| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Department of Neurology (H.Y., Y.N., Y.K.), Department of Brain
Pathophysiology (H.F.), Department of Radiology and Nuclear Medicine (H.O.),
Faculty of Medicine, Kyoto University (Japan), and the Shiga Medical Center
for Adult Disease (H.Y.), Moriyama, Japan.
Correspondence and reprint requests to Dr Hidenao Fukuyama, Department of Brain Pathophysiology, Kyoto University Hospital, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606, Japan. E-mail fukuyama{at}kuhp.kyoto-u.ac.jp
Methods—We used positron emission tomography to study seven
patients with unilateral internal carotid artery occlusion and no
cortical infarction in the chronic stage. The distributions of red
blood cell and plasma volumes were assessed using oxygen-15–labeled
carbon monoxide and copper-62–labeled human serum
albumin-dithiosemicarbazone tracers, respectively. The
calculated hematocrit value was compared with the
hemodynamic and metabolic
parameters measured with the oxygen-15 steady-state
technique.
Results—In the cerebral cortex, the value of the cerebral
hematocrit varied but was correlated with the
hemodynamic and metabolic status. Stepwise
regression analysis revealed that the large vessel hematocrit,
the cerebral metabolic rate of oxygen, and the cerebral
blood flow or the oxygen extraction fraction accounted for a
significant proportion of variance of the cerebral hematocrit. The
oxygen extraction fraction and the cerebral metabolic rate
of oxygen negatively correlated with the cerebral hematocrit, whereas
the cerebral blood flow correlated positively: patients with reduced
blood supply relative to metabolic demand (decreased blood
flow with increased oxygen extraction fraction) showed low hematocrit
values.
Conclusions—In carotid artery occlusion in the chronic stage,
regional cerebral hematocrit may vary according to cerebral
hemodynamics and metabolic status. Regional
cerebral hematocrit may decrease with hemodynamic
compromise unless oxygen metabolism concomitantly
decreases.
Two studies in which SPECT was used6 7 in the
heterogeneous population with ischemic stroke
disclosed variations of cerebral Hct. In some patients with the acute
stage of completed infarction, cerebral Hct was increased, especially
in the ischemic region with poor prognosis; whereas in the
region with good prognosis or in the patients with transient
ischemic attack, no change in cerebral Hct was found. The
possible relation between cerebral Hct and functional outcome suggests
that the variations in Hct may result from the differences in the
cerebral hemodynamic and metabolic status
among individual patients. However, no study has demonstrated a
relationship between regional cerebral Hct and any cerebral
hemodynamic or metabolic
parameter. Among patients with ICA occlusion, those with
reduced blood supply relative to metabolic demand
("misery perfusion"8 ) may be at high risk for
recurrent ischemic stroke.9 Thus, it is
especially important to identify the relationship between regional
cerebral Hct and cerebral hemodynamics or
metabolic state, for application of the rheologically
oriented therapy for patients with ICA occlusion to prevent recurrent
stroke.
Our preliminary study in seven patients with major cerebral
arterial occlusion,10 including five
of the patients with ICA occlusion in this study, suggested a reduction
in cerebral Hct distal to the major cerebral arterial
occlusion site but with variation among patients. The purpose of this
study was to determine whether in patients with ICA occlusion in the
chronic stage regional cerebral Hct correlates with cerebral
hemodynamics or metabolic state and, if so,
how the regional cerebral Hct changes in the
hemodynamically compromised region. We selected the
patients with unilateral ICA occlusion and no cortical infarction, and
examined the relationship between the cerebral Hct and the other
hemodynamic and metabolic
parameters in the cerebral cortex using PET.
All patients were scanned with a PCT-3600W system (Hitachi Medical Co).
A detailed description of this PET scanner has been published
previously.11 This system acquires 15 slices with
center-to-center distance of 7 mm and transaxial resolution of
6.5 mm FWHM at the center. The slice thickness at the center is
6.9-mm FWHM and 5.9-mm FWHM, respectively, for in-plane and cross-plane
slices.
The subject's head was immobilized with a head-holder and
positioned with light beams to obtain transaxial slices parallel to the
orbitomeatal line. As part of the scanning procedure but before the PET
study, Germanium-68–Gallium-68 transmission scanning was performed for
20 minutes for attenuation correction.
