Imaging Acute Stroke
LANDMARK ADVANCES POISED TO SHIFT THE PARADIGM OF ACUTE STROKE IMAGING AND TREATMENT
The basic premise underlying acute stroke therapy is to salvage the ischemic region from evolving into infarction, thereby maintaining brain function and improving outcome. The concept of the ischemic penumbra concept envisions not only potentially salvageable or at-risk ischemic tissue but also nonviable tissue known as the “ischemic core”. The Stanford Stroke Center has been at the forefront of developing acute imaging and image processing techniques that provide immediate and accurate visualization of both core and penumbra. These techniques, which involve MRI with diffusion weighted imaging (DWI) and perfusion weighed imaging (PWI), have proven to identify patients who can benefit from both intravenous and intra-arterial therapies well beyond established time frames.
A research collaboration coordinated at Stanford has helped establish that a lesion detected by DWI lesion is an extremely accurate surrogate for the ischemic core.
Furthermore, recent data from Stanford demonstrate that PWI, when optimally processed, can accurately identify critically hypoperfused penumbral tissue.
The DEFUSE Study
This Stanford study, sponsored by the NIH, demonstrated that patients with a favorable MRI profile, called Target Mismatch, have excellent outcomes following reperfusion, even when treated up to 6 hours after symptom onset with iv tPA. Other MRI profiles, including the No mismatch and Malignant profile failed to show any evidence of benefit from reperfusion.
In order to automatically process DWI and PWI data quickly and accurately, Stanford Stroke Center faculty members developed a unique software program called RAPID. Using the databases from 2 international studies, this software program has been retrospectively demonstrated to identify patients who benefit from reperfusion following iv tPA therapy.
This recently completed multicenter trial was designed and run by Stanford and funded by the NIH. The trial results demonstrated that using the RAPID software, selected patients can be identified who benefit for intra-arterial clot removal therapy up to 12 hours after symptom onset. These findings have the potential to substantially expand the number of patients eligible for successful stroke treatment and significantly improve the overall results of intra-arterial therapies.
The research findings described above imply that the paradigm for acute stroke treatment can now move away from arbitrary time windows. Identification of salvageable brain tissue and determining the site of vascular obstruction will become the focus of acute imaging. Treatment strategies can then be individualized to maximize reperfusion of viable tissue.
Magnetic resonance imaging profiles predict clinical response to early reperfusion: the diffusion and perfusion imaging evaluation for understanding stroke evolution (DEFUSE) study.
Albers GW, Thijs VN, Wechsler L, Kemp S, Schlaug G, Skalabrin E, Bammer R, Kakuda W, Lansberg MG, Shuaib A, Coplin W, Hamilton S, Moseley M, Marks MP; DEFUSE Investigators.
Ann Neurol. 2006 Nov;60(5):508-17.
PMID: 17066483 [PubMed - indexed for MEDLINE]
MRI profile and response to endovascular reperfusion after stroke (DEFUSE 2): a prospective cohort study.
Lansberg MG, Straka M, Kemp S, Mlynash M, Wechsler LR, Jovin TG, Wilder MJ, Lutsep HL, Czartoski TJ, Bernstein RA, Chang CW, Warach S, Fazekas F, Inoue M, Tipirneni A, Hamilton SA, Zaharchuk G, Marks MP, Bammer R, Albers GW; DEFUSE 2 study investigators.
Lancet Neurol. 2012 Oct;11(10):860-7. doi: 10.1016/S1474-4422(12)70203-X. Epub 2012 Sep 4.
Clinical outcomes strongly associated with the degree of reperfusion achieved in target mismatch patients: pooled data from the diffusion and perfusion imaging evaluation for understanding stroke evolution studies.
Inoue M, Mlynash M, Straka M, Kemp S, Jovin TG, Tipirneni A, Hamilton SA, Marks MP, Bammer R, Lansberg MG, Albers GW; DEFUSE 1 and 2 Investigators.
Stroke. 2013 Jul;44(7):1885-90. doi: 10.1161/STROKEAHA.111.000371. Epub 2013 May 23.
PMID: 23704106 [PubMed - in process]
Early diffusion-weighted imaging and perfusion-weighted imaging lesion volumes forecast final infarct size in DEFUSE 2.
Wheeler HM, Mlynash M, Inoue M, Tipirneni A, Liggins J, Zaharchuk G, Straka M, Kemp S, Bammer R, Lansberg MG, Albers GW; DEFUSE 2 Investigators.
Stroke. 2013 Mar;44(3):681-5. doi: 10.1161/STROKEAHA.111.000135. Epub 2013 Feb 6.
PMID: 23390119 [PubMed - indexed for MEDLINE]
Apparent diffusion coefficient threshold for delineation of ischemic core.
Purushotham A, Campbell BC, Straka M, Mlynash M, Olivot JM, Bammer R, Kemp SM, Albers GW, Lansberg MG.
Int J Stroke. 2013 Jun 27. doi: 10.1111/ijs.12068. [Epub ahead of print]
PMID: 23802548 [PubMed - as supplied by publisher]
The infarct core is well represented by the acute diffusion lesion: sustained reversal is infrequent.
Campbell BC, Purushotham A, Christensen S, Desmond PM, Nagakane Y, Parsons MW, Lansberg MG, Mlynash M, Straka M, De Silva DA, Olivot JM, Bammer R, Albers GW, Donnan GA, Davis SM; EPITHET–DEFUSE Investigators.
J Cereb Blood Flow Metab. 2012 Jan;32(1):50-6. doi: 10.1038/jcbfm.2011.102. Epub 2011 Jul 20.
PMID: 21772309 [PubMed - indexed for MEDLINE] Free PMC Article
RAPID automated patient selection for reperfusion therapy: a pooled analysis of the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET) and the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution (DEFUSE) Study.
Lansberg MG, Lee J, Christensen S, Straka M, De Silva DA, Mlynash M, Campbell BC, Bammer R, Olivot JM, Desmond P, Davis SM, Donnan GA, Albers GW.
Stroke. 2011 Jun;42(6):1608-14. doi: 10.1161/STROKEAHA.110.609008. Epub 2011 Apr 14.
PMID: 21493916 [PubMed - indexed for MEDLINE] Free PMC Article
Refining the definition of the malignant profile: insights from the DEFUSE-EPITHET pooled data set.
Mlynash M, Lansberg MG, De Silva DA, Lee J, Christensen S, Straka M, Campbell BC, Bammer R, Olivot JM, Desmond P, Donnan GA, Davis SM, Albers GW; DEFUSE-EPITHET Investigators.
Stroke. 2011 May;42(5):1270-5. doi: 10.1161/STROKEAHA.110.601609. Epub 2011 Apr 7.
PMID: 21474799 [PubMed - indexed for MEDLINE] Free PMC Article
Optimal Tmax threshold for predicting penumbral tissue in acute stroke.
Olivot JM, Mlynash M, Thijs VN, Kemp S, Lansberg MG, Wechsler L, Bammer R, Marks MP, Albers GW.
Stroke. 2009 Feb;40(2):469-75. doi: 10.1161/STROKEAHA.108.526954. Epub 2008 Dec 24.
PMID: 19109547 [PubMed - indexed for MEDLINE] Free PMC Article