J Neurosurg 62:539-546, 1985

Regional cerebral blood flow and metabolism in
reversible ischemia due to vasospasm
Determination by positron emission tomography
WILLIAM J. POWERS, M.D., ROSERT L. GRuns, JR., M.D., RoY P. BAKER, M.D.,
MARK A. MINTUN, M.D., ANO MARCUS E. RAICHLE, M.D.
Department of Neurology and Neurological Surgery, and Division of Radiation Sciences, The Edward
Mallinckrodt Institute of Radiology, and The McDonnell Centerfor Studies of Higher Brain Function,
Washington University School of Medicine, St. Louis, Missouri
v" Regional cerebral blood flow (rCBF) and regional cerebral metabolic rate of oxygen (rCMRO2) were
measured by positron emission tomography (PET) in four patients with subarachnoid hemorrhage and
hemiparesis due to cerebral vasospasm. With resolution of the vasospasm, two patients recovered and two
remained hemiparetic. Contralateral to the hemiparesis, rCBF was slightly higher in the two patients who
eventually recovered (15.0 and 16.2 ml/100 gm/min) than in the two who remained hemiparetic (12.0 and
11.7 ml/100 gm/min). The rCMRO2 measurements showed similar differences, with values of 1.34 and 2.60
ml/100 gm/min in the patients who recovered, and 0.72 and 1.66 ml/100 gm/min in those who did not. These
preliminary findings indicate that with PET studies it may be possible to prospectively differentiate patients
with neurological deficits due to reversible ischemia from patients with irreversible infarction.
KEY WORDS ~ cerebral blood flow
9 metabolism
9 vasospasm
positron emission tomography 9 subarachnoid hemorrhage

C

EREBRALischemia due to vasospasm accounts for
a major portion of the morbidity and mortality
that follows intracranial aneurysm rupture. The
neurological deficits produced by vasospastic ischemia
are potentially reversible if adequate blood flow can be
restored before permanent infarction has occurred. Intravascular volume expansion with induced arterial hypertension has proven to be the most successful treatment in this regard, reversing neurological deterioration
in over 75% of patients. 22 Since this therapeutic approach carries risks, especially in patients with unclipped aneurysms, the ability to differentiate patients
with reversible ischemia from those with irreversible
infarction would be of great clinical value.
Measurements of cerebral blood flow (CBF) during
cerebral ischemia have demonstrated that brain electrical activity diminishes at flows below approximately 20
ml/100 gm/min, whereas membrane failure and cell
death do not occur until CBF falls below approximately
l0 ml/100 gm/min. 2'5'16'21'25'36~38Values of CBF within
this range of l0 to 20 ml/100 gm/min have been
J. Neurosurg. / Volume 62/April, 1985

9

correlated with reversible neurological deficits in an
experimental study of cerebral ischemia in primates. 2~
Extension of these findings to clinical practice requires
a method for accurate quantitative measurement of
regional CBF (rCBF) in man. The development of
positron emission tomography (PET) has provided such
a method and, furthermore, allows measurement of the
regional cerebral metabolic rate of oxygen ( r C M R O 2 ) . 34
Given the normal dependence of the brain on oxidative
metabolism, rCMRO2 is likely to be a sensitive indicator
of the development of irreversible infarction. Although
PET has been widely used to study cerebral hemodynamics and metabolism in human subjects with cerebrovascular d i s e a s e , La'~2,26'3L32'4~ n o quantitative studies
of patients with transient reversible neurological deficits
have been reported.
As part of an ongoing study of rCBF and rCMRO2
in patients with subarachnoid hemorrhage (SAH)
caused by ruptured aneurysms, 3'~4'27we have used PET
to serially study four patients who developed focal
neurological deficits in association with arteriographic
539

W. J. Powers, et al.
vasospasm. Our findings are reported here. With resolution of the vasospasm, two patients recovered and
two remained hemiparetic. The PET measurements of
rCBF and rCMRO2, obtained early in the course of
vasospasm, prior to computerized tomography (CT)
demonstration of infarction, showed higher values in
those patients who eventually recovered. These preliminary data indicate that it may be possible to prospectively differentiate patients with reversible ischemic
neurological deficits from those with irreversible infarction. Furthermore, these data indicate that patients with
neurological deficits caused by cerebral vasospasm provide an excellent opportunity to study such phenomena
in man.

