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A recent coronavirus disease 2019-related shutdown of the main production facility of iohexol in China has led to massive shortages of iodinated contrast material across the globe. This shortage has also jeopardized neuroimaging. In this article, we describe remedies to reduce iodinated contrast material use for stroke imaging, which is its primary use in neuroimaging, that we have implemented in our hospital network.Copyright © 2022 by American Journal of Neuroradiology.

Global shortage of iodinated contrast medium (ICM) is the latest health care ripple-effect from the COVID-19 pandemic. Some public hospitals in Australia have less than a week's supply. Strategies are, therefore, urgently needed to conserve ICM for those diagnostic tests and interventions, which are time-critical, and without which patients would suffer death or significant morbidity. A plan is also required to continue providing best possible care to patients in the worst-case scenario of exhausted ICM supplies. This document, by representatives from two major public hospitals, will provide some guidance that is tailored to the Australian context.

AHA guidelines recommend use of perfusion imaging for patient selection in the 6-24 h window. Recently, the safety of gadolinium-based contrast agents for MR perfusion imaging has been questioned based on findings that gadolinium accumulates in brain tissue. Regulatory bodies have recommended to limit the use of gadolinium-based contrast agents where possible. Focusing specifically on the time to maximum of the tissue residue function (Tmax) parameter, used in DAWN and DEFUSE 3, we hypothesized that half-dose scans would yield a similar Tmax delay pattern to full-dose scans. We prospectively recruited 10 acute ischemic stroke patients imaged with two perfusion scans at their follow-up visit, one with a standard dose gadolinium followed by a half-dose injection a median of 7 min apart. The brain was parcellated into a grid of 3 x 3 regions and the mean of the difference in Tmax between the 3 x 3 regions on the half- and full-dose Tmax maps was 0.1 s (iqr 0.38 s). The fraction of brain tissue that differed by no more than +/-1 s was 93.7%. In patients with normal or modest Tmax delays, half-dose gadolinium appears to provide comparable Tmax measurements to those of full-dose scans.Copyright © The Author(s) 2020.

Background and Purpose: Distal medium vessel occlusions (DMVOs) are increasingly considered for endovascular thrombectomy but are difficult to detect on computed tomography angiography (CTA). We aimed to determine whether time-to-maximum of tissue residue function (Tmax) maps, derived from CT perfusion, can be used as a triage screening tool to accurately and rapidly identify patients with DMVOs. Method(s): Consecutive code stroke patients who underwent multimodal CT were screened retrospectively. Two experienced readers evaluated all patients' Tmax maps in consensus for presence of delay in an arterial territory (territorial Tmax delay). The diagnostic accuracy of this surrogate for identifying DMVOs was determined using receiver-operating characteristic analysis. CTA, interpreted by 2 experienced neuroradiologists with access to all imaging data, served as the reference standard. Diagnostic performance of 4 other readers with different levels of experience for identifying DMVOs on Tmax versus CTA was also assessed. These readers independently assessed patients' Tmax maps and CTAs in 2 separate timed sessions, and areas under the receiver-operating characteristic curves were compared using the DeLong algorithm. The Wilcoxon signed-rank test was used to comparatively assess diagnostic speed. Result(s): Three hundred seventy-three code stroke patients (median age, 70 years; 56% male, 70 with a DMVO) were included. Territorial Tmax delay had a sensitivity of 100% (CI95, 94.9%-100%) and specificity of 87.8% (CI95, 83.6%-91.3%) for presence of a DMVO, yielding an area under the receiver-operating characteristic curves of 0.939 (CI95, 0.920-0.957). All 4 readers achieved sensitivity >95% and specificity >84% for detecting DMVOs using Tmax maps, with diagnostic accuracy (area under the receiver-operating characteristic curves) and speed that were significantly (P<0.001) higher than on CTA. Conclusion(s): Territorial Tmax delay had perfect sensitivity and high specificity

