Procedure Guideline for Diuretic Renographyin Children 3.0*
Barry L. Shulkin1, Gerald A. Mandell2, Jeffrey A. Cooper3, Joe C. Leonard4, Massoud Majd5, Marguerite T. Parisi6,George N. Sfakianakis7, Helena R. Balon8, and Kevin J. Donohoe9
1St. Jude Children’s Research Hospital, Memphis, Tennessee; 2Phoenix Children’s Hospital, Phoenix, Arizona; 3Albany Medical Center,Albany, New York; 4Oklahoma Children’s Memorial Hospital, Oklahoma City, Oklahoma; 5Children’s National Medical Center,Washington, DC; 6Children’s Hospital and Regional Medical Center, Seattle, Washington; 7University of Miami School of Medicine,Miami, Florida; 8William Beaumont Hospital, Royal Oak, Michigan; and 9Beth Israel Deaconess Medical Center, Boston,Massachusetts
infused with increasing amounts of fluid, is relatively inva-
The purpose of this guideline is to assist nuclear medi-
sive. It may overestimate obstructive phenomena and diag-
cine practitioners in recommending, performing, inter-
nose obstruction in cases of reduced renal function, when
preting, and reporting the results of diuretic renography in
obstruction appears to occur at a flow rate that the kidney with
Diuretic renography is a safe and valuable method for
the evaluation of renal function and differentiation between
II. BACKGROUND INFORMATION AND DEFINITIONS
obstructive and nonobstructive causes of renal or ureteral
Pelvicaliectasis (distension of the pelvicalyceal system)
with or without megaureter (distension of the ureter) is the
Hydronephrosis detected in utero may resolve spontane-
most common indication for radionuclide evaluation of the
ously and is related to physiologic change during early
kidneys in pediatric patients. Pelvicaliectasis may result
development. The diagnosis of obstruction often requires
from either congenital or acquired etiologies. Included
sequential scintigraphic examinations.
among the causes of pelvicaliectasis are entities such as
Injection time for furosemide in relation to tracer injec-
an obstructed renal pelvis, an obstructed ureter, a duplex
tion is indicated by the letter ‘‘F.’’ As an example, injection
renal collecting system, vesicoureteral reflux, bladder ab-
of furosemide 20 min after tracer injection is indicated as
normalities including neurogenic bladder, bladder outlet
obstruction, and infection. Pelvicaliectasis and megauretercan result from obstructive or nonobstructive causes. Ob-struction may occur at the level of the ureteropelvic junc-
tion, the ureterovesical junction, the posterior/prostatic
urethra, or uncommonly in the ureter. Nonobstructive causes
1. Preparation before arrival in the department is usually
include vesicoureteral reflux, nonobstructive pelvicaliectasis
not necessary. If the patient is not going to receive
or megaureter, prune belly syndrome, and congenital mega-
intravenous fluids, oral hydration is encouraged be-
fore arrival and while in the department. Oral fluids in
Contrast intravenous urography, ultrasonography, and
the range recommended for intravenous administra-
conventional radionuclide renography cannot reliably dif-
tion are appropriate (see III A.2.e.).
ferentiate obstructive from nonobstructive causes of pelvi-
2. Preparation before injection of the radiopharma-
The pressure perfusion study (Whitaker test), which mea-
a. The procedure is explained to parents and all
sures collecting system pressure while the renal pelvis is
children old enough to understand. Parents can re-main and help with the examination if their pres-ence is beneficial.
Received Aug. 4, 2008; revision accepted Aug. 4, 2008. For correspondence or reprints contact: Kevin Donohoe, Beth Israel
b. Continual communication and reassurance with
Deaconess Medical Center, 330 Brookline Ave., Boston, MA 02215.
explanation of each step is essential for coopera-
E-mail: [email protected]*YOU CAN ACCESS THIS ACTIVITY THROUGH THE SNM WEB SITE
tion and successful intravenous injection of the
radiopharmaceutical and catheterization of the
COPYRIGHT Ó 2008 by the Society of Nuclear Medicine, Inc. DOI: 10.2967/jnmt.108.056622
JOURNAL OF NUCLEAR MEDICINE TECHNOLOGY • Vol. 36 • No. 3 • September 2008
c. Oral hydration (volume expansion) may be suffi-
g. Some laboratories do not use intravenous hydra-
cient in certain situations. Intravenous hydration is
tion or catheter bladder drainage for the initial
more reliable in the diagnosis of questionable cases
evaluation (particularly in older children) so that
of urinary obstruction. An indwelling venous cath-
kidneys can be evaluated without intervention.