Summary of Cases
Four patients with SAH due to ruptured intracranial
aneurysms were studied at a time when they had recently developed a focal neurological deficit in association with arteriographic evidence of vasospasm. All of
these patients underwent repeat PET studies when vasospasm had resolved. In addition, three of the four had
also undergone an initial PET study earlier in the course
of their illness, prior to the development of vasospasm.

Case 1
This 34-year-old fight-handed woman was admitted
to Barnes Hospital 1 day after experiencing a severe
headache, loss of consciousness, nausea, and vomiting.
Examination on admission was normal except for meningismus. Computerized tomography scanning revealed
blood in the suprasellar, interhemispheric, and Sylvian
cisterns. The ventricles were larger than anticipated for
the patient's age. Three-vessel arteriography performed
on Day 2 revealed a right posterior communicating
artery aneurysm with no evidence of vasospasm. An
initial PET study was performed (Fig. 1 left column).
At this time the patient was awake and alert with no
focal neurological deficits. On Day 8 she developed a
right hemiparesis and nonfluent dysphasia. Computerized tomography showed residual subarachnoid blood
with no increase in ventricular size. The hemiparesis
and dysphasia improved over the next 2 days but were
still present on Day 10 when bilateral carotid arteriography demonstrated severe spasm of the internal carotid, middle cerebral, and anterior cerebral arteries
bilaterally. Positron emission tomography studies (Fig.
1 center column) were performed immediately following arteriography. The hemiparesis and dysphasia continued to improve, and by Day 19 the patient was
neurologically normal. Computerized tomography on
Day 20 showed moderate hydrocephalus with no evidence of cerebral infarction. Right carotid arteriography on Day 23 showed marked relief of spasm with
only slight residual narrowing of the A~ segment. A
third PET study (Fig. 1 right column) was performed
immediately following arteriography. The aneurysm
was successfully clipped on Day 24 and the postopera540

tive course was uneventful. The patient was neurologically normal at the time of discharge.

Case 2
This 53-year-old fight-handed woman was admitted
after the sudden onset of occipital headache accompanied by loss of consciousness. On admission, she was
awake and oriented, with no focal neurological deficits.
Computerized tomography on Day 1 demonstrated
subarachnoid blood with an intracerebral hematoma in
the fight frontal operculum. Three-vessel arteriography
performed on Day 2 showed an aneurysm at the bifurcation of the fight middle cerebral artery, with no
evidence of vasospasm. Initial PET studies were performed on Day 4 when the patient was lethargic but
without focal neurological deficits. She remained somewhat sleepy. On Day 9 she became progressively more
lethargic and developed a left hemiparesis. Computerized tomography showed some increase in edema
around the fight-sided hematoma. A second series of
PET studies was performed at this time. A right brachial
arteriogram obtained on Day 10 revealed marked spasm
of the internal carotid, middle cerebral, and anterior
cerebral arteries. Over the next week her left hemiparesis gradually resolved. On Day 18 she was alert and
oriented, with no focal weakness. Right carotid arteriography performed at this time showed marked improvement of the vasospasm. A third set of PET studies
was performed immediately following arteriography.
On Day 19 the aneurysm was successfully clipped.
Postoperatively, the patient developed a left hemiparesis
in association with marked edema of the fight frontal
and temporal lobes. Over the next 2 weeks the edema
resolved and the hemiparesis improved, leaving her
with only minimal left-sided weakness at the time of
discharge.
Case 3
This 66-year-old left-handed man was admitted to
another hospital because of severe headache and vomiting. Computerized tomography showed blood in the
basal cisterns, and arteriography demonstrated a right
posterior communicating artery aneurysm. Examination on admission was normal except for meningismus.
On Day 7 he became drowsy and confused, and was
transferred to Barnes Hospital on Day 9. At that time,
he was lethargic and disoriented with mild left facial
weakness, a clumsy left hand, and inattention to the
left visual field. Computerized tomography showed
minimal SAH. Over the next few days his clinical
condition worsened. He became sleepier and developed
dense left facial weakness with mild weakness of the
left arm. Three-vessel carotid arteriography performed
on Day 13 showed spasm of the M~ and A~ segments
bilaterally. Initial PET studies were performed immediately thereafter. At this time the patient had left facial
weakness and mild left arm weakness, which persisted.
Right carotid arteriography on Day 23 showed no evidence of spasm. Repeat PET studies were performed.
J. Neurosurg. / Volume 62/April, 1985

