Feasibility and diagnostic accuracy of using brain attenuation changes on CT to estimate time of ischemic stroke onset

Abstract

Purpose: CT attenuation of ischemic brain reduces with time after stroke onset. We aimed to quantify this relationship and test the feasibility and accuracy of estimating stroke onset time using only CT attenuation of visible ischemic lesions, the CT-Clock Tool.

Methods: We selected CT scans with ischemic lesions representing a range of stroke-onset-to-scan times (elapsed time) from a well-defined stroke trial. We measured the attenuation of ischemic lesions and contralateral normal brain to derive attenuation ratio. We assigned scans to development (75%) or test (25%) datasets. We plotted the relationship between attenuation ratio and elapsed time in the development dataset and derived a best-fit curve. We calculated estimated time in the test dataset using only the attenuation ratio curve. We compared estimated time to elapsed time and derived absolute error for estimated time. We assessed area under the receiver operating characteristic (AUROC) curve for identifying scans ≤ 4.5 h elapsed time.

Results: We included 342 scans from 200 patients (41% male, median age 83 years). Elapsed time range: 22 min to 36 days. Estimation errors were least at early elapsed times (r = 0.82, p < 0.0001): median absolute error was 23, 106, 1030 and 1933 min for scans acquired ≤ 3, > 3-9, > 9-30 and > 30 h from stroke onset, respectively. AUROC was high at 0.955.

Conclusions: It is feasible to accurately estimate stroke onset time using simple attenuation measures of ischemic brain. Our method was most accurate 0-9 h from onset and may be useful for treatment eligibility assessment, especially where imaging resources are limited.

Keywords: Attenuation; CT; Ischemia; Stroke.

Conflict of interest statement

The authors report no disclosures or potential conflicts of interest relevant to this manuscript.

Figures

Fig. 1

ROI placement within the same ischemic lesions on sequential thin-slice CT scans for two different patients. Note: Upper panel: Two sequential scan measurements from the same patient, left image at 175 min from stroke symptom onset, right image at 36 h from onset. Lower panels: Three sequential scan measurements from the same patient, left image at 120 min, middle right image at 22 h, and lower right image at 100 h from stroke onset

Fig. 2

Flowchart for patient selection

Fig. 3

Best-fit logarithmic function for attenuation ratio versus elapsed time in the development dataset (n = 256)

Fig. 4

Bland-Altman analysis of error in estimated time results. Note: Difference between elapsed and estimated time (horizontal solid line) in the test dataset. For clarity of presentation, only includes results from the most clinically relevant early (≤ 3 h) and delayed (> 3 to 9 h) elapsed time subgroups. Mean − 0.2 h, SD 2.9, n = 42. Dotted lines represent ± 2 SD from mean

Fig. 5

ROC analysis testing the expected discriminative ability of attenuation ratio to determine intravenous alteplase eligibility as per 4.5 h European licensing limit, n = 342. Note: Area under curve = 0.955