Penumbra detection in acute stroke with perfusion magnetic resonance imaging: Validation with 15 O-positron emission tomography

Abstract

Objective: Accurate identification of the ischemic penumbra, the therapeutic target in acute clinical stroke, is of critical importance to identify patients who might benefit from reperfusion therapies beyond the established time windows. Therefore, we aimed to validate magnetic resonance imaging (MRI) mismatch-based penumbra detection against full quantitative positron emission tomography (¹⁵ O-PET), the gold standard for penumbra detection in acute ischemic stroke.

Methods: Ten patients (group A) with acute and subacute ischemic stroke underwent perfusion-weighted (PW)/diffusion-weighted MRI and consecutive full quantitative ¹⁵ O-PET within 48 hours of stroke onset. Penumbra as defined by ¹⁵ O-PET cerebral blood flow (CBF), oxygen extraction fraction, and oxygen metabolism was used to validate a wide range of established PW measures (eg, time-to-maximum [Tmax]) to optimize penumbral tissue detection. Validation was carried out using a voxel-based receiver-operating-characteristic curve analysis. The same validation based on penumbra as defined by quantitative ¹⁵ O-PET CBF was performed for comparative reasons in 23 patients measured within 48 hours of stroke onset (group B).

Results: The PW map Tmax (area-under-the-curve = 0.88) performed best in detecting penumbral tissue up to 48 hours after stroke onset. The optimal threshold to discriminate penumbra from oligemia was Tmax >5.6 seconds with a sensitivity and specificity of >80%.

Interpretation: The performance of the best PW measure Tmax to detect the upper penumbral flow threshold in ischemic stroke is excellent. Tmax >5.6 seconds-based penumbra detection is reliable to guide treatment decisions up to 48 hours after stroke onset and might help to expand reperfusion treatment beyond the current time windows. ANN NEUROL 2019;85:875-886.

Figure 1

Voxel‐based comparative analysis of positron emission tomography (PET)–cerebral blood flow (CBF), PET–oxygen extraction fraction (OEF), and PET–cerebral metabolic rate of oxygen (CMRO₂) with deconvolved perfusion‐weighted imaging (PWI)–CBF, –cerebral blood volume (CBV), –mean transit time (MTT) and –time to maximum (Tmax) as well as nondeconvolved PWI–time to peak (TTP), –bolus arrival time (BAT), –bolus end time (BET), –full width at half maximum (FWHM), –first moment (FM), –maximum concentration (Cmax), –negative enhancement integral (NEI), –normalized signal drop (dS/S), –maximum slope (MS), and –CBV of the tissue contrast concentration time curve (CBV_CTC). Deconvolved PWI maps calculated by standard deconvolution with an arterial input function (AIF) from the tissue response curve. Nondeconvolved PWI maps calculated without deconvolution with an AIF. A T1‐based grey matter mask was used for a voxel‐based comparison of the PET and PWI maps. Ventricles, white matter, large arteries, sinuses, and areas of severely delayed contrast agent were excluded. receiver operating characteristic curve analysis was performed with a combination of the classic penumbra thresholds: PET‐CBF < 20ml/100g/min, PET‐OEF > mean OEF of unaffected hemisphere + 2 standard deviations and PET‐CMRO₂ > 64μmol/100g/min. DC = delay correction; DWI = diffusion‐weighted imaging.

Figure 2

Coregistered images of multitracer ¹⁵O‐ positron emission tomography (PET), magnetic resonance perfusion‐weighted imaging (PWI) time to maximum (Tmax) and diffusion‐weighted imaging (DWI) in all 10 patients (group A) with acute and subacute ischemic stroke. All patients show penumbral tissue on PET with reduced cerebral blood flow (CBF), elevated oxygen extraction fraction (OEF), and normal to reduced cerebral metabolic rate of oxygen (CMRO₂).

Figure 3

Representative receiver operating characteristic curves of 4 patients illustrating the performance of time to maximum (Tmax) with respect to penumbral flow detection based on full quantitative positron emission tomography (PET)–cerebral blood flow, PET–oxygen extraction fraction, and cerebral metabolic rate of oxygen. The equal sensitivity and specificity threshold (ESST) is marked on the receiver operating characteristic curve. The corresponding optimal penumbral flow threshold with its sensitivity and specificity is shown. AUC = area under the curve.