Katharina Schregel

Demyelination reduces brain parenchymal stiffness quantified in vivo by magnetic resonance elastography.

The detection of pathological tissue alterations by manual palpation is a simple but essential diagnostic tool, which has been applied by physicians since the beginnings of medicine. Recently, the virtual “palpation” of the brain has become feasible using magnetic resonance elastography, which quantifies biomechanical properties of the brain parenchyma by analyzing the propagation of externally elicited shear waves. However, the precise molecular and cellular patterns underlying changes of viscoelasticity measured by magnetic resonance elastography have not been investigated up to date. We assessed changes of viscoelasticity in a murine model of multiple sclerosis, inducing reversible demyelination by feeding the copper chelator cuprizone, and correlated our results with detailed histological analyses, comprising myelination, extracellular matrix alterations, immune cell infiltration and axonal damage. We show firstly that the magnitude of the complex shear modulus decreases with progressive demyelination and global extracellular matrix degradation, secondly that the loss modulus decreases faster than the dynamic modulus during the destruction of the corpus callosum, and finally that those processes are reversible after remyelination.

Effects of Workflow Optimization in Endovascularly Treated Stroke Patients – A Pre-Post Effectiveness Study

Endovascular treatment of acute ischemic stroke has become standard of care for patients with large artery occlusion. Early restoration of blood flow is crucial for a good clinical outcome. We introduced an interdisciplinary standard operating procedure (SOP) between neuroradiologists, neurologists and anesthesiologists in order to streamline patient management. This study analyzes the effect of optimized workflow on periprocedural timings and its potential influence on clinical outcome. Data were extracted from a prospectively maintained university hospital stroke database. The standard operating procedure was established in February 2014. Of the 368 acute stroke patients undergoing endovascular treatment between 2008 and 2015, 278 patients were treated prior to and 90 after process optimization. Outcome measures were periprocedural time intervals and residual functional impairment. After implementation of the SOP, time from symptom onset to reperfusion was significantly reduced (median 264 min prior and 211 min after SOP-introduction (IQR 228–32 min and 161–278 min, respectively); P<0.001). Especially faster supply of imaging and prompt transfer of patients to the angiography suite contributed to this effect. Time between hospital admission and groin puncture was reduced by half after process optimization (median 64 min after versus 121 min prior to SOP-introduction (IQR 54–77 min and 96–161 min, respectively); P<0.001). Clinical outcome was significantly better after workflow optimization as measured with the modified Rankin Scale (common odds ratio (OR) 0.56; 95% CI 0.32–0.98; P = 0.038). Optimization of workflow and interdisciplinary teamwork significantly improved the outcome of patients with acute ischemic stroke due to a significant reduction of in-hospital examination, transportation, imaging and treatment times.

One-Stop Management of Acute Stroke Patients: Minimizing Door-to-Reperfusion Times

Background and Purpose— Intrahospital time delays significantly affect the neurological outcome of stroke patients with large-vessel occlusion. This study was conducted to determine whether a one-stop management can reduce intrahospital times of patients with acute large-vessel occlusion. Methods— In this observational study, we report the first 30 consecutive stroke patients imaged and treated in the same room. As part of our protocol, we transported patients with a National Institutes of Health Stroke Scale score of ≥10 directly to the angio suite, bypassing multidetector computed tomography (CT). Preinterventional imaging consisted of noncontrast flat detector CT and flat detector CT angiography, acquired with an angiography system. Patients with large-vessel occlusions remained on the angio table and were treated with mechanical thrombectomy; patients with small artery occlusions were treated with intravenous thrombolysis, whereas patients with an intracranial hemorrhage and stroke mimics were treated as per guidelines. Door-to-groin puncture times were recorded and compared with our past results. Results— Thirty patients were transferred directly to our angio suite from June to December 2016. The time from symptom onset to admission was 105 minutes. Ischemic stroke was diagnosed in 22 of 30 (73%) patients, 4 of 30 (13.5%) had an intracranial hemorrhage, and 4 of 30 (13.5) were diagnosed with a Todd’s paresis. Time from admission to groin puncture was 20.5 minutes. Compared with 44 patients imaged with multidetector CT in the first 6 months of 2016, door-to-groin times were significantly reduced (54.5 minutes [95% confidence interval, 47–61] versus 20.5 minutes [95% confidence interval, 17–26]). Conclusions— In this small series, a one-stop management protocol of selected stroke patients using latest generation flat detector CT led to a significant reduction of intrahospital times.

