Understanding the dynamic relationship between cerebral blood flow and the BOLD signal: Implications for quantitative functional MRI

Abstract

Calibrated BOLD imaging, in which traditional measurements of the BOLD signal are combined with measurements of cerebral blood flow (CBF) within a BOLD biophysical model to estimate changes in oxygen metabolism (CMRO2), has been a valuable tool for untangling the physiological processes associated with neural stimulus-induced BOLD activation. However, to date this technique has largely been applied to the study of essentially steady-state physiological changes (baseline to activation) associated with block-design stimuli, and it is unclear whether this approach may be directly extended to the study of more dynamic, naturalistic experimental designs. In this study we tested an assumption underlying this technique whose validity is critical to the application of calibrated BOLD to the study of more dynamic stimuli, that information about fluctuations in venous cerebral blood volume (CBVv) can be captured indirectly by measuring fluctuations in CBF, making the independent measurement of CBVv unnecessary. To accomplish this, simultaneous arterial spin labeling and BOLD imaging was used to measure the CBF and BOLD responses to flickering checkerboards with contrasts that oscillated continuously with frequencies of ~0.02-0.16Hz. The measurements were then fit to a dynamic physiological model of the BOLD response in order to explore the range of consistent CMRO2 and CBVv responses. We found that the BOLD and CBF responses were most consistent with relatively tight dynamic coupling between CBF and CMRO2 and a CBVv response that was an order of magnitude slower than either CBF or CMRO2. This finding suggests that the assumption of tight flow-volume coupling may not be strictly valid, complicating the extension of calibrated BOLD to more naturalistic experimental designs.

Fast fMRI can detect oscillatory neural activity in humans

“…The important influence of viscoelastic effects suggests that classic block designs induce steady-state dynamics with a slow HRF, whereas uncoupling of CBF and CBV during dynamic neural activity leads to a sharper HRF and stronger frequency response. Although we could not directly measure the CBF responses to these fast oscillations because of the limited temporal resolution and sensitivity of arterial spin-labeling methods, previous experiments have demonstrated that the CBF-CBV coupling is altered during dynamic stimulation (43) and have suggested that the CBV lags during dynamic neural activity; this suggestion is consistent with our proposed model. Further studies will be needed to assess the mechanism underlying our results more conclusively.…”

Ketamine and pharmacological imaging: use of functional magnetic resonance imaging to evaluate mechanisms of action

“…Increases in neuronal signaling lead to increases in metabolic rate as well as cerebral blood flow (CBF) to deliver more oxygen and glucose to meet the increased demand. The increases in CBF and anaerobic glucose metabolism are greater than the increase in oxidative metabolic rate (Fox et al, 1988), leading to a higher blood oxygen concentration and resultant changes in the blood-oxygenation-level dependent (BOLD) signal (Simon and Buxton, 2015). Measurement of the BOLD signal is utilized in phMRI to quantify the effects of drugs on neuronal signaling (Leslie and James, 2000).…”

Reduced Dynamic Coupling Between Spontaneous BOLD-CBF Fluctuations in Older Adults: A Dual-Echo pCASL Study

“…In a subsequent work, Wu et al ( 2009 ) obtained functional connectivity maps using CMRO 2 time series derived from simultaneous BOLD and CBF time series acquired with ASL. Although the CMRO 2 time courses were estimated assuming the steady-state biophysical BOLD model, that might have some limitations in a more dynamical situation (Simon and Buxton, 2015 ), the strong similarity observed by Wu et al ( 2009 ) between functional connectivity maps obtained from BOLD, CBF and CMRO 2 time courses added further evidence to a significant BOLD-CBF coupling during resting state. In a recent work the study of dynamic BOLD-CBF relationship during resting state was addressed with significant methodological improvements, including physiological noise correction in the tag and control ASL images and taking into account the influence of global cardiac fluctuations (Tak et al, 2014 ).…”

“…Alternative calibration techniques without gas administration have also been proposed based on particular MRI acquisition sequences or breath-hold tasks (Kastrup et al, 1999 ; Fujita et al, 2006 ; Bulte et al, 2009 ; Blockley et al, 2012 , 2015 ). Nevertheless, the calibrated BOLD technique has been mostly applied and validated in studies using block paradigms, and its extension to more dynamic experimental designs is not straightforward (Kida et al, 2006 ; Simon and Buxton, 2015 ).…”

“…In this regard, however, the combined acquisition of BOLD and CBF data using ASL has recently attracted increasing interest to study brain function, even without calibration measurements (Chen et al, 2015 ; Simon and Buxton, 2015 ; Storti et al, 2017 ).…”