Elective one-minute full brain multi-contrast MRI versus brain CT in pediatric patients: a prospective feasibility study.

BACKGROUND: Brain CT can be used to evaluate pediatric patients with suspicion of cerebral pathology when anesthetic and MRI resources are scarce. This study aimed to assess if pediatric patients referred for an elective brain CT could endure a diagnostic fast brain MRI without general anesthesia using a one-minute multi-contrast EPI-based sequence (EPIMix) with comparable diagnostic performance. METHODS: Pediatric patients referred for an elective brain CT between March 2019 and March 2020 were prospectively included and underwent EPIMix without general anesthesia in addition to CT. Three readers (R1-3) independently evaluated EPIMix and CT images on two separate occasions. The two main study outcomes were the tolerance to undergo an EPIMix scan without general anesthesia and its performance to classify a scan as normal or abnormal. Secondary outcomes were assessment of disease category, incidental findings, diagnostic image quality, diagnostic confidence, and image artifacts. Further, a side-by-side evaluation of EPIMix and CT was performed. The signal-to-noise ratio (SNR) was calculated for EPIMix on T1-weighted, T2-weighted, and ADC images. Descriptive statistics, Fisher's exact test, and Chi-squared test were used to compare the two imaging modalities. RESULTS: EPIMix was well tolerated by all included patients (n = 15) aged 5-16 (mean 11, SD 3) years old. Thirteen cases on EPIMix and twelve cases on CT were classified as normal by all readers (R1-3), while two cases on EPIMix and three cases on CT were classified as abnormal by one reader (R1), (R1-3, p = 1.00). There was no evidence of a difference in diagnostic confidence, image quality, or the presence of motion artifacts between EPIMix and CT (R1-3, p ≥ 0.10). Side-by-side evaluation (R2 + R4 + R5) reviewed all scans as lacking significant pathological findings on EPIMix and CT images. CONCLUSIONS: Full brain MRI-based EPIMix sequence was well tolerated without general anesthesia with a diagnostic performance comparable to CT in elective pediatric patients. TRIAL REGISTRATION: This study was approved by the Swedish Ethical Review Authority (ethical approval number/ID Ethical approval 2017/2424-31/1). This study was a clinical trial study, with study protocol published at ClinicalTrials.gov with Trial registration number NCT03847051, date of registration 18/02/2019.

Impact of prehospital stroke triage implementation on patients with intracerebral hemorrhage.

Background: Little is known about how prehospital triage using large vessel occlusion (LVO) stroke prediction scales affects patients with intracerebral hemorrhage (ICH). Objectives: We aimed to investigate whether the Stockholm Stroke Triage System (SSTS) implemented in 2017 has affected timing and outcomes of acute ICH neurosurgery, and to assess system triage accuracy for ICH with a neurosurgical indication or LVO thrombectomy. Design: Observational cohort study. Methods: In the Stockholm Region, we compared surgical timing, functional outcome, and death at 3 months in patients transported by code-stroke ground ambulance who had ICH neurosurgery, 2 years before versus 2 years after SSTS implementation. We also calculated triage precision metrics for treatment with either ICH neurosurgery or thrombectomy. Results: A total of 36 patients undergoing ICH neurosurgery were included before SSTS implementation and 30 after. No significant difference was found in timing of neurosurgery [median 7.5 (4.9-20.7) versus 9.1 (6.1-12.5) h after onset], distribution of functional outcomes (median 4 versus 4), and death at 3 months [3/29 (9%) versus 5/35 (17%)] before versus after implementation, respectively. The SSTS routed a larger proportion of patients subsequently undergoing ICH neurosurgery directly to the comprehensive stroke center: 13/36 (36%) before versus 18/30 (60%) after implementation. Overall system triage accuracy for ICH neurosurgery or thrombectomy was high at 90%, with 92% specificity and 65% sensitivity. Conclusion: The SSTS, initially designed for prehospital LVO stroke triage, routed more patients with neurosurgical indication for ICH directly to the comprehensive stroke center. This did not significantly affect surgical timing or outcomes.

11C-methionine PET/MRI in postoperative patients after craniotomy: zero echo time and head atlas versus CT-based attenuation correction.

