Measurement of Cerebral Blood Flow in the Rat with Intravenous Injection of [11C]Butanol by External Coincidence Counting: A Repeatable and Noninvasive Method in the Brain

No method has been reported for measuring CBF, repeatedly and noninvasively, in the rat brain. A new method is described, which is noninvasive to the brain, skull, or cervical large vessels. Two pairs of coincidence detectors were positioned, one over the rat brain and the other at the loop of a catheter inserted into the femoral artery. The coincidence head curve and arterial curve were recorded after intravenous injection of 1-[11C]butanol in 15 rats. CBF was calculated by one-compartment curve fitting (CBFo) from 1-min data and with the recirculation corrected height/area method from 3-min data (CBFh · 3min) and 5-min data (CBFh · 5min). CBFo agreed well with CBFh · 5min, although a slight overestimation was observed in CBFh · 3min. The normal CBFo in the normocapnic group (n = 6, paco2 36.7 ± 2.3 mm Hg) was 1.76 ± 0.49 ml/g min (mean ± SD). A good correlation was observed between CBFo (y) and Paco2 (x), and the regression line was y = 0.0629x – 0.715 (r = 0.88, p < 0.0001). We concluded that this method gives the stable blood flow values noninvasively and with a minimum loss of blood (<0.28 ml per measurement). Applications of this method include activation studies, studies on the effect of drugs and treatments, and water and oxygen extraction fraction studies using different tracers in the same rat.

[1]  B. Nilsson,et al.  Estimation of cerebral extraction of circulating compounds by the brain uptake index method: influence of circulation time, volume injection, and cerebral blood flow. , 1979, Acta physiologica Scandinavica.

[2]  J L Lear,et al.  Use of 123I and 14C in a double radionuclide autoradiographic technique for simultaneous measurement of LCBF and LCMRgl. Theory and method. , 1981, Stroke.

[3]  T. Duffy,et al.  Simultaneous Measurement of Cerebral Blood Flow and Unidirectional Movement of Substances Across the Blood‐Brain Barrier: Theory, Method, and Application to Leucine , 1981, Journal of neurochemistry.

[4]  Cerebral blood flow studies in man using recirculation corrected height/area (H/A) computations for intravenous injection of 133Xenon. , 1982, Stroke.

[5]  H I Glass,et al.  Effect of alterations in the arterial carbon dioxide tension on the blood flow through the cerebral cortex at normal and low arterial blood pressures. , 1965 .

[6]  N. Lassen,et al.  Blood flow and metabolic rate for oxygen in the cerebral cortex of the rat. , 1973, Acta physiologica Scandinavica.

[7]  H. E. Johns,et al.  Iterative Response Correction for a Scintillation Spectrometer , 1961 .

[8]  R. Hemmingsen,et al.  Rapid and repetitive measurements of blood flow and oxygen consumption in the rat brain using intraarterial xenon injection. , 1977, Acta physiologica Scandinavica.

[9]  M. Reivich,et al.  ARTERIAL PCO2 AND CEREBRAL HEMODYNAMICS. , 1965, The American journal of physiology.

[10]  M. Ingvar,et al.  Local versus regional cerebral blood flow in the rat at high (hypoxia) and low (phenobarbital anesthesia) flow rates. , 1979, Acta physiologica Scandinavica.

[11]  R. Busto,et al.  A radioisotopic method for the simultaneous quantitation of regional cerebral blood flow and glucose utilization in small dissected samples: Validation studies and values in the nitrous oxide-anesthetized rat , 1981, Brain Research.

[12]  D. Ingvar,et al.  Measurement of regional cerebral blood flow. , 1977, International journal of neurology.

[13]  B. Siesjö,et al.  Cerebral blood flow in ischemia caused by carotid artery ligation in the rat. , 1973, Acta physiologica Scandinavica.

