Ann-Christin Ostwaldt

Relationship Between Changes in the Temporal Dynamics of the Blood-Oxygen-Level-Dependent Signal and Hypoperfusion in Acute Ischemic Stroke

Background and Purpose— Changes in the blood-oxygen-level-dependent (BOLD) signal provide a noninvasive measure of blood flow, but a detailed comparison with established perfusion parameters in acute stroke is lacking. We investigated the relationship between BOLD signal temporal delay and dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) in stroke patients. Methods— In 30 patients with acute (<24 hours) ischemic stroke, we performed Pearson correlation and multiple linear regression between DSC-MRI parameters (time to maximum [Tmax], mean transit time, cerebral blood flow, and cerebral blood volume) and BOLD-based parameters (BOLD delay and coefficient of BOLD variation). Prediction of severe hypoperfusion (Tmax >6 seconds) was assessed using receiver–operator characteristic (ROC) analysis. Results— Correlation was highest between Tmax and BOLD delay (venous sinus reference; time shift range 7; median r=0.60; interquartile range=0.49–0.71). Coefficient of BOLD variation correlated with cerebral blood volume (median r= 0.37; interquartile range=0.24–0.51). Mean R2 for predicting BOLD delay by DSC-MRI was 0.54 (SD=0.2) and for predicting coefficient of BOLD variation was 0.37 (SD=0.17). BOLD delay (whole-brain reference, time shift range 3) had an area under the curve of 0.76 for predicting severe hypoperfusion (sensitivity=69.2%; specificity=80%), whereas BOLD delay (venous sinus reference, time shift range 3) had an area under the curve of 0.76 (sensitivity=67.3%; specificity=83.5%). Conclusions— BOLD delay is related to macrovascular delay and microvascular hypoperfusion, can identify severely hypoperfused tissue in acute stroke, and is a promising alternative to gadolinium contrast agent–based perfusion assessment in acute stroke. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00715533 and NCT02077582.

The Potential of Microvessel Density in Prediction of Infarct Growth: A Two-Month Experimental Study in Vessel Size Imaging

Objectives: Vessel size imaging is a novel technique to evaluate pathological changes of the microvessel density quantity Q and the mean vessel size index (VSI). As a follow-up study, we assessed these parameters for microscopic description of ischemic penumbra and their potentials in predicting lesion growth. Methods: Seventy-five patients with a perfusion-diffusion mismatch were examined within 24 h from symptom onset. We defined three regions of interest: the initial infarct (INF), the ischemic penumbra (IPE), and the healthy region (HEA) symmetric to the IPE. For 23 patients with a 6th-day follow-up, IPE regions were divided into areas of infarct growth and areas of oligemia. Result: The median values of Q and VSI were: for INF 0.29 s-1/3 and 15.8 µm, for IPE 0.33 s-1/3 and 20.6 µm and for HEA 0.36 s-1/3 and 17.4 µm. The Q in the IPE was significantly smaller than in HEA, and VSI was significantly larger. The Q with a threshold of 0.32 s-1/3 predicted the final infarction with a sensitivity of 69% and a specificity of 64%. Conclusions: The reduced Q and increased VSI in the IPE confirmed our previous pilot results. Although Q showed a trend to identify the severity of ischemia in an overall voxel population, its potential in predicting infarct growth needs to be further tested in a larger cohort including a clear status of reperfusion and recanalization.

DCE-MRI blood–brain barrier assessment in acute ischemic stroke

Objective: To quantitatively evaluate blood–brain barrier changes in ischemic stroke patients using dynamic contrast-enhanced (DCE) MRI. Methods: We examined 54 stroke patients (clinicaltrials.gov NCT00715533, NCT02077582) in a 3T MRI scanner within 48 hours after symptom onset. Twenty-eight patients had a follow-up examination on day 5–7. DCE T1 mapping and Patlak analysis were employed to assess BBB permeability changes. Results: Median stroke Ktrans values (0.7 × 10−3 min−1 [interquartile range (IQR) 0.4–1.8] × 10−3 min−1) were more than 3-fold higher compared to median mirror Ktrans values (0.2 × 10−3 min−1, IQR 0.1–0.7 × 10−3 min−1, p < 0.001) and further increased at follow-up (n = 28, 2.3 × 10−3 min−1, IQR 0.8–4.6 × 10−3 min−1, p < 0.001). By contrast, mirror Ktrans values decreased over time with a clear interaction of timepoint and stroke/mirror side (p < 0.001). Median stroke Ktrans values were 2.5 times lower than in hemorrhagic transformed regions (0.7 vs 1.8 × 10−3 min−1; p = 0.055). There was no association between stroke Ktrans values and the delay from symptom onset to baseline examination, age, and presence of hyperintense acute reperfusion marker. Conclusion: BBB in acute stroke patients can be successfully assessed quantitatively. The decrease of BBB permeability in unaffected regions at follow-up may be an indicator of global BBB leakage even in vessel territories remote from the index infarct.

Reliability of Two Diameters Method in Determining Acute Infarct Size. Validation as New Imaging Biomarker.