PET in evaluation of vasospastic ischemia

FIG. 1. Three sequential positron emission tomography studies performed in Case 1, a 34-year-old woman
with a ruptured posterior communicating artery aneurysm. Left Column: The first study, performed on Day
2 after hemorrhage when the patient was neurologically normal, reveals no abnormalities in regional cerebral
blood flow (rCBF, top row), regional cerebral metabolic rate of oxygen (rCMRO2, second row), regional
oxygen extraction fraction (rOEF, third row), or regional blood volume (rCBV, bottom row). Center Column:
The second study, performed on Day 10 when the patient was dysphasic with a fight hemiparesis due to
vasospasm, shows a widespread decrease in rCBF to both hemispheres, worse on the left. The rCMROz is also
decreased bilaterally, more so on the left. The rOEF is elevated on the left compared to the right, whereas
rCBV is lower. Right Column: The third study, performed on Day 23 well after the dysphasia had cleared,
reveals improved hemodynamics and metabolism bilaterally. Quantitative regional measurements derived
from these scans are shown in Table 1.

J. Neurosurg. / Volume 62/April, 1985

541

W. J. Powers, et al.
The patient continued to have marked left facial weakness and mild left arm weakness. The aneurysm was
successfully clipped on Day 24. The postoperative
course was complicated by the development of communicating hydrocephalus, requiring placement of a
shunt. Computerized tomography performed on Day
59 showed a well demarcated infarct in the fight frontal
lobe. He was discharged with left facial weakness.
Case 4
This 54-year-old right-handed woman was found in
bed, lethargic and complaining of headache. On admission to Barnes Hospital, she was drowsy but arousable,
with no focal neurological deficits. Computerized tomography showed diffuse subarachnoid and intraventricular blood, ventricular dilation, and an intracerebral
hematoma in the right frontotemporal region. Right
carotid arteriography demonstrated a right posterior
communicating artery aneurysm and no vasospasm. A
left frontal ventriculostomy was performed. Initial PET
studies were performed on Day 4 when the patient was
lethargic but had no focal neurological deficits. On Day
8 she developed left hemiparesis involving the face and
arm. This deficit persisted. Right carotid arteriography
performed on Day 10 revealed spasm of the internal
carotid and middle cerebral arteries bilaterally. A second PET study was performed immediately following
the angiogram. Computerized tomography on Day 10
showed partial resolution of the intracerebral hematoma with no evidence of infarction or hydrocephalus.
On Day 17 the hemiparesis was still present. Right
carotid arteriography showed no spasm of the middle
cerebral artery and only slight residual spasm of the AI
segment. A third series of PET studies was then performed. The aneurysm was successfully clipped on Day
19. Left hemiparesis persisted, and CT performed on
Day 27 showed an infarct of the right internal capsule
and temporoparietal white matter.
Positron Emission Tomography Studies
Materials and Methods
Measurements of regional cerebral hemodynamics
and metabolism were performed on a PETT VI machine in the low-resolution mode. This machine, which
was developed at our institution, collects seven contiguous tomographic slices 14.4 mm apart, with a transverse resolution of 12.4 to 14.9 mm and an axial
resolution of 9.7 to 20.5 mm. 41Patients were positioned
so that the lowest tomographic slice was at the canthomeatal line. Calibration of the PETT VI to achieve
quantitative measurements of local tissue radioactivity
was performed as described previously. 35 Venous and
arterial catheters were placed to permit injection of
radiotracer and collection of arterial blood samples.
A transmission scan with a germanium-68/gallium68 ring source was obtained for each subject to provide
the data on attenuation of photons that is necessary for
quantitative reconstruction of subsequent scans. Three
542