BACKGROUND AND PURPOSE: Detecting intracranial distal arterial occlusions on CTA is challenging but increasingly relevant to clinical decision-making. Our purpose was to determine whether the use of CTP-derived time-to-maximum of the tissue residue function maps improves diagnostic performance for detecting these occlusions. MATERIALS AND METHODS: Seventy consecutive patients with a distal arterial occlusion and 70 randomly selected controls who underwent multimodal CT with CTA and CTP for a suspected acute ischemic stroke were included in this retrospective study. Four readers with different levels of experience independently read the CTAs in 2 separate sessions, with and without time-to-maximum of the tissue residue function maps, recording the presence or absence of an occlusion, diagnostic confidence, and interpretation time. Accuracy for detecting distal occlusions was assessed using receiver operating characteristic analysis, and areas under curves were compared to assess whether accuracy improved with use of time-to-maximum of the tissue residue function. Changes in diagnostic confidence and interpretation time were assessed using the Wilcoxon signed rank test. RESULT(S): Mean sensitivity for detecting occlusions on CTA increased from 70.7% to 90.4% with use of time-to-maximum of the tissue residue function maps. Diagnostic accuracy improved significantly for the 4 readers (P, .001), with areas under the receiver operating characteristic curves increasing by 0.186, 0.136, 0.114, and 0.121, respectively. Diagnostic confidence and speed also significantly increased. CONCLUSION(S): All assessed metrics of diagnostic performance for detecting distal arterial occlusions improved with the use of time-to-maximum of the tissue residue function maps, encouraging their use to aid in interpretation of CTA by both experienced and inexperienced readers. These findings show the added diagnostic value of including CTP in the acute stroke imaging protocol.Copyright © 2021 Am

BACKGROUND AND PURPOSE: Patients with acute ischemic stroke due to a large vessel occlusion (AIS-LVO) undergo emergent neuroimaging triage for thrombectomy treatment. MRI is often utilized for this evaluation, and cerebral magnetic resonance perfusion (MRP) imaging is used to identify the presence of the salvageable penumbra. To determine if dose reduction is feasible, we assessed whether a half-dose reduction in gadobenate provided sufficient MRP quality in AIS-LVO patients. METHODS: A prospective observational study of all patients presenting to our neurovascular referral center with AIS-LVO was performed. MRP was done with a half-dose of gadolinium (0.1 ml/kg body weight) over a period of 10 months. MRP images were compared to a consecutive historical cohort of full-dose gadolinium (0.2 ml/kg body weight) MRP studies and rated for image quality (poor, borderline, or good) that determined thrombectomy eligibility. RESULTS: Fifty-four half-dose and 127 full-dose patients were included. No differences in patient demographics or stroke presentation details were identified. MRP quality differed between half- and full-dose scans (p < 0.001), which were rated as poor (40.7% vs. 6.3%), borderline (18.5% vs. 26.8%), and good quality (40.7% vs. 66.9%), respectively. MRP image quality was then dichotomized into poor and sufficient (borderline and good) quality groups; half-dose studies were more likely to have poor quality compared to full-dose studies (40.7% vs. 6.3%; p < 0.001). CONCLUSIONS: Half-dose gadolinium administration for MRP in AIS-LVO patients results in poor image quality in a substantial number of studies. MR cerebral perfusion performed with half-dose gadolinium may adversely affect stroke patient triage for thrombectomy.

