Contralateral Hemispheric Cerebral Blood Flow Measured With Arterial Spin Labeling Can Predict Outcome in Acute Stroke.

Background and Purpose- Imaging is frequently used to select acute stroke patients for intra-arterial therapy. Quantitative cerebral blood flow can be measured noninvasively with arterial spin labeling magnetic resonance imaging. Cerebral blood flow levels in the contralateral (unaffected) hemisphere may affect capacity for collateral flow and patient outcome. The goal of this study was to determine whether higher contralateral cerebral blood flow (cCBF) in acute stroke identifies patients with better 90-day functional outcome. Methods- Patients were part of the prospective, multicenter iCAS study (Imaging Collaterals in Acute Stroke) between 2013 and 2017. Consecutive patients were enrolled after being diagnosed with anterior circulation acute ischemic stroke. Inclusion criteria were ischemic anterior circulation stroke, baseline National Institutes of Health Stroke Scale score ≥1, prestroke modified Rankin Scale score ≤2, onset-to-imaging time <24 hours, with imaging including diffusion-weighted imaging and arterial spin labeling. Patients were dichotomized into high and low cCBF groups based on median cCBF. Outcomes were assessed by day-1 and day-5 National Institutes of Health Stroke Scale; and day-30 and day-90 modified Rankin Scale. Multivariable logistic regression was used to test whether cCBF predicted good neurological outcome (modified Rankin Scale score, 0-2) at 90 days. Results- Seventy-seven patients (41 women) met the inclusion criteria with median (interquartile range) age of 66 (55-76) yrs, onset-to-imaging time of 4.8 (3.6-7.7) hours, and baseline National Institutes of Health Stroke Scale score of 13 (9-20). Median cCBF was 38.9 (31.2-44.5) mL per 100 g/min. Higher cCBF predicted good outcome at day 90 (odds ratio, 4.6 [95% CI, 1.4-14.7]; P=0.01), after controlling for baseline National Institutes of Health Stroke Scale, diffusion-weighted imaging lesion volume, and intra-arterial therapy. Conclusions- Higher quantitative cCBF at baseline is a significant predictor of good neurological outcome at day 90. cCBF levels may inform decisions regarding stroke triage, treatment of acute stroke, and general outcome prognosis. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT02225730

Framework and baseline examination of the German National Cohort (NAKO)

The German National Cohort (NAKO) is a multidisciplinary, population-based prospective cohort study that aims to investigate the causes of widespread diseases, identify risk factors and improve early detection and prevention of disease. Specifically, NAKO is designed to identify novel and better characterize established risk and protection factors for the development of cardiovascular diseases, cancer, diabetes, neurodegenerative and psychiatric diseases, musculoskeletal diseases, respiratory and infectious diseases in a random sample of the general population. Between 2014 and 2019, a total of 205,415 men and women aged 19–74 years were recruited and examined in 18 study centres in Germany. The baseline assessment included a face-to-face interview, self-administered questionnaires and a wide range of biomedical examinations. Biomaterials were collected from all participants including serum, EDTA plasma, buffy coats, RNA and erythrocytes, urine, saliva, nasal swabs and stool. In 56,971 participants, an intensified examination programme was implemented. Whole-body 3T magnetic resonance imaging was performed in 30,861 participants on dedicated scanners. NAKO collects follow-up information on incident diseases through a combination of active follow-up using self-report via written questionnaires at 2–3 year intervals and passive follow-up via record linkages. All study participants are invited for re-examinations at the study centres in 4–5 year intervals. Thereby, longitudinal information on changes in risk factor profiles and in vascular, cardiac, metabolic, neurocognitive, pulmonary and sensory function is collected. NAKO is a major resource for population-based epidemiology to identify new and tailored strategies for early detection, prediction, prevention and treatment of major diseases for the next 30 years. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10654-022-00890-5

Non-invasive Magnetic Resonance Perfusion Imaging for Stroke Diagnosis, Treatment Management, and Outcome Prediction

