Evaluation of the ¹¹CO₂ Positron Emission Tomographic Method for Measuring Brain pH. II. Quantitative pH Mapping in Patients with Ischemic Cerebrovascular Diseases

Abstract

Summar y : A practical method has been developed that, using II COZ and positron emission tomography (PET), computes and maps (a) "effective pH" (pH,), a weighted average of intra-and extracellular pH, and (b) "clearance" (K\), product of blood flow and llCOZ ex traction. This method, together with measurements of ce rebral blood flow (CBF) and oxygen extraction fraction (OEF), was applied to 12 patients with cerebral ischemia or stroke. The regional K\ was positively correlated with CBF (n = +0.78). The k\/CBF ratio, representing the extraction fraction ratio of llCOZ to H/50, was nega tively correlated with CBF (r = -0.54), suggesting that I leoz extraction decreases as flow increases. In five acute stroke patients within 2 days of onset, the injured cortex had lower CBF (20.6 mi/min/IOO g), higher OEF Brain pH is tightly regulated by physicochemical buffering, by metabolic breakdown and production of acids, and perhaps by active transport of H + or HC03 -. Such tight control is necessary at least in part because of the pH dependence of the activity of several enzymes involved in energy metabolism and Received March 13, 1989; revised June 5, 1989; accepted June 8, 1989 Address correspondence and reprint requests to Dr. N. M. Alpert at Division of Nuclear Medicine, Massachusetts General Hospital, Fruit Street, Boston , MA 02 114, U.S.A.Abbreviations used: ANOVA, analysis of variance; CBF, ce rebral blood flow; CBV, cerebral blood volume; CMR02 , cere bral metabolic rate of 02; CSF, cerebrospinal fluid; CT, com puted tomography; DMO, 5,5-dimethyl-2,4-oxazolidinedione; FWHM, full width at half-maximum; GLM , General Linear Model; OEF, oxygen extraction fraction; OM, orbitomeatal; PET, positron emission tomography; ROI, region of interest; TIA, transient ischemic attack. 859(78. 1 %), and lower pH, (6.96) than the contralateral cor tex (CBF = 41.4 mi/min/IOO g, OEF = 53.3%, pH, = 7.00), suggesting intracellular acidosis with intact cell membranes. In three stroke patients 5-8 days after onset, the injured cortex had higher CBF (60.9 mllmin/IOO g), lower OEF (32.0%), and higher pH, (7. 12) than the con tralateral cortex (CBF = 45.3 ml/min/IOO g, OEF = 58.0%, pH, = 7.06), which suggested an increase in ex tracellular volume compartment reflecting loss of cell membrane integrity. This method provides information on the regional tissue acid-base status and cell membrane integrity, which may be prognostic of tissue viability. Ke y Words: Brain pH-Positron emission tomography \\ COz-Stroke-Cerebral acid-base status-Hydrogen ion concentration .

Pathophysiology of Acute Cerebral Ischemia: PET Studies in Humans

“…In patients with hypoper fusion, Hakim et al [11] reported a reduced pH, indicating tissue acidosis apparently unexplained by enhanced anaerobic glycolysis, as shown by a normal CMRglu/CMR02 ratio. Using the " C 0 2 whole tissue pH method, Senda et al [27] also observed tissue aci dosis in hypoperfused, acutely ischemic tissue; in less acute conditions, and in the setting of hyperperfusion and lowered OEF, these authors found an increased pH, in agreement with the earlier findings of Syrota et al [23],…”

Cerebral Metabolism of Patients with Stenosis of the Internal Carotid Artery before and after Endarterectomy

“…In the chronic phase of infarction it has been shown that in patients with severe stenosis or oc clusion of the ICA, infarcted tissue is still perfused at a low level (Myers, 1979;Symon et al , 1979;Hossmann and Schuier, 1980). This low regional perfusion is probably still sufficient to accommo date for the metabolic demands, since positron emission tomography (PET) studies have shown luxury perfusion in chronic infarcts (Syrota et al , 1985;Hakim, 1987;Senda et al, 1989). Although Lac is continuously produced from blood glucose in chronic infarctions (Rothman et al, 1991), anaerobe glycolysis is not the only source of Lac production in the chronic stage of infarction.…”

Metabolic Crisis without Brain Ischemia is Common after Traumatic Brain Injury: A Combined Microdialysis and Positron Emission Tomography Study

“…In this paper, we have used classic thresholds of PET OEF 40.75 as well as microdialysis metabolite values to define ischemia. The PET OEF 40.75 threshold is based in part on the work of Senda et al (1989) and Marchal et al (1999). In the former study (Senda et al, 1989), mean OEF in acute ischemic territories was 0.78 within 2 days of the ischemic stroke.…”

“…The PET OEF 40.75 threshold is based in part on the work of Senda et al (1989) and Marchal et al (1999). In the former study (Senda et al, 1989), mean OEF in acute ischemic territories was 0.78 within 2 days of the ischemic stroke. In the latter study, Marchal et al report that the upper limit of OEF beyond which acutely ischemic tissue was irreversibly injured was 40.73.…”