NEUROIMAGE 6, 75–80 (1997)
ARTICLE NO. NI970284

Mechanism of Reduction of Cortical Blood Flow in Striatocapsular
Infarction: Studies Using [123I]Iomazenil SPECT
Wakoh Takahashi, Youichi Ohnuki, Tami Ohta, Hitoshi Hamano, Masahiro Yamamoto, and Yukito Shinohara1
Department of Neurology, Tokai University School of Medicine, Isehara, Kanagawa 259-11, Japan
Received September 23, 1997

of cerebral blood flow (CBF) reduction in the cortex in
SCI was suggested to be stenosis of the middle cerebral
artery (MCA) (Skyhoj et al., 1986; Weiller et al., 1990)
or disconnection of neuronal networks between the
subcortical structure and cortex (Perani et al., 1987;
Vallar et al., 1988). However, there was no direct
evidence supporting the latter hypothesis because of
methodological limitations. Recently, a radioligand for
the central type of benzodiazepine receptor (BZR) has
been developed for SPECT examination (Beer et al.,
1988). Clinical trials of this ligand in patients with
epilepsy (Schubiger et al., 1991), degenerative disease
(Schubiger et al., 1991), and cerebral infarction
(Hatazawa et al., 1995) showed that it is a useful tracer
for detection of neuronal cell damage. To clarify the
mechanism of the reduction of CBF in the cerebral
cortex in patients with SCI, we performed SPECT
examinations using [123I]ethyl-7-iodo-5,6-dihydro-5methyl-6-oxo-4H-imidazo [1.5-a]-1,4-benzodiazepine-3carboxylate [123I]iomazenil) and technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO).

Single photon emission computed tomography
(SPECT) using [123I]iomazenil (radioligand of centraltype benzodiazepine receptors) was employed to examine two patients with striatocapsular infarction. Patient 1 was a 61-year-old female with motor aphasia
and hemiplegia on the right side. Magnetic resonance
imaging (MRI) showed a lesion in the anterior limb of
internal capsule and putamen on the left side. SPECT
using 99mTc-HMPAO revealed a reduction of cerebral
blood flow (CBF) in the frontoparietal region on the
left side, but the delayed images in SPECT using
[123I]iomazenil showed only a mild decrease of accumulation in the frontal lobe. Patient 2 was a 55-year-old
male with hemiplegia on the left side. MRI showed a
lesion localized in the basal ganglia and posterior limb
of the internal capsule on the right side. SPECT using
99mTc-HMPAO revealed a reduction of CBF in the frontoparietal region on the right side and in the cerebellar hemisphere on the left side, but the delayed images
in SPECT using [123I]iomazenil showed little decrease
of accumulation in parietal lobe. The discrepancy
between CBF and receptor images suggested that cortical hypoperfusion on striatocapsular infarction might
reflect hypometabolism due to disconnection of the
neuronal network between subcortical structure and
cortex. r 1997 Academic Press

MATERIALS AND METHODS
SPECT studies were performed on two patients with
SCI. Magnetic resonance imaging (MRI) examination
in patient 1 was performed on a Gyroscan-1.5 T (Philips, Eindhoven, The Netherlands); T1-weighted (TR
425 ms, TE 12 ms) and T2-weighted (TR 3000 ms, TE 90
ms) images were obtained. MRI in patient 2 was
performed with a Magnetom-1.0 T (Siemens, Erlangen,
Germany); T1-weighted (TR 500 ms, TE 15 ms) and
T2-weighted (TR 3000 ms, TE 90 ms) images were
obtained.
SPECT was performed by using a rotating gamma
camera (GCA-901A, Toshiba, Japan; matrix of collection, 64 3 64; full width at half maximum, 15 mm) with
a standard collimator. Data were prefiltered with a
Winer filter and reconstructed with a Ramp filter.
Reconstructed images were corrected by using Chang’s
attenuation correction, with an attenuation coefficient
of 0.08 cm21. Scatter correction was not done. SPECT

INTRODUCTION
Striatocapsular infarction (SCI) is frequently associated with higher cortical dysfunction (Bladin and Berkovic, 1984). Although the lesions of SCI are restricted to
basal ganglia and internal capsule, studies of cerebral
blood flow using single photon emission computed
tomography (SPECT) in patients with SCI have revealed hypoperfusion in both basal ganglia and cerebral cortex (Skyhoj et al., 1986; Perani et al., 1987;
Vallar et al., 1988; Weiller et al., 1990). The mechanism

1 To whom correspondence and reprint requests should be addressed. Fax: 463-94-8764.

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1053-8119/97 $25.00
Copyright r 1997 by Academic Press
All rights of reproduction in any form reserved.

