Ultrasonography Grading of Internal Carotid Artery Disease: Multiparametric German Society of Ultrasound in Medicine (DEGUM) versus Society of Radiologists in Ultrasound (SRU) Consensus Criteria.

PURPOSE: We sought to determine the diagnostic agreement between the revised ultrasonography approach by the German Society of Ultrasound in Medicine (DEGUM) and the established Society of Radiologists in Ultrasound (SRU) consensus criteria for the grading of carotid artery disease. MATERIALS AND METHODS: Post-hoc analysis of a prospective multicenter study, in which patients underwent ultrasonography and digital subtraction angiography (DSA) of carotid arteries for validation of the DEGUM approach. According to DEGUM and SRU ultrasonography criteria, carotid arteries were independently categorized into clinically relevant NASCET strata (normal, mild [1-49 %], moderate [50-69 %], severe [70-99 %], occlusion). On DSA, carotid artery findings according to NASCET were considered the reference standard. RESULTS: We analyzed 158 ultrasonography and DSA carotid artery pairs. There was substantial agreement between both ultrasonography approaches for severe (κw 0.76, CI95 %: 0.66-0.86), but only fair agreement for moderate (κw 0.38, CI95 %: 0.19-0.58) disease categories. Compared with DSA, both ultrasonography approaches were of equal sensitivity (79.7 % versus 79.7 %; p = 1.0) regarding the identification of severe stenosis, yet the DEGUM approach was more specific than the SRU approach (70.2 % versus 56.4 %, p = 0.0002). There was equality of accuracy parameters (p > 0.05) among both ultrasonography approaches for the other ranges of carotid artery disease. CONCLUSION: While the sensitivity was equivalent, false-positive identification of severe carotid artery stenosis appears to be more frequent when using the SRU ultrasonography approach than the revised multiparametric DEGUM approach.

Intravenous Thrombolysis by Telestroke in the 3- to 4.5-h Time Window.

Background: While intravenous thrombolysis (IVT) in ischemic stroke can be safely applied in telestroke networks within 3 h from symptom onset, there is a lack of evidence for safety in the expanded 3- to 4. 5-h time window. We assessed the safety and short-term efficacy of IVT in acute ischemic stroke (AIS) in the expanded time window delivered through a hub-and-spoke telestroke network. Methods: Observational study of patients with AIS who received IVT at the Stroke Eastern Saxony Telemedical Network between 01/2014 and 12/2015. We compared safety data including symptomatic intracerebral hemorrhage (sICH; according to European Cooperative Acute Stroke Study II definition) and any intracerebral hemorrhage (ICH) between patients admitted to telestroke spoke sites and patients directly admitted to a tertiary stroke center representing the hub of the network. We also assessed short-term efficacy data including favorable functional outcome (i.e., modified Rankin Scale ≤ 2) and National Institutes of Health Stroke Scale (NIHSS) at discharge, hospital discharge disposition, and in-hospital mortality. Results: In total, 152 patients with AIS were treated with IVT in the expanded time window [spoke sites, n = 104 (26.9%); hub site, n = 48 (25.9%)]. Patients treated at spoke sites had less frequently a large vessel occlusion [8/104 (7.7) vs. 20/48 (41.7%); p < 0.0001], a determined stroke etiology (p < 0.0001) and had slightly shorter onset-to-treatment times [210 (45) vs. 228 (58) min; p = 0.02] than patients who presented to the hub site. Both cohorts did not display any further differences in demographics, vascular risk factors, median baseline NIHSS scores, or median baseline Alberta stroke program early CT score (p > 0.05). There was no difference in the frequency of sICH (4.9 vs. 6.3%; p = 0.71) or any ICH (8.7 vs. 16.7%; p = 0.15). Neither there was a difference regarding favorable functional outcome (44.1 vs. 39.6%; p = 0.6) nor median NIHSS [3 (5.5) vs. 2.5 (5.75); p = 0.92] at discharge, hospital discharge disposition (p = 0.28), or in-hospital mortality (9.6 vs. 8.3%; p = 1.0). Multivariable modeling did not reveal an association between telestroke and sICH or favorable functional outcome (p > 0.05). Conclusions: Delivery of IVT in the expanded 3- to 4.5-h time window through a telestroke network appears to be safe with equivalent short-term functional outcomes for spoke-and-hub center admissions.

