Abstract WP124: Signal Intensity Ratio Does Not Predict Recurrent Stroke in Patients with Symptomatic Intracranial Atherosclerotic Disease

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Owaiz Ansari ◽  
Rajbeer S Sangha ◽  
Sameer Ansari ◽  
Shyam Prabhakaran

Background: Symptomatic intracranial atherosclerotic disease (ICAD) is associated with high risk for recurrent stroke. Identification of patients remains a challenge using clinical and radiographic markers. Recent research has identified signal intensity ratio (SIR) across stenotic lesions on time-of-flight magnetic resonance angiography (TOF-MRA) as a novel noninvasive marker of recurrent stroke risk. We sought to externally validate this approach in a single center analysis. Methods: From a prospective observational stroke registry since August 2012, we identified patients with ischemic stroke due to ICAD causing moderate-severe stenosis of the basilar, intracranial vertebral, intracranial internal carotid, or middle cerebral arteries. Using the method described previously, we calculated SIR values across the stenotic lesions corrected for background signal intensity from TOF-MRA performed within 7 days of index stroke admission. Outcomes were prospectively captured by phone interview at 1 and 3 months after stroke. Recurrent stroke was defined by new infarct in the territory of the stenotic artery or absent imaging confirmation, territory-specific clinical symptoms lasting > 24 hours. We evaluated whether baseline SIR values were different between patients with and without recurrent stroke overall and in subgroups by ICAD location. P-value < 0.05 was considered significant. Results: Among 99 consecutive patients with ICAD, 79 (80%) had interpretable MRAs at baseline (mean age 68.4 +11.2 years, 53.2% male, 53.2% black, median NIHSS score 3; 27.7% posterior circulation stenosis). Recurrent stroke occurred in 21.5% and 25.3% of patients at 1 and 3 months, respectively. Median SIR at baseline was 0.86 (interquartile range 0.56-1.04) and was not different those with vs. without recurrent stroke (1-month: 0.79 vs. 0.86, p=0.93; 3-month: 0.79 vs. 0.86, p=0.68). Results were not different by ICAD location. Discussion: In this single center prospective registry, we were unable to validate SIR on time-of-flight MRA as a marker of early recurrent stroke risk in patients with symptomatic ICAD. Further research is needed to identify novel predictors of recurrence in this high-risk cohort.

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
David S Liebeskind ◽  
Andrzej S Kosinski ◽  
Michael J Lynn ◽  
Fabien Scalzo ◽  
Albert K Fong ◽  
...  

Background: Intracranial stenosis carries a high risk of recurrent stroke, but there is no noninvasive method to identify high-risk lesions. Fractional flow, or the pressure gradient across a stenosis, may identify hemodynamic effects and ischemic risk beyond percent stenosis of an artery. TOF-MRA signal intensity correlates with blood flow and may serve as a useful, noninvasive risk marker. We hypothesized that diminished TOF-MRA signal intensity distal to an intracranial stenosis predicts stroke risk. Methods: TOF-MRA of the intracranial circulation acquired prospectively in the SONIA-WASID trials was digitized to enable measurement of relative signal intensity immediately distal and proximal to symptomatic intracranial stenoses. The distal/proximal signal intensity ratio (SIR) was calculated from 3 mm regions of interest distal and proximal to symptomatic stenoses, correcting for background intensity and blinded to outcome. Univariate and multivariate analyses included clinical variables, SIR, and invasive angiography measures (luminal stenosis, TICI, collateral grade) to identify predictors for risk of stroke in the territory in this SONIA-WASID cohort. Results: 189 patients with site-based 50-99% symptomatic intracranial stenosis in SONIA-WASID had TOF-MRA available. In a univariate analysis, the hazard ratio (HR) for stroke in the territory of the symptomatic artery with SIR < 0.9 (i.e. SIR below median) was 5.2 (1.8, 15.3; p=0.001) as compared to SIR ≥ 0.9. In a multivariate analysis correcting for baseline blood pressure, LDL, percent stenosis, recency of symptoms, TICI and downstream collaterals, the HR for SIR < 0.9 was 10.9 (2.0, 58.9; p=0.001). Only collaterals also had a significant independent association with stroke risk, HR 13.8 (3.4, 55.5; p<0.001). In the subset of patients with < 70% stenosis, a SIR < 0.9 maintained a significant association with recurrent stroke in the territory (p=0.006), with a two year event rate of 17.3%. Conclusions: Fractional flow assessed by TOF-MRA SIR may be a useful noninvasive tool to identify high-risk intracranial lesions, even in patients with moderate (< 70%) degrees of stenosis, and may be suitable for selection of high-risk patients for clinical trials or aggressive treatments.


Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
David S Liebeskind ◽  
Shyam Prabhakaran ◽  
Edward Feldmann ◽  
Xinjian Du ◽  
Linda Rose-Finnell ◽  
...  

Background: Fractional flow across an atherosclerotic lesion measured with TOF-MRA signal intensity ratio (SIR) may be used to gauge hemodynamic severity and to predict subsequent stroke. The degree of flow impairment may also be ascertained by quantitative MRA (QMRA). We analyzed performance of these noninvasive imaging parameters to estimate risk of subsequent posterior circulation events in VERiTAS. Methods: TOF-MRA data and QMRA were simultaneously acquired in VERiTAS. SIR were derived from TOF source images and normalized for analysis with volume flow ratios (VFR) on QMRA at standard anatomical landmarks and across the maximal stenosis. Statistics analyzed the correlation between SIR and VFR, and the ability of each to predict clinical events. Results: 72 subjects (mean age 65.6±10.3 years, 32 (44%) women) with posterior circulation atherosclerosis were enrolled in VERiTAS. Posterior communicating artery (PCOMM) flow to the posterior circulation was detected in 85% on the right, in 86% on the left, with bilateral PCOMM flow in 78%. Fractional flow measures or SIR across the maximal stenotic lesion evident on TOF MRA was reduced in 43%, increased in 16%, with no change in 40%. SIR from the proximal to distal basilar artery segments increased in 62%, was unchanged in 33% and decreased in 4% of cases. SI and VFR exhibited limited correlation at corresponding arterial segments. QMRA VFR indicative of low distal flow status predicted subsequent clinical events, unlike SIR. Conclusions: Evaluation of hemodynamics in posterior circulation atherosclerosis reveals superiority of QMRA to SIR in prospectively predicting recurrent ischemia. Collateral circulation, tandem disease and unique aspects of vertebrobasilar atherosclerosis likely influence the utility of SIR on TOF MRA.


Author(s):  
Amrish O. Chourasia ◽  
Mary E. Sesto ◽  
Youngkyoo Jung ◽  
Robert S. Howery ◽  
Robert G. Radwin

Work place exertions may include muscle shortening (concentric) or muscle lengthening (eccentric) contractions. This study investigates the upper limb mechanical properties and magnetic resonance images (MRI) of the involved muscles following submaximal eccentric and concentric exertions. Twelve participants were randomly assigned to perform at 30° per second eccentric or concentric forearm supination exertions at 50% isometric maximum voluntary contraction (MVC) for 30 minutes. Measurement of mechanical stiffness, isometric MVC, localized discomfort and MRI supinator: extensor signal intensity ratio was done before, immediately after, 1 hour after and 24 hours after the bout of exercise. A 53% average decrease in mechanical stiffness after 1 hour was observed for the eccentric group (p< 0.05) compared to a 1% average decrease for the concentric group (p> 0.05). Edema, indicative of swelling, was observed 24 hrs after exercise, with an average increase in the MRI supinator: extensor signal intensity ratio of 36% for the eccentric group and less than 10% for the concentric group (p<0.05).


Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Rajbeer S Sangha ◽  
Carlos Corado ◽  
Richard A Bernstein ◽  
Ilana Ruff ◽  
Yvonne Curran ◽  
...  

