++
Radionuclide imaging is used primarily for assessing cardiac
physiology. Although rarely used today for the assessment of right
and left ventricular function in pediatric patients, radionuclide
studies continue to provide valuable information for the evaluation
of intra- and extracardiac shunts and assessment of myocardial perfusion.
+++
Assessment of
Left‐to-Right Shunts
++
Echocardiography with Doppler is the most widely used method
for determining the presence and magnitude of left-to-right shunts in
congenital heart disease, although its accuracy in quantification
of multiple level shunts or shunts in the presence of valve insufficiency
or multiple shunts is not optimal. The radionuclide technique
for left-to-right shunt quantification was established and validated
more than 30 years ago and is not affected by such considerations.31
++
The radionuclide method is most often used to assess the size
of left-to-right shunts in 4 major congenital lesions: atrial septal
defect, ventricular septal defect, patent ductus arteriosis, and
partial anomalous pulmonary venous return. In uncomplicated atrial
septal defect, the shunt is principally from the left atrium to
the right atrium, leading to an increased volume load in the right
ventricle, which becomes dilated (eFig. 494.1).
The left ventricle does not participate in the shunt. Anomalous connections
of pulmonary veins, generally to the right atrium, also result in
left-to-right shunts where the right ventricle handles the increased
volume. In the typical perimembranous ventricular septal defect,
the shunt is principally from the left ventricle, across the ventricular
septum, into the right ventricular outflow tract, and out the pulmonary
trunk (eFig. 494.2). The left ventricle handles
the increased volume load and dilates. Large left to right shunts
associated with ventricular septal defects can lead to pulmonary
hypertension and subsequent right ventricular hypertrophy. In patent
ductus arteriosus, the shunt occurs between the high-pressure aortic trunk
to the lower-pressure pulmonary trunk (eFig. 494.3).
The left ventricle handles the increased volume and dilates. As with
large ventricular septal defects, large patent ductus arteriosus
can lead to pulmonary hypertension and right ventricular hypertrophy.
In each lesion, knowledge of the size of the shunt, expressed as
pulmonary-to-systemic flow ratio (Qp/Qs), is essential
for decisions regarding corrective surgery.
++
++
++
++
The scintigraphic technique
involves the rapid injection of a bolus of radionuclide (usually
technetium-99m–labeled diethylenetriamine pentaacetate, or 99mTc-DTPA)
into the circulation while monitoring the transit through the heart
and lungs with the gamma camera. For small infants (ie, premature
newborn infants), a butterfly needle can be used in a temporal scalp
vein to deliver a compact bolus of activity to the central circulation.
In older children and adults, either a butterfly needle or a small
cannula can be inserted, preferably into an external jugular vein,
although an antecubital vein may also be used. The delivery of a
compact, nonfragmented bolus of activity is essential to allow accurate determination
of the size of the shunt. With good technique, the success rate
should be greater than 90%. It may be necessary to sedate infants
and some children, because crying simulates a Valsalva maneuver
that can impede bolus entry into the thorax and lead to fragmentation
of the bolus. As mentioned, 99mTc-DTPA is most commonly
used for shunt studies. Doses are 200 microcuries (µCi) per kilogram
of body weight, with a minimum dose of 2 mCi. The advantage of 99mTc-DTPA
over other technetium based agents is the fairly rapid renal excretion
and thus prompt clearance of background activity. This becomes important
if it is necessary to perform a second injection to improve the
quality of the bolus. Generally, no more than 2 sequential injections
are performed due to dosimetry limitations.
++
The study is done in the anterior projection using a converging
collimator (which provides magnification) in infants and ideally
a high-sensitivity parallel collimator in older children and adults.
A dynamic acquisition with a sampling rate of 2 to 4 frames per
second is adequate for evaluation of shunts. If ejection fraction
measurements are to be made by the first pass method, a rate of
at least 25 frames per second should be used. The sequential flow
study is reviewed in order to provide useful information regarding
chamber orientation and vascular connections. In the presence of
normal anatomic relationships, right heart structures will appear,
followed by the main pulmonary artery, lungs, and subsequently,
the left ventricle (levophase), and descending aorta. Persistent
pulmonary activity, resulting in the absence of a distinct levophase
is consistent with a moderate to large left-to-right shunt (eFig. 494.4). This appearance results from
recirculation of activity from heart back to lungs and vice versa, across
the shunt. This appearance has been called the “smudge
sign,” and generally indicates a pulmonary to systemic
flow of at least 1.6/1.
++
++
For quantification, time-versus-radioactivity curves are generated
from regions of interest over the superior vena cava to assess the
quality of the bolus and the periphery of the right lung, for shunt
detection and magnitude (Fig. 494-5). A separate
curve may be generated from a region over the left lung if differential
shunting is expected (as may occur with a patent ductus arteriosus).