Noninvasive assessment and quantification of tumor vascularization using [18F]FDG-PET/CT and CE-CT in a tumor model with modifiable angiogenesis-an animal experimental prospective cohort study.

BACKGROUND: This study investigated the noninvasive assessment of tumor vascularization with clinical F-18-fluorodeoxyglucose positron emission tomography/computed tomography and contrast-enhanced computed tomography ([18F]FDG-PET/CT and CE-CT) in experimental human xenograft tumors with modifiable vascularization and compared results to histology. Tumor xenografts with modifiable vascularization were established in 71 athymic nude rats by subcutaneous transplantation of human non-small-cell lung cancer (NSCLC) cells. Four different groups were transplanted with two different tumor cell lines (either A549 or H1299) alone or tumors co-transplanted with rat glomerular endothelial (RGE) cells, the latter to increase vascularization. Tumors were assessed noninvasively by [18F]FDG PET/CT and contrast-enhanced CT (CE-CT) using clinical scanners. This was followed by histological examinations evaluating tumor vasculature (CD-31 and intravascular fluorescent beads). RESULTS: In both tumor lines (A549 and H1299), co-transplantation of RGE cells resulted in faster growth rates [maximal tumor diameter of 20 mm after 22 (± 1.2) as compared to 45 (± 1.8) days, p < 0.001], higher microvessel density (MVD) determined histologically after CD-31 staining [171.4 (± 18.9) as compared to 110.8 (± 11) vessels per mm2, p = 0.002], and higher perfusion as indicated by the number of beads [1.3 (± 0.1) as compared to 1.1 (± 0.04) beads per field of view, p = 0.001]. In [18F]FDG-PET/CT, co-transplanted tumors revealed significantly higher standardized uptake values [SUVmax, 2.8 (± 0.2) as compared to 1.1 (± 0.1), p < 0.001] and larger metabolic active volumes [2.4 (± 0.2) as compared to 0.4 (± 0.2) cm3, p < 0.001] than non-co-transplanted tumors. There were significant correlations for vascularization parameters derived from histology and [18F]FDG PET/CT [beads and SUVmax, r = 0.353, p = 0.005; CD-31 and SUVmax, r = 0.294, p = 0.036] as well as between CE-CT and [18F]FDG PET/CT [contrast enhancement and SUVmax, r = 0.63, p < 0.001; vital CT tumor volume and metabolic PET tumor volume, r = 0.919, p < 0.001]. CONCLUSIONS: In this study, a human xenograft tumor model with modifiable vascularization implementable for imaging, pharmacological, and radiation therapy studies was successfully established. Both [18F]FDG-PET/CT and CE-CT are capable to detect parameters closely connected to the degree of tumor vascularization, thus they can help to evaluate vascularization in tumors noninvasively. [18F]FDG-PET may be considered for characterization of tumors beyond pure glucose metabolism and have much greater contribution to diagnostics in oncology.

Validation of Multiparametric Ultrasonography Criteria with Digital Subtraction Angiography in Carotid Artery Disease: A Prospective Multicenter Study.

