Time-Resolved MRI Oximetry for Quantifying CMRO2 and Vascular Reactivity

This brief review of magnetic resonance susceptometry summarizes the methods conceived in the authors’ laboratory during the past several years. This article shows how venous oxygen saturation is quantified in large draining veins by field mapping and how this information, in concert with simultaneous measurement of cerebral blood flow, yields cerebral metabolic rate of oxygen, the brain’s rate of oxygen consumption. The accuracy of this model-based approach in which the blood vessel is approximated as a long, straight cylinder, for which an analytical solution for the induced field exists, is discussed. It is shown that the approach is remarkably robust, allowing for time-resolved quantification of whole-brain metabolism at rest and in response to stimuli, thereby providing detailed information on cerebral physiology in health and disease not previously amenable by noninvasive methods.

The human brain accounts for only 2% of the body’s weight, but 20% of the body’s total energy requirement . This enormous energy demand, necessary to maintain the default mode of brain activity, is incompletely understood. Oxygen consumption, typically quantified as the cerebral metabolic rate of oxygen ( CMRO 2 ), has been measured in various ways, most typically by positron emission tomography, which yielded values on the order of 130 μmol/min per 100 g in the resting awake state. Even during light sleep, CMRO 2 is only insignificantly lower , and only in deep sleep —and more so during anesthesia —is energy demand substantially lower. Further, incremental CMRO 2 increases in response to mental tasks have been found to be minor relative to the brain’s baseline demand. The brain’s default-mode energy demand is satisfied by oxidation of glucose to water and carbon dioxide. The resulting free energy generates adenosine triphosphate (ATP), the body’s universal currency of energy. In contrast, incremental demand during task activation is supplied via the glycolytic pathway of glucose oxidation.

The ratio of the oxygen consumed over the oxygen supplied by blood flow (oxygen extraction fraction [OEF]) has been found to be largely independent of the region of the brain in which it is measured . Even though oxygen consumption of gray matter is four to five times greater than that of white matter, the greater oxygen demand is offset by a commensurate increase in the rate of delivery in the form of cerebral blood flow. Once OEF is known, CMRO 2 can be quantified from a measurement of blood flow by invoking Fick’s principle, typically expressed as:

CMRO2=Ca⋅CBF⋅(SaO2−SvO2) C

(

−

)

Here, C a is the blood’s oxygen carrying capacity, CBF is the cerebral blood flow, and SaO 2 and SvO 2 are the arterial and venous oxygen saturations, respectively. The difference between arterial and venous oxygen saturation, SaO2−SvO2 S

−

2 , is also referred to as AvO2D A

D , arteriovenous oxygen saturation difference. It is related to oxygen extraction fraction as OEF=AVO2/SaO2 O

2 and, as long as arterial blood is fully saturated, AvO 2 D = AvO 2 D .

A recent review by Yablonskiy et al. examined the various magnetic resonance imaging (MRI)-based approaches for quantifying OEF, the key parameter that yields CMRO 2 via Equation (1) , along with the underlying theoretical models . In this brief review, we show how whole-brain OEF can be obtained by a quantitative MRI technique that relies on the measurement of the magnetic susceptibility of venous blood in one of the major cerebral veins, which, together with simultaneous measurement of CBF by phase-contrast blood-flow velocimetry, yields CMRO 2 .

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Principle of MRI susceptometry and alternative approaches to measure SvO 2

Magnetic Properties of Whole Blood

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Model-Based Approaches for Quantifying Blood Magnetic Susceptibility: Accuracy and Reproducibility

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ΔBint=Δχ2(cos2θ−13)B0 Δ

int

(

−

)

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ΔBext=(Δχ2sin2θ⋅a2r2⋅cos2ϕ)B0 Δ

(

cos

)

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Δχ=Δχdo⋅Hct⋅(1−SvO2) Δ

(

−

)

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Δφ(x,y)=γ⋅ΔB⋅ΔTE Δ

(

)

in which Δφ(x,y) Δ

(

) is the relative phase at pixel location (x,y) (

) , γ is the gyromagnetic ratio, and ΔTE Δ

E is the inter-echo time.

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SvO2=1−2ΔφieγB0⋅ΔTE⋅Δχdo⋅Hct(cos2θ−1/3) S

−

(

cos

−

)

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Numerical Approaches to Obtain Spatially Resolved Susceptibility from Induced Field Maps

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T 2 -Based Approaches

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Time-resolved quantification of whole-brain CMRO 2 at rest and in response to stimuli

Simultaneous Measurement of Flow and SvO 2

Resting-state CMRO 2 and response to isometabolic stimuli

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Clinical applications to the brain in neonates with congenital heart disease

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High-Speed CMRO 2 Measurement in Response to Non-Steady-State Stimuli

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Conclusions and future directions

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Time-Resolved MRI Oximetry for Quantifying CMRO2 and Vascular Reactivity

Principle of MRI susceptometry and alternative approaches to measure SvO 2

Magnetic Properties of Whole Blood

Model-Based Approaches for Quantifying Blood Magnetic Susceptibility: Accuracy and Reproducibility

Numerical Approaches to Obtain Spatially Resolved Susceptibility from Induced Field Maps

T 2 -Based Approaches

Time-resolved quantification of whole-brain CMRO 2 at rest and in response to stimuli

Simultaneous Measurement of Flow and SvO 2

Resting-state CMRO 2 and response to isometabolic stimuli

Clinical applications to the brain in neonates with congenital heart disease

High-Speed CMRO 2 Measurement in Response to Non-Steady-State Stimuli

Conclusions and future directions

References

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