (p < 0.01) . Cardiac output . however , was normal at rest (4 .7 ± 0.5 liters/min) and during
exercise (9.6 ± 2.4 liters/min) (Table I).
~
5/
°
~
t
a
-10
I
-5
/
/0
5
t:.
I
I
15
20
Simpson's
~RVEF[%1
-10
°
0
I
10
-5
0
-15
o PH ... LV dysfunction
• TOF + PS
A INF + RVM I
• normal subjects
Figure 3. Comparison of exercise-induced changes in right ventricular ejection fraction (6 RVEF) obtained by krypton-81 mequilibrium blood pool scans and biplane right ventricular cineangiography in 10normal subjects and 16 patients with right ventricular
abnormalities: pulmonary hypertension (PH) and left ventricular
(LV) dysfunction in 8, right ventricular outflow tract obstruction
(tetralogy of Fallot [TOF] and pulmonary stenosis [PS]) in 4 and
inferior wall and rightventricular infarction (lNF + RVMI) in 4.
y = 0.78 x + 1.9, r = 0.73 (p < 0.(01), SEE = 6.1.
Right ventricular function in right ventricular infarction (Fig. 4D). Complete obstruction of the proximal
crease in right ventricular afterload reflected as an exerciseinduced increase in pulmonary resistance. There was a marked
increase in mean pulmonary artery pressure from a baseline
value of 36 ± 19 to 49 ± 7 mm Hg (p < 0.01) and an
inadequate increase in cardiac output from 4.4 ± 1.3 to
6.5 ± 1.6 liters/min (p < 0.01) (Table 1), whereas heart
rate increased from 82 ± 13 to 134 ± II beats/min (p <
0.00 I) (Table 2). Mean right atrial pressure and the atrial
V wave also increased on exercise from I I ± 5 to 17 ±
4 mm Hg (p < 0.01) and from 14 ± 5 to 26 ± 8 mm Hg
(p < 0.01), respectively (Table 1). In Patient 10, right
A normal subjects
B
PH ... PPH
Kr81m
RVEF
6.
c
right coronary artery resulted in a right ventricular ejection
fraction at rest of 37.5 ± 5.4%, which was lower than
normal (p < 0.05). Moreover , during exercise no significant
functional increase was detected (38.75 ± 8.3%, p = NS).
In contrast to normal subjects and those with compensated
right ventricular outflow tract obstruction, pulmonary capillary wedge pressure was slightly elevated to 13 ± 2 mm
Hg at rest (p < 0.05) and 15 ± 3 mm Hg during exercise
(p < 0.05). Cardiac output was normal at rest (5.0 ± 0.5
o INF +RVMI
rOF+ PS
no t Inc l uCIed
In m ea n \Id! U~
I
[96]
f~!
40
r--
_
20
t.
0
t,
p<O.OO1-1
rest
exercise
L-
rest
693
-n s . ---.J
exercise
L
p<O.001-.J
rest
exercise
L.-
rest
n.s.-!
exercise
Figure 4. Krypton-81 m right ventricular ejection
fraction (RVEF) at rest and in response to dynamic
bicycle exercise in normal subjects; A, patients
with secondary pulmonary hypertension (PH) and
primary pulmonary hypertension (PPH). B, patients
with right ventricular outflow tract obstruction due
to residual pulmonary stenosis (PS) (three patients
with corrected tetralogy of Fallot (TOF) with residual pulmonary stenosis andone patient with subvalvular pulmonary stenosis and patients with complete obstruction of the right coronary artery and
right ventricular and inferior myocardial infarction
(INF + RVMI). Subjects in A andC show a physiologic response to exercise, whereas those in Band
Dhave adisturbed right ventricular functional reserve.
694
NIENABER ET AL.
RIGHT VENTRICULAR IMAGING WITH KRYPTON·81m
lACC Vol. 5. No. 3
March 1985:687-98
liters/min) , but subnormal during exercise (8.5 liters/min)
(p < 0 .01) (Table I) .
