Revisiting the Optimal Apparent Diffusion Coefficient Threshold for Ischemic Core Delineation

The widely used apparent diffusion coefficient (ADC) threshold of 620 × 10^-6 mm²/s to automatically delineate the ischemic core on diffusion-weighted imaging (DWI) was established in recanalized patients after IV thrombolysis. However, recanalization was assessed 3-6 hours after treatment, which may entail substantial core growth and in turn ADC threshold overestimation, while follow-up imaging was performed at day 30, implying potential infarct shrinkage. Other studies typically used follow-up MRI scans on days 2-5 but did not correct for vasogenic edema, implying potential infarct overestimation. We re-evaluated the ADC threshold in patients with very early recanalization after endovascular therapy (EVT), using 24-hour follow-up MRI and applying edema correction (EC).

Consecutive patients with modified Treatment In Cerebral Infarction 2c-3 recanalization within 90 minutes after baseline MRI and who underwent follow-up MRI ≈24 hours were identified from our center's EVT registry (2012-2021). Basilar occlusions and small DWI lesions (<3 mL) were excluded. The baseline ischemic lesion and the final infarct (Infarct_24h) were manually delineated on initial DWI (DWI₀) and 24-hour DWI. EC was performed by applying nonlinear coregistration of follow-up MRI onto MRI₀. The intersection between DWI₀ and Infarct_24h was overlaid onto the baseline ADC map. A receiver operating characteristic analysis compared "core" with "noncore" voxels (obtained by varying the ADC threshold) across patients, and the Youden index was computed to determine the optimized ADC threshold (OptADC) without and with EC.

Among 1,024 patients, 56 were eligible and included (median age 73 years; 52% female; median [interquartile range (IQR)] NIH Stroke Scale score 12 [8-19], median MRI₀-to-recanalization delay 70.5 [52-81] minutes). The OptADC was 611 × 10^-6 mm²/s (area under the curve = 0.704; sensitivity = 61.6%; specificity = 70.4%; Youden index = 0.320) and 612 × 10^-6 mm²/s without and with EC, respectively. The median (IQR) individual-OptADC was 621.5 (585.5-672.8) × 10^-6 mm²/s. The baseline core volume was significantly (p < 0.001), but only marginally, smaller using the optimized vs the reference ADC threshold (16.4 ± 25 mL and 17.0 ± 26 mL, respectively; volume difference larger than 3 mL in 1 patient only).

We revisited the ADC core threshold using a stringent methodology, including EVT-induced ultra-early documented complete recanalization, ≈24-hour follow-up MRI, and EC. The resulting OptADC was marginally smaller than the reference threshold and, accordingly, modestly influenced the measured baseline core volume. The methodological refinements implemented here, including EC, seem essential for future research exploring core ADC.