Low- or standard-dose edoxaban versus antiplatelet therapy for leaflet thrombus and cerebral thromboembolism after TAVR: A prespecified analysis of randomized ADAPT-TAVR trial.

BACKGROUND: The risks of leaflet thrombosis and the associated cerebral thromboembolism are unknown according to different anticoagulation dosing after transcatheter aortic valve replacement (TAVR). The aim was to evaluate the incidence of leaflet thrombosis and cerebral thromboembolism between low-dose (30 mg) or standard-dose (60 mg) edoxaban and dual antiplatelet therapy (DAPT) after TAVR. METHODS: In this prespecified subgroup analysis of the ADAPT-TAVR trial, the primary endpoint was the incidence of leaflet thrombosis on 4-dimensional computed tomography at 6-months. Key secondary endpoints were new cerebral lesions on brain magnetic resonance imaging and neurological and neurocognitive dysfunction. RESULTS: Of 229 patients enrolled in this study, 118 patients were DAPT group and 111 were edoxaban group (43 [39.1%] 60 mg vs 68 [61.3%] 30 mg). There was a significantly lower incidence of leaflet thrombosis in the standard-dose edoxaban group than in the DAPT group (2.4% vs 18.3%; odds ratio [OR] 0.11; 95% confidence interval [CI], 0.01-0.55; P = .03). However, no significant difference was observed between low-dose edoxaban and DAPT (15.0% vs 18.3%; OR 0.79; 95% CI, 0.32-1.81; P = .58). Irrespective of different antithrombotic regiments, the percentages of patients with new cerebral lesions on brain MRI and worsening neurological or neurocognitive function were not significantly different. CONCLUSIONS: In patients without an indication for anticoagulation after TAVR, the incidence of leaflet thrombosis was significantly lower with standard-dose edoxaban but not with low-dose edoxaban, as compared with DAPT. However, this differential effect of edoxaban on leaflet thrombosis was not associated with a reduction of new cerebral thromboembolism and neurological dysfunction.

Achieving imaging and computational reproducibility on multiparametric MRI radiomics features in brain tumor diagnosis: phantom and clinical validation.

OBJECTIVES: The Image Biomarker Standardization Initiative has helped improve the computational reproducibility of MRI radiomics features. Nonetheless, the MRI sequences and features with high imaging reproducibility are yet to be established. To determine reproducible multiparametric MRI radiomics features across test-retest, multi-scanner, and computational reproducibility comparisons, and to evaluate their clinical value in brain tumor diagnosis. METHODS: To assess reproducibility, T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), and diffusion-weighted imaging (DWI) were acquired from three 3-T MRI scanners using standardized phantom, and radiomics features were extracted using two computational algorithms. Reproducible radiomics features were selected when the concordance correlation coefficient value above 0.9 across multiple sessions, scanners, and computational algorithms. Random forest classifiers were trained with reproducible features (n = 117) and validated in a clinical cohort (n = 50) to evaluate whether features with high reproducibility improved the differentiation of glioblastoma from primary central nervous system lymphomas (PCNSLs). RESULTS: Radiomics features from T2WI demonstrated higher repeatability (65-94%) than those from DWI (38-48%) or T1WI (2-92%). Across test-retest, multi-scanner, and computational comparisons, T2WI provided 41 reproducible features, DWI provided six, and T1WI provided two. The performance of the classification model with reproducible features was higher than that using non-reproducible features in both training set (AUC, 0.916 vs. 0.877) and validation set (AUC, 0.957 vs. 0.869). CONCLUSION: Radiomics features with high reproducibility across multiple sessions, scanners, and computational algorithms were identified, and they showed higher diagnostic performance than non-reproducible radiomics features in the differentiation of glioblastoma from PCNSL. CLINICAL RELEVANCE STATEMENT: By identifying the radiomics features showing higher multi-machine reproducibility, our results also demonstrated higher radiomics diagnostic performance in the differentiation of glioblastoma from PCNSL, paving the way for further research designs and clinical application in neuro-oncology. KEY POINTS: • Highly reproducible radiomics features across multiple sessions, scanners, and computational algorithms were identified using phantom and applied to clinical diagnosis. • Radiomics features from T2-weighted imaging were more reproducible than those from T1-weighted and diffusion-weighted imaging. • Radiomics features with good reproducibility had better diagnostic performance for brain tumors than features with poor reproducibility.