Background: Since the SAMMPRIS trial, aggressive medical management (AMM) with the use of dual antiplatelets (aspirin, clopidogrel) and high dose statin therapy has been standard of care for patients with symptomatic intracranial atherosclerotic disease (ICAD). However, there is limited data on the “real-world” application of this regimen. We hypothesized that 30-day recurrent stroke risk among patients treated with AMM would be similar to that in SAMMPRIS medically-treated patients. Methods: Using the prospective Northwestern University Brain Attack Registry, we identified all patients admitted between 8/1/12 and 1/31/14 with 1) confirmed ischemic stroke or transient ischemic attack (TIA); 2) independently adjudicated symptomatic ICAD; and 3) discharged on AMM. At 30 days (28-35 day window) post-stroke, patients or proxies were contacted by telephone to review events and outcomes. We also utilized an electronic surveillance system of hospital records at any of 3 health system hospitals with confirmation by manual review of the medical record in all instances of reported recurrent stroke or TIA. Ischemic stroke in the territory of the symptomatic stenotic artery was the primary outcome. We calculated 30-day rate of stroke in the territory of the stenotic artery and 95% confidence intervals using the Wald method and compared it with that reported in the SAMMPRIS trial. Results: Among 36 patients who met study criteria, 13 (36.1%) were female and mean age was 65.4 (± 9.7) years. Median initial NIHSS score was 4 (interquartile range 0-17). Symptomatic ICAD was localized to the anterior circulation in 21 (58%) patients and posterior circulation in 15 (41.7%). At 30 days, 3 of the 36 patients (8.3%, 95% CI 2.1-22.6%) had recurrent stroke compared to 5.8% in the medical arm of SAMMPRIS (p=0.47). An additional 3 patients (8.3%) experienced TIA within 30 days. Conclusions: In a single-center observational cohort study, we found that AMM in patients with symptomatic ICAD yielded similar rates of recurrent stroke at 30-days as observed in the SAMMPRIS trial. Our study provides “real-world” confirmation of the potential benefits of AMM in this high-risk stroke subtype.


Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Ruchira M Jha ◽  
Thomas W Battey ◽  
Ly Pham ◽  
Hannah Irvine ◽  
Karen Furie ◽  
...  

Introduction: Increased Matrix Metalloproteinase-9 (MMP9) level is associated with symptomatic hemorrhagic transformation (HT) after stroke. Higher risk of HT has also been reported in patients with early FLAIR hyperintensity on brain MRI. Hypothesis: We assessed whether FLAIR hyperintensity is associated with MMP9 levels. Methods: We retrospectively analyzed a cohort of acute stroke subjects who had acute brain MRI images and blood samples within the first 12 hours after onset of stroke. FLAIR hyperintensity was quantitatively assessed using FLAIR signal intensity ratio between the stroke lesion and corresponding normal contralateral hemispheres. For each subject, the FLAIR ratio was generated from the average of 6 regions of interest: 2 white matter and 2 gray matter regions each on 2 separate slices. MMP9 was measured using standard ELISA technique. Univariate and multivariate analyses were used to evaluate the relationship between FR and MMP9 and clinical covariates. Results: 180 subjects had brain MRI and MMP9 available for analysis. MRI occurred within 6 ±3 hours and blood samples were drawn within 7 ± 4 hours from last seen well time. The mean MMP9 level was 238 ± 242 ng/mL and the mean FLAIR ratio was 1.40± 0.23. In univariate analysis, FLAIR ratio was associated with time to MRI (r= 0.18, p=0.01) and MMP9 (r=0.29, p<0.001). In multivariate analysis both FLAIR ratio (p<0.001) and time to MRI (p=0.003) remained associated with MMP9. Conclusions: There is a significant association between FLAIR ratio and MMP9 in acute stroke subjects. This raises the possibility that FLAIR hyperintensity reflects blood brain barrier changes during ischemia. Future studies to validate the prognostic value of FLAIR ratio in predicting symptomatic hemorrhagic transformation are warranted.


Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Shyam Prabhakaran ◽  
Rajbeer Sangha ◽  
Sameer Ansari ◽  
Jose Romano ◽  
PN Sylaja ◽  
...  

Introduction: Despite aggressive medical management, patients with symptomatic intracranial atherosclerotic disease (ICAD) remain at high risk for recurrent stroke. There are no reliable biomarkers to identify those at highest risk and in whom flow restorative procedures may be warranted. We hypothesized that a borderzone infarct pattern would predict 90-day recurrent stroke in the territory of symptomatic ICAD. Methods: Using the prospective registry at a single center, we identified consecutive patients admitted between 2012 and 2017 with confirmed ischemic stroke or transient ischemic attack (TIA) and independently adjudicated symptomatic ICAD with stenosis of >50%. We ascertained clinical events within 3 months of index stroke through telephone interview. Ischemic stroke in the territory of the symptomatic stenotic artery was the primary outcome. A blinded rater assessed infarct pattern: single perforator, territorial, borderzone, or mixed. We evaluated whether infarct pattern was a predictor of recurrent stroke using logistic regression adjusting for age, sex, prior stroke, initial NIHSS score, location of stenosis, degree of stenosis, and use of dual antiplatelet therapy at discharge. Results: Among 212 patients who met study criteria, the mean age was 68.2 (±12.2) years and median initial NIHSS score was 3 (interquartile range 1-6). Symptomatic ICAD was localized to the anterior circulation in 132 (64.2%) patients and 171 (80.7%) had stenosis >70%. Isolated borderzone infarcts were noted in 18 patients (8.5%) while they were present in 34 (16.0%) other patients with mixed pattern. At 3 months, 51 (24.1%) patients experienced recurrent stroke in the territory. Among patients with any borderzone infarct, 20 (38.7%) had recurrent stroke versus 31 (19.4%) in patients with other patterns (p=0.005). In adjusted analysis, presence of any borderzone infarct was independently associated with recurrent stroke (aOR 2.59, 95% CI 1.23-5.48, p=0.012). Conclusions: In a single-center observational cohort study, we found that a borderzone infarct pattern was a strong predictor of recurrent stroke at 3 months in patients with symptomatic ICAD. Our data suggest that hypoperfusion may be an important mechanism of recurrent stroke in this population.


Blood ◽  
1997 ◽  
Vol 89 (10) ◽  
pp. 3778-3786 ◽  
Author(s):  
Francis G. Blankenberg ◽  
Peter D. Katsikis ◽  
Richard W. Storrs ◽  
Christian Beaulieu ◽  
Daniel Spielman ◽  
...  

Abstract Quantification of apoptotic cell death in vivo has become an important area of investigation in patients with acute lymphoblastic leukemia (ALL). We have devised a noninvasive analytical method to estimate the percentage of apoptotic lymphoblasts in doxorubicin-treated Jurkat T-cell ALL cultures, using proton nuclear magnetic resonance spectroscopy (1H NMR). We have found that the ratio of the methylene (CH2 ) resonance (at 1.3 ppm) to the methyl (CH3 ) resonance (at 0.9 ppm) signal intensity, as observed by 1H NMR, is directly proportional to the percentage of apoptotic lymphoblasts in vitro. The correlation between the CH2/CH3 signal intensity ratio and the percentage of apoptotic lymphoblasts was optimal 24 to 28 hours after doxorubicin treatment (r2 = .947, N = 27 samples). There was also a direct temporal relationship between an increase in the CH2/CH3 signal intensity ratio and the onset of apoptosis as detected by nuclear morphologic analysis, fluorescein-annexin V flow cytometry, and DNA gel electrophoresis. Thin-layer chromatography confirmed that a dynamic and/or compositional change of the plasma membrane, rather than increases in lipase activity or fatty acid production, appears to account for the increase in the CH2/CH3 signal intensity ratio during apoptosis. 1H NMR may have clinical utility for the early noninvasive assessment of chemotherapeutic efficacy in patients with ALL.


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