Bridging-therapy with intravenous recombinant tissue plasminogen activator improves functional outcome in patients with endovascular treatment in acute stroke ☆

BACKGROUND Although endovascular treatment for proximal cerebral vessel occlusion is very effective, it remains controversial if intravenous thrombolysis (IVT) prior to endovascular treatment is superior compared to endovascular treatment alone. In this study we compared functional outcomes and recanalization rates of endovascularly treated stroke patients with and without bridging IVT. METHODS Patients with acute large artery occlusion within the anterior and posterior cerebral circulation eligible for intraarterial revascularization with and without prior IVT were included in this monocentric, prospective observational study. Modified Rankin Scale (mRS) and National Institute of Health Stroke Scale (NIHSS) were determined at baseline, discharge and 90-days follow up after stroke. Successful reperfusion was defined as a Thrombolysis in Cerebral Infarction (TICI) scale 2b-3. RESULTS Of the 109 patients included, 81 (74%) received bridging therapy with i.v.-rtPA prior to endovascular treatment, 28 (26%) received endovascular treatment alone. There was no difference in groin-to-reperfusion time between the groups (54 vs 50min; p=0.657), but a trend towards a higher reperfusion rate in patients with bridging therapy (69 vs 15 patients, p=0.099). Mean improvement of the NIHSS during hospitalization was 8 points (SD; ±8) in the bridging-group and 2 points (SD, ±7) in the non-bridging-group (p=0.001). Number of patients with discharge mRS 0-2 (34 vs 5; p=0.024) and 90-days mRS 0-2 (35 vs 6; p=0.061) was higher in the bridging-group compared to the non-bridging-group. CONCLUSIONS This study provides evidence that bridging therapy with i.v.-rtPA improves functional outcome in patients eligible for endovascular treatment. Further studies are needed to confirm our findings and to identify patients most likely benefitting from bridging therapy.

Association between Embolic Stroke Patterns, ESUS Etiology, and New Diagnosis of Atrial Fibrillation: A Secondary Data Analysis of the Find-AF Trial

Background. Atrial fibrillation (AF) is an important cause of embolic stroke of undetermined source (ESUS). Imaging-patterns like multiple infarcts, simultaneous involvement of different circulations, infarcts of different ages, and isolated cortical infarcts are likely to indicate cardioembolic stroke. The aim of our study was to evaluate the association between embolic stroke patterns, ESUS, and the new diagnosis of AF. Methods. Stroke etiology and imaging characteristics from patients included in the Find-AF study were obtained. Embolic stroke patterns in CT- or MR-imaging were correlated with the diagnosis of ESUS as well as the short- (on baseline ECG and during 7-day Holter) and long-term (12-month follow-up) diagnosis of AF. Results. From 281 patients included in the Find-AF study, 127 (45.2%) patients with ischemic lesions detected in CT or MRI were included. 26 (20.5%) of these patients had ESUS. At least one embolic stroke pattern was detected in 67 (52.7%) patients. Embolic stroke patterns were not associated with ESUS (OR 1.57, 0.65–3.79, p = 0.317), the short-term (OR 0.64, 0.26–1.58, p = 0.327) or long-term diagnosis of AF (OR 0.72, 0.31–1.68, p = 0.448). Conclusions. This secondary data analysis of the Find-AF study could not provide evidence for an association between embolic stroke patterns, ESUS, and the new diagnosis of AF.

Latest generation of flat detector CT as a peri-interventional diagnostic tool: a comparative study with multidetector CT

Background and purpose Flat detector CT (FDCT) has been used as a peri-interventional diagnostic tool in numerous studies with mixed results regarding image quality and detection of intracranial lesions. We compared the diagnostic aspects of the latest generation FDCT with standard multidetector CT (MDCT). Materials and methods 102 patients were included in our retrospective study. All patients had undergone interventional procedures. FDCT was acquired peri-interventionally and compared with postinterventional MDCT regarding depiction of ventricular/subarachnoidal spaces, detection of intracranial hemorrhage, and delineation of ischemic lesions using an ordinal scale. Ischemic lesions were quantified with the Alberta Stroke Program Early CT Scale (ASPECTS) on both examinations. Two neuroradiologists with varying grades of experience and a medical student scored the anonymized images separately, blinded to the clinical history. Results The two methods were of equal diagnostic value regarding evaluation of the ventricular system and the subarachnoidal spaces. Subarachnoidal, intraventricular, and parenchymal hemorrhages were detected with a sensitivity of 95%, 97%, and 100% and specificity of 97%, 100%, and 99%, respectively, using FDCT. Gray–white differentiation was feasible in the majority of FDCT scans, and ischemic lesions were detected with a sensitivity of 71% on FDCT, compared with MDCT scans. The mean difference in ASPECTS values on FDCT and MDCT was 0.5 points (95% CI 0.12 to 0.88). Conclusions The latest generation of FDCT is a reliable and accurate tool for the detection of intracranial hemorrhage. Gray–white differentiation is feasible in the supratentorial region.