PURPOSE: The German Society of Ultrasound in Medicine (DEGUM) recently revised its multiparametric criteria for duplex ultrasonography (DUS) grading of internal carotid artery (ICA) disease. We determined the diagnostic accuracy of the revised DEGUM criteria for ultrasonography grading of ICA disease in a prospective multicenter study. MATERIALS AND METHODS: We evaluated consecutive patients who underwent digital subtraction angiography of the extracranial carotid arteries at four tertiary care hospitals. Blinded investigators graded ICA disease according to DEGUM-recommended ultrasonography criteria and calculated NASCET-type percent stenosis from angiography images. Endpoints included overall classification accuracy, prediction of clinically relevant disease categories and between-test agreement in the continuous range of percent stenosis. RESULTS: A total of 121 patients (median age: 69 [IQR, 16] years; 74 % men; median time between DUS and angiography: 1 day [IQR, 2]) provided 163 DUS-angiography carotid artery pairs. The classification accuracy of the DEGUM criteria to predict stenosis within 10 % increments as compared to angiography was 34.9 % (95 % CI, 28.0 - 42.6). The sensitivity of DUS for the detection of moderate (50 - 69 %) and severe (70 - 99 %) stenosis was 35 % and 81 %, with an overall accuracy of 73 % and 74 %, respectively. The specificity was 89 % and 69 %, respectively. Considering the continuous spectrum of the disease (0 - 100 %), the Bland-Altman interval limit of agreement was 51 %. CONCLUSION: At laboratories experienced with ultrasound grading of the extracranial ICA, the revised DEGUM multiparametric ultrasonography criteria do not eliminate the need for a confirmatory test for the identification of clinically relevant grades of the disease.

Efficacy and safety of direct aspiration first pass technique versus stent-retriever thrombectomy in acute basilar artery occlusion-a retrospective single center experience.

INTRODUCTION: The study aimed to compare efficacy and safety of aspiration thrombectomy (AT) to stentriever thrombectomy (SRT) in patients with basilar artery (BA) occlusion (BAO). METHODS: We retrospectively included patients with the following characteristics: acute BAO or occlusion of the intracranial vertebral artery (ICVA) and endovascular therapy (EVT) with stentriever (SRT) or aspiration thrombectomy (AT). Additional extra- but not intracranial EVT and intravenous thrombolysis (IVT) were allowed. RESULTS: Between January 2013 and April 2016, 33 patients fulfilled the criteria (13 treated with SRT, 20 with AT). Prior to EVT, 23 (70%) patients received IVT. The proximal intracranial occlusion was ICVA in 2 patients, proximal BA in 5 patients, middle BA in 20 patients, and distal BA in 6 patients. Mean time to treatment was 334 min (95% CI 276-391 min). Procedure duration differed significantly (p = 0.002) as follows: 97 min with SRT (95% CI 69-124 min) and 55 min with AT (95% CI 43-66 min). Recanalization (arterial occlusive lesion (AOL) 2/3) was achieved in 26 patients (79%). Complete recanalization (AOL 3) happened more often with AT (75% (95% CI 65-85%)) compared to SRT (46% (95% CI 32-60%)). Conversion rate 6% (two patients). Hemorrhages occurred in 12 (36%) patients, periprocedural complications in eight (three dissections, five embolizations to new territory) (no group difference). Ten patients (30%) had a favorable outcome (mRS ≤3) at discharge; mortality rate was 24% (eight deaths) (no group difference). CONCLUSION: In primarily embolic BAO, aspiration thrombectomy was faster, effective and not detrimental to outcome as compared to stentriever thrombectomy. Thus, it may be justified to use aspiration thrombectomy as first-line treatment in these patients.

Collateral state and the effect of endovascular reperfusion therapy on clinical outcome in ischemic stroke patients.

