Functional Brain SPECT: The Emergence of A

Powerful Clinical Method

B. Leonard Holman and Michael D. Devous, Sr.

Department ofRadiology, Harvard Medical School and Brigham and Women ‘s Hospital, Boston, Massachusetts and
Department ofRadiology, University ofTexas Southwestern Medical Center, Dallas, Texas

it is completely extracted from the blood into the brain

J NucIMed 1992;33:1888—1904 and that it remains fixed within the brain without redistri
bution. Ofcourse, only microspheres injected directly into
the carotid artery satisfy these requirements completely.
Nevertheless, those radiotracers that are available for brain
ingle-photon emission computed tomography perfusion imaging follow rCBF closely enough to be din
(SPECT) techniques provide a powerful window into the ically useful. Furthermore, most routine clinical applica
function ofthe brain and promise to become an important tions of brain perfusion SPECT do not require quantita
component of the routine clinical evaluation of patients tion of TCBF and rely on the generation of images which
with neurological and psychiatric diseases. While it initially reflect tracer uptake and retention only. Quantitation of
appeared that brain SPECT would suffer from a number regional cerebral blood flow with these radiotracers re
of limitations relative to positron emission tomography quires arterial sampling and careful modeling to account
(PET), recent improvements in instrumentation and radio for incomplete extraction, back flux from the brain and
pharmaceuticals as well as increasingly compelling clinical other deviations from the theoretical model (1). Despite
evaluations suggest a primary role for SPECT in the diag these constraints, intravenous injection of brain perfusion
nosis ofa number ofhighly prevalent neurological diseases. radiotracers results in regional brain activity which corre
SPECT imaging, even with high-resolution systems, is lates well with independent measures of rCBF over a wide
substantially less expensive than PET and is more widely range of flows.
available. Furthermore, a number of novel approaches to Iodine-l23-isopropyl iodoamphetamine (IMP, Spec
diagnosis have been developed for SPECT exclusively. The tamine) was the first brain perfusion tracer to be synthe
implementation of this method into clinical practice has sized and remains the most ideal with respect to its kinetics
@ been slow, however, and its appropriate utilization will (2,3). Iodine-123 is not an ideal radionuclide since it is
require much closer collaboration between nuclear medi not generator-produced and emits high-energy photons.
cine physicians, neurologists, psychiatrists and neurosur The distribution of IMP reflects rCBF over a wide range
geons. of flows but may underestimate flow when plasma pH is
low, as in cerebral ischemia or acidosis (1). Its first-pass
RADIOPHARMACEUTICALS extraction by the brain is high, and peak activity is reached
within 15 to 20 mm (4). Brain imaging must be accom
Functional brain imaging requires radiotracers that plished quickly after injection since redistribution is fairly
cross the blood-brain barrier, distribute proportionally to rapid and significant changes can be observed after 60
regional cerebral blood flow and remain fixed in the brain mm. Since [‘23I)IMP is prelabeled by the commercial
for a sufficiently long time to permit SPECT imaging. supplier, logistic problems occur and emergency studies
Alternatively, blood flow can be measured quantitatively are difficult to schedule. With the standard injected dose
from the clearance of the inert gas ‘33Xe with highly of 3—6mCi, the photon flux is low and image quality is
sensitive instrumentation that can image its distribution not as good as that with the technetium-labeled ligands.
repeatedly during its rapid clearance from the brain. This becomes a particular problem with high-resolution
For radiotracers that have a very slow clearance from imaging systems.
the brain, estimates of regional cerebral blood flow (rCBF) Technetium-99m brain perfusion agents benefit from
are based on the microsphere model, which assumes that the optimal physical characteristics of the radionuclide,
the radiotracer is freely diffusible from the blood pool, that including its 140 keV monoenergetic photon, 6-hr half
life and potential for on-site labeling. Of the 99mTc radio
pharmaceuticals that have been synthesized, only 99mTc@
ReCeived Apr. 15, 1992; revision accepted Jun. 4, 1992.
For reprints contact: B. Leonard Holman, MD, c@h*man, Department of
HMPAO (hexamethylpropyleneamine oxime, Ceretec) is
Radiology,Brighamand women's Hospital,75 FrancisSt., Boston,MA02115. currently available in the United States. It is a highly

1888 The Journal of Nuclear Medicine•

Vol.33 •
No. 10 •
October 1992
soluble macrocyclic amine with rapid brain uptake but using 99mTcHMPAO or [‘231]IMP. Collimator exchange is
only moderate first-pass extraction, which results in under not difficult, permitting case-by-case selection between
estimation ‘33Xe
of rCBF (5,6). When regional cerebral blood and high-resolution scans. The Hitachi rotating de
tector array system is also capable of both ‘33Xe
flow is quantified, this underestimation can be corrected and high
by accounting for the freely exchangeable component of resolution (8—10mm) static imaging (13).
HMPAO. Of the brain perfusion agents, 99mTc@HMPAO The original fixed-detector research systems that use
is the closest to a microsphere with virtually no brain multiple detectors were the SPRINT (14) and the HEAD
washout. The tracer remains fixed in the brain following TOME (15). They were designed with fixed detectors
conversion to a hydrophilic compound in the presence of oriented in a ring geometry with an internally rotating
intercellular glutathione ( 7). Because blood clearance is collimator. The Shimadzu (HEADTOME) system, which
slow, perfusion defects are not seen as sharply as with other is commercially available, is capable of high sensitivity
brain perfusion tracers. Technetium-99m-HMPAO fol ‘33Xe
studies and moderate spatial resolution (10—12
mm)
lows blood flow and, when flow and metabolism are using 1231or 99mTc.
uncoupled as they are in luxury perfusion, 99mTc@HMPAO The original multidetector scanner was the unit devel
may be increased or normal, while [‘231]IMP may indicate oped by Stoddart and colleagues (16), also known as the
a profound metabolic defect (8). The radiopharmaceutical Harvard multidetector scanner (1 7), and is commercially
is chemically unstable in vitro and must be injected im available as the Strichman unit. This is a slice-based torn
mediately after preparation. ograph, as are the Hitachi, Shimadzu and Tornomatic, but
Technetium-99m-ECD (ethyl cysteinate dimer, Neurol it is built with very thick crystals that operate much like
ite) is currently undergoing clinical testing (9,10). Like pinhole cameras as they traverse through space to obtain
99mTc..HMPAO,it has moderate cerebral extraction and tomographic data. Hill et al. have demonstrated that this
underestimates rCBF. Brain uptake is rapid and clearance device can image not only 99mTcand 1231,but also ‘8F
in a
from the brain is very slow. Blood clearance is rapid, single-photon (not PET) mode (18). It cannot perform
resulting in a higher brain-to-background activity ratio ‘33XeSPECT.
than with HMPAO. Furthermore, 99mTc@ECD is stable in Gamma camera-based systems are more prevalent today
vitro. than dedicated tomographs, primarily because they can do
With the inert gas clearance technique, rCBF is esti both head and body SPECT. There are two forms: singje
mated from the clearance of ‘33Xe from the brain following head and multihead systems. Modern tomographs have
inhalation of the gas (11,12). This methodology can be overcome many of the limitations of the original systems,
coupled with SPECT with specially designed instrumen such as poor head alignment, magnetic field aberrations
tation. Because of the rapid clearance of the tracer, mul and inadequate uniformity and linearity for tomography.
tiple studies can be performed on the same day. Quanti A few of the modern single-head systems have also been
tative measures can be obtained without arterial sampling. designed to circumvent shoulders so that minimal radius
Limitations of ‘33XeSPECT include the low photon energy scanning is possible. Most of these systems provide fairly
ofthe tracer and its rapid clearance from the brain, which high-resolution images with static tracers. Unfortunately,
lead to poor spatial resolution. Specialized instrumenta they suffer from poor sensitivity and prolonged imaging
tion is required with very high sensitivity in order to obtain times.
multiple images during the clearance of the tracer from Researchersfrom the University of TexasSouthwestern
the brain. The inhalation technique is more technically Medical Center at Dallas, in collaboration with the nuclear
difficult than the intravenous method using brain perfu engineering division of Technicare, developed the first
sion radiotracers. three-head gamma camera SPECT system (19) to address
the limited sensitivity of single-head systems. Their intent
INSTRUMENTATION was to provide a system capable of both body and head
A wide variety of imaging systems capable of high SPECT at high resolution with static tracers and with
resolution brain SPECT are now available commercially. adequate sensitivity and rotation speed for dynamic to
They fall into two categories: noncamera-based and cam mography with ‘33Xe.The first three-head system was
era-based systems. Noncamera-based systems include ro installed in Dallas in late 1987 under the sponsorship of
tating detector arrays, fixed detector systems and multi Ohio Imaging, now a division of Picker. Additional three
detector scanners. The rotating detector array group in head SPECT instruments have been produced by Trionix
cludes the Hitachi four-head system, and the more and Toshiba. Prototype three-head instruments from Gen
prevalent Tomomatic two-, three- and five-slice machines eral Electric and Siemens are also under evaluation. Cur
(Medimatic, Inc). The Tomomatic's most characteristic rently, there are approximately 150 such units installed,
attribute is that it is capable of ‘33Xe
SPECT, because it indicating increasing acceptance of this technology.
has high sensitivity and can do rapid dynamic imaging A variant of the gamma camera approach utilizes a
(12). The Tomomatic, by changing collimators, can also single annular sodium iodide crystal (20—22). The AS
produce images of relatively high resolution (9—10mm) PECT system, which is now commercially available, uses

Functional Brain SPECT •

Holman and Devous 1889
a fixed annulus with rotating collimators (22). It yields SPECT systems should have adequate energy resolution
high spatial resolution (5.5—6.5mm) with excellent sensi and multiwindow capability in order to separate 99mTcand
tivity. Xenon-133 dynamic SPECT acquisition is currently 1231 radiotracers in the same patient (24,25). While typical
under development. gamma-camera energy resolution (12%—15%FWHM) is
State-of-the-art SPECT systems can be expected to pro insufficient to separate 140 keY (@mTc)from 159 keV
vide high-resolution (6—9mm) imaging of statically dis (1231) photopeaks, high-resolution multidetector SPECT
tributed brain radiopharmaceuticals with patient imaging units have substantially improved energy resolution. The
times of 10—20mm. All of the currently available three images shown in Figure 1 were obtained simultaneously
head, annular and fixed detector ring systems (Picker, using dual-isotope imaging of @mTc@HMPAO and [1231]
Trionix and Toshiba) offer excellent spatial resolution: IMP.
with appropriate collimators and 99mTc@HMPAO, 6 mm
resolution in the cortex and about 7 mm at the center of
the brain. With [‘231]IMP,
the photon flux is reduced, thus CEREBROVASCULAR DISEASE
requiring careful image processing to achieve equivalent The measurement of rCBF in patients with cerebrovas
spatial resolution. Images of99mTc@HMPAOand [‘231]IMPcular disease was the earliest application of SPECT of the
from the same normal control subject obtained on a three brain. Numerous reports in the last decade describe appli
headed tomograph are shown in (Fig. 1). cations for SPECT rCBF imaging in stroke, transient is
Systems should also be capable of sequential image chemic attacks (TIA), subarachnoid hemorrhage (SAH),
acquisition; it should be possible to acquire multiple short arteriovenous malformation (AVM) and other derange
studies back to back and subsequently discard segments ments ofcerebral hemodynamics. Several valuable reviews
degraded by patient motion. Software should support dy are available (26—28).Many ofthese reports promote both
namic filtering, multiple angle (oblique) reconstructions, diagnostic and prognostic roles for SPECT rCBF imaging
surface-variable attenuation correction and three-dimen of cerebrovascular disease, although criticisms have been
sional as well as conventional cross-sectional displays. The raised that current investigations do not directly address
merging ofanatomic information from CT and MRI with the questions of greatest importance to the referring phy
SPECT is also necessary for accurate diagnosis and local sician (29,30).
ization (23) and should be a critical element ofthe software SPECT is superior to anatomical imaging procedures in
package. Three-head and annular systems in theory should detecting cerebral ischemia during the first hours following
be capable of ‘33Xe SPECT. However, dynamic scanning an ictus because rCBF alterations occur earlier and are
has not been accomplished with any camera-based system. better defined than structural changes. Knowledge of per
There is work in progress demonstrating such feasibility fusion status has important clinical applications in the
for the Picker and Toshiba systems. differential diagnosis and initial management of patients

i@ * ta L@aa Thsk Taa@

flM@fl@o
*[email protected]

..,.......
!•
•S •,@S S S SS FIGURE 1. High-resolution

@S•SSiS•SSi SPECT images of

HMPAO (left) and [123I]IMP
(right) in the same normal vol
unteer. Images were obtained
@‘Tc

simultaneously by dual-isotope
1•1••Ii••• acquisitionof the two radiotra
cars injected sequentially. A
128 x 128 acquisitionmatrix
was employed using a high
resolution(7—8
mm)fanbeam
collimatorand a three-headed
SPECT system. Note similar
POST 1* posT image resolution for both brain
bloodflowtracers.