eter may be inserted to maintain sufficient hydra-tion for a good diuretic effect and obviate repeated
B. Information Pertinent to Performing the Procedure
traumas from multiple percutaneous injections. For
1. Awareness of a prenatal history of urinary tract di-
the administration of the diuretic at the time of
lation, a history of prior surgery to the urinary tract,
tracer injection (F0), a 21- or 23-gauge butterfly
and congenital urinary abnormalities (duplex systems,
needle is used for the simultaneous injection of the
renal fusion, etc.) are important for accurate interpre-
radiopharmaceutical and the diuretic and may be
2. The review of available past radiographic, ultrasound,
d. Bladder catheterization is not always necessary
and radionuclide studies adds to the accuracy of
but is suggested if it is necessary to evaluate
interpretation of the current study.
patients with bladder pathology or in questionable
3. Nonlatex materials should be used in patients prone
cases; it is also sometimes necessary to catheterize
to latex allergy (e.g., patients with congenital spinal
the patient after the study, to evaluate the effect of
defects and chronic urethral catheterization).
the urinary bladder. In some cases, the diagnosis
4. An allergy to sulfa drugs may prevent the use of
of obstruction may be more reliable with bladder
furosemide (cross reactivity between sulfa and fu-
or pelvic drainage catheterization. Older children
rosemide) in a small percentage of patients. Urethral
who are not catheterized are requested to void
anesthesia with lidocaine should not be used in
patients with an allergic history to lidocaine or itsderivatives.
i. Sterile urethral catheterization should be per-
formed with the largest-sized Foley or feeding
catheter that will comfortably pass the meatus
1. The examination table is covered with plastic-lined
(a 2.6-mm-diameter catheter [French 8] for
absorbent paper to contain spilled tracer and reduce
most patients and 1.8-mm-diameter [French 6]
contamination of the table during drainage and cath-
for infants). A French 8 feeding catheter
2. Gentle catheterization by a qualified individual can
prevent an overly traumatic and painful experience
ii. Continual drainage by catheterization of
and results in better cooperation during follow-up
the bladder may be required in patients with
hydroureter, vesicoureteral reflux, a neuro-
3. Slow, deep breathing and a gentle forward motion of
pathic bladder, a small-capacity bladder, a
the catheter should be used to relax a spastic external
dysfunctional bladder, or posterior urethral
4. An application of urethral anesthesia (3–5 mL of
iii. The diuretic effect can be assessed by com-
lidocaine jelly) in the male urethra 2–5 min before
paring the volume of urine excreted during the
catheterization helps decrease discomfort.
dynamic phase with the volume of urine ex-
5. A Foley balloon is inflated only after the catheter and its
balloon are confirmed to be in the bladder. Urine return
e. Hydration or volume expansion, in patients for
can be appreciated with the balloon still positioned in
whom there is no cardiovascular contraindication,
the posterior urethra. The balloon must be deflated
is suggested to reduce the incidence of false-
before removal from the bladder. When a feeding tube
positive findings. Ten to 15 mL/kg of one third
is used for bladder drainage, it should not be advanced
or greater normal saline (with or without 5%
too far, to avoid coiling and knot formation.
dextrose) for 30 min are infused before the di-
6. Caution should be observed with postural changes
uretic is administered. The slow administration of
because of possible diuresis-induced hypotension.
fluid is continued during the remainder of the
7. Sudden abdominal or flank pain can arise during acute
distension of the pelvicalyceal system in some patients.
f. If the rate of urine flow is low during hydration, a
8. There is a small risk of catheter-induced trauma and
larger amount of fluid (up to 40 mL/kg) can be
administered cautiously with careful assessmentof volume status (with particular attention to
patients who may have renal or cardiac compro-
1. The preferred radiotracer, 99mTc-mercaptoacetyltri-
glycine (99mTc-MAG3), is cleared mainly by tubular
DIURETIC RENOGRAPHY IN CHILDREN • Shulkin et al.
secretion. After about 3 h, 90% of the injected dose
static images before and after the patient is kept upright
can be recovered in the urine. 99mTc-MAG3 has a high
initial renal uptake, providing high kidney-to-backgroundratios with good temporal resolution. 99mTc-MAG3 is
recommended for neonatal renography and for visu-
1. The dose of furosemide (Lasix; Sanofi-Aventis) is
alization of kidneys in patients with compromised
1.0 mg/kg, with a usual maximum dose of 40 mg. A
renal function. The recommended administered dose
higher diuretic dose may be necessary in cases of
is 1.9 MBq (50 mCi) per kilogram of body weight
obesity, chronic use of diuretics, or impaired renal
(minimum, 19 MBq [0.5 mCi]). Some laboratories use
function, either unilateral or bilateral.