Background and Purpose-Accurate and rapid detection of anterior circulation large vessel occlusion (LVO) is of paramount importance in patients with acute stroke due to the potentially rapid infarction of at-risk tissue and the limited therapeutic window for endovascular clot retrieval. Hence, the optimal threshold of a new, fully automated software-based approach for LVO detection was determined, and its diagnostic performance evaluated in a large cohort study. Methods-For this retrospective study, data were pooled from: 2 stroke trials, DEFUSE 2 (n=62; 07/08-09/11) and DEFUSE 3 (n=213; 05/17-05/18); a cohort of endovascular clot retrieval candidates (n=82; August 2, 2014-August 30, 2015) and normals (n=111; June 6, 2017-January 28, 2019) from a single quaternary center; and code stroke patients (n=501; January 1, 2017-December 31, 2018) from a single regional hospital. All CTAs were assessed by the automated algorithm. Consensus reads by 2 neuroradiologists served as the reference standard. ROC analysis was used to assess diagnostic performance of the algorithm for detection of (1) anterior circulation LVOs involving the intracranial internal carotid artery or M1 segment middle cerebral artery (M1-MCA); (2) anterior circulation LVOs and proximal M2 segment MCA (M2-MCA) occlusions; and (3) individual segment occlusions. Results-CTAs from 926 patients (median age 70 years, interquartile range: 58-80; 422 females) were analyzed. Three hundred ninety-five patients had an anterior circulation LVO or M2-MCA occlusion (National Institutes of Health Stroke Scale 14 [median], interquartile range: 9-19). Sensitivity and specificity were 97% and 74%, respectively, for LVO detection, and 95% and 79%, respectively, when M2 occlusions were included. On analysis by occlusion site, sensitivities were 90% (M2-MCA), 97% (M1-MCA), and 97% (intracranial internal carotid artery) with corresponding area-under-the-ROC-curves of 0.874 (M2), 0.962 (M1), and 0.997 (intracranial internal ca

Background and Purpose-Endovascular thrombectomy is highly effective in acute ischemic stroke patients with an anterior circulation large vessel occlusion (LVO), decreasing morbidity and mortality. Accurate and prompt identification of LVOs is imperative because these patients have large volumes of tissue that are at risk of infarction without timely reperfusion, and the treatment window is limited to 24 hours. We assessed the accuracy and speed of a commercially available fully automated LVO-detection tool in a cohort of patients presenting to a regional hospital with suspected stroke. Methods-Consecutive patients who underwent multimodal computed tomography with thin-slice computed tomography angiography between January 1, 2017 and December 31, 2018 for suspected acute ischemic stroke within 24 hours of onset were retrospectively identified. The multimodal computed tomographies were assessed by 2 neuroradiologists in consensus for the presence of an intracranial anterior circulation LVO or M2-segment middle cerebral artery occlusion (the reference standard). The patients' computed tomography angiographies were then processed using an automated LVO-detection algorithm (RAPID CTA). Receiver-operating characteristic analysis was used to determine sensitivity, specificity, and negative predictive value of the algorithm for detection of (1) an LVO and (2) either an LVO or M2-segment middle cerebral artery occlusion. Results-CTAs from 477 patients were analyzed (271 men and 206 women; median age, 71; IQR, 60-80). Median processing time was 158 seconds (IQR, 150-167 seconds). Seventy-eight patients had an anterior circulation LVO, and 28 had an isolated M2-segment middle cerebral artery occlusion. The sensitivity, negative predictive value, and specificity were 0.94, 0.98, and 0.76, respectively for detection of an intracranial LVO and 0.92, 0.97, and 0.81, respectively for detection of either an intracranial LVO or M2-segment middle cerebral artery occlusion. Conclusion

Introduction: Australia has fortunately had a low prevalence coronavirus disease 2019 (COVID-19), and our healthcare system has not been overwhelmed. We aimed to determine whether, despite this, a decline in acute stroke presentations, imaging and intervention occurred during the pandemic at a busy stroke centre. Method(s): The number of 'code stroke' activations, multimodal CTs and endovascular clot retrievals (ECRs) performed during the pandemic period (3/1/2020-5/10/2020) at a large comprehensive stroke centre was compared against the pre-pandemic period (3/1/2019-1/31/2019) using Z-statistics. Year-on-year comparison of the number of patients with large vessel occlusions (LVOs) and ECRs performed per month was also made. Result(s): The number of 'code stroke' activations and patients undergoing multimodal CT per month decreased significantly (P < 0.0025) following lockdown on 29th March. The number of ECRs also decreased (P = 0.165). The nadir in the weekly number of CTs coincided with lockdown and the peak of new COVID-19 cases. The number of patients with LVOs and ECRs increased by 15% and 14%, respectively, in March but decreased by 55% and 48%, respectively, in April. Conclusion(s): The significant decrease in volume of 'code stroke' activations and acute stroke imaging following lockdown was accompanied by a concomitant decrease in patients with LVOs and ECRs. The decrease in imaging was therefore not driven purely by patients with mild strokes and stroke mimics, but also included those with severe strokes. Since Australia had a low prevalence of COVID-19, this observed decrease cannot be attributed to hospital congestion and is instead likely driven by patient fear.Copyright © 2020 The Royal Australian and New Zealand College of Radiologists

