Temporal and regional expression changes and co-staining patterns of metabolic and stemness-related markers during glioblastoma progression.

Glioblastomas (GBMs) are characterized by high heterogeneity, involving diverse cell types, including those with stem-like features contributing to GBM's malignancy. Moreover, metabolic alterations promote growth and therapeutic resistance of GBM. Depending on the metabolic state, antimetabolic treatments could be an effective strategy. Against this background, we investigated temporal and regional expression changes and co-staining patterns of selected metabolic markers [pyruvate kinase muscle isozyme 1/2 (PKM1/2), glucose transporter 1 (GLUT1), monocarboxylate transporter 1/4 (MCT1/4)] in a rodent model and patient-derived samples of GBM. To understand the cellular sources of marker expression, we also examined the connection of metabolic markers to markers related to stemness [Nestin, Krüppel-like factor 4 (KLF4)] in a regional and temporal context. Rat tumour biopsies revealed a temporally increasing expression of GLUT1, higher expression of MCT1/4, Nestin and KLF4, and lower expression of PKM1 compared to the contralateral hemisphere. Patient-derived tumours showed a higher expression of PKM2 and Nestin in the tumour centre vs. edge. Whereas rare co-staining of GLUT1/Nestin was found in tumour biopsies, PKM1/2 and MCT1/4 showed a more distinct co-staining with Nestin in rats and humans. KLF4 was mainly co-stained with GLUT1, MCT1 and PKM1/2 in rat and human tumours. All metabolic markers yielded individual co-staining patterns among themselves. Co-staining mainly occurred later in tumour progression and was more pronounced in tumour centres. Also, positive correlations were found amongst markers that showed co-staining. Our results highlight a link between metabolic alterations and stemness in GBM progression, with complex distinctions depending on studied markers, time points and regions.

IDH1 mutation is associated with improved resection rates, progression-free survival and overall survival in patients with anaplastic astrocytomas.

PURPOSE: The introduction of molecular markers in to the diagnosis of gliomas has changed the therapeutic approach to this tumors. The aim of this study was to examine the impact of surgery on anaplastic astrocytomas (AA), which has not previously been fully elucidated. METHODS: This was a retrospective study involving a total of 143 patients who underwent surgery for primary AA in our department between 1995 and 2020. RESULTS: Total tumor resection was achieved more often in patients with IDH-mutant tumors (41.09%) than in patients with IDH-wildtype tumors (30.76%). The median PFS was 1876 days for patients with IDH1 mutations and 238 days for patients with IDH-wildtype tumors. The 1-, 3-, 5- and 10-year PFS were longer in patients with total tumor resection and IDH-mutant AA (86.2%, 69%, 65.5% and 44.8%, respectively) than in patients with subtotal tumor resection and IDH-mutant AA (83.3%, 55.6%, 41.7% and 25%, respectively) and even longer compared to all IDH-wildtype tumors. The median OS was 2472 days for patients with IDH1 mutations and 434 days for patients with IDH-wildtype tumors. The 3-, 5- and 10-year OS times were longer in patients with total tumor resection and IDH-mutant AA (89.2%, 85.2% and 72.6%, respectively) than in patients with subtotal tumor resection and IDH-mutant AA (85.9%, 73.7% and 52.6%, respectively) and were even longer compared to all IDH-wildtype tumors. CONCLUSION: Total tumor resection is more common with IDH-mutant AA than with IDH-wildtype tumors. Patients with IDH-mutant AA had significantly better PFS and OS after total tumor resection than after subtotal tumor resection and biopsy.

Value of intravenous alteplase before thrombectomy among patients with tandem lesions and emergent carotid artery stenting: A subgroup analysis of the SWIFT DIRECT trial.

BACKGROUND AND PURPOSE: The value of intravenous thrombolysis (IVT) in eligible tandem lesion patients undergoing endovascular treatment (EVT) is unknown. We investigated treatment effect heterogeneity of EVT + IVT versus EVT-only in tandem lesion patients. Additional analyses were performed for patients undergoing emergent internal carotid artery (ICA) stenting. METHODS: SWIFT DIRECT randomized IVT-eligible patients to either EVT + IVT or EVT-only. Primary outcome was 90-day functional independence (modified Rankin Scale score 0-2) after the index event. Secondary endpoints were reperfusion success, 24 h intracranial hemorrhage rate, and 90-day all-cause mortality. Interaction models were fitted for all predefined outcomes. RESULTS: Among 408 included patients, 63 (15.4%) had a tandem lesion and 33 (52.4%) received IVT. In patients with tandem lesions, 20 had undergone emergent ICA stenting (EVT + IVT: 9/33, 27.3%; EVT: 11/30, 36.7%). Tandem lesion did not show treatment effect modification of IVT on rates of functional independence (tandem lesion EVT + IVT vs. EVT: 63.6% vs. 46.7%, non-tandem lesion EVT + IVT vs. EVT: 65.6% vs. 58.2%; p for interaction = 0.77). IVT also did not increase the risk of intracranial hemorrhage  among tandem lesion patients (tandem lesion EVT + IVT vs. EVT: 34.4% vs. 46.7%, non-tandem lesion EVT + IVT vs. EVT: 33.5% vs. 26.3%; p for interaction = 0.15). No heterogeneity was noted for other endpoints (p for interaction > 0.05). CONCLUSIONS: No treatment effect heterogeneity of EVT + IVT versus EVT-only was observed among tandem lesion patients. Administering IVT in patients with anticipated emergent ICA stenting seems safe, and the latter should not be a factor to consider when deciding to administer IVT before EVT.