The normal pulmonary arterial curve has an ascending limb, reflecting
the arrival of tracer in the pulmonary circulation, and a symmetric
descending limb, reflecting the tracer exiting the lungs and entering the
left side of the heart. A late peak wsill appear, reflecting systemic
recirculation. In a left-to-right shunt, a shoulder will be present
on the downslope, indicating recirculation of activity back to the
lungs across the shunt. For shunt quantification, the shape of the
pulmonary portion of the curve is approximated by an algebraic expression
called a gamma variate function (Fig. 494-6).31 In
practice, the computer is given the coordinates of the upslope and initial
downslope of the pulmonary curve, and a curve is generated that
approximates the shape of the curve. The area under this pulmonary
curve is proportional to pulmonary flow, Qp. This fitted curve is
then subtracted from the initial time-versus-radioactivity curve,
and another gamma variate fit is done on the remaining curve. The
area under this second fitted curve is proportional to the shunt
flow, Qsh. The difference between the two fitted curves is a measure
of systemic flow, Qs. The resultant calculation of pulmonary to
systemic flow, Qp/Qs, is performed as:
++
++
++
++
Ratios less than 1.2:1 are consistent with the absence of left-to-right
shunts. The Qp/Qs calculation, by the gamma variate method, has
shown excellent correlation with shunt size determined at cardiac
catheterization over a clinically significant range of 1.2:1 to 3.0:1.31 This
relationship remains valid even in the presence of pulmonary hypertension,
tricuspid regurgitation, and heart failure.31,32 In
these conditions, extensive dilution and slow flow lead to a slow downslope
to the pulmonary curve. However, the upslope should be proportionately
slowed, and the curve fit method should generally apply, although
caution should be exercised. Since the method depends on the full
passage of the administered radionuclide through the lungs, left-to-right
shunts will be overestimated in the presence of right-to-left shunts.
Shunts greater than 3.0:1 are difficult to fit by the gamma variate
method due to distortions in curve shape as a result of the large
and torrential shunt flow. This is not a practical limitation, however,
as any shunt greater than 3.0:1 is very large. In general, a shunt
of 2.0 or greater is sufficient to warrant surgical correction.
++
With the anatomic detail provided by echocardiography, the hemodynamic
correlates from Doppler examination, and the precise quantitation
available from a radionuclide shunt study, it is sometimes possible
to proceed directly to surgery without preoperative cardiac catheterization.
This is particularly true with uncomplicated patent ductus and secundum
atrial septal defect. In anomalous pulmonary venous return, the
radionuclide determination of shunt size may be more accurate than
that determined at catheterization by oximetric methods due to the inability
to obtain a good mixed venous blood sample at catheterization.33 The
radionuclide method has also been used to measure changes in shunt
magnitude in response to oxygen therapy, and to assess the reactivity
of the pulmonary vascular bed in patients with pulmonary arterial
hypertension and large shunts.34 This is a very
important consideration in determining operability in patients with
moderate to large ventricular septal defects.
++
One of the leading indications for radionuclide shunt studies
is the postoperative assessment of residual shunt size in patients
with murmurs and echo Doppler evidence of persistent shunting after
surgical correction of septal defects. Doppler quantification of
shunt size is often not very reliable after patch closure of defects
due to the turbulence generated in the vicinity of the patch. In
this situation, the radionuclide technique has been helpful for
assessing the need for repeat catheterization and possibly reoperation.
++
It is possible to calculate the extent of left-to-right shunts
using the equilibrium blood pool method. Stroke volume or amplitude
images can be used to measure the difference in stroke volume between
the ventricles, as is commonly performed for the evaluation of regurgitant
lesions (eFig. 494.5).35 With
a ventricular septal defect or a patent ductus arteriosus, the left ventricle
handles the excess volume of the shunt flow. The left ventricular
stroke volume is proportional to the pulmonary blood flow, and the
right ventricular stroke volume is proportional to the systemic
blood flow. The pulmonary-to-systemic flow ration can be calculated
as:
++
Qp/Qs = LV stroke volume/RV stroke volume
++
++
where, LV stroke volume equals LV end-diastolic volume minus
end-systolic volume, and RV stroke volume equals RV end diastolic volume
minus end-systolic volume.
++
For an atrial septal defect or anomalous pulmonary venous return, the
right ventricle carries the excess shunt flow. The Qp/Qs
can be calculated as:
++
Qp/Qs = RV stroke volume/LV stroke
volume
++
A good correlation (r = 0.79) has been
noted between the shunt Qp/Qs ratio calculated from stroke
volume ratios and oximetry.36 This approach may
be particularly useful in situations where attempts at a good bolus
injection were unsuccessful.
