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Schaefer, Pamela

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Schaefer

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Pamela

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Schaefer, Pamela
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    Time and Diffusion Lesion Size in Major Anterior Circulation Ischemic Strokes
    (Ovid Technologies (Wolters Kluwer Health), 2014) Hakimelahi, R.; Vachha, Behroze Adi; Copen, William; Papini, G. D. E.; He, J.; Higazi, Mahmoud Mohamad Mounir Ali; Lev, Michael; Schaefer, Pamela; Yoo, Albert J.; Schwamm, Lee; Gonzalez, Ramon
    Background: Major anterior circulation ischemic strokes caused by occlusion of the distal internal carotid artery (ICA) or proximal middle cerebral artery (MCA) or both account for about one-third of ischemic strokes with mostly poor outcomes. These strokes are treatable by IV-tPA and endovascular methods. However, dynamics of infarct growth in these strokes are poorly documented. The purpose was to help understand infarct growth dynamics by measuring acute infarct size with DWI at known times after stroke onset in patients with documented ICA/MCA occlusions. Methods: Retrospectively, we included 47 consecutive patients with documented ICA/MCA occlusions who underwent DWI within 30h of stroke onset. Prospectively, 139 patients were identified using the same inclusion criteria. DWI lesion volumes were measured and correlated to time since stroke onset. Perfusion data was reviewed in those who underwent perfusion imaging. Results: Acute infarct volumes ranged from 0.41-318.3ml. Infarct size and time did not correlate (R2=0.001). The majority of patients had DWI lesions that were less than 25% the territory at risk (<70ml) whether they were imaged < or >8h after stroke onset. DWI lesions corresponded to areas of greatly reduced perfusion. Conclusions: Poor correlation between infarct volume and time after stroke onset suggests that there are factors more powerful than time in determining infarct size within the first 30h. The observations suggest that highly variable cerebral perfusion via the collateral circulation may primarily determine infarct growth dynamics. If verified, clinical implications include the possibility of treating many patients outside traditional time windows.
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    Optimal Brain MRI Protocol for New Neurological Complaint
    (Public Library of Science, 2014) Mehan, William; González, R. Gilberto; Buchbinder, Bradley; Chen, John; Copen, William; Gupta, Rajiv; Hirsch, Joshua; Hunter, George; Hunter, Scott; Johnson, Jason M.; Kelly, Hillary R.; Larvie, Mykol; Lev, Michael; Pomerantz, Stuart; Rapalino, Otto; Rincon, Sandra; Romero, Javier; Schaefer, Pamela; Shah, Vinil
    Background/Purpose Patients with neurologic complaints are imaged with MRI protocols that may include many pulse sequences. It has not been documented which sequences are essential. We assessed the diagnostic accuracy of a limited number of sequences in patients with new neurologic complaints. Methods: 996 consecutive brain MRI studies from patients with new neurological complaints were divided into 2 groups. In group 1, reviewers used a 3-sequence set that included sagittal T1-weighted, axial T2-weighted fluid-attenuated inversion recovery, and axial diffusion-weighted images. Subsequently, another group of studies were reviewed using axial susceptibility-weighted images in addition to the 3 sequences. The reference standard was the study's official report. Discrepancies between the limited sequence review and the reference standard including Level I findings (that may require immediate change in patient management) were identified. Results: There were 84 major findings in 497 studies in group 1 with 21 not identified in the limited sequence evaluations: 12 enhancing lesions and 3 vascular abnormalities identified on MR angiography. The 3-sequence set did not reveal microhemorrhagic foci in 15 of 19 studies. There were 117 major findings in 499 studies in group 2 with 19 not identified on the 4-sequence set: 17 enhancing lesions and 2 vascular lesions identified on angiography. All 87 Level I findings were identified using limited sequence (56 acute infarcts, 16 hemorrhages, and 15 mass lesions). Conclusion: A 4-pulse sequence brain MRI study is sufficient to evaluate patients with a new neurological complaint except when contrast or angiography is indicated.
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    In Acute Stroke, Can CT Perfusion-Derived Cerebral Blood Volume Maps Substitute for Diffusion-Weighted Imaging in Identifying the Ischemic Core?