Optimal Chest Compression Point During Pediatric Resuscitation: Implications for Pediatric Resuscitation Practice by CT Scans.

OBJECTIVES: Current European guidelines for pediatric cardiopulmonary resuscitation (CPR) recommend the lower half of the sternum as the chest compression point (CP). In this study, we have used thoracic CT scans to evaluate recommended and optimal CP in relation to cardiac anatomy and structure. DESIGN: Analysis of routinely acquired thoracic CT scans acquired from 2000 to 2020. SETTING: Single-center pediatric department in a German University Hospital. PATIENTS: Imaging data were obtained from 290 patients of 3-16 years old. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We measured and analyzed 14 thoracic metrics in each thoracic CT scan. In 44 of 290 (15.2%) scans, the recommended CP did not match the level of the cardiac ventricles. Anatomically, the optimal CP was one rib or one vertebral body lower than the recommended CP, that is, the optimal CP was more caudal to the level of the body of the sternum in 67 of 290 (23.1%) scans. The recommended compression depth appeared reasonable in children younger than 12 years old. At 12 years old or older, the maximum compression depth of 6 cm is less than or equal to one-third of the thoracic depth. CONCLUSIONS: In this study of thoracic CT scans in children 3-16 years old, we have found that optimal CP for CPR appears to be more caudal than the recommended CP. Therefore, it seems reasonable to prefer to use the lower part of the sternum for CPR chest compressions. At 12 years old or older, a compression depth similar to that used in adults-6 cm limit-may be chosen.

Prevalence of degenerative vertebral disc changes in elite female Crossfit athletes - a cross-sectional study.

BACKGROUND: Crossfit athletes consistently recruit or transfer high levels of repetitive forces through the spine, and MRI has documented a higher rate of intervertebral disc degeneration in athletes compared with matched controls. The aim of this study was to evaluate early degenerative spinal disc changes in elite female CrossFit athletes quantified by 3.0 Tesla magnetic resonance imaging (MRI) matched with female none-athletes. METHODS: In a cross-sectional single-center study 19 asymptomatic adult participants, nine German female elite Crossfit athletes and ten female participants underwent spinal MRI (3.0T). Demographic data, spinal clinical examination results and sport-specific performance parameters were collected prior to the MRI. The primary outcome was the prevalence of degenerative spinal disc changes. The secondary outcome was the grade of degeneration using Pfirrmann grading. RESULTS: A total of 437 discs underwent spinal MRI (3.0T). The prevalence of early degenerative disc disease was not increased. Pfirrmann degenerative grade did not show significant differences among groups. CONCLUSION: Asymptomatic female elite Crossfit athletes do not show an increased prevalence of degenerative disc disease. Compared to a sex-matched control group, high training volume in Crossfit does not correlate to a higher incidence of degenerative disc changes in young females.

Clinical Value of Using Heart Rate Variability Biofeedback Before Elective CT Coronary Angiography to Reduce Heart Rate and the Need for Beta-Blockers.

The value of biofeedback before elective coronary computed tomography angiography (CCTA) to reduce patients' heart rates (HR) was investigated in the current work. Sixty patients who received CCTA to exclude coronary artery disease were included in our study and separated into two groups: with biofeedback (W-BF) and without biofeedback (WO-BF). The W-BF group used a biofeedback device for 15 min before CCTA. HR was determined in each patient at four measurement time points (MTP): during the pre-examination interview (MTP1), positioning on the CT patient table before CCTA (MTP2), during CCTA image acquisition (MTP3), and after completing CCTA (MTP4). If necessary, beta-blockers were administered in both groups after MTP2 until a HR of less than 65 bpm was achieved. Two board-certified radiologists subsequently assessed the image quality and analyzed the findings. Overall, the need for beta-blockers was significantly lower in patients in the W-BF group than the WO-BF group (p = 0.032). In patients with a HR of 81-90, beta-blockers were not required in four of six cases in the W-BF group, whereas in the WO-BF group all patients needed beta-blockers (p = 0.03). The amount of HR reduction between MTP1 and MTP2 was significantly higher in the W-BF compared to the WO-BF group (p = 0.028). There was no significant difference between the W-BF and WO-BF groups regarding image quality (p = 0.179). By using biofeedback prior to elective CCTA, beta-blocker use could be decreased without compromising CT image quality and analysis, especially in patients with an initial HR of 81-90 bpm.

