Background Stroke thrombolysis with alteplase is currently recommended 0-4•5 h after stroke onset. We aimed to determine whether perfusion imaging can identify patients with salvageable brain tissue with symptoms 4•5 h or more from stroke onset or with symptoms on waking who might benefit from thrombolysis.Methods In this systematic review and meta-analysis of individual patient data, we searched PubMed for randomised trials published in English between Jan 1, 2006, and March 1, 2019. We also reviewed the reference list of a previous systematic review of thrombolysis and searched ClinicalTrials.gov for interventional studies of ischaemic stroke. Studies of alteplase versus placebo in patients (aged ≥18 years) with ischaemic stroke treated more than 4•5 h after onset, or with wake-up stroke, who were imaged with perfusion-diffusion MRI or CT perfusion were eligible for inclusion. The primary outcome was excellent functional outcome (modified Rankin Scale [mRS] score 0-1) at 3 months, adjusted for baseline age and clinical severity. Safety outcomes were death and symptomatic intracerebral haemorrhage. We calculated odds ratios, adjusted for baseline age and National Institutes of Health Stroke Scale score, using mixed-effects logistic regression models. This study is registered with PROSPERO, number CRD42019128036. FindingsWe identified three trials that met eligibility criteria: EXTEND, ECASS4-EXTEND, and EPITHET. Of the 414 patients included in the three trials, 213 (51%) were assigned to receive alteplase and 201 (49%) were assigned to receive placebo. Overall, 211 patients in the alteplase group and 199 patients in the placebo group had mRS assessment data at 3 months and thus were included in the analysis of the primary outcome. 76 (36%) of 211 patients in the alteplase group and 58 (29%) of 199 patients in the placebo group had achieved excellent functional outcome at 3 months (adjusted odds ratio [OR] 1•86, 95% CI 1•15-2•99, p=0•011). Symptomatic intracerebral haemorrhage was more common in the alteplase group than the placebo group (ten [5%] of 213 patients vs one [<1%] of 201 patients in the placebo group; adjusted OR 9•7, 95% CI 1•23-76•55, p=0•031). 29 (14%) of 213 patients in the alteplase group and 18 (9%) of 201 patients in the placebo group died (adjusted OR 1•55, 0•81-2•96, p=0•66).Interpretation Patients with ischaemic stroke 4•5-9 h from stroke onset or wake-up stroke with salvageable brain tissue who were treated with alteplase achieved better functional outcomes than did patients given placebo. The rate of symptomatic intracerebral haemorrhage was higher with alteplase, but this increase did not negate the overall net benefit of thrombolysis.

BACKGROUND AND PURPOSE We have developed PC HYPRFlow, a comprehensive MRA technique that includes a whole-brain CE dynamic series followed by PC velocity-encoding, yielding a time series of high-resolution morphologic angiograms with associated velocity information. In this study, we present velocity data acquired by using the PC component of PC HYPRFlow (PC-VIPR). MATERIALS AND METHODS Ten healthy volunteers (6 women, 4 men) were scanned by using PC HYPRFlow and 2D-PC imaging, immediately followed by velocity measurements by using TCD. Velocity measurements were made in the M1 segments of the MCAs from the PC-VIPR, 2D-PC, and TCD examinations. RESULTS PC-VIPR showed approximately 30% lower mean velocity compared with TCD, consistent with other comparisons of TCD with PC-MRA. The correlation with TCD was r = 0.793, and the correlation of PC-VIPR with 2D-PC was r = 0.723. CONCLUSIONS PC-VIPR is a technique capable of acquiring high-resolution MRA of diagnostic quality with velocity data comparable with TCD and 2D-PC. The combination of velocity information and fast high-resolution whole-brain morphologic angiograms makes PC HYPRFlow an attractive alternative to current MRA methods.

BACKGROUND AND PURPOSE: Arteriovenous malformations have a high lifetime risk of hemorrhage; however, treatment carries a significant risk of morbidity and mortality, including permanent neurologic sequelae. WSS and other hemodynamic parameters are altered in patients with symptomatic AVMs, and analysis of hemodynamics may have value in stratifying patients into different risk groups. In this study, we examined hemodynamic data from patients with stable symptoms and those who presented with acute symptoms to identify trends which may help in risk stratification. MATERIALS AND METHODS: Phase-contrast MRA using a radial readout (PC-VIPR) is a fast, high-resolution technique that can acquire whole-brain velocity-encoded angiograms with scan times of approximately 5 minutes. Ten patients with AVMs were scanned using PC-VIPR; velocity, area, flow, and WSS in vessels feeding the AVMs and normal contralateral vessels were calculated using velocity data from the phase-contrast acquisition. RESULTS: Patients with an asymptomatic presentation or mild symptoms (n = 4) had no significant difference in WSS in feeding vessels compared with normal contralateral vessels, whereas patients presenting with hemorrhage, severe headaches/seizures, or focal neurologic deficits (n = 6) had significantly higher WSS in feeding vessels compared with contralateral vessels. CONCLUSIONS: In this study, we demonstrate that estimates of WSS and other hemodynamic parameters can be obtained noninvasively in patients with AVMs in clinically useful imaging times. Variation in WSS between feeders and normal vessels appears to relate to the clinical presentation of the patient. Further analysis of hemodynamic changes may improve characterization and staging of AVM patients, when combined with existing risk factors.

