Publications by Year: 2009

Wu O, Sorensen GA, Benner T, Singhal AB, Furie KL, Greer DM. Comatose patients with cardiac arrest: predicting clinical outcome with diffusion-weighted MR imaging. Radiology 2009;252(1):173-81.Abstract
PURPOSE: To examine whether the severity and spatial distribution of reductions in apparent diffusion coefficient (ADC) are associated with clinical outcomes in patients who become comatose after cardiac arrest. MATERIALS AND METHODS: This was an institutional review board-approved, HIPAA-compliant retrospective study of 80 comatose patients with cardiac arrest who underwent diffusion-weighted magnetic resonance imaging. The need to obtain informed consent was waived except when follow-up phone calls were required; in those cases, informed consent was obtained from the families. Mean patient age was 57 years +/- 16 (standard deviation); 31 (39%) patients were women. ADC maps were semiautomatically segmented into the following regions: subcortical white matter; cerebellum; insula; frontal, occipital, parietal, and temporal lobes; caudate nucleus; putamen; and thalamus. Median ADCs were measured in these regions and in the whole brain and were compared (with a two-tailed Wilcoxon test) as a function of clinical outcome. Outcome was defined by both early eye opening in the 1st week after arrest (either spontaneously or in response to external stimuli) and 6-month modified Rankin scale score. RESULTS: Whole-brain median ADC was a significant predictor of poor outcome as measured by no eye opening (specificity, 100% [95% confidence interval {CI}: 86%, 100%]; sensitivity, 30% [95% CI: 18%, 45%]) or 6-month modified Rankin scale score greater than 3 (specificity, 100% [95% CI: 73%, 100%]; sensitivity, 41% [95% CI: 29%, 54%]), with patients with poor outcomes having significantly lower ADCs for both outcome measures (P
Fujiwara N, Murata Y, Arai K, Egi Y, Lu J, Wu O, Singhal AB, Lo EH. Combination therapy with normobaric oxygen (NBO) plus thrombolysis in experimental ischemic stroke. BMC Neurosci 2009;10:79.Abstract
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.
Christensen S, Mouridsen K, Wu O, Hjort N, Karstoft H, Thomalla G, Röther J, Fiehler J, Kucinski T, Østergaard L. Comparison of 10 perfusion MRI parameters in 97 sub-6-hour stroke patients using voxel-based receiver operating characteristics analysis. Stroke 2009;40(6):2055-61.Abstract
BACKGROUND AND PURPOSE: Perfusion-weighted imaging can predict infarct growth in acute stroke and potentially be used to select patients with tissue at risk for reperfusion therapies. However, the lack of consensus and evidence on how to best create PWI maps that reflect tissue at risk challenges comparisons of results and acute decision-making in trials. Deconvolution using an arterial input function has been hypothesized to generate maps of a more quantitative nature and with better prognostic value than simpler summary measures such as time-to-peak or the first moment of the concentration time curve. We sought to compare 10 different perfusion parameters by their ability to predict tissue infarction in acute ischemic stroke. METHODS: In a retrospective analysis of 97 patients with acute stroke studied within 6 hours from symptom onset, we used receiver operating characteristics in a voxel-based analysis to compare 10 perfusion parameters: time-to-peak, first moment, cerebral blood volume and flow, and 6 variants of time to peak of the residue function and mean transit time maps. Subanalysis assessed the effect of reperfusion on outcome prediction. RESULTS: The most predictive maps were the summary measures first moment and time-to-peak. First moment was significantly more predictive than time to peak of the residue function and local arterial input function-based methods (P<0.05), but not significantly better than conventional mean transit time maps. CONCLUSIONS: Results indicated that if a single map type was to be used to predict infarction, first moment maps performed at least as well as deconvolved measures. Deconvolution decouples delay from tissue perfusion; we speculate this negatively impacts infarct prediction.
Copen WA, Rezai Gharai L, Barak ER, Schwamm LH, Wu O, Kamalian S, Gonzalez GR, Schaefer PW. Existence of the diffusion-perfusion mismatch within 24 hours after onset of acute stroke: dependence on proximal arterial occlusion. Radiology 2009;250(3):878-86.Abstract
PURPOSE: To assess the existence of a mismatch between lesions on diffusion-weighted (DW) and perfusion-weighted (PW) magnetic resonance (MR) images obtained within 24 hours after onset of acute stroke and to use mismatch data and angiographic evidence of proximal arterial occlusion (PAO) to investigate whether the existence of the mismatch depends on the existence of PAO. MATERIALS AND METHODS: In this institutional review board-approved, HIPAA-compliant study, 109 retrospectively identified patients had undergone DW and PW imaging within 24 hours of stroke onset. Relative mismatch was computed as the difference between lesion volumes on mean transit time maps and DW images, divided by DW lesion volume. Computed tomographic (CT) angiography or MR angiography distinguished patients with PAO (n = 68) from those with no PAO (NPAO; n = 41). Eligibility for hypothetical thrombolysis was assessed with two different criteria: (a) one derived from the successful Desmoteplase in Acute Ischemic Stroke Trial (DIAS) and Dose Escalation of Desmoteplase for Acute Ischemic Stroke Trial (DEDAS), and (b) another requiring 160% mismatch. RESULTS: Of the 109 patients, 77 (71%) satisfied the DIAS-DEDAS eligibility criteria, and 61 (56%) satisfied the 160% criterion. The NPAO patients demonstrated decreasing eligibility with increasing time after onset by using DIAS-DEDAS criteria (P = .015) and showed a similar trend with the 160% criterion (P = .078). The NPAO patients were less likely to be eligible after 9 hours than before 9 hours (17% for >9 hours vs 72% for <9 hours with DIAS-DEDAS criteria, P = .002; and 8% for >9 hours vs 45% for <9 hours with 160% criterion, P = .033). However, PAO patients demonstrated a trend toward increasing eligibility with the DIAS-DEDAS criteria (P = .099) and no significant difference for after 9 hours versus before 9 hours (84% for >9 hours vs 78% for <9 hours with DIAS-DEDAS criteria, P = .742; and 68% for >9 hours vs 69% for <9 hours with 160% criterion, P > .999). CONCLUSION: Persistence of mismatch after 9 hours is common and occurs most often in patients with PAO.