Dependence of Oxygen Delivery on Blood Flow in Rat Brain: A 7 Tesla Nuclear Magnetic Resonance Study

Abstract

Magnetic resonance imaging (MRI) and spectroscopy (MRS) were used at a magnetic field strength of 7 T to measure CBF and CMRO2 in the sensorimotor cortex of mature rats at different levels of cortical activity. In rats maintained on morphine anesthesia, transitions to lower activity and higher activity states were produced by administration of pentobarbital and nicotine, respectively. Under basal conditions of morphine sulfate anesthesia, CBF was 0.75 +/- 0.09 mL x g(-1) x min(-1) and CMRO2 was 3.15 +/- 0.18 micromol x g(-1) x min(-1). Administration of sodium pentobarbital reduced CBF and CMRO2 by 66% +/- 16% and 61% +/- 6%, respectively (i.e., "deactivation"). In contrast, administration of nicotine hydrogen tartrate increased CBF and CMRO2 by 41% +/- 5% and 30% +/- 3%, respectively (i.e., "activation"). The resting values of CBF and CMRO2 for alpha-chloralose anesthetized rats were 0.40 +/- 0.09 mL x g(-1) x min(-1) and 1.51 +/- 0.06 micromol x g(-1) x min(-1), respectively. Upon forepaw stimulation, CBF and CMRO2 were focally increased by 34% +/- 10% and 26% +/- 12%, respectively, above the resting nonanesthetized values (i.e., "activation"). Incremental changes in CBF and CMRO2, when expressed as a percentage change for "deactivation" and "activation" from the respective control conditions, were linear (R2 = 0.997) over the entire range examined with the global and local perturbations. This tight correlation for cerebral oxygen delivery in vivo is supported by a recent model where the consequence of a changing effective diffusivity of the capillary bed for oxygen, D, has been hypothetically shown to be linked to alterations in CMRO2 and CBF. This assumed functional characteristic of the capillary bed can be theoretically assessed by the ratio of fractional changes in D with respect to changes in CBF, signified by omega. A value 0.81 +/- 0.23 was calculated for omega with the in vivo data presented here, which in turn corresponds to a supposition that the effective oxygen diffusivity of the capillary bed is not constant but presumably varies to meet local requirements in oxygen demand in a similar manner with both "deactivation" and "activation."

Tightly coupled brain activity and cerebral ATP metabolic rate

“…The degree of CMR glc suppression by deep pentobarbital anesthesia was reported to be 40-60% compared with nitrous oxide analgesia, light ␣-chloralose anesthesia, or the conscious animal (24,27,28). It was also reported that administration of sodium pentobarbital reduced CBF and CMRO 2 by 66% and 61%, respectively, relative to a light anesthetic condition with morphine sulfate (21). Other reports showed that thiopentalinduced isoelectric condition resulted in a reduction of global CMRO 2 and CMR glc by 47% and 61%, respectively, in the non-human primate brain relative to the awake condition (29,30).…”

“…In this study, the rat brain activity was altered under four conditions by using three types of anesthetic chemicals [2% isoflurane (IsoF); ␣-chloralose (␣-Ch), and sodium pentobarbital (Pen)], and two Pen doses (low-Pen vs. high-Pen) were applied, in which high-Pen led to complete suppression of spontaneous EEG signal (i.e., isoelectric state) (21). The in vivo 31 P MT approach (9-12) was applied to measure both the forward chemical exchange fluxes (F f ) from PCr to ATP [i.e., forward CK reaction flux (F f , CK ) related to the PCr 3 ATP reaction catalyzed by CK] and from P i to ATP [i.e., forward ATPase reaction flux (F f,ATPase ) related to the Pi 3 ATP reaction catalyzed by ATPase] by selectively saturating the ␥-ATP resonance peak under varied brain activity states in the rat.…”

Cerebral energetics and spiking frequency: The neurophysiological basis of fMRI

“…All in vivo fMRI data were collected on a 7T Bruker (Billerica, MA) horizontal-bore spectrometer with a homogeneous transmit and local receive 1 H radio-frequency coil (10,16). Changes in CMR O2 were calculated from the BOLD signal (9, 10, 12)…”

“…*Significantly different values in condition I vs. condition II (consecutively) for all increments: P Ͻ 0.02, P Ͻ 0.03, P Ͻ 0.06, P Ͻ 0.02). † Significantly different basal CBF (P Ͻ 0.05; estimated from 0.9 Ϯ 0.2 ml͞g͞min in baseline of condition I vs. 0.6 Ϯ 0.2 ml͞g͞min in baseline of condition II) were measured by spin labeling MRI (16,17). On forepaw stimulation from baseline of conditions I and II the final CBF values were 1.4 Ϯ 0.2 and 1.5 Ϯ 0.3 ml͞g͞min, respectively, which were insignificantly different (P Ͻ 0.32).…”

Task-Related Signal Decrease on Functional Magnetic Resonance Imaging.

“…PET studies suggest that blood-brain transfer of oxygen in normal brain is not constant but presumably varies to meet local requirements in oxygen demand. 17,34) These factors interact to produce the BOLD contrast, so the mechanism is quite complicated even in normal subjects. This complexity is one reason why the BOLD response is reported to vary among individuals and areas in the brain, so fMR imaging in patients should be interpreted individually to consider the various factors affecting the neuronal function, especially when the fMR imaging is used to guide surgical planning.…”