Acute Stroke Imaging Research Roadmap

Department of Radiology, University of California, San Francisco, CA 94143-0628, USA.
American Journal of Neuroradiology (Impact Factor: 3.68). 06/2008; 29(5):e23-30. DOI: 10.1161/STROKEAHA.107.512319
Source: PubMed

ABSTRACT The recent "Advanced Neuroimaging for Acute Stroke Treatment" meeting on September 7 and 8, 2007 in Washington DC, brought together stroke neurologists, neuroradiologists, emergency physicians, neuroimaging research scientists, members of the National Institute of Neurological Disorders and Stroke (NINDS), the National Institute of Biomedical Imaging and Bioengineering (NIBIB), industry representatives, and members of the US Food and Drug Administration (FDA) to discuss the role of advanced neuroimaging in acute stroke treatment. The goals of the meeting were to assess state-of-the-art practice in terms of acute stroke imaging research and to propose specific recommendations regarding: (1) the standardization of perfusion and penumbral imaging techniques, (2) the validation of the accuracy and clinical utility of imaging markers of the ischemic penumbra, (3) the validation of imaging biomarkers relevant to clinical outcomes, and (4) the creation of a central repository to achieve these goals. The present article summarizes these recommendations and examines practical steps to achieve them.

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Available from: Steven J Warach, Aug 09, 2015
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    • "An important focus of imaging research in the ischemic stroke is the differentiation of the ischemic penumbra from the infarct core and the normal tissue. Especially in patients presenting beyond the established time window of 4.5 hours after the stroke, in candidates for endovascular treatment, and in patients older than 80 years, a precise characterization of brain ischemia is required (Wintermark et al, 2008). The mismatch between ischemic areas measured by diffusion-weighted imaging (DWI) and perfusion imaging (PI) has been considered to be a good approximation of the ischemic penumbra, yet it tends to overestimate it by containing regions of benign oligemia (Heiss et al, 2004; Sobesky et al, 2005). "
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    ABSTRACT: The aim of this study was to test the feasibility of vessel size imaging with precise evaluation of apparent diffusion coefficient and cerebral blood volume and to apply this novel technique in acute stroke patients within a pilot group to observe the microvascular responses in acute ischemic tissue. Microvessel density-related quantity Q and mean vessel size index (VSI) were assessed in 9 healthy volunteers and 13 acute stroke patients with vessel occlusion within 6 hours after symptom onset. Our results in healthy volunteers matched with general anatomical observations. Given the limitation of a small patient cohort, the median VSI in the ischemic area was higher than that in the mirrored region in the contralateral hemisphere (P<0.05). Decreased Q was observed in the ischemic region in 2 patients, whereas no obvious changes of Q were found in the remaining 11 patients. In a patient without recanalization, the VSI hyperintensity in the subcortical area matched well with the final infarct. These data reveal that different observations of microvascular response in the acute ischemic tissue seem to emerge and vessel size imaging may provide useful information for the definition of ischemic penumbra and have an impact on future therapeutic approaches.
    Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism 04/2011; 31(8):1687-95. DOI:10.1038/jcbfm.2011.38 · 5.34 Impact Factor
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    • "Over the past decade, the development of computed tomography (CT) perfusion (CTP) and magnetic resonance perfusion has provided powerful paradigms for the scientific study and clinical evaluation of acute stroke patients. Meanwhile, there is an increasing need to critically evaluate the available perfusion postprocessing techniques and resulting perfusion metrics (Butcher et al, 2005) to identify imaging paradigms and perfusion indices that provide efficient targets for treatment (Wintermark et al, 2008a, b). The time-to-maximum of the tissue residue function (T max ) has been established as an accurate perfusion metric to discriminate the infarct core and penumbra (Shih et al, 2003), and has been applied for the definition of the diffusion–perfusion mismatch in recent multicenter trials such as Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution (Albers et al, 2006) and Echoplanar Imaging Thrombolytic Evaluation Trial (Butcher et al, 2005; Davis et al, 2008). "
