Oxygen Consumption of the Living Human Brain Measured after a Single Inhalation of Positron Emitting Oxygen

Abstract

Summary:We measured the rate of washout of 150_ labeled water generated from labeled oxygen accumu lated in brain after bolus [150]02 inhalation, and com pared the washout with that of labeled water measured with H2150. Contrary to the original expectation, the ra dioactive water generated from labeled oxygen failed to leave the brain tissue at the rate predicted by exogenous water. Therefore, the use of a separately measured value for exogenous water clearance led to an error in the cal culation of oxygen consumption. A new method pre sented in this paper eliminated the error by yielding ox ygen consumption in a single oxygen study. We used Measurements of the oxygen consumption of in dividual brain regions have been possible only after the advent of positron emission tomography (PET). Two methods have been reported, both intended to yield the unidirectional clearance of the very short lived oxygen isotope, oxygen-15. The equilibrium method (Frackowiak et aI., 1980) yielded the oxy gen clearance from the steady-state balance be tween oxygen influx, radioactive oxygen decay, and radioactive water efflux. The autoradiographic method (Mintun et aI., 1984) yielded the clearance from a transient (non-steady-state) analysis of the uptake. Both methods required separately obtained information about blood flow and blood volume and assumed, therefore, that the physiological state of the subject, and its position in the scanner, re mained unchanged for 30-60 min, the time required Abbreviation used: CBV, cerebral blood volume; CMROz, ce rebral metabolic rate for oxygen; FWHM, full width at half max imum; OEF, oxygen extraction fraction; PET, positron emission tomography; RMS, root mean squared. 179time-weighted integration to estimate three parameters, including the unidirectional clearance from blood to brain (K? 2 ), the fractional clearance of the distribution volume in brain (k�2), and the vascular volume correction (yo) ' We showed that the clearance of oxygen from blood to brain can be estimated with acceptable precision by this new approach, and that the new method yields a reliable measure of oxygen consumption. Key Words: Positron emission tomography-Oxygen consumption-U nidirec tional clearance of oxygen-Single oxygen study-Time weighted integration method.to perform three separate studies by positron emis sion tomography. In addition, both methods de pended on several simplifying assumptions which may cast doubt on the results. However, the uncer tainty is not easy to resolve because of the absence of independently obtained regional values that might serve as the ultimate standard.To examine the consequences of the specific an alytic method for the calculated oxygen consump tion values, we modified the experimental approach to yield values of oxygen consumption from a single short (3 min) bolus e50]02 inhalation study, elimi nating some assumptions but introducing others.

Rapid Quantitative Measurement of CMRO2 and CBF by Dual Administration of 15O-Labeled Oxygen and Water During a Single PET Scan—a Validation Study and Error Analysis in Anesthetized Monkeys

“…Finally, it allows evaluation of coupling or uncoupling of CBF and CMRO 2 during functional activation or pharmacological stress, such as that induced by acetazolamide used for assessment of cerebral vascular reserves. Ohta et al (1992) showed another technique for the rapid estimation of CBF, OEF, and CMRO 2 from a 3-min single PET scan following bolus inhalation of 15 O 2 . This approach does not take into account recirculating water and involves a mathematical formula with weighted integration to calculate these quantitative values.…”

“…There have been other attempts to obtain CBF and CMRO 2 images more rapidly (Huang et al, 1986;Holden et al, 1988;Meyer et al, 1987;Ohta et al, 1992;Ho and Feng, 1999). Mathematical refinement has allowed images to be generated from data from a single scan alone on a bolus inhalation of 15 O 2 .…”

“…Mathematical refinement has allowed images to be generated from data from a single scan alone on a bolus inhalation of 15 O 2 . The quality of the image suffers, however, from statistical noise because of the lack of predictability of the multiple parameters of CBF, CMRO 2 , and the arterial vascular compartment (V 0 ) and the limited acquisition time (Meyer et al, 1987;Ohta et al, 1992). Therefore, this technique has not been generally applied in clinical settings, but has been used primarily for research purposes (Fujita et al, 1999;Vafaee and Gjedde, 2000;Okazawa et al, 2001a, b;Mintun et al, 2002).…”

Early Nonischemic Oxidative Metabolic Dysfunction Leads to Chronic Brain Atrophy in Traumatic Brain Injury

“…O (Ohta et al, 1992). The O 15 O raw images (voxel size: 1.471 Â 1.471 Â 2.45 mm 3 ) were smoothed using a three-dimensional filter (in plane full-width at half-maximum = 2.942 mm, axial full-width at half-maximum = 2.45 mm) before OEF images were generated on a voxel basis.…”

In vivo17O NMR approaches for brain study at high field

“…57,65 This could further reduce the diffusion distances within the same CMRO 2 measurement time. Therefore, the diffusion of H 2 17 O in the brain tissue is unlikely to be the major factor limiting spatial resolution of 17 17 O CSI in the human brain at 7 T using a 7.5 cm diameter surface coil with temporal resolution of 11 s and voxel size of 3.5 ml.…”