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TAKAHASHI ET AL.

FIG. 1. The locations of the ROI in the brain. ROI were located symmetrically in 12 or 14 regions, including lateral frontal, frontal,
parietal, temporal, occipital, basal ganglia, and cerebellum.

images were obtained in 15 consecutive axial slices
every 8 mm, parallel to and above the orbitomeatal line.
The regions of interest (ROI) (of 4 3 4 pixels; pixel size,
4 mm) were 12 or 14 symmetrically located regions in
the lateral frontal, frontal, parietal, temporal, and
occipital areas; basal ganglia; and cerebellar hemisphere, based on 3 axial slices (Fig. 1). On delayed
images with iomazenil, the ROI in basal ganglia were
not located because there was little accumulation in
these regions, reflecting the distribution of BZR in the
brain (Woods et al., 1992). The extent of change of CBF
or binding of BZR, expressed as uptake ratio of radioligand on the affected side to that on the unaffected side,
was calculated in the selected brain regions. SPECT
examination of CBF was conducted by intravenous
injection of 99mTc-HMPAO (740 MBq); data collection
was started 5 min after injection and continued for 20
min. SPECT imaging of BZR was done with [123I]iomazenil (167 MBq; Mediphysics, Japan). Early image
scans were started 5 min after intravenous injection of
[123I]iomazenil and data were collected for 20 min.
Delayed image scans were started 165 min after injection, and data were collected for 30 min. This study was
performed after the patients had given their informed
consent and with the approval of the ethics committee
of our hospital.
PATIENTS
Patient 1
A 61-year-old female was admitted to our hospital
with aphasia and hemiplegia on the right side. Neurological examinations revealed motor aphasia of the
Broca type, hemiplegia, sensory impairments and pathological reflexes on the right side. Higher cortical dysfunction other than motor aphasia was not recognized.
Chest X ray showed moderate cardiomegaly and ECG

revealed atrial fibrillation. Her common and internal
carotid arteries showed no abnormalities on ultrasonography. T1-weighted MRI images taken on the 10th day
after onset revealed low signal intensities in the anterior limb of the internal capsule and putamen on the
left side, while T2-weighted images revealed high signal
intensities in these regions (Fig. 2). SPECT using
99mTc-HMPAO on the 6th day after onset showed a
decrease of CBF in bilateral hemispheres, especially in
the frontal region on the left side (Fig. 3, top). Early
SPECT images using [123I]iomazenil on the 13th day
after onset showed a decrease of accumulation in basal
ganglia and frontotemporal regions on the left side and
cerebellum on the right side (Fig. 3, middle), while
delayed images showed a slight decrease of accumulation in the frontal region on the left side (Fig. 3,
bottom). Uptake ratios in CBF images and in early
images of iomazenil were low compared with those in
other regions, not only in the basal ganglia, but also in
the frontal, temporal, and parietal regions, but uptake
in delayed images in these regions showed little difference from the contralateral side (Table 1).
Patient 2
A 55-year-old male developed hemiparesis on the left
side. This gradually worsened, and he developed dysarthria on the evening of onset. Neurological examinations showed a confused state, sensory impairments,
hemiplegia, hyperreflexia, and pathological reflexes on
the left side. Laboratory examination showed hypercholesterolemia, increase of serum glucose concentration,
and mild polycythemia. T1-weighted MRI images on the
10th day after onset showed low signal intensities in
the putamen and posterior limb of the internal capsule
on the right side, and these lesions were seen as high
signal intensities on T2-weighted images (Fig. 4). MR
angiography on the 13th day showed a deficit in the M1