BACKGROUND: Attenuation correction (AC) is an important topic in PET/MRI and particularly challenging after brain tumor surgery, near metal implants, adjacent bone and burr holes. In this study, we evaluated the performance of two MR-driven AC methods, zero-echo-time AC (ZTE-AC) and atlas-AC, in comparison to reference standard CT-AC in patients with surgically treated brain tumors at 11C-methionine PET/MRI. METHODS: This retrospective study investigated seven postoperative patients with neuropathologically confirmed brain tumor at 11C-methionine PET/MRI. Three AC maps - ZTE-AC, atlas-AC and reference standard CT-AC - were generated for each patient. Standardized uptake values (SUV) were obtained at the metal implant, adjacent bone and burr hole. Standard uptake ratio (SUR) SURmetal/mirror, SURbone/mirror and SURburrhole/mirror were then calculated and analyzed with Bland-Altman, Pearson correlation and intraclass correlation reliability. RESULTS: Smaller mean percent bias range (Bland-Altman) was found for ZTE-AC than atlas-AC in all analyses (metal ZTE -0.46 to -0.02, metal atlas -3.57 to -3.26; bone ZTE -4.60 to -2.16, bone atlas -5.25 to -3.81; burr hole ZTE -0.95 to -0.52, burr hole atlas 7.86 to 8.87). Percent SD range (Bland-Altman) was large for both methods in all analyses, with lower absolute values for ZTE-AC (ZTE 7.02-8.49; atlas 11.47-14.83). A very strong correlation (Pearson correlation) was demonstrated for both methods compared to CT-AC (ZTE ρ 0.97-0.99, P<0.001; atlas ρ 0.88-0.91, P≤0.009) with higher absolute values for ZTE. An excellent intraclass correlation coefficient was found across all analyses for ZTE, atlas and CT maps (ICC ≥0.88). CONCLUSIONS: ZTE for MR-driven PET attenuation correction presented a more comparable performance to reference standard CT-AC at the postoperative site. ZTE-AC may serve as a useful diagnostic tool for MR-driven AC in patients with surgically treated brain tumors.

A 78 Seconds Complete Brain MRI Examination in Ischemic Stroke: A Prospective Cohort Study.

BACKGROUND: Fast 78-second multicontrast echo-planar MRI (EPIMix) has shown good diagnostic performance for detecting infarctions at a comprehensive stroke center, but its diagnostic performance has not been evaluated in a prospective study at a primary stroke center. PURPOSE: To prospectively determine whether EPIMix was noninferior in detecting ischemic lesions compared to routine clinical MRI. STUDY TYPE: Prospective cohort study. POPULATION: A total of 118 patients with acute MRI and symptoms of ischemic stroke. FIELD STRENGTH AND SEQUENCE: A 3 T. EPIMix (echo-planar based: T1-FLAIR, T2-weighted, T2-FLAIR, T2*, DWI) and routine clinical MRI sequences (T1-weighted fast spin echo, T2-weighted PROPELLER, T2-weighted-FLAIR fast spin echo, T2* gradient echo echo-planar, and DWI spin echo echo-planar). ASSESSMENT: Three radiologists, blinded for clinical information, assessed signs of ischemic lesions (DWI↑, ADC↓, and T2/T2-FLAIR↑) on EPIMix and routine clinical MRI, with disagreements solved in consensus with a fourth reader to establish the reference standard. STATISTICAL TESTS: Diagnostic performance including sensitivity and specificity against the reference standard was evaluated. EPIMix sensitivity was tested for noninferiority compared to the reference standard using Nam's restricted maximum likelihood estimation (RMLE) Score. A P-value < 0.05 was considered statistically significant. RESULTS: Of 118 patients (mean age 62 ± 16 years, 58% males), 25% (n = 30) had MRI signs of acute infarcts. EPIMix was noninferior with 97% (95% CI 83-100) sensitivity for reader 1, 100% (95% CI 88-100) sensitivity for reader 2, and 90% (95% CI 88-98) sensitivity for reader 3 vs. 93% (95% CI 78-99) sensitivity for readers 1 and 2 and 90% (95% CI 74-98) for reader 3 on routine clinical MRI. Specificity was 99% (95% CI 94-100) for reader 1, 100% (95% CI 96-100) for reader 2, and 98% (95% CI 92-100) for reader 3 on EPIMix vs. 100% (95% CI 96-100) for all readers on routine clinical MRI. CONCLUSION: EPIMix was noninferior to routine clinical MRI for the diagnosis of acute ischemic stroke. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Performance characterization of a prototype dual-layer cone-beam computed tomography system.

