A Guide to Myocardial Perfusion Analysis During Adenosine
Mediated Coronary Vasodilatation for Assessment of Myocardial
Dipyridamole is the prodrug of adenosine and is activated by metabolism in the liver. Thus, vasodilatory capacity depends on
Magnetic resonance perfusion imaging has
individual metabolism rate, usually resulting
in a longer half-life, prolonged side effects
studies and first larger patient trials. In
perfusion deficits is a very sensitive indicator of ischemia in the presence of significant coronary artery stenoses. Most
Both, normal and stenotic coronary arteries are dilated to their maximum using these
perfusion defects only occur during stress,
such as pharmacological vasodilation. This
can be optimally achieved using adenosine or dipyridamole as pharmacological stress
maximally dilated at rest (to allow maximal blood flow and compensate for the stenosis)
agents, both of which proved to be safe and
and cannot be dilated any further. Thus,
vasodilation with dipyridamole or adenosine induces an increase of blood flow in
Techniques currently used in clinical routine
coronary arteries ("coronary steal"),
disadvantage of radiation and low spatial
resolution, which prohibits the assessment
found in areas supplied by stenotic coronary
of subendocardial ischemia. This cookbook
arteries. With adenosine a maximal coronary
provides instructions for the application and
vasodilation can be achieved safely with an
with cardiac magnetic resonance imaging.
The vasodilatory effect of adenosine may
The methodology has been developed for a
result in a mild-to-moderate reduction in
systolic, diastolic and mean arterial blood
pressure (< 10 mmHg) with a reflex increase
a 30 mT Master gradient system (slew rate:
in heart rate. Most patients complain about
anginal chest pain. These effects, however,
synergy coil. Software: Release 8.1.1 and
are transient and usually do not require
Since adenosine exerts a direct depressant
first-, second- and third-degree AV block and
sinus bradycardia have been reported in 2.9%, 2.6% and 0.8% of patients. Also,
baroreceptor reflex are able to maintain
blood pressure in response to adenosine by
increasing cardiac output and heart rate. Adenosine can also cause a paradoxical
increase in systolic and diastolic blood
pressure, which mostly develops in individuals with significant left ventricular hypertrophy. These increases are transient
Adenosine, an endogenous nucleotide, is a
potent vasodilator of most vascular beds,
except for hepatic and renal arterioles. It
primarily through activation of carotid body
exerts its pharmacological effect through
chemoreceptors, intravenous administration
surface adenosine receptors. The essence of
reduction in arterial PCO2 and respiratory
the pharmacological mechanism lies in the
alkalosis. Approximately 14% of patients
inhibition of the slow inward Ca2+ current,
complain of dyspnea and an urge to breathe
thereby reducing calcium uptake, and in the
activation of adenylate cyclase through A2 receptors in smooth muscle cells.
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Adenosine should be used with caution in
bundle branch block and should be avoided
intravenous adenosine infusions in different
in patients with high-grade AV block or sinus
diagnostic modalities of cardiac imaging.
node dysfunction. Adenosine should be used with caution if a patient is receiving any
So far, there is evidence accumulated in
medications that already depress the sinus
over 10,500 patients studied in thallium
node and/or AV node (e.g. beta-blockers,
presents a safe method of acquiring stress imaging data.
Adenosine should be discontinued in patients who develop persistent or
symptomatic high-grade block or significant
drop in systolic blood pressure (>20 mmHg).
radionuclide imaging of 9,256 consecutive
The drug should be discontinued in case of
completed in 80% of patients, required dose reduction in 13% and was terminated early
Also, adenosine should be used with caution
in 7%. Interpretable imaging studies were
obtained in 98.7% of patients, and 0.8% of
stenotic valvular heart disease, pericarditis
patients received aminophylline. Minor and
and pericardial effusion, stenotic carotid
well tolerated side effects were reported in
artery disease, cerebrovascular insufficiency
81.1% of patients. There were no deaths, one
myocardial infarction, seven episodes of severe bronchospasm and one episode of
Adenosine infusion should be exercised with
pulmonary edema. Transient AV node block
caution in patients with obstructive lung
occurred in 706 patients (first-degree in
256, second-degree in 378 and third-degree
constriction (emphysema, bronchitis, etc),
in 72) and resolved spontaneously in most
patients (n = 508) without alteration in the
bronchoconstriction or bronchospasm (e.g.
adenosine infusion. There were no sustained
respiratory difficulties, adenosine should be immediately discontinued.