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    ABSTRACT: The time-to-maximum of the tissue residue function (T(max)) perfusion index has proven very predictive of infarct growth in large clinical trials, yet its dependency on simple tracer delays remains unknown. Here, we determine the dependency of computed tomography (CT) perfusion (CTP) T(max) estimates on tracer delay using a range of deconvolution techniques and digital phantoms. Digital phantom data sets simulating the tracer delay were created from CTP data of six healthy individuals, in which time frames of the left cerebral hemisphere were shifted forward and backward by up to ±5 seconds. These phantoms were postprocessed with three common singular value decomposition (SVD) deconvolution algorithms-standard SVD (sSVD), block-circulant SVD (bSVD), and delay-corrected SVD (dSVD)-with an arterial input function (AIF) obtained from the right middle cerebral artery (MCA). The T(max) values of the left hemisphere were compared among different tracer delays and algorithms by a region of interest-based analysis. The T(max) values by sSVD were positively correlated with 'positive shifts' but unchanged with 'negative shifts,' those by bSVD had an excellent positive linear correlation with both positive and negative shifts, and those by dSVD were relatively constant, although slightly increased with the positive shifts. The T(max) is a parameter highly dependent on tracer delays and deconvolution algorithm.
    Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism 03/2011; 31(3):908-12. DOI:10.1038/jcbfm.2010.169 · 5.34 Impact Factor
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    • "For this reason, other perfusion-related variables, particularly time-based variables such as the MTT, have been widely assessed as predictors of the at-risk tissue, and several pMR and pCT studies (Takasawa et al, 2008; Zaro-Weber et al, 2010a) have suggested that the MTT may reliably predict the penumbra flow threshold. However, although better than for CBF, the accuracy of pMR-and pCT-derived MTT remains suboptimal because of inaccuracies in arterial input function determination and issues with delay and dispersion of the tracer before arrival to the ischemic tissue (Calamante et al, 2002; Donnan et al, 2009; Wintermark et al, 2008; Wu et al, 2003). To optimally address the fundamental issue of whether the MTT reliably predicts the penumbra flow threshold, it would therefore be desirable to use PET-derived MTT, rather than pMR-or pCT-derived MTT, and to use PET-derived CBF as reference—a study not carried out so far. "
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    ABSTRACT: Depicting the salvageable tissue is increasingly used in the clinical setting following stroke. As absolute cerebral blood flow (CBF) is difficult to measure using perfusion magnetic resonance or computed tomography and has limitations as a penumbral marker, time-based variables, particularly the mean transit time (MTT), are routinely used as surrogates. However, a direct validation of MTT as a predictor of the penumbra threshold using gold-standard positron emission tomography (PET) is lacking. Using (15)O-PET data sets obtained from two independent acute stroke samples (N=7 and N=30, respectively), we derived areas under the curve (AUCs), optimal thresholds (OTs), and 90%-specificity thresholds (90%-Ts) from receiver operating characteristic curves for absolute MTT, MTT delay, and MTT ratio to predict three penumbra thresholds ('classic': CBF <20  mL/100  g per min; 'normalized': CBF ratio <0.5; and 'stringent': both CBF <20  mL/100  g per min and oxygen extraction fraction >0.55). In sample 1, AUCs ranged from 0.79 to 0.92, indicating good validity; OTs ranged from 7.8 to 8.3  seconds, 2.8 to 4.7  seconds, and 151% to 267% for absolute MTT, MTT delay, and MTT ratio, respectively, while as expected, 90%-Ts were longer. There was no significant difference between sample 1 and sample 2 for any of the above measurements, save for a single MTT parameter with a single penumbra threshold. These consistent findings from gold-standard PET obtained in two independent cohorts document that MTT is a very good surrogate to CBF for depicting the penumbra threshold.
    Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism 11/2010; 31(4):1027-35. DOI:10.1038/jcbfm.2010.197 · 5.34 Impact Factor
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