PURPOSE: Conventional cone-beam computed tomography CT (CBCT) provides limited discrimination between low-contrast tissues. Furthermore, it is limited to full-spectrum energy integration. A dual-energy CBCT system could be used to separate photon energy spectra with the potential to increase the visibility of clinically relevant features and acquire additional information relevant in a multitude of clinical imaging applications. In this work, the performance of a novel dual-layer dual-energy CBCT (DL-DE-CBCT) C-arm system is characterized for the first time. METHODS: A prototype dual-layer detector was fitted into a commercial interventional C-arm CBCT system to enable DL-DE-CBCT acquisitions. DL-DE reconstructions were derived from material-decomposed Compton scatter and photoelectric base functions. The modulation transfer function (MTF) of the prototype DL-DE-CBCT was compared to that of a commercial CBCT. Noise and uniformity characteristics were evaluated using a cylindrical water phantom. Effective atomic numbers and electron densities were estimated in clinically relevant tissue substitutes. Iodine quantification was performed (for 0.5-15 mg/ml concentrations) and virtual noncontrast (VNC) images were evaluated. Finally, contrast-to-noise ratios (CNR) and CT number accuracies were estimated. RESULTS: The prototype and commercial CBCT showed similar spatial resolution, with a mean 10% MTF of 5.98 cycles/cm and 6.28 cycles/cm, respectively, using a commercial standard reconstruction. The lowest noise was seen in the 80 keV virtual monoenergetic images (VMI) (7.40 HU) and the most uniform images were seen at VMI 60 keV (4.74 HU) or VMI 80 keV (1.98 HU), depending on the uniformity measure used. For all the tissue substitutes measured, the mean accuracy in effective atomic number was 98.2% (SD 1.2%) and the mean accuracy in electron density was 100.3% (SD 0.9%). Iodine quantification images showed a mean difference of -0.1 (SD 0.5) mg/ml compared to the true iodine concentration for all blood and iodine-containing objects. For VNC images, all blood substitutes containing iodine averaged a CT number of 43.2 HU, whereas a blood-only substitute measured 44.8 HU. All water-containing iodine substitutes measured a mean CT number of 2.6 in the VNC images. A noise-suppressed dataset showed a CNR peak at VMI 40 keV and low at VMI 120 keV. In the same dataset without noise suppression applied, a peak in CNR was obtained at VMI 70 keV and a low at VMI 120 keV. The estimated CT numbers of various clinically relevant objects were generally very close to the calculated CT number. CONCLUSIONS: The performance of a prototype dual-layer dual-energy C-arm CBCT system was characterized. Spatial resolution and noise were comparable with a commercially available C-arm CBCT system, while offering dual-energy capability. Iodine quantifications, effective atomic numbers, and electron densities were in good agreement with expected values, indicating that the system can be used to reliably evaluate the material composition of clinically relevant tissues. The VNC and monoenergetic images indicate a consistent ability to separate clinically relevant tissues. The results presented indicate that the system could find utility in diagnostic, interventional, and radiotherapy planning settings.

One-Minute Multi-contrast Echo Planar Brain MRI in Ischemic Stroke: A Retrospective Observational Study of Diagnostic Performance.

BACKGROUND: Fast multi-contrast echo planar MRI (EPIMix) has comparable diagnostic performance to standard MRI for detecting brain pathology but its performance in detecting acute cerebral infarctions has not been determined. PURPOSE: To assess the diagnostic performance of EPIMix for the detection of acute cerebral infarctions. STUDY TYPE: Retrospective observational cohort. POPULATION: One hundred and seventy-two consecutive patients with a clinical suspicion of non-hyperacute ischemic stroke (January 2018 to December 2019). FIELD STRENGTH AND SEQUENCE: 1.5 T or 3 T. EPIMix ((echo-planar based: diffusion weighted (DWI), T2*-weighted, T2-weighted, T2- and T1-fluid attenuated inversion recovery (FLAIR) images) vs. standard MRI: echo-planar DWI, echo-planar T2*-weighted or susceptibility weighted, turbo spin-echo T2-weighted, T2- and T1-FLAIR turbo spin-echo sequences. ASSESSMENT: Three neuroradiologists rated EPIMix and standard MRI on two separate occasions. Incongruent assessments were resolved in consensus with the fourth reader. The ratings included the diagnostic category (acute infarct, normal, and other pathology). Congruent diagnoses together with consensus diagnoses served as the reference standard. STATISTICAL TESTS: The diagnostic performance of EPIMix and standard MRI against the reference standard was calculated by the area under the receiver operating characteristic curve (AUC) and compared by DeLong's test. Sensitivity and specificity were determined. Inter-rater agreements were evaluated by Fleiss's kappa. RESULTS: Of 172 patients (61 ± 16 years, 103 men), acute infarcts were present in 80/172 (47%), normal findings in 60/172 (35%), and other pathology in 32/172 (19%). Across readers, the AUCs were .94-.95 for EPIMix and .95-.99 for standard MRI, with overlapping 95% CI (P = .02-.18). Inter-rater agreement for EPIMix was 0.90 and for standard MRI was 0.93. The sensitivity for EPIMix and standard MRI was 88-91% and 91-98%, respectively, while the specificity was 98-100% and 98-99%, both with overlapping 95% CI. CONCLUSION: Multi-contrast echo planar MRI showed a high but marginally lower diagnostic performance compared to standard MRI for the detection and characterization of acute brain infarct. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Performance of dual layer dual energy CT virtual monoenergetic images to identify early ischemic changes in patients with anterior circulation large vessel occlusion.

