Measurement of the Ischemic Penumbra With MRI: It’s About Time
2003; Lippincott Williams & Wilkins; Volume: 34; Issue: 10 Linguagem: Inglês
10.1161/01.str.0000092395.19554.9a
ISSN1524-4628
Autores Tópico(s)S100 Proteins and Annexins
ResumoHomeStrokeVol. 34, No. 10Measurement of the Ischemic Penumbra With MRI: It's About Time Free AccessArticle CommentaryPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessArticle CommentaryPDF/EPUBMeasurement of the Ischemic Penumbra With MRI: It's About Time Steven Warach Steven WarachSteven Warach From the National Institute of Neurological Disorders and Stroke, Bethesda, Md. Originally published11 Sep 2003https://doi.org/10.1161/01.STR.0000092395.19554.9AStroke. 2003;34:2533–2534Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: September 11, 2003: Previous Version 1 The idea that there exist 2 ischemic thresholds in the pathogenesis of cerebral infarction came from seminal microelectrode studies of the baboon cortex the late 1970s1,2 that measured the effects of progressive reductions in cerebral blood flow (CBF). These studies described a level of CBF reduction that led to cessation of cortical evoked responses in the absence of terminal increases in extracellular potassium or reductions in pH and a yet lower level of CBF reduction, at which occurred large increases in extracellular potassium and reductions in pH indicative of failure of membrane ion homeostasis and cell death.Derived from animals too few and results too variable to specify a precise threshold, the insight nonetheless emerged that there were 2 levels of ischemia, one for tissue dysfunction without destruction and a lower one for irreversible cell injury. The metaphor of the ischemic penumbra was coined to describe this intermediate zone of ischemia between functionally normal and dead brain tissue. Restoration of normal CBF to the penumbral zone may reverse the functional disturbance.Over the past 25 years, many investigators and clinicians have taken poetic liberties with the ischemic penumbra to suit their technologies and purposes. To some it is any variable that is intermediate in value between normal and that measured within the infarct. To others it is simply any noninfarcted brain with reduced CBF. To still others it is that region that is the optimal target of stroke therapy, destined for infarction if untreated but potentially salvageable if effectively treated. This last interpretation is of greatest relevance for the stroke patient and for the development of stroke therapies, and thus defines the modern ischemic penumbra.To the originators of the concept, the penumbra was defined by the tip of a microelectrode. Neither multitracer PET nor diffusion-perfusion MRI nor any noninvasive neuroimaging technique can accurately measure the penumbra by the original definition. None have determined reliable, validated absolute thresholds for the upper and lower CBF boundaries of the penumbral zone, and none will. As we have argued elsewhere,3 the very notion of a specifiable absolute CBF threshold of tissue viability is meaningless if it is not integrated with temporal, therapeutic, and tissue factors. Definitions of penumbra that do not account for the time course of the physiological perturbation and the effects of physiological or pharmacological manipulations will be of limited value. The quantitative precision and range of metabolic variables measurable by PET should, in principle, make it the method of choice for imaging the human penumbra. However, limited numbers of PET centers exist and even fewer that can routinely study patients within the critical first few hours after a stroke. This fact and other practical limitations related to availability, radiation exposure, and arterial catheterization constrain the use of PET as a tool for managing acute stroke patients and assessing investigational therapies.By contrast, diffusion and perfusion MRI of the less-than-6-hour