MRI-based diagnostic biomarkers for early onset pediatric multiple sclerosis

Currently, it is unclear whether pediatric multiple sclerosis (PMS) is a pathoetiologically homogeneous disease phenotype due to clinical and epidemiological differences between early and late onset PMS (EOPMS and LOPMS). Consequently, the question was raised whether diagnostic guidelines need to be complemented by specific EOPMS markers. To search for such markers, we analyzed cerebral MRI images acquired with standard protocols using computer-based classification techniques. Specifically, we applied classification algorithms to gray (GM) and white matter (WM) tissue probability parameters of small brain regions derived from T2-weighted MRI images of EOPMS patients (onset <12 years), LOPMS patients (onset ≥12 years), and healthy controls (HC). This was done for PMS subgroups matched for disease duration and participant age independently. As expected, maximal diagnostic information for distinguishing PMS patients and HC was found in a periventricular WM area containing lesions (87.1% accuracy, p < 2.2 × 10−5). MRI-based biomarkers specific for EOPMS were identified in prefrontal cortex. Specifically, a coordinate in middle frontal gyrus contained maximal diagnostic information (77.3%, p = 1.8 × 10−4). Taken together, we were able to identify biomarkers reflecting pathognomonic processes specific for MS patients with very early onset. Especially GM involvement in the separation between PMS subgroups suggests that conventional MRI contains a richer set of diagnostically informative features than previously assumed.

Validation of collateral scoring on flat-detector multiphase CT angiography in patients with acute ischemic stroke

Background The pivotal impact of collateral circulation on outcomes in endovascular therapy has fueled the development of numerous CTA collateral scales, yet synchronized validation with conventional angiography has never occurred. We validated multiphase flat-detector CTA (mpFDCTA) for collateral imaging in patients undergoing endovascular stroke treatment. Materials and methods Consecutive acute ischemic stroke patient data, including mpFDCTA shortly followed by digital subtraction angiography (DSA), in the setting of acute ICA- or MCA-occlusions were analyzed. An independent core lab scored mpFDCTA with an established collateral scale and separately graded American Society of Interventional and Therapeutic Neuroradiology (ASITN) collateral score on DSA, blind to all other data. Results 24 consecutive cases (age 76.7 ± 7.3 years; 58.3% women; baseline NIHSS median 17 (4–23)) of acute ICA- or MCA-occlusion were analyzed. Time from mpFDCTA to intracranial DSA was 23.04 ± 7.6 minutes. Median mpFDCTA collateral score was 3 (0–5) and median DSA ASITN collateral score was 2 (0–3), including the full range of potential collateral grades. mpFDCTA and ASITN collateral score were strongly correlated (r = 0.86, p<0.001). mpFDCTA provided more complete collateral data compared to selective DSA injections in cases of ICA-occlusion. ROC analyses for prediction of clinical outcomes revealed an AUC of 0.76 for mpFDCTA- and 0.70 for DSA ASITN collaterals. Conclusions mpFDCTA in the angiography suite provides a validated measure of collaterals, offering distinct advantages over conventional angiography. Direct patient transfer to the angiography suite and mpFDCTA collateral grading provides a novel and reliable triage paradigm for acute ischemic stroke.

Characterization of glioblastoma in an orthotopic mouse model with magnetic resonance elastography

Glioblastoma (GBM) is the most common primary brain tumor. It is highly malignant and has a correspondingly poor prognosis. Diagnosis and monitoring are mainly accomplished with MRI, but remain challenging in some cases. Therefore, complementary methods for tumor detection and characterization would be beneficial. Using magnetic resonance elastography (MRE), we performed a longitudinal study of the biomechanical properties of intracranially implanted GBM in mice and compared the results to histopathology. The biomechanical parameters of viscoelastic modulus, shear wave speed and phase angle were significantly lower in tumors compared with healthy brain tissue and decreased over time with tumor progression. Moreover, some MRE parameters revealed sub‐regions at later tumor stages, which were not easily detectable on anatomical MRI images. Comparison with histopathology showed that softer tumor regions contained necrosis and patches of viable tumor cells. In contrast, areas of densely packed tumor cells and blood vessels identified with histology coincided with higher values of viscoelastic modulus and shear wave speed. Interestingly, the phase angle was independent from these anatomical variations. In summary, MRE depicted longitudinal and morphological changes in GBM and may prove valuable for tumor characterization in patients.

Functional neuro-imaging with magnetic resonance elastography

Evaluate changes in the shear modulus of brain tissue as a new measure of localized brain function. A spin-echo magnetic resonance elastography (MRE) sequence was modified to allow two interleaved paradigms: stimulus ON/OFF. To avoid neuronal habituation, a paradigm was active for 9s before switching to the other paradigm. After each paradigm switch, a period of 1.8 s was allowed for hemodynamic equilibrium. Seven healthy black mice were studied. An electrical current to the hind limb, ~1 mA, 3 Hz, pulse width ~250 ms, was used as the functional stimulus. A separate control scan was also performed where no stimulus was applied for either paradigm. Vibration frequency = 1kHz. In six of the seven animals, a localized increase in G’ was observed in the somatosensory and motor cortex areas, whereas no difference was observed in the control scan. The average increase of G’ = 14%. Two potential mechanisms were considered: (i) a vascular effect similar to BOLD in fMRI and (ii) calcium influx into the neurons. Th...