The CBF was determined while the subject continuously inhaled 300 MBq
of CO15O per minute through a mask, and the
CMRO2 and OEF were measured during continuous
inhalation of 500 MBq of O15O per minute. Data
were collected for 5 minutes. For measurement of CRCV, 1.20 GBq of
C15O was inhaled, and the PET scan was started 30
seconds after the arrival of the peak count of the brain tissue and
continued for 3 minutes. We calculated CBF,
CMRO2, and OEF based on the steady-state
method.12 The cerebral blood volume was
calculated from the data of the C15O scan and was
incorporated into the correction of the CMRO2 and
OEF.13 14 In the calculation of the cerebral
blood volume, a conventional Hct ratio of 0.85 was used. Functional
images were reconstructed as 128x128 pixels, with each pixel
representing an area of 2.0x2.0 mm.
After the completion of the 15O-gas study, 296 to
740 MBq of 62Cu-HSA-DTS was injected
intravenously over 15 seconds in a total volume of 8 mL to
obtain CPV images. A
62Zn/62Cu generator was
prepared with 62ZnCl2
aqueous solution (1.1 GBq, pH 5.0), and HSA-DTS was synthesized by the
method reported in the previous studies.15 16
62Cu-labeling of HSA-DTS was performed by simple
mixing of 4 mL of HSA-DTS solution (5 mg/mL in saline buffer at pH 6.0)
and 4 mL of the 62Cu-generator eluate.
62Cu-HSA-DTS was readily obtained by a
ligand-exchange reaction.16 PET data acquisition
was started 3 minutes after administration of
62Cu-HSA-DTS and continued for 8 minutes. Blood
samples were obtained at 1, 5, and 7 minutes after injection of
62Cu-HSA-DTS, and both whole-blood and plasma
radioactivity were counted.10
Regional CRCV and CPV were calculated using the PET images acquired in
the C15O and 62Cu-HSA-DTS
studies according to the following equations: CRCV=Cco/(Aco/AHct)
(mL/g) and CPV=CHSA/PHSA (mL/g), where Cco and CHSA are the cerebral
tissue radioactivity of C15O and
62Cu-HSA-DTS, respectively; Aco is the
whole-blood radioactivity of C15O; PHSA is the
plasma count of 62Cu-HSA-DTS; and AHct is
the large vessel arterial Hct measured in the blood sampled
from the radial artery. The CHct was calculated from the CRCV and CPV
for each patient as CHct=CRCV/(CRCV+CPV), and the cerebral-to–large
vessel Hct ratio (r) was obtained as r=CHct/AHct. We also
calculated the mean transit times of blood (Tb), red blood cells (Tr),
and plasma (Tp), as follows: Tb=(CRCV+CPV)/CBF,
Tr=Tbx(CHct/AHct), and Tp=Tbx[(1-CHct/1-AHct)],
respectively.17
We analyzed six tomographic planes, respectively, 43, 50, 57,
64, 71, and 78 mm above and parallel to the orbitomeatal line,
which corresponded to the levels from the basal ganglia and thalamus to
the centrum semiovale. The ROI was placed on the CBF image, and
the method for MRI-PET imaging coregistration was not used. Each image
was examined by placing a total of 15 to 17 circular ROI 12 mm in
diameter compactly over the gray matter of the cortex. According to the
atlas prepared by Kretschmann and Weinrich,18 the
ROIs in all six images were included in the distribution of the
anterior cerebral artery, MCA, and posterior cerebral artery, as well
as the watershed areas between the anterior cerebral artery and MCA
(anterior watershed) and between the MCA and posterior cerebral artery
(posterior watershed). The mean hemispheric values were calculated as
the average of the MCA, anterior watershed, and posterior watershed
ROI, and each was weighted by region size.19
We compared the mean hemispheric values of the PET variables for
the cerebral cortices ipsilateral and contralateral to the site of ICA
occlusion using Wilcoxon signed-rank test. Statistical
significance was accepted at P<.05. Stepwise regression
analysis was used to test the independent predictive value of
hemodynamic or metabolic
parameters on cerebral Hct. We applied this
analysis to the hemispheric values of cerebral Hct as the
dependent variable and the value of large vessel Hct and the
hemispheric values for the PET parameters including CBF,
CMRO2, and OEF as the independent variables.
