Quantitative assessment of blood flow, blood volume and blood oxygenation effects in functional magnetic resonance imaging

The ability to measure the effects of local alterations in blood flow, blood volume and oxygenation by nuclear magnetic resonance has stimulated a surge of activity in functional MRI of many organs, particularly in its application to cognitive neuroscience. However, the exact description of these effects in terms of the interrelations between the MRI signal changes and the basic physiological parameters has remained an elusive goal. We here present this fundamental theory for spin-echo signal changes in perfused tissue and validate it in vivo in the cat brain by using the physiological alteration of hypoxic hypoxia. These experiments show that high-resolution absolute blood volume images can be obtained by using hemoglobin as a natural intravascular contrast agent. The theory also correctly predicts the magnitude of spin-echo MRI signal intensity changes on brain activation and thereby provides a sound physiological basis for these types of studies.

[1]  F. Hyder,et al.  Increased tricarboxylic acid cycle flux in rat brain during forepaw stimulation detected with 1H[13C]NMR. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[2]  V. P. Chacko,et al.  Oxygenation in the rabbit myocardium: assessment with susceptibility-dependent MR imaging. , 1993, Radiology.

[3]  S Zeger,et al.  Comparison of Cerebrovascular Response to Hypoxic and Carbon Monoxide Hypoxia in Newborn and Adult Sheep , 1984, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[4]  R. Turner,et al.  Dynamic magnetic resonance imaging of human brain activity during primary sensory stimulation. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[5]  Richard S. J. Frackowiak,et al.  Cerebral blood flow, blood volume and oxygen utilization. Normal values and effect of age. , 1990, Brain : a journal of neurology.

[6]  F. Ye,et al.  Relaxation enhancement of the transverse magnetization of water protons in paramagnetic suspensions of red blood cells , 1995, Magnetic resonance in medicine.

[7]  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.

[8]  R. P. Shockley,et al.  Determination of rat cerebral cortical blood volume changes by capillary mean transit time analysis during hypoxia, hypercapnia and hyperventilation , 1988, Brain Research.

[9]  O Henriksen,et al.  Signal changes in gradient echo images of human brain induced by hypo‐ and hyperoxia , 1995, NMR in biomedicine.

[10]  B. Siesjö,et al.  Brain energy metabolism , 1978 .

[11]  J A Frank,et al.  Functional magnetic resonance imaging in medicine and physiology. , 1990, Science.

[12]  M E Raichle,et al.  Evidence of the Limitations of Water as a Freely Diffusible Tracer in Brain of the Rhesus Monkey , 1974, Circulation research.

[13]  M A Williams,et al.  Cerebral O2 transport with hematocrit reduced by cross-linked hemoglobin transfusion. , 1996, The American journal of physiology.

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

[15]  R A Brooks,et al.  Explanation of cerebral white--gray contrast in computed tomography. , 1980, Journal of computer assisted tomography.

[16]  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.

[17]  A L Smith,et al.  Effect of arterial CO 2 tension on cerebral blood flow, mean transit time, and vascular volume. , 1971, Journal of applied physiology.

[18]  M D King,et al.  Identification of Collaterally Perfused Areas following Focal Cerebral Ischemia in the Rat by Comparison of Gradient Echo and Diffusion-Weighted MRI , 1995, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

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

[20]  P. Okunieff.  Towards noninvasive human tumor physiologic measurements. , 1995, International journal of radiation oncology, biology, physics.

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

[22]  Marcia Barinaga,et al.  Neuroscience: What Makes Brain Neurons Run? , 1997, Science.

[23]  R S Balaban,et al.  Comparison of EPI gradient‐echo contrast changes in cat brain caused by respiratory challenges with direct simultaneous evaluation of cerebral oxygenation via a cranial window , 1994, NMR in biomedicine.

[24]  M. D. Herbst,et al.  A review of water diffusion measurement by NMR in human red blood cells. , 1989, The American journal of physiology.

