Tissue at Risk of Infarction Rescued by Early Reperfusion: A Positron Emission Tomography Study in Systemic Recombinant Tissue Plasminogen Activator Thrombolysis of Acute Stroke

Abstract

Thrombolytic therapy of acute ischemic stroke can be successful only as long as there is penumbral tissue perfused at rates between the thresholds of normal function and irreversible structural damage, respectively. To determine the proportion of tissue at risk of infarction, cerebral perfusion was studied in 12 patients with acute ischemic stroke who underwent treatment with systemic recombinant tissue plasminogen activator (0.9 mg/kg body weight according to National Institute of Neurological Disorders and Stroke protocol) within 3 hours of onset of symptoms, using [15O]-H2O positron emission tomography (PET) before or during, and repeatedly after thrombolysis. The size of the regions of critically hypoperfused gray matter were identified on the initial PET scans, and changes of perfusion in those areas were related to the clinical course (followed by the National Institutes of Health stroke scale) and to the volume of infarcted gray matter demarcated on magnetic resonance imaging 3 weeks after the stroke. Whereas the initial clinical score was unrelated to the size of the ischemic area, after 3 weeks there was a strong correlation between clinical deficit and volume size of infarcted gray matter (Spearman's rho, 0.96; P < 0.001). All patients with a severely hypoperfused (< 12 mL/100 g/min) gray matter region measuring less than 15 mL on first PET showed full morphologic and clinical recovery (n = 5), whereas those with ischemic areas larger than 20 mL developed infarction and experienced persistent neurologic deficits of varying degree. Infarct sizes, however, were smaller than expected from previous correlative PET and morphologic studies of patients with acute stroke: only 22.7% of the gray matter initially perfused at rates below the conventional threshold of critical ischemia became necrotic. Actually, the percentage of initially ischemic voxels that became reperfused at almost normal levels clearly predicted the degree of clinical improvement achieved within 3 weeks. These sequential blood flow PET studies demonstrate that critically hypoperfused tissue can be preserved by early reperfusion, perhaps related to thrombolytic therapy. The results correspond with experimental findings demonstrating the prevention of large infarcts by early reperfusion to misery perfused but viable tissue.

Refining the Mismatch Concept in Acute Stroke: Lessons Learned from PET and MRI

“…It was also shown that, in addition to the core, the mismatch/ penumbra contributes to the neurologic deficit ('symptomatic tissue,' i.e., core plus penumbra). Finally, it was shown that the rescue of penumbral tissue correlates with clinical recovery (Alawneh et al, 2011;Furlan et al, 1996;Heiss et al, 1998;Marchal et al, 1999;Muir et al, 2006). Although this concept seems straightforward, the equation mismatch = penumbra has to be considered carefully as several methodological issues remain unresolved (Alawneh et al, 2011;Donnan and Davis, 2002;Kidwell et al, 2003;Sobesky et al, 2005) and as clinical studies of acute stroke therapy that used the mismatch concept for patient stratification produced inconclusive results (Mishra et al, 2010).…”

“…However, the definition of a single flow threshold in ischemia remains difficult because of several influential factors: (1) there is interindividual and age-dependent variability of CBF; (2) the thresholds obtained differ between white and gray matter (Pantano et al, 1984); (3) region of interest-based analyses yield different results compared with voxelbased analyses (Marchal et al, 1999); and (4) the duration of ischemia is an independent predictor of tissue outcome (Jones et al, 1981). In this respect, the CBF threshold that defines critical ischemia (leading to irreversible infarction) ranges from 8 to 12 mL/ 100 g per minute (Furlan et al, 1996;Heiss et al, 1998;Marchal et al, 1999). Tissue experiencing perfusion values below this threshold has a high probability to turn into irreversible infarction unless perfusion is quickly restored.…”

Crossed Cerebellar Diaschisis in Acute Human Stroke: A PET Study of Serial Changes and Response to Supratentorial Reperfusion

“…Positron emission tomography studies of cerebral blood flow (CBF) were performed in resting state on an ECAT EXACT or EXACT HR scanner (Siemens/CTI, Knoxville, TN, USA) as previously described (Heiss et al, 1998). Data reconstruction provided 47 contiguous 3-mm slices of 5 mm full-width at half-maximum in-plane reconstructed resolution.…”

PET/MR — a rapidly growing technique of imaging in oncology and neurology

“…15 O], where it was originally developed for MR imaging [61]. Another technique used to evaluate brain perfusion using MR is the method of arterial spin labeling (ASL [62].…”