Significance of Baseline Ischemic Core Volume on Stroke Outcome After Endovascular Therapy in Patients Age ≥75 Years: A Pooled Analysis of Individual Patient Data From 7 Trials.

BACKGROUND: Age and infarct volume are strong predictors of outcome in patients with ischemic stroke who underwent endovascular therapy (EVT). We aimed to investigate the impact of ischemic core volume (ICV) on stroke outcome after EVT in elderly. METHODS: Using the HERMES (Highly Effective Reperfusion Using Multiple Endovascular Devices) collaboration, a patient-level meta-analysis of 7 randomized trials in which patients were enrolled from December 2010 to April 2015) dataset, we categorized patients into those aged <75 and ≥75 years. ICV was calculated on computed tomography perfusion or magnetic resonance diffusion-weighted imaging. The association between ICV and the benefit of EVT over best medical treatment on outcome (modified Rankin Scale [mRS] at 90 days) and an ICV threshold for high likelihood (≥90%) of very poor outcome (mRS score ≥5) after EVT were investigated. RESULTS: A total of 899 patients who had baseline ICV data, 247 patients aged ≥75 years, of which 118 were randomized in the EVT arm. Patients aged ≥75 years required smaller ICV to achieve mRS score ≤3 than those aged <75 years in the EVT arm (median 10.7 mL versus 23.9 mL, P<0.001). In patients aged ≥75 years, modeling of outcome in both treatment arms revealed potential loss of effect for EVT at ICV of ≥50 mL or ≥85 mL for achieving mRS score ≤3 or ≤4, respectively. Treatment effect of EVT was significant in ICV <50 mL for mRS ≤3 (odds ratio 2.38, 95% confidence interval 1.35-4.22). ICV ≥132 mL was a threshold for high likelihood of very poor outcome after EVT. However, EVT still predicted at least 30% rate of mRS ≤3 at 150 mL ICV if near-complete or complete reperfusion was achieved. CONCLUSIONS: Baseline ICV has an impact on stroke outcome after EVT in the elderly, but elderly patients with large ICV may still benefit from EVT if near-complete or complete reperfusion is achieved. Young patients seem to benefit from EVT regardless of ICV status.

Does the primary soft-tissue sarcoma configuration predict configuration of recurrent tumors on magnetic resonance imaging?

BACKGROUND: Soft-tissue sarcomas (STS) are rare malignancies of the soft tissue. PURPOSE: To assess whether the magnetic resonance imaging (MRI) configuration of primary STS can predict the configuration of a recurring tumor and whether the MRI configuration of multiple recurrences differs in one and the same patient. MATERIAL AND METHODS: Thirty-nine patients with histologically proven recurrent STS were included in this retrospective study and underwent pre- and post-treatment MRI. Three main configurations of primary and recurrent tumors were identified: polycyclic/multilobulated; ovoid/nodular; and streaky. RESULTS: Sixty recurrent lesions were detected: 34 ovoid/nodular; 15 polycyclic/multilobulated; and 11 streaky. Five recurrences were multifocal and eight were bifocal. Of 39 patients, 28 (71.8%) presented one recurrence within the MRI follow-up period (P = 0.006); in 10 patients (25.6%), up to three different configurations of recurring STS were identified in one patient. Recurrences of polycyclic/multilobulated primaries were mostly ovoid/nodular (48%; P = 0.003) or polycyclic/multilobulated (37%; P = 0.014), and recurring ovoid/nodular STS significantly most often showed the same configuration as the primary tumor (85%; P < 0.001). Primary STS with a streaky configuration recurred in all three configurations in roughly equal proportions. Homogeneity/heterogeneity and tumor borders are significantly associated with the configuration of recurrences. CONCLUSION: Primary STS configuration may help predict recurrent tumor configuration when the primary STS had a polycyclic/multilobulated or ovoid/nodular configuration. However, recurrent STS configuration can also differ from primary STS configuration, especially when the primary STS had a streaky configuration, rendering recurrent STS difficult to predict. Different configurations of recurrent STS in one and the same patient are common.

