Relative changes of cerebral arterial and venous blood volumes during increased cerebral blood flow: Implications for BOLD fMRI

Measurement of cerebral arterial and venous blood volumes during increased cerebral blood flow can provide important information regarding hemodynamic regulation under normal, pathological, and neuronally active conditions. In particular, the change in venous blood volume induced by neural activity is one critical component of the blood oxygenation level‐dependent (BOLD) signal because BOLD contrast is dependent only on venous blood, not arterial blood. Thus, relative venous and arterial blood volume (rCBV) and cerebral blood flow (rCBF) in α‐chlorolase‐anesthetized rats under hypercapnia were measured by novel diffusion‐weighted 19F NMR following an i.v. administration of intravascular tracer, perfluorocarbons, and continuous arterial spin labeling methods, respectively. The relationship between rCBF and total rCBV during hypercapnia was rCBV(total) = rCBF0.40, which is consistent with previous PET measurement in monkeys. This relationship can be linearized in a CBF range of 50–130 ml/100 g/min as ΔrCBV(total)/ ΔrCBF = 0.31 where ΔrCBV and ΔrCBF represent rCBV and rCBF changes. The average arterial volume fraction was 0.25 at a basal condition with CBF of ∼60 ml/100 g/min and increased up to 0.4 during hypercapnia. The change in venous rCBV was 2‐fold smaller than that of total rCBV (ΔrCBV(vein)/ΔrCBF = 0.15), while the arterial rCBV change was 2.5 times larger than that of total rCBV (ΔrCBV(artery)/ΔrCBF = 0.79). These NMR results were confirmed by vessel diameter measurements with in vivo videomicroscopy. The absolute venous blood volume change contributes up to 36% of the total blood volume change during hypercapnia. Our findings provide a quantitative physiological model of BOLD contrast. Magn Reson Med 45:791–800, 2001. © 2001 Wiley‐Liss, Inc.

[1]  J. Pappenheimer Peripheral circulation. , 1952, Annual review of physiology.

[2]  A. Guyton,et al.  Textbook of Medical Physiology , 1961 .

[3]  J. E. Tanner,et al.  Spin diffusion measurements : spin echoes in the presence of a time-dependent field gradient , 1965 .

[4]  M. Raichle,et al.  The Effects of Changes in PaCO2 Cerebral Blood Volume, Blood Flow, and Vascular Mean Transit Time , 1974, Stroke.

[5]  J. Riess,et al.  Perfluoro compounds as blood substitutes. , 1978, Angewandte Chemie.

[6]  J M Seelig,et al.  Comparative responses of cerebellar and cerebral arterioles to changes in PaCO2 in cats. , 1984, The American journal of physiology.

[7]  M. Raichle,et al.  What is the Correct Value for the Brain-Blood Partition Coefficient for Water? , 1985, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[8]  P. Grenier,et al.  MR imaging of intravoxel incoherent motions: application to diffusion and perfusion in neurologic disorders. , 1986, Radiology.

[9]  M. Raichle,et al.  Cerebral Blood Volume Measured with Inhaled C15O and Positron Emission Tomography , 1987, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[10]  K. Lowe,et al.  Perfluorocarbons as oxygen-transport fluids. , 1987, Comparative biochemistry and physiology. A, Comparative physiology.

[11]  John C. Gore,et al.  Studies of diffusion in random fields produced by variations in susceptibility , 1988 .

[12]  D. Tank,et al.  Brain magnetic resonance imaging with contrast dependent on blood oxygenation. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[13]  B. Rosen,et al.  Perfusion imaging with NMR contrast agents , 1990, Magnetic resonance in medicine.

[14]  S. Ogawa Brain magnetic resonance imaging with contrast-dependent oxygenation , 1990 .

[15]  G P Stomp,et al.  Multiple inversion recovery reduces static tissue signal in angiograms , 1991, Magnetic resonance in medicine.

[16]  Jeffrey J. Neil,et al.  Detection of pseudodiffusion in rat brain following blood substitution with perfluorocarbon , 1992 .

[17]  Donald S. Williams,et al.  Measurement of rat brain perfusion by NMR using spin labeling of arterial water: In vivo determination of the degree of spin labeling , 1993, Magnetic resonance in medicine.