Edoxaban Versus Dual Antiplatelet Therapy for Leaflet Thrombosis and Cerebral Thromboembolism After TAVR: The ADAPT-TAVR Randomized Clinical Trial.

BACKGROUND: It is unknown whether the direct oral anticoagulant edoxaban can reduce leaflet thrombosis and the accompanying cerebral thromboembolic risk after transcatheter aortic valve replacement. In addition, the causal relationship of subclinical leaflet thrombosis with cerebral thromboembolism and neurological or neurocognitive dysfunction remains unclear. METHODS: We conducted a multicenter, open-label randomized trial comparing edoxaban with dual antiplatelet therapy (aspirin plus clopidogrel) in patients who had undergone successful transcatheter aortic valve replacement and did not have an indication for anticoagulation. The primary end point was an incidence of leaflet thrombosis on 4-dimensional computed tomography at 6 months. Key secondary end points were the number and volume of new cerebral lesions on brain magnetic resonance imaging and the serial changes of neurological and neurocognitive function between 6 months and immediately after transcatheter aortic valve replacement. RESULTS: A total of 229 patients were included in the final intention-to-treat population. There was a trend toward a lower incidence of leaflet thrombosis in the edoxaban group compared with the dual antiplatelet therapy group (9.8% versus 18.4%; absolute difference, -8.5% [95% CI, -17.8% to 0.8%]; P=0.076). The percentage of patients with new cerebral lesions on brain magnetic resonance imaging (edoxaban versus dual antiplatelet therapy, 25.0% versus 20.2%; difference, 4.8%; 95% CI, -6.4% to 16.0%) and median total new lesion number and volume were not different between the 2 groups. In addition, the percentages of patients with worsening of neurological and neurocognitive function were not different between the groups. The incidence of any or major bleeding events was not different between the 2 groups. We found no significant association between the presence or extent of leaflet thrombosis with new cerebral lesions and a change of neurological or neurocognitive function. CONCLUSIONS: In patients without an indication for long-term anticoagulation after successful transcatheter aortic valve replacement, the incidence of leaflet thrombosis was numerically lower with edoxaban than with dual antiplatelet therapy, but this was not statistically significant. The effects on new cerebral thromboembolism and neurological or neurocognitive function were also not different between the 2 groups. Because the study was underpowered, the results should be considered hypothesis generating, highlighting the need for further research. REGISTRATION: URL: https://www. CLINICALTRIALS: gov. Unique identifier: NCT03284827.

Impact of lesion size on reproducibility of quantitative measurement and radiomic features in vessel wall MRI.

OBJECTIVES: To investigate reproducibility of quantitative measurement and radiomic features in vessel wall MRI (VW-MRI), evaluate the impact of lesion size, and identify reproducible radiomic features. METHODS: This retrospective, single-center study included 251 patients (mean age, 53 ± 12 years; 128 women) with atherosclerosis, dissection, aneurysm, moyamoya disease, and vasculitis of the intracranial arteries who underwent three-dimensional turbo spin echo T1-weighted image. Lesion thickness, volume, and signal intensity were measured, and 157 radiomic features were extracted. Intra-observer reproducibility of quantitative measurement and radiomic features was evaluated by calculating the concordance correlation coefficient (CCC) and proportion of radiomic features above the predefined CCC. The reproducibility of quantitative measurement and radiomic features according to lesion size (binary comparison and stratification into 5 and 18 groups) was evaluated. RESULTS: There was an overall serial increase in CCC for thickness measurement when stratified by lesion thickness and volume. There was an overall serial increase in the median CCC for radiomic features and proportion of radiomic features with CCC > 0.85 when stratified by lesion thickness and volume. Reproducibility of radiomic features was higher in the lesions with thickness ≥ 2.5 mm (median CCC, 0.97 vs. 0.89, p < .001; proportion with CCC > 0.85, 88.5% vs. 59.6%, p < .001) and volume ≥ 50 mm3 (median CCC, 0.97 vs. 0.88, p < .001; proportion with CCC > 0.85, 90.4% vs. 59.0%, p < .001). Intensity-based statistical features remained most reproducible in the thinnest and smallest lesions. CONCLUSIONS: Intra-observer reproducibility of thickness measurement and radiomic features was affected by lesion size in VW-MRI although intensity-based statistical features remained most reproducible. KEY POINTS: • There was an overall serial increase in CCC for thickness measurement when stratified by lesion size. • There was an overall serial increase in the median CCC for radiomic features and proportion of radiomic features with CCC > 0.85 when stratified by lesion size. • Intensity-based statistical features remained most reproducible in the thinnest and smallest lesions.