We adopted data pairs from the two hemispheres for each patient to
analyze the factors that determine the hemispheric difference
of cerebral Ht values at the same large vessel Hct, although the data
are not independent from each other despite the unilateral nature of
the ICA disease. In addition, the values of CBF, OEF, and
CMRO2 are not strictly independent, because
CMRO2 is calculated from CBF and OEF.
In the group as a whole, the value of cerebral Hct in the cerebral
cortex ipsilateral to the ICA occlusion was not different from that in
the contralateral cortex, whereas significant decreases of CBF and
CMRO2 with an increase of OEF were found
(Table 2
Analysis of data for individual patients revealed that
the values of cerebral Hct varied among patients or between hemispheres
in the same patient but were correlated with parameters of
cerebral hemodynamics and metabolic status.
When the values of CBF, OEF, CMRO2, and
large vessel Hct were entered in a stepwise regression
analysis, it produced a model including the values of OEF,
CMRO2, and large vessel
arterial Hct with a correlation coefficient of .864 for the
cerebral Hct: [model A],
CHct=0.47AHct-0.003OEF-0.047CMRO2+0.444, P=.0025, or a model including the values of CBF,
CMRO2, and large vessel arterial Hct
with a correlation coefficient of .867 for the cerebral Hct;
[model B],
CHct=0.715AHct+0.004 CBF-0.091CMRO2+0.173,
P=.0023 (Table 3
The reason for the decrease in Hct in the
hemodynamically compromised region is uncertain from
this study. However, we found that the total blood volume was increased
in this region and that the more pronounced increase in CPV than in
CRCV caused the decrease in Hct. In addition, because CBF was decreased
in this region, the calculated mean transit time of blood was
increased, with a greater increase in the Tp than in the Tr. Therefore,
one possible cause of the decrease in Hct is that the lesser decrease
in the velocity of red blood cells than in that of plasma may result in
concentration of red blood cells in the centers of vessels with an
increase in marginal cell-free plasma layer.20 A
study of cerebral microvessels in the cat demonstrated that the
thickness of the cell-free plasma layer was increased with a decrease
in the pseudo–shear rate defined as the ratio of cell velocity to
vessel radius, possibly due to aggregation of red blood
cells.21 Reductions in the perfusion pressure due
to ICA occlusion cause vasodilatation and slowing of
blood.22 23 Thus, in the
hemodynamically compromised region with increased blood
volume and slow mean transit time of blood, the thickness of the
cell-free plasma layer of vessels may increase, resulting in the more
pronounced increase in CPV than in CRCV. Another possibility is that
the leakage of plasma tracer 62Cu-HSA-DTS into
the cerebral parenchyma due to dysfunction of the blood-brain barrier
may cause an artifactual increase in CPV that is disproportionate to
any increase in CRCV. Although this effect depends on the actual size
of the tracer molecule, none of our patients with only a small
subcortical infarction in the chronic stage showed any enhancement of
the brain on the MRI study, a negative finding that does not support
this mechanism.
There are basic problems with respect to theoretical hemorheology that
make our results intrinsically difficult to interpret in terms of
either mechanisms or clinical implications.24 The
pathophysiological role of hemorheology in cerebral
ischemia is generally viewed as amenable to extrapolation from
results of blood viscosity measurements performed with coaxial
viscometry. However, the applicability of viscosity values determined
by coaxial viscometry to blood flow in the microvascular network of the
cerebral circulation is uncertain. Thus, the importance of
hemorheological factors per se in cerebral ischemia remains
highly controversial. Furthermore, the stress on the importance of
viscosity or Hct in the cerebral ischemia, if justified,
applies primarily to capillary blood flow. Thus, the clinical
importance of our results depends on the validity of the assumption
that the Hct in this study, which was estimated for brain tissue
overall, reflects the change in capillary Hct. Although this assumption
cannot be verified from these results, it is supported by directly
measured data for capillary Hct in animal experiments. In the rabbit
bilateral common carotid artery occlusion model, which causes a 48%
reduction of CBF without infarct, a decrease in capillary Hct as well
as in venous Hct was reported.25 Although the
severity of hemodynamic compromise cannot be evaluated
by CBF only, the severity of CBF reduction was comparable to that
observed in our patients with hemodynamic compromise.