PURPOSE: Clinically successful endovascular therapy (EVT) in ischemic stroke requires reliable noninvasive pretherapeutic selection criteria. We investigated the association of imaging parameters including CT angiographic collaterals and degree of reperfusion with clinical outcome after EVT. METHODS: In our database, we identified 93 patients with large vessel occlusion in the anterior circulation treated with EVT. Besides clinical data, we assessed the baseline Alberta Stroke Program Early CT score (ASPECTS) on noncontrast CT (NCCT) and CT angiography (CTA) source images, collaterals (CT-CS) and clot burden score (CBS) on CTA and the degree of reperfusion after EVT on angiography. Three readers, blinded to clinical information, evaluated the images in consensus. Data-driven multivariable ordinal regression analysis identified predictors of good outcome after 90 days as measured with the modified Rankin Scale. RESULTS: Successful angiographic reperfusion (OR 26.50; 95%-CI 9.33-83.61) and good collaterals (OR 9.69; 95%-CI 2.28-59.27) were independent predictors of favorable outcome along with female sex (OR 0.35; 95%-CI 0.14-0.85), younger age (OR 0.88; 95%-CI 0.83-0.92) and higher NCCT ASPECTS (OR 2.54; 95%-CI 1.01-6.63). Outcome was best in patients with good collaterals and successful reperfusion, but there was no statistical interaction between collaterals and reperfusion. CONCLUSIONS: CTA-collateral status was the strongest pretherapeutic predictor of favorable outcome in ischemic stroke patients treated with EVT. CTA-collaterals are thus well suited for patient selection in EVT. However, the independent effect of reperfusion on outcome tended to be stronger than that of CTA-collaterals.

Telemedical Brain Computed Tomography Misinterpretation by Stroke Neurologists Is Not Associated with Thrombolysis-Related Intracranial Hemorrhage.

BACKGROUND: The Stroke Eastern Saxony Network (SOS-NET) provides telecare for acute stroke patients. Stroke neurologists recommend intravenous thrombolysis based on clinical assessment and cerebral computed tomography (CT) evaluation using Alberta Stroke Program Early CT score (ASPECTS). We sought to assess whether ASPECTS misinterpretation by stroke neurologists was associated with thrombolysis-related symptomatic intracranial hemorrhage (sICH). METHODS: We retrospectively analyzed consecutive SOS-NET patients treated with thrombolytics from July 2007 to July 2012. Experienced neuroradiologists re-evaluated CT scans blinded to clinical information providing reference standard. We defined ASPECTS underestimation as ASPECTS stroke neurologist--ASPECTS neuroradiologist more than 1 point. Primary outcome was sICH by European Cooperative Acute Stroke Study II criteria. Secondary outcome was unfavorable outcome at discharge defined as modified Rankin Scale scores 3 or more. RESULTS: Of 1659 patients with acute ischemic stroke, thrombolysis was performed in 657 patients. Complete primary outcome and imaging data were available for 432 patients (median age, 75; interquartile range [IQR], 12 years; National Institutes of Health Stroke Scale score, 12 [IQR, 11]; 52.8% women). Nineteen patients (4.4%) had sICH, and 259 patients (60.0%) had an unfavorable outcome at discharge. Interobserver agreement between ASPECTS assessment was fair (κ = .51). ASPECTS underestimation was neither associated with sICH (adjusted odds ratio (OR), 1.32; 95% confidence interval (CI), .36-4.83, P = .68) nor unfavorable outcome (adjusted OR, 1.10; 95% CI, .47-2.54; P = .83). CONCLUSIONS: Despite fair interrater agreement between stroke neurologists and expert neuroradiologists, underestimation of ASPECTS by the former was not associated with thrombolysis-related sICH in our telestroke network.

Exploratory prospective trial of hypoxia-specific PET imaging during radiochemotherapy in patients with locally advanced head-and-neck cancer.

PURPOSE: To explore in a prospective trial the prognostic value of hypoxia imaging before and during radiochemotherapy in patients with locally advanced head and neck cancer. PATIENTS AND METHODS: Twenty-five patients with stage III/IV head and neck cancer were investigated with [(18)F]-fluoromisonidazole (FMISO) PET/CT at four time points during radiochemotherapy (baseline, 8-10 Gy, 18-20 Gy,50-60 Gy). FMISO PET/CT image parameters were extracted including maximum-tumour-to-background (TBR(max)) and thresholded volume at different TBR ratios. CT volume and baseline FDG-PET/CT image parameters were also included. Parameters at all time points were investigated for their prognostic value with the local-progression-free-survival endpoint (LPFS). Significance was evaluated with multivariate Cox (including clinical parameters) and Log-rank tests. RESULTS: FMISO-image parameters were found to have a strong association with the LPFS endpoint, and were strongest at the week 1 and 2 time points (p = 0.023-0.048 and 0.042-0.061 respectively on multivariate Cox). Parameters measured at baseline were only significant on univariate analysis. None of the clinical parameters, and also FDG- or CT-delineated volumes, were significantly associated with LPFS. CONCLUSION: This prospective, exploratory study demonstrated that FMISO-PET/CT imaging during the initial phase of treatment carries strong prognostic value. FMISO-PET/CT imaging at 1 or 2 weeks during treatment could be promising way to select patients that would benefit from hypoxia modification or dose-escalated treatment. A validation study is on-going.