Aims: The objective of this study was to compare the diagnostic performance of the baseline pre-contrast images of dynamic susceptibility contrast perfusion-weighted imaging (DSC-PWI) with conventional T2*gradient recalled echo (GRE) imaging for detection of hemorrhage in acute ischemic stroke patients. Material(s) and Method(s): T2*GRE and DSC-PWI from 393 magnetic resonance imaging scans from 221 patients enrolled in three prospective stroke studies were independently evaluated by two readers blinded to clinical and other imaging data. Agreement between T2*GRE and DSC-PWI for the presence of hemorrhage, and acute hemorrhagic transformation, was assessed using the kappa statistic. Inter-reader agreement was also assessed using the kappa statistic. Result(s): Agreement between the baseline images of DSC-PWI and T2*GRE regarding the presence of hemorrhage was almost perfect (kreader 1 : 0.90, 95% confidence interval 0.86-0.95 and kreader 2 : 0.91, 95% confidence interval 0.87-0.96). Agreement between the sequences was still higher for detection of acute hemorrhagic transformation (kreader 1 : 0.94, 95% confidence interval 0.91-0.98 and kreader 2 : 0.95, 95% confidence interval 0.92-0.98). Inter-reader agreement for detection of hemorrhage was also almost perfect for both T2*GRE (k: 0.95, 95% confidence interval 0.91-0.98) and DSC-PWI (k: 0.96, 95% confidence interval 0.93-0.99). Acute hemorrhagic transformation detected on T2*GRE was missed on DSC-PWI by one or both readers in 5/393 (1.3%) scans. Conclusion(s): The almost perfect statistical agreement between DSC-PWI and conventional T2*GRE suggests that DSC-PWI is sufficient for hemorrhage screening prior to thrombolysis in stroke patients. T2*GRE can therefore be omitted when DSC-PWI is included, thereby shortening the acute ischemic stroke magnetic resonance imaging protocol and expediting treatment. Trial registration: ClinicalTrials.gov Identifier: NCT02586415.Copyright © 2019 World Stroke Organization.

PURPOSE: Prospective motion correction is arguably the "silver bullet" solution for magnetic resonance imaging (MRI) studies impacted by motion, applicable to almost any pulse sequence and immune from the spin history artifacts introduced by a moving object. In prospective motion correction, the magnetic field gradients and radio frequency waveforms are adjusted in real time in response to measured head motion so as to maintain the head in a stationary reference frame relative to the scanner. Vital for this approach are accurate and rapidly sampled head pose measurements, which may be obtained optically using cameras. However, most optical methods are limited by the need to attach physical markers to the skin, which leads to decoupling of head and marker motion and reduces the effectiveness of correction. In this work we investigate the feasibility and initial performance of a stereo-optical motion tracking method which does not require any attached markers. METHODS: The method relies on detecting distinctive natural features or amplified features (using skin stamps) directly on the forehead in multiple camera views, and then deriving pose estimates via a 3D-2D registration between the skin features and a database of forehead landmarks. To demonstrate the feasibility and potential accuracy of the marker-free method for discrete (step-wise) head motion, we performed out-of-bore and in-bore experiments using robotically and manually controlled phantoms in addition to in-bore testing on human volunteers. We also developed a convenient out-of-bore test bed to benchmark and optimize the motion tracking performance. RESULTS: For out-of-bore phantom tests, the pose estimation accuracy (compared to robotic ground truth) was 0.14 mm and 0.23 degrees for incremental translation and rotation, respectively. For arbitrary motion, the pose accuracy obtained using the smallest forehead feature patch was equivalent to 0.21 ± 0.11 mm positional accuracy in the striatum. For in-bore