The main implication of the observed decrease in Hct in the
hemodynamically compromised region is that the often
proposed increase of viscosity under low-flow conditions is not
supported. In the cerebral cortex, which escaped infarct, there was no
vicious cycle wherein elevated blood viscosity caused by an increase in
Hct further compromises blood flow and deepens cerebral
ischemia, although it is unclear how the plasma viscosity
changes. If one considers that an increase in Hct is reported to occur
in some patients during the acute stage of
stroke,6 7 it may be within the limit of
compensation for reduced blood supply that reduced CBF due to ICA
occlusion causes a decrease in Hct in the
hemodynamically compromised region. In patients with
more severe hemodynamic disturbance above the
limit of compensation that results in metabolic impairment
leading to irreversible ischemic changes, Hct might increase at
some stage of acute stroke. Because the extrapolation of the changes in
the acute stage from the results in the chronic stage must be made with
caution, it should be investigated whether Hct is increased in the
hypoperfused but viable areas with increased OEF and preserved
CMRO2 in acute stroke.26 27
Another implication of the decrease in Hct in the
hemodynamically compromised region with reduced CBF is
that it leads to hypoxia due to a reduction in oxygen delivery
[product of CBF and oxygen content (Hct)], the degree of which
may be greater than is expected from the severity of hypoperfusion.
This is among the main disorders to be targeted for therapy in the
patients studied. The decrease in Hct does not strongly support the
application of rheologically oriented therapy. However, one study
demonstrated that the lowering of Hct by isovolemic hemodilution
improves oxygen delivery as well as CBF in patients with ICA occlusion
showing a compromised hemodynamic
state.28 In the ischemic brain, the
homeostatic relationship between oxygen content and CBF that maintains
oxygen delivery constant under normal conditions is not present,
and a direct hemorheological effect is suggested to augment CBF in
hemodilution.29 Thus, the decrease in oxygen
delivery in the hemodynamically compromised region with
decreased Hct might be relieved by a further decrease in Hct by
hemodilution, especially in the patients with high large vessel Hct
values, although the level of optimal Hct remains to be elucidated.
There are problems in the interpretation of the relationship between
cerebral Hct and the other PET variables. The equation for OEF
calculated by the steady-state method assumes that the cerebral
arterial oxygen content is the same as the
peripheral arterial oxygen content. The
equation includes, in the denominator, the 15O
concentration in the form of hemoglobin-bound molecular oxygen in the
arterial blood that may be related to cerebral Hct. Thus, a
mathematical phenomenon might in part contribute to the negative
relationship between CHct and OEF. The effects of CHct might also
affect the calculations of the other PET parameters
assessed in this study. Although these potential problems need thorough
theoretical and simulation studies for better comprehension of their
effects on the various calculations done in this work, preliminary
estimations in the previous studies suggested that the effects may not
be meaningfully large.13 30
In conclusion, in patients with ICA occlusion in the chronic stage,
regional CHct varies according to cerebral hemodynamics
and metabolic status. Regional CHct may decrease with
hemodynamic compromise unless oxygen
metabolism concomitantly decreases. Thus, in the
hemodynamically compromised region, the degree of
hypoxia may be greater than is expected from the severity of
hypoperfusion.
Received May 12, 1997;
revision received October 20, 1997;
accepted October 30, 1997.
2.
Bogousslavsky J, Regli FA. Borderzone infarctions
distal to internal carotid artery occlusion: prognostic implications.
Ann Neurol. 1986;20:346–350.[Medline]
[Order article via Infotrieve]
3.
Lammertsma AA, Brooks DJ, Beaney RP, Turton DR,
Kensett MJ, Heather JD, Marshall J, Jones T. In vivo measurement of
regional cerebral hematocrit using positron emission tomography.
J Cereb Blood Flow Metab. 1984;4:317–322.[Medline]
[Order article via Infotrieve]
4.
