An Intravenous Technique for the Measurement of Cerebral Vascular Extraction Fraction in the Rat

Clark, Helen E.; Hartman, Boyd K.; Raichle, Marcus E.; Preskorn, Sheldon; Larson, Kenneth B.

doi:10.1038/jcbfm.1982.18

Cited by 14 publications

(7 citation statements)

References 19 publications

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“…They still required intracarotid catheterization and jugular vein cannulation; hence, the application was confined to patients who underwent cerebral angi ography. The intravenous injection method devel oped by Clark et al (1982) results in an overesti mation of WEF with increasing measurement time, because the washout rates of the test and the ref erence tracers are different. An approach to mea suring the extraction fraction as the ratio of CBF values of sequentially administered test and refer ence tracers has been recently proposed (Raichle, 1980).…”

Section: Two Compartmentsmentioning

confidence: 99%

A Quantitative Model for the Measurement of Cerebral Vascular Extraction Fraction In vivo following Intravenous Injection: Simulation Studies

Takagi

Kenny

Gilson

1984

J Cereb Blood Flow Metab

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A mathematical method has been developed by which the cerebral vascular extraction fraction of flow- and diffusion-limited tracers injected intravenously can be measured quantitatively. Successive injections of three tracers are required: a test tracer such as 15O-labeled water; a completely diffusible tracer as a reference tracer and also as a flow tracer; and a tracer for cerebral blood volume (CBV). The arterial tracer concentration curves and total integrated head counts of the test and reference tracers, as well as CBF and CBV values, are required to calculate the extraction fraction. No calibration is required between the head counts and arterial curves. No decay correction of the head and arterial activity is required, because isotopic decay is explicitly included in the equation. The effect of nonextracted test tracer can be corrected. Simulation studies have shown that the calculated extraction fraction values are not sensitive to measurement error in CBF, CBV, partition coefficient, change in measurement time, or time shift effect between the arterial and head data. If there is mixing of two different tissues in the brain, the calculated extraction fraction values are close to the weighted mean values of extraction fraction by relative weight of the tissues. It is concluded that it is possible to apply this method to human studies with a positron emission tomograph scanner and to animal studies with external coincidence detectors.

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Section: Two Compartmentsmentioning

confidence: 99%

A Quantitative Model for the Measurement of Cerebral Vascular Extraction Fraction In vivo following Intravenous Injection: Simulation Studies

Takagi

Kenny

Gilson

1984

J Cereb Blood Flow Metab

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“…Evidence from a variety of techniques shows that water cannot always be assumed to be a freely diffusible tracer in the brain (15,(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28). Reduced water extraction fractions have been reported as a function of CBF in monkeys (17,18,23,28), rats (15,(19)(20)(21)(25)(26)(27), and humans (28). An important aspect of the use of endogenous water as a perfusion tracer is to determine to what extent arterial and tissue water can exchange.…”

Section: Introductionmentioning

confidence: 99%

Evidence for the exchange of arterial spin‐labeled water with tissue water in rat brain from diffusion‐sensitized measurements of perfusion

Silva

Williams

Koretsky

1997

Magnetic Resonance in Med

122

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The extraction fraction of vascular water in rat brain is investigated by means of diffusion measurements of arterial spin labeled water at varying cerebral blood flow (CBF) values. The apparent diffusion coefficient (ADC) of the difference of the proton magnetization signal in the brain acquired with and without continuous arterial spin labeling is modeled to provide a measure of the amount of arterial water in tissue and vasculature and thus of the extraction fraction. The tissue and vascular portion of the arterial spin labeled water are differentiated based on their diffusion characteristics in a manner analogous to the intravoxel incoherent motion (IVIM) method. The amount of labeled arterial water that exchanges with tissue water is determined by estimating the fraction of the total signal that is associated with the slow-decaying component of a biexponential fit to the normalized difference signal between the magnetization of brain tissue acquired with and without arterial spin labeling. The results indicate that, at normal CBF (1.15 +/- 0.21 ml x g(-1) x min[-1]), about 90% of the arterial spin labeled water diffuses with an ADC of (1.21 +/- 0.37) x 10[-3] mm2 s[-1]), which is equal to tissue. At high CBF, an increasing fraction of the labeling water has a fast-pseudo-diffusion coefficient due to a decrease in water extraction fractions. The results also show that the contribution of vascular water to the measurement of perfusion by techniques that use endogenous water as a tracer can be efficiently eliminated by the use of diffusion sensitizing gradients with small effective b values (b approximately 20 s/mm2), enabling these techniques to monitor true changes in tissue perfusion.