PURPOSE: Motion artifact limits the clinical translation of high-field MR. We present an optical prospective motion correction system for 7 Tesla MRI using a custom-built, within-coil camera to track an optical marker mounted on a subject. METHODS: The camera was constructed to fit between the transmit-receive coils with direct line of sight to a forehead-mounted marker, improving upon prior mouthpiece work at 7 Tesla MRI. We validated the system by acquiring a 3D-IR-FSPGR on a phantom with deliberate motion applied. The same 3D-IR-FSPGR and a 2D gradient echo were then acquired on 7 volunteers, with/without deliberate motion and with/without motion correction. Three neuroradiologists blindly assessed image quality. In 1 subject, an ultrahigh-resolution 2D gradient echo with 4 averages was acquired with motion correction. Four single-average acquisitions were then acquired serially, with the subject allowed to move between acquisitions. A fifth single-average 2D gradient echo was acquired following subject removal and reentry. RESULTS: In both the phantom and human subjects, deliberate and involuntary motion were well corrected. Despite marked levels of motion, high-quality images were produced without spurious artifacts. The quantitative ratings confirmed significant improvements in image quality in the absence and presence of deliberate motion across both acquisitions (P < .001). The system enabled ultrahigh-resolution visualization of the hippocampus during a long scan and robust alignment of serially acquired scans with interspersed movement. CONCLUSION: We demonstrate the use of a within-coil camera to perform optical prospective motion correction and ultrahigh-resolution imaging at 7 Tesla MRI. The setup does not require a mouthpiece, which could improve accessibility of motion correction during 7 Tesla MRI exams.

OBJECTIVE: To assess the utility of computed tomographic (CT) perfusion for selection of patients for endovascular therapy up to 18 hours after symptom onset. METHODS: We conducted a multicenter cohort study of consecutive acute stroke patients scheduled to undergo endovascular therapy within 90 minutes after a baseline CT perfusion. Patients were classified as "target mismatch" if they had a small ischemic core and a large penumbra on their baseline CT perfusion. Reperfusion was defined as >50% reduction in critical hypoperfusion between the baseline CT perfusion and the 36-hour follow-up magnetic resonance imaging. RESULTS: Of the 201 patients enrolled, 190 patients with an adequate baseline CT perfusion study who underwent angiography were included (mean age = 66 years, median NIH Stroke Scale [NIHSS] = 16, median time from symptom onset to endovascular therapy = 5.2 hours). Rate of reperfusion was 89%. In patients with target mismatch (n = 131), reperfusion was associated with higher odds of favorable clinical response, defined as an improvement of ≥8 points on the NIHSS (83% vs 44%; p = 0.002, adjusted odds ratio [OR] = 6.6, 95% confidence interval [CI] = 2.1-20.9). This association did not differ between patients treated within 6 hours (OR = 6.4, 95% CI = 1.5-27.8) and those treated > 6 hours after symptom onset (OR = 13.7, 95% CI = 1.4-140). INTERPRETATION: The robust association between endovascular reperfusion and good outcome among patients with the CT perfusion target mismatch profile treated up to 18 hours after symptom onset supports a randomized trial of endovascular therapy in this patient population. Ann Neurol 2017;81:849-856.

BACKGROUND AND PURPOSE: The perfusion-weighted imaging (PWI)/diffusion-weighted imaging (DWI) mismatch profile is used to select patients for endovascular treatment. A PWI map of Tmax is commonly used to identify tissue with critical hypoperfusion. A time to peak (TTP) map reflects similar hemodynamic properties with the added benefit that it does not require arterial input function (AIF) selection and deconvolution. We aimed to determine if TTP could substitute Tmax for mismatch categorization. METHODS: Imaging data of the DEFUSE 2 trial were reprocessed to generate relative TTP (rTTP) maps. We identified the rTTP threshold that yielded lesion volumes comparable to Tmax > 6 s and assessed the effect of reperfusion according to mismatch status, determined based on Tmax and rTTP volumes. RESULTS: Among 102 included cases, the Tmax > 6 s lesion volumes corresponded most closely with rTTP > 4.5 s lesion volumes: median absolute difference 6.9 mL (IQR: 2.3-13.0). There was 94% agreement in mismatch classification between Tmax and rTTP-based criteria. When mismatch was assessed by Tmax criteria, the odds ratio (OR) for favorable clinical response associated with reperfusion was 7.4 (95% CI 2.3-24.1) in patients with mismatch vs. 0.4 (95% CI 0.1-2.6) in patients without mismatch. When mismatch was assessed with rTTP criteria, these ORs were 7.2 (95% CI 2.3-22.2) and 0.3 (95% CI 0.1-2.2), respectively. CONCLUSION: rTTP yields lesion volumes that are comparable to Tmax and reliably identifies the PWI/DWI mismatch profile. Since rTTP is void of the problems associated with AIF selection, it is a suitable substitute for Tmax that could improve the robustness and reproducibility of mismatch classification in acute stroke.