Table 1: Dipyridamole / Adenosine stress protocol
No caffeine (tea, coffee, 0.56 mg/kg/min for 4 Aminophylline 250 mg
chocolate, etc.) or minutes, maximal effect i.v. slowly injected medications such as after approximately 3–4 under ECG monitoring aminophylline or nitrates 24 minutes. hours prior to the
i.v. slowly injected under ECG monitoring)
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Table 3: Contraindications for dipyridamole / adenosine
A gadolinium derivative is used (e.g. Gd-
• Asthma or severe obstructive pulmonary
0.05 mmol/kg bodyweight injected with 4 ml
per second. The bolus is followed by a 20 ml
saline flush (infusion rate: 4 ml per second)
to facilitate a compact bolus passage. We
antagonists or cardiac glycosides (due to
recommend the use of an automatic infusion
system ( e.g. Medrad, Spectris MR injector)
preparation and practice for rapid removal
of the patient from the magnet needs to be practiced in addition to a close compliance with the termination criteria (Table 4).
During stress examinations monitoring of the patient within the magnet is mandatory.
The monitoring of blood pressure, cardiac
rhythm and patients' symptoms can either
examination requires the same precautions
outside the scanner room connected to the
patient with special extensions through a
recommendations are listed in table 2. Apart
waveguide in the radiofrequency cage, or by
from the known specific contraindications
using special CMR compatible equipment. A
for MR, the drug related contraindications
for adenosine and dipyridamole infusion are
emergency treatment must be available at
adenosine/dipyridamole stress MR imaging
• persistent or symptomatic hypotension
*When the Vector-ECG is used, pulse oximetry is not
Image Interpretation Visual Assessment
Currently, only limited data is available regarding the accuracy of visual assessment and extensive experience is required to reach an acceptable standard. The alteration of the upslope of the myocardial response curve from stress to rest yields the highest difference between ischemic and normal myocardium. This parameter is superior to
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maximal signal intensity, which is mainly
upslope of each myocardial segment by the
intensity curve. Perfusion reserve index is
results in improved visual assessment, but
calculated by dividing the results of stress
often renders semiquantification difficult.
by the results at rest. This approach has
yielded sensitivities and specificities of
interpretation need to be taken into account:
> 90% in selected patient populations. Its value in unselected patients remains to be
wraparound) or misleadingly be interpreted
(e.g. susceptibility) as perfusion deficits. Thus, training in MR image interpretation
Table 5: Criteria for Visual Assessment of
together with the interplay of the visual
criteria given in table 5 will result in a
sufficiently high diagnostic accuracy (own
unpublished data showed: sensitivity 89%,
• Signal -intensity Pattern & Location:
initial passage of the contrast bolus are due
subendocardial perfusion deficits difficult.
Especially the trabeculae of the papillary
muscles reaching into the left ventricular
persistent over a few (2 to 10) dynamics
cavity are washed with contrast agent and,
epicardial border (epicardial "filling up"
interpreted as regional ischemic perfusion
Visual criteria for left ventricular myocardial
perfusion deficits are given in table 5.