BACKGROUND AND PURPOSE: Dual energy CT is increasingly available and used in the standard diagnostic setting of ischemic stroke patients. We aimed to evaluate how different dual energy CT virtual monoenergetic energy levels impact identification of early ischemic changes, compared to conventional polyenergetic CT images. MATERIALS AND METHODS: This retrospective single-center study included patients presenting with acute ischemic stroke caused by an occlusion of the intracranial internal carotid artery or proximal middle cerebral artery. Data was gathered on consecutive patients admitted to our institution who underwent initial diagnostic stroke imaging with dual layer dual energy CT and a subsequent follow-up CT one to three days after admission. Automated ASPECTS results from conventional polyenergetic and different virtual monoenergetic energy level reconstructions at admission were generated and compared to reference standard ASPECTS. Confidence intervals (CI) for sensitivity, specificity, negative and positive predictive value were calculated. RESULTS: A total of 24 patients were included. Virtual monoenergetic reconstructions of 70 keV had the highest region-based ASPECTS accuracy, 0.90 (sensitivity 0.82 (95% CI 0.72-0.93), specificity 0.92 (0.88-0.97), negative predictive value 0.94 (0.90-0.96)), whereas virtual monoenergetic reconstructions of 40 keV had the lowest, 0.77 (sensitivity 0.34 (0.26-0.42), specificity 0.90 (0.89-0.96), negative predictive value 0.80 (0.77-0.83)). CONCLUSIONS: Automated 70 keV ASPECTS had the highest diagnostic accuracy, sensitivity and negative predictive value overall. Our results indicate that virtual monoenergetic energy levels impact the identification of early ischemic changes on CT.

Validation of PET/MRI attenuation correction methodology in the study of brain tumours.

BACKGROUND: This study aims to compare proton density weighted magnetic resonance imaging (MRI) zero echo time (ZTE) and head atlas attenuation correction (AC) to the reference standard computed tomography (CT) based AC for 11C-methionine positron emission tomography (PET)/MRI. METHODS: A retrospective cohort of 14 patients with suspected or confirmed brain tumour and 11C-Methionine PET/MRI was included in the study. For each scan, three AC maps were generated: ZTE-AC, atlas-AC and reference standard CT-AC. Maximum and mean standardised uptake values (SUV) were measured in the hotspot, mirror region and frontal cortex. In postoperative patients (n = 8), SUV values were additionally obtained adjacent to the metal implant and mirror region. Standardised uptake ratios (SUR) hotspot/mirror, hotspot/cortex and metal/mirror were then calculated and analysed with Bland-Altman, Pearson correlation and intraclass correlation reliability in the overall group and subgroups. RESULTS: ZTE-AC demonstrated narrower SD and 95% CI (Bland-Altman) than atlas-AC in the hotspot analysis for all groups (ZTE overall ≤ 2.84, - 1.41 to 1.70; metal ≤ 1.67, - 3.00 to 2.20; non-metal ≤ 3.04, - 0.96 to 3.38; Atlas overall ≤ 4.56, - 1.05 to 3.83; metal ≤ 3.87, - 3.81 to 4.64; non-metal ≤ 4.90, - 1.68 to 5.86). The mean bias for both ZTE-AC and atlas-AC was ≤ 2.4% compared to CT-AC. In the metal region analysis, ZTE-AC demonstrated a narrower mean bias range-closer to zero-and narrower SD and 95% CI (ZTE 0.21-0.48, ≤ 2.50, - 1.70 to 2.57; Atlas 0.56-1.54, ≤ 4.01, - 1.81 to 4.89). The mean bias for both ZTE-AC and atlas-AC was within 1.6%. A perfect correlation (Pearson correlation) was found for both ZTE-AC and atlas-AC compared to CT-AC in the hotspot and metal analysis (ZTE ρ 1.00, p < 0.0001; atlas ρ 1.00, p < 0.0001). An almost perfect intraclass correlation coefficient for absolute agreement was found between Atlas-, ZTE and CT maps for maxSUR and meanSUR values in all the analyses (ICC > 0.99). CONCLUSIONS: Both ZTE and atlas-AC showed a good performance against CT-AC in patients with brain tumour.

Nervous System Involvement in Coronavirus Disease 2019: Results from a Retrospective Consecutive Neuroimaging Cohort.