The SITS Open Study: A Prospective, Open Label Blinded Evaluation Study of Thrombectomy in Clinical Practice.

BACKGROUND AND PURPOSE: We designed SITS (Safe Implementation of Treatment in Stroke) Open to determine benefit and safety of thrombectomy in clinical practice for large artery occlusion stroke, using selected stent retrievers plus standard care versus standard care alone. METHODS: SITS Open was a prospective, open, blinded evaluation, international, multicenter, controlled, nonrandomized registry study. Centers lacking access to thrombectomy contributed controls. Primary end point was categorical shift in modified Rankin Scale score at 3 months in the per protocol (PP) population. Principal secondary outcomes were symptomatic intracranial hemorrhage, functional independency (modified Rankin Scale score 0-2) and death at 3 months. Patients independently evaluated by video-recorded modified Rankin Scale interviews blinded to treatment or center identity by central core laboratory were regarded as PP population. Propensity score matching with covariate adjusted analysis was performed. RESULTS: During 2014 to 2017, 293 patients (257 thrombectomy, 36 control) from 26 centers in 10 countries fulfilled intention-to-treat and 200 (170 thrombectomy, 30 control) PP criteria; enrollment of controls was limited by rapid uptake of thrombectomy. In PP analysis, median age was 71 versus 71 years, and baseline National Institutes of Health Stroke Scale 17 versus 17 in the thrombectomy and control arms, respectively. The propensity score matching analysis for PP showed a significant shift for modified Rankin Scale at 3 months favoring the thrombectomy group (odds ratio, 3.8 [95% CI, 1.61-8.95]; P=0.002). Regarding safety, there were 4 cases of symptomatic intracranial hemorrhage in the thrombectomy group (2.4%) and none in the control group. CONCLUSIONS: In clinical practice, thrombectomy for patients with large artery occlusion stroke is superior to standard of care in our study. Registration: URL: https://www.clinicaltrials.gov. Unique Identifier: NCT02326428.

Absence of Consistent Sex Differences in Outcomes From Symptomatic Carotid Endarterectomy and Stenting Randomized Trials.

BACKGROUND AND PURPOSE: CREST (Carotid Revascularization Endarterectomy Versus Stenting Trial) reported a higher periprocedural risk for any stroke, death, or myocardial infarction for women randomized to carotid artery stenting (CAS) compared with women randomized to carotid endarterectomy (CEA). No difference in risk by treatment was detected for women relative to men in the 4-year primary outcome. We aimed to conduct a pooled analysis among symptomatic patients in large randomized trials to provide more precise estimates of sex differences in the CAS-to-CEA risk for any stroke or death during the 120-day periprocedural period and ipsilateral stroke thereafter. METHODS: Data from the Carotid Stenosis Trialists' Collaboration included outcomes from symptomatic patients in EVA-3S (Endarterectomy Versus Angioplasty in Patients With Symptomatic Severe Carotid Stenosis), SPACE (Stent-Protected Angioplasty Versus Carotid Endarterectomy in Symptomatic Patients), ICSS (International Carotid Stenting Study), and CREST. The primary outcome was any stroke or death within 120 days after randomization and ipsilateral stroke thereafter. Event rates and relative risks were estimated using Poisson regression; effect modification by sex was assessed with a sex-by-treatment-by-trial interaction term, with significant interaction defined a priori as P≤0.10. RESULTS: Over a median 2.7 years of follow-up, 433 outcomes occurred in 3317 men and 1437 women. The CAS-to-CEA relative risk of the primary outcome was significantly lower for women compared with men in 1 trial, nominally lower in another, and nominally higher in the other two. The sex-by-treatment-by-trial interaction term was significant (P=0.065), indicating heterogeneity among trials. Contributors to this heterogeneity are primarily differences in periprocedural period. When the trials are nevertheless pooled, there were no significant sex differences in risk in any follow-up period. CONCLUSIONS: There were significant differences between trials in the magnitude of sex differences in treatment effect (CAS-to-CEA relative risk), indicating pooling data from these trials to estimate sex differences might not be valid. Whether sex is acting as an effect modifier of the CAS-to-CEA treatment effect in symptomatic patients remains uncertain. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00190398 (EVA-3S) and NCT00004732 (CREST). URL: https://www.isrctn.com; Unique identifier: ISRCTN57874028 (SPACE) and ISRCTN25337470 (ICSS).

Diagnostic value of MRI for detecting recurrent soft-tissue sarcoma in a long-term analysis at a multidisciplinary sarcoma center.

