Diffusion and perfusion correlates of the 18F-MISO PET lesion in acute stroke: pilot study.

PURPOSE: Mapping the ischaemic penumbra in acute stroke is of considerable clinical interest. For this purpose, mapping tissue hypoxia with (18)F-misonidazole (FMISO) PET is attractive, and is straightforward compared to (15)O PET. Given the current emphasis on penumbra imaging using diffusion/perfusion MR or CT perfusion, investigating the relationships between FMISO uptake and abnormalities with these modalities is important. METHODS: According to a prospective design, three patients (age 54-81 years; admission NIH stroke scale scores 16-22) with an anterior circulation stroke and extensive penumbra on CT- or MR-based perfusion imaging successfully completed FMISO PET, diffusion-weighted imaging and MR angiography 6-26 h after stroke onset, and follow-up FLAIR to map the final infarction. All had persistent proximal occlusion and a poor outcome despite thrombolysis. Significant FMISO trapping was defined voxel-wise relative to ten age-matched controls and mapped onto coregistered maps of the penumbra and irreversibly damaged ischaemic core. RESULTS: FMISO trapping was present in all patients (volume range 18-119 ml) and overlapped mainly with the penumbra but also with the core in each patient. There was a significant (p ≤ 0.001) correlation in the expected direction between FMISO uptake and perfusion, with a sharp FMISO uptake bend around the expected penumbra threshold. CONCLUSION: FMISO uptake had the expected overlap with the penumbra and relationship with local perfusion. However, consistent with recent animal data, our study suggests FMISO trapping may not be specific to the penumbra. If confirmed in larger samples, this preliminary finding would have potential implications for the clinical application of FMISO PET in acute ischaemic stroke.

Interaction of age with the ischaemic penumbra, leptomeningeal collateral circulation and haemodynamic variables in acute stroke: a pilot study.

BACKGROUND: Increasing age is the single largest non-modifiable risk factor for ischaemic stroke. Animal models have substantiated the view that age related neuron vulnerability to ischaemia plays a role in stroke and other age related neurological diseases. Given the key role of the ischaemic penumbra in stroke pathophysiology, we hypothesised that age has an impact on penumbral tissue and its acute determinants. METHODS: We studied a prospective cohort of patients (n=39) at a mean time of 154.7 min from stroke onset, using state of the art whole brain perfusion CT and CT angiography. Penumbral and core were defined using quantitative voxel based thresholds for mean transit time and cerebral blood volume (CBV). Collateral vessel scores were assessed and haemodynamic variables (ie, cerebral blood flow and CBV) were measured in affected and unaffected tissues. RESULTS: While age correlated negatively with normalised penumbral volume (Kendall's τ b=-0.234, p=0.048) and lesion volume (Kendall's τ b=0.238, p=0.045), core volume remained unchanged, accompanied by an incremental collateral response with age (Kendall's τ b=0.496, p<0.0001). Haemodynamic variables remained unaffected by age in our cohort. CONCLUSIONS: These findings, described for the first time in a clinical cohort using whole brain CT perfusion and concomitant vascular imaging, suggest that age has a differential effect on acute tissue compartments in the wake of a preserved collateral vascular response and haemodynamic parameters. In agreement with the preclinical literature, the results point to a distinct tissue response to acute ischaemia in the ageing brain and merit validation studies in larger cohorts, particularly in relation to clinical outcomes.

Is CT-Based Perfusion and Collateral Imaging Sensitive to Time Since Stroke Onset?

PURPOSE: CT-based perfusion and collateral imaging is increasingly used in the assessment of patients with acute stroke. Time of stroke onset is a critical factor in determining eligibility for and benefit from thrombolysis. Animal studies predict that the volume of ischemic penumbra decreases with time. Here, we evaluate if CT is able to detect a relationship between perfusion or collateral status, as assessed by CT, and time since stroke onset. MATERIALS AND METHODS: We studied 53 consecutive patients with proximal vessel occlusions, mean (SD) age of 71.3 (14.9) years, at a mean (SD) of 125.2 (55.3) minutes from onset, using whole-brain CT perfusion (CTp) imaging. Penumbra was defined using voxel-based thresholds for cerebral blood flow (CBF) and mean transit time (MTT); core was defined by cerebral blood volume (CBV). Normalized penumbra fraction was calculated as Penumbra volume/(Penumbra volume + Core volume) for both CBF and MTT (PenCBF and PenMTT, respectively). Collaterals were assessed on CT angiography (CTA). CTp ASPECTS score was applied visually, lower scores indicating larger lesions. ASPECTS ratios were calculated corresponding to penumbra fractions. RESULTS: Both PenCBF and PenMTT showed decremental trends with increasing time since onset (Kendall's tau-b = -0.196, p = 0.055, and -0.187, p = 0.068, respectively). The CBF/CBV ASPECTS ratio, which showed a relationship to PenCBF (Kendall's tau-b = 0.190, p = 0.070), decreased with increasing time since onset (Kendall's tau-b = -0.265, p = 0.006). Collateral response did not relate to time (Kendall's tau-b = -0.039, p = 0.724). CONCLUSION: Even within 4.5 h since stroke onset, a decremental relationship between penumbra and time, but not between collateral status and time, may be detected using perfusion CT imaging. The trends that we demonstrate merit evaluation in larger datasets to confirm our results, which may have potential wider applications, e.g., in the setting of strokes of unknown onset time.