    (Public Library of Science, 2015) Copen, William; Morais, Livia T.; Wu, Ona; Schwamm, Lee; Schaefer, Pamela; González, R. Gilberto; Yoo, Albert J.
    Background and Purpose In the treatment of patients with suspected acute ischemic stroke, increasing evidence suggests the importance of measuring the volume of the irreversibly injured “ischemic core.” The gold standard method for doing this in the clinical setting is diffusion-weighted magnetic resonance imaging (DWI), but many authors suggest that maps of regional cerebral blood volume (CBV) derived from computed tomography perfusion imaging (CTP) can substitute for DWI. We sought to determine whether DWI and CTP-derived CBV maps are equivalent in measuring core volume. Methods: 58 patients with suspected stroke underwent CTP and DWI within 6 hours of symptom onset. We measured low-CBV lesion volumes using three methods: “objective absolute,” i.e. the volume of tissue with CBV below each of six published absolute thresholds (0.9–2.5 mL/100 g), “objective relative,” whose six thresholds (51%-60%) were fractions of mean contralateral CBV, and “subjective,” in which two radiologists (R1, R2) outlined lesions subjectively. We assessed the sensitivity and specificity of each method, threshold, and radiologist in detecting infarction, and the degree to which each over- or underestimated the DWI core volume. Additionally, in the subset of 32 patients for whom follow-up CT or MRI was available, we measured the proportion of CBV- or DWI-defined core lesions that exceeded the follow-up infarct volume, and the maximum amount by which this occurred. Results: DWI was positive in 72% (42/58) of patients. CBV maps’ sensitivity/specificity in identifying DWI-positive patients were 100%/0% for both objective methods with all thresholds, 43%/94% for R1, and 83%/44% for R2. Mean core overestimation was 156–699 mL for objective absolute thresholds, and 127–200 mL for objective relative thresholds. For R1 and R2, respectively, mean±SD subjective overestimation were -11±26 mL and -11±23 mL, but subjective volumes differed from DWI volumes by up to 117 and 124 mL in individual patients. Inter-rater agreement regarding the presence of infarction on CBV maps was poor (kappa = 0.21). Core lesions defined by the six objective absolute CBV thresholds exceeded follow-up infarct volumes for 81%-100% of patients, by up to 430–1002 mL. Core estimates produced by objective relative thresholds exceeded follow-up volumes in 91% of patients, by up to 210-280 mL. Subjective lesions defined by R1 and R2 exceeded follow-up volumes in 18% and 26% of cases, by up to 71 and 15 mL, respectively. Only 1 of 23 DWI lesions (4%) exceeded final infarct volume, by 3 mL. Conclusion: CTP-derived CBV maps cannot reliably substitute for DWI in measuring core volume, or even establish which patients have DWI lesions.
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    Rapid identification of a major diffusion/perfusion mismatch in distal internal carotid artery or middle cerebral artery ischemic stroke
    (BioMed Central, 2012) Hakimelahi, Reza; Yoo, Albert J.; He, Julian; Schwamm, Lee; Lev, Michael; Schaefer, Pamela; González, Ramon Gilberto
    Background: We tested the hypothesis that in patients with occlusion of the terminal internal carotid artery and/or the proximal middle cerebral artery, a diffusion abnormality of 70 ml or less is accompanied by a diffusion/perfusion mismatch of at least 100%. Methods: Sixty-eight consecutive patients with terminal ICA and/or proximal MCA occlusions and who underwent diffusion/perfusion MRI within 24 hours of stroke onset were retrospectively identified. DWI and mean transit time (MTT) volumes were measured. Prospectively, 48 consecutive patients were identified with the same inclusion criteria. DWI and time to peak (TTP) lesion volumes were measured. A large mismatch volume was defined as an MTT or TTP abnormality at least twice the DWI lesion volume. Results: In the retrospective study, 49 of 68 patients had a DWI lesion volume ≤ 70 ml (mean 20.2 ml; SEM 2.9 ml). A DWI/MTT mismatch of > 100% was observed in all 49 patients (P < .0001). In the prospective study, there were 35/48 patients with DWI volumes ≤ 70 ml (mean 18.7 ml; SEM 3.0 ml). A mismatch > 100% was present in all 35 (P < .0001). Conclusions: Acute stroke patients with major anterior circulation artery occlusion are exceedingly likely to have a major diffusion/perfusion mismatch if the diffusion lesion volume is 70 ml or less. This suggests that physiology-based patient assessments may be made using only vessel imaging and diffusion MRI as a simple alternative to perfusion imaging.