2. There are 3 different approaches for the time of injec-
2. 99mTc-diethylene triamine pentaacetic acid (99mTc-
tion of the diuretic furosemide (F).
DTPA) is a glomerular agent. The biologic half-life is
a. In the method endorsed by the American Society
less than 2.5 h, and 95% of the administered dose is
of Fetal Urology, the diuretic is injected at 20 min
cleared by 24 h. The recommended administered dose
or later after the radiopharmaceutical (F 1 20 or
is 3.7 MBq (100 mCi) per kilogram of body weight
later), when the entire dilated system is filled with
Radiation dose estimates are shown in Tables 1 and 2.
b. In the method developed in Europe, the diuretic is
injected 15 min before the injection of the radio-
1. The study is a dynamic renal scan with the patient supine
c. In the F 2 0 method, used by some laboratories in
and with the patient’s back to the camera. Serial 15- to
the United States and Australia, there is simulta-
30-s images (64 · 64 or 128 · 128 matrix) are acquired
neous injection of the radiopharmaceutical and the
for 30–60 min, depending on the technique chosen.
2. A 1-min flow study may be acquired, but the data
from the flow should be incorporated into the function
study mentioned above. Grouping the data into 2-min
1. From the dynamic renal study, careful evaluation of the
images simplifies the visual interpretation.
parenchymal phase reveals renal function, size, and
3. For F 1 20 or later technique, the prediuretic and
position. Cortical transit time and dilatation of the
postdiuretic phases are acquired either as a single
collecting system may be examined in the excretory
dynamic study starting immediately after the injection
of the radiopharmaceutical and continued for 20–30
2. Baseline images of the diuretic phase are used for
min after the injection of furosemide or as 2 separate
3. Cinematic viewing of the diuretic phase assesses pa-
4. For F 2 15 and F 2 0 techniques, dynamic images are
tient movement. If there is considerable patient mo-
acquired for 20–30 min after injection of the radio-
tion, regions of interest around the collecting systems
of individual frames will have to be compared at
5. If postdiuresis clearance with the patient supine is poor,
various intervals of the study to assess drainage.
additional dynamic images with the patient prone may
4. Regions of interest are drawn around the dilated
be obtained. An alternative technique is acquisition of
pelvicalyceal system for curve analysis and calcula-
Estimated radiation dose equivalent (mSv/MBq)
1Stabin and Gelfand. Q J Nucl Med. 1998;42:93–112.
JOURNAL OF NUCLEAR MEDICINE TECHNOLOGY • Vol. 36 • No. 3 • September 2008
Radiation Dose Estimates for 99mTc-DTPA Injection1
Estimated radiation dose equivalent (mSv/MBq)
1Stabin and Gelfand. Q J Nucl Med. 1998;42:93–112.
tion of the half-time (T1/2). One to 2 background
4. With the injection of the diuretic after the radiophar-
regions can also be drawn. The reader is referred to a
maceutical (F 1 20 or later), a T1/2 less than 10 min
standardized technique of the ‘‘well-tempered’’ diu-
usually means the absence of obstruction, and a T1/2
retic renogram and recommendations by international
greater than 20 min usually identifies obstruction. A
T1/2 with a value between 10 and 20 min is an
5. The diuretic T1/2 is the time at which the time–activity
equivocal result. These T1/2 measurements are appli-
curve decreases to half its maximal activity. A re-
cable to neonatal hydronephrosis. The natural history
search study applying F 2 15, F0, and F 1 20
of neonatal hydronephrosis is variable. Drainage may
indicated that the 3 methods are equivalent for indi-
gradually improve or worsen. Therefore, follow-up
cating obstruction. They differ in duration (shorter F0)
examinations are usually necessary. These T1/2 values
and in patient acceptance and cost (F0 favored). F0
refer to kidneys with normal or near-normal function.
