Calibrated functional MRI: Mapping the dynamics of oxidative metabolism

Abstract

MRI was extended to the measurement of changes in oxidative metabolism in the normal human during functionally induced changes in cellular activity. A noninvasive MRI method that is model-independent calibrates the blood oxygen level dependent (BOLD) signal of functional MRI (fMRI) against perfusion-sensitive MRI, using carbon dioxide breathing as a physiological reference standard. This calibration procedure provides a regional measurement of the expected sensitivity of the fMRI BOLD signal to changes in the cellular activity of the brain. Maps of the BOLD signal calibration factor showed regional heterogeneity, indicating that the magnitude of functionally induced changes in the BOLD signal will be dependent on both the local change in blood f low and the local baseline physiology of the cerebral cortex. BOLD signal magnitude is shown to be reduced by 32% from its expected level by the action of oxygen metabolism. The calibrated fMRI technique was applied to stimulation of the human visual cortex with an alternating radial checkerboard pattern. With this stimulus oxygen consumption increased 16% whereas blood f low increased 45%. Although this result is consistent with previous findings of a significant difference between the increase in blood f low and oxygen consumption, it does indicate clearly that oxidative metabolism is a significant component of the metabolic response of the brain to functionally induced changes in cellular activity.Functionally related changes in neuronal activity in the normal brain are reliably accompanied by changes in local cerebral blood flow (CBF) (1). The degree to which the cerebral metabolic rate for oxygen (CMR O2 ) also changes with activityrelated increases and decreases in neuronal activity remains controversial. Although some reports show little or no taskinduced increase in CMR O2 (2-4), others have shown varying degrees of coupling of oxidative metabolism to glucose consumption and blood flow (5-7), both of which increase dramatically with task activation (3,4,8). Some have suggested that the reason CBF changes more than CMR O2 during functionally related increases in neuronal activity (decreases have not been addressed) is to enhance the diffusion-limited delivery of oxygen to the tissue (9-11).Current functional MRI (fMRI) methods rely on the fact that CBF changes more than CMR O2 , producing localized changes in tissue oxygen content. These localized changes in tissue oxygen content change magnetic fields in a manner that can be detected with MRI. This signal has been termed the blood oxygen level dependent (BOLD) signal of fMRI (12, 13). The fMRI BOLD signal has been viewed as a reasonable marker of functionally related changes in neuronal activity. The magnitude of the BOLD signal, of course, is dependent on the relationship between changes, if any, in CMR O2 and the changes in CBF. The greater the increase in CMR O2 for any increase in CBF, the smaller the BOLD signal becomes and vice versa.In this paper we examine the degree to which the relationship betw...

Human Cerebral Blood Flow and Metabolism in Acute Insulin-Induced Hypoglycemia

“…The flow and transverse relaxation data have been incorporated into a model of deoxyhemoglobin concentration, oxygen extraction, and consumption by numerous workers (Ogawa et al, 1993;Davis et al, 1998;Hoge et al, 1999;Oja et al, 1999) expressed in equation (1). The blood susceptibility-induced transverse relaxation rate, R 2 0 , is calculated from the time reversible gradient echo relaxation rate, R 2 *, and time irreversible spin echo intrinsic relaxation rate, R 2intrinsic , corrected by the loss of signal from B o homogeneity (An and Lin, 2002;Yablonskiy, 2002).…”

“…These coupling ratios are consistent with several recent estimates of flow metabolism coupling during task activation. For example, using MR, Hoge et al (1999) reported fM/fP ratio of 0.52 for graded visual stimulation while Davis et al (1998) reported an fM/fP ratio of 0.35 using a 12 Hz visual stimulation paradigm. Using PET, Marrett and Gjedde (1997) report an fM/fP ratio of 0.37 with a 4 Hz visual stimulation protocol, while Fox and Raichle (1986) report an fM/fP ratio of 0.1 using somatosensory stimulation in their early PET studies.…”

Modeling the hemodynamic response to brain activation

“…Most recent experimental measurements find n = 2-3 (Davis et al, 1998;Hoge et al, 1999;Kastrup et al, 2002;Marrett and Gjedde, 1997;Seitz and Roland, 1992), although larger values have also been reported (Fox and Raichle, 1986;Kuwabara et al, 1992).…”

“…7. There is a growing body of evidence suggesting that the baseline CBF can have a strong effect on the magnitude of the BOLD response to the same stimulus (Corfield et al, 2001;Davis et al, 1998;Hoge et al, 1999;Kastrup et al, 1999Kastrup et al, , 2002Kim et al, 1999;Li et al, 1999). For example, if baseline CBF is increased by breathing CO 2 , the BOLD response to the same task is reduced substantially.…”

“…Following Davis et al (1998), these ideas can be combined to model the MR signal in terms of the blood volume (V) and the oxygen extraction fraction (E):…”