Background Neurologic complications in coronavirus disease 2019 (COVID-19) have been described, but the understanding of their pathophysiologic causes and neuroanatomical correlates remains limited. Purpose To report on the frequency and type of neuroradiological findings in COVID-19. Materials and Methods In this retrospective study, all consecutive adult hospitalized patients with polymerase chain reaction positivity for severe acute respiratory syndrome coronavirus 2 and who underwent neuroimaging at Karolinska University Hospital between March 2 and May 24, 2020, were included. All examinations were systematically re-evaluated by 12 readers. Summary descriptive statistics were calculated. Results A total of 185 patients with COVID-19 (62 years ± 14 [standard deviation]; 138 men) underwent neuroimaging. In total, 222 brain CT, 47 brain MRI, and seven spinal MRI examinations were performed. Intra-axial susceptibility abnormalities were the most common finding (29 of 39; 74%, 95% CI: 58, 87) in patients who underwent brain MRI, often with an ovoid shape suggestive of microvascular pathology and with a predilection for the corpus callosum (23 of 39; 59%; 95% CI: 42, 74) and juxtacortical areas (14 of 39; 36%; 95% CI: 21, 53). Ischemic and macrohemorrhagic manifestations were also observed, but vascular imaging did not demonstrate overt abnormalities. Dynamic susceptibility contrast perfusion MRI in 19 patients did not reveal consistent asymmetries between hemispheres or regions. Many patients (18 of 41; 44%; 95% CI: 28, 60) had leukoencephalopathy and one patient had a cytotoxic lesion of the corpus callosum. Other findings included olfactory bulb signal abnormalities (seven of 37; 19%), prominent optic nerve subarachnoid spaces (20 of 36; 56%), and enhancement of the parenchyma (three of 20; 15%), leptomeninges (three of 20; 15%), cranial nerves (two of 20; 10%), and spinal nerves (two of four; 50%). At MRI follow-up, regression of leukoencephalopathy and progressive leptomeningeal enhancement was observed in one patient each, respectively, which is suggestive of dynamic processes. Conclusion Patients with coronavirus disease 2019 had a wide spectrum of vascular and inflammatory involvement of both the central and peripheral nervous system. © RSNA, 2020 Online supplemental material is available for this article.

Radiological evaluation in patients with clinical suspicion of cerebral venous sinus thrombosis presenting with nontraumatic headache - a retrospective observational study with a validation cohort.

BACKGROUND: Clinical suspicion of cerebral venous sinus thrombosis (CVST) is imprecise due to non-specific symptoms such as headache. The aim was to retrospectively assess the diagnostic value of nonenhanced CT (neCT) in patients with nontraumatic headache and clinically suspected CVST. METHODS: A retrospective consecutive series of patients referred 2013-2015 for radiology were evaluated. Eligible patients had nontraumatic headache and suspicion of CVST stated in the referral, investigated with CT venography (CTV) and nonenhanced CT (neCT). neCT scans were re-evaluated for the presence of CVST or other pathology. All CTVs were checked for the presence of CVST. The validation cohort consisted of 10 patients with nontraumatic CVT (2017-2019). RESULTS: Less than 1% (1/104) had a suspected thrombus on neCT, confirmed by subsequent CTV. The remaining 99% had a CTV excluding CVST. Eleven percent had other imaging findings explaining their symptoms. In the patient with CVST, the thrombosed dural sinus was high attenuating (maximum HU 89) leading to the suspicion of CVST confirmed by CTV. The validation cohort (n = 10) confirmed the presence of a high attenuating (HU > 65) venous structure in the presence of a confirmed thrombus in all patients presenting within 10 days (suspicion written in referral, 10%). CONCLUSIONS: Despite clinical suspicion, imaging findings of CVST in nontraumatic headache are uncommon. Evaluating neCT for high attenuation in dural sinuses, followed by CTV for confirmation in selected cases seems reasonable. CVST should be recognized by all radiologists and requires a high level of awareness when reading neCT for other indications.

Diagnostic value of alternative techniques to gadolinium-based contrast agents in MR neuroimaging-a comprehensive overview.