Sakai F, Nakazawa K, Tazaki Y, Ishii K, Hino H, Kanda
T. Regional cerebral blood volume and hematocrit measured in normal
human volunteers by single-photon emission computed tomography. J
Cereb Blood Flow Metab. 1985;5:207–213.[Medline]
[Order article via Infotrieve]
5.
Asplund K. Hemodilution in acute stroke.
Cerebrovasc Dis. 1991;1(suppl 1):129–138.
6.
Loutfi I, Frackowiak RSJ, Myers MJ, Lavender JP.
Regional brain hematocrit in stroke by single photon emission computed
tomography imaging. Am J Physiol Imaging. 1987;2:10–16.[Medline]
[Order article via Infotrieve]
7.
Sakai F, Igarashi H, Suzuki S, Tazaki Y. Cerebral
blood flow and cerebral hematocrit in patients with cerebral
ischemia measured by single-photon emission computed
tomography. Acta Neurol Scand. 1989;127(suppl):9–13.
8.
Baron JC, Bousser MG, Rey A, Guillard A, Comar D,
Castaigne P. Reversal of focal "misery-perfusion syndrome" by
extra-intracranial arterial bypass in
hemodynamic cerebral ischemia. A case study
with 15O positron emission tomography.
Stroke. 1981;12:454–459.
9.
Yamauchi H, Fukuyama H, Nagahama Y, Nabatame H,
Nakamura K, Yamamoto Y, Yonekura Y, Konishi J, Kimura J. Evidence of
misery perfusion and risk for recurrent stroke in major cerebral
arterial occlusive diseases from PET. J Neurol
Neurosurg Psychiatry. 1996;61:18–25.
10.
Okazawa H, Yonekura Y, Fujibayashi Y, Yamauchi H,
Ishizu K, Nishizawa S, Magata Y, Tamaki N, Fukuyama H, Yokoyama A,
Konishi J. Measurement of regional cerebral plasma pool and hematocrit
with copper-62-labeled HSA-DTS. J Nucl Med. 1996;37:1080–1085.
11.
Sadato N, Yonekura Y, Senda M, Iwasaki Y, Matoba N,
Tamaki N, Sasayama S, Magata Y, Konishi J. PET and the
autoradiographic method with continuous inhalation of
oxygen-15-gas: theoretical analysis and comparison with
conventional steady-state methods. J Nucl Med. 1993;34:1672–1680.
12.
Frackowiak RSJ, Lenzi GL, Jones T, Heather JD.
Quantitative measurement of regional cerebral blood flow and oxygen
metabolism in man using 15O and
positron emission tomography: theory, procedure, and normal values.
J Comput Assist Tomogr. 1980;4:727–736.[Medline]
[Order article via Infotrieve]
13.
Lammertsma AA, Jones T. Correction for the presence of
intravascular oxygen-15 in the steady-state technique for measuring
regional oxygen extraction ratio in the brain, 1: description of the
method. J Cereb Blood Flow Metab. 1983;3:416–424.[Medline]
[Order article via Infotrieve]
14.
Lammertsma AA, Baron JC, Jones T. Correction for
intravascular activity in the oxygen-15 steady-state technique is
independent of the regional hematocrit. J Cereb Blood Flow
Metab. 1987;7:372–374.[Medline]
[Order article via Infotrieve]
15.
Fujibayashi Y, Matsumoto K, Yonekura Y, Konishi J,
Yokoyama A. A new zinc-62/copper-62 generator as a copper-62 source for
PET radiopharmaceuticals. J Nucl Med. 1989;30:1838–1842.
16.
Fujibayashi Y, Matsumoto K, Arano Y, Yonekura Y,
Konishi J, Yokoyama A. 62Cu-labeling of human serum
albumin-dithiosemicarbazone (HSA-DTS) conjugate for regional
plasma volume measurement: application of new 62Zn/62Cu generator
system. Chem Pharm Bull (Tokyo). 1990;38:1946–1948.[Medline]
[Order article via Infotrieve]
17.
Pries AR, Ley K, Gaehtgens P. Generalization of the
Fahraeus principle for microvessel networks. Am J
Physiol. 1986;251:H1324–1332.
18.
Kretschmann HJ, Weinrich W. Neuroanatomy
and Cranial Computed Tomography. New York, NY: Thieme-Stratton
Inc; 1986:70–74.