Perfusionsbildgebung unterstützt die Diagnostik im ischämischen Schlaganfall und verbessert dadurch eine individualisierte Therapie. Kontrastmittelfreie und nicht-invasive Bildgebungsverfahren wie arterial spin labeling (ASL) und phase-contrast (PC) Magnetresonanztomographie (MRT) gewinnen hier zunehmend an Bedeutung. Im Rahmen dieser Promotionsarbeit wurde die Anwendung von ASL bei Schlaganfall im chronischen, subakuten und hyperakuten Zeitfenster für den klinischen Gebrauch evaluiert (TOPUP Projekt, Publikation 1; PAS Projekt, Publikation 2; cCBF Projekt, Publikation 3). Zudem wurde ein neues Verfahren zur Quantifizierung des absoluten cerebral blood flows (CBF) für den chronischen Schlaganfall beschrieben (PC-PET Projekt, Publikation 4). Im chronischen Schlaganfall (Charité, TOPUP Projekt, Publikation 1) wurden 13 Patienten mit Stenosen der Hirngefäße untersucht. Dabei wurde CBF mittels ASL und dynamic susceptibility contrast (DSC) MRT gemessen und nach TOPUP-Artefaktkorrektur verglichen. ASL-CBF und DSC-CBF korrelierten bereits vor TOPUP-Korrektur gut im hinteren und mittleren Stromgebiet; nach TOPUP-Korrektur auch im vorderen Stromgebiet. Zur Darstellung des diagnostischen Mehrwertes der ASL-CBF Messung im subakuten Schlaganfall (Charité, PAS Projekt, Publikation 2) wurden 38 Patienten eingeschlossen. Die Hinzunahme der ASL-Perfusionsbildgebung zum klinischen Schlaganfallbildgebungsprotokoll erbrachte eine deutliche Verbesserung der Prognoseabschätzung; Hyperperfusion zeigte sich hierbei als prognostisch günstig, während Hypoperfusion und höhergradige Gefäßstenosen ungünstige Parameter waren. Zur Darstellung der ASL-basierten Hirnperfusion beim hyperakuten Schlaganfall vor Rekanalisation mittels Thrombektomie (Stanford, cCBF Projekt, Publikation 3) wurden 77 Patienten untersucht und eine Methode zur absoluten Quantifizierung der ASL-CBF Werte etabliert. Es wurde gezeigt, dass ein hoher kontralateraler cerebral blood flow (cCBF) Marker einer günstigen Prognose ist. Damit konnte erstmals der prognostische Wert der kontralateralen Hirnperfusion nach fokaler Ischämie beschrieben werden. Zur Kalibrierung der Hirnperfusion im PET/MRT-Scanner wurden 13 Moyamoya-Patienten und 12 gesunde Kontrollpersonen untersucht (Stanford, PC-PET Projekt, Publikation 4). Eine absolute CBF-Quantifizierung ohne arterial input function (AIF) wurde durch nicht-invasive Skalierung der regionalen PET-CBF maps erreicht. Durch dieses Verfahren konnten die Hirnperfusion (PC-PET-CBF) und die zerebrovaskuläre Reaktivität (CVR) in absoluten Werten gemessen werden. Die in dieser Dissertation vorgestellten Studien liefern auf methodischer und inhaltlicher Ebene relevante Beiträge zur klinischen Evaluation nicht-invasiver MRT-Perfusionsbildgebung. Insbesondere ASL steht bereits für klinische Bildgebungsprotokolle routinemäßig zur Verfügung und kann durch kontrastmittelfreie Perfusionsmessungen zukünftig klinische Entscheidungen bei Schlaganfallpatienten unterstützen.Perfusion imaging supports stroke diagnostics and enables informed stroke therapy decisions. Arterial spin labeling (ASL) and phase-contrast (PC) magnetic resonance imaging (MRI) offer contrast-free and non-invasive perfusion measurements. This thesis evaluated the use of ASL in stroke during chronic, subacute, and hyperacute time windows (TOPUP project, publication 1; PAS project, publication 2; cCBF project, publication 3). In addition, a new method was described for quantifying absolute cerebral blood flow (CBF) for chronic strokes (PC-PET project, publication 4). In chronic stroke, 13 patients with stenoses of cerebral vessels were examined (Charité, TOPUP project, publication 1). CBF was measured using ASL and, after TOPUP artifact correction, compared with CBF measurements from dynamic susceptibility contrast (DSC) MRI. ASL-CBF and DSC-CBF values were well correlated in the posterior and middle cerebral artery territory prior to TOPUP correction; after TOPUP correction, that was also the case in the anterior cerebral artery territory. To evaluate the additional diagnostic value of ASL-based CBF in subacute stroke, 38 patients were scanned using a clinically certified ASL sequence (Charité, PAS project, publication 2). Adding ASL perfusion imaging to the standard imaging protocol resulted in a significant improvement in outcome prediction; hyperperfusion was found to be a favorable predictor, while hypoperfusion and high-grade vascular stenosis indicated unfavorable outcome. In 77 patients with hyperacute stroke prior to thrombectomy, absolute quantification of ASL-CBF values was established (Stanford, cCBF project, publication 3). The contralateral cerebral blood flow (cCBF) was investigated as a biomarker for outcome after 90 days. High cCBF values proved to be prognostically favorable. For the first time, the prognostic value of contralateral cerebral perfusion after focal ischemia was determined. To calibrate brain perfusion in the PET/MRI scanner, 13 Moyamoya patients and 12 healthy controls were studied (Stanford, PC-PET project, publication 4). An absolute CBF quantification without arterial input function (AIF) was achieved by scaling regional PET-CBF maps using non-invasive PC-CBF from MRI. This method enabled quantitative measurements of brain perfusion (PC-PET-CBF) and cerebrovascular reactivity (CVR). The studies in this thesis characterized the diagnostic value of new perfusion imaging methods in various clinical settings. ASL is already routinely available for clinical imaging protocols and can support clinical decision making through additional diagnostic information derived from contrast-free and non-invasive perfusion measurements in stroke patients

