Can intracranial time-of-flight-MR angiography predict extracranial carotid artery stenosis?

Objectives: Extracranial stenosis of the internal carotid artery (ICA) is an important cause of ischemic stroke and transient ischemic attack (TIA). It can be diagnosed using contrast-enhanced CT or MR angiography (MRA) as well as Doppler ultrasound. In this study, we assessed the diagnostic value of intracranial time-of-flight (TOF) MRA to predict extracranial ICA stenosis (ICAS). Methods: We retrospectively analyzed consecutive patients with acute ischemic stroke or TIA and middle- (50-69%) or high-grade (70-99%) unilateral extracranial ICAS according to NASCET criteria assessed by ultrasound between January 2016 and August 2018. The control group consisted of patients without extracranial ICAS. Intraluminal signal intensities (SI) of the intracranial ICA on the side of the extracranial stenosis were compared to the contralesional side on TOF-MRA source images. SI ratios (SIR) of contralesional:lesional side were compared between groups. Results: In total, 151 patients were included in the main analysis. Contralesional:lesional SIR in the intracranial C4-segment was significantly higher in patients with ipsilateral extracranial ICA stenosis (n = 51, median 74 years, 57% male) compared to the control group (n = 100, median 68 years, 48% male). Mean SIR was 1.463 vs. 1.035 (p < 0.001) for right-sided stenosis and 1.362 vs. 1.000 (p < 0.001) for left-sided stenosis. Receiver-operating characteristic curve demonstrated a cut-off value of 1.086 for right-sided [sensitivity/specificity 75%/81%; area under the curve (AUC) 0.81] and 1.104 for left-sided stenosis (sensitivity/specificity 70%/84%; AUC 0.80) in C4 as a good predictor for high-grade extracranial ICAS. Conclusions: SIR on TOF-MRA can be a marker of extracranial ICAS

Two simple and rapid methods based on maximum diameter accurately estimate large lesion volumes in acute stroke

Background: We compared two simple and rapid diameter-based methods (ABC/2, od-value) in terms of their accuracy in predicting lesion volume >70 ml and >100 ml. Methods: In 238 DWI images of ischemic stroke patients from the AXIS2 trial, maximum lesion diameter and corresponding maximum orthogonal diameter were measured. Estimation of infarct volume based on od-value and ABC/2 calculation was compared to volumetric assessments. Results: Accuracy of od-value and ABC/2 was similar for >70 ml (92.0 vs. 87.4) and >100 ml (92.9 vs. 93.3). ABC/2 overestimated lesion volume by 29.9%, resulting in a lower specificity. Conclusions: Od-value is a robust tool for patient selection in trials

IL-6 Plasma Levels Correlate With Cerebral Perfusion Deficits and Infarct Sizes in Stroke Patients Without Associated Infections

Introduction: We aimed to investigate several blood-based biomarkers related to inflammation, immunity, and stress response in a cohort of patients without stroke-associated infections regarding their predictive abilities for functional outcome and explore whether they correlate with MRI markers, such as infarct size or location. Methods: We combined the clinical and radiological data of patients participating in two observational acute stroke cohorts: the PREDICT and 1000Plus studies. The following blood-based biomarkers were measured in these patients: monocytic HLA-DR, IL-6, IL-8, IL-10, LBP, MRproANP, MRproADM, CTproET, Copeptin, and PCT. Multiparametric stroke MRI was performed including T2*, DWI, FLAIR, TOF-MRA, and perfusion imaging. Standard descriptive sum statistics were used to describe the sample. Associations were analyzed using Fischer's exact test, independent samples t-test and Spearmans correlation, where appropriate. Results: Demographics and stroke characteristics were as follows: 94 patients without infections, mean age 68 years (SD 10.5), 32.2% of subjects were female, median NIHSS score at admission 3 (IQR 2-5), median mRS 3 months after stroke 1 (IQR 0-2), mean volume of DWI lesion at admission 5.7 ml (SD 12.8), mean FLAIR final infarct volume 10 ml (SD 14.9), cortical affection in 61% of infarctions. Acute DWI lesion volume on admission MRI was moderately correlated to admission/maximum IL-6 as well as maximum LBP. Extent of perfusion deficit and mismatch were moderately correlated to admission/maximum IL-6 levels. Final lesion volume on FLAIR was moderately correlated to admission IL-6 levels. Conclusion: We found IL-6 to be associated with several parameters from acute stroke MRI (acute DWI lesion, perfusion deficit, final infarct size, and affection of cortex) in a cohort of patients not influenced by infections