+++
Assessment of
Right‐to-Left Shunts
++
Right-to-left shunts can be detected by inspection of the first-pass radionuclide
angiogram, which reveals a premature appearance of radioactivity
in the left-sided chambers or aorta. Time-versus-radioactivity curves
generated from regions of interest over the carotid artery can be
analyzed by curve-fitting methods to quantify shunt size.37 Intravenous
injections of an inert radioactive gas, such as 133Xe or
krypton-81m, can also be used for detecting right-to-left shunts.38 Significant
systemic activity of these agents, which should be totally extracted
by the lungs and exhaled in the alveolar gas, indicates shunting.
++
The easiest and most commonly used method to assess right-to-left
shunts is the intravenous injection of 99mTc-labeled macroaggregated
albumin particles, similar to those used for the assessment of pulmonary perfusion.39 In
the absence of right-to-left shunting, all of the particles are trapped
in the lungs. When right-to-left shunting occurs at any level, particles
will enter the systemic circulation in proportion to the shunt flow,
lodging in the capillary and precapillary beds of systemic organs.
A series of whole body images are taken to determine the percentage
of right-to-left shunt as:
+
++
Pulmonary-to-systemic flow ratio can be calculated as:
++
Qp/Qs = lung counts/whole body counts
++
Radiolabeled macroaggregrated albumin particles can be used to assess
Qp/Qs in admixture lesions, where complete mixing of pulmonary
and systemic blood occurs in 1 cardiac chamber. Images in eFigure 494.6 were obtained from a 16-year-old cyanotic
patient who presented with a history of pulmonic atresia with intact
ventricular septum and hypoplastic tricuspid valve. He received
a Waterston aortic-to-right pulmonary artery shunt as a child. In
addition, a left subclavian-to-central pulmonary shunt (Blalock-Taussig
shunt) was done, with flow primarily to the left lung. The procedure
was done to assess the patency of the shunts.
++
++
Although technically there is a left-to-right shunt of blood
from the aorta to pulmonary artery, the major hemodynamic abnormality in
this cyanotic lesion is complete admixture of systemic venous and pulmonary
venous blood at the level of the left atrium. Both pulmonary and
systemic blood arise from the aorta. Note the presence of brain
and kidney uptake, consistent with right-to-left shunt. In this example,
differential pulmonary perfusion was measured by determining relative
counts in both lungs. Left lung activity represented 45% of
total lung activity, whereas right lung activity was 55% of
total. These findings suggested that both the Waterston and Blalock-Taussig
shunts were functioning. Additional important data were obtainable
from this macroaggregated albumin study. The pulmonary-to-systemic
flow ratio, Qp/Qs, was calculated as Qp = lung
counts, Qs = whole body counts – lung counts.
This formula is applicable since the patient has an admixture lesion.
There is complete mixing of the particles by the time the injected
dose reaches the aorta. The particles are subsequently distributed
in proportion to regional blood flow to the lungs and the body.
The pulmonary/systemic flow ratio, Qp/Qs, is a
very important determinant of systemic arterial oxygen saturation
in patients with admixture lesions.40 In the example
shown above, the Qp/Qs was 1.6. This modest ratio suggested
that pulmonary flow was not excessive, and increased systemic saturation
would likely result with a slightly larger degree of pulmonary blood
flow, that is, a larger Qp/Qs.
++
In spite of the general reluctance to administer particles to
patients with known right-to-left shunts, the method has proven
to be safe, accurate, and very easy to perform.39 The
particle number should be kept below 50,000 in pediatric patients.
++
The microparticle study is very useful for visualizing maldistribution
of pulmonary blood flow after surgery for congenital heart disease.
Pruckmayer et al41 studied 46 patients (mean age
8.2 years) with complex cardiac anomalies who had undergone either
a Glenn shunt or Fontan procedure. Glenn shunt and Fontan procedures
may be associated with abnormal pulmonary flow patterns and the
development of pulmonary atrioventricular fistula.41 Imaging
was done following sequential injections of ch494ref99mTc-microspheres
into upper and lower limb veins. In 31 of 46 patients, blood flow
from the superior vena cava (arm injection) drained preferentially
to the right lung, whereas blood flow from the inferior vena cava
(foot injection) drained equally to both lungs (eFig.
494.7). Lung perfusion scintigraphy after upper and lower extremity
injections detected more abnormal pulmonary flow patterns than did contrast
echo. In addition, the technique was able to quantify R-L shunt
volumes individually from the superior vena cava and inferior vena
cava, a unique attribute compared to any other imaging method. Quantitative
assessment of relative pulmonary perfusion before and after percutaneous
intervention for peripheral pulmonary artery stenosis42 has
become one of the most commonly ordered scintigraphic procedures
for cardiovascular assessment in pediatric patients in our practice
(eFig. 494.8).