separate physiological studies were then carried out.
During each, sequential arterial blood samples were
drawn to permit conversion of the quantitative regional
radioactivity data obtained with the PETT VI machine
to quantitative physiological measurement. All studies
were carried out in a darkened room with a low ambient
noise level. The patients' eyes and ears were not masked.
The rCBF was measured using a bolus intravenous
injection of oxygen- 15 (JsO)-labeled water. 17,35Regional
cerebral blood volume (rCBV) was measured following
single-breath inhalation of air containing trace amounts
of 1SO-labeled carbon monoxide. 15.29The rCMRO2 was
measured using single-breath inhalation of 150-labeled
oxygen in combination with data supplied from the
previous rCBF and rCBV studies. This technique directly measures the regional oxygen extraction fraction
(rOEF). The rCMRO2 is then calculated as the product
of rOEF, rCBF, and the arterial oxygen content. 29 The
short half-life (123 seconds) of 150 permitted all these
studies to be performed in rapid succession. All radionuclides were produced in the Washington University
Medical Cyclotron. Identical studies were performed in
10 normal subjects, aged between 20 and 74 years.
Informed written consent from the subject or next
of kin was obtained prior to each PET study. All
protocols were approved by the Human Studies Committee and the Radioactive Drug Research Committee
of the Washington University School of Medicine.
Data Analysis
For each patient, two regions of interest were constructed using the rCBF scan obtained during vasospasm. First, a rectangular region measuring 4.7 to 7.3
sq cm was drawn around the area of decreased rCBF
in the hemisphere contralateral to the neurological deficit. This region was superior to and clearly separate
from the region of decreased rCBF caused by the intracerebral hematoma in Cases 2 and 4. A homologous
region in the opposite hemisphere located symmetrically around the biparietal midline was then outlined.
Values for rCBF, rCMRO2, rCBV, and rOEF for these
two regions during vasospasm were then determined.
Using a computer-based stereotaxic method for anatomical localization recently developed in this laboratory,8the same regions were then placed on the subject's
other PET studies and the corresponding regional physiological values were obtained.
Results
Values for rCBF, rCMROz, rOEF, and rCBV obtained from the three studies performed prior to the
development of vasospasm were all within the normal
range (Table 1 and Fig. 2). With the development of
cerebral vasospasm, rCBF and rCMRO2 in both hemispheres decreased in all four patients: however, the
values were always lower in the symptomatic hemisphere contralateral to the clinical neurological deficit
(Table 1 and Fig. 2). The rCBF in the symptomatic
J. Neurosurg. / Volume 62/April, 1985

PET in evaluation of vasospastic ischemia
TABLE 1

Regional measurements of cerebral hemodynamics and metabolism in Cases I to 4*
Case
No.

Days Post- NeurologiSAH
cal Grade]"

1

3
I
10
III
23
I1
2
4
II1
9
Ill-IV
18
III
3
13
III
23
Ill
4
4
11
10
III
17
III
normal mean values
normal range

Focal
Deficits

Vasospasm

none
rt HP
none
none
It HP
none
It HP
It HP
none
It HP
It HP

none
severe
minimal
none
severe
minimal
severe
none
none
severe
none

rCBF
(ml/100 gm/min)

rCMRO2
(ml/100 gm/min)

Right

Left

Right

Left

Right

Left

Right

Left

45.3
24.4
30.5
34.1
16.2
36.4
12.0
14.9
35.1
11.7
23.1

37.8
15.0
25.1
35.7
28.1
37.2
16.4
19.6
42.6
23.6
24.9

2.54
1.49
2.20
2.70
2.60
1.16
0.72
0.77
2.29
1.66
1.21

2.27
1.34
1.94
2.40
3.07
1.42
1.49
1.34
3.11
2.29
2.07

0.30
0.35
0.42
0.40
0.99
0.23
0.33
0.33
0.37
0.76
0.27

0.33
0.49
0.45
0.43
0.68
0.28
0.50
0.43
0.41
0.51
0.42

4.13
5.03
3.71
3.14
4.01
3.92
3.70
2.39
2.70
2.18
3.91

3.43
3.53
3.53
3.63
3.58
4.54
2.91
2.79
3.33
2.19
3.99

50.7
31.1-83.7

rOEF

3.19
2.34-4.22

rCBV (ml/100 gm)

0.40
0.23-0.60

3.98
2.61-6.50

* SAH = subarachnoid hemorrhage; rCBF = regional cerebral blood flow; ICMRO2 = regional cerebral metabolic rate of oxygen; rOEF =
regional oxygen extraction fraction; rCBV = regional cerebral blood volume; HP = hemiparesis.
t Neurological grading according to Hunt and Hess. as

4

60

50
O

--= 40
E

[]

O b
'vo

30
20

g

o

I

11"

TIT

O

E

[]

Q

8

I
0

SAH
N O SPASM

i

9

2

10

I

13

3

c

I

I

VASOSPASM

11"

TIT

I

SAH
N O SPASM

111
J

SAH
N O SPASM

!

