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Wu, Ona

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Ona

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Wu, Ona

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2009 - 200912010 - 20187

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Author's Publications: search.filters.isAuthorOfPublication.5f115500-0b26-410e-abda-985dbfda3066

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Now showing 1 - 8 of 8
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    Neuroimaging Paradigms to Identify Patients for Reperfusion Therapy in Stroke of Unknown Onset
    (Frontiers Media S.A., 2018) Etherton, Mark; Barreto, Andrew D.; Schwamm, Lee; Wu, Ona
    Despite the proven efficacy of intravenous alteplase or endovascular thrombectomy for the treatment of patients with acute ischemic stroke, only a minority receive these treatments. This low treatment rate is due in large part to delay in hospital arrival or uncertainty as to the exact time of onset of ischemic stroke, which renders patients outside the current guideline-recommended window of eligibility for receiving these therapeutics. However, recent pivotal clinical trials of late-window thrombectomy now force us to rethink the value of a simplistic chronological formulation that “time is brain.” We must recognize a more nuanced concept that the rate of tissue death as a function of time is not invariant, that still salvageable tissue at risk of infarction may be present up to 24 h after last-known well, and that those patients may strongly benefit from reperfusion. Multiple studies have sought to address this clinical dilemma using neuroimaging methods to identify a radiographic time-stamp of stroke onset or evidence of salvageable ischemic tissue and thereby increase the number of patients eligible for reperfusion therapies. In this review, we provide a critical analysis of the current state of neuroimaging techniques to select patients with unwitnessed stroke for revascularization therapies and speculate on the future direction of this clinically relevant area of stroke research.
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    Impact of Lesion Load Thresholds on Alberta Stroke Program Early Computed Tomographic Score in Diffusion-Weighted Imaging
    (Frontiers Media S.A., 2018) Schröder, Julian; Cheng, Bastian; Malherbe, Caroline; Ebinger, Martin; Köhrmann, Martin; Wu, Ona; Kang, Dong-Wha; Liebeskind, David S.; Tourdias, Thomas; Singer, Oliver C.; Campbell, Bruce; Luby, Marie; Warach, Steven; Fiehler, Jens; Kemmling, André; Fiebach, Jochen B.; Gerloff, Christian; Thomalla, Götz
    Background and aims Assessment of ischemic lesions on computed tomography or MRI diffusion-weighted imaging (DWI) using the Alberta Stroke Program Early Computed Tomography Score (ASPECTS) is widely used to guide acute stroke treatment. However, it has never been defined how many voxels need to be affected to label a DWI-ASPECTS region ischemic. We aimed to assess the effect of various lesion load thresholds on DWI-ASPECTS and compare this automated analysis with visual rating. Materials and methods We analyzed overlap of individual DWI lesions of 315 patients from the previously published predictive value of fluid-attenuated inversion recovery study with a probabilistic ASPECTS template derived from 221 CT images. We applied multiple lesion load thresholds per DWI-ASPECTS region (>0, >1, >10, and >20% in each DWI-ASPECTS region) to compute DWI-ASPECTS for each patient and compared the results to visual reading by an experienced stroke neurologist. Results: By visual rating, median ASPECTS was 9, 84 patients had a DWI-ASPECTS score ≤7. Mean DWI lesion volume was 22.1 (±35) ml. In contrast, by use of >0, >1-, >10-, and >20%-thresholds, median DWI-ASPECTS was 1, 5, 8, and 10; 97.1% (306), 72.7% (229), 41% (129), and 25.7% (81) had DWI-ASPECTS ≤7, respectively. Overall agreement between automated assessment and visual rating was low for every threshold used (>0%: κw = 0.020 1%: κw = 0.151; 10%: κw = 0.386; 20% κw = 0.381). Agreement for dichotomized DWI-ASPECTS ranged from fair to substantial (≤7: >10% κ = 0.48; >20% κ = 0.45; ≤5: >10% κ = 0.528; and >20% κ = 0.695). Conclusion: Overall agreement between automated and the standard used visual scoring is low regardless of the lesion load threshold used. However, dichotomized scoring achieved more comparable results. Varying lesion load thresholds had a critical impact on patient selection by ASPECTS. Of note, the relatively low lesion volume and lack of patients with large artery occlusion in our cohort may limit generalizability of these findings.