Structural Changes of Intra and Extracranial Artery Dissection: a Study of High-Resolution Magnetic Resonance Imaging.

OBJECTIVES: The prognosis of a cerebral artery dissection is known to be benign, but the structural changes of vessel wall at follow-up are not well known. The natural course of an intracranial and extracranial artery dissection may differ due to structural differences. We aimed to figure out how stenosis and other wall features change, according to the dissection location. MATERIALS AND METHODS: We retrospectively enrolled patients who suffered an ischemic stroke or transient ischemic attack due to a dissection and who had undergone both initial and follow-up high-resolution magnetic resonance imaging (HRMRI). Patients were dichotomized to intracranial or extracranial dissection group. The clinical and HRMRI characteristics of two groups were compared. Factors associated with stenosis changes were also investigated. RESULTS: A total of 57 patients (intracranial, n = 43; and extracranial, n = 14) were enrolled. The mean age (45.6 vs. 32.2, p < 0.001) was higher and hypertension (37.2% vs. 7.1%, p = 0.04) was more frequent in the intracranial dissection group. In HRMRI analysis, stenosis improvement (27.9% vs. 85.7%, p < 0.001) were more frequent whereas residual wall enhancement (86.0% vs. 46.2%, p = 0.006) and intramural hematoma (62.8% vs. 21.4%, p = 0.007) were less frequent in the extracranial dissection group. Multivariate analysis indicated that extracranial location was the only independent factor (odds ratio 8.98, 95 % confidence interval 1.45-55.65; p = 0.02) associated with stenosis improvement. CONCLUSIONS: Younger age, stenosis improvement, disappearance of wall enhancement and intramural hematoma were more frequent in an extracranial dissection compared with an intracranial dissection. An extracranial location is independently associated with stenosis improvement in dissection patients.

Reproducibility of radiomic features in SENSE and compressed SENSE: impact of acceleration factors.

OBJECTIVES: To investigate the impact of acceleration factors on reproducibility of radiomic features in sensitivity encoding (SENSE) and compressed SENSE (CS), compare between SENSE and CS, and identify reproducible radiomic features. METHODS: Three-dimensional turbo spin echo T1-weighted imaging was performed in 14 healthy volunteers (mean age, 57 years; range, 33-67 years; 7 men) under SENSE and CS with accelerator factors of 5.5, 6.8, and 9.7. Eight anatomical locations (brain parenchyma, salivary glands, masseter muscle, tongue, pharyngeal mucosal space, eyeballs) were evaluated. Reproducibility of radiomic features was evaluated by calculating concordance correlation coefficient (CCC) in reference to the original image (SENSE with acceleration factor of 3.5). Reproducibility of radiomic features among acceleration factors and between SENSE and CS was compared. RESULTS: Proportion of radiomic features with CCC > 0.85 in reference to the original image was lower with higher acceleration factors in both SENSE and CS across all anatomical locations (p < .001). Proportion of radiomic features with CCC > 0.85 in reference to the original image was higher in SENSE compared with CS (SENSE, 6.7-7.3% vs CS, 4.4-5.0%; p < .001). Run percentage of gray-level run-length matrix (GLRLM) with wavelet D showed CCC > 0.85 in reference to the original image in both SENSE and CS at acceleration factor of 9.7 in the highest number of anatomical locations. CONCLUSIONS: Higher acceleration factors resulted in lower reproducibility of radiomic features in both SENSE and CS, and SENSE showed higher reproducibility of radiomic features than CS in reference to the original image. Run percentage of GLRLM with wavelet D was identified as the most reproducible feature. KEY POINTS: • Reproducibility of radiomic features in reference to the original image was lower with higher acceleration factors in both sensitivity encoding (SENSE) and compressed SENSE (CS) across all anatomical locations (p < .001). • SENSE showed higher proportions of radiomic features with CCC > 0.85 in reference to the original image (SENSE, 6.7-7.3% vs CS, 4.4-5.0%; p < .001) compared with CS. • Run percentage of gray-level run-length matrix (GLRLM) with wavelet D showed CCC > 0.85 in reference to the original image in both SENSE and CS with the highest acceleration factor.

