Compensatory increase in oxygen extraction fraction is associated with age-related cerebrovascular disease, 2025, McFadden et al.

Compensatory increase in oxygen extraction fraction is associated with age-related cerebrovascular disease
McFadden; Matthews; Scott; Herholz; Dickie; Haroon; Sparasci; Ahmed; Kyrtata; Parker; Emsley; Handley; Lohezic; Parkes

Cerebrovascular disease is an important contributor to dementia with reductions in cerebral blood flow (CBF) potentially compromising oxygen supply. In early stages, reduced CBF may be associated with a compensatory increase in oxygen extraction fraction (OEF) to maintain the cerebral metabolic rate of oxygen consumption (CMRO2).

We used a simultaneous PET-MRI protocol to measure OEF, CBF, CMRO2, and arterial transit time (ATT) in elderly people (age n = 24) with a range of vascular disease risk (QRisk 18.7 ± 10.8%) and cognitive abilities (MoCA scores 26.7 ± 3.4) to determine if a) vascular disease risk (parameterised with QRisk2 score) is associated with altered CBF, ATT, OEF and CMRO2, b) if impaired blood supply and increasing transit times are associated with elevated OEF and c) if these physiological measures are associated with impaired cognition.

ATT rose by 132 ms per 10 point increase in QRisk and there was a trend for reduced CBF. Compensatory increases in OEF occurred in association with modified ATT and CBF, preserving CMRO2 . There was no regional variation to these relationships. Cognitive impairment was associated with prolonged ATT.

These findings demonstrate the potential use of multi-delay time ASL and Quantitative Susceptibility Mapping for the early detection of cerebrovascular changes and provide evidence for compensatory increases in oxygen extraction in the presence of reduced blood flow.

Link (NeuroImage: Clinical) [Open Access]

 

Summary quote-notes —

• Cerebral blood flow (CBF) is a key parameter in mechanistic models of vascular supply to the brain, describing the blood volume that flows through a given mass of brain tissue per unit time

• Oxygen is a critical molecule exchanged between the blood and tissue, the degree of which can be quantified by the oxygen extraction fraction (OEF) can be used to estimate the cerebral metabolic rate of oxygen consumption (CMRO2 in μmol O2/min/100 ml tissue)

• does not take into account the smaller contribution of dissolved oxygen

• arterial transit time (ATT, the time required for blood to travel from the labelling slab to the capillary bed), could be associated with cerebrovascular resistance to blood flow on the arterial side

• In fluid dynamics, this resistance is a product of the length and diameter of a blood vessel and so is reflective of the underlying anatomy of the capillary network, with fewer, longer or narrower vessels leading to greater resistance and prolonged ATT.

• dominated mainly by transit through the arterioles and capillaries where velocity is lowest

• (BOLD) imaging provide maps of OEF but require long acquisition times and/or use of physiological assumptions in the modelling that may not hold in disease.

• Susceptibility based oximetry (SBO) exchanges regional information for a rapid estimation of global OEF, but still relies on assumptions on vessel geometry. T2-relaxation-under-spin-tagging (TRUST) is limited to a global measurement.

• we use quantitative susceptibility mapping (QSM)

• hypothesize that CBF will be reduced in subclinical cerebrovascular disease and ATT prolonged if there is a compensatory relationship between OEF and both CBF and ATT

• consider whether our physiological measurements are associated with cognitive impairment, above and beyond the impact of amyloid.

• We found evidence that ATT was significantly altered in those with greater vascular risk and in those who were cognitively impaired, and that OEF was significantly increased in those with elevated ATT or CBF.

• suggests that OEF elevation could be occurring in compensation for reduced CBF

• OEF was observed to rise in those with a greater number of vascular risk factors and with faster growing volumes of white matter hyperintensities

• On the other hand, recent work has demonstrated OEF-CBF association in younger individuals who were unlikely to have the potentially lengthened and rarefied capillary network of an older individual, suggesting that the compensatory mechanism might also occur during dynamic processes such as vessel tone modulation.

• prolonged ATT was significantly associated with poorer cognition, suggesting that the degree of vascular damage is affecting cognition

• We demonstrated that those most affected by vascular dysfunction had both the highest level of oxygen extraction but also the greatest amount of cognitive impairment. In particular we have demonstrated the potential utility of ATT as a tool sensitive to both vascular dysfunction and mild cognitive impairment.