and F 2 15 also allow evaluation of the renal pa-
Kidneys with reduced function may have prolonged
renchyma in nonobstructed cases and contribute to the
work-up of parenchymal disorders such as focal acute
5. With the injection of the diuretic before the radio-
pyelonephritis, HIV nephropathy (AIDS nephropa-
pharmaceutical (F 2 15), a T1/2 greater than 20 min is
6. For F 1 20 studies, residual activity can be reported
6. With the simultaneous injection of the radiopharma-
by estimating the percentage of tracer activity that
ceutical and furosemide (F0), a T1/2 greater than 20 min
remains at 20 min after injection of the diuretic,
is compatible with obstruction. In cases, however, of
compared with the activity at the time of diuretic
extrarenal pelvis, nonobstructing pelviectasis and
injection. Individual curves from the renal cortices
megaureters of long standing, and particularly post-
should be produced by carefully assigning the renal
operative patients with residual dilatation of the
cortex away from the collecting system. Such curves
collecting system, the possibility of obstruction is
can be useful in cases of extrarenal pelvis, non-
studied mainly by observing the cortex and the cor-
obstructing pelviectasis, and megaureter and espe-
tical graphs. When the cortical graphs are normal and
cially in postoperative cases with residual dilatation of
the cortices appear empty, then there is no obstruc-
the collecting system but no obstruction.
tion, even if the curves of the total kidneys have a T1/2greater than 20 min. The F0 study should therefore beinterpreted not only for the behavior of the collecting
system but also for the behavior of the cortex of the
1. The diuretic effect usually begins within 1–2 min after
The neonatal kidney is functionally immature. As a
2. In the absence of obstruction, rapid and almost
result, in the F0 study, neonatal kidneys may show
complete washout of the radiotracer occurs before
increased residual cortical activity, retaining up to
injection of diuretic. However, if function is de-
50% or more of the peak because of immaturity of the
creased, there may be slow emptying of the kidneys.
kidneys. Such a phenomenon disappears after the age
3. Obstructed systems can result in delayed drainage
from the collecting system. The amount of activity
This method (F0) applied in the neonate with a
proximal to the obstruction can also increase over
dilated collecting system has been observed to provide
definitive indications for the existence of obstruction if
DIURETIC RENOGRAPHY IN CHILDREN • Shulkin et al.
the renogram of the entire kidney is upsloping contin-
4. Poor renal function from prolonged severe obstruction
uously. Such patients often require surgery. Patients
can result in slow tracer accumulation in the dilated
with a downsloping curve usually compensate and
collecting system and result in difficulty in interpreta-
do not need an immediate operation, but follow-up.
tion of the diuretic phase. The F0 study provides
Patients with a horizontal graph need close observation
additional help by indicating a normal emptying cortex
because some of them require surgery.
in cases of no obstruction. In cases of obstruction, the
In acquired obstruction (tumors, renal stones, etc.)
cortex shows prolonged retention of the activity.
complete obstruction is characterized by nonvisuali-
5. A large, unobstructed collecting system with rela-
zation of the collecting system, associated with a
tively good renal function can exhibit slow drainage
rising curve from the parenchyma; blood flow is often
of the radiotracer (prolonged T1/2). The F0 method
decreased. Partial obstruction is characterized by
indicates normal emptying of the cortex.
delayed and persistent visualization of the drainage
6. When the obstruction is at both the pelvicalyceal and
system and cortical retention of the activity, associ-
the ureterovesical junctions, detection of the uretero-
ated with decreased blood flow. The acute postob-
vesical junction obstruction may be difficult.
struction/postdecompression image (stunned kidney)
7. Patient movement may invalidate curve analysis.
shows cortical retention, relatively better flow, faint (if
8. Urinary systems considered normal in the prediuretic
any) visualization of the intrarenal collecting system,
phase may not be evaluated for postdiuresis drainage.
but always visualization of the ureter (may need
A prolonged T1/2 can be obtained because of the
relatively small amount of residual activity in the col-
7. The shape of the resulting time–activity curves of the
lecting system to respond to the diuretic challenge.
washout study has been used for differentiation of
With the F0 approach, in rare cases the use of the
stasis from obstruction. Lack of radiotracer decline
diuretic has uncovered borderline obstructions asso-
after furosemide suggests obstruction, although this
ciated with normal baseline studies in symptomatic
can be mimicked by impaired renal function. A brisk
patients (pain after much drinking).
decline in activity after diuretic is consistent withstasis without obstruction.