• Myocardial Distribution of the Defect:
Evaluate the equatorial slice first, then
Semiquantification
check whether the suspected perfusion defect can be followed in corresponding
semiquantification, as described briefly: the
If a regional defect is found in the stress
scan, but not in the rest scan, inducible
diaphragmatic position due to breathing or
diaphragmatic drift. Care needs to be taken
lesion"). Regional persistence of the
and to exclude the left ventricular cavity and
the pericardium. The myocardium is then divided into 6 equiangular segments per
slice and numbered clockwise beginning with the anterior septal insertion of the right
Quantification
ventricle. An additional region of interest is placed within the cavity of the left ventricle
excluding the myocardial segments and the
prerequisites, not fully fulfilled with the
papillary muscles. Images acquired after
current contrast agents such as: linearity
premature ventricular beats or insufficient
between signal intensity and contrast agent
cardiac triggering need to be excluded from
concentration or adequate downslope. Most
conditions. Signal intensity is determined for
all dynamics and segments. The upslope of
the resulting signal intensity time curve is
image inhomogeneities, water exchange and
determined by the use of a linear fit. To
correct for possible differences of the input function, the results of the myocardial segments are corrected by dividing the
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To cover 16 segments we use 3 short axis
apical segment (segment 17) is neglected
Look at the images and check if the coil is
"DSMR cookbook). A standardized way to
reproducibly plan a short axis view can be found in the application guide.
Define the plane on transversal slices parallel to the septum through the apex of
the left ventricle and the coaptation point of
which are all breathhold bFFE scans (scan
duration ragning from 8 to 12 sec.), except for the multistack survey (bFFE, but free
breathing patient) and the TFE-EPI perfusion
Flip the orientation (90°) and adjust the
plane on the first RAO through the apex and
the middle of the mitral valve to get a second long axis view (nearly 4 chamber
view). This slice orientation helps to prevent
any angulation errors while planning the short axis views.
(4) wall motion scan short axis (3 slices)
Make use of the double-angulated image to
define 3 slices perpendicular to the long axis
of the heart representing the short axis geometry.
The perfusion scan will be performed during stress and at rest (after an equlibration time
Note: Under stress conditions even the normal heart experiences a change in its basal-to-apex dimensions
≥ 15 min after the first bolus injection).
due to rotational deformation. To avoid visualization of
the left ventricular outflow tract as well as to ensure sufficient imaging of the left ventricular cavity (esp.
critical is the apical slice), we recommend to perform the planning on the endsystolic images: divide the
distance from the apical epicardial border to the mitral valve plane in 5 equal parts. Then, distribute the 3 short
It is of special importance to explain not only
axes equally within the inner three-fifth of the distance
the course of the examination to the patient
but also the breathhold procedure. Generally
the breathhold should be performed during
endexpiration to ensure reproducible slice geometry.
Plan the 4-chamber view on the equatorial short axis view, the stack should be aligned
through the apex of the right ventricle and
breathhold periods. The first is a short one
(about 10-12 seconds, baseline acquisition of myocardial intensity), then the patient is
asked to inhale and exhale once and hold
Plan the 2-chamber view on the previously
breath as long as possible. Before starting
acquired 4-chamber view by just switching
this breathhold-command the contrast bolus
is administered. The patient should stop
angulation (through the left ventricular apex
and the coaptation point of the mitral valve).
resulting in a fixed slice geometry during the
first-pass of the contrast agent; in case the patient cannot hold his breath throughout
the whole scan: ask the patient to inhale and
orientation identical to the short axis cine
previously acquired (scan 4). Wraparound has to be avoided carefully! We recommend
Put venous line (≥ 18 gauge) in cubital vein
to perform a TFE-EPI prior to the start of
with two connections: one for adenosine,
the adenosine infusion (e.g. 5 dynamics) with
a breathhold command If necessary enlarge the field-of-view (results in decreasing
Monitor blood pressure and heart frequency
Repeat scan 7 at rest after ≥ 15 min delay.
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Flow chart 1: Adenosine Stress MR Perfusion Imaging
(1) transversal(2) single-angulated view(3) double-angulated view
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TFE prepulse/before each shot/delay (ms)
1 (!!), (if not, adjust trigger delay !!!)
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This cookbook has been assembled from the knowledge available at the time of writing. The authors cannot take liability for dose regimen, infusion schemes, etc. If you find any errors or would like to suggest any improvements, please let us know at eike.nagel@dhzb.de or info@cmr-academy.com.
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