The Determination of Regional Cerebral Blood Flow by Means of Water Labeled with Radioactive Oxygen 15

Abstract

THE NUMBER of methods devised for the in vivo evaluation of regional cerebral flow (rCBF) attest to the elusiveness of this parameter. One of the methods for this purpose is the injection, into the internal carotid artery of a subject, of a diffusible indicator labeled with a gammaemitting radioisotope, followed by the external measurement of the rate of washout of the indicator from various regions of the brain. This approach (1, 2), a modification of the Kety–Schmidt method (3–5), has most frequently utilized saline solutions of radioactive inert gases such as krypton 85 (1, 2) and xenon 133 (6). At this time, 133Xe appears to be the most widely used diffusible indicator despite inherent limitations which include: (a) a different solubility in lipids and in water; (b) a brain–blood partition coefficient difficult to evaluate accurately; and (c) the low–energy electromagnetic radiation of 133Xe. The first two factors render absolute flow determinations by this indicator uncertain and the third one favors surface detection at the expense of deep–lying tissues and precludes efficient elimination of scattered radiation. Radioactive Water as a Diffusible Indicator The limitations listed above call for an indicator superior to xenon 133 in its physiological behavior and in the photon energy of its radioactive label. A logical choice for this purpose is radioactively labeled water. Water, which is highly diffusible in tissues, is the carrier of all metabolites and should consequently be a good indicator of tissue perfusion. It has been shown that, in perfused dog heart and skeletal muscle, blood flow is of major importance in the delivery of deuteriumlabeled water to tissue water (7). The tagging of water with a gammaemitting radioactive label can be achieved only with radioactive oxygen because hydrogen does not possess any gammaemitting isotope. Oxygen 15, a positron–emitter with a half–life of one hundred and twenty–three seconds, is an adequate label for this purpose. The annihilation of positrons in matter results in the production of 511 keV photons which are well suited for external counting. It might appear that the short half–life of oxygen 15 would preclude its use for this purpose. In fact, an rCBF study can be completed in less than twelve minutes, and, since the labeled water is not lost by the subject, the short half–life is advantageous because it allows repeated studies with a low absorbed dose of radiation. Water labeled with oxygen 15 offers a number of advantages over inert gases for the in vivo determination of rCBF. a. Labeled water is an ideal indicator for the water compartments in tissues whereas most inert gases exhibit different solubilities for water and lipids.