1890 The Journal of Nuclear Medicine•

Vol.33 •
No. 10 •
October1992
with cerebrovascular disease. In patients with TIA, SPECT day0 dayl day7 day33
may provide the only objective documentation ofthe ictus.
The detection of hemodynamic alterations is also impor
tant in patients with silent strokes and other asymptomatic
lesions to facilitate patient subtyping and management.
Stroke
SPECT is useful in the detection ofacute cerebral ische
mia. Regional CBF alterations occur instantly in patients
with stroke, while CT and MRI are typically normal during
the first hours to days after the ictus (Fig. 2). For example,
by 8 hr after infarction, only 20% of CT scans will be
p‘@ *
positive (31,32), while at the same time approximately
90% of SPECT rCBF scans will be abnormal (33,34). The ISS3WM
difference in sensitivity between structural and functional FIGURE 3. Mid-levelandinferiorlevel(containing cerebellum)
imaging modalities disappears within about 72 hr. In SPECT brain blood flow images in a stroke subject demonstrate
addition, the sensitivity of SPECT is significantly reduced a left hemispheric flow deficit on the day of the ictus that partially
for lacunar infarctions. resolvesby 24 hr. Apparentresolutionof the deficitat Day 7
Sensitivity for lesion detection is also affected by luxury representsluxury perfUSiOn
to an infarctedand metabolically
abnormal zone. By Day 33, the flow disturbance retums to a
perfusion (35), wherein perfusion and metabolism become level similar to that seen initially. Note that crossed cerebellar
decoupled beginning approximately 5 days after the ictus, diaschisisis present and does not resolveduringluxuryperfusion.
and continuing for as much as 20 days (Fig. 3). Although
this phenomenon is not well understood, it is well docu
mented (8,12,26,27) and false-negative studies can result (28,30). In acute infarctions, distinguishing between the
during this period. Thus, acute rCBF imaging may be appropriateness of anticoagulation or thrombolytic ther
effective, but imaging during the subacute phase is insen apy may depend on the demonstration of the physiologic
sitive, particularly with 99mTc@HMPAO (8). significance of an angiographically demonstrable lesion.
Crossed-cerebellar diaschisis frequently accompanies The use ofcalcium channel blockers may only be effective
cortical strokes because cortico-pontine-cerebellar linkages prior to induced or spontaneous reperfusion.
normally provide stimulation to the cerebellum contralat The measurement of cerebrovascular reserve is partic
eral to the indicated cortex. Reduced perfusion to the ularly well suited to rCBF imaging. Two indices of reserve
contralateral cerebellum is a common secondary phenom can be obtained. The rCBF-to-rCBV (flow/volume) ratio
enon following cerebral ischemia, which continues even may be related to the regional oxygen extraction ratio and
during luxury perfusion (36,37). provides an indirect measure of perfusion pressure (38—
SPECT rCBF imaging may also be useful in delineation 40). Cerebrovascular reserve can also be measured follow
of stroke subtypes. Since evolving therapeutic regimens ing the vasodilatory response to C02, or acetazolamide, a
are subtype-specific, it is increasingly important to provide carbonic anhydrase inhibitor and potent cerebral vasodi
rapid, accurate classification of the acute episodes. For lator (41—43). Measurements of cerebrovascular reserve
example, case selection for endarterectomy may depend are useful in assessing either the need for acute interven
on the identification of patients with ongoing low-flow tions following stroke or the risk status for secondary
states even in the presence ofasymptomatic carotid disease strokes. A recently developed dual-isotope imaging tech
nique (24) facilitates the measurement of cerebrovascular
reserveby SPECT (25) (Fig. 4).
Several recent studies also suggest a prognostic role for
SPECT in stroke. A direct relationship between rCBF and
clinical outcome has both been supported (44—48) and
refuted (49-51). Improved correlation between rCBF and
outcome has been achieved with measurement of the
volume of the rCBF defect relative to the volume of
structural defect (52) or of the volume of the flow lesion
alone (28,53—55).One ofthese studies (55) showed a 92%
predictive power of ICBF SPECT obtained within 6 hr of
the ictus for poor neurologic outcome.
Distinctions between [‘231]IMP and 99mTc@HMPAO
FIGURE 2. Abnormalperfusionin the distribution
of the right
middle cerebral artery in an acute stroke patient 6 hr after onset have been reported. IMP may provide more contrast for
of symptoms. A concurrent CT scan was normal. A repeat CT areas of ischemia than HMPAO, particularly in the sub
study was abnormal three days after ictus. acute phase (8,56). Reduced lesion contrast with HMPAO

Functional Brain SPECT •

Holman and Devous 1891
may be a consequence of flow-dependent backdiffusion Arteriovenous Malformation
(57) and high initial bloodlevels(58). A comparisonof Patients with arteriovenous malformation are at risk for
early and delayed (4 hr postinjection) IMP uptake has been three major complications: (1) intracerebral or intraven
proposed as an indicator of tissue viability (47), although tricular bleeding, which may occur at any time and may
this is not well established (54). be fatal [the incidence of spontaneous hemorrhage ranges
from 35% to 60% (71)]; (2) seizures; and (3) intracerebral
“steal,―
in which relative ischemia is produced in parts of
Transient Ischemic Attacks the brain either adjacent to or remote from the arteriove
Determination of the cause of a TIA (thrombotic, em nous malformation due to high arterial-to-venous shunting
bolic or hemodynamic) has substantial impact on patient through the arteriovenous malformation (72). Xenon-l33
management. Structural imaging contributes little. For SPECT studies have demonstrated a high incidence of
example, Crow and Guinto found that 82/100 TIA pa steal (72-75). Documentation of steal has provided a
tients had normal CT scans; the 12 patients with abnormal motivation for staging of surgical resection and for pre
scans showed only the nonspecific finding ofatrophy (59). surgical treatment with arterial embolization (74, 75). The
SPECT rCBF imaging may clarify the mechanism of is arteriovenous malformation itself appears as a high-flow
chemia (60) and may identify patients at the highest risk region on ‘33XeSPECT, but as an area of reduced tracer
for subsequent infarction in the first week following TIA uptake with IMP or HMPAO since the vascular malfor
(61). The value of SPECT imaging in TIA patients may mation does not retain these tracers. Devous, Batjer and
be increased by assessing the status of vasodilatory reserve colleagues found that the examination of cerebrovascular
and the response to medical or surgical intervention. Such reserve with acetazolamide in arteriovenous malformation
assessments are important since as many as 60% of TIA patients was prognostic for postoperative outcome (76,
patients will go on to have a completed stroke (62). The 77).
sensitivity of rCBF imaging in TIA declines with time,
from 60% in the first 24 hr (63) to less than 40% 1 wk
after the event (34). This sensitivity may be enhanced both
early and late after the ischemic event by examination of Future Prospects
cerebrovascular reserve with acetazolamide (61,64). Even though SPECT rCBF measures provide sensitive
early detection ofcerebrai ischemia, and may provide both
Subarachnoid Hemorrhage diagnostic and prognostic information in stroke patients,
Subarachnoid hemorrhage accounts for approximately no significant change in the frequency of referral from
one-halfofall intracranial hemorrhagic strokes. Post-hem neurologists for SPECT has been observed. Brass and
orrhage neurologic deficits that appear within 2 wk are Ratner have identified several relevant factors (30). First,
most commonly a consequence of vasospasm (65). Con the complete implementation of rCBF SPECT imaging in
sequent delayed cerebral ischemia and possible infarction the evaluation ofpatients with cerebrovascular disease will
make vasospasm an equally important factor with recur require a far more thorough interdigitization ofthe nuclear
rent hemorrhage in the morbidity or mortality of subarach medicine physician and the neurologist in evaluating, im
noid hemorrhage. Management of subarachnoid hemor proving and implementing this potentially valuable tech
rhage patients requires the differentiation of vasospasm nique. Second, purely descriptive studies, often performed
from edema, elevated intracranial pressure, hydrocephalus in isolation from a clear statement of relevant clinical
and electrolyte aberrations (66). Vasospasm is accom problems, contribute little to understanding the role of
panied by decreased rCBF, decreased cerebral metabolism, SPECT rCBF measurements in patient management or
increased neurologic deficit and increased cerebral blood enhancing the referring physician's perception of the use
volume (67,68). Davis et al. found a correlation between fulness of this technique. Prospective studies should be
regional hypoperfusion evidenced by HMPAO SPECT and designed to answer focused questions relating to issues of
the presence and severity of a delayed neurologic deficit clinical management. Finally, thorough evaluation of
in subarachnoid hemorrhage patients (69). While the pres “brainstress tests,―specifically the measurement of vaso
ence of vasospasm can be documented by transcranial dilatory reserve, is important since current clinical or
Doppler (70) or angiography, these studies only indirectly structural imaging measures are limited in their ability to
relate to the risk for cerebral infarction. Regional CBF or determine risk status. An increased recognition of the
rCBF/rCBV imaging provide a more direct measure of the importance of hemodynamic measures relative to struc
hemodynamic significance ofobserved vasospasm. By pro tural assessments ( 78) places new emphasis on the evolu
viding early evidence of cerebral ischemia, SPECT may tion of activation or intervention studies (42) which en
help to differentiate vasospasm from other causes of neu hance risk assessment. The current role for rCBF SPECT
rologic deterioration following subarachnoid hemorrhage imaging in cerebrovascular disease can only be recognized
and thus enhance delivery of therapeutic measures de and expanded through careful cooperative efforts between
signed to reduce its effects. the nuclear medicine and neurological communities.

1892 The Journal of Nuclear Medicine•

Vol.33 •
No. 10 •
October 1992
@ c@
@ D@ b@ip A . .
@ 01Tc-I@

@ I—
@M.PAO

@ 3, t@ t@\j@

FIGURE4. Three-dimensionalsurface-renderedimages
showing a right frontopanetal resting rCBF deficit with expansion
following vasodilation with Diamox in a stroke patient. The differ
ence in affected areas in the resting and vasodilated studies
@.
representstheareaof failedvasodilatoryreserve.

@ DEMENTIA t@ p
Alzheimer'sDisease
Approximately halfofthe patients presenting with early FIGURE 5. Technetium-99m-HMPAO
SPECT usingthe high
resolution
ASPECTsystem.Bilateral
temporoparietal
perfusion
clinical symptoms of dementia cannot be accurately diag defects in a patient with Alzheimer's disease. Axial(A)and sagittal
nosed by clinical criteria. Early diagnosis is important (B) planes.
because dementia-like symptoms may mask reversible
conditions, such as depression, or treatable diseases, such
as vascular dementia. Furthermore, early diagnosis of Alz While bilateral posterior cortical defects are highly pre
heimer's disease can avoid the financial and emotional dictive in Alzheimer's disease, this scintigraphic pattern
drain that often occurs if the time to final diagnosis is has also been described in patients with vascular dementia
needlessly delayed. (91), Parkinson's disease (94,95), mitochondrial ence
Brain perfusion SPECT is useful in the diagnostic eval phalomyopathy (96), hypoglycemia (97) and carbon mon
uation of patients with memory and cognitive abnormali oxide poisoning (97). The scintigraphic pattern of Parkin
ties (79). Initial clinical studies comparing patients with son's disease with dementia cannot be distinguished from
Alzheimer's disease and normal control subjects (80—87) that of Alzheimer's disease by visual assessment alone.
or patients with multi-infarct dementia (88—91)found that While Parkinson's disease patients with dementia have a
SPECT is highly accurate. In severely impaired patients, variety of scintigraphic patterns, the most common in
sensitivity is 95% or greater ( 79,83). The sensitivity of volves the temporoparietal cortex (94,95).
SPECT in the classification of mildly impaired patients is The reduced tracer uptake in the posterior association
also high, with rates reported between 80% and 87% (79, cortex in patients with Alzheimer's disease is probably due
86,92). to multiple factors, including reduced rCBF, decreased
The predominant finding ofbilateral posterior temporal cortical thickness in the temporoparietal cortex (98) and
and parietal perfusion defects in these patients is highly a reduced number of neurons in the affected areas (99).
predictive of Alzheimer's disease (Fig. 5). In a prospective Most of the reduced tracer activity is due to reduced
study of over 100 patients with memory loss, bilateral regional blood flow, however, particularly in early disease
posterior association cortex defects were detected with (100). In any case, the combined effect of flow reduction
99mTcHMPAO SPECT in 65% of the patients with Alz and atrophy serve to increase the diagnostic sensitivity of
heimer's disease (93). This pattern, with or without addi the test, and atrophy corrections are probably not war
tional association cortex defects, has a predictive value of ranted for routine applications.
over 80% for the diagnosis of Alzheimer's disease. Patients with Alzheimer's disease can present with other