BACKGROUND: Soft-tissue sarcomas (STS) are rare tumors of the soft tissue. Recent diagnostic studies on STS mainly dealt with only few cases of STS and did not investigate the post-therapeutic performance of MRI in a routine clinical setting. Therefore, we assessed the long-term diagnostic accuracy of MRI for detecting recurrent STS at a multidisciplinary sarcoma center. METHODS: In all, 1055 postoperative follow-up MRIs of 204 patients were included in the study. MRI follow-up scans were systematically reviewed for diagnostic values (true-positive/-negative and false-positive/-negative results) in detecting recurrences. Pathological reports and follow-up MRIs were set as baseline references. RESULTS: The median age of the patients was 55.3 ± 18.2 years. Of the patients, 34.8% presented with recurrences. Here, 65 follow-up scans were true positive, 23 false positive, 6 false negative, and 961 true negative. The overall sensitivity and specificity of MRI for detecting recurrences were 92 and 98%, respectively, with an accuracy of 97%. For intramuscular lesions and after surgery alone the sensitivity was higher (95 and 97%, respectively) than for subcutaneous lesions and surgery with additional radiation therapy (83 and 86%, respectively), at similarly high specificities (96-98%). The 6 false-negative results were found in streaky (n = 2) and small ovoid/nodular (n = 4) recurring lesions. The false-positive lesions imitated streaky (n = 14), ovoid/nodular (n = 8), and polycyclic/multilobulated recurring tumors (n = 1). All false-positive results were found in patients in whom the primary tumors were polycyclic/multilobulated in appearance. CONCLUSION: MRI shows a high diagnostic accuracy for detecting recurrent STS, with a high sensitivity and specificity. The diagnostic accuracy decreases in subcutaneous lesions and after surgery with radiation therapy, compared to intramuscular lesions and surgery alone. Radiologists should pay particular attention to streaky and small ovoid/nodular recurring lesions and patients with polycyclic/multilobulated primary tumors.

Pseudo-Enhancement in Intracranial Aneurysms on Black-Blood MRI: Effects of Flow Rate, Spatial Resolution, and Additional Flow Suppression.

BACKGROUND: Vessel-wall enhancement (VWE) on black-blood MRI (BB MRI) has been proposed as an imaging marker for a higher risk of rupture and associated with wall inflammation. Whether VWE is causally linked to inflammation or rather induced by flow phenomena has been a subject of debate. PURPOSE: To study the effects of slow flow, spatial resolution, and motion-sensitized driven equilibrium (MSDE) preparation on signal intensities in BB MRI of patient-specific aneurysm flow models. STUDY TYPE: Prospective. SUBJECTS/FLOW ANEURYSM MODEL/VIRTUAL VESSELS: Aneurysm flow models based on 3D rotational angiography datasets of three patients with intracranial aneurysms were 3D printed and perfused at two different flow rates, with and without Gd-containing contrast agent. FIELD STRENGTH/SEQUENCE: Variable refocusing flip angle 3D fast-spin echo sequence at 3 T with and without MSDE with three voxel sizes ((0.5 mm)3 , (0.7 mm)3 , and (0.9 mm)3 ); time-resolved with phase-contrast velocity-encoding 3D spoiled gradient echo sequence (4D flow MRI). ASSESSMENT: Three independent observers performed a qualitative visual assessment of flow patterns and signal enhancement. Quantitative analysis included voxel-wise evaluation of signal intensities and magnitude velocity distributions in the aneurysm. STATISTICAL TESTS: Kruskal-Wallis test, potential regressions. RESULTS: A hyperintense signal in the lumen and adjacent to the aneurysm walls on BB MRI was colocalized with slow flow. Signal intensities increased by a factor of 2.56 ± 0.68 (P < 0.01) after administering Gd contrast. After Gd contrast administration, the signal was suppressed most in conjunction with high flows and with MSDE (2.41 ± 2.07 for slow flow without MSDE, and 0.87 ± 0.99 for high flow with MSDE). A clear result was not achieved by modifying the spatial resolution . DATA CONCLUSIONS: Slow-flow phenomena contribute substantially to aneurysm enhancement and vary with MRI parameters. This should be considered in the clinical setting when assessing VWE in patients with an unruptured aneurysm. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Risks and neurological benefits of meningioma surgery in elderly patients compared to young patients.