Identification of Early Response to Anti-Angiogenic Therapy in Recurrent Glioblastoma: Amide Proton Transfer-weighted and Perfusion-weighted MRI compared with Diffusion-weighted MRI.

Background Amide proton transfer (APT) MRI has the potential to demonstrate antitumor effects by reflecting biologically active tumor portion, providing different information from diffusion-weighted imaging (DWI) or dynamic susceptibility contrast (DSC) imaging. Purpose To evaluate whether a change in APT signal intensity after antiangiogenic treatment is predictive of early treatment response in recurrent glioblastoma. Materials and Methods In this retrospective study, APT MRI, DWI, and DSC imaging were performed in patients with recurrent glioblastoma from July 2015 to April 2019, both before treatment and 4-6 weeks after initiation of bevacizumab (follow-up). Progression was based on pathologic confirmation or clinical-radiologic assessment, and progression patterns were defined as local enhancing or diffuse nonenhancing. Changes in mean and histogram parameters (fifth and 95th percentiles) of APT signal intensity, apparent diffusion coefficient, and normalized cerebral blood volume (CBV) between imaging time points were calculated. Predictors of 12-month progression and progression-free survival (PFS) were determined by using logistic regression and Cox proportional hazard modeling and according to progression type. Results A total of 54 patients were included (median age, 56 years [interquartile range, 49-64 years]; 24 men). Mean APT signal intensity change after bevacizumab treatment indicated a low 12-month progression rate (odds ratio [OR], 0.36; 95% confidence interval [CI]: 0.13, 0.90; P = .04) and longer PFS (hazard ratio: 0.38; 95% CI: 0.20, 0.74; P = .004). High mean normalized CBV at follow-up was associated with a high 12-month progression rate (OR, 20; 95% CI: 2.7, 32; P = .04) and shorter PFS (hazard ratio, 9.4; 95% CI: 2.3, 38; P = .002). Mean APT signal intensity change was a significant predictor of diffuse nonenhancing progression (OR, 0.27; 95% CI: 0.06, 0.85; P = .047), whereas follow-up 95th percentile of the normalized CBV was a predictor of local enhancing progression (OR, 7.1; 95% CI: 2.4, 15; P = .04). Conclusion Early reduction in mean amide proton transfer signal intensity at 4-6 weeks after initiation of antiangiogenic treatment was predictive of a better response at 12 months and longer progression-free survival in patients with recurrent glioblastoma, especially in those with diffuse nonenhancing progression. © RSNA, 2020 Online supplemental material is available for this article.

Repeatability of amide proton transfer-weighted signals in the brain according to clinical condition and anatomical location.

OBJECTIVES: To investigate whether clinical condition, imaging session, and locations affect repeatability of amide proton transfer-weighted (APTw) magnetic resonance imaging (MRI) in the brain. MATERIALS AND METHODS: Three APTw MRI data sets were acquired, involving two intrasession scans and one intersession scan for 19 healthy, 15 glioma, and 12 acute stroke adult participants (mean age 53.8, 54.6, and 68.5, respectively) on a 3T MR scanner. The mean APTw signals from five locations in healthy brain (supratentorial and infratentorial locations) and from entire tumor and stroke lesions (supratentorial location) were calculated. The within-subject coefficient of variation (wCV) and intraclass correlation coefficient (ICC) were calculated for each clinical conditions, image sessions, and anatomic locations. Differences in APTw signals between sessions were analyzed using repeated-measures analysis of variance. RESULTS: The ICC and wCV were 0.96 (95% confidence interval [CI], 0.91-0.99) and 16.1 (12.6-21.3) in glioma, 0.93 (0.82-0.98) and 15.0 (11.4-20.6) in stroke, and 0.84 (0.72-0.91) and 34.0 (28.7-41.0) in healthy brain. There were no significant differences in APTw signal between three sessions, irrespective of disease condition and location. The ICC and wCV were 0.85 (0.68-0.94) and 27.4 (21.8-35.6) in supratentorial, and 0.44 (- 0.18 to 0.76) and 32.7 (25.9 to 42.9) in infratentorial locations. There were significant differences in APTw signal between supra- (mean, 0.49%; 95% CI, 0.38-0.61) and infratentorial locations (1.09%, 0.98-1.20; p < 0.001). CONCLUSION: The repeatability of APTw signal was excellent in supratentorial locations, while it was poor in infratentorial locations due to severe B0 inhomogeneity and susceptibility which affects MTR asymmetry. KEY POINTS: • In supratentorial locations, APTw MRI showed excellent intrasession and intersession repeatability in brains of healthy controls and patients with glioma, as well as in stroke-affected regions. • APTw MRI showed excellent repeatability in supratentorial locations, but poor repeatability in infratentorial locations. • Considering poor repeatability in the infratentorial locations, the use of APTw MRI in longitudinal assessment in infratentorial locations is not indicated.