Functional Brain SPECT •

Holman and Devous 1893
@ I .

scintigraphic patterns, although they are less frequent than AIDS Dementia Complex
bilateral posterior cortical defects (93). Unilateral tempo The early clinical signs of AIDS dementia complex
roparietal defects are not predictive either for or against (ADC) or HIV encephalopathy are often subtle and may
Alzheimer's disease. With 99mTc@HMPAO,unilateral pos be indistinguishable from depression, psychosis or focal
tenor defects are seen in 15%—20%of patients with Alz neurologic disease. Since treatment such as zidovudine
heimer's disease (93), significantly more than with [1231] (AZT) can improve cognitive function in ADC, its early
IMP (80). Consequently, vascular dementia involving the detection is important. Computed tomography (CT) and
posterior branches of the middle cerebral artery may re magnetic resonance imaging (MRI) play a role in diagnos
semble Alzheimer's disease when the latter presents as a ing focal neurologic disease, such as infection or tumor,
unilateral pattern. but are nonspecific for ADC. Brain perfusion SPECT is
Some investigators recognize dementia of the frontal highly sensitive for the detection ofADC (102—104).Early
type as an entity separate from Alzheimer's disease (92), disease is easily separated from normal subjects and non
with the former presenting with personality and behavioral HIV psychoses (105—106).The perfusion pattern is usually
changes and with less severe memory deficits. These in described as multifocal or patchy cortical and subcortical
vestigators find that the two dementias can be distin hypoperfusion. With high-resolution SPECT, we found a
guished scintigraphically, with bilateral frontal or fronto high incidence of cortical defects in ADC, which are most
temporal deficits characteristic of frontal lobe dementia. frequent in the frontal, temporal and parietal lobes (107)
Frontal dementia is considered by many to be a subset of (Fig. 6). Background activity is high, involving more than
Alzheimer's disease. In either case, bilateral frontal deficits halfofthe patients in our series. Basal ganglia involvement
by themselves are not diagnostic and are seen in patients is also frequent. A high number of patients have focal
with schizophrenia, depression, progressive supranuclear areas of increased activity as well. The perfusion pattern
palsy (usually with basal ganglia involvement) and Pick's improves with ADC therapy (105). Brain perfusion
disease as well as in Alzheimer's disease and/or frontal SPECT should be applied cautiously in patients with sus
lobe dementia. pected ADC because an identical brain perfusion pattern
The probability of Alzheimer's disease with normal is seen among chronic cocaine polydrug users (107). It is
perfusion or with perfusion defects outside the temporo also not clear whether the perfusion pattern is limited to
parietal cortex is low. The predictive value of a normal ADC or may be seen with nonspecific changes such as
scan depends on the clinical setting. When patients are white matter pallor, astrocytic proliferation and mononu
well screened before referral for SPECT, few of them will clear infiltration which are present in almost all AIDS
be without central nervous system disease. In our experi patients. It may not matter since SPECT imaging may
ence, when patients are screened by a memory disorder prove to be an indicator ofthe severity ofbrain dysfunction
clinic, the negative predictive value of a normal study is and therefore may be quite useful in planning therapy and
about 80%. The predictive value will increase as more in evaluating its effectiveness.
normal patients are included in the population.
EPILEPSY
VascularDementia Functional brain imaging with either SPECT or PET is
Vascular dementia is related to a number of distinct now a well-established technique to localize the epileptic
underlying diseases (101). Binswanger's disease or subcor focus in patients with refractory complex partial seizures
tical atherosclerotic encephalopathy involves the microcir
culation, presents as white matter disease and is attributed
@ to atherosclerosis of penetrating cerebral arteries. Multi ‘.@4 s@
infarct dementia involves the large vessels and results from
large cerebral infarcts. A third disease, a form of multi
infarct dementia but not usually involving large-vessel
occlusion, results from multiple small, deep, subcortical
lacunar and pericapsular infarctions. Mixed forms of these
three vascular diseases often occur. Technetium-99m-
HMPAO SPECT appears reasonably accurate for distin
guishing vascular dementia from Alzheimer's disease when
bilateral temporoparietal defects are present (82,83). The
scintigraphic pattern of multi-infarct dementia is usually
described as multiple asymmetrical perfusion defects, often
involving the primary cortex and deep structures. Vascular
dementias which involve the subcortical structure are as FIGURE6. Technetium-99m-HMPAO
SPECT(axialplanes).
sociated with patchy or diffuse patterns of blood flow Multiple small perfusion defects throughout the cerebral cortex
reduction. in a patient with AIDS dementia complex.

1894 The Journal of Nuclear Medicine•

Vol.33 •
No. 10 •
October1992
(108). From 30% to 60% ofpatients with complex partial TLE Interictal HypprIo@
seizures ultimately become refractory to medical treatment
and may be referred for surgical removal of a discrete
seizure focus. Since most complex partial seizures arise
from temporal lobe foci (109), temporal lobectomy is the
appropriate surgical therapy. Successful excision of well
localized foci leads to elimination of seizures or signifi
cantly improved pharmacologic control in 80% of surgical
patients (110). Traditionally, localization has been per
formed with scalp, cortical or depth EEG. However, scalp
EEG may be misleading in the localization of the primary
site of seizure onset because it has inherently low spatial
resolution and is fundamentally dependent upon primarily
cortical surface effects. Surface electrocorticography is also
limited by the area of brain sampled and its sensitivity to
and localization of deep-lying generators. Depth EEG can
RD 2BWF
monitor deeper structures but samples only limited regions
ofbrain. Both corticography and depth EEG are extremely FIGURE7. Interictalrighttemporallobehypoperfusion in a
invasive and present a surgical risk. Ward has reported patient with temporal lobe epilepsy (TLE)on transverse and
that in the United States there are 50,000 patients with coronalslicesusing[123l]IMP.The asymmetryof temporallobe
medically refractory complex partial seizures possibly ben perfusion is typical of the interictal state in such patients.
efiting from temporal lobectomy (11 1). Of these, only
approximately 500 per year receive surgery, partially due tion (Fig. 7). Rowe et al. (133) studied 32 patients with
to the difficulty of adequate focus localization. HMPAO, 30 of whom had temporal lobe localization by
Interictal SPECT rCBF imaging is the most convenient ictal EEG; 18 of 30 patients had focal hypoperfusion at
and cost-effective technique for the localization of a tem the site ofthe EEG focus interictally. Devous et al. studied
poral lobe focus in adult patients with medically refractory 38patients
witheitherIMPorHMPAO
interictally,
and
complex partial seizures. Studies to date would suggest in those patients with EEG-identified foci, approximately
that, when an area of focal temporal lobe hypoperfusion 75%hadinterictalhypoperfusion
(134).
is observed, the need for further studies is minimal (partic Ictal Studies. HIPDM and IMP can be effectively used
ularly if scalp EEG is concordant). for ictal studies as long as careful EEG monitoring is used
to document seizure onset (Fig. 8). In the postictal phase,
Partial Complex Seizures cerebral blood flow decouples from glucose metabolism;
Interictal Studies. Interictal PET studies of glucose me
rCBF remains elevated (127,135), while glucose metabo
tabolism have consistently demonstrated that approxi
mately 70% of patients with complex partial seizures have
discrete foci of hypometabolism and that these sites may ThE Ictal Hyperperfusioii
occur in more than one brain region in the same patient
(112—121).There is a strong correlation between the area
of hypometabolism and the site of electrophysiologic ab
normality determined by a combination of electrophysio
logic data. I
In rCBF studies employing ‘33Xe SPECT, only 50%
demonstrate interictal hypoperfusion (122-124). Most
often, hypoperfusion is found at the site of the EEG
abnormality, but flow deficits are also seen in other remote
areas. No specific type of EEG abnormality is associated
with reduced rCBF; equal flow reductions were seen in the
presence of focal spiking alone, focal spikes and slowing
and focal slowing alone (125). The first high-resolution
interictal scans with SPECT employed [‘231]IMPand
HIPDM (126—129).More recently, interictal scans have
RD 28WF
been obtained with @mTc@HMPAO by a variety of inves
tigators (130—134).Interictal SPECT findings with the FIGURE8. Hyperperfusion
oftherighttemporal
lobeisshown
during an ictus in a patient with temporal lobe epilepsy (TLE).
iodinated amines and @mTc@HMPAO show a frequency of This is the same patient shown in the interictal state in Figure 7.
abnormal interictal hypoperfusion (70%—75%) similar to Note the reversal in asymmetry documenting seizure localization
PET studies and excellent correlation with EEG localiza to the right temporal lobe.

Functional
BrainSPECT•
HolmanandDevous 1895
lism declines rapidly (118). In addition, secondary gener functional brain imaging. By far, the most common path
alization may occur. Ictal studies with iodinated agents ologic finding is mesial temporal sclerosis, which is thought
have been more successfulin identifying seizurefoci than to be the consequence of an older lesion now manifested
interictal studies (126,128,129,134). Unfortunately, true as a gliotic scar (143). A review ofSPECT and PET studies
ictal studieswith HMPAO are nearly impossibleto obtain demonstrates a 34% incidenceof focalMRI abnormalities
because this compound is unstable in vitro, leading to and a 17% incidence on CT. This is contrasted to a 71%
delays between seizure onset and injection of 5—20mm. incidence of focal EEG changes and a 59% incidence of
In the study by Rowe et a!., 22/30 patients with focal EEG focal abnormalities on interictal functional imaging meas
findings showed increased postictal HMPAO uptake at the ures (108). A few studies demonstrate a close relationship
site of the EEG focus (133). These data suggest that early between the severity of interictal ICBF reductions and
postictal studies (within 5 mm) may be as effective as true eitherclinicalsymptomatologyor cognitiveimpairment
ictal injections. (144). Homan et al. compared SPECT and neuropsycho
In a recent review, the combination ofall EEG data was logical assessments in 50 patients with partial seizures
localizing in 71 % of the patients (108). By contrast, func (145). Even though rCBF and neuropsychological deficits
tional imaging (SPECT or PET) was localizing in 59% of were relatively mild in many patients, at least one low
the interictal studies and 65% of ictal studies. These data flow region matched an area of neuropsychologically im
suggest that ofthe patients with EEG-localized seizure foci, paired function in 43 ofSO patients. There was a significant
79% were equally well localized by functional brain im correlation between areas of visually identified hypoper
aging. It is interesting to note that the localizing power of fusion and neuropsychological impairment (p < 0.001).
interictal functional imaging is not substantially different Stepwise discriminate function analyses revealed predic
between SPECT and PET, nor is it significantly different tive relationships between deficits on specific neuropsy
between IMP, HIPDM and HMPAO. chological tests and visually identified hypoperfusion, par
ticularly in the left and right temporal regions. Similar
PrimaryGeneralizedSeizures
data were reported by Berent et al. (146).
There are few data concerning functional abnormalities
in generalized seizures (12,136—138). These results are Pediatric Studies
consistent with the failure of surface or depth EEG or Seizures in children may result from a variety of under
structural imaging modalities such as CT and MRI to lying pathologies. There may be no relationship between
definea specificanatomicregionof seizureoriginin these clinical symptoms and either electrographic or radio
patients (139). Leroy et al. did not detect quantitative graphic findings, and the patients often have unpredictable
asymmetries in rCBF (137) and Theodore et al. found no courses. Functional brain imaging could be useful in un
significant differences in glucose metabolic rates (136). derstanding clinical pleomorphisms associated with partic
ular diseases, or as a device for subcategorizations useful
FrontalLobe Seizures
in predicting progression. Unfortunately, there are only
In recent years, there has been increased interest in
seven published studies concerning functional brain im
partial seizures originating from areas other than the tem
aging in pediatric epilepsy, excluding case reports and
poral lobe (140). Frontal lobe seizures have been difficult
abstracts. Six of these involve PET (147—152)and one is
to localize using standard EEG technique, and stereotactic
an IMP SPECT study (153). The only clear conclusion
depth electrodes have not proven to be as beneficial for
that may be drawn is that more work needs to be done. It
localizing the site of the seizure origin as in temporal lobe
is likely, given the adult experience and the limited pedi
seizures. The results ofsurgical treatment of extratemporal
atric results, that functional brain imaging abnormalities
partial seizures has been disappointing in comparison to
will precede structural signs in infants and will likely
the results of temporal lobe surgery. Functional imaging
provide an insight into observed seizure activity. The
holds promise for localization of the site of extratemporal
limited studies available for review suggest of a prognostic
seizures, but limited data currently exist. It appears that
as well as a diagnostic role for functional brain imaging in
60%—70%of subjects with proven extratemporal seizures
pediatric patients, but such a role is not yet established.
demonstrate hypometabolism interictally (141). These hy
pometabolic areas appear widespread and are less localized PRIMARY BRAIN TUMORS
than in temporal lobe seizures.
Malignant gliomas carry a dismal prognosis due to their
Structural,Clinicaland CognitiveCorrelations aggressive biological behavior. Newer treatment modali
Patients with partial and secondarily generalized sei ties, however, including radiosurgery and brachytherapy,
zures are much more likely to have structural abnormali have resulted in increased local control and survival rates
ties observable on CT or MRI than patients with primary (154). With aggressive treatment, an increasing number of
generalized tonic-clonic seizures or absence attacks (142). patients will present with symptoms and signs that may
It is not always true that abnormalities detected on struc be secondary to recurrent tumor or to radiation changes
tural imaging studies are correlated with the seizure focus alone. Establishing the cause of clinical deterioration in
defined by clinical or EEG criteria or, for that matter, with malignant glioma patients treated with high dose radiation