stroke patient are routinely performed in hundreds of centers and have been a key element in several multicenter acute stroke trials.4 The goal in measuring the penumbra is to identify the patient with salvageable tissue-at-risk that is amenable to therapy. This requires a methodology that can be used emergently and used in large-scale randomized controlled trials to select patients and evaluate interventions. From the initial observations of whole brain diffusion and perfusion MRI in hyperacute stroke patients, it was evident that a larger region of hemodynamic compromise on PWI was present than the region of reduced apparent diffusion coefficient (ADC) induced by critically low CBF.5 The ADC on DWI reflects the CBF history of the tissue and evolves into infarction without reperfusion or neuroprotection. Hemodynamic abnormalities on PWI predict the possible futures of lesion evolution, futures affected by reperfusion and other potentially therapeutic interventions. This mismatch region is the tissue-at-risk and related to worse clinical outcome and infarct growth if early reperfusion does not occur.6,7 The importance of this mismatch in predicting lesion expansion and growth has been described in many series from many different centers, and prospectively confirmed in a multicenter clinical trial.8 Quantitative models of multiparametric MRI markers of the penumbra have been developed and may lead to improvements in MRI patient selection beyond qualitative diffusion-perfusion mismatch assessments. Considerable data have emerged suggesting that the selection of patients by the diffusion-perfusion mismatch may identify the appropriate patient for effective intravenous thrombolytic therapy beyond 3 hours from onset,9–11 and several randomized, placebo-controlled, multicenter trials are in progress to test that hypothesis.The superior quantification by PET is indisputable but, paradoxically, not relevant to this discussion. What is the better measure of the ischemic penumbra in human stroke? The better technique is the one that will lead to effective stroke therapies. MRI is more likely than PET to achieve that goal.Section Editors: Geoffry A. Donnan, MD, FRACP and Stephen M. Davis, MD, FRACPThe opinions expressed in this editorial are not necessarily those of the editors or of the American Stroke Association.FootnotesCorrespondence to Steven Warach, MD, PhD, National Institute of Neurological Disorders and Stroke, 10 Center Dr, MSC 1063, Bldg 10, Rm B1D733, Bethesda, MD 20892-1063. E-mail [email protected] References 1 Branston NM, Strong AJ, Symon L. Extracellular potassium activity, evoked potential and tissue blood flow: relationships during progressive ischaemia in baboon cerebral cortex. J Neurol Sci. 1977; 32: 305–321.CrossrefMedlineGoogle Scholar2 Astrup J, Symon L, Branston NM, Lassen NA. Cortical evoked potential and extracellular K+ and H+ at critical levels of brain ischemia. Stroke. 1977; 8: 51–57.CrossrefMedlineGoogle Scholar3 Warach S. Tissue viability thresholds in acute stroke: the 4-factor model. Stroke. 2001; 32: 2460–2461.LinkGoogle Scholar4 Warach S. Use of diffusion and perfusion magnetic resonance imaging as a tool in acute stroke clinical trials. Curr Control Trials Cardiovasc Med. 2001; 2: 38–44.CrossrefMedlineGoogle Scholar5 Warach S, Wielopolski P, Edelman RR. Identification and characterization of the ischemic penumbra of acute human stroke using echo planar diffusion and perfusion imaging. Proceedings of the Twelfth Annual Scientific Meeting of the Society of Magnetic Resonance in Medicine. 1993;12:263.Google Scholar6 Warach S, Dashe JF, Edelman RR. Clinical outcome in ischemic stroke predicted by early diffusion-weighted and perfusion magnetic resonance imaging: a preliminary analysis. J Cereb Blood Flow Metab. 1996; 16: 53–59.CrossrefMedlineGoogle Scholar7 Baird AE, Benfield A, Schlaug G, Siewert B, Lovblad KO, Edelman RR, Warach S. Enlargement of human cerebral ischemic lesion volumes measured by diffusion-weighted magnetic resonance imaging. Ann Neurol. 