Background In order to select patients most likely to benefit for thrombolysis and to predict patient outcome in acute ischemic stroke, the volumetric assessment of the infarcted tissue is used. However, infarct volume estimation on Diffusion weighted imaging (DWI) has moderate interrater variability despite the excellent contrast between ischemic lesion and healthy tissue. In this study, we compared volumetric measurements of DWI hyperintensity to a simple maximum orthogonal diameter approach to identify thresholds indicating infarct size >70 ml and >100 ml. Methods Patients presenting with ischemic stroke with an NIHSS of ≥ 8 were examined with stroke MRI within 24 h after symptom onset. For assessment of the orthogonal DWI lesion diameters (od-values) the image with the largest lesion appearance was chosen. The maximal diameter of the lesion was determined and a second diameter was measured perpendicular. Both diameters were multiplied. Od-values were compared to volumetric measurement and od-value thresholds identifying a lesion size of > 70 ml and > 100 ml were determined. In a selected dataset with an even distribution of lesion sizes we compared the results of the od value thresholds with results of the ABC/2 and estimations of lesion volumes made by two resident physicians. Results For 108 included patients (53 female, mean age 71.36 years) with a median infarct volume of 13.4 ml we found an excellent correlation between volumetric measures and od-values (r2 = 0.951). Infarct volume >100 ml corresponds to an od-value cut off of 42; > 70 ml corresponds to an od-value of 32. In the compiled dataset (n = 50) od-value thresholds identified infarcts > 100 ml / > 70 ml with a sensitivity of 90%/ 93% and with a specificity of 98%/ 89%. The od-value offered a higher accuracy in identifying large infarctions compared to both visual estimations and the ABC/2 method. Conclusion The simple od-value enables identification of large DWI lesions in acute stroke. The cutoff of 42 is useful to identify large infarctions with volume larger than 100 ml. Further studies can analyze the therapeutic utility of this new method. Trail Registration ClinicalTrials.org NCT00715533

Early neurological stability predicts adverse outcome after acute ischemic stroke

Background Deterioration in the National Institutes of Health Stroke Scale (NIHSS) in the early days after stroke is associated with progressive infarction, brain edema, and/or hemorrhage, leading to worse outcome. Aims We sought to determine whether a stable NIHSS score represents an adverse or favorable course. Methods Brain magnetic resonance images from a research cohort of acute ischemic stroke patients were analyzed. Using NIHSS scores at baseline and follow-up (day 3–5), patients were categorized into early neurological deterioration (ΔNIHSS ≥ 4), early neurological recovery (ΔNIHSS ≤ −4) or early neurological stability (ΔNIHSS between −3 and 3). The association between these categories and volume of infarct growth, volume of swelling, parenchymal hemorrhage, and 3-month modified Rankin Scale score were evaluated. Results Patients with early neurological deterioration or early neurological stability were less likely to be independent (modified Rankin Scale = 0–2) at 3 months compared to those with early neurological recovery (P < 0.001). Patients with early neurological deterioration or early neurological stability were observed to have significantly greater infarct growth and swelling volumes than those with early neurological recovery (P = 0.03; P < 0.001, respectively). Brain edema was more common than the other imaging markers investigated and was independently associated with a stable or worsening NIHSS score after adjustment for age, baseline stroke volume, infarct growth volume, presence of parenchymal hemorrhage, and reperfusion (P < 0.0001). Conclusions Stable NIHSS score in the subacute period after ischemic stroke may not be benign and is associated with tissue injury, including infarct growth and brain edema. Early improvement is considerably more likely to occur in the absence of these factors.

Comparative Analysis of Markers of Mass Effect after Ischemic Stroke: Markers of Mass Effect to Predict Stroke Outcome

Midline shift determined on magnetic resonance imaging (MRI) or computed tomography (CT) images is a well‐validated marker of mass effect after large hemispheric infarction and associated with mortality. In this study, we targeted a population with moderately sized strokes. We compared midline shift to other imaging markers and determined their ability to predict long‐term outcome.

MRI follow-up after 24 h is an accurate surrogate parameter for treatment success after thrombolysis.

Eleven patients had no initial vessel occlusion, 19 showed re-canalization at 1–6 h (early recanalizers), and 6 additional patients showed recanalization at 24 h (late recanalizers). Four patients were nonrecanalizers. Age, gender and time to treatment did not differ between the subgroups. At baseline, nonrecanalizers had significantly larger perfusion deficits (p = 0.011) and patients with no initial occlusion had significantly smaller DWI and hypoperfu-sion volumes. Median lesion growth until 1–6 h was not signifi-cantly different between the groups (p = 0.167). The median lesion growth from baseline until 24 h was significantly larger in the nonrecanalizers compared to the other groups (71.4 vs. 2.8 ml, p < 0.05). The median perfusion deficit at 24 h and final lesion size did not differ between early and late recanalizers; both were sig-nificantly larger in nonrecanalizers. A modified Rankin Scale score of 0–2 at 3 months was reached by 66% of the recanalizers while no nonrecanalizer reached an independent outcome (p = 0.02).