1896 The Journal of Nudear Medicine•

Vol.33 •
No. 10 •
October1992
 is necessary for determining appropriate management. PSYCHIATRIC DISEASE
Progressive radiation necrosis requires surgical debulking, SPECT applications in psychiatric disorders are not yet
while solid tumor recurrence may require adjuvant ther clinically useful. We have not yet discovered diagnostic or
apy. CT and MRI are nonspecific and cannot distinguish prognostic functional abnormalities in the major psychi
radiation necrosis from treated tumor (155,156). Even atric diseases. However, SPECT may be of value in iden
CT-guided biopsy may be unreliable. While PET has been tifying unsuspected functional lesions. SPECT may also
useful to assess tumor viability and to differentiate recur be useful to rule out organic complications not evident on
rent glioma from radiation change (15 7), it is not readily other diagnostic tests. Promising research into mood dis
available in most medical centers. orders, schizophrenia and anxiety disorders suggests that
Thallium-20l localizes in primary and metastatic brain diagnostic and prognostic roles for SPECT may soon
tumors (158). Its mechanism of uptake is unknown, but emerge.
may involve transmembrane transport into viable tumor
cells (159). When 201Tl tumor uptake was compared to Depression
activity in the contralateral hemisphere, high-grade Twenty studies in the last 10 years found alterations in
gliomas were differentiated from low-grade lesions (160, cerebralperfusionor metabolismin depressedsubjects
161). Since this distinction has both prognostic and ther (164-183). Others have reported on effects of medication,
apeutic implications, preoperative 201TlSPECT may aid electroconvulsive therapy and cognitive tasking in such
in the timing of biopsy or surgery. patients (184—188).Unfortunately, findings are inconsist
Combined 2oI'fl/99mTcHMPAO SPECT is useful for ent. There are numerous reasons, including error due to
discriminating radiation changes from tumor necrosis as small samples, variations in age and gender distribution,
the cause of clinical deterioration in patients with malig diagnostic heterogeneity, study conditions, severity of
nant glioma who have also been treated with high dose depression, and medication status. However, there are
radiation. While 20Tl-chloride scintigraphy is highly sen consistent indications ofreduced global blood flow (gCBF)
sitive for identifying recurrent tumors (162), in our expe or glucose metabolism (gCGM), particularly in patients
rience it is insufficiently specific to be clinically useful by with major depressive disorder (MDD), and possible re
itself (163). When combined with 99mTcHMPAO how ductions in the basal ganglia in both bipolar depressed
ever, three patterns of uptake can be identified. High phase (BP) and MDD samples. There are also suggestions
thallium activity (a tumor-to-scalp ratio of greater than ofalterations in the anterior-to-posterior gradient. Studies
3.5) is highly predictive of solid tumor recurrence in these have reported a relationship between cerebral biochemistry
patients (Fig. 9). When the thallium activity ratio is mod and symptom severity. Baxter recently suggested an emerg
erateor low (lessthan 3.5) and 99mTcuptakeis alsolow ing consensus for involvement oflateral prefrontal cortex,
(less than 50% ofcerebellar activity), the likelihood of solid noting decreased rCGM in lateral prefrontal cortex in
tumor recurrence is low. In those patients with moderate depression and elevated rCGM in orbital cortex in obses
thallium uptake and high perfusion, SPECT is not predic sive-compulsive disorder (OCD) (189). While some con
tive of either tumor or reactive tissue. This method may ceptual consensus is developing, firm conclusions would
also prove useful for identifying the appropriate target for be premature. For example, striatal abnormalities, while
stereotactic biopsy excision or ablation once the SPECT reportedfor both disorders,have not been consistently
and structural image are accurately merged (25). identified.
One explanation for the diversity of findings seen in the
existing literature is that no single region of the brain
.‘@. , distinguishes depressed individuals from controls or is
consistently related over time to the symptomatology ob
J@j‘%@,. “@j
served in depression. For example, Sackeim et al. found
that an interacting network of regions explained the top
ographic distinctions between their BP patients and nor

(@@_) mal controls and that these regional effects existed sepa
rately from global alterations (181 ). Also, Devous et al.
recently compared ‘33Xe SPECT in rCBF in 48 sympto
matic MDD patients (13 nonendogenous, 24 endogenous

(. I •@
(‘ (.-@ :‘ and 11 psychotic) to 48 age- and gender-matched normal
controls (188). Results revealed a significant age-by-de
@ [email protected] t\11@@1_) @: _@ pressive subtype interaction for gCBF and for rCBF ratios.
Age effects on rCBF differed not only by region but also
FIGURE 9. Thallium-201SPECT (axial planes).Horseshoe among the three diagnostic subtypes. These findings of age
shapedregionof high20111 uptakein a patientwith a recurrent
glioblastoma in the right temporal lobe following surgery and effects among depressive subgroups are only one indication
brachytherapy. ofthe heterogenous nature ofthe population. For example,

FunctionalBrainSPECT •
Holmanand Devous 1897
the notion of global reductions in cerebral blood flow in Technetium-99m-HMPAO SPECT has been shown to be
depression has been both supported and opposed. Such a more sensitive than CT in detecting abnormalities in pa
diversity of results may be explained by examining the tients with a history oftraumatic brain injury, particularly
endogenous/nonendogenous and psychotic/nonpsychotic in the minor head injury group (223). Thus, 42 patients
patient mixtures in each study. (80%)showed
rCBFdeficits
withSPECT
compared
with
29 patients (55%) with CT. In addition to its higher
ObsessiveCompulsiveDisorder sensitivity, SPECT reflects changes in perfusion at an
PET studies have revealed abnormalities in glucose met earlier time than CT (224). In a preliminary study, patients
abolic rates in obsessive compulsive disorder (OCD) pa
with large lesions, multiple defects and lesions involving
tients, but the implicated areas vary from study to study.
the brain stem appeared to have a worse prognosis than
Baxter et al. have found increased metabolism in the those patients with nonfocal, small lesions, particularly if
caudate nuclei, orbital gyri, hemispheres and orbital gyrus
they involved frontal or occipital lobes. SPECT may also
to-hemisphere ratio bilaterally ( 190, 191 ). Nordahl et al.
predict the degree ofpermanent damage and those patients
did not report global, hemispheric or caudate abnormali
who will develop post-traumatic headache (225). Roper et
ties, but did find increased orbital frontal metabolism
al. has shown that with HMPAO SPECT some patients
bilaterally and decreased right parietal and left parieto
with traumatic brain injury may have cerebral blood flow
occipital metabolism in OCD as compared to normals
equal to that of surrounding brain (226). This informa
(192). Another conflicting study reports increased metab
tion may be of prognostic value or may simply indicate
olism in the right prefrontal cortex and in the left anterior
luxury perfusion with disassociation between metabolism
cingulate (193). A 33Xe SPECT study in 14 OCD patients
and flow. At this point, the number of studies of SPECT
found significantly lower mean blood flow, but no regional
and traumatic brain injury are small and involve only a
differences between OCD and matched normals (194).
few patients, but this application appears promising.
Similarly, Nordahl et al. found lower glucose metabolic
rates in OCD than in normal controls in most brain
regions. NEURORECEPTOR IMAGING
Neuroreceptor imaging now plays a very limited role in
Schizophrenia clinical practice. Early clinical trials and the much larger
Recent reviews suggest that SPECT and PET, as well as PET experience suggest that useful applications will
the nonimaging ‘33Xe
inhalation probe technique, provideemerge and that a wide spectrum of radioligands will
evidencefor frontallobedysfunctionin certainsubtypes become available. SPECT ligands have been developed for
ofschizophrenia (195,196). While hypofrontality has been muscarinic cholinergic receptors (‘231-3-quinuclidinyl-4-
reportedfrequently(197—200), not all investigators
have iodobenzilate, IQNB), the dopamine D-2 receptors ([1231]
observed it (201—203). Inconsistent findings have been iodobenzamide, IBZM), the serotonin-2 receptor ([123!]
attributed to variability in study populations with regard iodoketanserin) and the benzodiazepine receptor (‘23I-Ro
to age, duration of disease, clinical state, subtyping (espe 16-0154m, lomazenil).
cially along the paranoid/nonparanoid dimension) and The dopaminergic system plays an important role in
medication status (204-208). Frontal lobe dysfunction the coordination ofnormal brain function and is a primary
may be more evident during the performance of cognitive action site for neuroleptic drugs for treating schizophrenia
tasks designed for frontal lobe activation (197,199,207, and Parkinson's disease. Furthermore, a number of central
209—213). Hypofrontality also appears to be associated nervous system diseases, including schizophrenia, tardive
with the negative symptoms of schizophrenia (195,199). dyskinesia, Parkinson's disease and Huntington's chorea,
Temporal lobe abnormalities have also been reported (199, are associated with changes in dopamine receptor density
209,214). The combination ofboth anterior and posterior in the brain. Iodine-l23-IBZM has been imaged in humans
functional alterations is often expressed as an abnormality and has a distribution similar to that of positron-labeled
in the anterior/posterior gradient. Buchsbaum et al. and D-2 receptor antagonists with localization primarily in the
others have also reported subcortical abnormalities, partic basal ganglia (227).
ularly on the left side (198,203,21 7—221).Generalized left lomazenil is a specific ligand for benzodiazepine recep
hemispheric dysfunction (laterality) has also been reported tors in the human brain (228). The highest concentration
(195,203,204,222). ofthis receptor antagonist is in the medial occipital cortex.
lomazenil distribution is altered in partial epilepsy and, in
HEAD INJURY early qualitative imaging studies, appears to be abnormal
Traumatic brain injury has an overall incidence similar even when perfusion studies are normal.
to that of stroke, with a particularly high mortality in the Iodine-l23-IQNB studies of muscarinic acetylcholine
first 48 hr post-trauma (223). Proper management of these receptor binding in patients with Alzheimer's disease result
patients requires an accurate assessment of underlying in images which are similar or less abnormal than images
brain function and, consequently, emission computed to of perfusion in the same patients with Alzheimer's disease
mography has been investigated as a possible monitor. (229,230). Studies of the muscarinic acetylcholine system