[14]  M. Ginsberg,et al.  Synthesis of C-11 iodoantipyrine for positron emission tomography. , 1981, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[15]  M. Purves,et al.  Observations on the Extrinsic Neural Control of Cerebral Blood Flow in the Baboon , 1969, Circulation research.

[16]  T. Pedley,et al.  Regional Cerebral Blood Flow in the Rat as Determined by Particle Distribution and by Diffusible Tracer , 1980, Stroke.

[17]  M D Ginsberg,et al.  A Simplified in vivo Autoradiographic Strategy for the Determination of Regional Cerebral Blood Flow by Positron Emission Tomography: Theoretical Considerations and Validation Studies in the Rat , 1982, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[18]  Measurement of overall blood flow and oxygen consumption in the rat brain. , 1974, Acta physiologica Scandinavica.

[19]  A. Gjedde,et al.  Rapid simultaneous determination of regional blood flow and blood-brain glucose transfer in brain of rat. , 1980, Acta physiologica Scandinavica.

[20]  Michael E. Phelps,et al.  Error Sensitivity of Fluorodeoxyglucose Method for Measurement of Cerebral Metabolic Rate of Glucose , 1981 .

[21]  G. Gibson,et al.  Impaired Synthesis of Acetylcholine by Mild Hypoxic Hypoxia or Nitrous Oxide , 1981, Journal of neurochemistry.

[22]  R. Busto,et al.  11C-Iodoantipyrine for the measurement of regional cerebral blood flow by positron emission tomography. Validation studies. , 1981, Stroke.

[23]  M. D. Turner,et al.  Local cerebral blood flow in young and old rats during hypoxia and hypercapnia. , 1970, The American journal of physiology.

[24]  David E. Kuhl,et al.  Effect of Ischemia on Quantification of Local Cerebral Glucose Metabolic Rate in Man , 1981, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[25]  K. Kogure,et al.  The Measurement of Cerebral Blood Flow in the Rat , 1975, Stroke.

[26]  N. Lassen,et al.  Regional Cerebral Blood Flow in the Rat Measured by the Tissue Sampling Technique; a Critical Evaluation Using Four Indicators C14‐Antipyrine, C14‐Ethanol H3‐Water and Xenon133 , 1974 .

[27]  A. Gjedde,et al.  Cerebral blood flow and oxygen consumption in rat, measured with microspheres or xenon. , 1977, Acta physiologica Scandinavica.

[28]  M. D. Turner,et al.  Measurement of Local Cerebral Blood Flow in the Unanesthetized Rat Using a Hydrogen Clearance Method , 1968, Circulation research.

[29]  J. Bean,et al.  Continuous recording of regional changes in brain blood flow by a probe. , 1967, Journal of applied physiology.

[30]  B. Siesjö,et al.  Quantitative measurement of blood flow and oxygen consumption in the rat brain. , 1974, Acta physiologica Scandinavica.

[31]  T. Hougen,et al.  Insulin effects on monovalent cation transport and Na-K-ATPase activity. , 1978, The American journal of physiology.

[32]  L. Sokoloff,et al.  Measurement of local cerebral blood flow with iodo [14C] antipyrine. , 1978, The American journal of physiology.

[33]  P. Kenny,et al.  Theory for Noninvasive Measurement of Oxygen Extraction Fraction by Intravenous Bolus Injection or Bolus Inhalation of 15-Oxygen , 1985 .

[34]  T. Duffy,et al.  Comparison of radio-labeled butanol and iodoantipyrine as cerebral blood flow markers , 1981, Brain Research.

[35]  P J Kenny,et al.  Serial Measurements of Positron‐Emitting Isotope Activity in Rat Brain , 1981, Stroke.

[36]  P. Humphrey Measurement of cerebral blood flow , 1984 .

[37]  F. Plum,et al.  Whole-brain blood flow and oxygen metabolism in the rat during nitrous oxide anesthesia. , 1975, The American journal of physiology.