VASOSPASM
100

4

>o

0

0. 75

~

3

I,,L

w
0

2

n

|

0.50

O

025

I
0
t

I

"IT
,

TIT

'

SAH
N O SPASM

G
i

I

1"[
i

VASOSPASM
VASOSPASM
FIG. 2. Regional measurements of cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2),
cerebral blood volume (CBV), a n d oxygen extraction fraction (OEF) in four patients with neurological deficits
due to cerebral vasospasm following subarachnoid hemorrhage (SAH). Values from the symptomatic hemisphere contralateral to the neurological deficit in the two patients with irreversible deficits (I) are compared
with those from the two patients with reversible deficits (II). Values from the other hemisphere during
vasospasm are given for all four patients (III). Three of these patients also underwent positron emission
tomography studies early in the course of their disease prior to vasospasm and these values are shown for
comparison. White circles = Case 1; white squares = Case 2; black circles = Case 3; and black squares =
Case 4.

J. Neurosurg. / Volume 62/April, 1985

543

W. J. Powers, et al.
hemisphere was below 20 ml/100 gm/min in all four
patients, but was slightly higher (15.0 and 16.2 ml/100
gm/min) in the patients who eventually recovered from
their hemiparesis (Cases 1 and 2) than it was in those
who did not (12.0 and 11.7 ml/100 gm/min in Cases 3
and 4). A similar but not as consistent pattern was also
seen for rCMRO2. In Cases 1 and 2, rCMRO2 in the
hemisphere contralateral to the neurological deficit was
1.34 and 2.60 ml/100 gm/min, respectively, whereas in
Cases 3 and 4 it was 0.72 and 1.66. With resolution of
vasospasm, all four patients showed an increase in CBF
bilaterally regardless of the clinical outcome. The rCBF
rose above 20 ml/100 gm/min in both patients who
recovered and in one who did not (Case 4). Changes in
rCMRO2 were more variable. Values of 2.20 and 1.16
ml/100 gm/min occurred in the contralateral hemisphere of those two patients who recovered from hemiparesis, and values of 0.77 and 1.21 ml/100 gm/min
occurred in those who did not. Measurements of rCBV
and rOEF exhibited no consistent pattern (Table 1 and
Fig. 2).

Discussion
Measurements of rCBF in these four cases have
demonstrated thresholds for reversible ischemia and
irreversible infarction similar to those described in experimental animals by other investigators. 2'5'16'21 Regional values for CBF below 20 but higher than 12 ml/
100 gm/min were associated with clinical neurological
deficits that were reversible. Regional values for CBF
of 12 ml/100 gm/min or less were associated with
clinical deficits that were not reversible when vasospasm
resolved. Previous studies of ischemic thresholds in
man have been primarily restricted to establishing the
relationship between rCBF and electroencephalographic (EEG) changes in patients undergoing carotid
endarterectomy while under general anesthesia. 25,36,38
These studies have demonstrated that slowing or flattening of the EEG occurs when rCBF is less than 17 or
18 ml/100 gm/min. Using drug-induced hypotension,
Finnerty and colleagues7 demonstrated that signs of
global cerebral ischemia appear when CBF falls to approximately 30 ml/100 gm/min without any change in
CMRO2. Our observations represent the first correlation between rCBF and rCMRO2 and the reversibility
of focal neurological deficits in man.
Experimental models of cerebral ischemia have demonstrated that the relationship between ICBF and the
occurrence of cerebral infarction is more complex than
a simple threshold phenomenon. The development of
irreversible neuronal damage depends not only on the
magnitude of blood flow reduction but also on its
duration, as well as on a variety of other factors including antecedent cerebral glucose stores and the selective
vulnerability of specific neuronal p o p u l a t i o n s . 2'9'16'21'33
The complexity of these interactions, taken together
with the well known phenomenon of luxury perfusion 24"3~(as seen in the third PET study in Case 4),
makes it unlikely that measurements of rCBF alone
544