1898 The Journal of Nuclear Medicine•

Vol.33 •
No. 10 •
October1992
are currently limited by nonspecific ligands such as IQNB, potential as a diagnostic tool will emerge only when clearly
which label most or all of the muscarinic receptor sites defined applications demonstrate scintigraphic findings
and cannot differentiate presynaptic from postsynaptic which facilitate critical management decisions. Such ap
binding. plications are now beginning to emerge (Table 1) and
A number of problems will have to be overcome if more will become evident as well-designed clinical trials
SPECT imaging is to play an important role in the assess of efficacy and patient outcome establish its utility (Table
ment ofneurotransmitter function. High spatial resolution 2). Functional tests such as perfusion SPECT require care
will be necessary to quantify absolute tracer concentration. ful and imaginative investigations to determine the proper
While receptor affinity can be determined from relative diagnostic role of the physiological information that they
measurements ofradioactive concentrations (231), careful provide as well as close cooperation between nuclear med
modeling will be necessary to account for radiotracer icine physicians and their clinical colleagues to assure that
kinetics and the effect ofblood flow on tracer distribution. the most relevant clinical questions are being answered.
It is possible, however, that scintigraphic imaging alone Properly approached, functional SPECT provides a unique
may provide enough information to be diagnostically use window to explore the hemodynamic and biochemical
ful, as it has been with perfusion imaging. Furthermore, consequences of diseases that affect the brain.
many neurotransmitters bind to a family of receptors.
Unless ligands are developed for specific receptor sites, the
full value of this method will not be realized.
REFERENCES
1. KuhI DE, Barrco JR. Huang SC, et al. Quantifying local cerebral blood
CONCLUSION flow with N-isopropyl-p-I-l23iodoamphetamine (IMP) tomography.J
NuciMed 1982;23:196—203.
Substantial literature has emerged over the past decade 2. Winchell HS, Baldwin RM, Lin TH. Development of 1-123-labeled
charting potentially powerful applications of functional amines for brain studies:localizationofl-123 iodophenyalkylamines in
rat brain. JNucIMed 1980,2l:947—952.
brain SPECT in cerebrovascular disease, dementia, epi
3. Hill IC, Holman BL, Lovett R, et at. Initial experiencewith SPECT
lepsy, cancer and psychiatric disease. Nevertheless, its full (singlephoton emissioncomputerizedtomography)ofthe brain usingN-
isopropyl 1-123 p-iodoamphetamine. J NuciMed l982;23:l91—l95.
4. Holman BL,LeeRGL, HillIC, LovetiRD. Lister-Jamesi.A comparison
TABLE I oftwo cerebral perfusion tracers. N-isopropyl.l-123 p-iodoamphetamine
WidelyAcceptedUsesof BrainSPECT and 1-123HIPDM in the human. JNuclMed 1984;25:25—30.
5. ElIPJ,Hocknell
JML,JarrittPH,cial.ATc-99m-labeled
radiotracer
for
Alzheimer's
disease the investigation of cerebral vascular disease. Nuci Med Commun 1985;
Acutestroke 6:437—441.
Transient
ischemic
attacks 6. Anderson AR, Friberg H, Knudsen KMB, et al. Extraction of Tc-99m-
Epilepsy d,l,HM-PAO across the blood-brain barrier. I Cereb Blood Flow and
Recurrent primarytumor Metab 1988;8:S44—ssl.
Headtrauma 7. Neirinckx RD. BurkeJF, Harrison RC, ForsterAM, Andersen AR, Lassen
NA. The retention mechanism ofTc-99m HMPAO: intracellular reaction
with glutathione. I Cereb Blood Flow Metab l988;8:S4—S12.
8. Moretti J-L, Defer 0, Cinoni L, et al. “Luxury-perfusion―
with Tc-99m-
HMPAO and 1-123-IMPSPECT imagingduring the subacute phase of
TABLE 2 stroke. EurJ NuclMed l990;16:17—22.
Potential Applicationsof Brain SPECT 9. Holman BL,HellmanRS,GoldsmithSi, etal. Biodistribution,dosimetry,
Cerebrovascular
disease and clinical evaluation of technetium-99m ethyl cysteinate dimer in
Delineation of stroke subtypes normal subjectsand in patients with chronic cerebralinfarction.I Nucl
Med 1989;30:1018—l025.
Cerebrovascularreserve 10. Walovitch RC, Hill TC, Garrity ST, et al. Characterization of technetium
Strokeprognosis 99m-l, I-ECD for brain perfusion imaging. Part I. Pharmacologyof
Strokerisk technetium-99m ECD in non-human primates. J NucI Med l989;30:
Subarachnoid
hemorrhage
prognosis 1892—1901.
Dementia I 1. Obrist WD, Thompson HK, Wang HS, Wilkinson WF. Regional cerebral
AIDS dementia complex blood flow estimated by xenon-l33 inhalation. Stroke 1975;6:245—256.
Huntington'sdisease 12. Devous MD Sr. Stokely EM, Bonte Fi. Quantitative imaging of regional
Dementiaseverity, prognosis and treatment cerebralblood flowby dynamic single-photontomography.In: Holman
Psychiatric
disease BL, ed. Radionuclidelmaging ofthe Brain. New York: Churchill Living
stone; 1985:135—162.
Schizophrenia
13. Kimura K, Hashikawa K, Etani H, et aL A new apparatus for brain
Depression imaging four-headrotatinggamma camera single-photonemissioncorn
Anxietydisorders puted tomography.J NuclMed 1990;31:603-609.
Parkinson's disease 14. RogersWL, Clinthorne NH, StamosJ, et al. Performanceevaluationof
Substance abuse SPRINT, a single-photon ring tomograph for brain imaging. I NucI Med
CNS involvementin systemic disease l984;25: 1013—1018.
Chronicfatiguesyndrome 15. Kanno I, Uernura K, Miyura S, Miyura Y. HEADTOME: a hybrid
Lupus emission tomograph for single-photon and positron emission imaging of
Others the brain. J Co,npuzAssistTomogr1981;5:2l6—226.
16. Stoddart HF, Stoddart HA. A new developmentin single-gammatrans.
Pharmacologicand cognitivechallenge tests
axial tomography. Union Carbide focused collimator scanner. IEEE

Functional Brain SPECT •

Holman and Devous 1899
 Trans NuclSci l979;26:2710—2712. 42. Tikofsky RS, Hellman RS. Brain single photon emission computed
17. Kirsch C-M, Moore SC, Zimmerman RE, English Ri, Holman BL tomography:New activation and intervention studies.Semin NuclMed
characteristics of a scanning, multidetector, single-photon ECT body 199I;21:40—57.
imager.JNuclMed 198l22:726—73l. 43. Bonte FJ, Devous MD Sr. Reisch JS. The effect of acetazolamideon
18. HillIC, StoddartHF, DohertyMD, AlpertNM, WolfeAP.Simultaneous regionalcerebralblood flow in normal human subjectsas measuredby
SPEd acquisition ofCBF and metabolism. JNuclMed 198&,29:876. single photon emission computed tomography. Invest Radio! l98&,23:
19. DevousMD Sr,BonteFJ. Initialevaluationofcerebralbloodflowimaging 564—568.
with a high-resolution, high-sensitivity three-headed SPECT system 44. Heiss W, Zeiler K, Havelec L, Reisner T, Bruck J. Long-term prognosis
(PRISM).J NuclMed 1988;29:912. in stroke related to cerebral blood flow. Arch Neurol l988;34:671—676.
20. Logan KW, Holmes RA. Missouri University Multiplane Imager 45. Nagata K, Yunoki K, Kabe S. Suzuki A, Araki 0. Regional cerebral
(MUMPI):a high sensitivityrapid dynamic ECI' brain imager.J NucI blood flow correlates of aphasia outcome in cerebral hemorrhage and
Med 1984,25:P105. cerebral infarction. Stroke l986;l7:417—423.
21. Smith AP, Genna S. Imagingcharacteristicsofa single-crystal ring camera 46. Kushner M, Reivich M, Fieschi C, et al. Metabolic and clinical correlates
for dedicatedbrain SPECT.J NuclMed 1989;30:796. ofacute ischemic infarction. Neurology l987;37:l103—ll10.
22. Holman BL, Carvaiho PA, Zimmerman RE, etal. Brain perfusion SPECT 47. Defer 0, Moretti JL, Cesaro P, Sergent A, Raynaud C, Degos JD. Early
using an annular single crystal carnera initial clinical experience. I NucI and delayedSPECTusingN-isopropylp-iodoamphetamineiodine-123in
Med l990;3l:l456—l46l. cerebral ischemia. A prognostic index for clinical recovery. Arch Neurol
23. Holman BL, Zimmerman RE, Johnson KA, et al. Computer-assisted l987;44:7l5—7l8.
superimposition of magnetic resonance and higJ-resolution technetium 48. Lee RGL, Hill TC, Holman BL, Royal HD, O'Leary DH, Clouse ME.
99m-HMPAO and thallium-20l SPECT ofihe brain. J NucI Med 1991; Predictive value of perfusion defect size using N-isopmpyl-(I-23)-p-io
32:1478—1484. doamphetamine emission tomography in acute stroke. I Neurosurg 1984;
24. DevousMD Sr, Gassaway5K. SimultaneousSPECTimagingof Tc-99m 61:449—452.
and 1-123-labeled brain agents in patients using the PRISM@ scanner. J 49. Demeurisse0, VerhasM, Capon A, Paternot 3. Lack ofevolution of the
NuclMed l990;31:877. cerebral blood flow during clinical recovery ofa stroke. Stroke 1983;l4:
25. Devous MD Sr, Payne JK, Lowe JL. Dual-isotope SPECT imaging of 77—81.
resting TCBF and cerebrovascular reserve [Abstract]. J NucI Med 1991; 50. HaymanLA,TaberKH,JhingranSO,KillianJM,CarrollRG.Cerebral
32:972. infarction.Diagnosisandassessmentofprognosisbyusing‘231MP-SPEC1'
26. Hellman as, TikofskyRS. An overviewofthe contributionsof regional and CT. AJNR 1989;10:557—562.
cerebral blood flow studies in cerebrovascular disease. Is there a role for 51. Vallar 0, Perani D, Cappa SF, Messa C, Lenzi GL, Fazio F. Recovery
single photon emission computed tomography? Semin Nuci Med 1990; from aphasiaand neglectafter subcorticalstroke:neuropsychologicaland
20:303—324. cerebral perfusion study. J Neurol Neurosurg Psychiatry l988;51:
27. A1aVi
A,HirschLI.Studiesofcentralnervoussystem
disorderswithsingle 1269—1276.
photon emissioncomputed tomographyand positronemissiontomogra 52. Mountz JM, Model JO, Foster NL, ci aL Prognostication of recovery
phy: evolution over the past two decades. Semin Nucl Med l9912l: following stroke using the comparison ofCr and technetium-99m HM
58—81. PAO SPECT.JNuclMed l990;3l:6l-66.
28. FayadPB,BrassLM.Singlephotonemissioncomputedtomographyin 53. LimburgM, Van Royen EA, Hijdra A, VerbeetenB Jr. rCBF-SPECrin
cerebrovascular disease. Stroke 199 l;22:950—954. brain infarction: when does it predict outcome? J Nucl Med l99l;32:
29. Caplan LR. Question-driventechnologyassessment SPECT as an cx 382—387.
ample. Neurology l99l;4l:l87—l9l. 54. BushnellDL, Gupta 5, MicochAG, BarnesWE. Predictionof language
30. BrassLM, Rattner Z. Singlephoton emissioncomputed tomographyin and neurologicalrecoveryafter cerebralinfarction with SPECF imaging
cerebral vascular disease. In: Weber DA, Devous MD, Tikofsky RS, eds. using N-isopropyl-(I-123)-p-iodoamphetamine. Arch Neurol 1989;46:
Workshopon Brain SPECT perfusionimaging:optimizing imaging ac 665—669.
quisition andprocessing. DOE CONF-9l 10368, 1992:77—88. 55. GiubileiF, LenziGL, DiPieroV. ci al. Predictivevalueofbrain perfusion
31. Fieschi C, Argentino C, Lenzi GL, Sacchetti ML, Toni D, Bozzao L single-photon emission computed tomography in acute cerebral ischemia.
Clinical and instrumental evaluation of patients with ischemic stroke Stroke l990;21:895—900.
within the first six hours. JNeurolPsychiazry l989;91:31 1-322. 56. Nakano5, KinoshitaK,Jinnouchi5, HiroakiH, WatanabeK.Compar
32. BoseA, PaciaSB,FayadP, SmithEO, BrassLM, HotTerP. Cerebral ativestudyofregionalcerebralbloodflowimagesbySPECTusingxenon
bloodflowimagingcomparedtoC1@duringthe initial24 hoursofcerebral 133,iodine-123IMP and technetium-99mHM-PAO.I NuclMed 1989;
infarction.Neurologyl990;40:l90. 30:157—164.
33. Podreka I, SuessE, GoldenbergG, et aL Initial experiencewith techne 57. Yonekura Y, Nishizawa S. Mukai T, et al. SPECF with (@TcJ4,l
tium-99m HM-PAObrain SPECT.I NuclMed l987;28:l657-1666. hexamethyl propylene amine oxime (HM-PAO) compared with regional
34. Dc Roo M, Mortelmans L, Devos P. ci al Clinical experience with Tc cerebral blood flow measured by PET. Effects of linearization. I Cereb
99m HM-PAO high resolution SPECT of the brain in patients with BloodFlow Metab l988;8:S82—S89.
cerebrovascularaccidents.Ear) NuciMed 1989;l5:9-l5. 58. HayashitaK,NishimuraT,ImakitaS.VeharaT. Fillingoutphenomenon
35. Lassen NA. The luxury-perfusion syndrome and its possible relation to withtechnetium-99m
HM-PAObrainSPECFat thesiteofmildcerebral
metabolic acidosis located with the brain. Lancet 19662:l 113-1115. ischemia. JNuclMed l989;30:59l—598.
36. Pantano P, Baron JC, Samson Y, BousserMG, DerouesneC, Comar D. 59. Crow W, Guinto FC Jr. LimitationsofCl' in the evaluationof transient
Crossedcerebellardiaschisis@
Further studies.Brain 1986;l09:677-694. ischemicattacks. TexMedJ 1982;78:65—7l.
37. Kushner M, A1aV1A, Reivich M, Dann R, Burke A, Robinson 0. 60. Chollet F, Celsis P, Clanet M, Guiraud CB, Rascol A, Marc VJP. SPECr
Contralateralcerebellarhypometabolismfollowingcerebralinsult:a poe study ofcerebral blood flow reactivity afteracetazolamide in patients with
itron emission tomographic study. Ann Neurol l984;l5:425—434. transient ischemicattacks.Stroke l98920:458—464.
38. Gibbs JM, Wise RSJ, Leenders KL, Jones T. Evaluation of cerebral 61. BogousslavskyJ, Delaloye-BischofA, Regli F, Delaloye B. Prolonged
perfusionreservein patients with carotid-arteryocclusion.Lancet 1984; hypoperfusionand early stroke after transient ischemic attack. Stroke
8372:310—314. l99021:40-46.
39. Bud U, Braun H, Ferbert A, Stirner H, Weiller C, Ringelstein EB. 62. Brust3CM.Transientischemicattacks:Naturalhistoryandanticoagula
Combined SPECF imagingof regionalcerebralblood flow(‘@Tc-hexa tion. Neurology197727:70l—707.
methyl-propyleneamineoxime, HM-PAO) and blood volume (@‘Tc 63. Hartmann A. Prolongeddisturbancesof regionalcerebralblood flowin
RBC) to assess regional cerebral perfusion reserve in patients with care transient ischemic attacks. Stroke l985;16:932—939.
brovascular disease. Nuklear Medizin l98827:5l—56. 64. Devous MD Sr, Baijer HH, Ajmani AK, Samson DS, Bonte FJ. SPECT
40. Devous MD Sr. Arora GD. Direct measurement of rOER, rCBF, and measurements of cerebrovascular reserve in patients with hemodynamic
ICBv define a relationship between IOER and the ICBF/TCBV ratio in risk. J NuclMed l98829:9l 1.
acute stroke.I NuclMed 1991;32(5):960. 65. Voldby B. Alterations in vasomotor reactivity in subarachnoid hemor
41. Vorstrup 5, Boysen0, Brun B, Engell HC. Evaluation of the regional rhage.In: WoodJH, ed. CerebralBloodFlow.NewYork, NY: McGraw
cerebral vasodilatorycapacity before carotid endarterectomyby the ac Hill; 1987:402—412.
cetazolamide test. NeurolRes 1987;9:lO—l8. 66. Biller J, Godersky JC, Adams HP Jr. Management of aneurysmal sub

