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Society of Nuclear Medicine Procedure Guideline for

Brain Perfusion Single Photon Emission
Computed Tomography (SPECT) Using
Tc-99m Radiopharmaceuticals
version 2.0, approved February 7, 1999

Authors: Jack E. Juni, MD (William Beaumont Hospital, Royal Oak, MI); Alan D. Waxman, MD (Cedars Sinai Medical Center,
Los Angeles, CA); Michael D. Devous, Sr., PhD (University of Texas South West Medical Center, Dallas, TX); Ronald S. Tikof-
sky, PhD (College of Physicians and Surgeons of Columbia University, Harlem Hospital Affiliation, New York, NY);
Masanori Ichise, MD (Mount Sinai Hospital and University of Toronto, Toronto, Ontario, Canada); Ronald L. Van Heertum,
MD (Columbia-Presbyterian Medical Center, New York, NY); B. Leonard Holman, MD (Brigham and Women’s Hospital,
Boston, MA); Robert F. Carretta, MD (Sutter Roseville Medical Center, Roseville, CA); and Charles C. Chen, MD (Saint Fran-
cis Medical Center, Peoria, IL).

I. Purpose 2. Pre-Injection
a. The most important aspect of patient
The purpose of this guideline is to assist nuclear
preparation is to evaluate the patient for
medicine practitioners in recommending, perform-
his/her ability to cooperate.
ing, interpreting, and reporting the results of brain b. Achieve a consistent environment at the
perfusion SPECT studies using Tc-99m radiophar- time of injection and uptake:
maceuticals. i. Place the patient in a quiet, dimly-lit
room.
II. Background Information and Definitions ii. Instruct the patient to keep his/her
eyes and ears open.
Single Photon Emission Computed Tomography iii. Ensure that the patient is seated or re-
(SPECT) of the brain is a technique for obtaining to- clining comfortably.
mographic images of the 3-dimensional distribution iv. Place intravenous access at least 10 min
of a radiopharmaceutical, which reflects regional prior to injection to permit accommo-
cerebral perfusion. dation.
v. Instruct the patient not to speak or read.
III. Common Indications vi. Have no interaction with the patient
prior to, during or up to 5 min post-in-
A. Detection and evaluation of cerebrovascular jection.
disease B. Information Pertinent to Performing the
B. Evaluation of patients with suspected dementia Procedure
C. Presurgical localization of epileptic foci Relevant patient data suggested for optimal inter-
D. Evaluation of suspected brain trauma pretation of scans includes: patient history (includ-
Additional indications not listed here are under ac- ing any past drug use or trauma), neurologic exam,
tive evaluation, many of which appear promising psychiatric exam, mental status exam (e.g. Folstein
at this time. mini-mental exam or other neuropsychological
test), recent morphologic imaging studies (e.g. CT,
MRI), current medication and when last taken.
IV. Procedure
C. Precautions
A. Patient Preparation 1. Demented patients must be closely monitored
1. Pre-Arrival at all times.
Patients should be instructed, if possible, to 2. Patients with neurologic deficits may require
avoid caffeine, alcohol or other drugs known special care and monitoring.
to affect cerebral blood flow (CBF). 3. If sedation is required, it should be given af-
114 • BRAIN SPECT

Radiation Dosimetry in Adults

Radiopharmaceutical Administered Activity Organ Receiving the Effective Dose*
Largest Radiation Dose*
MBq mGy mSv
(mCi) (rad) (rem)
Tc-99m HMPAO1 555 – 1110 i.v. 0.034 0.0093
kidneys
(15 – 30) (0.126) (0.034)
Tc-99m ECD 555 – 1110 i.v. 0.073 0.011
bladder wall
(15 – 30) (0.27) (0.041)
*per MBq (per mCi)
1ICRP 62, page 13

