Physiological basis for BOLD MR signal changes due to neuronal stimulation: Separation of blood volume and magnetic susceptibility effects

An NMR method is applied for separating blood volume and magnetic susceptibility effects in response to neuronal stimulation in a rat model. The method uses high susceptibility contrast agents to enhance blood volume induced signal changes. In the absence of exogenous agent, the dominant source of signal change on neuronal activation is associated with the signal increase from the blood oxygen level dependent (BOLD) effect. The relative negative contribution of blood volume changes to BOLD changes is maximally estimated to be 34%. The blood volume changes associated with median nerve stimulation (7 Hz) in the motor cortex are 26 ± 7% and the corresponding blood susceptibility changes are 0.021 ± 0.006 ppm. These methods can be applied to enhance the sensitivity of fMRl signal response and provide accurate quantitative measures of blood volume response to stimulation.

[1]  R. Seitz,et al.  Learning of Sequential Finger Movements in Man: A Combined Kinematic and Positron Emission Tomography (PET) Study , 1992, The European journal of neuroscience.

[2]  S. Ogawa,et al.  Oxygenation‐sensitive contrast in magnetic resonance image of rodent brain at high magnetic fields , 1990, Magnetic resonance in medicine.

[3]  J C Gore,et al.  Physiologic basis for BOLD MR signal changes due to hypoxia/hyperoxia: Separation of blood volume and magnetic susceptibility effects , 1997, Magnetic resonance in medicine.

[4]  S. Ogawa,et al.  The sensitivity of magnetic resonance image signals of a rat brain to changes in the cerebral venous blood oxygenation , 1993, Magnetic resonance in medicine.

[5]  J. Gore,et al.  Intravascular susceptibility contrast mechanisms in tissues , 1994, Magnetic resonance in medicine.

[6]  B R Rosen,et al.  Mr contrast due to intravascular magnetic susceptibility perturbations , 1995, Magnetic resonance in medicine.

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

[8]  R. S. Hinks,et al.  Spin‐echo and gradient‐echo epi of human brain activation using bold contrast: A comparative study at 1.5 T , 1994, NMR in biomedicine.

[9]  P. Roland,et al.  Supplementary motor area and other cortical areas in organization of voluntary movements in man. , 1980, Journal of neurophysiology.

[10]  W. Anderson,et al.  Reference-Independent Nuclear Magnetic Resonance Solvent Shifts , 1970 .

[11]  B. Rosen,et al.  Functional mapping of the human visual cortex by magnetic resonance imaging. , 1991, Science.

[12]  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.

[13]  E. Haacke,et al.  Theory of NMR signal behavior in magnetically inhomogeneous tissues: The static dephasing regime , 1994, Magnetic resonance in medicine.

[14]  S G Kim,et al.  Perfusion imaging by a flow‐sensitive alternating inversion recovery (Fair) technique: Application to functional brain imaging , 1997, Magnetic resonance in medicine.

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

[16]  M. Dimitrijevic,et al.  Characteristics of spinal cord-evoked responses in man. , 1980, Applied neurophysiology.

[17]  X. Hu,et al.  Evaluation of the early response in fMRI in individual subjects using short stimulus duration , 1997, Magnetic resonance in medicine.

[18]  Karl J. Friston,et al.  Regional cerebral blood flow during voluntary arm and hand movements in human subjects. , 1991, Journal of neurophysiology.

[19]  D. Tank,et al.  4 Tesla gradient recalled echo characteristics of photic stimulation‐induced signal changes in the human primary visual cortex , 1993 .

[20]  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.

[21]  F. Hyder,et al.  Dynamic Magnetic Resonance Imaging of the Rat Brain during Forepaw Stimulation , 1994, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[22]  Prof. Dr. Karl Zilles The Cortex of the Rat , 1985, Springer Berlin Heidelberg.

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

[24]  J C Gore,et al.  Functional magnetic resonance imaging of median nerve stimulation in rats at 2.0 T , 1997, Magnetic resonance in medicine.

[25]  B. Rosen,et al.  Measurement of regional blood oxygenation and cerebral hemodynamics , 1993, Magnetic resonance in medicine.

[26]  J. Frahm,et al.  Cerebral blood oxygenation in rat brain during hypoxic hypoxia. Quantitative MRI of effective transverse relaxation rates , 1994, Magnetic resonance in medicine.

[27]  A. Toga,et al.  Functional Increases in Cerebral Blood Volume over Somatosensory Cortex , 1995, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[28]  M Hoehn-Berlage,et al.  Variation of functional MRI signal in response to frequency of somatosensory stimulation in α‐chloralose anesthetized rats , 1996, Magnetic resonance in medicine.

[29]  J C Mazziotta,et al.  Somatotopic mapping of the primary motor cortex in humans: activation studies with cerebral blood flow and positron emission tomography. , 1991, Journal of neurophysiology.

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