1900 The Journal of Nuclear Medicine•

Vol.33 •
No. 10 •
October 1992
 arachnoid hemorrhage. Curr Concepts Cerebrovas Dis Stroke 1988;23: Alzheimer's disease and the dementias. Semin Nuc Med l990;20:
13—18. 342—352.
67. Powers Wi, Grubb RL Jr. Baker RP, Mintun MA, Raichle ME. Regional 93. HolmanBL,JohnsonKA,GaradaB,CarvaihoPA,SatlinA.Thescinti
cerebral blood flow and metabolism in reversible ischemia due to vaso graphic appearance of Alzheimer's disease: a prospective study using
spasm. Determination by positron emission tomography. J Neurosurg technetium-99m HMPAO SPEC1'. JNuclMed l992;33:l8l-l85.
1985;62:539—546. 94. Pizzolato G, Dam M, Borsato N, et al Tc-99m-HM-PAO SPECT in
68. Grubb RL, RaichleME, EichlingJO, Gado MH. Effectsof subarachnoid Parkinson'sdisease.I CerebBloodFlowMetab 1988;8:SlOl—S108.
hemorrhageon cerebralblood volume,blood flowand oxygenutilization 95. NageliS, IchiseM, HolmanBL.Thescintigraphicevaluationof Hunt
in humans. I Neurosurg l977;46:446—453. ington'sdiseaseand other movementdisordersusingsinglephoton emis
69. Davis 5, Andrews J, Lichtenstein M, et al. A single-photonemission sion computed tomography perfusion brain scans. Semin NuclMed 1991;
computed tomography study of hypoperfusion after subarachnoid hem 21:11—23.
orrhage.Stroke 1990;21:252—259. 96. Grunwald F, Zierz 5, Broich K, Schumacher 5, Bockisch A, Biersack Hi.
70. Caplan LR, Brass LM, DeWitt LD, et al. Transcranial Doppler ultra HMPAO-SPECT imaging resembling Alzheimer-type dementia in mito
sound. Present status. Neurology l990;40:696—700. chondrial encephalomyopathywith lactic acidosisand stroke-like episodes
71. Samson D. Surgical treatment of intracranial arteriovenous malforma (MELAS). JNuclMed 1990;31:l740—1742.
tions. TexMedl l983;79:52—57. 97. Kuwabara Y, Ichiya Y, Otsuka M, et al. Differential diagnosis of bilateral
72. Homan RW, Devous MD Sr, Stokely EM, Bonte FL Quantification of parietal abnormalities in 1-123 IMP SPECT imaging. Clin Nucl Med
intracerebral steal in patients with arteriovenous malformation. Arch l990;15:893—899.
Neurol l986;43:779—785. 98. Herscovitch P, Auchus AP, Garb M, Chi D, Raichle ME. Correction of
73. BatjerHH,DevousMDSr,SeibertGB,et al. Intracranialarteriovenous positron emissiontomographydata for cerebralatrophy. I Cereb Blood
malformation. Relationshipsbetween clinical and radiographicfactors Flow Metab 1986;6:l20—124.
and ipsilateral steal severity. Neurosurgery l988;23:322—328. 99. Brun A, Englund E. Regional pattern of degeneration in Alzheimer's
74. Batjer HH, Devous MD Sr. Meyer YJ, et al. Cerebrovascular hemody disease: neuronallossand histopathologicalgrading. Histopathology 1981;
namics in arteriovenous malformation complicated by normal perfusion 5:549—564.
pressure breakthrough. Neurosurgery l988;22:503—509. 100. Frieldland RP, Brun A, BudingerTF. Pathological and positron emission
75. Batjer HH, Devous MD Sr, Seibert GB, Purdy PD, Bonte FJ. Intracranial tomographiccorrelationsin Alzheimer'sdisease.Lancet l985;l:228.
arteriovenous malformation. Relationship between clinical factors and 101. Buell U, Costa DC, Kirsch G, Moretti JL, Van Royen EA, Schober 0.
surgical complications. Neurosurgery l989;24:74—79. The investigation ofdementia with single photon emission tomography.
76. DevousMDSr.BatjerHH,MickeyB,SamsonDS,WhiteSR.BonteFJ. NucIMed Commun 1990;l 1:823-841.
Dynamic SPECT measurements of vasodilatoryreserve in regions of 102. PohI P, Vogl 0, Fill H, Rossler H, Zangerle R, Gerstenbrand F. Single
cerebral steal in patients with arteriovenous malformations. J Cereb Blood photon emission computed tomography in AIDS dementia complex. I
Flow Metab 1987;7:S200. NuclMed l988;29:l382—l386.
77. Batjer HH, Devous MD Sr. The use of acetazolamide-enhanced rCBF 103. Tran Dink YR. Mamo H, Cervoni C, Saimot AC. Disturbancesin the
measurement to predict risk to AVM patients. Neurosurgery 1992: in cerebral perfusion of human immune deficiency virus-l seropositive
press. asymptomaticsubjects:a quantitative tomographystudy of 18 cases.I
78. Powers WJ. Cerebral hemodynamics in ischemic cerebrovascular disease. NuclMed l990;31:l6Ol—1607.
Ann Neuroll991,29:23l—240. 104. ElI PJ, Costa DC, Harrison M. Imagingcerebral damage in HIV infection.
79. Johnson KA, Holman BL, Rosen Ti, Nagel iS, EnglishRi, Growdon Lancet 1987;2:569—570.
JH. lofetamine 1-123 single photon emission computed tomography is 105. Masdeu iC, Yudd A, Van Heertum RL, ci al. Single photon emission
accurate in the diagnosis of Alzheimer's disease. Arch Intern Med 1990; computed tomography in human immunodeficiencyvirus encephalop
150:752—756. athy: a preliminary report. INucIMed l99l;32:l47l—l475.
80. CohenMB,GrahamLS,LakeR, ci al. DiagnosisofAlzheimer'sdisease 106. Schielke E, Tatsch K, Pfister HW, et al. Reduced cerebral blood flow in
and multiple infarct dementia by tomographic imaging of iodine-123 early stages of human immunodeficiency virus infection. Arch Neurol
IMP. JNuclMed l986;27:769—774. l990;47:l342—1345.
81. Sharp P. Gemmell H, Cherryman G, Besson J, Crawford J, Smith F. 107. Holman BL, Garada B, Johnson KA, et al. A comparison of brain
Application of iodine-123-labeled isopropylamphetamine imaging to the perfusion SPECT in cocaine abuse and AIDS dementia complex. I Nod
study ofdementia. JNuclMed 1986,27:761—768. Med l992;33:l3l2—l315.
82. SmithFW,GemmellHG,SharpPF. The useof Tc-99m-HM-PAO
for 108. Devous MD Sr, Leroy RF, Homan RW. Single photon emission corn
the diagnosisofdementia. NuclMed Commun I987;8:525—533. puted tomography in epilepsy. Semin NuclMed 1990,20:325—341.
83. Jagust Wi, BudingerTF, Reed BR.The diagnosisofdementia withsingle 109. Williamson PD, Wieser HG, Delgado-Escueta AV. Clinical characteristics
photon emission computed tomography. Arch Neurol l987;44:258—262. ofpartial seizures. In: Engel J ir, ed. Surgical treatment ofzhe epilepsies.
84. NearyD, SnowdenJS,ShieldsRA,ci al.Singlephotonemissiontomog New York, NY: Raven Press; 1987:101—120.
raphy usingTc-99m-HM-PAOin the investigationofdementia. JNeurol 110. Engel i Jr. Outcome with respect to epileptic seizures. In: Engel J ir, ed.
NeurosurgPsychiatry
l987;50:l
101—I
109. Surgical treatment ofthe epilepsies. New York, NY: Raven Press; 1987:
85. JohnsonKA,MuellerST,WalsheTM,EnglishRi, HolmanBL Cerebral 553—571.
perfusionimagingin Alzheimer'sdisease:use of singlephoton emission 111. Ward AA. Perspectives for surgical therapy of epilepsy. In: Ward AA,
computed tomography and iofetamine hydrochloride 1.123. Arch Neurol Penry JK, Purpura D, eds. Epilepsy (ARNMD 61). New York, NY:
l987;44:l65—168. Raven Press; 1983:371—390.
86. PeraniD, DiPieroV,Vallar0, et al.Technetium-99m
HM.PAOSPECT 112. Kuhl DE, Engel J Jr, Phelps ME, Scm C. Epileptic patterns of local
study of regionalcerebralperfusionin early Alzheimer'sdisease.J Nod cerebral metabolism and perfusion in humans determined by emission
Med l988;29:l507—l514. computed tomography of @FDGand ‘3NH3. Ann Neurol l980;8:
87. BonteFJ,RossED,ChehabiHH,DevousMD.SPED' studyofregional 348—360.
cerebralblood flow in Alzheimer'sdisease. JCompuzAssist Tomogr 1986; 113. Engel J ir, KuhI DE, Phelps ME, Mazziotta JC. Interictal cerebral glucose
10:579—583. metabolism in partial epilepsy and its relation to EEG changes. Ann
88. Tests Hi, SnowdeniS, Neary D, et al. The use ofTc-99m HM-PAOin Neurol 1982;l2:5l0—5l7.
the diagnosis of primary degenerative dementia. I Cereb Blood Flow 114. Engel J Jr, Brown WJ, KuhI DE, Phelps ME, Mazziotta JC, Crandall PH.
Metab 1988;8:5123—Sl26. Pathologicalfindingsunderlyingfocaltemporal lobe hypometabolismin
89. Hellman RS, Tikofsky RS, Collier BD, et al. Alzheimer's disease: quan partial epilepsy. Ann Neurol l982;l2:518—528.
titative analysis of I-123-iodoamphetamine SPECT brain imaging. Ra 115. Engel J ir, Kuhl DE, Phelps ME, Crandall PH. Comparative localization
diology 1989;172:183—188. of the epileptic foci in partial epilepsy by PCT and EEG. Ann Neurol
90. Deutsch G, Tweedy JR. Cerebral blood flow in severity-matched Ak 1982;12:529—537.
heimer and multi-infarct patients. Neurology 1987;37:431—438. 116. Theodore W, Newmark M, Sato 5, etal. F-18-fluorodeoxyglucose positron
91. Launes J, Sulkava R, Erkinjuntti T, et al. Tc-99m HMPAO SPECT in emission tomography in refractory complex partial seizures. Ann Neurol
suspected dementia. NuclMed Commun l991;l2:757—765. l983;l4:429—437.
92. Bonte FJ, Horn J, Tintner R, WeinerMF. Singlephoton tomographyin 117. Bernardi 5, Trimble MR. FracowiakRSi, Wise RJS, JonesT. An interictal