Gadolinium-based contrast agents (GBCAs) increase lesion detection and improve disease characterization for many cerebral pathologies investigated with MRI. These agents, introduced in the late 1980s, are in wide use today. However, some non-ionic linear GBCAs have been associated with the development of nephrogenic systemic fibrosis in patients with kidney failure. Gadolinium deposition has also been found in deep brain structures, although it is of unclear clinical relevance. Hence, new guidelines from the International Society for Magnetic Resonance in Medicine advocate cautious use of GBCA in clinical and research practice. Some linear GBCAs were restricted from use by the European Medicines Agency (EMA) in 2017.This review focuses on non-contrast-enhanced MRI techniques that can serve as alternatives for the use of GBCAs. Clinical studies on the diagnostic performance of non-contrast-enhanced as well as contrast-enhanced MRI methods, both well established and newly proposed, were included. Advantages and disadvantages together with the diagnostic performance of each method are detailed. Non-contrast-enhanced MRIs discussed in this review are arterial spin labeling (ASL), time of flight (TOF), phase contrast (PC), diffusion-weighted imaging (DWI), magnetic resonance spectroscopy (MRS), susceptibility weighted imaging (SWI), and amide proton transfer (APT) imaging.Ten common diseases were identified for which studies reported comparisons of non-contrast-enhanced and contrast-enhanced MRI. These specific diseases include primary brain tumors, metastases, abscess, multiple sclerosis, and vascular conditions such as aneurysm, arteriovenous malformation, arteriovenous fistula, intracranial carotid artery occlusive disease, hemorrhagic, and ischemic stroke.In general, non-contrast-enhanced techniques showed comparable diagnostic performance to contrast-enhanced MRI for specific diagnostic questions. However, some diagnoses still require contrast-enhanced imaging for a complete examination.

Sentinel Lymph Node Biopsy and Complete Lymph Node Dissection for Melanoma.

PURPOSE OF REVIEW: The main surgical treatment for invasive malignant melanoma consists of wide surgical and examination of the sentinel node and in selected cases complete lymph node dissection. The aim of this review is to present data for the optimal surgical management of patients with malignant melanoma. RECENT FINDINGS: A surgical excision margin of 1-2 cm is recommended for invasive melanoma depending on the thickness of the melanoma. Sentinel node biopsy may be considered for patients with at least T1b melanomas thickness 0.8 to 1.0 mm or less than 0.8 mm Breslow thickness with ulceration, classified as T1b lesion, per recent AJCC guidelines. Two randomized controlled trials have been published-DeCOG (German Dermatologic Cooperative Oncology Group Selective Lymphadenectomy) and MSLT-2 (Multicenter Selective Lymphadenectomy Trial) comparing the complete lymph node dissection (CLND) with observation after positive sentinel node biopsy. In the MSLT-2 study, the disease control rate was improved in the immediate CLND group compared with observation but there was no difference in 3-year melanoma specific survival (86% ± 1.3% and 86% ± 1.2%, respectively; p = 0.42). Isolated limb perfusion (ILP) or isolated limb infusion (ILI) with melphalan and actinomycin D is recommended for large and multiple in-transit metastases and satellite metastases in the extremities when local excision is considered ineffective or too extensive. In light of new adjuvant treatment options and new indications for checkpoint inhibitors, and the lack of survival benefit after CLND, we can expect open surgery to decrease in melanoma disease.

Arterial spin labeling MR imaging for differentiation between high- and low-grade glioma-a meta-analysis.

Background: Arterial spin labeling is an MR imaging technique that measures cerebral blood flow (CBF) non-invasively. The aim of the study is to assess the diagnostic performance of arterial spin labeling (ASL) MR imaging for differentiation between high-grade glioma and low-grade glioma. Methods: Cochrane Library, Embase, Medline, and Web of Science Core Collection were searched. Study selection ended November 2017. This study was prospectively registered in PROSPERO (CRD42017080885). Two authors screened all titles and abstracts for possible inclusion. Data were extracted independently by 2 authors. Bivariate random effects meta-analysis was used to describe summary receiver operating characteristics. Trial sequential analysis (TSA) was performed. Results: In total, 15 studies with 505 patients were included. The diagnostic performance of ASL CBF for glioma grading was 0.90 with summary sensitivity 0.89 (0.79-0.90) and specificity 0.80 (0.72-0.89). The diagnostic performance was similar between pulsed ASL (AUC 0.90) with a sensitivity 0.85 (0.71-0.91) and specificity 0.83 (0.69-0.92) and pseudocontinuous ASL (AUC 0.88) with a sensitivity 0.86 (0.79-0.91) and specificity 0.80 (0.65-0.87). In astrocytomas, the diagnostic performance was 0.89 with sensitivity 0.86 (0.79 to 0.91) and specificity 0.79 (0.63 to 0.89). Sensitivity analysis confirmed the robustness of the findings. TSA revealed that the meta-analysis was adequately powered. Conclusion: Arterial spin labeling MR imaging had an excellent diagnostic accuracy for differentiation between high-grade and low-grade glioma. Given its low cost, non-invasiveness, and efficacy, ASL MR imaging should be considered for implementation in the routine workup of patients with glioma.

Home institution bias in the New England Journal of Medicine? A noninferiority study on citation rates.