1997; 41: 581–589.CrossrefMedlineGoogle Scholar8 Warach S, Pettigrew LC, Dashe JF, Pullicino P, Lefkowitz DM, Sabounjian L, Harnett K, Schwiderski U, Gammans R. Effect of citicoline on ischemic lesions as measured by diffusion-weighted magnetic resonance imaging: Citicoline 010 Investigators. Ann Neurol. 2000; 48: 713–722.CrossrefMedlineGoogle Scholar9 Parsons MW, Barber PA, Chalk J, Darby DG, Rose S, Desmond PM, Gerraty RP, Tress BM, Wright PM, Donnan GA, Davis SM. Diffusion- and perfusion-weighted MRI response to thrombolysis in stroke. Ann Neurol. 2002; 51: 28–37.CrossrefMedlineGoogle Scholar10 Rother J, Schellinger PD, Gass A, Siebler M, Villringer A, Fiebach JB, Fiehler J, Jansen O, Kucinski T, Schoder V, et al. Effect of intravenous thrombolysis on MRI parameters and functional outcome in acute stroke <6 hours. Stroke. 2002; 33: 2438–2445.LinkGoogle Scholar11 Warach S. Thrombolysis in stroke beyond three hours: targeting patients with diffusion and perfusion MRI. Ann Neurol. 2002; 51: 11–13.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Chalet L, Boutelier T, Christen T, Raguenes D, Debatisse J, Eker O, Becker G, Nighoghossian N, Cho T, Canet-Soulas E and Mechtouff L (2022) Clinical Imaging of the Penumbra in Ischemic Stroke: From the Concept to the Era of Mechanical Thrombectomy, Frontiers in Cardiovascular Medicine, 10.3389/fcvm.2022.861913, 9 Yang S and Liu R (2021) Four Decades of Ischemic Penumbra and Its Implication for Ischemic Stroke, Translational Stroke Research, 10.1007/s12975-021-00916-2, 12:6, (937-945), Online publication date: 1-Dec-2021. Lee C, Hong K, Kim N, Han K, Kim D, Jung H, Lee S, Park J, Lee K, Lee J, Choi Y and Cho M (2021) Feasibility study of portable multi-energy computed tomography with photon-counting detector for preclinical and clinical applications, Scientific Reports, 10.1038/s41598-021-02210-5, 11:1 Jiang Z, Alamuri T, Muir E, Choi D and Duong T (2020) Longitudinal multiparametric MRI study of hydrogen-enriched water with minocycline combination therapy in experimental ischemic stroke in rats, Brain Research, 10.1016/j.brainres.2020.147122, 1748, (147122), Online publication date: 1-Dec-2020. Strubakos C, Malik M, Wider J, Lee I, Reynolds C, Mitsias P, Przyklenk K, Hüttemann M and Sanderson T (2019) Non-invasive treatment with near-infrared light: A novel mechanisms-based strategy that evokes sustained reduction in brain injury after stroke, Journal of Cerebral Blood Flow & Metabolism, 10.1177/0271678X19845149, 40:4, (833-844), Online publication date: 1-Apr-2020. Choi W, Li Y and Wang R Monitoring Acute Stroke Progression: Multi-Parametric OCT Imaging of Cortical Perfusion, Flow, and Tissue Scattering in a Mouse Model of Permanent Focal Ischemia, IEEE Transactions on Medical Imaging, 10.1109/TMI.2019.2895779, 38:6, (1427-1437) Wang E, Wu Y, Cheung J, Igarashi T, Wu L, Zhang X and Sun P (2019) Mapping tissue pH in an experimental model of acute stroke – Determination of graded regional tissue pH changes with non-invasive quantitative amide proton transfer MRI, NeuroImage, 10.1016/j.neuroimage.2019.02.022, 191, (610-617), Online publication date: 1-May-2019. Berge E and Sandercock P (2019) Specific treatment of acute ischemic stroke Warlow's Stroke, 10.1002/9781118492390.ch13, (587-656) Yin J, Sun H, Wang Z, Ni H, Shen W and Sun P (2018) Diffusion Kurtosis Imaging of Acute Infarction: Comparison with Routine Diffusion and Follow-up MR Imaging, Radiology, 10.1148/radiol.2017170553, 287:2, (651-657), Online publication date: 1-May-2018. McCabe C, Arroja M, Reid E and Macrae I (2018) Animal models of ischaemic stroke and characterisation of the ischaemic penumbra, Neuropharmacology, 10.1016/j.neuropharm.2017.09.022, 134, (169-177), Online publication date: 1-May-2018. Krejza J, Arkuszewski M and Melhem E (2018) Evidence-Based Emergency Neuroimaging in Children