Discussion
Correlation of radionuclide and cineangiographic assessment of right ventricular ejection fraction. This study
describes and validates the clinical use of a new noninvasive
scintigraphic method using ultrashort-lived krypton-81 m to
determine ejection fraction from multiple gated equilibrium
blood pool images of the isolated right heart chambers and
the pulmonary artery . Special attention was given to dynamic right ventricular function and anatomy (Fig. 5). A
high degree of correlation was found with cineangiographically determined right ventricular ejection fraction (Simpson 's rule based on geometric assumptions) both in normal
subjects and patients with a variety of right ventricular
abnormalities .
Since most of the studies were done in the resting state
and during dynamic submaximal bicycle exercise, an extended range of right ventricular ejection fraction measurements could be studied. In both normal subjects and those
with heart disease, the two methods correlated well, with a
tendency to slightly more variability during dynamic exercise in patients with right ventricular abnormalities. Whereas
different levels of exercise in both studies in each subject
were carefully avoided (Table 2), the reason for that increas ed variably with exercise could be a decreasing accuracy in defining cineangiographic ventricular contours and
axes with rapid contrast washout. Although we extended
the axes to the maximal even faintly opacified outline of
the radiopaque projection (30), all formulas for calculating
right ventricular volume were validated in rest studies (10-15)
and then may be less useful for estimating right cavity volume during dynamic exercise. Count-based methods for
assessing right ventricular function , however, are known to
be relatively independent of geometric assumptions . With
continuous infusion of krypton-81 m and equilibrium acquisition, the right-sided radioactivity is almost homogeneously distributed since the exch ange rate in the heart is
higher than the half-life of krypton-81 m. Thus , even if
streaming or incomplete mixing occurred, the calculation
of ejection fraction using count density ratio methods remains valid. Moreover, unstable delivery of krypton-81m
was excluded by recording stable baseline count rates.
Advantages of imaging with krypton-81m compared
with technetium-99m. Due to high photon flux, rapid decay and complete clearance of radioactivity on the alveolar
surface, superimposition of right- with left-sided activity is
negligible (9). These phy sical properties of krypton-81 m
allow the use of multiple different projections for right heart
imaging. In initial pilot trials , we found a variable 15 to
30° right anterior oblique view to provide the best separation
between the right atrium and right ventricle, especially in
RVED frame with RVED ROI
RVES frame with RVED and RVES ROI
Figure 5. Normal right ventricular function. Krypton-8l m gated
blood pool scan in the right anterior oblique view showing norma l
right heart structures: right ventricular end-diastolic (RVED) frame
with right ventricular end-diastol ic region of interest (RO!) in the
upper panel and the corresponding end-systolic (RVES ) frame
with end-diastolic and end-sy stolic region of interest in the lower
panel (right ventricular eject ion fraction = 54%). The 25° right
anterior oblique view provides a clear outline of the right atrium
(RA), right ventricle (RV) and pulmonary artery (PA) as well as
demarcation of the swinging tricuspid valve (TV) and the relatively
stable pulmonary valve (PV) plane.
patients with enlarged right heart dimensions due to chronic
pressure or volume overload . No overlap even with a dilated
atrium was encountered, and both the tricuspid and the
pulmonary valve planes were clearly detectable without the
help of phase images in the majority of our patients (Fig.
5, 6 and 7).
Imaging with krypton-81 m provides insight into morphologic abnormalities that are not accessible with conven tional technetium-99m radiopharmaceutical agents using
equilibrium mode acquisition in the 30 to 45° left anterior
oblique view. This position, however, requires variable right
ventricular regions of interest to minimize overlapping activity from the right atrium (20,22). In our study , separate
end-diastolic and end-sy stolic regions of interest were drawn
to compensate for extensi ve motion of the tricuspid valve
plane (Fig. 5), especially in the six patients with associated
tricuspid valve regurgitation (Fig . 7).
Limitations of imaging with krypton 81-m. Right ventricular volume determination is not included in our analysis
of right ventricular function. Volume measurements would
NIENABER ET AL.