ter injection of radiopharmaceutical, when tracer no sooner than 10 min pre- and no
possible. more than 30 min post-reconstitution. For
D. Radiopharmaceutical seizure disorders, it is important to inject
1. Radiopharmaceuticals the tracer as soon as possible after reconsti-
a. Tc99m-HMPAO (Exametazime [unstabi- tution (within 1 min).
lized]) b. Tc99m-HMPAO (stabilized): Tracer should
b. Tc99m-HMPAO (Exametazime [stabi- be injected no sooner than 10 min pre-
lized]) and no more than four hr post-reconstitu-
c. Tc99m-Bicisate (Ethyl cystine dimer tion.
[ECD]) c. Tc99m-Bicisate (ECD): Inject tracer no
2. Radiopharmaceutical Preparation sooner than 10 min pre- and no more than
a. Use fresh generator eluate (<2 hr old) for 6 hr post-reconstitution.
optimal results with Tc99m-HMPAO. d. Patients should be instructed to void
b. Do not use pertechnetate obtained from a within 2 hr post-injection to minimize radi-
generator which has not been eluted for 24 ation exposure.
hr or more. 4. Delay Time from Injection to Imaging
3. Radiopharmaceutical Injection a. Tc99m-HMPAO (unstabilized and stabi-
a. Tc99m-HMPAO (unstabilized): Inject lized): $90 min delay from injection to

Radiation Dosimetry in Children
(5 years old)

Radiopharmaceutical Administered Activity Organ Receiving the Largest Effective Dose*
Radiation Dose*
MBq/kg mGy mSv
(mCi/kg) (rad) (rem)
Tc-99m HMPAO1 7.4 – 11.1 i.v. 0.14 0.026
thyroid
(0.2 – 0.3) (0.52) (0.096)
Tc-99m ECD2 7.4 – 11.1 i.v. 0.083 0.023
bladder wall
(0.2 – 0.3) (0.31) (0.085)
*per MBq (per mCi)
1ICRP 62, page 13
2Treves ST. Pediatric Nuclear Medicine, 2nd edition. Springer-Verlag, 1995, p. 576.
SOCIETY OF NUCLEAR MEDICINE PROCEDURE GUIDELINES MANUAL J UNE 2002 • 115