MRI for prediction of hemorrhagic transformation in acute ischemic stroke: a systematic review and meta-analysis.

BACKGROUND: Hemorrhagic transformation increases mortality and morbidity in patients with acute ischemic stroke. PURPOSE: The purpose of this study is to evaluate the diagnostic performance of magnetic resonance imaging (MRI) for prediction of hemorrhagic transformation in acute ischemic stroke. MATERIAL AND METHODS: A systematic literature search of MEDLINE and EMBASE was performed up to 27 July 2018, including the search terms "acute ischemic stroke," "hemorrhagic transformation," and "MRI." Studies evaluating the diagnostic performance of MRI for prediction of hemorrhagic transformation in acute ischemic stroke were included. Diagnostic meta-analysis was conducted with a bivariate random-effects model to calculate the pooled sensitivity and specificity. Subgroup analysis was performed including studies using advanced MRI techniques including perfusion-weighted imaging, diffusion-weighted imaging, and susceptibility-weighted imaging. RESULTS: Nine original articles with 665 patients were included. Hemorrhagic transformation is associated with high permeability, hypoperfusion, low apparent diffusion coefficient (ADC), and FLAIR hyperintensity. The pooled sensitivity was 82% (95% confidence interval [CI] 61-93) and the pooled specificity was 79% (95% CI 71-85). The area under the hierarchical summary receiver operating characteristic curve was 0.85 (95% CI 0.82-0.88). Although study heterogeneity was present in both sensitivity (I2=67.96%) and specificity (I2=78.93%), a threshold effect was confirmed. Studies using advanced MRI showed sensitivity of 92% (95% CI 70-98) and specificity of 78% (95% CI 65-87) to conventional MRI. CONCLUSION: MRI may show moderate diagnostic performance for predicting hemorrhage in acute ischemic stroke although the clinical significance of this hemorrhage is somewhat uncertain.

Primary Central Nervous System Lymphoma: Diagnostic Yield of Whole-Body CT and FDG PET/CT for Initial Systemic Imaging.

Background Updated guidelines for suspected primary central nervous system lymphoma (PCNSL) are lacking. Purpose To investigate the diagnostic yield of initial systemic imaging in patients suspected of having PCNSL by using contrast material-enhanced chest and abdominopelvic CT and/or whole-body fluorine 18 fluorodeoxyglucose (FDG) PET/CT. Materials and Methods This retrospective study included 304 patients examined at a single tertiary hospital between January 1998 and October 2018. Consecutive adults (age >18 years) who were confirmed to have newly diagnosed PCNSL on the basis of findings at stereotactic brain biopsy were recruited. All patients were examined with contrast-enhanced chest and abdominopelvic CT and/or whole-body FDG PET/CT before initiation of PCNSL treatment. The diagnostic yield of CT and PET/CT was determined before therapy and at the time of recurrence in the brain. A χ2 test was performed to compare the diagnostic yield according to study date in order to assess for possible changes in technology during the study period. Results A total of 304 patients (180 men with a mean age [±standard deviation] of 58 years ± 13 and 124 women with a mean age of 59 years ± 13) were included. The diagnostic yield of CT and PET/CT for initial staging was 2% (six of 304 patients; 95% confidence interval [CI]: 0.7%, 4.3%), and these tests yielded false-positive findings in 13 of the 304 patients (4%; 95% CI: 2.3%, 7.2%). Diagnostic yield did not differ between patients evaluated before 2009 and those evaluated in 2009 and later (P = .82). The diagnostic yield of systemic imaging at recurrence was 1.5% (one of 68 patients; 95% CI: 0.0%, 7.9%), and these tests yielded false-positive findings in four of those 68 patients (6%; 95% CI: 1.6%, 14.4%). Conclusion Contrast-enhanced chest and abdominopelvic CT and/or whole-body fluorine 18 fluorodeoxyglucose PET/CT for initial staging, as well as for recurrence of suspected primary central nervous system lymphoma, had a low diagnostic yield. © RSNA, 2019 See also the editorial by Jara in this issue.

