The principal of these are background or Macroscopic Field Gradients (MFGs) from air/tissue interfaces, which can be corrected with Z-shimmingġ9. R2′ is not only affected by deoxygenated blood, but by any source of susceptibility gradients. We found that we could not reliably fit the data for both DBV and OEF at 9.4T and hence we fixed the value of DBV to 3.3% (see discussion) In previous clinical studies it has been possible to estimate DBV from the ASE dataġ9. −6 is the susceptibility difference between oxygenated and deoxygenated blood cells, and we used a haematocrit (Hct) value of 0.34ġ9.
Γ =2π × 42.577 MHz is the proton gyro-magnetic ratio, B We have neglected the dependence ofĢ for clarity.
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In preference to the asymptotic equations used by Stone and Blockeyġ8 we adapt the full qBOLD equation from He and Yablonskiy The principle biological contributor to such gradients is the presence of deoxyhaemoglobin (dHb) in capillaries and draining veinsġ7. This discrepancy can be attributed to static dephasing of spins in susceptibility gradients. Τ = 0 is less than would be expected from extrapolating the signal curve for However, in brain tissue the observed signal value at Τ values, we can measure a mono-exponential R By observing the signal in each voxel from multiple T 2-weighting, but different amounts of additional TĢ′) weighting. Τ/2, which can be either positive (the pulse occurs later thanĮ/2 or negative (the pulse occurs earlier than We chose to measure OEF from R2′, which is defined as the difference between the combined relaxation rate RĢ′), where relaxation rates are the inverses of relaxation times (RĢ′-weighting using an Asymmetric Spin-Echo (ASE) sequence where the refocusing pulse is offset from the standard time to produce a spin echo, The measurement of CBF (measured in ml/100g/min) with ASL is a well-established MR methodĢ2. Typical values used for healthy humans are 8.04 and 8.33 µmol/ml Throughout this paper we use a value of CĪ=8.48 µmol/ml, calculated from the values for mice given in GagnonĮt al. TheoryĢ, here measured in µmol/100g/min, is defined as the product of CBF, measured in ml/100g/min, and OEF multiplied by the constantĪ which describes the amount of oxygen carried in arterial blood: There were no exclusion criteria for the animals. Animals were group housed under standard laboratory conditions with freely available food and water.
All harm to animals was prevented as procedures were performed under terminal anaesthesia.
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Study procedures were conducted in accordance with the Animal (Scientific Procedures) Act 1986 and with ethical approval from the King’s College London Animal Welfare And Ethical Review Body (AWERB) under the authorisation of license number P023CC39A. Although we found our MRI methods underestimated metabolism, we could still detect a relative effect between anesthetics. We demonstrated our method by imaging rats with two anaesthetics known to affect brain metabolism differently, and compared these MRI measurements to gold-standard autoradiography measurements of glucose metabolism under the same anaesthetics. OEF maps were constructed by measuring the reversible rate of transverse relaxation R2′, which is related to the concentration of deoxyhaemoglobin (dHb) We calculated CBF maps using Arterial Spin Labelling (ASL)ġ6. Recent years have seen the emergence of methods including whole-brain measurements of CMROĢ using a combination of T2-mapping and phase-contrast velocity measurementsġ1, voxel-wise mapping using quantitative Blood Oxygenation Level Dependent (qBOLD)ġ2, BOLD calibrated with gas administrationġ4 and high-resolution mapping methods based on Quantitative Susceptibility Mapping (QSM)įor this study we implemented a straightforward and robust method to measure CMROĢ, which combines measurements of Cerebral Blood Flow (CBF) and Oxygen Extraction Fraction (OEF) made with a pre-clinical MRI scanner. Although methods exist using oxygen isotopes with either Magnetic Resonance (MR) spectroscopic imaging or Positron Emission Tomography (PET)ĩ, it would be advantageous to use proton-based Magnetic Resonance Imaging (MRI) methods due to their low invasiveness, lower cost, and wider availability. There is great interest in being able to quantitatively map the Cerebral Metabolic Rate of Oxygen (CMROĢ) consumption, both as a marker of pathology and for the study of healthy ageingĦ. The brain requires around 20% of a human’s energy production, and hence requires a similar proportion of the body’s oxygen supplyĢ.
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