Functional Brain SPECT •

Holman and Devous 1901
 study of partial epilepsy using positron emission tomography and the 547—588.
oxygen-15 inhalation technique. I Neurol Neurosurg Psychiatry 1983; 142. Theodore WH. Neuroimaging. Neurol Clin l986;4:645—668.
46:473—477. 143. Falconer MA. Mesial temporal (Ammon's horn) sclerosis as a common
I 18. MazziottaJC, EngelJ Jr. The useand impactof positroncomputed cause of epilepsy: etiology, treatment and prevention. Lancet l974;ii:
tomographyscanningin epilepsy.Epilepsia 1984;25(Suppl2):S86—S104. 767—770.
119. Theodore WH, Fishbein D, Dubinsky R. Patterns of cerebral glucose 144. Valmier J, Touchon J, Daures P. Zanca M, Baldy-Moulinier M. Corre
metabolism in patients with partial seizures. Neurology l988;38:l2Ol lations between cerebral blood flow variations and clinical parameters in
1206. temporal lobe epilepsy: an interictal study. J NeurolNeurosurg Psychiatry
120. Engel i ir, KuhI DE, Phelps ME. Patterns of human local cerebral l987;50:1306—1311.
metabolismduring epilepticseizures.Science1982;218:64—66. 145. Homan RW, Paulman RG, Devous MD Sr, Walker P, Jennings LW,
121. Depresseux iC, Franck G, Sadzot B. Regional cerebral blood flow and Bonte Fi. Cognitivefunction and regionalcerebralblood flowin partial
oxygen uptake rate in human focal epilepsy. In: Baldy-Moulinier M, seizures.ArchNeurol l989;46:964—970.
Ingvar DH, Meldrum B5, eds. Currentproblemsin epilepsy:I. cerebral 146. Berent 5, SackellaresiC, Abou-KhalilB, et al. PET studies of cerebral
bloodfiow, metabolism and epilepsy. London: John Libbey; 1984:76—81. glucose metabolic activity in temporal lobe epilepsy. The functional
122. Bonte Fi, Stokely EM, Devous MD Sr, Homan RW. Single-photon implications of lateralized hypometabolism. Neurology l986;36:
tomographic study of regional cerebral blood flow in epilepsy. A prelim 337—338.
mary report. Arch Neurol l983;40:267—27l. 147. Chugani HT, Mazziotta iC, Engel i Jr. Phelps ME. The Lennox-Gastaut
123. Bonte Fi, Devous MD Sr. Stokely EM, Homan RW. Single-photon syndrome: Metabolic subtypes determined by 2-deoxy-2[―F]fluoro-D-
tomographicdetermination of regionalcerebral blood flow in epilepsy. glucosepositronemissiontomography.Ann Neurol 1987;21:4—l3.
AJNR l983;4:544—546. 148. Theodore WH, Rose D, Patronas N, et al. Cerebral glucose metabolism
124. Bonte FJ, Devous MD Sr, Stokely EM, Homan RW, Paulman RG. in the Lennox-Gastaut syndrome. Ann Neurol l987;2l:l4—2l.
Single-photoncomputed tomographic determination of regional brain 149. Yanai K, linuma K, Matsuzawa T, et al. Cerebral glucose utilization in
blood flow in the seizure disorders. Am I Physiol Imaging l988;3: pediatricneurologicaldisordersdeterminedby positron emissiontomog
30—3
1. raphy.Eur J NuclMed 1987;13:292—296.
125. Homan RW, Devous MD Sr, Stokely EM, Bonte FJ. Correlation of EEG 150. Chugani HI, Mazziotta JC, Phelps ME. Sturge-Weber syndrome: a study
findings and cerebral blood flow in patients with partial seizures. Neurol of cerebral glucose utilization with positron emission tomography. I
ogy l984;34(Suppl l):124. Pediatr l989;l 14:244—253.
126. Magistretti PL, Uren RF. Cerebral blood flow patterns in epilepsy. In: I5 1. Engel J Jr. Lubens P, Kuhl DE, Phelps ME. Local cerebral metabolic rate
Nistico G, DiPerri R, Meinardi H, eds. Epilepsy: an update on research for glucose during petit mal absences. Ann Neurol 1985;17:l2l—l28.
and therapy. New York, NY: Allan R. Liss; 1983:241—247. 152. Chugani HI, Shewmon DA, Peacock Wi, Shields WD, Mazziotta JC,
127. Lee Bl, Markand ON, Siddiqui AR, et a). Single photon emission Phelps ME. Surgical treatment of intractable neonatal-onset seizures: the
computed tomography(SPECT)brain imagingusing N,N,N'-trimethyl role ofpositron emissiontomography.NeurologyI988;38:lI78—lI88.
N'-(2-hydroxy-3-methyl-5-'231-iodobenzyl)-1,3-propanediamine 2 HCI 153. Denays R, Rubenstein M, Ham H, Piepsz A, Noel P. Single photon
(HIPDM): Intractable complex partial seizures. Neurology l986;36: emission computedtomography in seizuredisorders. Arch DisChild 1988;
147 1—1477. 63:1184—1188.
128. Lee BI, Markand ON, Wellman HN, et al. HIPDM single photon emission 154.Loeffler iS, Alexander E III. The role of stereotactic radiosurgery in the
computed tomography brain imaging in partial onset secondarily gener management of intracranial tumors. Oncology 1990;4:2l—31.
alized tonic-clonic seizures. Epilepsia l987;28:305—311. 155. Dooms GC, Hecht S. Brant-Zawadzki M, Berthiaume Y, Norman D,
129. Lee BI, Markand ON, Wellman HN, et al. HIPDM-SPECT in patients Newton TH. Brain radiation lesions: MR imaging. Radiology l986;l58:
with medically intractable complex partial seizures. Ictal study. Arch 149—155.
Neurol 1988;45:397—402. 156. Wallner KE, Galicich iH, Malkin MG, Arbit E, KrolG, Rosenblum MK.
130. Stefan H, Kuhnen C, Biersack HJ, Reichmann K. Initial experience with Inability of computed tomography appearance of recurrent malignant
“mTchexamethyl-propylene amine oxime (HM-PAO) single photon astrocytomato predictsurvivalfollowingreoperation.I Clin Oncol 1989;
emission computed tomography (SPECT) in patients with focal epilepsy. 7:1492—1496.
Epilepsy Res 1987;l:l34—l38. 157. Brooks Di, Beaney RP, Thomas DGT. The role of positron emission
131. Andersen AR, Gram L, Kjaer L, et al. SPECT in partial epilepsy: tomographyin the study ofcerebral tumors. Semin Oncol l986;3:83—93.
Identifying side ofthe focus. Acta NeurolScand 1988;l 17:90—95. I58. KaplanWD, TakvorianI, Morris iH, RumbaughCL, ConnollyBT,
132. Ryding E, Rosen I, Elmqvist B, Ingvar DH. SPECT measurements with AtkinsHL Thallium-20l brain tumor imaging:a comparativestudywith
99mTCHMPAOin focal epilepsy.I Cereb Blood Flow Metab l988;8: pathological correlation. I NuclMed l987;28:47—52.
S95—SlOO. 159. Brismar I, Collins VP, Kesselberg M. Thallium-20l uptake relates to
133. Rowe CC, Berkovic SF, Sia STB, et al. Localization ofepileptic foci with membrane potential and potassium permeability in human glioma cells.
post ictal single photon emission computed tomography. Ann Neurol Brain Res l989;500:30—36.
l989;26:660—668. 160. Black KL, Hawkins RA, Kim KI, Becker DP, Lerner C, Marciano D.
134. Devous MD Sr. Leroy RF. Comparison of interictal and ictal regional Use of thallium-20l SPECT to quantitate malignancy grade of gliomas.
cerebral blood flow findings with scalp and depth electrode seizure focus J Neurosurg1989;7 1:342—346.
localization. I Cereb Blood Flow Metab 1989;9(suppl l):S91. 161. Kim KT, Black KL, Marciano D, et al. Thallium SPECT imaging of
135. Howse PC, Caronna ii, Duffy TE, Plum F. Cerebral energy metabolism, brain tumors: Methodsand results.I NuclMed I990;31:965—969.
pH and blood flow during seizures in cat. Am I Physiol l974;227: 162. Mountz JM, Stafl'ord-Schuck K, McKeever PE. Thallium-201 tumor/
1444—1451. cardiac ratio estimation of residual astrocytoma.I Neurosurg l988;68:
136. Theodore W, Brooks R, Margolin R, et al. Positron emission tomography 705—709.
in generalized seizures. Neurology 1985;35:684—690. 163. Schwartz RB, Carvalho PA, Alexander III E, Loeffler JS, Folkerth R,
137. Leroy RF, Devous MD, Ajmani AK, Rao KK, Bonte Fi. Regional Holman BL. Radiation necrosis vs high-grade recurrent glioma: differ
cerebral blood flow determined by xenon-l33 inhalation and SPECI' scan entiation by using dual-isotope SPECT with @°‘T1
and @“Tc-HMPAO.
among epileptics with primary generalized seizures. Neurology 1987; AJNR l991;l2:1l87—l 192.
37(suppl l):102. 164. Matthew Ri, Meyer JS, Francis DJ, Semchuk KM, Mortel K, Claghorn
138. Mazziotta JC, Engel i Jr. The use and impact of positron computed iL. Cerebral blood flow in depression. Am I Psychiatry 1980;137:
tomographyscanningin epilepsy.Epilepsia 1984;25:S86—Sl04. 1449—1450.
139. Gloor P. Generalized epilepsy with spike-and-wave discharge: a reinter 165. Rush AJ, Schlesser MA, Stokely EM, Bonte Fi, Altshuler KZ. Cerebral
pretation ofits electrographic and clinical manifestations. Epilepsia 1979; blood flowin depressionand mania. PsychopharmBull l982;18:6—8.
20:517—588. 166. UytdenhoefP, PortelangeP, iacquy i, Charles0, LinkowskiP. Mendle
140. Williamson, PD, Spencer DD, Spencer SS, Novelly RA, Mattson RH. wicz J. Regional cerebral blood flow and lateralized hemispheric dysfunc
Complex partial seizures of frontal lobe origin. Ann Neurol l985;l8: tion in depression.BrlPsychiatry l983;l43:128—l32.
497—504. 167. Our RE, Skolnick BE, Gur RC, et al. Brain function in psychiatric
141. Swartz BE, Halgren E, Delgado-Escueta AV, et al. Neuroimaging in disorders. II. Regional cerebral blood flow in medicated unipolar depres
patients with seizures of probable frontal lobe origin. Epilepsia l989;30: sives. Arch Gen Psychiatry l984;4l:695—699.