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“…One possibility is a lack of radiochemical purity of the labeled butanol used. Clark et al (1982), using gas chromatographic analysis, observed that commer cially obtained [14C]butanol was subject to contami nation with other 14C-Iabeled entities that appeared to be less permeable than butanol. Such a contami nation would result in an underestimation of Eb• Furthermore, Pardridge and Fierer (1985) assume that IMP is completely extracted and retained by rat brain in a single capillary passage.…”

Section: Blood-brain Barrier Permeability Of [11c]butanolmentioning

confidence: 99%

Positron Emission Tomographic Measurement of Cerebral Blood Flow and Permeability—Surface Area Product of Water Using [¹⁵O]Water and [¹¹C]Butanol

Herscovitch

Raichle

Kilbourn

et al. 1987

J Cereb Blood Flow Metab

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196

148

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We have previously adapted Kety's tissue autoradiographic method for measuring regional CBF in laboratory animals to the measurement of CBF in humans with positron emission tomography (PET) and H215O. Because this model assumes diffusion equilibrium between tissue and venous blood, the use of a diffusion-limited tracer, such as H215O, may lead to an underestimation of CBF. We therefore validated the use of [11C]butanol as an alternative freely diffusible tracer for PET. We then used it in humans to determine the underestimation of CBF that occurs with H215O, and thereby were able to calculate the extraction Ew and permeability–surface area product PSw of H215O. Measurements of the permeability of rhesus monkey brain to [11C]butanol, obtained by means of an intracarotid injection, external detection technique, demonstrated that this tracer is freely diffusible up to a CBF of at least 170 ml/min-100 g. CBF measured in baboons with the PET autoradiographic method and [11C]butanol was then compared with CBF measured in the same animals with a standard residue detection method. An excellent correspondence was obtained between both of these measurements. Finally, paired PET measurements of CBF were made with both H215O and [11C]butanol in 17 normal human subjects. Average global CBF was significantly greater when measured with [11C]butanol (53.1 ml/min-100 g) than with H215O (44.4 ml/min-100 g). Average global Ew was 0.84 and global PSw was 104 ml/min-100 g. Regional measurements showed a linear relationship between local PSw and CBF, while Ew was relatively uniform throughout the brain. Simulations were used to determine the potential error associated with the use of an incorrect value for the brain–blood partition coefficient for [11C]butanol and to calculate the effect of tissue heterogeneity and errors in flow measurement on the calculation of PSw.

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An Intravenous Technique for the Measurement of Cerebral Vascular Extraction Fraction in the Rat

Cited by 14 publications

References 19 publications

A Quantitative Model for the Measurement of Cerebral Vascular Extraction Fraction In vivo following Intravenous Injection: Simulation Studies

A Quantitative Model for the Measurement of Cerebral Vascular Extraction Fraction In vivo following Intravenous Injection: Simulation Studies

Evidence for the exchange of arterial spin‐labeled water with tissue water in rat brain from diffusion‐sensitized measurements of perfusion

Positron Emission Tomographic Measurement of Cerebral Blood Flow and Permeability—Surface Area Product of Water Using [¹⁵O]Water and [¹¹C]Butanol

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An Intravenous Technique for the Measurement of Cerebral Vascular Extraction Fraction in the Rat

Cited by 14 publications

References 19 publications

A Quantitative Model for the Measurement of Cerebral Vascular Extraction Fraction In vivo following Intravenous Injection: Simulation Studies

A Quantitative Model for the Measurement of Cerebral Vascular Extraction Fraction In vivo following Intravenous Injection: Simulation Studies

Evidence for the exchange of arterial spin‐labeled water with tissue water in rat brain from diffusion‐sensitized measurements of perfusion

Positron Emission Tomographic Measurement of Cerebral Blood Flow and Permeability—Surface Area Product of Water Using [15O]Water and [11C]Butanol

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Positron Emission Tomographic Measurement of Cerebral Blood Flow and Permeability—Surface Area Product of Water Using [¹⁵O]Water and [¹¹C]Butanol