[123I]IOMAZENIL SPECT IN STRIATOCAPSULAR INFARCTION

portion of the middle cerebral artery on the right side,
and SPECT using 99mTc-HMPAO on the 11th day showed
hypoperfusion in the frontal, parietal, and temporal
regions on the right side and cerebellar hemisphere on
the left side (Fig. 5, top). Early images using [123I]iomazenil showed a severe decrease of accumulation in the
basal ganglia and a mild decrease in the frontal,
temporal, and occipital regions on the right side and
cerebellar hemisphere on the left side (Fig. 5, middle),
though delayed images showed a slight decrease of
accumulation in right parietal region (Fig. 5, bottom).
Uptake ratios in CBF images and in early images of
benzodiazepine receptors in the cerebral hemisphere
tended to be low, excluding that in the cerebellum, but
uptake in delayed images in these regions showed little
difference from the contralateral side (Table 1).
DISCUSSION
The diagnosis of SCI was based on clinical manifestations and CT or MRI identification of a lesion localized

FIG. 2. T2-weighted MRI imaging on the 10th day after onset of
cerebral infarction in patient 1. High signal intensity is seen in the
anterior limb of the internal capsule and basal ganglia on the left side.
The right side of these images represents the left side in the patients.

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in the basal ganglia and internal capsule with a
maximum diameter of 3.0 cm or more (Bladin and
Berkovic, 1984). The etiology of SCI is usually cardiogenic embolism (Weiller et al., 1990; Donnan et al.,
1991), but severe stenosis or obstruction of the internal
carotid artery or a proximal segment of the middle
cerebral artery has been reported in some cases with
SCI (Weiller et al., 1990; Donnan et al., 1991). There are
several reports which demonstrate a reduction of CBF
in the cerebral cortex in addition to basal ganglia in
patients with SCI (Skyhoj et al., 1986; Perani et al.,
1987; Vallar et al., 1988; Weiller et al., 1990). Weiller et
al. (1990) reported that reduction of CBF in these
regions can be explained by stenosis of major vessels,
based on the findings of angiography, and they afterward asserted that it is most likely due to selective
neuronal loss of the cerebral cortex due to prolonged
MCA occlusion (Weiller et al., 1993).
However, we (Meyer et al., 1970) and others (Baron et
al., 1980) reported a reduction of CBF probably due to a
reduction of cerebral metabolism, in an area remote
from the lesion in acute CVD, and explained it in terms
of diaschisis. Perani et al. (1987) speculated that the
reduction of CBF observed in SCI is a reflection of
hypometabolism in cerebral cortex due to disconnection
between subcortical structures and cerebral cortex, in
accordance with the concept of diaschisis. Vallar et al.
(1988) supported the latter hypothesis on the basis of
SPECT studies in patients with subcortical cerebrovascular diseases, including SCI.
Although CBF images obtained by SPECT using
99mTc-HMPAO in the present patients revealed hypoperfusion in cortical regions of the side with infarction,
regions in the basal ganglia did not show a decrease of
CBF. SPECT using HMPAO in our patients was performed in the subacute stage of infarction, on the 6th
and the 11th day after onset, respectively. Sperling et
al. (1993) reported that the estimation of CBF by
SPECT using HMPAO in subacute ischemic stroke
might give erroneously high values due to focal hyperfixation of HMPAO. The poor delineation of CBF to the
infarct area in basal ganglia in the present study might
reflect this characteristic of HMPAO.
Recently, a radioligand for human BZR has been
developed for use in SPECT studies (Beer et al., 1988).
BZR are classified into two types, central and peripheral (Souza et al., 1985); the central type is expressed
on neuronal cells and the peripheral type on glial cells
(Souza et al., 1985). This radioligand, iomazenil (Ro160154), has a high affinity for central-type BZR and is
characterized by a high ratio of specific to nonspecific
binding (Beer et al., 1990). When SPECT is performed
using [123I]iomazenil, the early image scanned from 5
min after intravenous administration is determined
mainly by the cerebral blood flow (Woods et al., 1992),
but the delayed image from 120 min after administra-