and Adults with Sickle Cell Disease and Symptoms of Stroke Evidence-Based Emergency Imaging, 10.1007/978-3-319-67066-9_33, (519-543), . Wang E, Wu Y, Cheung J, Zhou I, Igarashi T, Zhang X and Sun P (2017) pH imaging reveals worsened tissue acidification in diffusion kurtosis lesion than the kurtosis/diffusion lesion mismatch in an animal model of acute stroke, Journal of Cerebral Blood Flow & Metabolism, 10.1177/0271678X17721431, 37:10, (3325-3333), Online publication date: 1-Oct-2017. Catana C (2017) Principles of Simultaneous PET/MR Imaging, Magnetic Resonance Imaging Clinics of North America, 10.1016/j.mric.2017.01.002, 25:2, (231-243), Online publication date: 1-May-2017. AlSibai A and Qureshi A (2016) Management of Acute Hypertensive Response in Patients With Ischemic Stroke, The Neurohospitalist, 10.1177/1941874416630029, 6:3, (122-129), Online publication date: 1-Jul-2016. Tajiri N, Borlongan C and Kaneko Y (2016) Cyclosporine A Treatment Abrogates Ischemia‐Induced Neuronal Cell Death by Preserving Mitochondrial Integrity through Upregulation of the Parkinson's Disease‐Associated Protein DJ‐1, CNS Neuroscience & Therapeutics, 10.1111/cns.12546, 22:7, (602-610), Online publication date: 1-Jul-2016. Tiwari Y, Jiang Z, Sun Y, Du F, Rodriguez P, Shen Q and Duong T (2016) Effects of stroke severity and treatment duration in normobaric hyperoxia treatment of ischemic stroke, Brain Research, 10.1016/j.brainres.2016.01.030, 1635, (121-129), Online publication date: 1-Mar-2016. Pacheco F and da Rocha A (2016) Ischemic Stroke in Adults Critical Findings in Neuroradiology, 10.1007/978-3-319-27987-9_4, (29-44), . Siemonsen S, Forkert N, Hansen A, Kemmling A, Thomalla G and Fiehler J (2014) Spatial Distribution of Perfusion Abnormality in Acute MCA Occlusion is Associated with Likelihood of Later Recanalization, Journal of Cerebral Blood Flow & Metabolism, 10.1038/jcbfm.2014.13, 34:5, (813-819), Online publication date: 1-May-2014. Tuchin V, Larin K, Leahy M, Wang R, Qin J, Shi L, Dziennis S and Wang R (2014) Multi-parametric imaging of cerebral hemodynamic and metabolic response followed by ischemic injury SPIE BiOS, 10.1117/12.2041699, , (89420U), Online publication date: 26-Feb-2014. Pantcheva P, Elias M, Duncan K, Borlongan C, Tajiri N and Kaneko Y (2014) The role of DJ-1 in the oxidative stress cell death cascade after stroke, Neural Regeneration Research, 10.4103/1673-5374.139458, 9:15, (1430), . Thulborn K and Atkinson I (2014) Quantitative Metabolic Magnetic Resonance Imaging of Sodium, Oxygen, Phosphorus and Potassium in the Human Brain Magnetic Resonance Spectroscopy, 10.1016/B978-0-12-401688-0.00022-7, (291-311), . Jauch E, Saver J, Adams H, Bruno A, Connors J, Demaerschalk B, Khatri P, McMullan P, Qureshi A, Rosenfield K, Scott P, Summers D, Wang D, Wintermark M and Yonas H (2013) Guidelines for the Early Management of Patients With Acute Ischemic Stroke, Stroke, 44:3, (870-947), Online publication date: 1-Mar-2013. Catana C, Drzezga A, Heiss W and Rosen B (2012) PET/MRI for Neurologic Applications, Journal of Nuclear Medicine, 10.2967/jnumed.112.105346, 53:12, (1916-1925), Online publication date: 1-Dec-2012. Nemoto E, Mendez O, Kerr M, Firlik A, Stevenson K, Jovin T and Yonas H (2012) CT Density Changes with Rapid Onset Acute, Severe, Focal Cerebral Ischemia in Monkeys, Translational Stroke Research, 10.1007/s12975-012-0193-6, 3:3, (369-374), Online publication date: 1-Sep-2012. Azizyan A, Sanossian N, Mogensen M and Liebeskind D (2010) Fluid-Attenuated Inversion Recovery Vascular Hyperintensities: An Important Imaging Marker for Cerebrovascular Disease, American Journal of Neuroradiology, 10.3174/ajnr.A2265, 32:10, (1771-1775), Online publication date: 1-Nov-2011. Huang S, Shen Q and Duong T (2011) Quantitative prediction of acute ischemic tissue fate using support vector machine, Brain Research, 10.1016/j.brainres.2011.05.066, 1405, (77-84), Online publication date: 1-Aug-2011. Konstas