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on March 4, 2004

Stroke. 2004
Published online before print March 4, 2004, doi: 10.1161/01.STR.0000122624.32167.e0
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Submitted on November 30, 2003
Accepted on January 8, 2004

Decrease in Cortical Benzodiazepine Receptors in Symptomatic Patients With Leukoaraiosis. A Positron Emission Tomography Study

M. Ihara MD, PhD*; H. Tomimoto MD, PhD; K. Ishizu MD, PhD; T. Mukai PhD; H. Yoshida MD; N. Sawamoto MD, PhD; M. Inoue MD; T. Doi MD; K. Hashikawa MD, PhD; J. Konishi MD, PhD; H. Shibasaki MD, PhD; and H. Fukuyama MD, PhD

From the Department of Neurology (M.I., H.T., H.S.), the Horizontal Medical Research Organization (M.I.), the Department of Nuclear Medicine and Diagnostic Radiology (K.I., T.M., J.K.), and the Human Brain Research Center (H.Y., N.S., M.I., T.D., K.H., H.S., H.F.), Kyoto University Graduate School of Medicine, Shogoin, Sakyo, Kyoto, Japan; National Institute of Neurological Disorders and Stroke (H.S.), National Institutes of Health, Bethesda, Md.

* To whom correspondence should be addressed. E-mail: ihara{at}kuhp.kyoto-u.ac.jp.

Background and Purpose--[11C]flumazenil (FMZ), a ligand that selectively binds to the central benzodiazepine receptor in the neuronal membrane, is useful for evaluating neuronal viability in a positron emission tomography (PET) scan. Using this ligand, we investigated whether there was a correlation between neuronal integrity in various brain structures and dementia in patients with leukoaraiosis.

Methods--Twelve patients with extensive leukoaraiosis on magnetic resonance imaging were divided into groups of patients with or without dementia. Based on a 2-compartment, 2-parameter model that included metabolite-corrected arterial input and PET-measured cerebral radioactivity, the distribution volume of FMZ (FMZ-Vd) was calculated in various regions of interest by nonlinear curve fitting. Additionally, tracer kinetic analysis was applied for voxel-by-voxel quantification of FMZ-Vd, and data analysis was performed by statistical parametric mapping.

Results--The presence of dementia was associated with a reduced FMZ-Vd in widespread areas of the cerebral cortex, including the bilateral frontopolar and frontal/insular areas, the left temporo-occipital border areas, and the left marginal cortical areas.

Conclusions--Differences in neuronal integrity in the cerebral cortex might determine whether patients with leukoaraiosis become symptomatic or not.


Key words: leukoaraiosis • Binswanger’s disease • receptors, benzodiazepine • tomography, emission computed




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