will be adequate for reliable identification of tissues in
which ischemia is reversible. Given the normal dependence of the brain on oxidative metabolism, it seems
probable that the level of regional oxygen consumption
will also be critical in determining the survival of
cerebral tissue. Measurements of rCMRO2 in combination with rCBF determinations may therefore aid in
the identification of reversible ischemia. Our data indicate that there is a threshold for irreversible infarction
at rCMRO2 levels of 1.0 to 1.5 ml/100 gm/min. The
data are not as consistent as those for rCBF, however.
These findings are in accord with our previous observation that patients with carotid occlusion and no neurological deficits have rCMRO2 values of 1.43 ml/100
gm/min or greater. 31 They are also in agreement with a
recent PET study of 25 patients with acute ischemic
stroke" in which those areas of brain that later showed
CT evidence of infarction had values for rCMRO2
below 1.5 ml/100 gm/min.
While the present findings indicate that measurements of rCBF and rCMRO2 early in the course of
vasospastic ischemia may be useful in differentiating
patients with reversible ischemia from those with irreversible infarction, there are several factors that must
be taken into account when interpreting these results.
The response of the brain to ischemia is a dynamic
one, involving a complex cascade of biochemical reactions that may eventually culminate in cell death. 33
Threshold values for rCBF and rCMRO2 may be different at different points during this cascade. Furthermore,
cerebral vasospasm itself is not a static process. Reversible ischemia may become irreversible as vasospasm
worsens and blood flow decreases further. Our failure
to find absolutely consistent thresholds for reversible
ischemia and irreversible infarction, especially for
rCMRO2, may reflect the fact that we were studying a
dynamic process with only a single set of measurements
at one point in time during the period of ischemia.
The accuracy of PET in measuring rCBF and
rCMRO2 in small cerebral lesions is limited by the
resolution of the PET scanner, which was 1 to 2 cm for
the machine that we used. This means that rCBF or
rCMRO2 measured at any point in the brain represents
a weighted average of the actual values at that point
and of the values in the surrounding several centimeters
of tissue. As a result, PET measurements of small
regions tend to be higher or lower than they actually
are, depending upon the values in the surrounding
tissue. This partial volume effect may also account for
some of the scatter in our data.
Previous studies of cerebral ischemia have also
demonstrated increases in both rCBV and rOEF.I'7'~ 2-14,
20,27,31,32These increases are believed to reflect the compensatory mechanisms used by the brain to maintain
oxidative metabolism in the face of decreased perfusion
pressure. 31 Positron emission tomography measurements of rCBV and rOEF in human cerebrovascular
disease have recently shown that focal increases of both
rCBV and rOEF can occur in infarcted as well as in
J. Neurosurg. / Volume 62/April, 1985

PET in evaluation of vasospastic ischemia
ischemic tissue, demonstrating the nonspecific nature
of these findings. 4'23'26,4~The underlying pathophysiological basis for the changes observed in rCBV and
rOEF is still poorly understood and requires further
study.31 We did not find these two measurements useful
in differentiating reversible ischemia from irreversible
infarction in the present study.
Clinical deterioration following SAH can occur for a
variety of reasons in addition to vasospasm. Changes
in CBF and neurological status may also be caused by
edema, hydrocephalus, or rebleeding. 6:9'28~39 Although
none of these factors appeared to be of major importance in our four cases, some contribution cannot be
entirely excluded. Since our primary purpose was to
investigate the relationship between rCBF, rCMRO2,
and neurological function, the precise cause of the
changes in rCBF and rCMRO2 is less important than
the consequences that these changes produced.
Previous studies of CBF following aneurysm rupture
have often shown a poor correlation between focal areas
of decreased blood flow and the presence of neurological deficits) ~ 1.14.37Our findings suggest that these discrepancies can be explained by the variable degree of
local CBF reduction. Unless flow is reduced below 20
ml/100 gm/min, no corresponding clinical findings
would be expected.
The results of this study suggest that accurate quantitative measurements of rCBF and rCMRO2 may be
useful in differentiating patients with reversible ischemic neurological deficits from those with irreversible
infarction. Although of great clinical importance, investigations of the reversibility of ischemic neurological
deficits in man are difficult to perform. Patients who
develop vasospasm present a unique opportunity to
perform studies of cerebral hemodynamics and metabolism before, during, and after an ischemic insult that
may produce no clinical symptoms, a transient neurological deficit, or permanent infarction. During the past
3 years we have been fortunate to study four such
patients who developed neurological deficits, two of
whom recovered completely. Even though our findings
are consistent with other experimental and clinical observations, this small number of patients provides insufficient data to draw any firm conclusions. We would
suggest, however, that this approach to the study of
reversible ischemia is important as well as clinically
feasible, and that further research along these lines
should be pursued.
Acknowledgments

The authors would like to thank the members of the
Department of Neurology and Neurological Surgery for their
cooperation in allowing us to study their patients, and the
staff of the Division of Radiation Sciences, The Edward
Mallinckrodt Institute of Radiology, for their assistance.
References

