Objective: CTP is an important diagnostic tool in managing patients with acute ischemic stroke, but challenges persist in the reliability of stroke lesion volumes determined with different software. We investigated a systematic method to calibrate CTP lesion thresholds between deconvolution algorithms using a digital perfusion phantom. Approach: The accuracy of one model-independent and two model-based deconvolution algorithms in estimating ground truth cerebral blood flow (CBF) and Tmax in the phantom was quantified. Reference thresholds for ischemic core and penumbra were model-independent CBF<30% and Tmax>6 s, respectively, which is the current clinical standard. The equivalent model-based CBF and Tmax thresholds were determined by comparing linear regressions of phantom ground truth and deconvolution-estimated perfusion between algorithms. Calibrated thresholds were then validated in 63 patients with large vessel stroke by comparing admission CTP ischemic core and <3-hour diffusion-weighted imaging (DWI) lesion volume by Bland-Altman analysis. Agreement in target mismatch (core < 70 ml, penumbra ≥ 15 ml, mismatch ratio ≥ 1.8) determined by the three methods was assessed by Cohen's kappa (κ) and concordance. Main Results: The calibrated thresholds were CBF<15% and Tmax>6 s for both model-based methods. DWI minus CTP lesion mean volume differences (95% limits of agreement) were +16.2 (-30.9 to 63.3) ml, +10.9 (-32.9 to 54.7) ml, and +13.8 (-48.1 to 75.7) ml for model-independent and the two calibrated model-based approaches, respectively. Agreement in mismatch profiles with the two model-based deconvolution methods versus model-independent assessment was κ = 0.87 (95% confidence interval [CI]: 0.72 to 1.00) and κ = 0.86 (95% CI: 0.70 to 1.00), and both achieved 95% concordance. Significance: We reported a systematic method of calibrating perfusion thresholds between deconvolution algorithms based on their quantitative accuracy. This may harmonize ischemic lesion volumes determined by different CTP software.
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