Mapping a Reliable Stroke Onset Time Course Using Signal Intensity on DWI Scans

Introduction and hypothesis: In acute stroke patients the intensity of a FLAIR lesion in a region of diffusion restriction is associated with time from symptom onset. The DWI/FLAIR mismatch is currently used in trials for treatment of stroke patients with unknown onset time. However the accuracy of the DWI/FLAIR mismatch to predict symptom onset before 4.5h remains moderate. We hypothesized that collateral status, as assessed by the previously described hypoperfusion intensity ratio (HIR) could modify the association between time from stroke onset and FLAIR lesion intensity. Methods: From the ‘Ax200 for ischemic stroke trial’ 141 patients were included. Quantitative FLAIR maps were calculated in a voxel-based manner. For each voxel the relative signal intensity (rSI) was determined by the ratio of the signal intensity in that voxel and the median of the signal intensity in a sphere with radius 15mm positioned in the homologue voxel in the other hemisphere. Lesion volumes based on diffusion-weighted imaging and perfusion-weighted imaging were determined using RAPID software. The HIR was defined as the proportion of a Tmax >6 s lesion volume with a Tmax >10 s delay. A previously defined HIR-threshold of ≤ 0.4 dichotomized good versus poor collaterals. We studied the interaction between collateral circulation and the association between time from symptom onset and FLAIR intensity. Results: Time from symptom onset was associated with the mean FLAIR intensity in the region of non-reperfused core (b=1.05; 95%CI: 1.01-1.1). We identified an interaction between this association and collateral status (p=0.036). ROC analysis of FLAIR intensity to predict stroke onset before 4.5h showed an AUC of 0.66 (95% CI: 0. 49-0.83) for patients with good collaterals and 0.80 (95%CI: 0.71-0.90) for patients with poor collaterals. Conclusions: Our findings suggest that the progression of FLAIR intensity with time varies depending on the quality of the collateral flow. Accordingly collateral circulation influences the accuracy of FLAIR lesion intensity to predict stroke onset before 4.5h. This could be of particular importance for clinical trials enrolling patients based on the DWI/FLAIR mismatch.

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DETERMINING STROKE ONSET TIME USING QUANTIATIVE MRI: PRELIMINARY EVIDENCE OF AN ADC/QT2 MISMATCH IN ACUTE ISCHAEMIC STROKE PATIENTS

10.26226/morressier.58e389b1d462b802923850c8 ◽

2017 ◽

Author(s):

Bryony McGarry

Keyword(s):

Ischaemic Stroke ◽

Acute Ischaemic Stroke ◽

Onset Time ◽

Preliminary Evidence ◽

Stroke Onset ◽

Stroke Patients

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Intra-domain task-adaptive transfer learning to determine acute ischemic stroke onset time

Computerized Medical Imaging and Graphics ◽

10.1016/j.compmedimag.2021.101926 ◽

2021 ◽

Vol 90 ◽

pp. 101926

Author(s):

Haoyue Zhang ◽

Jennifer S Polson ◽

Kambiz Nael ◽

Noriko Salamon ◽

Bryan Yoo ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Transfer Learning ◽

Onset Time ◽

Stroke Onset

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Abstract W P32: Association of Low Cerebral Blood Volume With Negative FLAIR Hyperintensity in Acute Ischemic Stroke

Stroke ◽

10.1161/str.45.suppl_1.wp32 ◽

2014 ◽

Vol 45 (suppl_1) ◽

Author(s):

Nandakumar Nagaraja ◽

Marie Luby ◽

Matthew Edwardson ◽

Ramin Zand ◽

Lawrence L Latour

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Blood Volume ◽

Early Phase ◽

Cerebral Blood Volume ◽

Time Window ◽

Linear Regression Analysis ◽

Onset Time ◽

Stroke Onset ◽

Imaging Biomarker

Objective: FLAIR hyperintensity is being used in clinical trials as a surrogate imaging biomarker for stroke onset time to test the safety of thrombolysis. Studies have shown that patients with negative and positive FLAIR hyperintensity overlap at similar time points from stroke onset in the early phase of acute ischemic stroke (AIS). Hyperintensity on FLAIR MRI likely represents increased tissue water content. We sought to determine if cerebral blood volume (CBV) mediates FLAIR hyperintensity in the early phase of AIS. Methods: AIS patients seen in 2012 were included in the study if i) onset time was known, ii) an MRI with perfusion was performed within 12 hours of onset time, iii) had imaging confirmed vascular occlusion of ICA, M1, or M2. Following co-registration of raw perfusion images with FLAIR, CBV maps were generated using PMA ASIST™ software. Two raters blinded to clinical information separately evaluated the DWI, FLAIR and CBV maps and measured the signal intensity ratio (SIR) for the brightest region on FLAIR normalized by homologous contra-lateral tissue. The SIR was similarly measured for CBV in same region. FLAIR negative was defined as SIR<1.15, “Low CBV” was defined as CBV SIR <0.5. Results: One hundred eighty two patients were screened and 30 met all study criteria; 21 women, with mean age of 71 (± 16) years and median NIHSS 18 (IQR 9-22). Using linear regression analysis, CBV SIR was associated with FLAIR SIR (p <0.049). In the 0-3hr time window, overall CBV was not associated with FLAIR hyperintensity. However, in the 3-7.5hr time window, patients with negative FLAIR were more likely to have low CBV and conversely, patients with positive FLAIR were more likely to have normal CBV. Conclusion: CBV likely mediates FLAIR hyperintensity in 3-7.5hr of stroke onset but it has less impact on FLAIR hyperintensity in the first 3 hours of AIS. Low CBV could be a potential surrogate imaging biomarker in addition to FLAIR hyperintensity in the early phase of AIS.