A, Wintermark M and Lev M (2011) CT Perfusion Imaging in Acute Stroke, Neuroimaging Clinics of North America, 10.1016/j.nic.2011.01.008, 21:2, (215-238), Online publication date: 1-May-2011. Konstas A, González R and Lev M (2011) CT Perfusion (CTP) Acute Ischemic Stroke, 10.1007/978-3-642-12751-9_5, (83-121), . Catana C, Sorensen A and Rosen B (2011) Simultaneous PET and MR Imaging of the Human Brain Functional Neuroradiology, 10.1007/978-1-4419-0345-7_42, (867-892), . Huang S, Shen Q and Duong T (2010) Artificial Neural Network Prediction of Ischemic Tissue Fate in Acute Stroke Imaging, Journal of Cerebral Blood Flow & Metabolism, 10.1038/jcbfm.2010.56, 30:9, (1661-1670), Online publication date: 1-Sep-2010. (2010) Diagnostic Evaluation of Stroke Toole's Cerebrovascular Disorders, 10.1017/CBO9781139644235.008, (75-93) Mishra N, Albers G, Davis S, Donnan G, Furlan A, Hacke W and Lees K (2009) Mismatch-Based Delayed Thrombolysis, Stroke, 41:1, (e25-e33), Online publication date: 1-Jan-2010.Latchaw R, Alberts M, Lev M, Connors J, Harbaugh R, Higashida R, Hobson R, Kidwell C, Koroshetz W, Mathews V, Villablanca P, Warach S and Walters B (2009) Recommendations for Imaging of Acute Ischemic Stroke, Stroke, 40:11, (3646-3678), Online publication date: 1-Nov-2009. Kranz P and Eastwood J (2009) Does Diffusion-Weighted Imaging Represent the Ischemic Core? An Evidence-Based Systematic Review, American Journal of Neuroradiology, 10.3174/ajnr.A1547, 30:6, (1206-1212), Online publication date: 1-Jun-2009. Konstas A, Goldmakher G, Lee T and Lev M (2009) Theoretic Basis and Technical Implementations of CT Perfusion in Acute Ischemic Stroke, Part 2: Technical Implementations, American Journal of Neuroradiology, 10.3174/ajnr.A1492, 30:5, (885-892), Online publication date: 1-May-2009. Hakimelahi R and González R (2014) Neuroimaging of ischemic stroke with CT and MRI: advancing towards physiology-based diagnosis and therapy, Expert Review of Cardiovascular Therapy, 10.1586/14779072.7.1.29, 7:1, (29-48), Online publication date: 1-Jan-2009. Adams H (2008) Extending the time frame for emergency intravenous thrombolytic therapy for treatment of acute ischemic stroke, Current Neurology and Neuroscience Reports, 10.1007/s11910-009-0001-1, 9:1, (3-5), Online publication date: 1-Jan-2009. Shen Q and Duong T (2008) Quantitative prediction of ischemic stroke tissue fate, NMR in Biomedicine, 10.1002/nbm.1264, 21:8, (839-848), Online publication date: 1-Oct-2008. Sun P, Benner T, Kumar A and Sorensen A (2008) Investigation of optimizing and translating pH-sensitive pulsed-chemical exchange saturation transfer (CEST) imaging to a 3T clinical scanner, Magnetic Resonance in Medicine, 10.1002/mrm.21714, 60:4, (834-841), Online publication date: 1-Oct-2008. Bristow M, Poulin B, Simon J, Hill M, Kosior J, Coutts S, Frayne R, Mitchell J and Demchuk A (2008) Identifying lesion growth with MR imaging in acute ischemic stroke, Journal of Magnetic Resonance Imaging, 10.1002/jmri.21507, 28:4, (837-846), Online publication date: 1-Oct-2008. Sun P and Sorensen A (2008) Imaging pH using the chemical exchange saturation transfer (CEST) MRI: Correction of concomitant RF irradiation effects to quantify CEST MRI for chemical exchange rate and pH, Magnetic Resonance in Medicine, 10.1002/mrm.21653, 60:2, (390-397), Online publication date: 1-Aug-2008. Lo E (2008) A new penumbra: transitioning from injury into repair after stroke, Nature Medicine, 10.1038/nm1735, 14:5, (497-500), Online publication date: 1-May-2008. Paiva F, Tannús A, Talagala S and Silva A (2008) Arterial spin labeling of cerebral perfusion territories using a separate labeling coil, Journal of Magnetic Resonance Imaging, 10.1002/jmri.21320, 27:5, (970-977), Online publication date: 1-May-2008. CHEN F, LIU Q, WANG H, SUZUKI Y, NAGAI N, YU J, MARCHAL G and NI Y (2008) Comparing two methods for assessment of perfusion–diffusion mismatch in a rodent model of ischaemic stroke: a pilot study, The British Journal of Radiology, 10.1259/bjr/70940134, 81:963, (192-198), Online publication date: 1-Mar-2008. Schellinger P, Köhrmann M and Hacke W (2008) Chapter 57 Thrombolytic therapy for acute stroke Stroke Part III: Investigation and Management, 10.1016/S0072-9752(08)94057-4, (1155-1193), . Hossmann K and Traystman R (2008) Chapter 4 Cerebral blood flow and the ischemic penumbra Stroke, 10.1016/S0072-9752(08)01904-0, (67-92), . Shetty S and Lev M (2008) MDCT Perfusion in Acute Stroke MDCT, 10.1007/978-88-470-0832-8_23, (295-309), . Paiva F, Tannús A and Silva A (2007) Measurement of cerebral perfusion territories using arterial spin labelling, NMR in Biomedicine, 10.1002/nbm.1177, 20:7, (633-642), Online publication date: 1-Nov-2007. Leary M and Caplan L (2007) Technology Insight: brain MRI and cardiac surgery—detection of postoperative brain ischemia, Nature Clinical Practice Cardiovascular Medicine, 10.1038/ncpcardio0915, 4:7, (379-388), Online publication date: 1-Jul-2007. Chen F, Suzuki Y, Nagai N, Sun X, Coudyzer W, Yu J, Marchal G and Ni Y (2007) Delayed perfusion phenomenon in a rat stroke model at 1.5T MR: An imaging sign parallel to spontaneous reperfusion and ischemic penumbra?, European Journal of Radiology, 10.1016/j.ejrad.2006.08.019, 61:1, (70-78), Online publication date: 1-Jan-2007. Schellinger P, Latour L, Wu C, Chalela J and Warach S (2005) The association between neurological deficit in acute ischemic stroke and mean transit time, Neuroradiology, 10.1007/s00234-005-0012-9, 48:2, (69-77), Online publication date: 1-Feb-2006. Shetty S and Lev M MDCT Perfusion in Acute Stroke MDCT:A Practical Approach, 10.1007/88-470-0413-6_14, (167-181) Shetty S and Lev M CT Perfusion (CTP) Acute Ischemic Stroke, 10.1007/3-540-30810-5_5, (87-113) Shetty S and Lev M (2005) CT Perfusion in Acute Stroke*, Seminars in Ultrasound, CT and MRI, 10.1053/j.sult.2005.09.001, 26:6, (404-421), Online publication date: 1-Dec-2005. Bristow M, Simon J, Brown R, Eliasziw M, Hill M, Coutts S, Frayne R, Demchuk A and Mitchell J (2005) MR Perfusion and Diffusion in Acute Ischemic Stroke: Human Gray and White Matter have Different Thresholds for Infarction, Journal of Cerebral Blood Flow & Metabolism, 10.1038/sj.jcbfm.9600135, 25:10, (1280-1287), Online publication date: 1-Oct-2005. Shetty S and Lev M (2005) CT Perfusion in Acute Stroke, Neuroimaging Clinics of North America, 10.1016/j.nic.2005.08.004, 15:3, (481-501), Online publication date: 1-Aug-2005. Rowley H (2005) Extending the Time Window for Thrombolysis: Evidence from Acute Stroke Trials, Neuroimaging Clinics of North America, 10.1016/j.nic.2005.08.002, 15:3, (575-587), Online publication date: 1-Aug-2005. James M and Lunnon M (2005) Making Progress in the Acute Treatment of Stroke, International Journal of Pharmaceutical Medicine, 10.2165/00124363-200519020-00003, 19:2, (77-88), . Kelley R and Gonzalez‐Toledo E (2005) Stroke Neuroimaging, Part B, 10.1016/S0074-7742(05)67007-9, (203-238), . Marshall R (2004) The functional relevance of cerebral hemodynamics: why blood flow matters to the injured and recovering brain, Current Opinion in Neurology, 10.1097/00019052-200412000-00010, 17:6, (705-709), Online publication date: 1-Dec-2004. Coles J (2004) Regional ischemia after head injury, Current Opinion in Critical Care, 10.1097/00075198-200404000-00008, 10:2, (120-125), Online publication date: 1-Apr-2004. Rowley H and Roberts T (2004) Clinical Perspectives in Perfusion, Topics in Magnetic Resonance Imaging, 10.1097/00002142-200402000-00004, 15:1, (28-40), Online publication date: 1-Feb-2004. October 2003Vol 34, Issue 10 Advertisement Article InformationMetrics https://doi.org/10.1161/01.STR.0000092395.19554.9APMID: 12970511 Originally publishedSeptember 11, 2003 Keywordsmagnetic resonance imagingcerebral blood flowrandomized controlled trialspenumbraPDF download Advertisement
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