IV. ISSUES REQUIRING FURTHER CLARIFICATION
A. The calculation method of the postdiuresis drainage
1. The procedure, date of the study, activity and route of
is variable, but a standardized technique is available
administration of the radiopharmaceutical, and a pre-
vious study for comparison are included.
B. The curve analysis has been questioned because of
2. The history includes symptoms or diagnosis.
poor correlation with pressure perfusion studies in
3. The technique includes catheter size and type if
implemented, amount and kind of intravenous fluid
C. The results of the alternative method of simultaneous
if administered, the imaging sequence, the amount
injection of the radiopharmaceutical and diuretic
and time of diuretic administration, and the urine
remain to be validated. However, in some laboratories
volumes before and after the diuretic, if measured.
the method provides valuable and accurate diag-
4. The findings may include renal perfusion, split renal
nostic and prognostic information noninvasively and
function, transit times, and the T1/2 of collecting
There are no issues of quality control.
A. Bird VG, Gomez-Marin O, Leveillee RJ, Sfakianakis
GN, Rivas LA, Amendola MA. A comparison of
1. Infiltration of the radiopharmaceutical or diuretic may
unenhanced helical computerized tomography find-
ings and renal obstruction determined by furosemide
2. Insufficient hydration can result in delayed uptake and
99m-technetium mercaptoacetyl-triglycine diuretic
excretion, simulating poor function, or can demon-
scintirenography for patients with acute renal colic.
strate a normal response in the presence of significant
B. Conway JJ. Radionuclide cystography. In: Tauxe
3. If the diuretic is administered before the maximum
WN, Dubovsky EV, eds. Nuclear Medicine in Clin-
distension of the collecting system, the response may
ical Urology and Nephrology. East Norwalk, CT:
not reflect the true physiologic state. However, in the
Appleton, Century and Crofts; 1985:305–320.
F0 method, the cortex empties appropriately, and this
C. Conway JJ. ‘‘Well-tempered’’ diuresis renography: its
observation compensates for this phenomenon.
historical development, physiological and technical
JOURNAL OF NUCLEAR MEDICINE TECHNOLOGY • Vol. 36 • No. 3 • September 2008
pitfalls, and standardized technique protocol. Semin
R. Sfakianakis GN, Carmona AJ, Sharma A, et al.
Diuretic MAG3 scintirenography in children with
D. Donoso G, Kuyvenhoven JD, Ham H, Piepsz A.
HIV nephropathy: diffuse parenchymal dysfunction.
99mTc-MAG3 diuretic renography in children: a com-
parison between F0 and F120. Nucl Med Commun.
S. Sfakianakis GN, Sfakianakis E. Renal scintigraphy
in infants and children. Urology. 2001;57:1167–
E. Eskild-Jensen A, Gordon I, Piepsz A, Frokiaer J.
Congenital unilateral hydronephrosis: a review of the
T. Sfakianakis GN, Vensel EE, Tapia-Palacios M, et al.
impact of diuretic renography on clinical treatment.
The value of MAG3-Fo diuretic renography in
predicting the need for surgery in the neonate with
F. Foda MM, Garfield CT, Matzinger M, et al. A
uretero-pelvic junction obstruction [abstract]. J Nucl
prospective randomized trial comparing 2 diuresis
renography techniques for evaluation of suspected
U. Shokeir AA, El-Sherbiny MT, Gad HM, et al. Post-
upper urinary tract obstruction in children. J Urol.
natal unilateral pelviureteral junction obstruction:
impact of pyeloplasty and conservative management
G. Houle AM, Cheikhelard A, Barrieras D, Rivest MC,
on renal function. Urology. 2005;65:980–985.
Gaudreault V. Impact of early screening for reflux in
V. Stabin MG, Gelfand MJ. Dosimetry of pediatric nuclear
siblings on the detection of renal damage. Br J Urol
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W. Vlajkovic M, Ilic S, Rajic M, Petronijevic V, Bubanj T,
H. Jung HS, Chung YA, Kim EN, et al. Influence of
Artiko V. Diuresis renal scintigraphy ‘‘F20’’ in di-
hydration status in normal subjects: fractional analy-
agnosing of upper urinary tract obstruction in chil-
sis of parameters of Tc-99m DTPA and Tc-99m
dren: the clinical significance. Nucl Med Rev. 2005:8:
MAG3 renography. Ann Nucl Med. 2005;19:1–7.