RIGHT VENTRICULAR IMAGING WITH KRYPTON-81m
lACC Vol. 5. No.3
March 1985:687-98
695
RVED frame
end-diastolic frame
RVES frame
end-systolic frame
Figure 6. Patient 4. Krypton-81 m gated blood pool scan in right
ventricular end-diastolic (RVED) and end-systolic (RVES) frame
in the 30° right ventricular oblique projection in Patient 4 with
secondary pulmonary hypertension, chronic obstructive pulmonary
disease and associated tricuspid regurgitation . Right ventricular
ejection fraction at rest is 44%. The right atrium (RA) is enlarged .
Other abbreviations as in Figure 5.
Figure 7. Patient 10. Krypton -81m right ventricular gated blood
pool scan in Patient 10 with primary pulmonary hypertension . The
image shows enlarged right atrial (RA) and right ventricular (RV)
cavities, with minimal contractile motion due to highly elevated
pulmonary resistance . Right ventricular ejection fraction at rest is
14%. The pulmonary valve (PV) is clearly defined , whereas the
tricuspid valve (TV) is more difficult to recognize as a result of
pressure and volume overload of the right heart chambers.
only be accessible by geometry-based calculation from single plane or biplane krypton-81 m images; the physical properties of krypton-81 m do not provide peripheral blood sampling for reference activity (31) such as with technetium99m (32).
Conventional radionuclide methods thus far are critically
dependent on the relative surface of the diastolic and systolic
areas (20) or on the relative sampling of atrial and pulmonary
structures (22) . Imaging with krypton-81 m does not necessitate any of these background corrections to achieve an
excellent correlation (Fig. 1 and 2) . However, with extremely low ejection fraction values. the lung activity included in the end-diastolic region of interest may possibly
increase and become significant. It is unknown whether this
potential source of error is completely counterbalanced by
the rapid decay of krypton-81 m.
To date, the krypton-Sl m generator is not yet commercially available. Because of the half-life of the parent
rubidium-81, its use is limited to 18 hours after charge .
Radiation of krypton-81m. The radiation dose of krypton-81 m is calculated to be substantially lower as compared
tion is a well established method for estimating right ventricular volume and right ejection fraction (13,14,36) and
is probably the most useful for validation . However, as an
invasive procedure , it is not suitable for serial measurements
and bears inherent difficulties related to the geometry of the
right ventricle and complex mathematical formulas for volume calculations. Recentl y, several radionuclide techniques
using either first pass (1,19 ,37) , gated first pass (38) or
gated equilibrium acquisition mode (20 ,22) and even echocardiographic methods (39-42) have been used to " measure " right ventricular ejection fraction. The count-based
radionuclide methods using technetium 99-m are less dependent on assumptions about complex geometry. A good
with conventional doses of technetium-99m or even repeated
correlation was found among these methods when patients
injections of short-lived gold-196m (33.34). While the activity delivered to the right ventricle was calculated to be 2
with coronary artery disease were included (17,22,42). Our
data obtained from isolated right-sided equilibrium images
to 3 mCi/min, the radiation burden to the patient is almost
insignificant due to short half-life and complete exhalation
(35). Rubidium-81 breakthrough (half-life 4.7 hours) accounts for only 0.1 JLClml and is, therefore, not a quantitatively important source of radiation .
Comparison with results by other noninvasive methods. Contrast ventriculography during cardiac catheteriza-
696
NIENABER ET AL.
RIGHT VENTRICULAR IMAGING WITH KRYPTON-81m
lACC Vol. 5, No.3
March 1985:687-98
using ultrashort-lived krypton-81m are almost identical to
results by others (1,9,19,20,22,37,38,42) using the first
pass and equilibrium methods both in normal subjects and
patients with coronary artery disease.
pulmonary artery in the 30° right anterior oblique view.
However, the normal pulmonary capillary wedge pressure
suggests normal pulmonary vascular resistance (afterload)
and normal left ventricular function (Table I).
