175 Physiological MRI Biomarkers & Cognition after SRS for Brain Metastases Data acquisition Imaging protocol The participants were scanned on a 3 Tesla MRI scanner (Achieva, Philips Medical Systems, Best, The Netherlands) using a 32-channel receive coil. The same scanning protocol was used as described before.14 To acquire CVR measurements, a wholebrain multi-slice single shot gradient-echo EPI BOLD images (TR = 1050 ms, TE = 30 ms, flip angle 65°, voxel size 2.292 x 2.292 x 2.5 mm3, acquisition matrix 96 x 96 x 51, 1000 dynamics, multi-band factor = 3, SENSE factor = 1.8) were acquired throughout a computer-controlled hypercapnic breathing protocol (described below). An additional dataset pair was acquired for EPI phase (distortion) correction. Perfusion data were acquired using a multi-delay ASL sequence. A whole volume was acquired at 4 post-labeling delays (660, 1325, 1989, 2654ms), using a pCASL Look-Locker multi-slice EPI read-out (total scan time = 240 s, labelling train duration = 1650ms, TR = 5s, TE = 12 ms, flip angle 25°, acquired resolution: 3 x 3 x 7 mm3, acquisition matrix: 80 x 80 x 17, 23 volumes of label- control pair, SENSE factor = 2, 2 background suppression pulses. The first volume contains the calibration (M0) images for each post-label delay where the labelling, saturation pulses and background suppression were turned off. No breathing challenges were performed during ASL imaging. The ASL was planned using a fast phase contrast angiography scan, with the labeling plane carefully placed perpendicular to the internal carotid arteries and vertebral arteries. The whole brain SWI was acquired using a multi-echo gradient-echo (MEGRE) sequence (TE1 = 8.5 ms, TE2 = 17.5 ms, TE3 = 26.5 ms, TE4 = 35.5 ms, TE5 = 44.5 ms, echo spacing 8 ms, TR 50 ms, flip angle 17°, voxels size 0.342 x 0.342 x 2 mm3, acquisition matrix 384 x 383 x 63) was acquired. Additionally, a 3D T1-weighted magnetization prepared rapid gradient echo imaging (MPRAGE) sequence (TR = 8 ms, TE = 3.25 ms, flip angle 10°, isotropic resolution 1 mm, acquisition matrix 240 x 240 x 180) and a 3D T2-weighted FLAIR sequence (TR 4800 ms, TE 240 ms, TI = 1650 ms, flip angle 90°, isotropic resolution: 1 mm, acquisition matrix 256 x 256 x 182) were acquired for anatomical reference. Clinical CT and MRI acquisition CT and MRI scans were acquired as part of clinical care as usual 1 to 5 days before receiving SRS. CT scans were acquired on a Brilliance Big bore 22 scanner (Philips Medical Systems, Best, The Netherlands) with a tube potential of 120 kVp, matrix size of 512 × 512 and inplane slice thickness of 1 mm. The participants were scanned on a 1.5 Tesla MRI scanner (Ingenia, Philips Medical Systems, Best, The Netherlands) using a 15-channel receive coil. A 3D SPGR sequence after injection of 0.1 ml gadovist/kg was performed (TR = 7.6 ms, TE = 3.4 ms, flip angle 8°, isotropic resolution: 1 mm, acquisition matrix 232 x 232 x 170). The clinician uses this clinically acquired MRI 7
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