a. Patient Selection

A total of 969 patients were included in this retrospective study (Figure. I in the online-only Supplement). The patient population comprised five individual cohorts which constituted a well-represented sample of scanner models from all major CT vendors and typical variants of CTA protocols seen at hospitals: 275 patients pooled from DEFUSE 2 (n=62) (07/08–09/11) and DEFUSE 3 (n=213) (05/17–05/18), two large multi-center stroke trials^{7, 12}; 193 patients came from a single quaternary center of which 82 were patients who had been imaged as potential ECR candidates (08/02/14–08/30/15), and 111 were imaged for non-stroke related indications (06/06/17–01/28/19) with normal anterior circulation. The fifth cohort was a consecutive series of 501 patients who had CTA as part of a ‘code stroke’ work up at a regional hospital that is a primary stroke center (01/01/17–12/31/18). Note that for DEFUSE 2 and 3, only the subset of consented patients who had undergone acute CTA were used.

43 patients (4.4%) were excluded due to: 1. screen failures (n=4, from DEFUSE 2); 2. CTA not being included in the acute CT protocol (n = 7); 3. inadequate data format (thin slice CTA raw data unavailable); and 4. the CTA being deemed by an experienced neuroradiologist (S.A.A) to be technically inadequate therefore of insufficient quality to allow accurate interpretation by a human reader (n = 15 with severe motion in 3, poor/no contrast bolus in 8 and incomplete coverage of the intracranial arteries in 4).

The remaining 926 patients (age 70 [median] IQR: 58–80 years) were analyzed, of which 504 were female (age 69 IQR: 58–78) and 422 male (age 71, IQR: 59–82) (Table 1). 531 of these patients, who were imaged for a diagnostic workup of their cervico-cerebral vasculature, had either no evidence of an anterior circulation vessel occlusion or distal (M3/M4 segments) occlusions only, and for this study were considered controls. Based on CTA expert reads, the remaining 395 patients had an occlusion in the anterior circulation at the following location:

Single site (n=241): cervical ICA (n=15); intracranial ICA (n=16); M1-MCA (n=161); M2-MCA (n=37); and distal MCA (n=12).

Tandem/multiple lesions (n=154): any ICA+M1 (n=124); any ICA+M2 (n=8); M1+M2 (n=5); cervical ICA+intracranial ICA (n=9); and M2+distal MCA (n=8).

Patient Demographics

Note. – IQR = Interquartile Range. D2 = DEFUSE 2 cohort. D3 = DEFUSE 3 cohort. A1 = ECR cohort + controls from quaternary hospital. A2 = ‘Code Stroke’ cohort from regional tertiary hospital.

Of those 395 patients with occluded vessels (Figure 1), 15 patients had isolated cervical ICA occlusions and 60 had M2-MCA occlusions without any intracranial LVOs. Of the remaining 320 patients with intracranial LVOs, 16 had isolated intracranial ICA, 161 had isolated M1-MCA occlusions, and 143 had tandem/multiple occlusions: M1+M2 (n=5); cervical ICA+M1 (n=21); intracranial ICA+M1 (n=103); intracranial ICA+M2 (n=5); and intracranial and cervical ICA (n=9).

After (1) importing raw, thin-slice CTA DICOM images, (2) only slices above C1 are used for further processing and the CT head holder is removed. A (3) CT head template is then co-registered to the patient’s CTA and subsequently the CTA analysis regions (which were previously defined on the CT template) are spatially transformed onto the patient’s CTA scan. Next, all bone is removed (4). Tubular filters are applied (5) to extract vessels. Then, (6) the density (in Hounsfield units) sum of all voxels constituting the large vessels and the density sum of all voxels constituting distal vessels are computed and (7) hemispheric comparisons are made. (8) Areas where the vessel density sum drops below prespecified threshold are highlight as color overlays on maximum intensity projections.