Right ventricular function in pulmonary hypertension. Our results further indicate that right ventricular sys-
Right ventricular function in inferior myocardial infarction. The abnormal right ventricular ejection fraction
tolic function is frequently depressed in adults with chronic
pulmonary hypertension (Fig. 4B). Although the left ventricle is not visible and accessible with intravenous krypton81m, it can be anticipated from the elevated left ventricular
end-diastolic pressure in this subgroup of patients (Table I)
that a depressed right ventricular function at rest and especially during exercise is caused by an increased afterload
or systolic wall stress due to valvular heart disease or left
ventricular dysfunction, or both (43-46); variables of right
ventricular performance independent of afterload (that is,
maximal rate of isovolumic pressure increase) are normal
in pulmonary hypertension (37,44). Depressed right ventricular systolic function in this group of patients probably
results from abnormally high wall stress according to the
law of Laplace rather than from decreased contractility
(19,47-50), resulting in tricuspid regurgitation, particularly
in relation to exercise, and a right atrial V wave of 26 ±
8 mm Hg (p < 0.01). Forward cardiac output is severely
depressed.
Role of tricuspid regurgitation. In six patients with
globally compromised right and left ventricular function
after both mitral and aortic valve replacement, functional
(or dilative) tricuspid regurgitation was observed (Patients
1,2,4,5,6 and 7, Table I). Under resting conditions, an
almost normal ejection fraction was found despite a low
(anterograde) output state (Fig. 6). With dynamic exercise,
however, the right ventricle dilates even more and ejection
fraction decreases as pulmonary hypertension (afterload)
and venous return (preload) increase (51). This indicates
that in these patients, the abnormal right ventricular reserve
may be a physiologic response to augmented loading rather
than evidence for intrinsic right ventricular dysfunction.
in patients with inferior myocardial infarction involving parts
of the right ventricle (Fig. 4B) is probably not a reflection
of an altered loading condition since the pulmonary artery
pressures are normal. However, it does suggest regional
alteration in the right ventricular contraction pattern (57,58).
The mildly elevated left ventricular end-diastolic pressure
is probably the result of additional inferior wall infarction.
From a methodologic point of view, the analysis of regional wall and septal motion is feasible, especially with
variable camera projections and with the help of phase and
amplitude motion images. Further studies with emphasis on
regional wall motion analysis are required to substantiate
the use of krypton-Sl m ventriculography.
Clinical applications. Blood pool imaging with krypton-81 m appears to be useful whenever serial nontraumatic
assessment of right ventricular function is required. It can
be sequentially applied in the coronary care unit, either for
Figure 8. Patient 13. Krypton-81 m right ventricular gated blood
pool scan in Patient 13 with corrected tetralogy of Fallot and
residual pulmonary stenosis (PS). Right ventricular ejection fraction is normal at rest (51%) and during physical exercise (69%).
The anatomic site of the pulmonary stenosis can be located on the
30° right anterior oblique krypton-81 m image. Other abbreviations
as in Figure 5.
Right ventricular function in right ventricular outflow
tract obstruction. The degree of right ventricular hypertrophy obviously accounts for much of the variability of
right ventricular performance in the presence of pressure
overload. Children with isolated pulmonary stenosis and
severe right-sided hypertrophy have a normal or increased
ejection fraction (12,16). This was observed in our patients
with residual pulmonary stenosis after surgical repair of
tetralogy of Fallot and organic pulmonary stenosis, respectively (Fig. 4C). In contrast to the results of Reduto et al.
(52), both rest right ventricular ejection fraction and functional reserve were normal, but right ventricular volume
was elevated; thus, right ventricular dysfunction is obviously prevented by compensatory chronic hypertrophy
(53-56), resulting in normal systolic wall stress and normal
ejection fraction. Figure 8 clearly demonstrates the dimensional difference between the enlarged right cavity and the
end-diastolic frame
end-systolic frame
NIENABER ET AL.
RIGHT VENTRICULAR IMAGING WITH KRYPTON-81m
lACC Vol. 5, No.3
March 1985:687-98
postoperative patients or in the setting of acute myocardial
infarction or pulmonary embolism. In combination with
physical exercise, it may be used to screen for right ventricular dysfunction and pulmonary hypertension. Moreover, since the generator can alternatively be used for lung
ventilation scintigrams in conjunction with perfusion scans,
it may be, despite its relatively high costs, of particular
interest to a cardiopulmonary unit in cooperation with the
nuclear medicine departments.
