Optimal Brain Perfusion CT Coverage in Patients with Acute Middle Cerebral Artery Stroke

Study Design

Imaging data obtained as part of standard clinical stroke care at our institution were retrospectively reviewed with the approval of the institutional review board. At our institution, patients with suspicion of acute stroke and no history of significant renal insufficiency or contrast allergy routinely undergo a stroke CT survey including the following imaging protocol: NCCT, PCT at 2 cross-sectional positions, CTA of the cervical and intracranial vessels, and postcontrast cerebral CT, obtained in this chronologic sequence.

We retrospectively identified a consecutive series of 51 patients admitted to the University of California, San Francisco Medical Center, from January 2006 to June 2007, who met the following inclusion criteria: 1) admission to the emergency department with signs and symptoms suggesting hemispheric stroke within 24 hours after symptom onset, 2) no evidence of intracerebral hemorrhage on the admission NCCT, and 3) evidence of new infarct involving the MCA territory on follow-up NCCT performed within 3 days to 3 months after the admission stroke CT study. Exclusion criteria included evidence of old infarcts on admission NCCT, perfusion deficits in the anterior cerebral artery or posterior cerebral artery distribution, and poor contrast bolus during acquisition of the PCT series. Patients' charts were reviewed for demographic and clinical data.

Imaging Protocol

PCT studies were performed on a 64-section CT scanner. Each PCT study involved successive gantry rotations performed in cine mode during intravenous administration of iodinated contrast material. Images were acquired and reconstructed at a temporal sampling rate of 1 image per second for the first 45 seconds. Acquisition parameters were 80 kV(p) and 100 mAs. Two successive PCT series at 2 different levels were performed following the NCCT and before the CTA. To obtain a z-axis coverage of 80 mm, 2 continuous PCT series were performed without gaps or overlaps, parallel to the hard palate, from the first level above the orbits to avoid the lens. For each PCT level, eight 5-mm-thick CT sections were assessed. The first PCT series was obtained at the level of the third ventricle, the basal ganglia, and the internal capsule; and the second PCT series, 4 cm above the first one, was obtained at the level of the lateral ventricles, contiguous to the first PCT series. For each PCT series, a 4-mL bolus of iohexol (300-mg/mL of iodine, Omnipaque; Amersham Health, Princeton, New Jersey) was administered into an antecubital vein by using a power injector at an injection rate of 5 mL per second for all patients. CT scanning was initiated 7 seconds after the start of the injection of the contrast bolus.

Image Postprocessing

PCT data were analyzed using PCT software developed by Extended Brilliance Workstation (Philips Medical Systems Cleveland, Ohio). This software relies on the central volume principle, which is the most accurate for low injection rates of iodinated contrast material.²⁴ After motion correction and noise reduction by an anisotropic (ie, edge-preserving spatial) filter, the software applies curve fitting by the least mean squares to obtain mathematic descriptions of the time-attenuation curves for each pixel. A closed-form noniterative deconvolution is then applied to calculate the MTT map.²⁵ The deconvolution operation requires a reference arterial input function (most often within the anterior cerebral artery), selected by the PCT software within a region of interest drawn by the user. The CBV map is calculated from the area under the time-attenuation curves.²⁶ The PCT infarct core and salvageable brain tissue, as well as their volumes on each PCT section, are automatically calculated by the software by using CBV and MTT thresholds, as reported in the literature (PCT salvageable brain tissue: MTT > 7 seconds or 145% of the contralateral side values, CBV ≥ 2.0 mL × 100 g⁻¹; PCT infarct core: area of CBV < 2.0 mL × 100 g⁻¹.¹⁵ The volume of the final infarct on FU NCCT was measured manually.

We calculated the contribution of each 5-mm PCT section in the z-axis from 5 mm above the orbits to 80 mm of z-axis coverage to estimate infarct-penumbra mismatch and the size of the infarct relative to MCA territory.

The volume of the MCA territory sections was measured from the admission NCCT by using standard anatomic landmarks as described by Barber at al.¹ and was used to calculate the ratio between perfusion infarct core and MCA territory in percentages. The final infarct volume was calculated on a follow-up NCCT.

Statistical Analysis

For each patient, we plotted the absolute infarct volume (in milliliters), the PCT infarct core/MCA territory ratio (in percentages), the absolute penumbra volume (in milliliters), and the penumbra / (infarct + penumbra) ratio (in percentages) as a function of the z-axis coverage (in millimeters). The value measured for 80-mm z-axis coverage was considered as the criterion standard—maximal coverage obtained.

For each patient and for each of these plots, we calculated if and when a plateau was reached. The measurements for each extent of z-axis coverage were considered successively and compared with the measurements for the 80-mm coverage, and a plateau was defined when the measurements for a shorter z-axis coverage were within 5% of the corresponding measurement for 80-mm coverage and when the slope with the next coverage (+ 5 mm) was <0.2. For each parameter (absolute infarct volume in milliliters, the perfusion infarct core/MCA territory ratio in percentages, the absolute penumbra volume in milliliters, and the penumbra / [infarct + penumbra] ratio in percentages), we calculated the coverage for which a plateau was reached for 50% of the patients (p50), 95% of the patients (p95), and all (100%) patients (p100). We reported the p50, p95, and p100 coverage for all patients as a group, as well as for the patients stratified according to absolute penumbra (<50 mL, 50–150 mL, and >150 mL), absolute perfusion infarct core (<25 mL, 25–75 mL, and >75 mL), mismatch (<20% and <50%), and relative final infarct size (<33% and ≥33%).

We then focused on the perfusion infarct core/MCA territory ratio (in percentages) and selected the threshold of 33%, which is usually used to determine the eligibility of patients with acute stroke for reperfusion therapy.^1–7 Hypothetic treatment decisions for shorter extents of z-axis coverage were compared with the criterion standard (true-negative if no treatment both at 80-mm coverage and at a shorter coverage; false-negative if treatment at 80-mm coverage, but no treatment at a shorter coverage; true-positive if treatment both at 80-mm coverage and at a shorter coverage; false-positive if no treatment at 80-mm coverage, but treatment at a shorter coverage). The sensitivity and specificity of treatment decisions were calculated for each coverage.

Similarly, we calculated the sensitivity and specificity for each extent of z-axis coverage in terms of treatment decisions based on the penumbra / (infarct + penumbra) ratios, with 2 thresholds considered for these ratios (20% and 50%): penumbra / (infarct + penumbra) ratios >20% or 50% treatment or positive; penumbra / (infarct + penumbra) ratios <20% or 50% no treatment or negative.