[18]  Ravi S. Menon,et al.  Functional brain mapping by blood oxygenation level-dependent contrast magnetic resonance imaging. A comparison of signal characteristics with a biophysical model. , 1993, Biophysical journal.

[19]  R Gruetter,et al.  Automatic, localized in Vivo adjustment of all first‐and second‐order shim coils , 1993, Magnetic resonance in medicine.

[20]  J J Neil,et al.  An evaluation of the sensitivity of the intravoxel incoherent motion (IVIM) method of blood flow measurement to changes in cerebral blood flow , 1994, Magnetic resonance in medicine.

[21]  B. Dardzinski,et al.  Rapid tissue oxygen tension mapping using 19F inversion‐recovery echo‐planar imaging of P erfluoro‐15 ‐crown‐5‐ether , 1994, Magnetic resonance in medicine.

[22]  X. Xu,et al.  Nitro-L-arginine attenuates hypercapnic cerebrovasodilation without affecting cerebral metabolism. , 1994, The American journal of physiology.

[23]  J. R. Baker,et al.  The intravascular contribution to fmri signal change: monte carlo modeling and diffusion‐weighted studies in vivo , 1995, Magnetic resonance in medicine.

[24]  Donald S. Williams,et al.  Multi‐Slice MRI of Rat Brain Perfusion During Amphetamine Stimulation Using Arterial Spin Labeling , 1995, Magnetic resonance in medicine.

[25]  A. Song,et al.  Diffusion weighted fMRI at 1.5 T , 1996, Magnetic resonance in medicine.

[26]  B R Rosen,et al.  Improving MR quantification of regional blood volume with intravascular T1 contrast agents: Accuracy, precision, and water exchange , 1996, Magnetic resonance in medicine.

[27]  G L Wolf,et al.  Measurement of cerebral blood volume with subtraction three-dimensional functional CT. , 1996, AJNR. American journal of neuroradiology.

[28]  T A Woolsey,et al.  Neuronal units linked to microvascular modules in cerebral cortex: response elements for imaging the brain. , 1996, Cerebral cortex.

[29]  Seong‐gi Kim Cmrr,et al.  Comparison of blood oxygenattion and cerebral blood flow effect in fMRI: Estimation of relative oxygen consumption change , 1997, Magnetic resonance in medicine.

[30]  T. Ebner,et al.  Local and propagated vascular responses evoked by focal synaptic activity in cerebellar cortex. , 1997, Journal of neurophysiology.

[31]  J C Gore,et al.  Quantification of intravascular and extravascular contributions to BOLD effects induced by alteration in oxygenation or intravascular contrast agents , 1998, Magnetic resonance in medicine.

[32]  B. Rosen,et al.  Dynamic functional imaging of relative cerebral blood volume during rat forepaw stimulation , 1998, Magnetic resonance in medicine.

[33]  Hellmut Merkle,et al.  Quantitative measurements of cerebral blood flow in rats using the FAIR technique: Correlation with previous lodoantipyrine autoradiographic studies , 1998, Magnetic resonance in medicine.

[34]  Egill Rostrup,et al.  Determination of relative CMRO2 from CBF and BOLD changes: Significant increase of oxygen consumption rate during visual stimulation , 1999, Magnetic resonance in medicine.

[35]  B. Rosen,et al.  Evidence of a Cerebrovascular Postarteriole Windkessel with Delayed Compliance , 1999, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[36]  R. Gruetter,et al.  In vivo 1H NMR spectroscopy of rat brain at 1 ms echo time , 1999, Magnetic resonance in medicine.

[37]  K. Uğurbil,et al.  Diffusion‐weighted spin‐echo fMRI at 9.4 T: Microvascular/tissue contribution to BOLD signal changes , 1999, Magnetic resonance in medicine.

[38]  N. Akgören,et al.  Functional recruitment of red blood cells to rat brain microcirculation accompanying increased neuronal activity in cerebellar cortex. , 1999, Neuroreport.

[39]  Seong-Gi Kim,et al.  Simultaneous Blood Oxygenation Level-Dependent and Cerebral Blood Flow Functional Magnetic Resonance Imaging during Forepaw Stimulation in the Rat , 1999, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[40]  Seong-Gi Kim,et al.  In vivo MR measurements of regional arterial and venous blood volume fractions in intact rat brain , 2000, Magnetic resonance in medicine.