I. Kass EJ, Majd M. Evaluation and management of the
X. Wackman J, Brewer E, Gelfand MJ, et al. Low grade
upper urinary tract obstruction in infancy and child
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hood. Urol Clin North Am. 1985;12:122–141.
raphy. Br J Urol. 1986;58:364–367.
J. Kuyvenhoven JD, Ham HR, Piepsz A. The estimation
Y. Whitaker RH, Buxton TMS. A comparison of pres-
of renal transit using renography: our opinion. Nucl
sure flow studies and renography in equivocal upper
tract obstruction. J Urol. 1986;131:446–449.
K. Liu Y, Ghesani NV, Skurnick JH, Zuckier LS. The
F 1 0 protocol for diuretic renography results infewer interrupted studies due to voiding than the F 2
15 protocol. J Nucl Med. 2005;46:1317–1320.
The SNM has written and approved this Procedure Guide-
L. Meller ST, Eckstein HB. Renal scintigraphy: quanti-
line as an educational tool designed to promote the cost-
tative assessment of upper urinary tract dilatation in
effective use of high-quality nuclear medicine procedures in
children. J Pediatr Surg. 1981;16:123–126.
medical practice or in the conduct of research and to assist
M. Piepsz A, Ham HR. Pediatric applications of renal
practitioners in providing appropriate care for patients. The
nuclear medicine. Semin Nucl Med. 2006;36:16–35.
Procedure Guideline should not be deemed inclusive of all
N. Piepsz A, Ismaili K, Hall M, Collier F, Tondeur M,
proper procedures or exclusive of other procedures reason-
Ham H. How to interpret a deterioration of split
ably directed to obtaining the same results. The guidelines
function. Eur Urol. 2005;47:686–690.
are neither inflexible rules nor requirements of practice and
O. Prigent A, Cosgriff P, Gates GF, et al. Consensus
are not intended nor should they be used to establish a legal
report on quality control of quantitative measure-
standard of care. For these reasons, the SNM cautions
ments of renal function obtained from the renogram:
against the use of this Procedure Guideline in litigation in
International Consensus Committee from the Scien-
which the clinical decisions of a practitioner are called into
tific Committee of Radionuclides in Nephrourology.
The ultimate judgment about the propriety of any spe-
P. Senac MO, Miller JH, Stanley P. Evaluation of
cific procedure or course of action must be made by the
obstructive uropathy in children: radionuclide re-
physician when considering the circumstances presented.
nography versus the Whitaker test. AJR. 1984;143:
Therefore, an approach that differs from the Procedure
Guideline is not necessarily below the standard of care. A
Q. Sfakianaki E, Panagakos GM, Rodriquez JA, Georgiou
conscientious practitioner may responsibly adopt a course
MF, Leveilee RJ, Sfakianakis GN. Evaluation of
of action different from that set forth in the Procedure
obstruction in patients with extrarenal pelvis using
Guideline when, in his or her reasonable judgment, that
time zero diuretic renography [abstract]. J Nucl Med.
course of action is indicated by the condition of the patient,
limitations on available resources, or advances in knowl-
DIURETIC RENOGRAPHY IN CHILDREN • Shulkin et al.
edge or technology subsequent to publication of the Pro-
Advances in medicine occur at a rapid rate. The date of a
Procedure Guideline should always be considered in deter-
All that should be expected is that the practitioner will
follow a reasonable course of action based on currentknowledge, available resources, and the needs of the patientto deliver effective and safe medical care. The sole purpose of
this Procedure Guideline is to assist practitioners in achiev-
This Procedure Guideline was approved by the Board of
Directors of the SNM on April 15, 2007.
JOURNAL OF NUCLEAR MEDICINE TECHNOLOGY • Vol. 36 • No. 3 • September 2008
European Heart Journal (2010) 31, 1036–1037Depression and cardiovascular disease: havea happy day—just smile!University of Michigan School of Medicine, Cardiovascular Center, 1500 E. Medical Center Drive, Ann Arbor, MI 48109, USAOnline publish-ahead-of-print 17 February 2010This editorial refers to ‘Don’t worry, be happy: positiveDavidson et al.10 have examined the association betwe