Amino acid uptake in ischemically compromised brain tissue.
OBJECTIVE
Multitracer positron emission tomography (PET) was used to investigate local amino acid accumulation in brain tissue surrounding focal ischemia.


METHODS
PET using 15O-labeled oxygen and water for measuring cerebral metabolic rate of oxygen (CMRO2) and cerebral blood flow (CBF), C15O for determination of blood volume (CBV) and calculation of oxygen extraction fraction, and L-[11C]methylmethionine (11C-MET) for the assessment of amino acid accumulation was applied in 14 patients (mean age, 52 +/- 9.1 years) with acute ischemic hemispheric stroke. Two multitracer PET studies were completed, the first 8 to 24 hours after onset of neurological symptoms and the follow-up study 14 +/- 1 days after the ischemic attack. Functional changes were compared with morphological damage on cranial CT or MRI. Three-dimensional matching and volume of interest evaluation procedures were used to study 11C-MET accumulation in relation to various physiological variables in infarcted and noninfarcted tissue.


RESULTS
Compared with contralateral mirror regions, initially increased regional 11C-MET uptake (21.2 +/- 10.9%, P < .001) was found in patchy areas in the immediate vicinity of infarction as well as in distant areas within the same hemisphere. In those areas, regional CBF (-11.4 +/- 21.2%, P < .01) and oxygen extraction fraction (2.8 +/- 29.1%, P = NS) were highly variable, and regional CMRO2 was preserved or slightly reduced (-12.4 +/- 16.0%, P < .001). CBF data comprised severely ischemic as well as high values (14.6 to 64.2 mL/100 g per minute). Cranial CT and coregistered MRI in five patients demonstrated preserved morphology. In all peri-infarct areas (n = 62), the 11C-MET uptake showed a positive correlation with delta CMRO2 as the relative improvement of ipsilateral CMRO2 between the two PET studies (r = .378, P < .01). Particularly in areas with increased oxygen extraction fraction (n = 42), the 11C-MET uptake showed a mild correlation with CMRO2 at follow-up measurement (r = .31, P < .05). In all peri-infarct areas, 11C-MET uptake showed a negative correlation with oxygen extraction fraction (r = -.672, P < .001) and a positive correlation with CBF (r = .4, P = .001). In all infarcted and peri-infarct areas, normalized initial 11C-MET uptake was positively correlated with CMRO2 at follow-up (r = .603, P < .001).


CONCLUSIONS
Focal increases of 11C-MET uptake seen in this study were generally mild. They might be seen in the core of ischemia, indicating breakdown of the blood-brain barrier with poor tissue prognosis, but they also frequently occurred during or after ischemic compromise in surviving brain tissue surrounding focal cerebral infarction, perhaps representing alterations of amino acid transport or protein synthesis in brain tissue with a favorable prognosis.
Jacobs
A
A
Max-Planck-Institut für neurologische Forschung and Neurologische Universitätsklinik Köln, Germany.
D000328:Adult; D000368:Aged; D001810:Blood Volume; D001921:Brain / Q000378:metabolism*; D002560:Cerebrovascular Circulation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007089:Image Enhancement; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D008297:Male; D008715:Methionine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D008875:Middle Aged; D009460:Neurologic Examination; D010101:Oxygen Consumption; D010104:Oxygen Radioisotopes; D014055:Tomography, Emission-Computed; D014057:Tomography, X-Ray Computed; D014867:Water
D010104:Oxygen Radioisotopes; D014867:Water; D008715:Methionine; C038344:methionine methyl ester