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Minimally-invasive procedures for monitoring onset, time-course, and intensity of general anesthetic-induced developmental neurotoxicity: Imaging and behavior

Neurotoxicology and Teratology ◽

10.1016/j.ntt.2013.03.034 ◽

2013 ◽

Vol 37 ◽

pp. 83

Author(s):

Merle G. Paule

Keyword(s):

Minimally Invasive ◽

Time Course ◽

Onset Time ◽

Developmental Neurotoxicity ◽

Minimally Invasive Procedures ◽

Invasive Procedures ◽

General Anesthetic ◽

And Behavior

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Factors that influence clinicians’ decisions to offer intravenous alteplase in acute ischemic stroke patients with uncertain treatment indication: Results of a discrete choice experiment

International Journal of Stroke ◽

10.1177/1747493017690755 ◽

2017 ◽

Vol 13 (1) ◽

pp. 74-82 ◽

Cited By ~ 1

Author(s):

Aoife De Brún ◽

Darren Flynn ◽

Laura Ternent ◽

Christopher I Price ◽

Helen Rodgers ◽

...

Keyword(s):

Decision Making ◽

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Discrete Choice Experiment ◽

Discrete Choice ◽

Choice Experiment ◽

Onset Time ◽

Stroke Onset ◽

Related Factors ◽

Intravenous Alteplase

Background Treatment with intravenous alteplase for eligible patients with acute ischemic stroke is underused, with variation in treatment rates across the UK. This study sought to elucidate factors influencing variation in clinicians’ decision-making about this thrombolytic treatment. Methods A discrete choice experiment using hypothetical patient vignettes framed around areas of clinical uncertainty was conducted with UK-based clinicians. Mixed logit regression analyses were conducted on the data. Results A total of 138 clinicians completed the discrete choice experiment. Seven patient factors were individually predictive of increased likelihood of immediately offering IV alteplase (compared to reference levels in brackets): stroke onset time 2 h 30 min [50 min]; pre-stroke dependency mRS 3 [mRS 4]; systolic blood pressure 185 mm/Hg [140 mm/Hg]; stroke severity scores of NIHSS 5 without aphasia, NIHSS 14 and NIHSS 23 [NIHSS 2 without aphasia]; age 85 [68]; Afro-Caribbean [white]. Factors predictive of withholding treatment with IV alteplase were: age 95 [68]; stroke onset time of 4 h 15 min [50 min]; severe dementia [no memory problems]; SBP 200 mm/Hg [140 mm/Hg]. Three clinician-related factors were predictive of an increased likelihood of offering IV alteplase (perceived robustness of the evidence for IV alteplase; thrombolyzing more patients in the past 12 months; and high discomfort with uncertainty) and one with a decreased likelihood (high clinician comfort with treating patients outside the licensing criteria). Conclusions Both patient- and clinician-related factors have a major influence on the use of alteplase to treat patients with acute ischemic stroke. Clinicians’ views of the evidence, comfort with uncertainty and treating patients outside the license criteria are important factors to address in programs that seek to reduce variation in care quality regarding treatment with IV alteplase. Further research is needed to further understand the differences in clinical decision-making about treating patients with acute ischemic stroke with IV alteplase.

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Ventricular volume expansion in presymptomatic genetic frontotemporal dementia

Neurology ◽

10.1212/wnl.0000000000008386 ◽

2019 ◽

Vol 93 (18) ◽

pp. e1699-e1706 ◽

Cited By ~ 5

Author(s):

Tamara P. Tavares ◽

Derek G.V. Mitchell ◽

Kristy Coleman ◽

Christen Shoesmith ◽

Robert Bartha ◽

...