19.
Yamauchi H, Fukuyama H, Kimura J, Konishi J, Kameyama
M. Hemodynamics in internal carotid artery occlusion
examined by positron emission tomography. Stroke. 1990;21:1400–1406.
20.
Reinke W, Gaehtgens P, Johnson PC. Blood viscosity in
small tubes: effect of shear rate, aggregation, and sedimentation.
Am J Physiol. 1987;253:H540–547.
21.
Yamaguchi S, Yamakawa T, Niimi H. Cell-free plasma
layer in cerebral microvessels. Biorheology. 1992;29:251–260.[Medline]
[Order article via Infotrieve]
22.
Powers WJ, Grubb RL, Raichle ME.
Physiological response to focal cerebral
ischemia in humans. Ann Neurol. 1984;16:546–552.[Medline]
[Order article via Infotrieve]
23.
Gibbs JM, Wise RJS, Leenders KL, Jones T. Evaluation of
cerebral perfusion reserve in patients with carotid artery occlusion.
Lancet. 1984;1:310–314.[Medline]
[Order article via Infotrieve]
24.
Gaethgens P, Marx P. Hemorheological aspects of the
pathophysiology of cerebral ischemia. J Cereb Blood Flow
Metab. 1987;7:259–265.[Medline]
[Order article via Infotrieve]
25.
McHedlishvili G, Varazashvili M. Hematocrit in cerebral
capillaries and veins under control and ischemic conditions.
J Cereb Blood Flow Metab. 1987;7:739–744.[Medline]
[Order article via Infotrieve]
26.
Baron JC. Positron emission tomography (PET) in acute
ischemic stroke: pathophysiological and
clinical implications. In: Caplan LR, ed. Brain Ischemia:
Basic Concepts and Clinical Relevance. vol 2. London, UK:
Springer; 1995:19–27.
27.
Heiss WD, Graf R. The ischemic penumbra.
Curr Opin Neurol. 1994;7:11–19.[Medline]
[Order article via Infotrieve]
28.
Yamauchi H, Fukuyama H, Ogawa M, Ouchi Y, Kimura J.
Hemodilution improves cerebral hemodynamics in internal
carotid artery occlusion. Stroke. 1993;24:1885–1890.
29.
Kurosue K, Heros RC. Mechanism of cerebral blood flow
augmentation by hemodilution in rabbits. Stroke. 1992;23:1487–1493.
30.
Sette G, Baron JC, Mazoyer B, Levasseur M, Pappata S,
Crouzel C. Local brain haemodynamics and oxygen metabolism
in cerebrovascular disease. Brain. 1989;112:931–951.
© 1998 American Heart Association, Inc.
Original Contributions
Cerebral Hematocrit Decreases With Hemodynamic Compromise in Carotid Artery Occlusion
A PET Study
Abstract
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
Background and Purpose—This study
investigated whether in patients with internal carotid artery occlusion
the regional cerebral hematocrit correlates with cerebral
hemodynamics or metabolic state and, if so,
how the regional cerebral hematocrit changes in the
hemodynamically compromised region.
Key Words: carotid artery diseases • cerebral ischemia • hematocrit • tomography, emission computed
Introduction
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
In ischemic
cerebrovascular disease, hemorheological factors may be important in
the development of ischemia.1 This may be
particularly true in the genesis of hemodynamic
ischemia due to ICA occlusion, in which elevated Hct was
reported to be an important factor.2 Cerebral Hct
in humans can be measured in vivo using radiotracer method and PET or
single photon emission computed tomography
(SPECT).3 4 Hct is the strongest determinant of
blood viscosity.1 Therefore, in patients with
ischemic cerebrovascular disease, the in vivo measurement of
regional cerebral Hct is useful in estimating how the viscosity
contributes to the development of cerebral ischemia: High Hct
in low-flow areas implies that ischemia may be adversely
affected by elevated blood viscosity, and the lowering of Hct may be
important in improving the ischemic state. In the therapeutic
manipulation of blood rheology in stroke, the clinical effects of which
are very controversial,5 it seems essential to
investigate the change in regional cerebral Hct. However, few data on
regional cerebral Hct in patients with ischemic cerebrovascular
disease are reported in the literature.