We thank Manfred Prinz and Barbara Zink for their excellent graphic and
technical assistance and Roswitha Hartfelder for preparing the manuscript
and expert secretarial assistance.
References
I. Yano Y, Anger HO. Ultrashort-lived radioisotopes for visualizing
blood vessels and organs. 1 Nucl Med 1968;9:2-6.
2. Clark lC, Horlock PL, Watson IA. Krypton-81m generators. Radiochem Radioanal Let 1976;25:245-8.
3. Jones T, Clark lC. A cyclotron produced 8IRb-8Im'Kr generator and
its uses in gamma camera studies (abstr). Br 1 Radiol 1969;42:237-41.
4. Yano Y, McRae 1, Anger HO. Lung function studies using shortlived radionuclides and the scintillation camera. 1 Nucl Med
1970;11:764-9.
5. Arnot RN, Glass HI, Clark lC. Radioaktive Isotope. In: Hofer R, ed.
Klinik and Forschung. vol 9. Munchen: Urban-Schwarzenberg,
1970:76-8.
6. Selwyn AP, Jones T, Turner JH, Pratt T, Clark 1, Lavender P. Continuous assessment of regional myocardial perfusion in dogs using
krypton-81m. Circ Res 1978;42:771-80.
7. Selwyn AP, Forese G, Fox K, Jonathan A, Steiner R. Patterns of
disturbed myocardial perfusion in patients with coronary artery disease: regional myocardial perfusion in angina pectoris. Circulation
1981;64:83-90.
697
19. Berger Hl, Matthay RA, Loke 1, Marshall RC, Gottschalk A, Zaret
BL. Assessment of cardiac performance with quantitative radionuclide
angiography: right ventricular ejection fraction with reference to findings in chronic obstructive pulmonary disease. Am 1 Cardiol
1978;41:897-901.
20. Maddahi 1, Berman DS, Matsuoka DT, et al. A new technique for
assessment of right ventricular ejection fraction using rapid multiple
gated equilibrium cardiac blood pool scintigraphy. Description, validation and findings in chronic coronary artery disease. Circulation
1979;60:581-90.
21. Borer IS, Bacharach SL, Green MV, Kent KM, Epstein SE, Johnson
GS. Real-time radionuclide cineangiography in the noninvasive evaluation of global and regional left ventricular dysfunction at rest and
during exercise in patients with coronary artery disease. N Eng 1 Med
1977;296:839-44.
22. Slutsky R, Hooper W, Gerber R, et al. Assessment of right ventricular
function at rest and during exercise in patients with coronary heart
disease: a new approach using equilibrium radionuclide angiography.
Am 1 Cardiol 1980;45:63-71.
23. Colobetti LG, Mayron LW, Kaplan E, et al. Continuous radionuclide
generation. I. Production and evaluation of a krypton-81m minigenerator. 1 Nucl Med 1974;15:868-74.
24. Mayron LW, Friedman AM, Kaplan E, etal. A sterile multicomponent
81 Rb-8lm Kr minigenerator and delivery system. Int 1 Nucl Med
Bioi 1975;2:141-5.
25. Kaplan E, Mayron LN. Evaluation of perfusion with the 81 Rb-8lm
Kr generator. Semin Nucl Med 1976;6: 163-7.
26. lones T, Clark lC, Hughes 1M, et al. 8lm-Kr generator and its uses
in cardiopulmonary studies with the scintilation camera. 1 Nucl Med
1970;11:118-24.
27. Clark JC, Horlock PL, Watson IA. Krypton-81m generators. Radiochem Radioanal Let 1976;25:245-54.
28. Chan WWC, Kalff V, MacDonald D II, et al. Topography of preemptying ventricular segments in patients with Wolff-Parkinson-White
syndrome using scintigraphic phase mapping and esophageal pacing.
Circulation 1983;67:1139-46.
29. Botvinik EH, Frais MA, Shosa DW, et al. An accurate means of
detecting and characterizing abnormal pattern of ventricular activation
by phase image analysis. Am 1 Cardiol 1982;50:280-5.
