Neuroimaging With Calibrated fMRI

The conventional functional MRI (fMRI) map offers information indirectly about localized changes in neuronal activity because it reflects changes in blood oxygenation, not actual neuronal activity. To provide a neurophysiological basis of fMRI, researchers have used electrophysiology to show correlations of fMRI and electric signals. However, quantitative interpretation of the degree to which neuronal activity has changed still cannot be made from conventional fMRI data. The fMRI signal has 2 parts: one describes the correlation between oxidative metabolism (cerebral metabolic rate of oxygen [CMRO2]) and cerebral blood flow (CBF), which supports the bioelectric work to sustain neuronal excitability; the other is the requisite dilation of blood vessels (cerebral blood volume [CBV]), which is the mechanical response involved in removal of waste while providing nutrients. Since changes in energy metabolism are related to bioelectric work, we tested whether spiking frequency of a neuronal ensemble (&ngr;) is reflected by local energy metabolism (CMRO2) in rat brain. We used extracellular recordings to measure &Dgr;&ngr;/&ngr; and calibrated fMRI (ie, using fMRI signal, CBF, and CBV maps) to measure &Dgr;CMRO2/CMRO2 during sensory stimulation. We found that &Dgr;CMRO2/CMRO2 is ≈&Dgr;&ngr;/&ngr;, which suggests efficient energy use during brain work. Thus, calibrated fMRI provides data on where and by how much the neuronal activity has changed. Possibilities of utilizing calibrated fMRI as a neuroimaging method are discussed.

[1]  S. Ogawa,et al.  An approach to probe some neural systems interaction by functional MRI at neural time scale down to milliseconds. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[2]  R G Shulman,et al.  Lactate efflux and the neuroenergetic basis of brain function , 2001, NMR in biomedicine.

[3]  Fahmeed Hyder,et al.  Dynamic fMRI and EEG Recordings during Spike-Wave Seizures and Generalized Tonic-Clonic Seizures in WAG/Rij Rats , 2004, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[4]  Lars Garby,et al.  Bioenergetics : its thermodynamic foundations , 1995 .

[5]  Alan C. Evans,et al.  Cerebral blood flow and metabolism during nonspecific bilateral visual stimulation in normal subjects , 1993 .

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

[7]  G. Bonvento,et al.  Is α-chloralose plus halothane induction a suitable anesthetic regimen for cerebrovascular research? , 1994, Brain Research.

[8]  R. J. Seitz,et al.  Vibratory stimulation increases and decreases the regional cerebral blood flow and oxidative metabolism: a positron emission tomography (PET) study , 1992, Acta neurologica Scandinavica.

[9]  J. Greenberg,et al.  Positron emission tomography of the brain. , 1989, Computerized medical imaging and graphics : the official journal of the Computerized Medical Imaging Society.

[10]  R. Dudley,et al.  Influence of chloralose on brain regional glucose utilization , 1982, Brain Research.

[11]  E Meyer,et al.  Density of perfused capillaries in living human brain during functional activation. , 1992, Progress in brain research.

[12]  Wilder Penfield,et al.  THE EVIDENCE FOR A CEREBRAL VASCULAR MECHANISM IN EPILEPSY , 1933 .

[13]  M. Young,et al.  Neuronal population activity and functional imaging , 1999, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[14]  A. Towe,et al.  Relative effects of pentobarbital and chloralose on the responsiveness of neurons in sensorimotor cerebral cortex of the domestic cat , 1979, Neuroscience.

[15]  M. Kawakami,et al.  Vidarabine therapy for virus-associated cystitis after allogeneic bone marrow transplantation , 1997, Bone Marrow Transplantation.

[16]  Fahmeed Hyder,et al.  Relationship between CMRO2 and Neuronal Activity , 2005 .

[17]  G F Mason,et al.  Dependence of Oxygen Delivery on Blood Flow in Rat Brain: A 7 Tesla Nuclear Magnetic Resonance Study , 2000, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[18]  R G Shulman,et al.  Assessment and discrimination of odor stimuli in rat olfactory bulb by dynamic functional MRI. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[19]  Deriving Changes in CMRO2 from Calibrated fMRI , 2005 .

[20]  F. Hyder,et al.  Stimulated changes in localized cerebral energy consumption under anesthesia. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[21]  D. Ciraulo Neuropsychopharmacology: The Fifth Generation of Progress , 2003 .

[22]  D L Rothman,et al.  High-Resolution CMRO2 Mapping in Rat Cortex: A Multiparametric Approach to Calibration of BOLD Image Contrast at 7 Tesla , 2000, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[23]  N. Logothetis,et al.  Neurophysiological investigation of the basis of the fMRI signal , 2001, Nature.

[24]  Keiji Tanaka,et al.  Inferotemporal cortex and object vision. , 1996, Annual review of neuroscience.

[25]  D C Reutens,et al.  Oxygen Consumption of Cerebral Cortex Fails to Increase during Continued Vibrotactile Stimulation , 1999, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[26]  Dennis S. Charney,et al.  Neuropsychopharmacology : The Fifth Generation of Progress , 2002 .

[27]  K. Hossmann,et al.  Simultaneous recording of evoked potentials and T  *2 ‐weighted MR images during somatosensory stimulation of rat , 1999, Magnetic resonance in medicine.