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    The Massachusetts General Hospital Acute Stroke Imaging Algorithm: An Experience and Evidence Based Approach
    (BMJ Publishing Group, 2013) Gonzalez, Ramon; Copen, William; Schaefer, Pamela; Lev, Michael; Pomerantz, Stuart; Rapalino, Otto; Chen, John; Hunter, George; Romero, Javier; Buchbinder, Bradley; Larvie, Mykol; Hirsch, Joshua; Gupta, Rajiv
    The Massachusetts General Hospital Neuroradiology Division employed an experience and evidence based approach to develop a neuroimaging algorithm to best select patients with severe ischemic strokes caused by anterior circulation occlusions (ACOs) for intravenous tissue plasminogen activator and endovascular treatment. Methods found to be of value included the National Institutes of Health Stroke Scale (NIHSS), non-contrast CT, CT angiography (CTA) and diffusion MRI. Perfusion imaging by CT and MRI were found to be unnecessary for safe and effective triage of patients with severe ACOs. An algorithm was adopted that includes: non-contrast CT to identify hemorrhage and large hypodensity followed by CTA to identify the ACO; diffusion MRI to estimate the core infarct; and NIHSS in conjunction with diffusion data to estimate the clinical penumbra.
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    Predictors of Functional Outcome Vary by the Hemisphere of Involvement in Major Ischemic Stroke Treated with Intra-arterial Therapy: A Retrospective Cohort Study
    (BioMed Central, 2010) Yoo, Albert J.; Romero, Javier; Hakimelahi, Reza; Nogueira, Raul Gomes; Rabinov, James; Pryor, Johnny Craig; González, R Gilberto; Hirsch, Joshua; Schaefer, Pamela
    Background: Conflicting data exists regarding the effect of hemispheric lateralization on acute ischemic stroke outcome. Some of this variability may be related to heterogeneous study populations, particularly with respect to the level of arterial occlusion. Furthermore, little is known about the relationship between stroke lateralization and predictors of outcome. The purpose of this study was to characterize the impact of stroke lateralization on both functional outcome and its predictors in a well-defined population of anterior circulation proximal artery occlusions treated with IAT. Methods: Thirty-five consecutive left- and 35 consecutive right-sided stroke patients with intracranial ICA and/or MCA occlusions who underwent IAT were retrospectively analyzed. Ischemic change on pre-treatment imaging was quantified. Reperfusion success was graded using the Mori scale. Good outcome at three months was defined as an mRS ≤ 2. Left- and right-sided strokes were compared for outcome and its predictors. Result: Of 70 patients with median NIHSS score of 18 (IQR, 14-21), 19 (27.1%) had a good outcome. There were 21 terminal ICA and 49 MCA occlusions. There was no difference in the rate of good outcomes between left- (n = 9) and right-sided (n = 10) strokes (p = 0.99). There were no significant differences in occlusion level, age, ischemic change on initial imaging and degree of reperfusion between left- and right-sided strokes. Left-sided strokes had higher baseline NIHSS scores (p = 0.02) and lower admission SBP (p = 0.009). Independent predictors of outcome for left-sided strokes were NIHSS (p = 0.0002) and reperfusion (p = 0.006), and for right-sided strokes were age (p = 0.002) and reperfusion (p = 0.003). In univariate analysis, pre-treatment ischemic change on NCCT was associated with outcome only for left-sided strokes (p = 0.05). Conclusions: In anterior circulation proximal artery occlusions treated with IAT, hemispheric lateralization influences the clinical and imaging predictors of outcome. Most notably, NIHSS predicts outcome only for the left-sided strokes in this population. This finding has important implications for outcome prediction in the acute setting and indicates a need for stroke severity scales more sensitive to right hemispheric deficits.