INTRODUCTION: While surgery is the primary treatment choice for intracranial meningiomas in young patients, surgery in elderly patients, especially those with pre-existing comorbidities, has been the subject of repeated discussion. This study investigated the postoperative risks and neurological benefits of meningioma surgery in elderly patients compared to young patients. METHODS: In total, 768 patients were included and divided into two main groups: group I (age: ≤ 64 years; 484 young patients) and group II (age: ≥ 65 years; 284 elderly patients). Group II was subdivided into: IIa (age: 65-69 years), IIb (age: 70-79 years); and IIc (age: ≥ 80 years). RESULTS: The total tumor resection rate was higher in the elderly cohort than in the young cohort (84.5 and 76.2%, respectively). 154 young patients (31.8%) and 132 elderly patients (46.5%) developed postoperative morbidities, with the three most common being bleeding (12.9%), cranial nerve disorder (10%) and CSF fistula (8.1%). Postoperative bleeding, palsy, speech disorder, pneumonia and renal insufficiency were dependent on age (r = 0.123, p = 0.001; r = 0.089, p = 0.014; r = 0.100, p = 0.006; r = 0.098, p = 0.007 and r = 0.084, p = 0.020) and presented more often in elderly patients. 6 young and 15 elderly patients died during the 17.4-year observation period. Most patients showed a significant improvement in postoperative KPS (p < 0.001), except those over 80 years old (p = 0.753). The KPS at the last follow-up was significantly improved in all patients (p < 0.001). CONCLUSION: Meningioma surgery is associated with a higher rate of postoperative complications in elderly patients than in young patients. Most elderly patients, similar to young patients, show a significant improvement in neurological status postoperatively.

Editor's Choice - Risk of Stroke before Revascularisation in Patients with Symptomatic Carotid Stenosis: A Pooled Analysis of Randomised Controlled Trials.

OBJECTIVE: Current guidelines recommending rapid revascularisation of symptomatic carotid stenosis are largely based on data from clinical trials performed at a time when best medical therapy was potentially less effective than today. The risk of stroke and its predictors among patients with symptomatic carotid stenosis awaiting revascularisation in recent randomised controlled trials (RCTs) and in medical arms of earlier RCTs was assessed. METHODS: The pooled data of individual patients with symptomatic carotid stenosis randomised to stenting (CAS) or endarterectomy (CEA) in four recent RCTs, and of patients randomised to medical therapy in three earlier RCTs comparing CEA vs. medical therapy, were compared. The primary outcome event was any stroke occurring between randomisation and treatment by CAS or CEA, or within 120 days after randomisation. RESULTS: A total of 4 754 patients from recent trials and 1 227 from earlier trials were included. In recent trials, patients were randomised a median of 18 (IQR 7, 50) days after the qualifying event (QE). Twenty-three suffered a stroke while waiting for revascularisation (cumulative 120 day risk 1.97%, 95% confidence interval [CI] 0.75 - 3.17). Shorter time from QE until randomisation increased stroke risk after randomisation (χ2 = 6.58, p = .011). Sixty-one patients had a stroke within 120 days of randomisation in the medical arms of earlier trials (cumulative risk 5%, 95% CI 3.8 - 6.2). Stroke risk was lower in recent than earlier trials when adjusted for time between QE and randomisation, age, severity of QE, and degree of carotid stenosis (HR 0.47, 95% CI 0.25 - 0.88, p = .019). CONCLUSION: Patients with symptomatic carotid stenosis enrolled in recent large RCTs had a lower risk of stroke after randomisation than historical controls. The added benefit of carotid revascularisation to modern medical care needs to be revisited in future studies. Until then, adhering to current recommendations for early revascularisation of patients with symptomatic carotid stenosis considered to require invasive treatment is advisable.

Contralateral Stenosis and Echolucent Plaque Morphology are Associated with Elevated Stroke Risk in Patients Treated with Asymptomatic Carotid Artery Stenosis within a Controlled Clinical Trial (SPACE-2).

BACKGROUND: Asymptomatic carotid artery stenosis (ACS) has a low risk of stroke. To achieve an advantage over noninterventional best medical treatment (BMT), carotid endarterectomy (CEA) or carotid artery stenting (CAS) must be performed with the lowest possible risk of stroke. Therefore, an analysis of risk-elevating factors is essential. Grade of ipsilateral and contralateral stenosis as well as plaque morphology are known risk factors in ACS. METHODS: The randomized, controlled, multicenter SPACE-2 trial had to be stopped prematurely after recruiting 513 patients. 203 patients were randomized to CEA, 197 to CAS, and 113 to BMT. Within one year, risk factors such as grade of stenosis and plaque morphology were analyzed. RESULTS: Grade of contralateral stenosis (GCS) was higher in patients with any stroke (50%ECST vs. 20%ECST; p=0.012). Echolucent plaque morphology was associated with any stroke on the day of intervention (OR 5.23; p=0.041). In the periprocedural period, any stroke was correlated with GCS in the CEA group (70%ECST vs. 20%ECST; p=0.026) and with echolucent plaque morphology in the CAS group (6% vs. 1%; p=0.048). In multivariate analysis, occlusion of the contralateral carotid artery (CCO) was associated with risk of any stroke (OR 7.00; p=0.006), without heterogeneity between CEA and CAS. CONCLUSION: In patients with asymptomatic carotid artery stenosis, GCS, CCO, as well as echolucent plaque morphology were associated with a higher risk of cerebrovascular events. The risk of stroke in the periprocedural period was increased by GCS in CEA and by echolucent plaque in CAS. Due to small sample size, results must be interpreted carefully.