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    Repeatability of Cerebral Perfusion Using Dynamic Susceptibility Contrast MRI in Glioblastoma Patients12
    (Neoplasia Press, 2015) Jafari-Khouzani, Kourosh; Emblem, Kyrre E.; Kalpathy-Cramer, Jayashree; Bjørnerud, Atle; Vangel, Mark; Gerstner, Elizabeth; Schmainda, Kathleen M.; Paynabar, Kamran; Wu, Ona; Wen, Patrick Y.; Batchelor, Tracy; Rosen, Bruce; Stufflebeam, Steven
    OBJECTIVES This study evaluates the repeatability of brain perfusion using dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) with a variety of post-processing methods. METHODS Thirty-two patients with newly diagnosed glioblastoma were recruited. On a 3-T MRI using a dual-echo, gradient-echo spin-echo DSC-MRI protocol, the patients were scanned twice 1 to 5 days apart. Perfusion maps including cerebral blood volume (CBV) and cerebral blood flow (CBF) were generated using two contrast agent leakage correction methods, along with testing normalization to reference tissue, and application of arterial input function (AIF). Repeatability of CBV and CBF within tumor regions and healthy tissues, identified by structural images, was assessed with intra-class correlation coefficients (ICCs) and repeatability coefficients (RCs). Coefficients of variation (CVs) were reported for selected methods. RESULTS CBV and CBF were highly repeatable within tumor with ICC values up to 0.97. However, both CBV and CBF showed lower ICCs for healthy cortical tissues (up to 0.83), healthy gray matter (up to 0.95), and healthy white matter (WM; up to 0.93). The values of CV ranged from 6% to 10% in tumor and 3% to 11% in healthy tissues. The values of RC relative to the mean value of measurement within healthy WM ranged from 22% to 42% in tumor and 7% to 43% in healthy tissues. These percentages show how much variation in perfusion parameter, relative to that in healthy WM, we expect to observe to consider it statistically significant. We also found that normalization improved repeatability, but AIF deconvolution did not. CONCLUSIONS DSC-MRI is highly repeatable in high-grade glioma patients.
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    EEG functional connectivity is partially predicted by underlying white matter connectivity
    (Elsevier BV, 2015) Chu, Catherine; Tanaka, Naoaki; Diaz, J.; Edlow, Brian; Wu, Ona; Hamalainen, Matti; Stufflebeam, Steven; Cash, Sydney; Kramer, M.A.
    Over the past decade, networks have become a leading model to illustrate both the anatomical relationships (structural networks) and the coupling of dynamic physiology (functional networks) linking separate brain regions. The relationship between these two levels of description remains incompletely understood and an area of intense research interest. In particular, it is unclear how cortical currents relate to underlying brain structural architecture. In addition, although theory suggests that brain communication is highly frequency dependent, how structural connections influence overlying functional connectivity in different frequency bands has not been previously explored. Here we relate functional networks inferred from statistical associations between source imaging of EEG activity and underlying cortico-cortical structural brain connectivity determined by probabilistic white matter tractography. We evaluate spontaneous fluctuating cortical brain activity over a long time scale (minutes) and relate inferred functional networks to underlying structural connectivity for broadband signals, as well as in seven distinct frequency bands. We find that cortical networks derived from source EEG estimates partially reflect both direct and indirect underlying white matter connectivity in all frequency bands evaluated. In addition, we find that when structural support is absent, functional connectivity is significantly reduced for high frequency bands compared to low frequency bands. The association between cortical currents and underlying white matter connectivity highlights the obligatory interdependence of functional and structural networks in the human brain. The increased dependence on structural support for the coupling of higher frequency brain rhythms provides new evidence for how underlying anatomy directly shapes emergent brain dynamics at fast time scales.