Quantitative modifications of TNM staging, clinical staging and therapeutic intent by FDG-PET/CT in patients with non small cell lung cancer scheduled for radiotherapy--a retrospective study.

It is obvious that FDG-PET has added value to CT, but there is still insufficient data to define the role of FDG-PET/CT in clinical practice. Usually data are gathered from multiple sources and in consequence the information obtained is heterogeneous and not always comparable between patients. To alleviate this lack of data, we attempted to investigate the differences in staging and therapeutic intent as compared with conventional staging in non small cell lung cancer (NSCLC) patients scheduled for RT after adding FDG-PET/CT to conventional staging in 104 included subjects. In contrary to the multicentric studies relying on patients medical records from outside institutions, these data were generated entirely with the institution's PET/CT unit. Significant modifications of both, M-stage and clinical stage were detected after inclusion of FDG-PET/CT data (p<0.001), while there was no statistically significant T- and N-stage modification. Overall implenting FDG-PET/CT revised RT intention decision in 34% of patients. FDG-PET/CT provides enhanced staging capabilities compared to conventional CT in staging of non small cell lung carcinoma and allows improved selection of patients suitable for curative intention, while avoiding unnecessary irradiation and costs in patients eligible to palliative intention.

Early FDG PET at 10 or 20 Gy under chemoradiotherapy is prognostic for locoregional control and overall survival in patients with head and neck cancer.

PURPOSE: Our study aimed to explore the optimal timing as well as the most appropriate prognostic parameter of (18)F-fluorodeoxyglucose positron emission tomography (FDG PET) during chemoradiotherapy (CRT) for an early prediction of outcome for patients with head and neck squamous cell carcinoma (HNSCC). METHODS: Serial PET data (before and three times during CRT) of 37 patients with advanced stage HNSCC, receiving combined CRT between 2005 and 2009, were evaluated. The maximum standardized uptake value (SUV(max)), the average SUV (SUV(mean)) and the gross tumour volume determined by FDG PET (GTV PET), based on a source to background algorithm, were analysed. Stratified actuarial analysis was performed for overall survival (OS), disease-free survival (DFS) and locoregional control (LRC). The median follow-up time was 26 months (range 8-50). RESULTS: For all patients, OS was 51%, DFS 44% and LRC 55% after 2 years. The 2-year OS (88%) and 2-year LRC (88%) were higher for patients whose SUV(max) of the primary tumour decreased 50% or more from the beginning (0 Gy) to week 1 or 2 (10 or 20 Gy) of CRT (ΔSUV(max10/20) ≥ 50%) than for patients with ΔSUV(max20) < 50% (2-year OS = 38%; p = 0.02; 2-year LRC 40%; p = 0.06). A pretreatment GTV PET below the median of 10.2 ml predicted a better 2-year OS (34% for GTV PET ≥ 10.2 ml vs 83% for GTV PET < 10.2 ml; p = 0.02). CONCLUSION: The decrease of SUV(max) from before (0 Gy) to week 1 or 2 (10 or 20 Gy) of CRT is a potential prognostic marker for patients with HNSCC. Because GTV PET depends on the applied method of analysis, we suggest the use of SUV(max), especially ΔSUV(max10/20), for an early estimation of therapy outcome. Confirmatory studies are warranted.