BACKGROUND AND PURPOSE: HYPRFlow is a novel imaging strategy that provides fast, high-resolution contrast-enhanced time-resolved images and measurement of the velocity of the entire cerebrovascular system. Our hypothesis was that the images obtained with this strategy are of adequate diagnostic image quality to delineate the major components of AVMs. MATERIALS AND METHODS: HYPRFlow and 3D TOF scans were obtained in 21 patients with AVMs with correlative DSA examinations in 14 patients. The examinations were scored for image quality and graded by using the Spetzler-Martin criteria. Mean arterial transit time and overlap integrals were calculated from the dynamic image data. Volume flow rates in normal arteries and AVM feeding arteries were measured from the phase contrast data. RESULTS: HYPRFlow was equivalent to 3D-TOF in delineating normal arterial anatomy, arterial feeders, and nidus size and was concordant with DSA for AVM grading and venous drainage in 13 of the 14 examinations. Mean arterial transit time on the AVM side was 0.49 seconds, and on the normal contralateral side, 2.53 seconds with P < .001. Across all 21 subjects, the mean arterial volume flow rate in the M1 segment ipsilateral to the AVM was 4.07 ± 3.04 mL/s; on the contralateral M1 segment, it was 2.09 ± 0.64 mL/s. The mean volume flow rate in the largest feeding artery to the AVM was 3.86 ± 2.74 mL/s. CONCLUSIONS: HYPRFlow provides an alternative approach to the MRA evaluation of AVMs, with the advantages of increased coverage, 0.75-second temporal resolution, 0.68-mm isotropic spatial resolution, and quantitative measurement of flow in 6 minutes.

SUMMARYWe report on the image quality obtained by using fast contrast-enhanced whole-brain 4D radial MRA with 0.75-second temporal resolution, isotropic submillimeter spatial resolution, and velocity encoding (HYPRFlow). Images generated by HYPR-LR by using the velocity-encoded data as the constraining image were of diagnostic quality. In addition, we demonstrate that measurements of shear stress within the middle cerebral artery can be derived from the highresolution 3D velocity data.Whole-brain 4D contrast-enhanced MRA has been previously described by using Cartesian acquisitions, partial-Fourier encoding, and parallel imaging with multiple coils. [1][2][3] However, performing high-resolution whole-brain 4D contrast-enhanced MRA examinations is challenging using conventional imaging methods because acquisition time increases proportionally with matrix size. Radial acquisitions like 2D projection reconstruction [4][5][6]8 can be effective in accelerating MR angiography; however, image quality is limited by undersampling artifacts and decreased SNR at high acceleration factors. Innovative reconstruction algorithms, such as HYPR and HYPR-LR 9-11 ), which exploit prior information to constrain individual images, are able to reduce the severity of undersampling artifacts and SNR loss even at high levels of acceleration. Combining undersampled radial acquisition with HYPR reconstruction can dramatically improve frame rates and image coverage without degradation of image quality. 12 HYPRFlow is one of the hybrid HYPR techniques that uses the phase-contrast image from a separate scan as the vascular constraint to provide whole-brain 4D contrast-enhanced MRA with subsecond temporal resolution and submillimeter isotropic spatial resolution as well as flow dynamics. [12][13][14] In this article, we investigate the clinical utility of this technique by assessing the image quality of HYPRFlow and estimate WSS in the middle cerebral arteries by using the time-average velocity through a single cardiac cycle. TechniqueVolunteer studies were performed in compliance with the Health Insurance Portability and Accountability Act regulations and by using a protocol approved by the local institutional NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript review board. Eight adult subjects ranging from 24 to 40 years of age were imaged (4 women, 4 men) with a clinical 3T MR imaging system (Excite HD, TwinSpeed, Signa; GE Healthcare, Waukesha, Wisconsin) with an 8-channel head coil (HD Brain Coil, GE Healthcare). Each HYPRFlow study involved 2 encoding methods. First, during contrast injection, spatial encoding was performed by using a time-resolved multiecho 3D radial acquisition (CE-VIPR). 15 Subsequently, velocity encoding was performed by using a highresolution dual-echo 3D radial phase-contrast acquisition (PC-VIPR). The PC-VIPR data were used to form a composite image (angiographic constraint) for HYPR-LR reconstruction and for hemodynamic evaluation. MR Imaging ProtocolImaging parameters for CE-VIPR were th...