Factors that determine penumbral tissue loss in acute ischaemic stroke.

The goal of acute stroke treatment with intravenous thrombolysis or endovascular recanalization techniques is to rescue the penumbral tissue. Therefore, knowing the factors that influence the loss of penumbral tissue is of major interest. In this study we aimed to identify factors that determine the evolution of the penumbra in patients with proximal (M1 or M2) middle cerebral artery occlusion. Among these factors collaterals as seen on angiography were of special interest. Forty-four patients were included in this analysis. They had all received endovascular therapy and at least minimal reperfusion was achieved. Their penumbra was assessed with perfusion- and diffusion-weighted imaging. Perfusion-weighted imaging volumes were defined by circular singular value decomposition deconvolution maps (Tmax > 6 s) and results were compared with volumes obtained with non-deconvolved maps (time to peak > 4 s). Loss of penumbral volume was defined as difference of post- minus pretreatment diffusion-weighted imaging volumes and calculated in per cent of pretreatment penumbral volume. Correlations between baseline characteristics, reperfusion, collaterals, time to reperfusion and penumbral volume loss were assessed using analysis of covariance. Collaterals (P = 0.021), reperfusion (P = 0.003) and their interaction (P = 0.031) independently influenced penumbral tissue loss, but not time from magnetic resonance (P = 0.254) or from symptom onset (P = 0.360) to reperfusion. Good collaterals markedly slowed down and reduced the penumbra loss: in patients with thrombolysis in cerebral infarction 2 b-3 reperfusion and without any haemorrhage, 27% of the penumbra was lost with 8.9 ml/h with grade 0 collaterals, whereas 11% with 3.4 ml/h were lost with grade 1 collaterals. With grade 2 collaterals the penumbral volume change was -2% with -1.5 ml/h, indicating an overall diffusion-weighted imaging lesion reversal. We conclude that collaterals and reperfusion are the main factors determining loss of penumbral tissue in patients with middle cerebral artery occlusions. Collaterals markedly reduce and slow down penumbra loss. In patients with good collaterals, time to successful reperfusion accounts only for a minor fraction of penumbra loss. These results support the hypothesis that good collaterals extend the time window for acute stroke treatment.

[1]  Hiroki Shirato,et al.  Difference in tracer delay-induced effect among deconvolution algorithms in CT perfusion analysis: quantitative evaluation with digital phantoms. , 2009, Radiology.

[2]  Leif Østergaard,et al.  How Reliable Is Perfusion MR in Acute Stroke?: Validation and Determination of the Penumbra Threshold Against Quantitative PET , 2008, Stroke.

[3]  G. Schroth,et al.  Recanalization and Outcome After Intra-Arterial Thrombolysis in Middle Cerebral Artery and Internal Carotid Artery Occlusion: Does Sex Matter? , 2007, Stroke.

[4]  S. Jasko,et al.  Therapy , 1881, The American journal of dental science.

[5]  R. Higashida,et al.  Trial design and reporting standards for intraarterial cerebral thrombolysis for acute ischemic stroke. 2003. , 2003, Journal of vascular and interventional radiology : JVIR.

[6]  J. Olivot,et al.  Magnetic Resonance Imaging in the Evaluation of Acute Stroke , 2008, Topics in magnetic resonance imaging : TMRI.

[7]  R. Higashida,et al.  Computed Tomographic Findings in Patients Undergoing Intra-arterial Thrombolysis for Acute Ischemic Stroke due to Middle Cerebral Artery Occlusion: Results From the PROACT II Trial , 2002, Stroke.

[8]  D. Liebeskind Reperfusion for acute ischemic stroke: arterial revascularization and collateral therapeutics , 2010, Current opinion in neurology.

[9]  G. Christoforidis,et al.  Angiographic assessment of pial collaterals as a prognostic indicator following intra-arterial thrombolysis for acute ischemic stroke. , 2005, AJNR. American journal of neuroradiology.

[10]  G. Schroth,et al.  A Novel Method for Analyzing DSCE-Images With an Application to Tumor Grading , 2008, Investigative radiology.

[11]  W. Heiss,et al.  Does the Mismatch Match the Penumbra?: Magnetic Resonance Imaging and Positron Emission Tomography in Early Ischemic Stroke , 2005, Stroke.

