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(Stroke. 2006;37:534.)
© 2006 American Heart Association, Inc.

Research Reports

Relationship Between Cerebral Circulatory Reserve and Oxygen Extraction Fraction in Patients With Major Cerebral Artery Occlusive Disease

A Positron Emission Tomography Study

Kenichiro Yata, MD; Akifumi Suzuki, MD, PhD; Jun Hatazawa, MD, PhD; Eku Shimosegawa, MD, PhD; Ken Nagata, MD, PhD; Mika Sato, MD, PhD Junta Moroi, MD, PhD

From the Departments of Strokology (K.Y., A.S., K.N., M.S., J.M.) and Radiology (J.H., E.S.), Research Institute for Brain and Blood Vessels, Akita, Japan.

Correspondence to Akifumi Suzuki, MD, Department of Strokology, Research Institute for Brain and Blood Vessels, Akita, 6-10 Senshu-kubota-machi, Akita 010-0874, Japan. E-mail akifumi{at}akita-noken.go.jp

	Abstract

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Background and Purpose— The present study examined the relationship between circulatory and metabolic reserve in patients with hemodynamic impairment.

Methods— Positron emission tomography was used to investigate 40 patients with major cerebral artery occlusive disease. The ratio of cerebral blood volume to cerebral blood flow (CBV/CBF) and vasoreactivity in response to hypercapnia (%CBF_hypercapnia) and acetazolamide (ACZ) stress (%CBF_ACZ) were measured to evaluate circulatory reserve. Oxygen extraction fraction (OEF) was measured to evaluate metabolic reserve. To detect relationships between circulation reserve and OEF, cerebral hemispheres were grouped into 5 or 6 stepwise groups based on reduction of circulation reserve.

Results— OEF was significantly elevated in hemispheres with CBV/CBF 0.11 minutes and in hemispheres with %CBF_hypercapnia <0%. OEF was significantly increased according to %CBF_ACZ in hemispheres with %CBF_ACZ <15% and plateaued at levels below –15%.

Conclusions— Metabolic reserve consumption began at CBV/CBF 0.11 minutes, CBF_hypercapnia <0%, and CBF_ACZ <15%.

Key Words: ischemia • tomography, emission computed

	Introduction

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Decreases in cerebral perfusion pressure attributable to steno-occlusive lesions of the cerebral artery are compensated for via 2 mechanisms.^1–3 The first involves maintaining cerebral blood flow (CBF) by autoregulatory vasodilation of the resistant vessels (circulatory reserve). The second involves maintenance of cerebral metabolic rate of oxygen (CMRO₂) by increasing oxygen extraction fraction (OEF) from the blood to the brain (metabolic reserve). The relationship between circulatory and metabolic reserve in various clinical scenarios has remained unclear.^4,5 To clarify the relationship between circulatory and metabolic reserve, the present study investigated correlations between cerebral blood volume/CBF ratio (CBV/CBF) and OEF, between vasoreactivity in response to hypercapnia and OEF, and between vasoreactivity in response to acetazolamide (ACZ) stress and OEF.

	Materials and Methods

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Subjects
Table 1 shows patient characters and exclusion criteria.

View this table: [in this window] [in a new window]   TABLE 1. Patient Characters and Exclusion Criteria

Positron Emission Tomography and Data Analysis
CBF, OEF, CBV, and CMRO₂ were measured by positron emission tomography (PET), as reported previously.⁶ CBF measurements were performed during the resting state and under hypercapnia and ACZ stress in each subject. Hypercapnia was induced by inhalation of 7% CO₂, beginning at 60 s before and continuing throughout CBF measurement. For ACZ stress, 1 g of ACZ was administered intravenously over 2 minutes, beginning at 10 minutes before the start of scanning. Two transaxial slices were selected, including the corona radiata and centrum semiovale, and regions of interest (20 mm) were drawn on 3 superficial portions covering the cortical territory of the middle cerebral artery (MCA) in each ipsilateral and contralateral hemisphere. Mean CBF, CBV, OEF, and CMRO₂ values were calculated in each hemisphere. For each mean value, vascular response to hypercapnia (%CBF_hypercapnia) was calculated as the percentage change in resting CBF per absolute change in PaCO₂ (mm Hg), and vascular response to ACZ stress (%CBF_ACZ) was calculated as the percentage change in resting CBF.

To detect trends between each parameter (CBV/CBF, %CBF_hypercapnia, and %CBF_ACZ) and OEF, we used the moving average method (7-point simple moving average). Based on these trends, we divided the hemispheres into 5 or 6 groups by reduction of circulation reserve (Figure).

View larger version (21K): [in this window] [in a new window]   Group division and relationships between 3 parameters, circulation reserve, and OEF. Black dots indicate absolute values for each hemisphere. Blue dots indicate moving average values. Red dots indicate average values within each group. a, Relationship between CBV/CBF and OEF. OEF consumption began at CBV/CBF >0.11 minutes. b, Relationship between %CBFhypercapnia and OEF. OEF consumption began at CBFhypercapnia <0%. c, Relationship between %CBFACZ and OEF. OEF consumption began at CBFACZ <15%, plateauing at CBFACZ <–15%.

All data are expressed as means±SD. Data were evaluated statistically using 1-way ANOVA or paired t tests. Values of P<0.05 were considered statistically significant.

	Results

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Table 2 and 3 show the physiological changes during the resting state, and under hypercapnia and ACZ stress, as well as the mean values measured by PET of the bilateral MCA territories in all patients.

View this table: [in this window] [in a new window]   TABLE 2. Physiological Change During Resting State, Hypercapnia, and ACZ Stress

View this table: [in this window] [in a new window]   TABLE 3. Mean Values Measured by PET

The Figure a shows the relationship between OEF and CBV/CBF; OEF differed significantly between groups 5 and 6 (P<0.05; 1-way ANOVA) but not between any of the other consecutive groups.

The Figure b shows the relationship between OEF and %CBF_hypercapnia; OEF differed significantly between groups 1 and 2 (P<0.05; 1-way ANOVA) but not between any of the other consecutive groups.

The Figure c shows the relationship between OEF and %CBF_ACZ; OEF differed significantly between groups 2 and 3 (P<0.05; 1-way ANOVA) and between groups 3 and 4 (P<0.05; 1-way ANOVA) but not between any of the other consecutive groups.

	Discussion

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Cerebral circulatory reserve has been estimated by measuring CBV, the ratio of CBV to CBF (CBV/CBF), and vascular response to vasodilatory agents.^1–5 However, whether these methods allow direct evaluation of circulation reserve remains unclear.^3,7–10 Metabolic reserve has only been estimated by measuring OEF on PET, but PET facilities are insufficient for widespread clinical use.

To date, the precise relationship between circulatory and metabolic reserve has been unclear.^4,5 In this study, we investigated the relationship between 3 parameters (CBV, CBV/CBF, and vascular response to vasodilatory agents) and metabolic reserve. We identified the point at which consumption of the metabolic reserve begins for each parameter. These points may be the most important factors for evaluating hemodynamics, and reconstructive surgery may prove to be more useful in patients with hemodynamics below these thresholds.

Conclusion
The present study confirmed relationships between circulatory and metabolic reserve, with consumption of the metabolic reserve beginning when CBV/CBF increased to 0.11 minutes, %CBF_hypercapnia decreased to <0%, and %CBF_ACZ decreased to <15%.

Received October 13, 2005; accepted November 3, 2005.

	References

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