[25]  O. Yu,et al.  NMR relaxation rates and blood oxygenation level , 1995, Magnetic resonance in medicine.

[26]  Peter A. Bandettini,et al.  Effects of biophysical and physiologic parameters on brain activation‐induced R2* and R2 changes: Simulations using a deterministic diffusion model , 1995, Int. J. Imaging Syst. Technol..

[27]  M. Moseley,et al.  Real‐time observation of transient focal ischemia and hyperemia in cat brain , 1992, Magnetic resonance in medicine.

[28]  E. Ritman,et al.  In Vivo Relation of Intramyocardial Blood Volume to Myocardial Perfusion: Evidence Supporting Microvascular Site for Autoregulation , 1992, Circulation.

[29]  M. Ueki,et al.  Effect of alpha‐chloralose, halothane, pentobarbital and nitrous oxide anesthesia on metabolic coupling in somatosensory cortex of rat , 1992, Acta anaesthesiologica Scandinavica.

[30]  C. von Essen,et al.  Cerebral blood flow, cerebrovascular resistance and cerebral metabolic rate of oxygen in severe arterial hypoxia in dogs , 1979, Acta neurologica Scandinavica.

[31]  Ravi S. Menon,et al.  Intrinsic signal changes accompanying sensory stimulation: functional brain mapping with magnetic resonance imaging. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[32]  M. Fabry,et al.  Effect of magnetic susceptibility on nuclear magnetic resonance signals arising from red cells: a warning. , 1983, Biochemistry.

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

[34]  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.

[35]  S. Vijayakumar,et al.  Effects of hyperoxia on T  2* and resonance frequency weighted magnetic resonance images of rodent tumours , 1994, NMR in biomedicine.

[36]  F. Howe,et al.  Noninvasive monitoring of carbogen-induced changes in tumor blood flow and oxygenation by functional magnetic resonance imaging. , 1995, International journal of radiation oncology, biology, physics.

[37]  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.

[38]  G. Radda,et al.  Oxygenation dependence of the transverse relaxation time of water protons in whole blood at high field. , 1982, Biochimica et biophysica acta.

[39]  R. Bryant,et al.  Magnetic relaxation in blood and blood clots , 1990, Magnetic resonance in medicine.

[40]  R. S. Hinks,et al.  Time course EPI of human brain function during task activation , 1992, Magnetic resonance in medicine.

[41]  G. Pawlik,et al.  Quantitative capillary topography and blood flow in the cerebral cortex of cats: an in vivo microscopic study , 1981, Brain Research.

[42]  Weili Lin,et al.  In vivo validation of the bold mechanism: A review of signal changes in gradient echo functional MRI in the presence of flow , 1995, Int. J. Imaging Syst. Technol..

[43]  H. S. Gutowsky,et al.  Spin—Echo NMR Studies of Chemical Exchange. I. Some General Aspects , 1964 .

[44]  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.

[45]  R. Turner,et al.  Echo‐planar time course MRI of cat brain oxygenation changes , 1991, Magnetic resonance in medicine.

[46]  O B Paulson,et al.  Filtration and diffusion of water across the blood-brain barrier in man. , 1977, Microvascular research.

[47]  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.

[48]  T Asakura,et al.  NMR Relaxation Times of Blood: Dependence on Field Strength, Oxidation State, and Cell Integrity , 1987, Journal of computer assisted tomography.

[49]  C. Cuénod,et al.  Proton Transverse Nuclear Magnetic Relaxation in Oxidized Blood: a Numerical Approach , 1995, Magnetic resonance in medicine.

[50]  N. Lassen,et al.  Persistent Resetting of the Cerebral Oxygen/Glucose Uptake Ratio by Brain Activation: Evidence Obtained with the Kety—Schmidt Technique , 1995, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

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

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

[53]  R G Shulman,et al.  Nuclear magnetic resonance imaging and spectroscopy of human brain function. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

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