[12]  S. Warach,et al.  Erratum: Trial Design and Reporting Standards for Intra-Arterial Cerebral Thrombolysis for Acute Ischemic Stroke (Stroke (August 2003) 34:8 (1156-1162)) , 2003 .

[13]  W. Heiss,et al.  Maps of Time to Maximum and Time to Peak for Mismatch Definition in Clinical Stroke Studies Validated With Positron Emission Tomography , 2010, Stroke.

[14]  Gerhard Schroth,et al.  Endovascular Therapy of 623 Patients With Anterior Circulation Stroke , 2012, Stroke.

[15]  W. Heiss The Ischemic Penumbra: Correlates in Imaging and Implications for Treatment of Ischemic Stroke , 2011, Cerebrovascular Diseases.

[16]  Manabu Inoue,et al.  MRI profile and response to endovascular reperfusion after stroke (DEFUSE 2): a prospective cohort study , 2012, The Lancet Neurology.

[17]  R. Higashida,et al.  Trial Design and Reporting Standards for Intra-Arterial Cerebral Thrombolysis for Acute Ischemic Stroke , 2003, Stroke.

[18]  J. Faber,et al.  Wide Genetic Variation in the Native Pial Collateral Circulation is a Major Determinant of Variation in Severity of Stroke , 2010, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[19]  B. Siesjö,et al.  Thresholds in cerebral ischemia - the ischemic penumbra. , 1981, Stroke.

[20]  S. Warach,et al.  Intravenous desmoteplase in patients with acute ischaemic stroke selected by MRI perfusion–diffusion weighted imaging or perfusion CT (DIAS-2): a prospective, randomised, double-blind, placebo-controlled study , 2009, The Lancet Neurology.

[21]  Jan Sobesky,et al.  Identifying Thresholds for Penumbra and Irreversible Tissue Damage , 2004, Stroke.

[22]  Max Wintermark,et al.  A trial of imaging selection and endovascular treatment for ischemic stroke. , 2013, The New England journal of medicine.

[23]  F Viñuela,et al.  Impact of collateral flow on tissue fate in acute ischaemic stroke , 2007, Journal of Neurology, Neurosurgery, and Psychiatry.

[24]  Kaspar Anton Schindler,et al.  Adverse Effect of Early Epileptic Seizures in Patients Receiving Endovascular Therapy for Acute Stroke , 2012, Stroke.

[25]  R. Higashida,et al.  Cerebral hemorrhage after intra-arterial thrombolysis for ischemic stroke , 2001, Neurology.

[26]  Gregory W Albers,et al.  Time to treatment with intravenous alteplase and outcome in stroke: an updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials , 2010, The Lancet.

[27]  B. Rosen,et al.  Tracer arrival timing‐insensitive technique for estimating flow in MR perfusion‐weighted imaging using singular value decomposition with a block‐circulant deconvolution matrix , 2003, Magnetic resonance in medicine.

[28]  J. Saver Time Is Brain—Quantified , 2006, Stroke.

[29]  R. Bammer,et al.  The Infarct Core is Well Represented by the Acute Diffusion Lesion: Sustained Reversal is Infrequent , 2012, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[30]  Keith Muir,et al.  Effects of alteplase beyond 3 h after stroke in the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET): a placebo-controlled randomised trial , 2008, The Lancet Neurology.

[31]  Z. Chaudhry,et al.  Infarct Volume Is a Pivotal Biomarker After Intra-Arterial Stroke Therapy , 2012, Stroke.

[32]  G. Schroth,et al.  Three-Month and Long-Term Outcomes and Their Predictors in Acute Basilar Artery Occlusion Treated With Intra-Arterial Thrombolysis , 2011, Stroke.

[33]  W D Heiss,et al.  Ischemic Penumbra: Evidence From Functional Imaging in Man , 2000, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[34]  C. Levi,et al.  The independent predictive utility of computed tomography angiographic collateral status in acute ischaemic stroke. , 2009, Brain : a journal of neurology.

[35]  Ken Butcher,et al.  Collateral blood vessels in acute ischaemic stroke: a potential therapeutic target , 2011, The Lancet Neurology.