imaging for best image quality. Images ob- ceptable if adequate counts are obtained.
tained after a 40 min delay will be inter- Slant hole collimation may be used.
pretable. 8. A 128 x 128 or greater acquisition matrix
b. Tc99m-ECD: Approximately 45 min delay should be used.
from injection to imaging for best image 9. Use 3° or better angular sampling. Acquisi-
quality. Images obtained after a 20 min de- tion pixel size should be 1/3–1/2 the ex-
lay will be interpretable. pected reconstructed resolution. It may be
c. Imaging should be completed within 4 hr necessary to use a hardware zoom to achieve
post injection if possible. Excessive delay an appropriate pixel size. Different zoom
should be avoided. factors may be used in the x and y dimen-
5. Dosage: Adults 555–1110 MBq (15–30 mCi sions of a fan-beam collimator.
Tc99m-HMPAO or Bicisate [ECD], typically 10. Continuous acquisition may provide shorter
20 mCi [740 MBq] for HMPAO or 30 mCi total scan duration and reduced mechanical
[1110 MBq] for ECD). Children 7.4–11.1 wear to the system when compared to step
MBq/kg (0.2–0.3 mCi/kg). Minimum dose is and shoot technique.
3–5 mCi. 11. Segmentation of data acquisition into multi-
6. Quality Control: Radiochemical purity deter- ple sequential acquisitions will permit exclu-
minations should be performed on each vial sion of bad data, e.g. removing segments of
prior to injection using the method outlined in projection data with patient motion.
the package insert. A shortened one-step tech- 12. It is frequently useful to use detector pan and
nique may also be used for Tc99m-HMPAO. zoom capabilities to ensure that the entire
E. Image Acquisition brain is included in the field of view while al-
Set-up & acquisition lowing the detector to clear the patient’s
1. Multiple detector or other dedicated SPECT shoulders.
cameras generally produce results superior to F. Interventions
single-detector general-purpose units. How- Vasodilatory challenge with acetazolamide (Di-
ever, with meticulous attention to procedure, amox) or equivalent.
high-quality images can be produced on sin- Indication: Evaluation of cerebrovascular re-
gle-detector units with appropriately longer serve in TIA, completed stroke and/or vascular
scan times (5 x 106 total counts or more are de- anomalies (e.g. arterial-venous malformation)
sirable). and to aid in distinguishing vascular from neu-
2. Patient should void prior to study for maxi- ronal causes of dementia.
mum comfort during the study. Acetazolamide (Diamox):
3. The patient should be positioned for maxi- Contraindications: Known sulfa allergy (skin
mum comfort. Minor obliquities of head ori- rash, bronchospasm, anaphylactoid reaction).
entation can be corrected in most systems May induce migraine in patients with migraine
during processing. history. Generally avoided within three days of
4. The patient’s head should be lightly re- an acute stroke.
strained to facilitate patient cooperation in Various protocols have been used, including
minimizing motion during acquisition. It is split-dose, two-day repeat study and dual-iso-
not possible to rigidly bind the head in place. tope techniques. The two-day repeat study tech-
Patient cooperation is necessary. Sedation nique is simplest and may therefore be prefer-
may be used following the injection of radio- able. Typically, the challenge portion is
pharmaceutical if patient is uncooperative. performed first. If this is normal, consideration
5. Use the smallest radius of rotation possible may be given to omitting the baseline study. If a
with appropriate patient safeguards. baseline scan is performed, allow sufficient time
6. Use of high-resolution or ultra high-resolu- for residual activity to clear (typically 24 hr).
tion collimation is recommended. All purpose Acetazolamide (Diamox):
collimation is not suitable. As a general rule of Dosage: Adults 1000 mg by slow iv push for
thumb, use the highest resolution collimation typical patient. Children 14 mg/kg. Wait 15–20
available. min after administering acetazolamide before in-
7. Fan-beam or other focused collimators are jecting tracer.
generally preferable to parallel-hole as they Acetazolamide is a diuretic. The patient
provide improved resolution and higher should be instructed to void immediately before
count rates. Parallel-hole collimation is ac- beginning of image acquisition. Acquisition and
116 • BRAIN SPECT