The ratio between cerebral blood flow and Tmax predicts the quality of collaterals in acute ischemic stroke

Background In acute ischemic stroke the status of collateral circulation is a critical factor in determining outcome. We propose a less invasive alternative to digital subtraction angiography for evaluating collaterals based on dynamic-susceptibility contrast magnetic resonance imaging. Methods Perfusion maps of Tmax and cerebral blood flow (CBF) were created for 35 patients with baseline occlusion of a major cerebral artery. Volumes of hypoperfusion were defined as having a Tmax delay of > 4 seconds (Tmax4s) and > 6 seconds (Tmax6s) and a CBF drop below 80% of healthy, contralateral tissue. For each patient a ratio between the volume of the CBF and the Tmax based perfusion deficit was calculated. Associations with collateral status and radiological outcome were assessed with the Mann-Whitney-U test, uni- and multivariable logistic regression analyses as well as area under the receiver-operator- characteristic (ROC) curve. Results The CBF/Tmax volume ratios were significantly associated with bad collateral status in crude logistic regression analysis as well as with adjustment for NIHSS at admission and baseline infarct volume (OR = 2.5 95% CI[1.2–5.4] p = 0.020 for CBF/Tmax 4s volume ratio and OR = 1.6 95% CI[1.0–2.6] p = 0.031 for CBF/Tmax6s volume ratio). Moreover, the ratios were significantly correlated to final infarct size (Spearman’s rho = 0.711 and 0.619, respectively for the CBF/Tmax4s volume ratio and CBF/Tmax6s volume ration, all p<0.001). The ratios also had a high area under the ROC curve of 0.93 95%CI[0.86–1.00]) and 0.90 95%CI[0.80–1.00]respectively for predicting poor radiological outcome. Conclusions In the setting of acute ischemic stroke the CBF/Tmax volume ratio can be used to differentiate between good and insufficient collateral circulation without the need for invasive procedures like conventional angiography

Striatal Infarction Elicits Secondary Extrafocal MRI Changes in Ipsilateral Substantia Nigra

Focal ischemia may induce pathological alterations in brain areas distant from the primary lesion. In animal models, exofocal neuron death in the ipsilateral midbrain has been described after occlusion of the middle cerebral artery (MCA). Using sequential magnetic resonance imaging (T2- and diffusion- weighted) at 3 Tesla, we investigated acute ischemic stroke patients on days 1, 2, 6, 8, and 10 after stroke onset. Sixteen consecutive patients who had suffered a stroke involving the caudate nucleus and/or putamen of either hemisphere were recruited into the study. Four additional patients with strokes sparing the caudate nucleus and putamen but encompassing at least one- third of the MCA territory served as controls. Ischemic lesions involving striatal structures resulted in hyperintense lesions in ipsilateral midbrain that emerged between days 6 and 10 after stroke and were not present on the initial scans. In contrast, none of the control stroke patients developed secondary midbrain lesions. Hyperintense lesions in the pyramidal tract or the brain stem caused by degeneration of the corticospinal tract could be clearly distinguished from these secondary midbrain gray matter lesions and were detectable from day 2 after ischemia. Co-registration of high-resolution images with a digitized anatomic atlas revealed localization of secondary lesions primarily in the substantia nigra pars compacta. Apparent diffusion coefficient (ADC) values in the secondary lesions showed a delayed sharp decline through day 10. Normalization of ADC values was observed at late measurements. Taken together, our study demonstrates that striatal infarction elicits delayed degenerative changes in ipsilateral substantia nigra pars compacta