Plasticity of white matter tracts is thought to be essential for cognitive development and academic skill acquisition in children. However, a dearth of high-quality diffusion tensor imaging (DTI) data measuring longitudinal changes with learning, as well as methodological difficulties in multi-time point tract identification have limited our ability to investigate plasticity of specific white matter tracts. Here, we examine learning-related changes of white matter tracts innervating inferior parietal, prefrontal and temporal regions following an intense 2-month math tutoring program. DTI data were acquired from 18 third grade children, both before and after tutoring. A novel fiber tracking algorithm based on a White Matter Query Language (WMQL) was used to identify three sections of the superior longitudinal fasciculus (SLF) linking frontal and parietal (SLF-FP), parietal and temporal (SLF-PT) and frontal and temporal (SLF-FT) cortices, from which we created child-specific probabilistic maps. The SLF-FP, SLF-FT, and SLF-PT tracts identified with the WMQL method were highly reliable across the two time points and showed close correspondence to tracts previously described in adults. Notably, individual differences in behavioral gains after 2 months of tutoring were specifically correlated with plasticity in the left SLF-FT tract. Our results extend previous findings of individual differences in white matter integrity, and provide important new insights into white matter plasticity related to math learning in childhood. More generally, our quantitative approach will be useful for future studies examining longitudinal changes in white matter integrity associated with cognitive skill development.

Evaluation of neurodegenerative disease progression may be assisted by quantification of the volume of structures in the human brain using magnetic resonance imaging (MRI). Automated segmentation software has improved the feasibility of this approach, but often the reliability of measurements is uncertain. We have established a unique dataset to assess the repeatability of brain segmentation and analysis methods. We acquired 120 T1-weighted volumes from 3 subjects (40 volumes/subject) in 20 sessions spanning 31 days, using the protocol recommended by the Alzheimer's Disease Neuroimaging Initiative (ADNI). Each subject was scanned twice within each session, with repositioning between the two scans, allowing determination of test-retest reliability both within a single session (intra-session) and from day to day (inter-session). To demonstrate the application of the dataset, all 3D volumes were processed using FreeSurfer v5.1. The coefficient of variation of volumetric measurements was between 1.6% (caudate) and 6.1% (thalamus). Inter-session variability exceeded intra-session variability for lateral ventricle volume (P<0.0001), indicating that ventricle volume in the subjects varied between days.

Background and Purpose-: Two phase 2 studies of alteplase in acute ischemic stroke 3 to 6 hours after onset, Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET; a randomized, controlled, double-blinded trial), and Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution Study (DEFUSE; open-label, treatment only) using MR imaging-based outcomes have been conducted. We have pooled individual patient data from these to assess the response to alteplase. The primary hypothesis was that alteplase would significantly attenuate infarct growth compared with placebo in mismatch-selected patients using coregistration techniques. Methods-: The EPITHET-DEFUSE study datasets were pooled while retaining the original inclusion and exclusion criteria. Significant hypoperfusion was defined as a Tmax delay >6 seconds), and coregistration techniques were used to define MR diffusion-weighted imaging/perfusion-weighted imaging mismatch. Neuroimaging, parameters including reperfusion, recanalization, symptomatic intracerebral hemorrhage, and clinical outcomes were assessed. Alteplase and placebo groups were compared for the primary outcome of infarct growth as well for secondary outcome measures. Results-: From 165 patients with adequate MR scans in the EPITHET-DEFUSE pooled data, 121 patients (73.3%) were found to have mismatch. For the primary outcome analysis, 60 patients received alteplase and 41 placebo. Mismatch patients receiving alteplase had significantly attenuated infarct growth compared with placebo (P=0.025). The reperfusion rate was also increased (62.7% vs 31.7%; P=0.003). Mortality and clinical outcomes were not different between groups. Conclusions-: The data provide further evidence that alteplase significantly attenuates infarct growth and increases reperfusion compared with placebo in the 3-to 6-hour time window in patients selected based on MR penumbral imaging. Clinical Trial Registration-: URL: http://www.clinicaltrials. gov. Unique ident