False-Positive Measurement at 2-Hydroxyglutarate MR Spectroscopy in Isocitrate Dehydrogenase Wild-Type Glioblastoma: A Multifactorial Analysis.

Background Isocitrate dehydrogenase (IDH) mutation has become one of the most important prognostic biomarkers in glioma management. Measurement of 2-hydroxyglutarate (2HG) with MR spectroscopy has shown high pooled sensitivity, although false-positive results with MR spectroscopy have been reported. Purpose To investigate factors associated with false-positive 2HG measurements at MR spectroscopy in patients with IDH wild-type glioblastoma. Materials and Methods This retrospective study was approved by the institutional review board, and informed consent was waived. Consecutive patients with histopathologically confirmed pre- and posttreatment glioblastoma were evaluated between December 2017 and August 2018. Spectroscopy parameters, including 2HG measurements, were obtained with single-voxel point-resolved spectroscopy, and apparent diffusion coefficient (ADC) values were calculated. Necrosis was graded according to the proportion of necrosis within a volume of interest. Poisson regression analyses were performed to determine factors related to false-positive 2HG measurements. Results A total of 82 patients were included (mean age, 55 years ± 12 [standard deviation]; 40 men). The 2HG measurement showed a false-positive rate of 21% (17 of 82; 95% CI: 13%, 31%) in patients with IDH wild-type glioblastoma. Multivariable analysis revealed that necrosis (prevalence ratio [PR], 3.9; 95% CI: 1.6, 9.4; P = .01) and ADC value (PR, 0.1 × 10-3 mm2/sec; 95% CI: [0.0, 0.7] × 10-3 mm2/sec; P = .02) were associated with a greater false-positive rate for the 2HG measurement. Necrosis of more than 20% was associated with a higher rate of false-positive 2HG measurements (50%) than was necrosis of 20% or less (15%, P = .01). The 2HG false-positive rate was higher in patients with pretreatment glioblastoma (46%) than in those with posttreatment glioblastoma (14%, P < .01). Among 17 patients with false-positive findings, 15 (88%; 95% CI: 64%, 99%) had a lactate concentration of 2.0 mmol/L or higher, and 14 (82%, 95% CI: 57%, 96%) had a lactate concentration of 3.0 mmol/L or higher. Conclusion Necrosis and apparent diffusion coefficient were associated with false-positive measurements of 2-hydroxyglutarate at MR spectroscopy in patients with isocitrate dehydrogenase wild-type glioblastoma. © RSNA, 2019 Online supplemental material is available for this article.

MRI as a diagnostic biomarker for differentiating primary central nervous system lymphoma from glioblastoma: A systematic review and meta-analysis.