IL-6 Plasma Levels Correlate With Cerebral Perfusion Deficits and Infarct Sizes in Stroke Patients Without Associated Infections

Introduction: We aimed to investigate several blood-based biomarkers related to inflammation, immunity, and stress response in a cohort of patients without stroke-associated infections regarding their predictive abilities for functional outcome and explore whether they correlate with MRI markers, such as infarct size or location.Methods: We combined the clinical and radiological data of patients participating in two observational acute stroke cohorts: the PREDICT and 1000Plus studies. The following blood-based biomarkers were measured in these patients: monocytic HLA-DR, IL-6, IL-8, IL-10, LBP, MRproANP, MRproADM, CTproET, Copeptin, and PCT. Multiparametric stroke MRI was performed including T2*, DWI, FLAIR, TOF-MRA, and perfusion imaging. Standard descriptive sum statistics were used to describe the sample. Associations were analyzed using Fischer's exact test, independent samples t-test and Spearmans correlation, where appropriate.Results: Demographics and stroke characteristics were as follows: 94 patients without infections, mean age 68 years (SD 10.5), 32.2% of subjects were female, median NIHSS score at admission 3 (IQR 2–5), median mRS 3 months after stroke 1 (IQR 0–2), mean volume of DWI lesion at admission 5.7 ml (SD 12.8), mean FLAIR final infarct volume 10 ml (SD 14.9), cortical affection in 61% of infarctions. Acute DWI lesion volume on admission MRI was moderately correlated to admission/maximum IL-6 as well as maximum LBP. Extent of perfusion deficit and mismatch were moderately correlated to admission/maximum IL-6 levels. Final lesion volume on FLAIR was moderately correlated to admission IL-6 levels.Conclusion: We found IL-6 to be associated with several parameters from acute stroke MRI (acute DWI lesion, perfusion deficit, final infarct size, and affection of cortex) in a cohort of patients not influenced by infections.Clinical Trial Registration:www.ClinicalTrials.gov, identifiers NCT01079728 and NCT0071553

The Association Between Recanalization, Collateral Flow, and Reperfusion in Acute Stroke Patients: A Dynamic Susceptibility Contrast MRI Study

Background: Collateral circulation in ischemic stroke patients plays an important role in infarct evolution und assessing patients' eligibility for endovascular treatment. By means of dynamic susceptibility contrast MRI, we aimed to investigate the effects of reperfusion, recanalization, and collateral flow on clinical and imaging outcomes after stroke. Methods: Retrospective analysis of 184 patients enrolled into the prospective observational 1000Plus study (clinicaltrials.org NCT00715533). Inclusion criteria were vessel occlusion on baseline MR-angiography, imaging within 24 h after stroke onset and follow-up perfusion imaging. Baseline Higashida score using subtracted dynamic MR perfusion source images was used to quantify collateral flow. The influence of these variables, and their interaction with vessel recanalization, on clinical and imaging outcomes was assessed using robust linear regression. Results: Ninety-eight patients (53.3%) showed vessel recanalization. Higashida score (p = 0.002), and recanalization (p = 0.0004) were independently associated with reperfusion. However, we found no evidence that the association between Higashida score and reperfusion relied on recanalization status (p = 0.2). NIHSS on admission (p < 0.0001) and recanalization (p = 0.001) were independently associated with long-term outcome at 3 months, however, Higashida score (p = 0.228) was not. Conclusion: Higashida score and recanalization were independently associated with reperfusion, but the association between recanalization and reperfusion was similar regardless of collateral flow quality. Recanalization was associated with long-term outcome. DSC-based measures of collateral flow were not associated with long-term outcome, possibly due to the complex dynamic nature of collateral recruitment, timing of imaging and the employed post-processing