[28]  F. Hyder,et al.  Activation of single whisker barrel in rat brain localized by functional magnetic resonance imaging. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[29]  S Marrett,et al.  Changes of blood flow and oxygen consumption in visual cortex of living humans. , 1997, Advances in experimental medicine and biology.

[30]  R G Shulman,et al.  In vivo nuclear magnetic resonance spectroscopy studies of the relationship between the glutamate-glutamine neurotransmitter cycle and functional neuroenergetics. , 1999, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[31]  J. Hainsworth,et al.  A phase I–II study of high-dose melphalan, mitoxantrone and carboplatin with peripheral blood stem cell support in patients with advanced ovarian or breast carcinoma , 1997, Bone Marrow Transplantation.

[32]  A. Hill The Combinations of Haemoglobin with Oxygen and with Carbon Monoxide. I. , 1913, The Biochemical journal.

[33]  A. Gjedde,et al.  Model of Blood–Brain Transfer of Oxygen Explains Nonlinear Flow-Metabolism Coupling During Stimulation of Visual Cortex , 2000, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[34]  M D Ginsberg,et al.  Increases in both cerebral glucose utilization and blood flow during execution of a somatosensory task , 1988, Annals of neurology.

[35]  Robert G. Shulman,et al.  Brain Energetics and Neuronal Activity: Applications to fMRI and Medicine , 2005 .

[36]  F. Hyder,et al.  25 IN VIVO MAGNETIC RESONANCE SPECTROSCOPY STUDIES OF THE GLUTAMATE AND GABA NEUROTRANSMITTER CYCLES AND FUNCTIONAL NEUROENERGETICS , 2002 .

[37]  M. Raichle,et al.  Focal physiological uncoupling of cerebral blood flow and oxidative metabolism during somatosensory stimulation in human subjects. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[38]  D L Rothman,et al.  Quantitative multi-modal functional MRI with blood oxygenation level dependent exponential decays adjusted for flow attenuated inversion recovery (BOLDED AFFAIR). , 2000, Magnetic resonance imaging.

[39]  D. Hadley Brain energetics and neuronal activity: applications to fMRI and medicine , 2005 .

[40]  R. Desimone,et al.  Neural mechanisms for visual memory and their role in attention. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[41]  P E Roland,et al.  Does mental activity change the oxidative metabolism of the brain? , 1987, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[42]  M. Desban,et al.  Local cerebral glucose consumption in the rat. I. Effects of halothane anesthesia , 1983, The Journal of comparative neurology.

[43]  M E Raichle,et al.  Correlation Between Regional Cerebral Blood Flow and Oxidative Metabolism: In Vivo Studies in Man , 1976 .

[44]  J. Hodes,et al.  Selective Changes in Local Cerebral Glucose Utilization Induced by Phenobarbital in the Rat , 1985, Anesthesiology.

[45]  R G Shulman,et al.  A model for the regulation of cerebral oxygen delivery. , 1998, Journal of applied physiology.

[46]  K. Nagata [Brain energy metabolism]. , 1997, Nihon rinsho. Japanese journal of clinical medicine.

[47]  F. Hyder,et al.  Total neuroenergetics support localized brain activity: Implications for the interpretation of fMRI , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[48]  Fahmeed Hyder,et al.  Energetic basis of brain activity: implications for neuroimaging , 2004, Trends in Neurosciences.

[49]  Charles M. Gray,et al.  Synchronous oscillations in neuronal systems: Mechanisms and functions , 1994, Journal of Computational Neuroscience.

[50]  H. Mayberg Brain Activation , 1994, Neurology.

[51]  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.

[52]  P. Goldman-Rakic Regional and cellular fractionation of working memory. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[53]  J. S. McCasland,et al.  High‐resolution 2‐deoxyglucose mapping of functional cortical columns in mouse barrel cortex , 1988, The Journal of comparative neurology.

[54]  M. Nicolelis,et al.  Principal component analysis of neuronal ensemble activity reveals multidimensional somatosensory representations , 1999, Journal of Neuroscience Methods.

[55]  C. Sherrington,et al.  On the Regulation of the Blood‐supply of the Brain , 1890, The Journal of physiology.

[56]  Fahmeed Hyder,et al.  Functional MRI bold signal coincides with electrical activity in the rat whisker barrels , 1997, Magnetic resonance in medicine.

[57]  F. Hyder,et al.  Quantitative functional imaging of the brain: towards mapping neuronal activity by BOLD fMRI , 2001, NMR in biomedicine.

[58]  Fahmeed Hyder,et al.  Biophysical basis of brain activity: implications for neuroimaging , 2002, Quarterly Reviews of Biophysics (print).

[59]  Y. Katayama,et al.  Response of Regional Cerebral Blood Flow and Oxygen Metabolism to Thalamic Stimulation in Humans as Revealed by Positron Emission Tomography , 1986, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[60]  Karl J. Friston,et al.  A direct quantitative relationship between the functional properties of human and macaque V5 , 2000, Nature Neuroscience.

[61]  M. Mintun,et al.  Nonoxidative glucose consumption during focal physiologic neural activity. , 1988, Science.

[62]  F. Hyder,et al.  Cerebral energetics and spiking frequency: The neurophysiological basis of fMRI , 2002, Proceedings of the National Academy of Sciences of the United States of America.