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    Stability of Large Diffusion/Perfusion Mismatch in Anterior Circulation Strokes for 4 or More Hours
    (BioMed Central, 2010) González, R Gilberto; Hakimelahi, Reza; Schaefer, Pamela; Roccatagliata, Luca; Sorensen, Alma Gregory; Singhal, Aneesh
    Background: The stability of hypoperfused brain tissue in stroke patients with major artery occlusions is unknown. The purpose of this study was to determine the persistence of a diffusion/perfusion mismatch in patients with ICA or proximal MCA occlusions. Methods: Fourteen patients with ICA and/or proximal MCA occlusion and a diffusion/perfusion mismatch at presentation were studied. All were enrolled in a pilot randomized study of normobaric oxygen therapy. None received thrombolytic therapy; 8 received normobaric oxygen and 6 room air. Diffusion/perfusion MRI was performed at baseline, 4 hours, 24 hours, and 1 week. Abnormal DWI, ADC, and MTT volumes were determined using standard image analysis methods. Results: The mean time from symptom onset to baseline MRI was 7.5 ± 1 hours. Across all 4 time points there was a significant difference in DWI lesion (ANOVA, P < 0.0001) and abnormal MTT volumes (ANOVA, P < 0.01) with the 24 hour and 1 week abnormal volumes different from the earlier studies. However, comparing baseline and 4 hour scans, there was no significant interval change in the mean abnormal DWI volume (29.4 ± 8.2 ml vs. 28.1 ± 7.4 ml) or abnormal MTT volumes (137 ± 17.7 ml vs. 130.9 ± 13.8). By 24 hours, only 2 patients did not maintain a mismatch of 20% or greater. Conclusions: Patients who present outside the time window for thrombolytic therapy, and who have a large diffusion/perfusion mismatch on MRI may have a stable mismatch for 4 or more hours.
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    In patients with suspected acute stroke, CT perfusion-based cerebral blood flow maps cannot substitute for DWI in measuring the ischemic core
    (Public Library of Science, 2017) Copen, William; Yoo, Albert J.; Rost, Natalia S.; Morais, Lívia T.; Schaefer, Pamela; González, R. Gilberto; Wu, Ona
    Background: Neuroimaging may guide acute stroke treatment by measuring the volume of brain tissue in the irreversibly injured “ischemic core.” The most widely accepted core volume measurement technique is diffusion-weighted MRI (DWI). However, some claim that measuring regional cerebral blood flow (CBF) with CT perfusion imaging (CTP), and labeling tissue below some threshold as the core, provides equivalent estimates. We tested whether any threshold allows reliable substitution of CBF for DWI. Methods: 58 patients with suspected stroke underwent DWI and CTP within six hours of symptom onset. A neuroradiologist outlined DWI lesions. In CBF maps, core pixels were defined by thresholds ranging from 0%-100% of normal, in 1% increments. Replicating prior studies, we used receiver operating characteristic (ROC) curves to select thresholds that optimized sensitivity and specificity in predicting DWI-positive pixels, first using only pixels on the side of the brain where infarction was clinically suspected (“unilateral” method), then including both sides (“bilateral”). We quantified each method and threshold’s accuracy in estimating DWI volumes, using sums of squared errors (SSE). For the 23 patients with follow-up studies, we assessed whether CBF-derived volumes inaccurately exceeded follow-up infarct volumes. Results: The areas under the ROC curves were 0.89 (unilateral) and 0.90 (bilateral). Various metrics selected optimum CBF thresholds ranging from 29%-32%, with sensitivities of 0.79–0.81, and specificities of 0.83–0.85. However, for the unilateral and bilateral methods respectively, volume estimates derived from all CBF thresholds above 28% and 22% were less accurate than disregarding imaging and presuming every patient’s core volume to be zero. The unilateral method with a 30% threshold, which recent clinical trials have employed, produced a mean core overestimation of 65 mL (range: –82–191), and exceeded follow-up volumes for 83% of patients, by up to 191 mL. Conclusion: CTP-derived CBF maps cannot substitute for DWI in measuring the ischemic core.