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    Diffusion tensor imaging in acute-to-subacute traumatic brain injury: a longitudinal analysis
    (BioMed Central, 2016) Edlow, Brian; Copen, William; Izzy, Saef; Bakhadirov, Khamid; Van Der Kouwe, Andre; Glenn, Mel; Greenberg, Steven; Greer, David M.; Wu, Ona
    Background: Diffusion tensor imaging (DTI) may have prognostic utility in patients with traumatic brain injury (TBI), but the optimal timing of DTI data acquisition is unknown because of dynamic changes in white matter water diffusion during the acute and subacute stages of TBI. We aimed to characterize the direction and magnitude of early longitudinal changes in white matter fractional anisotropy (FA) and to determine whether acute or subacute FA values correlate more reliably with functional outcomes after TBI. Methods: From a prospective TBI outcomes database, 11 patients who underwent acute (≤7 days) and subacute (8 days to rehabilitation discharge) DTI were retrospectively analyzed. Longitudinal changes in FA were measured in 11 white matter regions susceptible to traumatic axonal injury. Correlations were assessed between acute FA, subacute FA and the disability rating scale (DRS) score, which was ascertained at discharge from inpatient rehabilitation. Results: FA declined from the acute-to-subacute period in the genu of the corpus callosum (0.70 ± 0.02 vs. 0.55 ± 0.11, p < 0.05) and inferior longitudinal fasciculus (0.54+/−0.07 vs. 0.49+/−0.07, p < 0.01). Acute correlations between FA and DRS score were variable: higher FA in the body (R = −0.78, p = 0.02) and splenium (R = −0.83, p = 0.003) of the corpus callosum was associated with better outcomes (i.e. lower DRS scores), whereas higher FA in the genu of the corpus callosum (R = 0.83, p = 0.02) corresponded with worse outcomes (i.e. higher DRS scores). In contrast, in the subacute period higher FA in the splenium correlated with better outcomes (R = −0.63, p < 0.05) and no inverse correlations were observed. Conclusions: White matter FA declined during the acute-to-subacute stages of TBI. Variability in acute FA correlations with outcome suggests that the optimal timing of DTI for TBI prognostication may be in the subacute period.
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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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    Combination Therapy with Normobaric Oxygen (NBO) Plus Thrombolysis in Experimental Ischemic Stroke
    (BioMed Central, 2009) Fujiwara, Norio; Murata, Yoshihiro; Arai, Ken; Egi, Yasuhiro; Lu, J; Wu, Ona; Singhal, Aneesh; Lo, Eng
    Background: The widespread use of tissue plasminogen activator (tPA), the only FDA-approved acute stroke treatment, remains limited by its narrow therapeutic time window and related risks of brain hemorrhage. Normobaric oxygen therapy (NBO) may be a useful physiological strategy that slows down the process of cerebral infarction, thus potentially allowing for delayed or more effective thrombolysis. In this study we investigated the effects of NBO started simultaneously with intravenous tPA, in spontaneously hypertensive rats subjected to embolic middle cerebral artery (MCA) stroke. After homologous clot injection, animals were randomized into different treatment groups: saline injected at 1 hour; tPA at 1 hour; saline at 1 hour plus NBO; tPA at 1 hour plus NBO. NBO was maintained for 3 hours. Infarct volume, brain swelling and hemorrhagic transformation were quantified at 24 hours. Outcome assessments were blinded to therapy. Results: Upon clot injection, cerebral perfusion in the MCA territory dropped below 20% of pre-ischemic baselines. Both tPA-treated groups showed effective thrombolysis (perfusion restored to nearly 100%) and smaller infarct volumes (379 ± 57 mm3 saline controls; 309 ± 58 mm3 NBO; 201 ± 78 mm3 tPA; 138 ± 30 mm3 tPA plus NBO), showing that tPA-induced reperfusion salvages ischemic tissue and that NBO does not significantly alter this neuroprotective effect. NBO had no significant effect on hemorrhagic conversion, brain swelling, or mortality. Conclusion: NBO can be safely co-administered with tPA. The efficacy of tPA thrombolysis is not affected and there is no induction of brain hemorrhage or edema. These experimental results require clinical confirmation.
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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.