Evidence of the Limitations of Water as a Freely Diffusible Tracer in Brain of the Rhesus Monkey

Abstract

The extraction of 16 O-labeled water by the brain during a single capillary transit was studied in vivo in 20 adult rhesus monkeys by external detection of the time course of the tracer subsequent to the internal carotid injection of 0.2 ml of whole blood labeled with H, 1B O. The data showed that labeled water does not freely equilibrate with the exchangeable water in the brain when the mean cerebral blood flow exceeds 30 ml/100 g min" 1 . At the normal cerebral blood flow in the rhesus monkey (~50 ml/100 g min~'), only 90% of the H 2 15

Tracer-Kinetic Models for Measuring Cerebral Blood Flow Using Externally Detected Radiotracers

“…, E = BfA. As devel oped in detail by ourselves (Eichling et al ., 1974;Raichle et al , 1975Raichle et al , , 1976Raichle and Larson, 1981) and others (Sangren and Sheppard , 1953;Renkin, 1959;Crone , 1963) , the extracted fr action can be used along with the CBF computed from the same residue-data record to compute the BBB permeability-surface-area product for water. We can obtain the equation used for this purpose by the above authors in terms of our present notation for our two-barrier distributed-parameter model by dividing numerator and denominator of 19 or 46 by total tissue weight and solving for the global-average specific perme ability-surface-area product in the fo rm…”

“…The technique used to compute CBF is based upon the well-established Central Volume Principle of tracer ki netics (Stephenson, 1948(Stephenson, , 1958Meier and Zierler, 1954 ;Zierler, 1963) . The details of our CBF technique have been published (Ter-Pogossian et al, 1969;Eichling et a! ., 1974 ;Raichle et a!…”

“…This single-injec tion, external-registration technique (Eichling et al ., 1974 ;Raichle et al ., 1976) uses the first 30 s of a residue-data record to compute E. As shown in Fig. 6, E is obtained on a semilogarithmic plot fr om a straight-line fit by eye to the data points that correspond to the relatively slow clearance of labeled water from brain tissue .…”

“…In spite of the steady-state assumption central to the derivation of 59, Eichling et al (1974) , Raichle et al (1976), Phelps et al (1977), Raichle and Larson (1981), and others have not hesitated to use it to interpret their residue-detection data from dy namic experiments in which the tracer steady state never prevails. Justification for this can be based partly on criteria developed by Bassingthwaighte (1974) , who tested the validity of 59 for outflow-de tection experiments against simulations using a more general distributed-parameter unit-capillary model.…”

“…CBF and the extracted fr action of oxygen-15-labeled water were measured in fo ur adult rhesus monkeys (Ma caca mullata) by empirical techniques that we have de veloped previously (Ter-Pogossian et al, 1969;Eichling et al ., 1974;Raichle et al ., 1975Raichle et al ., , 1976 and that are inde pendent of any of our present models. To ensure that the complete 0.2-ml volume of an injectant consisting of a small aliquot of the monkey's blood mixed with labeled water was deposited in its entirety into the internal ca rotid artery alone, the right external carotid artery was ligated at its origin from the common carotid artery.…”