Dural Arteriovenous Fistulae After Cerebral Venous Thrombosis.

BACKGROUND AND PURPOSE: This analysis examined the frequency of dural arteriovenous fistulae (dAVF) after cerebral venous thrombosis (CVT) in patients included in a randomized controlled trial comparing dabigatran etexilate with dose-adjusted warfarin (RE-SPECT CVT [A Clinical Trial Comparing Efficacy and Safety of Dabigatran Etexilate With Warfarin in Patients With Cerebral Venous and Dural Sinus Thrombosis]), who had systematic follow-up magnetic resonance (MR) imaging. METHODS: RE-SPECT CVT was a Phase 3, prospective, randomized, parallel-group, open-label, multicenter, exploratory trial with blinded end point adjudication. We allocated patients with acute CVT to dabigatran 150 mg twice daily or dose-adjusted warfarin, for 24 weeks and obtained a standardized MR protocol including time-of-flight MR angiography, 3-dimensional phase-contrast venography, and 3-dimensional contrast-enhanced MR venography at the end of the treatment period. A blinded adjudication committee assessed the presence of dAVF in a predefined substudy of the trial. RESULTS: We analyzed development of dAVF in 112 of 120 randomized patients; 57 allocated to dabigatran and 55 to warfarin. For 3 (2.7%) of these 112 patients, quality of follow-up imaging was insufficient to evaluate dAVF. A dAVF (Borden I) was found in 1 patient (0.9%) allocated to warfarin; however, this dAVF was already present at baseline. The patient did not present with hemorrhage at baseline or during the trial and was asymptomatic at follow-up. CONCLUSIONS: Despite systematic imaging, we found no new dAVF 6 months after CVT. Routine follow-up cerebral MR angiography aiming to detect new dAVF 6 months after CVT has a very low yield. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02913326.

Clinical Value of Noncontrast-Enhanced Radial Quiescent-Interval Slice-Selective (QISS) Magnetic Resonance Angiography for the Diagnosis of Acute Pulmonary Embolism Compared to Contrast-Enhanced Computed Tomography and Cartesian Balanced Steady-State Free Precession.

BACKGROUND: Free-breathing noncontrast-enhanced (non-CE) magnetic resonance angiography (MRA) techniques are of considerable interest for the diagnosis of acute pulmonary embolism (APE), due to the possibility for repeated examinations, avoidance of side effects from iodine-based contrast agents, and the absence of ionizing radiation exposure as compared to CE-computed tomographic angiography (CTA). PURPOSE: To analyze the clinical performance of free-breathing and electrocardiogram (ECG)-gated radial quiescent-interval slice-selective (QISS)-MRA compared to CE-CTA and to Cartesian balanced steady-state free precession (bSSFP)-MRA. STUDY TYPE: Prospective. SUBJECTS: Thirty patients with confirmed APE and 30 healthy volunteers (HVs). FIELD STRENGTH/SEQUENCE: Radial QISS- and bSSFP-MRA at 1.5T. ASSESSMENT: Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were computed to compare the pulmonary imaging quality between MRA methods. The pulmonary arterial tree was divided into 25 branches and an ordinal scoring system was used to assess the image quality of each pulmonary branch. The clinical performance of the two MRA techniques in accurately assessing APE was evaluated with respect to CE-CTA as the clinical reference standard. STATISTICAL TESTS: Wilcoxon signed-rank and Spearman's correlation tests were performed. Sensitivity and specificity of the MRA techniques were determined using CE-CTA as the clinical reference standard. RESULTS: Thrombus-mimicking artifacts appeared more frequently in lobar and peripheral arteries of patients with Cartesian bSSFP than with radial QISS-MRA (pulmonary trunk: 12.2% vs. 14.0%, P = 0.64; lobar arteries: 35.6% vs. 22.0%, P = 0.005, peripheral arteries: 74.4% vs. 49.0%, P < 0.001). The relative increases in SNR and of CNR provided by radial QISS-MRA with respect to Cartesian bSSFP-MRA were 30-35% (P-values of SNR/CNR, HVs: 0.09/0.09, patients: 0.03/0.02). The image quality of pulmonary arterial branches was considered good to excellent in 77.2% of patients with radial QISS-MRA and in 43.2% with Cartesian bSSFP-MRA (P < 0.0001). The clinical performance of radial QISS-MRA was higher than Cartesian bSSFP-MRA for grading embolism, with a total sensitivity of 86.0% vs. 80.6% and a specificity of 93.3% vs. 84.0%, respectively. DATA CONCLUSION: Radial QISS-MRA is a reliable and safe non-CE angiographic technique with promising clinical potential compared to Cartesian bSSFP-MRA and as an alternative technique to CE-CTA for the diagnosis of APE. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 3.