processing are identical to non-acetazolamide of tomographic sections. Projection data
study. should be assessed for the presence and de-
Adverse effects: Mild vertigo, tinnitus, pares- gree of patient motion, target-to-background
thesias and, rarely, nausea may be experienced. ratio and other potential artifacts. Inspection
These are generally self-limited and do not re- of the projection data in sinogram form may
quire specific treatment. Patients may experience also be useful.
postural hypotension when arising and should be 3. Images should be viewed on a computer
appropriately warned and assisted, if necessary.
screen rather than from film or paper copy to
G. Processing
permit interactive adjustment of contrast,
Image Processing
background subtraction and color table.
1. Filter all studies in 3 dimensions (x, y and z).
This can be achieved either by two-dimen- 4. Caution must be used in selecting levels of
sionally prefiltering the projection data or by contrast and background subtraction. Non-
applying a 3-dimensional post-filter to the re- continuous color scales may be confusing or
constructed data. misleading if abrupt color changes occur in
2. Low-pass (e.g., Butterworth) filters should the range of expected gray matter activity.
generally be used. Resolution recovery or spa- Thresholding, if used, must be based upon
tially varying filters should be used with cau- knowledge of a normal database for specific
tion, as they may produce artifacts. radiopharmaceuticals and instruments used
3. When possible reconstruct the entire brain. in acquiring the study. Artifacts can be cre-
Use care not to exclude the cerebellum or ated when inappropriate thresholding is per-
vertex. formed.
4. Reconstruct data at highest pixel resolution, 5. Three-dimensional renderings may be useful
i.e. one pixel thick. If slices are to be summed, in appreciating overall patterns of disease.
this should be done only after reconstruction
Care must be exercised in choice of threshold,
and oblique reorientation (if performed).
as artifactual defects are easily generated.
5. Attenuation correction should be performed
6. Images must be evaluated in the context of
in all cases unless a specific application or cir-
cumstance would dictate otherwise. Use relevant structural information (CT/MRI).
shape contouring if available. Be sure that Specific attention should be paid to the ex-
contour includes scalp and not just gray mat- tent of perfusion abnormalities relative to
ter. Whenever possible, the surface contour underlying morphologic defects (e.g. is-
should be defined individually for each chemic penumbra versus infarct) as well as
transaxial slice. to the possible effects of atrophy and partial-
6. Reformat transaxial data into at least three or- volume effect.
thogonal planes. Generate transverse sections 7. Epilepsy evaluation: Images must be corre-
relative to a repeatable anatomic orientation lated with the relevant EEG data and clinical
(e.g., AC-PC line), and coronal and sagittal observations in seizure patients. The exact
sections orthogonal to the transverse. Addi- timing of tracer injection relative to observed
tional sections along a plane parallel to the behavioral or electrical seizure activity must
long axis of the temporal lobes are frequently be known. The scintigraphic appearance and
useful. extent of seizure foci may change dramati-
H. Interpretation Criteria
cally depending on the exact timing of tracer
1. The extent of normal variability must be ap-
injection relative to seizure onset. Ictal and in-
preciated during scan interpretation. Substan-
terictal studies should be compared for opti-
tial variability may be noted between normal
mal patient evaluation. Ictal studies are more
individuals and between scans of a single sub-
ject obtained at different times. Individual reliable for seizure foci localization.
laboratories should obtain or be familiar with 8. Interpreters should be familiar with the docu-
a normal database to best interpret patient ment issued by the Ethical Subcommittee for
studies. The Brain Imaging Council of the Functional Brain Imaging, a subcommittee of
SNM is developing a publicly available the SNM Brain Imaging Council (see refer-
database. ence G, Mayberg, HS. The ethical clinical
2. Unprocessed projection images should be re- practice of functional brain imaging. J Nucl
viewed in cinematic display prior to viewing Med 1996;37:1256–1259).
SOCIETY OF NUCLEAR MEDICINE PROCEDURE GUIDELINES MANUAL JUNE 2002 • 117