8. Selwyn AP, Steiner R, Kivisaari H, Fox K, Forese G. Krypton-81m
in the physiologic assessment of coronary arterial stenosis in man.
Am 1 Cardiol 1979;43:547-53.
30. Sandler H. Dimension analysis of the heart. A review. Am 1 Med
1970;260:56-61 .
9. Knapp WH, Helms F, Lambrecht RM, Elfner R, Gasper H, Vollhaser
HH. Kr-81m for determination of right ventricular ejection fraction.
Eur 1 Nucl Med 1980;5:487-92.
31. Nickel 0, Schad N, Andrews El, Fleming rw, Mello M. Scintigraphic
measurements of left ventricular volumes from the count-density distribution. 1 Nucl Med 1982;23:404-10.
10. Goerke Rl, Carlsson E. Calculation of right and left cardiac ventricular
volumes. Invest Radiol 1967;2:360-5.
32. Sorensen SG, Ritchie Jl., Caldwell JH, Hamilton GW, Kennedy lW.
Serial exercise radionuclide angiography: validation of count-derived
changes in cardiac output and quantitation of maximal exercise ventricular volume changes after nitroglycerin and propranolol in normal
men. Circulation 1980;61:600-9.
II. Arcilla RA, Tsai P, Thilenius 0, Ranninger K. Angiographic method
for volume estimation of right and left ventricles. Chest 1971;60:446-50.
12. Graham TP, larmakani 1M, Atwood GF, Canent RV. Right ventricular
volume determination in children. Circulation 1973;47: 144-9.
13. Gentzler RD, Brisilli MF, Gault JH. Angiographic estimation of right
ventricular volume in man. Circulation 1974;50:324-8.
14. Ferlinz 1, Gorlin R, Cohn PF, Herman MW. Right ventricular performance in patients with coronary artery disease. Circulation
1975;52:608-15.
15. Thilenius OG, Arcilla RA. Angiographic right and left ventricular
volume determination in normal infants and children. Pediatr Res
1974;8:67-73.
33. Dymond DS, Elliot AT, Flatman W, et al. The clinical validation of
gold-195m: a new short half-life radiopharmaceutical for rapid sequential, first-pass angiography in patients. 1 Am Coil Cardiol
1983;2:85-92.
34. Ackers lG, de long RB1. Dosimetry consequence of eluates from Hg195m/Au-195m generators (abstr). 1 Nucl Med 1982;23:68.
35. Goris M, Daspit T. Krypton-81m. In: Guter M, ed. Progress in Nuclear
Medicine. vol. 5. New Radiogases in Practice. New York: S. Karger,
1978:209-28.
16. Fisher EA, Dubrow IW, Hasterreiter AR. Right ventricular volume
in congenital heart disease. Am 1 Cardiol 1975;36:67-75.
36. Chapman CB, Baker 0, Reynolds 1, et al. Use of biplane cinefluorography for measurements of ventricular volume. Circulation
1958;18:1105-9.
17. Steele P, Kirch D, LeFree M, Dennis B. Measurement of right and
left ventricular ejection fraction by radionuclide angiography and coronary artery disease. Chest 1976;70:51-9.
37. lohnson LL, McCarthy DM, Sciaca RR, Cannon Pl. Right ventricular
ejection fraction during exercise in patients with coronary artery disease. Circulation 1979;60: 1284-91.
18. Schuler G, Petersen K, Ashburn W, et al. Right ventricular performance following surgical relief of pulmonary hypertension. 1 Nucl Med
1978;19:736-44.
38. Dehmer Gl, Firth BG, Hillis LD, Nicod P, Willerson rr, Lewis SE.
Nongeometric determination of right ventricular volumes from equilibrium blood pool scans. Am 1 Cardiol 1982;49:78-84.
698
NIENABER ET AL.
RIGHT VENTRICULAR IMAGING WITH KRYPTON-81m
JACC Vol. 5, No.3
March 1985:687-98
39. Bommer W, Weinert L, Neumann A, Neffe J, Mason DT, DeMaria
A. Determination of right atrial and right ventricular size by twodimensional echocardiography. Circulation 1979;60:91-100.