MRI in patients with implanted active devices: how to combine safety and image quality using a limited transmission field?

OBJECTIVES: Radio frequency (RF) pulses in magnetic resonance imaging (MRI) can interact with implanted devices and cause tissue damage. However, there are new devices that can safely perform measurements with liberal MRI conditions such as an RF transmission field B1+rms ≤ 2.0 µT. We investigated whether MRI in this case is limited for these technical reasons. METHODS: We selected typical MRI protocols of six body regions (brain, cervical spine, lumbar spine, knee, liver, heart) using two typical 1.5T MRI scanners. Overall, we adapted 62 sequences to B1+rms conditions and evaluated their diagnostic quality. For this, we measured signal-to-noise-ratio (SNR), contrast-to-noise-ratio (CNR), and geometric deviation (GD) as quality parameters, using phantom studies. For questionnaire studies, we selected pairs of original and adapted sequences in healthy volunteers. Blinded radiologists rated the images as single sequence rating and in direct comparison. RESULTS: Roughly one-third of the checked sequences were below the B1+rms limit. Here, 56 of the 62 adapted sequences showed at least the same image quality in single ratings. A reduction in SNR and/or CNR was found with 31 sequences and only one sequence with considerably increased GD. Especially, sequences with original high B1+rms values, PD sequences, and sequences of the Siemens knee and heart protocol were difficult to adapt, whereas most TSE and IR sequences had no clinical limitations. CONCLUSION: By limiting the transmission field to B1+rms ≤ 2.0 µT, clinically relevant MR sequences can be adapted with nearly no reduction in image quality. Despite limiting the transmission field, high-quality MR imaging is possible. We could derive strategies for adaptation. KEY POINTS: • Despite limiting the transmission field, high-quality MRI is possible. • We could derive strategies for adapting the sequences to B1+rms≤ 2.0 µT. • This enables high-quality MRI of different body regions for patients with AD.

Multimodal validation of focal enhancement in intracranial aneurysms as a surrogate marker for aneurysm instability.

PURPOSE: Circumferential enhancement on MR vessel wall imaging has been proposed as a biomarker of a higher risk of rupture in intracranial aneurysms. Focal enhancement is frequently encountered in unruptured aneurysms, but its implication for risk stratification and patient management remains unclear. This study investigates the association of focal wall enhancement with hemodynamic and morphological risk factors and histologic markers of wall inflammation and degeneration. METHODS: Patients with an unruptured middle cerebral artery aneurysm who underwent 3D rotational angiography and 3T MR vessel wall imaging showing focal wall enhancement were included. Hemodynamic parameters were calculated based on flow simulations and compared between enhanced regions and the entire aneurysm surface. Morphological parameters were semiautomatically extracted and quantitatively associated with wall enhancement. Histological analysis included detection of vasa vasorum, CD34, and myeloperoxidase staining in a subset of patients. RESULTS: Twenty-two aneurysms were analyzed. Enhanced regions were significantly associated with lower AWSS, lower maxOSI, and increased LSA. In multivariate analysis, higher ellipticity index was an independent predictor of wall enhancement. Histologic signs of inflammation and degeneration and higher PHASES score were significantly associated with focal enhancement. CONCLUSION: Focal wall enhancement is colocalized with hemodynamic factors that have been related to a higher rupture risk. It is correlated with morphological factors linked to rupture risk, higher PHASES score, and histologic markers of wall destabilization. The results support the hypothesis that focal enhancement could serve as a surrogate marker for aneurysm instability.

Standards for European training requirements in interventional neuroradiology : Guidelines by the Division of Neuroradiology/Section of Radiology European Union of Medical Specialists (UEMS), in cooperation with the Division of Interventional Radiology/UEMS, the European Society of Neuroradiology (ESNR), and the European Society of Minimally Invasive Neurological Therapy (ESMINT).

This document sets out standards for training in Interventional Neuroradiology (INR) in Europe. These standards have been developed by a working group of the European Society of Neuroradiology (ESNR) and the European Society of Minimally Invasive Neurological Therapy (ESMINT) on the initiative and under the umbrella of the Division of Neuroradiology/Section of Radiology of the European Union of Medical Specialists (UEMS).