Recently, in the four top journals of humanities, an institutional bias towards publication of authors from Harvard and Yale was shown. The New England Journal of Medicine (NEJM) is today the highest ranked general medical journal. It is unknown if there exists institutional bias favoring publication of articles originating from Harvard University, since the NEJM is produced by the Massachusetts Medical Society with close connections to the Harvard University. We examined if studies originating from the Harvard University published in the NEJM were noninferior in terms of citation rates compared to articles with an origin outside Harvard University. We evaluated original research articles published in the NEJM in 2000 up until June 2001. A two-sample noninferiority test based on the primary endpoint of citations was performed. Twenty-two studies were affiliated to the Harvard University and 280 studies were not affiliated to the Harvard University. The mean number of citations for Harvard affiliated studies was 625 (95% CI 358-952, median 354) and for non-Harvard affiliated studies 493 (95% CI 421-569, median 303). The mean difference was not statistically different between affiliations, but fulfilled the requirements for noninferiority [132 (95% CI - 138-402, P = 0.343), Δ 200]. In summary, citation rates were comparable between studies origination from the Harvard University compared to non-Harvard Institutions. Based on these results there appears to be low risk of institutional bias in the publishing process of original studies in the NEJM.

Discrimination between primary low-grade and high-grade glioma with 11C-methionine PET: a bivariate diagnostic test accuracy meta-analysis.

OBJECTIVE: To perform a meta-analysis evaluating the diagnostic accuracy of 11C-methionine (MET) positron emission tomography (PET) to discriminate between primary low-grade glioma (LGG) and high-grade glioma (HGG). METHODS: A systematic database search was performed by a librarian in relevant databases with the latest search on 07 November 2016. Hits were assessed for inclusion independently by two authors. Individual patient data on relative MET uptake was extracted on patients examined pre-operatively with MET PET and subsequent neuropathological diagnosis of astrocytoma or oligodendroglioma. Individual patient data were analysed for diagnostic accuracy using a bivariate diagnostic random-effects meta-analysis model with restricted maximum likelihood estimation method. Bivariate meta-regression and subgroup analyses assessed study heterogeneity and validity. This study is registered with PROSPERO, number CRD42016050747. RESULTS: Out of 1828 hits, 13 studies comprising of 241 individuals were included in the quantitative and qualitative analysis. MET PET had an area under the bivariate summary receiver operating characteristics curve of 0.78 to discriminate between LGG and HGG and a summary sensitivity of 0.80 with 95% confidence interval (CI) (0.66-0.88) and a summary false positive rate of 0.28, 95% CI (0.19-0.38). Heterogeneity was described by; bias in patient inclusion, study quality, and ratio method. Optimal cutoff for relative MET uptake was 2.21. CONCLUSION: MET PET had a moderately high diagnostic accuracy for the discrimination between primary LGG and HGG. Advances in knowledge: MET PET can be used as a clinical tool for the non-invasive discrimination between LGG and HGG with a moderately high accuracy at cut-off 2.21.

Glioma Grade Discrimination with MR Diffusion Kurtosis Imaging: A Meta-Analysis of Diagnostic Accuracy.

Purpose To assess the diagnostic test accuracy and sources of heterogeneity for the discriminative potential of diffusion kurtosis imaging (DKI) to differentiate low-grade glioma (LGG) (World Health Organization [WHO] grade II) from high-grade glioma (HGG) (WHO grade III or IV). Materials and Methods The Cochrane Library, Embase, Medline, and the Web of Science Core Collection were systematically searched by two librarians. Retrieved hits were screened for inclusion and were evaluated with the revised tool for quality assessment for diagnostic accuracy studies (commonly known as QUADAS-2) by two researchers. Statistical analysis comprised a random-effects model with associated heterogeneity analysis for mean differences in mean kurtosis (MK) in patients with LGG or HGG. A bivariate restricted maximum likelihood estimation method was used to describe the summary receiver operating characteristics curve and bivariate meta-regression. Results Ten studies involving 430 patients were included. The mean difference in MK between LGG and HGG was 0.17 (95% confidence interval [CI]: 0.11, 0.22) with a z score equal to 5.86 (P < .001). The statistical heterogeneity was explained by glioma subtype, echo time, and the proportion of recurrent glioma versus primary glioma. The pooled area under the curve was 0.94 for discrimination of HGG from LGG, with 0.85 (95% CI: 0.74, 0.92) sensitivity and 0.92 (95% CI: 0.81, 0.96) specificity. Heterogeneity was driven by neuropathologic subtype and DKI technique. Conclusion MK shows high diagnostic accuracy in the discrimination of LGG from HGG. © RSNA, 2017 Online supplemental material is available for this article.