Diagnostic and prognostic benefit of arterial spin labeling in subacute stroke

Background and Purpose: Brain perfusion measurement in the subacute phase of stroke may support therapeutic decisions. We evaluated whether arterial spin labeling (ASL), a noninvasive perfusion imaging technique based on magnetic resonance imaging (MRI), adds diagnostic and prognostic benefit to diffusion-weighted imaging (DWI) in subacute stroke. Methods: In a single-center imaging study, patients with DWI lesion(s) in the middle cerebral artery (MCA) territory were included. Onset to imaging time was ≤ 7 days and imaging included ASL and DWI sequences. Qualitative (standardized visual analysis) and quantitative perfusion analyses (region of interest analysis) were performed. Dichotomized early outcome (modified Rankin Scale [mRS] 0-2 vs. 3-6) was analyzed in two logistic regression models. Model 1 included DWI lesion volume, age, vascular pathology, admission NIHSS, and acute stroke treatment as covariates. Model 2 added the ASL-based perfusion pattern to Model 1. Receiver-operating-characteristic (ROC) and area-under-the-curve (AUC) were calculated for both models to assess their predictive power. The likelihood-ratio-test compared both models. Results: Thirty-eight patients were included (median age 70 years, admission NIHSS 4, onset to imaging time 67 hr, discharge mRS 2). Qualitative perfusion analysis yielded additional diagnostic information in 84% of the patients. In the quantitative analysis, AUC for outcome prediction was 0.88 (95% CI 0.77-0.99) for Model 1 and 0.97 (95% CI 0.91-1.00) for Model 2. Inclusion of perfusion data significantly improved performance and outcome prediction (p = 0.002) of stroke imaging. Conclusions: In patients with subacute stroke, our study showed that adding perfusion imaging to structural imaging and clinical data significantly improved outcome prediction. This highlights the usefulness of ASL and noninvasive perfusion biomarkers in stroke diagnosis and management

Simultaneous phase‐contrast MRI and PET for noninvasive quantification of cerebral blood flow and reactivity in healthy subjects and patients with cerebrovascular disease

BackgroundH2 15 O-positron emission tomography (PET) is considered the reference standard for absolute cerebral blood flow (CBF). However, this technique requires an arterial input function measured through continuous sampling of arterial blood, which is invasive and has limitations with tracer delay and dispersion.PurposeTo demonstrate a new noninvasive method to quantify absolute CBF with a PET/MRI hybrid scanner. This blood-free approach, called PC-PET, takes the spatial CBF distribution from a static H2 15 O-PET scan, and scales it to the whole-brain average CBF value measured by simultaneous phase-contrast MRI.Study typeObservational.SubjectsTwelve healthy controls (HC) and 13 patients with Moyamoya disease (MM) as a model of chronic ischemic disease.Field strength/sequences3T/2D cardiac-gated phase-contrast MRI and H2 15 O-PET.AssessmentPC-PET CBF values from whole brain (WB), gray matter (GM), and white matter (WM) in HCs were compared with literature values since 2000. CBF and cerebrovascular reactivity (CVR), which is defined as the percent CBF change between baseline and post-acetazolamide (vasodilator) scans, were measured by PC-PET in MM patients and HCs within cortical regions corresponding to major vascular territories. Statistical Tests: Linear, mixed effects models were created to compare CBF and CVR, respectively, between patients and controls, and between different degrees of stenosis.ResultsThe mean CBF values in WB, GM, and WM in HC were 42 ± 7 ml/100 g/min, 50 ± 7 ml/100 g/min, and 23 ± 3 ml/100 g/min, respectively, which agree well with literature values. Compared with normal regions (57 ± 23%), patients showed significantly decreased CVR in areas with mild/moderate stenosis (47 ± 17%, P = 0.011) and in severe/occluded areas (40 ± 16%, P = 0.016). Data Conclusion: PC-PET identifies differences in cerebrovascular reactivity between healthy controls and cerebrovascular patients. PC-PET is suitable for CBF measurement when arterial blood sampling is not accessible, and warrants comparison to fully quantitative H2 15 O-PET in future studies.Level of evidence3 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2019. J. Magn. Reson. Imaging 2020;51:183-194

