Voxel-based mapping of irreversible ischaemic damage with PET in acute stroke

Abstract

Objective mapping of irreversible tissue damage in the acute stage of ischaemic stroke would be useful for prognosis and in assessing the efficacy of therapeutic manoeuvres in impeding extension of infarction. From our database of 30 patients studied with 15O-PET within 5-18 h after onset of first-ever middle cerebral artery territory stroke, we extracted a subgroup of 19 survivors (age 74.6 +/- 8.5 years) in whom late CT coregistered with PET was available to determine final infarct topography. By means of a voxel-based analysis of the PET data, we determined putative thresholds for irreversible tissue damage as the lower limit of the 95% confidence interval calculated from all voxels within the ultimately non-infarcted brain parenchyma ipsilateral to the insult. The following values were found: 8.43 ml/100 ml/min, 0.87 ml/100 ml/min, 1.64 ml/100 ml, 0.27 and 2.21/min, for cerebral blood flow (CBF), oxygen consumption (CMRO2), blood volume (CBV), oxygen extraction fraction and the ratio CBF : CBV, respectively. Voxels below these thresholds occurred significantly more frequently in the final infarct region than in the non-infarcted parenchyma for CBF and CMRO2 (P = 0.016 and P = 0.0045, respectively, Wilcoxon test), but not for the other PET variables. Furthermore, with both CBF and CMRO2, the percentage of irreversible tissue damage voxels in the affected hemisphere relative to the opposite hemisphere was significantly positively correlated to both the volume of final infarct and the neurological outcome at 2 months (all P < 0.005, Spearman ranked test). These findings validate our voxel-based CBF and CMRO2 thresholds for probabilistic mapping of irreversible tissue damage within the 5-18 h interval after stroke onset; however, whether they would be applicable to earlier intervals remains to be determined. Transfer of our procedure for determination of irreversible tissue damage thresholds to other imaging modalities such as single proton emission computed tomography and diffusion-weighted MRI should be straightforward.

Prognostic value of blood pressure in acute stroke

“…25,31 Since PET-studies suggest that the penumbra may exist up to 18 h after stroke onset, [32][33][34][35] we included BP-values taken within the first 24 h, instead of BP-values measured within a shorter period following stroke onset. Our data do not contradict the idea of therapeutic manipulation of post-stroke blood pressure.…”

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.…”

“…This metabolic threshold is method dependent. It refers to large cortical regions of interest and is lower in a voxel-based analysis (Marchal et al, 1999). Put simply, the balance of CBF and cerebral metabolic rate of oxygen, i.e., the oxygen consumption per unit of oxygen supply, is expressed by the oxygen extraction fraction (OEF).…”

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.…”