Keyword(s):

Frontotemporal Dementia ◽

Volume Expansion ◽

Time Course ◽

Automatic Segmentation ◽

Disease Onset ◽

Onset Time ◽

Ventricular Volume ◽

Mutation Carriers ◽

Mri Scans

ObjectiveTo characterize the time course of ventricular volume expansion in genetic frontotemporal dementia (FTD) and identify the onset time and rates of ventricular expansion in presymptomatic FTD mutation carriers.MethodsParticipants included patients with a mutation in MAPT, PGRN, or C9orf72, or first-degree relatives of mutation carriers from the GENFI study with MRI scans at study baseline and at 1 year follow-up. Ventricular volumes were obtained from MRI scans using FreeSurfer, with manual editing of segmentation and comparison to fully automated segmentation to establish reliability. Linear mixed models were used to identify differences in ventricular volume and in expansion rates as a function of time to expected disease onset between presymptomatic carriers and noncarriers.ResultsA total of 123 participants met the inclusion criteria and were included in the analysis (18 symptomatic carriers, 46 presymptomatic mutation carriers, and 56 noncarriers). Ventricular volume differences were observed 4 years prior to symptom disease onset for presymptomatic carriers compared to noncarriers. Annualized rates of ventricular volume expansion were greater in presymptomatic carriers relative to noncarriers. Importantly, time-intensive manually edited and fully automated ventricular volume resulted in similar findings.ConclusionsVentricular volume differences are detectable in presymptomatic genetic FTD. Concordance of results from time-intensive manual editing and fully automatic segmentation approaches support its value as a measure of disease onset and progression in future studies in both presymptomatic and symptomatic genetic FTD.

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A Machine Learning Approach for Classifying Ischemic Stroke Onset Time From Imaging

IEEE Transactions on Medical Imaging ◽

10.1109/tmi.2019.2901445 ◽

2019 ◽

Vol 38 (7) ◽

pp. 1666-1676 ◽

Cited By ~ 12

Author(s):

King Chung Ho ◽

William Speier ◽

Haoyue Zhang ◽

Fabien Scalzo ◽

Suzie El-Saden ◽

...

Keyword(s):

Machine Learning ◽

Ischemic Stroke ◽

Onset Time ◽

Stroke Onset ◽

Learning Approach ◽

Machine Learning Approach

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Stroke Onset Time Using Sodium MRI in Rat Focal Cerebral Ischemia

Stroke ◽

10.1161/01.str.0000198845.79254.0f ◽

2006 ◽

Vol 37 (3) ◽

pp. 883-888 ◽

Cited By ~ 49

Author(s):

Stephen C. Jones ◽

Alexander Kharlamov ◽

Boris Yanovski ◽

D. Kyle Kim ◽

Kirk A. Easley ◽

...

Keyword(s):

Cerebral Ischemia ◽

Focal Cerebral Ischemia ◽

Onset Time ◽

Stroke Onset ◽

Sodium Mri

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Results of Contracture Tests with Halothane, Caffeine, and Ryanodine Depend on Different Malignant Hyperthermia-associated Ryanodine Receptor Gene Mutations

Anesthesiology ◽

10.1097/00000542-200208000-00010 ◽

2002 ◽

Vol 97 (2) ◽

pp. 345-350 ◽

Cited By ~ 16

Author(s):

Marko Fiege ◽

Frank Wappler ◽

Ralf Weisshorn ◽

Mark Ulrich Gerbershagen ◽

Markus Steinfath ◽

...

Keyword(s):

Malignant Hyperthermia ◽

Ryanodine Receptor ◽

Time Course ◽

Clinical Symptoms ◽

Receptor Gene ◽

Gene Mutations ◽

Onset Time ◽

Release Channel ◽

Ryr1 Gene

Background More than 20 mutations in the gene encoding for the ryanodine receptor (RYR1), a Ca2+ release channel of the skeletal muscle sarcoplasmic reticulum, have been found to be associated with malignant hyperthermia (MH). This study was designed to investigate the effects of different mutations in the RYR1 gene on contracture development in in vitro contracture tests (IVCT) with halothane, caffeine, and ryanodine. Methods Ninety-three MH-susceptible (MHS) patients, diagnosed by the standard IVCT with halothane and caffeine, were included in this prospective study. Surplus muscle specimens were used for an IVCT with 1 microm ryanodine. The contracture course during the ryanodine IVCT was described by the attainment of different time points: onset time of contracture and times when contracture reached 2 mN or 10 mN. In addition, all patients were screened for mutations of the RYR1 gene. Results In 36 patients, four different mutations of the RYR1 gene (C487-T, G1021-A, C1840-T, G7300-A) were found. The IVCT threshold concentrations of halothane and caffeine were lower in patients with the C487-T mutation compared with patients without a detected mutation in the RYR1 gene. In the IVCT with ryanodine, contracture levels of 2 mN and 10 mN were reached earlier in muscle specimens from patients with C487-T, C1840-T, and G7300-A mutations compared with specimens from patients with the G1021-A mutation and patients without detected mutation in the RYR1 gene. Conclusions The differences between the groups in the halothane and caffeine IVCT threshold concentrations and in the time course of contracture development in the ryanodine IVCT underline the hypothesis that certain mutations in the RYR1 gene could make the ryanodine receptor more sensitive to specific ligands. This may be an explanation for varying clinical symptoms of MH crisis in humans.

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