Subjects and Methods
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
We studied seven patients with unilateral ICA occlusion in whom
no cortical infarctions were demonstrated on MRI. These patients were
five men and two women, aged 61 to 74 years (mean±SD, 65±5). The
diagnosis of ICA occlusion was based on conventional angiography, which
also disclosed no significant arterial disease
contralateral to the ICA occlusion in any patient. One patient had no
symptoms, one had transient ischemic attacks, and five had
minor hemispheric stroke with mild disability. All symptoms were
related to the affected carotid distribution. In the
asymptomatic patient, ICA occlusion was suspected because
of the observation of flow void loss on MRI performed because of
hoarseness. In each of the six symptomatic patients,
T1-weighted MRI disclosed only one minor subcortical infarction,
defined as a well-demarcated hypointense area in the middle cerebral
artery (MCA) territory or watershed area of the hemisphere with ICA
occlusion. The size of the infarct ranged from 70 to 240
mm2. On T2-weighted MRI, punctate or patchy
high-intensity areas were observed in the cerebral white matter with
ICA occlusion in all of the patients. Four patients showed a confluent
high-intensity lesion in the centrum semiovale ipsilateral to
the ICA occlusion that was considered to be ischemic change in
the deep watershed area due to low flow. The punctate or patchy
high-intensity areas of lesser degree were found on the nonaffected
side in three patients, but no patient showed confluent high-intensity
areas. The clinical and neuroradiological data are summarized in Table 1
. All patients were treated with
antiplatelet therapy (aspirin or ticlopidine HCl), but none took
medication that might specifically affect blood rheology such as
pentoxifylline. The interval between the PET and MRI evaluations and
the latest ischemic event ranged from 2 to 64 months (mean±SD,
28±21). In the asymptomatic patient, ICA occlusion was
confirmed on angiography 28 months before the PET study. All patients
and their relatives gave informed consent to the conventional
angiography and PET studies.
View this table:
[in a new window]
Table 1. Clinical and Radiographic Data for 7
Patients with ICA Occlusion
Results
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
The value of large vessel arterial Hct in the
patients ranged from 0.34 to 0.41 (mean±SD, 0.37±0.03). No patient
showed a significant change in PaO2
or Paco2 during PET scanning. ).
View this table:
[in a new window]
Table 2. Regional CBF, CMRO2, OEF, CRCV, CPV,
Regional Cerebral Hematocrit (Hct), the Cerebral-to–Large Vessel Hct
Ratio (CHct/AHct), Tr and Tp for the Cerebral Cortices Ipsilateral and
Contralateral to the ICA Occlusion ). The
CMRO2 and the CBF or OEF accounted for 32% of
variance of the cerebral Hct, although AHct was the most
heavily-weighted factor, which accounted for 42% of the variance. The
CBF was negatively correlated with the OEF (r=-.89,
P<.001), indicating that in the hemisphere with decreased
CBF the OEF was increased. In these models, the CBF value positively
correlated with the cerebral Hct value, whereas the OEF value
correlated negatively. Thus, in patients with reduced blood supply
relative to metabolic demand (decreased CBF with increased
OEF), the value of cerebral Hct was low (Figure
).
View this table:
[in a new window]
Table 3. Multiple Linear Regression Analysis with
Cerebral Hematocrit as Dependent Variable
View larger version (78K):
[in a new window]
Figure 1. Examples of PET images at the level through the centrum
semiovale in patient 4 with left (Lt) ICA occlusion and
border-zone (centrum semiovale) infarction. The value of large
vessel Hct was 0.37. Upper row (from left to right): CBF (according to
a pseudocolor scale ranging from 0 to 50 mL · 100
g-1 · min-1), CMRO2 (from
0 to 4 mL · 100 g-1 · min-1),
OEF (from 0% to 90%), cerebral hematocrit (Hct, from 0 to 0.6). Lower
row: CRCV (from 0 to 5 mL/100 g) CPV (from 0 to 5 mL/100 g), Tr (from 0
to 0.7 minutes) and Tp (from 0 to 0.7 minutes). In the left hemisphere
with arterial occlusion, which showed a decrease in CBF
(the mean hemispheric value was 22.7 mL · 100
g-1 · min-1) with an increase in OEF
(53.7%), the value of cerebral Hct was low (0.32). Also note the more
pronounced increase in CPV than in CRCV and the more pronounced
increase in Tp than in Tr in the hemisphere with arterial
occlusion.