BACKGROUND: Spontaneous intracerebral hemorrhage (ICH) is associated with blood-brain barrier (BBB) injury, which is a poorly understood factor in ICH pathogenesis, potentially contributing to edema formation and perihematomal tissue injury. We aimed to assess and quantify BBB permeability following human spontaneous ICH using dynamic contrast-enhanced magnetic resonance imaging (DCE MRI). We also investigated whether hematoma size or location affected the amount of BBB leakage. METHODS AND RESULTS: Twenty-five prospectively enrolled patients from the Diagnostic Accuracy of MRI in Spontaneous intracerebral Hemorrhage (DASH) study were examined using DCE MRI at 1 week after symptom onset. Contrast agent dynamics in the brain tissue and general tracer kinetic modeling were used to estimate the forward leakage rate (K(trans)) in regions of interest (ROI) in and surrounding the hematoma and in contralateral mirror-image locations (control ROI). In all patients BBB permeability was significantly increased in the brain tissue immediately adjacent to the hematoma, that is, the hematoma rim, compared to the contralateral mirror ROI (P<0.0001). Large hematomas (>30 mL) had higher K(trans) values than small hematomas (P<0.005). K(trans) values of lobar hemorrhages were significantly higher than the K(trans) values of deep hemorrhages (P<0.005), independent of hematoma volume. Higher K(trans) values were associated with larger edema volumes. CONCLUSIONS: BBB leakage in the brain tissue immediately bordering the hematoma can be measured and quantified by DCE MRI in human ICH. BBB leakage at 1 week is greater in larger hematomas as well as in hematomas in lobar locations and is associated with larger edema volumes.

OBJECTIVE: Very low cerebral blood volume (VLCBV), diffusion, and hypoperfusion lesion volumes have been proposed as predictors of hemorrhagic transformation following stroke thrombolysis. We aimed to compare these parameters, validate VLCBV in an independent cohort using DEFUSE study data, and investigate the interaction of VLCBV with regional reperfusion. METHODS: The EPITHET and DEFUSE studies obtained diffusion and perfusion magnetic resonance imaging (MRI) in patients 3 to 6 hours from onset of ischemic stroke. EPITHET randomized patients to tissue plasminogen activator (tPA) or placebo, and all DEFUSE patients received tPA. VLCBV was defined as cerebral blood volume<2.5th percentile of brain contralateral to the infarct. Parenchymal hematoma (PH) was defined using European Cooperative Acute Stroke Study criteria. Reperfusion was assessed using subacute perfusion MRI coregistered to baseline imaging. RESULTS: In DEFUSE, 69 patients were analyzed, including 9 who developed PH. The >2 ml VLCBV threshold defined in EPITHET predicted PH with 100% sensitivity, 72% specificity, 35% positive predictive value, and 100% negative predictive value. Pooling EPITHET and DEFUSE (163 patients, including 23 with PH), regression models using VLCBV (p<0.001) and tPA (p=0.02) predicted PH independent of clinical factors better than models using diffusion or time to maximum>8 seconds lesion volumes. Excluding VLCBV in regions without reperfusion improved specificity from 61 to 78% in the pooled analysis. INTERPRETATION: VLCBV predicts PH after stroke thrombolysis and appears to be a more powerful predictor than baseline diffusion or hypoperfusion lesion volumes. Reperfusion of regions of VLCBV is strongly associated with post-thrombolysis PH. VLCBV may be clinically useful to identify patients at significant risk of hemorrhage following reperfusion.