Quantitative measurement of cerebral physiology using respiratory-calibrated MRI

Abstract

Functional magnetic resonance imaging typically measures signal increases arising from changes in the transverse relaxation rate over small regions of the brain and associates these with local changes in cerebral blood flow, blood volume and oxygen metabolism. Recent developments in pulse sequences and image analysis methods have improved the specificity of the measurements by focussing on changes in blood flow or changes in blood volume alone. However, FMRI is still unable to match the physiological information obtainable from positron emission tomography (PET), which is capable of quantitative measurements of blood flow and volume, and can indirectly measure resting metabolism. The disadvantages of PET are its cost, its availability, its poor spatial resolution and its use of ionising radiation. The MRI techniques introduced here address some of these limitations and provide physiological data comparable with PET measurements. We present an 18-minute MRI protocol that produces multi-slice whole-brain coverage and yields quantitative images of resting cerebral blood flow, cerebral blood volume, oxygen extraction fraction, CMRO(2), arterial arrival time and cerebrovascular reactivity of the human brain in the absence of any specific functional task. The technique uses a combined hyperoxia and hypercapnia paradigm with a modified arterial spin labelling sequence.

Fig. 1

Schematic of the stimulus paradigm

Fig. 2

Schematic of the data and the sections from which each relevant aspect is extracted (not to scale)

Fig. 3

Results from a single slice, from a representative subject. Units are in mL/100g/min for CBF, mL/100g for CBV, μmol/100g/min for CMRO₂, %ΔCBF/mmHg ΔPETCO₂ for CVR, and seconds for AAT. The AAT results are not shown, please see the main text.

Fig. 4

All slices of the CMRO₂ data for the same subject as shown in Figure 3. Units are μmol/100g/min (empty top slice omitted)

Fig. 5

(Top) Plot of calculated OEF values against the measured mean end-tidal oxygen levels (fraction) during the 2-minute plateaus of the hyperoxia stimuli. (Bottom) Plot of calculated M values against the measured end-tidal carbon dioxide levels (percentage) during the peak of the hypercapnia stimuli. Error bars are ± 1 standard deviation