++
++
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Assessment of Ventricular
Function
++
Although radionuclide methods are well suited for the assessment
of ventricular size and function in congenital heart lesions, these
methods have been largely replaced by echocardiography in current
clinical practice. Both first-pass and gated equilibrium methods
for the determination of ejection fraction have been validated in
the pediatric age group.43,44 Quantitative assessment
of absolute ventricular volumes45 and determination
of regurgitant fraction have been reported in children as well.46,47 For
infants, the imaging is optimized with the use of a converging collimator
to improve spatial resolution and increase the sensitivity. It is
feasible to measure ejection fraction even in tiny premature infants
with the pinhole collimator.48 Ventricular size
and function evaluation are useful at rest and with dynamic stress
in a variety of congenital lesions, both before and after surgical
correction.49,50 Residual structural and functional abnormalities
are very common, and careful, long-term follow-up is important.
+++
Assessment of Myocardial
Perfusion
++
Myocardial perfusion scintigraphy has been used for clinical
assessment in children for a number of years.51,52 In
the pediatric patient, perfusion imaging has been most widely used
for the noninvasive identification of anomalous left coronary artery.53-56To
evaluate patients for possible anomalous left coronary artery, a perfusion
tracer is injected intravenously, at rest, and images are acquired
in multiple planar projections, or single photon emission computed
tomography (SPECT) imaging is done. The usual anatomy in this rather
rare disease is for the left main coronary artery to arise from
the main pulmonary artery. This situation can lead to regional ischemia
and infarction of the left ventricle due to low perfusion pressure
from the pulmonary artery, which can create a coronary steal. Perfusion scintigraphy
typically reveals a segmental perfusion abnormality at rest (eFig. 494.9). This pattern is useful for identifying
anomalous left coronary, as opposed to myocarditis or cardiomyopathy,
as the etiology for poor ventricular function in infants. The condition
is often associated with Q-waves on the electrocardiogram. Echocardiography
is sometimes able to identify the aberrant origin of the left coronary,
but catheterization is required for confirmation. Multidetector
CT has shown promise for the noninvasive detection of anomalous
origins of coronary arteries.57,58 Direct aortic
implantation of the anomalous coronary artery is the preferred approach
to surgical correction.59,60
++
++
Another clinical condition for which perfusion scintigraphy may
be useful is Kawasaki disease.61 This syndrome
is associated initially with persistent fevers, rash, adenopathy,
and mucous membrane abnormalities. Before the introduction of intravenous
gamma globulin therapy, about 20% to 25% of these
patients developed aneurysms of the coronary arteries. Treatment
with gamma globulin within 10 days of the onset of the illness reduces
the frequency of coronary aneurysms to about 4%. About
30% to 50% of such aneurysms will spontaneously
regress within the first 2 years of illness. The remaining aneurysms may
later thrombose and cause myocardial ischemia and infarction.62,63 Bypass
surgery has been advocated for some patients with objective evidence
of ischemia.64
++
Assessment of myocardial perfusion is important in the evaluation
and follow-up of patients with transposition of the great vessels
who have undergone the arterial switch procedure.65,66 D-transposition
of the great arteries is a lethal congenital malformation and represents
the most common cardiac cause of cyanosis in the neonate. Historically,
left untreated up to 90% of infants with the condition
died within the first year of life.67 The prognosis
for these infants, however, has been remarkably improved with the
introduction of palliative and corrective surgical techniques. Among
the earliest and most successful surgical procedures is a physiologic
correction of the circulation by redirecting the pulmonary and systemic venous
returns to the appropriate ventricles using intra-atrial baffles (Mustard
or Senning procedure).67 This atrial switch operation
has met with great success in the early operative period, and survival rates
at 10 and 20 years postoperatively of 90% and 80%,
respectively.67 Enthusiasm for this approach has been
dampened somewhat due to concerns that the right ventricle may be
unable to function successfully as the systemic ventricle for long
periods of time.
++
Anatomic correction of transposition is now commonly performed.68 The
procedure consists of switching the great vessels to the proper ventricles
and reimplantation of the coronary arteries to the newly formed
aorta. The morphologic left ventricle then becomes the systemic
pumping chamber for which it is better suited. Although technically
demanding, the procedure is best performed during the neonatal period,
prior to the regression of left ventricular mass as a result of
the progressive decrease in pulmonary vascular resistance that occurs
after birth. Alternatively, the left ventricle can be conditioned
to accept the high systemic vascular resistance by performing pulmonary
banding as an initial procedure. Concerns have been raised since
the inception of the arterial switch procedure about the possibility
that distortion or growth failure of the newly implanted coronary
arteries may result in myocardial ischemia and possibly infarction.
++
Some studies suggest that coronary artery manipulation and reimplantation
do not result in late myocardial perfusion abnormalities, at least
in those infants with successful initial results.68 However,
large perfusion abnormalities have been seen in the territories
of stenosed coronary arteries following the switch procedure (eFig. 494.10).
++