Discussion
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
This study revealed that in patients with ICA occlusion in the
chronic stage regional cerebral Hct correlates with cerebral
hemodynamics and metabolic status and that
it is decreased in the part of the hemodynamically
compromised region examined. We found that in the cerebral cortex,
which escaped infarct, the large vessel Hct, the
CMRO2, and the CBF or OEF accounted for a
significant proportion of variance of the cerebral Hct. These
hemodynamic and metabolic
parameters independently contributed to the prediction of
the cerebral Hct, although the large vessel Hct was the most heavily
weighted factor. Because of the strong negative correlation between the
CBF and OEF in our patients, entering of either value into the model
resulted in a similar degree of correlation. The CBF value positively
correlated with the cerebral Hct value, whereas the OEF value
correlated negatively. Thus, in patients with reduced blood supply
relative to metabolic demand (decrease in CBF with increase
in OEF), the value of cerebral Hct was low. The value of
CMRO2 was negatively related to the value of
cerebral Hct. Therefore, as a whole, no significant hemispheric
asymmetry in cerebral Hct was found in our patients, who showed a
significant decrease in CMRO2, a decrease in CBF,
and an increase in OEF. Regional CHct may decrease with the severity of
hemodynamic compromise unless oxygen
metabolism concomitantly decreases.
Selected Abbreviations and Acronyms
CBF
=
cerebral blood flow
CHct
=
cerebral Hct
CMRO2
=
cerebral metabolic rate of oxygen
CPV
=
cerebral plasma volume
CRCV
=
cerebral red blood cell volume
62Cu-HSA-DTS
=
copper-62–labeled human serum albumin–dithiosemicarbazone
FWHM
=
full width at half maximum
Hct
=
hematocrit
ICA
=
internal carotid artery
MCA
=
middle cerebral artery
OEF
=
oxygen extraction fraction
PET
=
positron emission tomography
ROI
=
region of interest
Tb
=
mean transit time of blood
Tp
=
mean transit time of plasma
Tr
=
mean transit time of red blood cells
Acknowledgments
We thank Dr Yoshiharu Yonekura (Biomedical Imaging Research
Center, Fukui Medical School, Fukui, Japan), the staff of the
Department of Radiology and Nuclear Medicine, Faculty of Medicine (Drs
Yasuhiro Magata and Koichi Ishizu), and Faculty of Pharmaceutical
Sciences (Dr Yasuhisa Fujibayashi), Kyoto University, for their support
and technical help. We also thank Drs Yasuomi Ouchi and Shigeru
Matsuzaki (Department of Neurology, Faculty of Medicine, Kyoto
University) for their cooperation.
References
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
1.
Wood JH, Kee DB. Hemorheology of the cerebral
circulation in stroke. Stroke. 1985;16:765–772.
This article has been cited by other articles:
 |
|
 |
|
  K. Sheikh, M. J. Schipper, and E. G. Hoeffner Feasibility of Superficial Temporal Artery as the Input Artery for Cerebral Perfusion CT Am. J. Roentgenol., June 1, 2009; 192(6): W321 - W329. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Calamante, D.G. Gadian, and A. Connelly Quantification of Perfusion Using Bolus Tracking Magnetic Resonance Imaging in Stroke: Assumptions, Limitations, and Potential Implications for Clinical Use Stroke, April 1, 2002; 33(4): 1146 - 1151. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. P. Derdeyn, T. O. Videen, K. D. Yundt, S. M. Fritsch, D. A. Carpenter, R. L. Grubb, and W. J. Powers Variability of cerebral blood volume and oxygen extraction: stages of cerebral haemodynamic impairment revisited Brain, March 1, 2002; 125(3): 595 - 607. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Yamauchi, H. Fukuyama, Y. Nagahama, H. Okazawa, and J. Konishi A Decrease in Regional Cerebral Blood Volume and Hematocrit in Crossed Cerebellar Diaschisis Stroke, July 1, 1999; 30(7): 1429 - 1431. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||