A Pilot Study

Background There is an ongoing debate whether stroke patients presenting with minor or moderate symptoms benefit from thrombolysis. Up until now, stroke severity on admission is typically measured with the NIHSS, and subsequently used for treatment decision. Hypothesis Acute MRI lesion volume assessment can aid in therapy decision for iv-tPA in minor stroke. Methods We analysed 164 patients with NIHSS 0–7 from a prospective stroke MRI registry, the 1000+ study (clinicaltrials.org NCT00715533). Patients were examined in a 3 T MRI scanner and either received (n = 62) or did not receive thrombolysis (n = 102). DWI (diffusion weighted imaging) and PI (perfusion imaging) at admission were evaluated for diffusion - perfusion mismatch. Our primary outcome parameter was final lesion volume, defined by lesion volume on day 6 FLAIR images. Results The association between t-PA and FLAIR lesion volume on day 6 was significantly different for patients with smaller DWI volume compared to patients with larger DWI volume (interaction between DWI and t-PA: p = 0.021). Baseline DWI lesion volume was dichotomized at the median (0.7 ml): final lesion volume at day 6 was larger in patients with large baseline DWI volumes without t-PA treatment (median difference 3, IQR −0.4–9.3 ml). Conversely, in patients with larger baseline DWI volumes final lesion volumes were smaller after t-PA treatment (median difference 0, IQR −4.1–5 ml). However, this did not translate into a significant difference in the mRS at day 90 (p = 0.577). Conclusion Though this study is only hypothesis generating considering the number of cases, we believe that the size of DWI lesion volume may support therapy decision in patients with minor stroke

HEart and BRain interfaces in Acute ischemic Stroke (HEBRAS) – rationale and design of a prospective oberservational cohort study

Background An effective diagnostic work-up in hospitalized patients with acute ischemic stroke is vital to optimize secondary stroke prevention. The HEart and BRain interfaces in Acute ischemic Stroke (HEBRAS) study aims to assess whether an enhanced MRI set-up and a prolonged Holter-ECG monitoring yields a higher rate of pathologic findings as compared to diagnostic procedures recommended by guidelines (including stroke unit monitoring for at least 24 h, echocardiography and ultrasound of brain-supplying arteries). Methods/Design Prospective observational single-center study in 475 patients with acute ischemic stroke and without known atrial fibrillation. Patients will receive routine diagnostic care in hospital as wells as brain MRI, cardiac MRI, MR angiography of the brain-supplying arteries and Holter-monitoring for up to 10 days. Study patients will be followed up for cardiovascular outcomes at 3 and 12 months after enrolment. Discussion By comparing the results of routine diagnostic care to the study-specific MRI/ECG approach, the primary outcome of HEBRAS is the proportion of stroke patients with pathologic diagnostic findings. Predefined secondary outcomes are the association of stroke localization, autonomic dysbalance and cardiac dysfunction as well as the effect of impaired heart-rate-variability on long-term clinical outcome. The investigator-initiated HEBRAS study will assess whether an enhanced MRI approach and a prolonged ECG monitoring yield a higher rate of pathological findings than current standard diagnostic care to determine stroke etiology. These findings might influence current diagnostic recommendations after acute ischemic stroke. Moreover, HEBRAS will determine the extent and clinical impact of stroke-induced cardiac damage

Frequency of silent brain infarction in transient global amnesia

Background: and purpose To determine the frequency and distribution pattern of acute DWI lesions outside the hippocampus in patients clinically presenting with Transient Global Amnesia (TGA). Methods: Consecutive patients clinically presenting with TGA between January 2010 and January 2017 admitted to our hospital were retrospectively evaluated. All patients fulfilled diagnostic criteria of TGA. We analyzed imaging and clinical data of all patients undergoing MRI with high-resolution diffusion-weighted imaging within 72 h from symptom onset. Results: A total of 126 cases were included into the study. Fifty-three percent (n = 71/126) presented with one or more acute lesions in hippocampal CA1-area. Additional acute DWI lesions in other cortical regions were found in 11% (n = 14/126). All patients with DWI lesions outside the hippocampus presented with neurological symptoms typical for TGA (without additional symptoms.) Conclusions: In a relevant proportion of clinical TGA patients, MRI reveals acute ischemic cerebral lesions. Therefore, cerebral MRI should be performed in patients with TGA to identify a possible cardiac involvement and to detect stroke chameleons