Dynamics of Changes in Blood Flow, Volume, and Oxygenation: Implications for Dynamic Functional Magnetic Resonance Imaging Calibration

Abstract

Changes in cerebral blood flow (CBF), volume (CBV), and oxygenation (blood-oxygenation level dependent (BOLD)) during functional activation are important for calculating changes in cerebral metabolic rate of oxygen consumption (CMRo 2 ) from calibrated functional MRI (fMRI). An important part of this process is the CBF/CBV relationship, which is signified by a power-law parameter: c = ln (1 + DCBV/CBV)/ln (1 + DCBF/CBF). Because of difficulty in measuring CBF and CBV with MRI, the value of c is therefore assumed to be B0.4 from a prior primate study under hypercapnia. For dynamic fMRI calibration, it is important to know if the value of c varies after stimulation onset. We measured transient relationships between DCBF, DCBV, and DBOLD by multimodal MRI with temporal resolution of 500 ms (at 7.0 T) from the rat somatosensory cortex during forepaw stimulation, where the stimulus duration ranged from 4 to 32 secs. Changes in CBF and BOLD were measured before the administration of the contrast agent for CBV measurements in the same subjects. We observed that the relationship between DCBF and DCBV varied dynamically from stimulation onset for all stimulus durations. Typically after stimulation onset and at the peak or plateau of the DCBF, the value of c ranged between 0.1 and 0.2. However, after stimulation offset, the value of c increased to 0.4 primarily because of rapid and slow decays in DCBF and DCBV, respectively. These results suggest caution in using dynamic measurements of DCBF and DBOLD required for calculating DCMRo 2 for functional stimulation, when either DCBV has not been accurately measured or a fixed value of c during hypercapnia perturbation is used.

Basal Cerebral Blood Volume during the Poststimulation Undershoot in BOLD MRI of the Human Brain

“…This raises the question why opposing results have frequently been reported in animal studies (Kennan et al, 1998;Kida et al, 2007;Kim et al, 2007;Leite et al, 2002;Mandeville et al, 1998Mandeville et al, , 1999a. Previously, we suggested interspecies differences, the need for anesthesia, and the use of long-lasting iron oxide contrast agents as candidates for the discrepant findings (Frahm et al, 2008).…”

“…Although CBF and CBV normalize comparably fast in both visual and motor systems, the BOLD undershoot was found to return more quickly to baseline in the motor cortex (Donahue et al, 2009a). In fact, most human studies of the BOLD undershoot used visual stimulation (Blockley et al, 2009;Donahue et al, 2009b;Frahm et al, 1996;Jones et al, 1998;Krü ger et al, 1999aKrü ger et al, , b, 1998Lu et al, 2004;Tuunanen et al, 2006), whereas stimulation of the somatosensory system is preferred in anesthesized animals because of technical reasons (Kennan et al, 1998;Kida et al, 2007;Kim et al, 2007;Mandeville et al, 1998Mandeville et al, , 1999aShen et al, 2008). So far, no definite conclusions can be drawn about respective differences.…”

“…Although human studies consistently found normalized CBV values after the end of stimulation (Blockley et al, 2009;Frahm et al, 2008;Jasdzewski et al, 2003;Lu et al, 2004;Poser and Norris, 2007;Schroeter et al, 2006;Toronov et al, 2003;Tuunanen et al, 2006), several animal experiments reported elevated CBV during the BOLD undershoot (Jones et al, 2001(Jones et al, , 2002Kida et al, 2007;Kim et al, 2007;Leite et al, 2002;Mandeville et al, 1998Mandeville et al, , 1999a. One possible reason for these discrepancies is a methodological difference as most of the animal studies are based on blood-pool contrast agents with iron oxide particles (Jin and Kim, 2008;Kennan et al, 1998;Kida et al, 2007;Kim et al, 2007;Mandeville et al, 1998Mandeville et al, , 1999aSmirnakis et al, 2007). Thus, to investigate the impact of the specific contrast agent used for assessing CBV effects, we set up an experiment using dynamic T1-weighted three-dimensional (3D) MRI and the blood-pool contrast agent Vasovist, containing gadofosveset trisodium (Majos et al, 2009;Morton et al, 2006).…”

Near-infrared measurements of brain oxygenation in stroke

“…As the metabolism (CMRO 2 ) increases, the CBF increases, leading to an increased delivery of oxygen by blood per unit of time, resulting in a stable OEF (CBF and CMRO 2 are matched) and a stable S t O 2 . 30 When CMRO 2 and CBF are not matched, changes in CMRO 2 or CBF lead to corresponding changes in OEF to maintain optimal tissue oxygenation. In an acute stroke, neurovascular coupling is lost and OEF and its NIRS counterpart (HbO 2 and S t O 2 ) are influenced by both the degree of pathologic regional reduction in blood flow (CBF) and the evolution of the infarction process (dictating tissue oxygen demand or CMRO 2 ).…”

Simulation study of brain blood flow regulation by intra-cortical arterioles in an anatomically accurate large human vascular network. Part II: Flow variations induced by global or localized modifications of arteriolar diameters

“…Thus, it is not surprising to observe a large spectrum of variations in response to prescribed global arteriolar vasodilations. Actually, such heterogeneities in the spatiotemporal characteristics of cerebral blood volume (CBV) and flow (CBF) responses have also been observed between different areas (Wu et al, 2002;Chiarelli et al, 2007b;Vafaee and Gjedde, 2004), or even within the same cortical region (Kida et al, 2007;Jin and Kim, 2008). Several authors (Bandettini, 2007;Muller et al, 2005;Formisano and Goebel, 2003) have noted that the sources of this variability across the brain are likely dominated by variations in the vasculature rather than underlying neuronal activity.…”