Outcome switching in randomized controlled oncology trials reporting on surrogate endpoints: a cross-sectional analysis.

Inconsistent reporting of clinical trials is well-known in the literature. Despite this, factors associated with poor practice such as outcome switching in clinical trials are poorly understood. We performed a cross-sectional analysis to evaluate the prevalence of, and the factors associated with outcome switching. PubMed and Embase were searched for pharmaceutical randomized controlled trials (RCTs) in oncology reporting on a surrogate primary outcome published in 2015. Outcome switching was present in 18% (39/216). First-author male sex was significantly more likely associated with outcome switching compared to female sex with an OR of 3.05 (95% CI 1.07-8.64, p = 0.04) after multivariable adjustment. For-profit funded RCTs were less likely associated with outcome switching compared to non-profit funded research with an OR of 0.22 (95% CI 0.07-0.74, p = 0.01). First author male sex was more likely associated with outcome switching compared to female sex in drug oncology RCTs reporting on a primary surrogate endpoint. For-profit funded research was less likely associated with outcome switching compared to research funded by non-profit organizations. Furthermore, 18 percent of drug oncology trials reporting on a surrogate endpoint could have a higher risk of false positive results due to primary outcome switching.

Self-declared stock ownership and association with positive trial outcome in randomized controlled trials with binary outcomes published in general medical journals: a cross-sectional study.

BACKGROUND: Describe the prevalence and types of conflicts of interest (COI) in published randomized controlled trials (RCTs) in general medical journals with a binary primary outcome and assess the association between conflicts of interest and favorable outcome. METHODS: Parallel-group RCTs with a binary primary outcome published in three general medical journals during 2013-2015 were identified. COI type, funding source, and outcome were extracted. Binomial logistic regression model was performed to assess association between COI and funding source with outcome. RESULTS: A total of 509 consecutive parallel-group RCTs were included in the study. COI was reported in 74% in mixed funded RCTs and in 99% in for-profit funded RCTs. Stock ownership was reported in none of the non-profit RCTs, in 7% of mixed funded RCTs, and in 50% of for-profit funded RCTs. Mixed-funded RCTs had employees from the funding company in 11% and for-profit RCTs in 76%. Multivariable logistic regression revealed that stock ownership in the funding company among any of the authors was associated with a favorable outcome (odds ratio = 3.53; 95% confidence interval = 1.59-7.86; p < 0.01). CONCLUSION: COI in for-profit funded RCTs is extensive, because the factors related to COI are not fully independent, a multivariable analysis should be cautiously interpreted. However, after multivariable adjustment only stock ownership from the funding company among authors is associated with a favorable outcome.

Ruptured carotid-ophthalmic aneurysm treatment: a non-inferiority meta-analysis comparing endovascular coiling and surgical clipping.

INTRODUCTION: Aneurysms of the carotid-ophthalmic segment are relatively rare, comprising only five percent of all intracranial aneurysms. There is no consensus regarding the optimal management for ruptured carotid-ophthalmic aneurysms, whether endovascular coiling or surgical clipping provide the most favourable patient outcome. The aim of this meta-analysis is to analyse these two treatment modalities for ruptured carotid-ophthalmic aneurysms with respect to independent clinical outcome. METHODS: We performed a systematic literature search in PubMed, Cochrane Central Registry of Controlled Trials and Clinicaltrials.gov for treatment of ruptured carotid-ophthalmic aneurysms, comparing endovascular coiling and surgical clipping. Primary outcome in the study was independent clinical patient outcome at follow up (defined as Glasgow Outcome Scale four-five). Secondary outcomes were poor clinical patient outcome, mortality and total angiographic occlusion. The meta-analysis was performed using the Mantel-Haenszel method for dichotomous outcome. RESULTS: Four studies met the inclusion criteria and were included in the meta-analysis. In total, 152 patients were included. Sixty-seven of these patients were treated with endovascular coiling and 85 patients were treated with microsurgical clipping. The proportion of patients with an independent clinical outcome after coiling and clipping was comparable, OR 1.04 (95% CI: 0.40, 2.71). The proportion of patients with an independent outcome in the endovascular group was 76% and in the surgical group 71%. Mortality between the two treatment arms was equal. CONCLUSION: Clinical outcome after endovascular coiling and surgical clipping for ruptured carotid-ophthalmic aneurysms was comparable between surgical clipping and endovascular coiling. There was no proven difference in clinical outcome after endovascular coiling and surgical clipping for ruptured carotid-ophthalmic aneurysms but the evidence was based on few studies of moderate to low quality and we cannot rule out the possibility of a difference in clinical outcome between the two treatment modalities.