1. Ackerman RH, Correia JA, Alpert NM, et al: Positron
imaging in ischemic stroke disease using compounds la-

J. Neurosurg. / Volume 62/April, 1985

beled with oxygen 15. Initial results of clinicophysiologic
correlations. Arch Neurol 38:537-543, 1982
2. Astrup J: Energy-requiting cell functions in the ischemic
brain. Their critical supply and possible inhibition in
protective therapy. J Neurosurg 56:482-497, 1982
3. Baker RP, Martin WRW, Herscovitch P, et al: Evaluation
by positron emission tomography of cerebral hemodynamics and metabolism following subarachnoid hemorrhage. J Nucl Med 23:P5, 1982 (Abstract)
4. Baron JC, Rougemont D, Bousser MG, et al: Local CBF,
oxygen extraction fraction (OEF), and CMRO2: prognostic value in recent supratentorial infarction in humans.
J Cereb Blood Flow Metab 3 (Suppl 1):S1-$2, 1983
5. Branston NM, Ladds A, Symon A, et al: Comparison of
the effects of ischaemia on early components of the
somatosensory evoked potential in brainstem, thalamus,
and cerebral cortex. J Cereb Blood Flow Metab 4:68-81,
1984
6. Ferguson GG, Harper AM, Fitch W, et al: Cerebral blood
flow measurements after spontaneous subarachnoid haemorrhage. Eur Neuroi 8:15-22, 1972
7. Finnerty FA Jr, Witkin L, Fazekas JF: Cerebral hemodynamics during cerebral ischemia induced by acute hypotension. J Clin Invest 33:1227-1232, 1954
8. Fox PT, Perlmutter JS, Raichle ME: A stereotactic
method of anatomical localization for positron emission
tomography. J Comput Assist Tomogr 9:141-153, 1985
9. Garcia JH, Mitchem HL, Briggs L, et al: Transient focal
ischemia in subhuman primates. Neuronal injury as a
function of local cerebral blood flow. J Neuropathol Exp
Neurol 42:44-60, 1983
10. Gelmers HJ, Beks JWF, Journre HL: Regional cerebral
blood flow in patients with subarachnoid haemorrhagc.
Acta Neurochir 47:245-251, 1979
11. G~raud G, Tremoulet M, Guell A, et al: The prognostic
value of noninvasive CBF measurement in subarachnoid
hemorrhage. Stroke 15:301-305, 1984
12. Gibbs JM, Wise RJS, Leenders KL, et al: Evaluation of
cerebral perfusion reserve in patients with carotid-artery
occlusion. Lancet 1:310-314, 1984
13. Grubb RL Jr, Phelps ME, Raichle ME: The effects of
arterial blood pressure on the regional cerebral blood
volume by x-ray fluorescence. Stroke 4:390-399, 1973
14. Grubb RL Jr, Raichle ME, Eichling JO, et al: Effects of
subarachnoid hemorrhage on cerebral blood volume,
blood flow, and oxygen utilization in humans. J Nenrosurg 46:446-453, 1977
15. Grubb RL Jr, Raichle ME, Higgins CS, et at: Measurement of regional cerebral blood volume by emission
tomography. Ann Neurol 4:322-328, 1978
16. Heiss WD, Rosner G: Functional recovery of cortical
neurons as related to degree and duration of ischemia.
Ann Neurol 14:294-301, 1983
17. Herscovitch P, Markham J, Raichle ME: Brain blood
flow measured with intravenous HflSO. 1. Theory and
error analysis. J Nucl Med 24:782-789, 1983
18. Hunt WE, Hess RM: Surgical risk as related to time of
intervention in the repair of intracranial aneurysms. J
Neurosurg 28:14-20, 1968
19. Ishii R: Regional cerebral blood flow in patients with ruptured intracranial aneurysms. J Neurusurg 50:587-594,
1979
20. Jawad K, Miller JD, Fitch W, et al: Measurement of
jugular venous blood gases for prediction of brain ischaemia following carotid ligation. A comparison with direct
measurements of cerebral blood flow. Eur Neurol 14:
43-52, 1976
21. Jones TH, Morawetz RB, Crowell RM, et al: Thresholds
545