I. Reporting area] is a pattern not proven by well-
Study reports should describe the extent and accepted, peer-reviewed published
severity of defects, their correlation with mor- studies to be related to a specific dis-
phologic and clinical abnormalities and, when ease entity.
relevant, a differential diagnosis and/or the sig- iii. The accumulation or reduction of ac-
nificance of abnormality. It must be recognized tivity in the [anatomical area] could be
that many patients will present with non-specific interpreted as an artifact associated
perfusion patterns which cannot be directly at- with insufficient resolution or statisti-
tributed to a specific disorder or causative agent. cal variations.
Care must be taken to avoid implying the exis- J. Quality Control
tence of cause and effect relationships between See Society of Nuclear Medicine Procedure Guideline
scan and behavioral/neurologic abnormalities. for General Imaging.
Each clinical report should include the fol- K. Sources of Error
lowing: 1. Presence of sedating medications at the time of
1. Indications for the study (brief synopsis) tracer injection may alter tracer distribution. If
2. Assessment of the technical quality of the scan sedation is absolutely necessary it should,
(good, adequate, poor, including presence of whenever possible, be administered at least 5
patient movement, deviations from usual lab min after tracer injection. When sedation is
protocol, etc., if relevant) used, record type and dosage of the sedative,
3. Description of abnormalities (including crite- and time at which sedative was administered
ria for definition of abnormal, i.e. visual in- in relation to time of tracer injection.
spection criteria, regions of interest, compari- 2. Patient motion during data acquisition may
son to lab database, reference paper, etc.) produce blurring of image data and may re-
4. Interpretation and conclusions sult in artifacts.
a. Provide a full differential diagnosis based
on peer-reviewed and generally accepted
disease-specific patterns. Any interpretive V. Issues Requiring Further Clarification
statements not based on such criteria
should be explicitly identified as such. A. Normal database issues
b. As appropriate, qualify the scan interpreta- B. Quantification techniques
tion in the context of known clinical his- C. Coregistration techniques with MRI and CT
tory, associated co-morbid conditions,
medications, and other diagnostic studies
(CT, MRI, EEG). Alternatively, state the VI. Concise Bibliography
limitations of the offered differential diag- Devous MD Sr. SPECT functional brain imaging. In:
nosis if relevant clinical data are not avail- Kramer EL, Sanger J, eds. Clinical SPECT Imaging.
able, and recommend additional tests as Raven Press, Ltd., New York, NY 1995;97–128.
indicated. Fayad PB, Brass LM. Single-photon emission computed
c. If the instrument and/or methodology used tomography in cerebrovascular disease. Stroke
is significantly different than that which is 1991;22:950–954.
typically used (e.g., as described in this Holman BL, Devous MD Sr. Functional brain SPECT:
guideline), the differences should be explic- the emergence of a powerful clinical method. J Nucl
itly stated in the report. Any limitations of Med 1992;33:1888–1904.
the study should be explicitly described. Holman BL, Johnson KA, Garada B, et al. The scinti-
d. If a study cannot be interpreted based on graphic appearance of Alzheimer’s disease: a
well-accepted criteria, the clinical report prospective study using technetium-99m-
may, where relevant, include one or more HMPAO SPECT. J Nucl Med 1992;33:181–185.
statements similar to the following: Hung JC, Corlija M, Volkert WA, et al. Kinetic analysis
i. Although abnormalities are present in of technetium-99m d, 1-HMPAO decomposition in
this study, there are no established aqueous media. J Nucl Med 1988;29:1568–1576.
cause and effect relationships between Juni JE. Taking brain SPECT seriously: reflections on re-
these observed abnormalities and the cent clinical report in the Journal of Nuclear
patient’s clinical history or behavior in Medicine. J Nucl Med 1994;35:1891– 1895.
question. Mayberg, HS. The ethical clinical practice of functional
ii. The abnormal pattern of increased or brain imaging. J Nucl Med 1996;37: 1256–1259.
decreased activity in the [anatomical Report of the Therapeutics and Technology Assess-
118 • BRAIN SPECT

ment Subcommittee of the American Academy of to all patients in all practice settings. The guide-
Neurology. Assessment of brain SPECT. Neurology lines should not be deemed inclusive of all proper
1996;46:278–285. procedures or exclusive of other procedures rea-
Van Heertum RL, Miller SH, Mosesson RE. SPECT sonably directed to obtaining the same results. The
brain imaging in neurologic disease. Radiol Clin spectrum of patients seen in a specialized practice
North Am 1993;31:881–907. setting may be quite different from the spectrum
Van Heertum RL, Tikofsky RS (ed). Cerebral Brain of patients seen in a more general practice setting.
SPECT Imaging. Raven Press, 2nd ed. New York The appropriateness of a procedure will depend,
City, NY: 1995. in part, on the prevalence of disease in the patient
population. In addition, the resources available to
care for patients may vary greatly from one medi-
VII. Disclaimer
cal facility to another. For these reasons, guide-
The Society of Nuclear Medicine has written and lines cannot be rigidly applied.
approved guidelines to promote the cost-effective Advances in medicine occur at a rapid rate. The
use of high-quality nuclear medicine procedures. date of a guideline should always be considered in
These generic recommendations cannot be applied determining its current applicability.