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[123I]IOMAZENIL SPECT IN STRIATOCAPSULAR INFARCTION

79

TABLE 1
Uptake Ratios of Affected Side to Unaffected Side in CBF
Images Obtained with HMPAO and Early and Delayed
Images with Iomazenil
ROI

HMPAO

Lateral frontal
Frontal
Parietal
Temporal
Occipital
Basal ganglia
Cerebellum

0.92
0.93
0.98
1.05
1.10
0.91
1.09

Iomazenil
(early)

Iomazenil
(delayed)

0.90
0.94
0.93
0.78
1.10
0.83
1.07

0.96
0.95
0.98
0.93
1.05
—
1.02

0.87
0.82
0.84
0.78
0.90
0.80
1.20

0.96
0.95
0.93
1.03
0.93
—
1.10

Patient 1

Patient 2
Lateral frontal
Frontal
Parietal
Temporal
Occipital
Basal ganglia
Cerebellum

0.88
0.88
0.86
0.87
0.88
1.11
1.37

tion reflects the distribution of BZR in the brain (Woods
et al., 1992). This delayed image reveals a higher
accumulation in cerebral cortex and cerebellar cortex
than in white matter, striatum, and thalamus, reflecting the distribution of BZR in the brain (Woods et al.,
1992).
In our present studies, delayed images in cortical
regions of SCI demonstrated little decrease of accumulation, although the CBF image obtained by SPECT
using 99mTc-HMPAO revealed an obvious reduction of
CBF. Since the delayed images of SPECT using [123I]iomazenil reflect the density and the binding ability of
BZR in neuronal cells (Woods et al., 1992), this phenomenon could be accounted for by the hypothesis that most
of the neuronal cells in cortical regions that show a
decrease of CBF survive or at least retain their membrane structures. Sette et al. reported that the brain
benzodiazepine receptors were preserved in periinfarcted cortical areas after ischemia, although these
areas revealed hypometabolism by positron emission
tomography in an animal model (Sette et al., 1993).
Their report is consistent with the above consider-

FIG. 4. T2-weighted MRI imaging in patient 2 on the 10th day
after onset of cerebral infarction. High signal intensity is seen in the
basal ganglia and the posterior limb of the internal capsule on the
right side.

ations. In patient 2 in the present study, MR angiography showed a deficit in the middle cerebral artery on
the infarcted side. As the mechanism of a decrease of
cortical flow in this patient, the possibility of occlusion
or stenosis of the MCA cannot be rejected. But since the
delayed images of iomazenil in this patient certified
that most of the neuronal cells in the cortical regions
were preserved, it is speculated that a decrease of CBF
in the cortical regions in this patient was associated
with hypometabolism in these regions rather than

FIG. 3. SPECT imaging in patient 1. Imaging using 99mTc-HMPAO (top) was performed on the 6th day after onset of cerebral infarction.
Hypoperfusion is apparent in the bilateral hemispheres, especially in the frontal region on the left side. Early images using [123I]iomazenil
(middle) on the 21st day after onset revealed a decrease in the frontotemporal and basal ganglial regions on the left side. Delayed images 3 h
after injection of [123I]iomazenil demonstrated a mild decrease of accumulation in the lateral region of frontal lobe on the left side (bottom).
FIG. 5. SPECT images in patient 2. Imaging using 99mTc-HMPAO (top) revealed hypoperfusion in the right frontal, parietal, and temporal
regions and left cerebellar hemisphere. Early images using [123I]iomazenil showed decreased accumulation in the frontal; parietal, temporal,
and basal ganglial regions on the right side and cerebellar hemisphere on the left side (middle), but delayed images showed a slight decrease of
accumulation in right parietal region (bottom).

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direct ischemic damage in the neuronal cells of the
cortex by occlusion or severe stenosis of the MCA.
Although the possibility remains that the ischemic
event induces hyperexpression of BZR in neuronal
cells, or the incomplete infarction in the cortex by
prolonged obstruction of the MCA, it seems more likely
that the disconnection of neuronal networks, that is,
diaschisis, plays the main role in causing the decrease
of CBF in cortex of patients with SCI.
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