W. J. Powers, et al.
of focal cerebral ischemia in awake monkeys. J Nenrosurg
54:773-782, 1981
22. Kassell NF, Peerless SJ, Durward Q J, et al: Treatment of
ischemic deficits from vasospasm with intravascular volume expansion and induced arterial hypertension. Neurosurgery 11:337-343, 1982
23. Lammertsma AA, Wise ILl, Heather JD, et al: Correction
for the presence of intravascular oxygen- 15 in the steadystate technique for measuring regional oxygen extraction
ratio in the brain: 2. Results in normal subjects and brain
tumour and stroke patients. J Cereb Blood Flow Metab
3:425-431, 1983
24. Lassen NA: The luxury-perfusion syndrome and its possible relation to acute metabolic acidosis localised within
the brain. Lancet 2:1113-1115, 1966
25. Leech PJ, Miller JD, Fitch W, et al: Cerebral blood flow,
internal carotid artery pressure, and the EEG as a guide
to the safety of carotid ligation. J Neurol Neurosurg
Psychiatry 37:854-862, 1974
26. Lenzi GL, Frackowiak RS, Jones T: Cerebral oxygen
metabolism and blood flow in human cerebral ischemic
infarction. J Cereb Blood Flow Metab 2:321-335, 1982
27. Martin WRW, Baker RP, Grubb RL, et al: Cerebral blood
volume, blood flow, oxygen metabolism in cerebral ischaemia and subarachnoid haemorrhage: an in-vivo study
using positron emission tomography. Acta Neurochir 70:
3-9, 1984
28. Mathew NT, Meyer JS, Hartmann A: Diagnosis and
treatment of factors complicating subarachnoid hemorrhage. Neuroradiology 6:237-245, 1974
29. Mintun MA, Raichle ME, Martin WRW, et al: Brain
oxygen utilization measured with O-15 radiotracers and
positron emission tomography. J Nucl Med 25:177-187,
1984
30. Olsen TS, Larsen B, Skriver EB, et al: Focal cerebral
hyperemia in acute stroke. Incidence, pathophysiology
and clinical significance. Stroke 12:598-607, 1981
31. Powers W J, Grubb RL Jr, Raichle ME: Physiologic responses to focal cerebral ischemia in humans. Ann Neurol
16:546-552, 1984
32. Powers W J, Martin WRW, Herscovitch P, et al: Extracranial-intracranial bypass surgery: hemodynamic and
metabolic effects. Neurology 34:1168-1174, 1984

546

33. Raichle ME: The pathophysiology of brain ischemia. Ann
Neural 13:2-10, 1983
34. Raichle ME: Positron emission tomography. Annu Rev
Neurosci 6:249-267, 1983
35. Raichle ME, Martin WRW, Herscovitch P, et al: Brain
blood flow measured with intravenous H2150.II. Implementation and validation. J Nuci Med 24:790-798, 1983
36. Sundt TM Jr, Sharbrough FW, Anderson RE, et al: Cerebral blood flow measurements and electroencephalograms
during carotid endarterectomy. J Neurosurg 41:310-320,
1974
37. Symon L, Ackerman R, Bull JWD, et al: The use of the
xenon clearance method in subarachnoid haemorrhage.
Post-operative studies with clinical and angiographic correlation. Eur Neural 8:8-14, 1972
38. Trojaborg W, Boysen G: Relation between EEG, regional
cerebral blood flow and internal carotid artery pressure
during carotid endarterectomy. Electroencephalogr Clin
Neurophysio134:61-69, 1973
39. Weir B, Menon D, Overton T: Regional cerebral blood
flow in patients with aneurysms: estimation by Xenon
133 inhalation. Can J Neurol Sci 5:301-305, 1978
40. Wise RJS, Bernardi S, Frackowiak RSJ, et al: Serial
observations on the pathophysiology of acute stroke. The
transition from ischaemia to infarction as reflected in
regional oxygen extraction. Brain 106:197-222, 1983
41. Yamamoto M, Ficke DC, Ter-Pogossian MM: Performance study of PETT VI, a positron computed tomograph
with 288 cesium fluoride detectors. IEEE Trans Nucl Sci
29:529-533, 1982

Manuscript received July 19, 1984.
This work was supported by National Institutes of Health
Grants NS06833 and HL1385 l, and by Teacher Investigator
Development Award NS00647 from the National Institute for
Neurological and Communicative Disorders and Stroke to Dr.
Powers.
Address reprint requests to: William J. Powers, M.D.,
Division of Radiation Sciences, Mallinckrodt Institute of
Radiology, Washington University School of Medicine, 5 l0
South Kingshighway, St. Louis, Missouri 63110.

J. Neurosurg. / Volume 6 2 / A p r i l 1985