1902 The Journal of Nudear Medicine •

Vol. 33 •
No. 10 •
October1992
 168. DevousMD Sr, Rush AJ, SchlesserMA,et al. Single-photontomographic in childhood-onset obsessive compulsive disorder. Arch Gen Psychiatry
determination of regional cerebral blood flow in psychiatric disorders. J 1989:46:518—523.
NiwlMed l984:25:P57. 194. Debus JR. Devous MD Sr. Cain JW, Battaglia i, Ahmed SN, Rush AJ.
169. Buchsbaum MS. DeLisi LE, Holcomb HH, et al. Antero-posterior gra Dynanic single photon emission computerized tomography in patients
dients in cerebral glucose use in schizophreniaand affectivedisorders. with obsessive compulsive disorder. BiolPsychiazry l989;25:9A.
Are/i Gen Ps,rhiairi' 1984:41:1159—1
166. 195. Devous MD Sr. Imaging brain function by single-photon emission com
170. KuhI DE. Metter El, Riege WH. Patterns of cerebral glucose utilization puted tomography. In: Andreasen N, ed Brain imaging: applications in
in depression. multiple infarct dementia, and Alzheimer's disease. In: psychiatry. Washington, DC: American Psychiatric Press; 1988:147—234.
SokoloffL, ed. Brain imagingand brainfunction.NewYork, NY: Raven 196. Pearlson GD. PET scans in schizophrenia: what have we learned? Ann
Press:
1985:211—225. C/inPsychiatry 1991:3:97—101.
Ill. BaxterLR, PhelpsME. MazziottaJC, et al. Cerebralmetabolicrates for 197. Weinberger DR. Berman KF. Speculation of the meaning of cerebral
glucosein mood disorders.ArchGen Psychiatry1985;42:44l—447. metabolic hypofrontality in schizophrenia. Schizophr Bull l988;l4:
172. Buchsbaum MS. Wu J, DeLisi LE, et al. Frontal cortex and basal ganglia 157—168.
metabolic rates assessed by positron emission tomography with ‘SF2- l98. Wolkin A, Jaeger J, Brodie JD, et al. Persistence of cerebral metabolic
deoxyglucose in affective illness. JAffective Disord 1986:10:137—152. abnormalitiesin chronic schizophreniaas determined by positron emis
173. Post RM. DeLisi LE, Holcomb HH, Uhde TW, Cohen R, Buchsbaum sion tomography. Am J Psychiatry 1985;l42:564—57I.
MS. Glucose utilization in the temporal cortex of affectively ill patients: 199. Paulman RG, Devous MD Sr. Gregory RR, et al. Hypofrontality and
Positronemissiontomography.BiolPs.vchiairv1987:22:545—553. cognitiveimpairmentin schizophrenia:dynamic single-photontomogra
@ 174. Kishimoto H. Takazu 0, Ohno S. et al. ‘C-glucosemetabolism in manic phy and neuropsychologicalassessmentof schizophrenicbrain function.
and depressed patients. Psychiatry Res 1987:22:81—88. BiolPsychiatry
1990;27:377—399.
175. Baxter LR, Schwartz iM, Phelps ME, et al. Reduction ofprefrontal cortex 200. MatthewRJ, WilsonWH, Tant SR. Robinson L, Prakash R. Abnormal
glucose metabolism common to three types of depression. Arch Gen resting regional cerebral blood flow patterns and their correlates in schiz
Psvchiairi' 1989:46:243—250. ophrenia. Arch Gen Psychiatry l988;45:542—549.
176. Schlegel 5, AldenhoffiB, EisnerD, Lindner P. NickelO. Regional cerebral 201. Our RE, Skolnick BE, Our RC, et al. Brain function in psychiatric
blood flow in depression: Associations with psychopathology. J Affective disorders. I: regional cerebral blood flow in medicated schizophrenics.
Disord1989:17:21 1—218. Arch Ge,, Psychiair.v 1983:40:1250—1254.
177. Silfverskiold P, Risberg J. Regional cerebral blood flow in depression and 202. Volkow ND, Brodie JD, Wolfe AP, Angrist B, Russell i, Cancro R. Brain
mania. Arch Gen Psychiatry 1989:46:253—259. metabolism in patients with schizophrenia before and after acute neuro
178. Cohen RM, Semple WE, Gross M, et al. Evidence for common alterations leptic administration. J Neurol 1986:49:1 199—1202.
in cerebral glucose metabolism in major affective disorders and schizo 203. Our RE. Resnick SM, Alavi A, ci al. Regional brain function in schizo
phrenia.Neuropsvchopharmacology
1989:2:241—254. phrenia. I: A positron emission tomography study. Arch Gen Psychiatry
179. Reisches FM, Hedde iP, Drochner R. Clinical correlates ofcerebral blood 1987:44:119—125.
flow and depression. Psychiatry Res 1989:29:323—326. 204. Alavi A, Hirsch U. Studies of central nervous system disorders with
180. O'ConnellRA,Van HeertumRL, BillickSB,et al. Singlephotonemission single-photon emission computed tomography and positron emission
computed tomography(SPECT)with 1231IMP in the diflerential diagnosis tomography:Evolutionoverthe past twodecades.SeminNuclMed 1992;
ofpsychiatric disorders. J Neuropsychiatry 1989:1:145—153. 21:58—81.
181. SackeimHA, ProhovnikI, MoelleriR, et al. Regionalcerebralbloodflow 205. Andreasen NC. Evaluation ofbrain imaging techniques in mental illness.
in mood disorders. I. Comparison of major depressives and normal Ann Rev Med 1988:39:335—345.
controlsat rest.ArchGenPsychiatr.v1990:47:60—70. 206. BajcM, MedvedV, BasicM, TopuzovicN, BabicD. Cerebralperfusion
182. Martinot JL, Hardy P. Feline A, ci al. Left prefrontalglucose hypometab inhomogeneities in schizophrenia demonstrated with single-photon emis
olism in the depressed state: A confirmation. Am J Psychiatry 1990:147: sion computed tomography and Tc-99m-hexamethylpropyleneamine-ox
1313—1317. ime. Ada Psychiat Scand 1989:80:427—433.
183. Delvenne V. Delecluse F, Hubain P, Schoutens A, Dc Maertelaer V. 207. Devous MD Sr. Raese iD, Herman JH, ci al. Regional cerebral blood
Mendlewicz i. Regional cerebral blood flow in patients with affective flow in schizophrenicpatients at rest and during WisconsinCard Sort
disorders. Br J Psychiatry l990;l57:359—365. task.J CerebBloodF/owMetab l985;5:S20l—S203.
184. Silfverskiöld
P, GustafsonL, Risbergi, Rosen I. Acuteand late effectsof 208. Geraud G, Arne-Bes MC, Ouch A, Bes A. Reversibility of hemodynamic
eleciroconvulsivetherapy.Clinicaloutcome, regionalcerebralblood and hypofrontality in schizophrenia.I Cereb Blood Flow Metab 1987:7:
electroencephalogram.AnnNYAcad Sci 1986:462:237—249. 9—12.
185. Prohovnik I, Sackeim HA, Decina P. Malitz S. Acute reductions of 209. Devous MD Sr. Paulman RG, Herman J, Gregory RR, Bonte Fi, Raese
regional cerebral blood flow following electroconvulsive therapy. Inter iD. Single-photon tomography studies with schizophrenic patients. I C/in
actionswith modalityand time. Ann NYAcad Sci 1986:462:249—262. Exp Neuropsychol1988;l0:32l—322.
186. SilfverskiöldP, Rosen 1, Risberg i, Gustafson L. Changes in psychiatric 2 10. Berman KF, Zec RF, Weinberger DR. Physiological dysfunction of
symptoms related to EEG and cerebral blood flow following electrocon dorsolateral prefrontal cortex in schizophrenia. II: role of neuroleptic
vulsive therapy in depression. Eur Arch Psychiatry Neurol Sci 1987:236: treatment, attention and mental effort. Arch Ge,, Psychiatry l986;43:
195—201. 127—135.
187. Guenther W, Moser E, Mueller-Spahn F, von Oefele K, Buell U, Hippius 2 11. Berman KF. Cortical “stress tests―in schizophrenia: regional cerebral
H. Pathological cerebral blood flow during motor function in schizo blood flow studies. BiolPsychiatry l987;22:l304—l326.
phrenic and endogenous depressed patients. Biol Psychiatry 1986:21: 212. Daniel DO, Weinberger DR, Jones DW, et al. The effect of amphetamine
889—899. on regional cerebral blood flow during cognitive activation in schizophre
188. Devous MD Sr. Gullion C, Granneman B, Rush AJ. Regionalcerebral nia.JNeuroscience 199l;ll:l907—l9l7.
blood flow alterations in unipolardepression [Abstracti. JNuclMed 1991; 213. DeLisi LE, Buchsbaum MS. Holcomb HH, et al. Increased temporal lobe
32(5):95 1—952. glucoseuse in chronic schizophrenicpatients. Biol Psychiatry l989;25:
189. BaxterLR Jr. PET studiesofcerebral function in major depressionand 835—851.
obsessive-compulsive
disorder:the emergingprefrontalcortexconsensus. 2 14. Cohen RM, Semple WE, Gross M, ci al. Evidence for common alterations
Ann ClinPsychiatry 1991:3:103—109. in cerebral glucose metabolism in major affective disorders and schizo
190. Baxter LR, Phelps ME, Mazziotta JC, Guze BH, Schwartz iM, Selin CE. phrenia. Neuropsychopharmacology l989;2:24l—254.
Local cerebral glucose metabolic rates in obsessive-compulsive disorder. 215. Buchsbaum MS, DeLisi LE, Holcomb HH, et al. Anteroposterior gra
Arch Gen Psychiatry l987;44:21 1—228. dients in cerebral glucoseuse in schizophreniaand affectivedisorders.
191. Baxter LR, ir, Schwartz JM, Mazziotta JC, et al. Cerebral glucose mets ArchGen Psychiatry
1984;4l:l
159—1166.
bolic rates in nondepressed patients with obsessive-compulsive disorder. 216. Farkas T, Wolfe AP, Jaeger J, Brodie JD, Chrisiman DR. Fowler iS.
Am JPsychiairy l988;l45:l560—l563. Regional brain glucose metabolism in chronic schizophrenia: a positron
192. Nordahl TE, Benkelfat C, Semple WE, Gross M, King AC, Cohen RM. emission transaxial tomographic study. Arch Gen Psychiatry l984;4l:
Cerebral glucose metabolic rates in obsessive compulsive disorder. Neu 293—300.
ropsychopharmacology 1989;2:23—28. 2 17. Buchsbaum MS. Ingvar DH, Kessler R, et al. Cerebral glucography with
193. Swedo SE, Schapiro MB, Grady CL, ci al. Cerebral glucose metabolism positron tomography:use in normal subjectsand in patients with schiz

FunctionalBrainSPECT•
HolmanandDevous 1903
 ophrenia. Arch Gen Psychiatry l982;39:25 1—259. 225. Abdel-Dayem HM, Sadek SA, Kouris K, et al. Changes in cerebral
218. Buchsbaum MS. Wu JC, DeLisi LE, et al. Positron emission tomography perfusion after acute head injury: comparison of CT with Ic-99m HM
studiesofbasal gangliaand somatosensorycortexneurolepticdrugeffects: PAO SPECT. Radiology 1987:165:221—226.
differencesbetween normal controls and schizophrenic patients. Biol 226. Roper SN, lsmael MI, King WA, et al. An analysis ofcerebral blood flow
Psi'chiatri' 1987:22:479—494. in acute closed-head injury using Tc-99m-HMPAO SPECT in computed
2 19. Early TS, Reiman EM, Raichle ME, Spitznagel EL. Left globus pallidus tomography.JNuclMed 1991:32:684—687.
abnormality in never-medicated patients with schizophrenia. Proc Nail 227. Kung HF, Alavi A, Chang W, et al. In vivo SPECT imaging ofCNS D-2
AcadSciUSA 1987:84:561—563. dopamine receptors: initial studies with iodine-l23-IBZM in humans. I
220. Resnick SM, Our RE, Alavi A, Our RC, Reivich M. Positron emission Nuc/Med 1990:31:573—579.
tomography and subcortical glucose metabolism in schizophrenia. Psy 228. Schubiger PA, Hasler PH, Beer-Wohlfahrt H, et al. Evaluation of multi
chiairvRes 1987:24:1—Il. centre studywith iomazenil:a benzodiazepinereceptorligand.Nuc/Med
221. Van Heertum RL, O'Connell RA. Functional brain imaging in the Commun 1991:12:569—582.
evaluation ofpsychiatric illness. Semin Nuc/Med 199l;2l:24—39. 229. Holman BL Gibson RE, Hill IC, Eckelman WC, Albert M, Reba RC.
222. Our RE, Resnick SM, Our RC. Laterality and frontality ofcerebral blood Muscarinicacetylcholinereceptorsin Alzheimer'sdisease:in vivoimaging
flow and metabolism in schizophrenia: relationship to symptom specific with iodine-l23-labeled 3-quinuclidinyl-4-iodobenzilate and emission to
ity. Psi'chiatrv Res 1989:27:325—334. mography. JAMA 1985:254:3063.
223. Gray SO, Ichise M, Chung D-G, Kirsh iC, Franks W. Technetium-99m- 230. Weinberger DR, Gibson R, Coppola R, et al. The distribution of cerebral
HMPAO SPECT in the evaluation of patients with a remote history of muscarinicacetylcholinereceptorsin vivo in patients with dementia. A
traumatic brain injury: a comparison with x-ray computed tomography. controlled study with ‘23IQNB
and single photon emission computed
J N,iclMed 1992:33:52—58. tomography. Arch Neuro/ 199 l;48(2):169—176.
224. Reid RH, Gulenchyn KY, Ballinger JR. Venturey RA, ECG. Cerebral 231. Innis RB, Al-Tikriti MS. Zoghbi SS, et al. SPECT imaging ofthe benzo
perfusion imaging with technetium-99m HMPAO following cerebral diazepine receptor: feasibility of in vivo potency measurements from
trauma: initial experience. C/in Nuc/ Med 1990:15:383—388. stepwise displacement curves. I NuclMed 1991:32:1754—1761.

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