Contralateral Hemispheric Cerebral Blood Flow Measured With Arterial Spin Labeling Can Predict Outcome in Acute Stroke.

Background and Purpose- Imaging is frequently used to select acute stroke patients for intra-arterial therapy. Quantitative cerebral blood flow can be measured noninvasively with arterial spin labeling magnetic resonance imaging. Cerebral blood flow levels in the contralateral (unaffected) hemisphere may affect capacity for collateral flow and patient outcome. The goal of this study was to determine whether higher contralateral cerebral blood flow (cCBF) in acute stroke identifies patients with better 90-day functional outcome. Methods- Patients were part of the prospective, multicenter iCAS study (Imaging Collaterals in Acute Stroke) between 2013 and 2017. Consecutive patients were enrolled after being diagnosed with anterior circulation acute ischemic stroke. Inclusion criteria were ischemic anterior circulation stroke, baseline National Institutes of Health Stroke Scale score ≥1, prestroke modified Rankin Scale score ≤2, onset-to-imaging time <24 hours, with imaging including diffusion-weighted imaging and arterial spin labeling. Patients were dichotomized into high and low cCBF groups based on median cCBF. Outcomes were assessed by day-1 and day-5 National Institutes of Health Stroke Scale; and day-30 and day-90 modified Rankin Scale. Multivariable logistic regression was used to test whether cCBF predicted good neurological outcome (modified Rankin Scale score, 0-2) at 90 days. Results- Seventy-seven patients (41 women) met the inclusion criteria with median (interquartile range) age of 66 (55-76) yrs, onset-to-imaging time of 4.8 (3.6-7.7) hours, and baseline National Institutes of Health Stroke Scale score of 13 (9-20). Median cCBF was 38.9 (31.2-44.5) mL per 100 g/min. Higher cCBF predicted good outcome at day 90 (odds ratio, 4.6 [95% CI, 1.4-14.7]; P=0.01), after controlling for baseline National Institutes of Health Stroke Scale, diffusion-weighted imaging lesion volume, and intra-arterial therapy. Conclusions- Higher quantitative cCBF at baseline is a significant predictor of good neurological outcome at day 90. cCBF levels may inform decisions regarding stroke triage, treatment of acute stroke, and general outcome prognosis. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT02225730

Framework and baseline examination of the German National Cohort (NAKO)

The German National Cohort (NAKO) is a multidisciplinary, population-based prospective cohort study that aims to investigate the causes of widespread diseases, identify risk factors and improve early detection and prevention of disease. Specifically, NAKO is designed to identify novel and better characterize established risk and protection factors for the development of cardiovascular diseases, cancer, diabetes, neurodegenerative and psychiatric diseases, musculoskeletal diseases, respiratory and infectious diseases in a random sample of the general population. Between 2014 and 2019, a total of 205,415 men and women aged 19–74 years were recruited and examined in 18 study centres in Germany. The baseline assessment included a face-to-face interview, self-administered questionnaires and a wide range of biomedical examinations. Biomaterials were collected from all participants including serum, EDTA plasma, buffy coats, RNA and erythrocytes, urine, saliva, nasal swabs and stool. In 56,971 participants, an intensified examination programme was implemented. Whole-body 3T magnetic resonance imaging was performed in 30,861 participants on dedicated scanners. NAKO collects follow-up information on incident diseases through a combination of active follow-up using self-report via written questionnaires at 2–3 year intervals and passive follow-up via record linkages. All study participants are invited for re-examinations at the study centres in 4–5 year intervals. Thereby, longitudinal information on changes in risk factor profiles and in vascular, cardiac, metabolic, neurocognitive, pulmonary and sensory function is collected. NAKO is a major resource for population-based epidemiology to identify new and tailored strategies for early detection, prediction, prevention and treatment of major diseases for the next 30 years