49. Matthay RA, Berger HJ, Davies RA, et al. Right and left ventricular
exercise performance in chronic obstructive pulmonary disease: radionuclide assessment. Ann Intern Med 1980;93:234-9.
40. Limacher MC, Quinones MA, Poliner LR, Nelson JG, Winters WL,
Waggoner AD. Detection of coronary artery disease with exercise
two-dimensional echocardiography. Description of a clinically applicable method and comparison with radionuclide ventriculography.
Circulation 1983;67: 1211-8.
50. Slutsky RA, Ackerman W, Karliner JS, Ashburg WL, Moser KM.
Right and left ventricular dysfunction in patients with chronic obstructive lung disease. Assessment by first-pass radionuclide angiography.
Am J Med 1980;68:197-205.
41. Zwehl W, Gueret P, Meerbaum 5, Holt D, Corday E. Quantitative
two-dimensional echocardiography during bicycle exercise in normal
subjects. Am J Cardiol 1981;47:865-73.
42. Panidis IP, Ren J-F, Kotler MN, et al. Two-dimensional echocardiographic estimation of right ventricular ejection fraction in patients with
coronary artery disease. J Am Coli Cardiol 1983;2:911-8.
43. Borer JS, Bacharach SL, Green MV, et al. Left ventricular function
in aortic stenosis: a response to exercise and effects of operation. Am
J Cardiol 1978;41:382-6.
44. Borer JS, Gottdiener JS, Rosing DR, et al. Left ventricular function
in mitral regurgitation: determination during exercise (abstr). Circulation 1979;59:60(suppl II):II-38.
45. Borer JS, Bacharach SL, Green MV, et al. Exercise-induced left
ventricular dysfunction in symptomatic and asymptomatic patients
with aortic regurgitation: assessment with radionuclide cineangiography. Am J Cardiol 1978;42:341-57.
46. Slutsky R, Ackermann W, Hooper W, et al. The response of left
ventricular ejection fraction and volume to supine exercise in patients
with severe COPD (abstr). Circulation 1979;59,60(suppl II):II-234.
47. Rushmer R. Functional anatomy and control of the heart. In: Rushmer
R, ed. Cardiovascular Dynamics, 4th ed. Philadelphia: WB Saunders,
1976:89-98.
48. Jezek V, Schrigen F, Sadoul P. Right ventricular function and pulmonary hemodynamics during exercise in patients with chronic obstructive bronchopulmonary disease. Cardiology 1973;58:20-31.
51. Stein PD, Sabbah HN, Anbe DT, Marzilli M. Performance of the
failing and nonfailing right ventricle of patients with pulmonary hypertension. Am J Cardiol 1979;44:1050-5.
52. Reduto LA, Berger HJ, Johnstone DE, et al. Radionuclide assessment
of right and left ventricular exercise reserve after total correction of
tetralogy of Fallot. Am J Cardiol 1980;45: 1013-8.
53. Ruzyllo W, Nihill MR, Mullins CE, McNamara DG. Hemodynamic
evaluation of 221 patients after intracardiac repair of tetralogy of
Fallot. Am J Cardiol 1974;34:565-70.
54. Hawe A, McGoon DC, Kincaid DW, Ritter DG. Fate of outflow tract
in tetralogy of Fallot. Ann Thorac Surg 1982;13:137-41.
55. Halm JR, Bowman Fa, Jaoneson AG, Ellis K, Griffith SP, Blumenthal
S. An evaluation of total correction of tetralogy of Fallot. Circulation
1963;27:805-10.
56. Oku H, Shirotani H, Yokoyama T, et al. Right ventricular outflow
tract prosthesis in total correction of tetralogy of Fallot. Circulation
1980;62:604-9.
57. Berger HJ, Johnstone DE, Sands JM, Gottschalk A, Zaret BL. Response of right ventricular ejection fraction to upright exercise in
coronary artery disease. Circulation 1979;60:1292-9.
58. Bodenheimer MM, Banka VS, Foshee CM, Helfant RH. Simultaneous
right and left ventricular performance in coronary heart disease:
disassociation of ejection fraction and asynergy. Clin Res 1978;26:
220-6.