This Article Full Text Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jacobs, A. Search for Related Content PubMed PubMed Citation Articles by Jacobs, A.

(Stroke. 1995;26:1859-1866.)
© 1995 American Heart Association, Inc.

Articles

Amino Acid Uptake in Ischemically Compromised Brain Tissue

Andreas Jacobs, MD

From the Max-Planck-Institut für neurologische Forschung and Neurologische Universitätsklinik Köln, Köln, Germany.

Correspondence to Dr A. Jacobs, Max-Planck-Institut für neurologische Forschung and Neurologische Universitätsklinik Köln, Josef-Stelzmann-Strasse 9, D-50931 Köln, Germany.

Background and Purpose 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 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.

Key Words: amino acids • cerebral ischemia, focal • tomography, emission-computed • protein synthesis

This article has been cited by other articles:

				M. Morooka, K. Kubota, H. Kadowaki, K. Ito, O. Okazaki, M. Kashida, T. Mitsumoto, R. Iwata, K. Ohtomo, and M. Hiroe 11C-Methionine PET of Acute Myocardial Infarction J. Nucl. Med., August 1, 2009; 50(8): 1283 - 1287. [Abstract] [Full Text] [PDF]

				S. Ceyssens, K. Van Laere, T. de Groot, J. Goffin, G. Bormans, and L. Mortelmans [11C]Methionine PET, Histopathology, and Survival in Primary Brain Tumors and Recurrence AJNR Am. J. Neuroradiol., August 1, 2006; 27(7): 1432 - 1437. [Abstract] [Full Text] [PDF]

				P. V. Madakasira, R. Simkins, T. Narayanan, K. Dunigan, R. J. Poelstra, and J. Mantil Cortical Dysplasia Localized by [11C]Methionine Positron Emission Tomography: Case Report AJNR Am. J. Neuroradiol., May 1, 2002; 23(5): 844 - 846. [Abstract] [Full Text] [PDF]