BACKGROUND: Accurate preoperative differentiation of primary central nervous system lymphoma (PCNSL) and glioblastoma is clinically crucial because the treatment strategies differ substantially. PURPOSE: To evaluate the diagnostic performance of MRI for differentiating PCNSL from glioblastoma. STUDY TYPE: Systematic review and meta-analysis. SUBJECTS: Ovid-MEDLINE and EMBASE databases were searched to find relevant original articles up to November 25, 2018. The search term combined synonyms for "lymphoma," "glioblastoma," and "MRI." FIELD STRENGTH/SEQUENCE: Patients underwent at least one MRI sequence including diffusion-weighted imaging (DWI), dynamic susceptibility-weighted contrast-enhanced imaging (DSC), dynamic contrast-enhanced imaging (DCE), arterial spin labeling (ASL), susceptibility-weighted imaging (SWI), intravoxel incoherent motion (IVIM), and magnetic resonance spectroscopy (MRS) using 1.5 or 3 T. ASSESSMENT: Quality assessment was performed according to the Quality Assessment of Diagnostic Accuracy Studies-2 tool. STATISTICAL TESTS: Hierarchical logistic regression modeling was used to obtain pooled sensitivity and specificity. Meta-regression was performed. RESULTS: Twenty-two studies with 1182 patients were included. MRI sequences demonstrated high overall diagnostic performance with pooled sensitivity of 91% (95% confidence interval [CI], 87-93%) and specificity of 89% (95% CI, 85-93%). The area under the hierarchical summary receiver operating characteristic curve was 0.92 (95% CI, 0.90-0.94). Studies using DSC or ASL showed high diagnostic performance (sensitivity of 93% [95% CI, 89-97%] and specificity of 91% [95% CI, 86-96%]). Heterogeneity was only detected in specificity (I2 = 66.84%) and magnetic field strength was revealed to be a significant factor affecting study heterogeneity. DATA CONCLUSION: MRI showed overall high diagnostic performance for differentiating PCNSL from glioblastoma, with studies using DSC or ASL showing high diagnostic performance. Therefore, MRI sequences including DSC or ASL is a potential diagnostic tool for differentiating PCNSL from glioblastoma. LEVEL OF EVIDENCE: 3 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2019;50:560-572.

Imaging prediction of isocitrate dehydrogenase (IDH) mutation in patients with glioma: a systemic review and meta-analysis.

OBJECTIVES: To evaluate the imaging features of isocitrate dehydrogenase (IDH) mutant glioma and to assess the diagnostic performance of magnetic resonance imaging (MRI) for prediction of IDH mutation in patients with glioma. METHODS: A systematic search of Ovid-MEDLINE and EMBASE up to 10 October 2017 was conducted to find relevant studies. The search terms combined synonyms for 'glioma', 'IDH mutation' and 'MRI'. Studies evaluating the imaging features of IDH mutant glioma and the diagnostic performance of MRI for prediction of IDH mutation in patients with glioma were selected. The pooled summary estimates of sensitivity and specificity and their 95% confidence intervals (CIs) were calculated using a bivariate random-effects model. The results of multiple subgroup analyses are reported. RESULTS: Twenty-eight original articles in a total of 2,146 patients with glioma were included. IDH mutant glioma showed frontal lobe predominance, less contrast enhancement, well-defined border, high apparent diffusion coefficient (ADC) value and low relative cerebral blood volume (rCBV) value. For the meta-analysis that included 18 original articles, the summary sensitivity was 86% (95% CI, 79%-91%) and the summary specificity was 87% (95% CI, 78-92%). In a subgroup analysis, the summary sensitivity of 2-hydroxyglutarate magnetic resonance spectroscopy (MRS) [96% (95% CI, 91-100%)] was higher than the summary sensitivities of other imaging modalities. CONCLUSIONS: IDH mutant glioma consistently demonstrated less aggressive imaging features than IDH wild-type glioma. Despite the variety of different MRI techniques used, MRI showed the potential to non-invasively predict IDH mutation in patients with glioma. 2-Hydroxyglutarate MRS shows higher pooled sensitivity than other imaging modalities. KEY POINTS: • IDH mutant glioma showed frontal lobe predominance, less contrast enhancement, well-defined border, high ADC value, and low rCBV value. • The diagnostic performance of MRI for prediction of IDH mutation in patients with glioma is within a clinically acceptable range, the summary sensitivity was 86% (95% CI, 79-91%) and the summary specificity was 87% (95% CI, 78-92%). • In a subgroup analysis, the summary sensitivity of 2-hydroxyglutarate MRS [96% (95% CI, 91-100%)] was higher than the summary sensitivities of other imaging modalities.

Technical performance of shear wave elastography for measuring liver stiffness in pediatric and adolescent patients: a systematic review and meta-analysis.

OBJECTIVE: To assess the technical performance (proportion of technical failure and unreliable measurements) of shear wave elastography (SWE) for assessing liver stiffness in pediatric and adolescent patients. METHODS: We searched Ovid-MEDLINE and EMBASE databases for eligible studies and selected original articles investigating transient elastography (TE), point shear wave elastography (pSWE), or two-dimensional SWE (2D-SWE) for measuring liver stiffness in pediatric and adolescent patients. A quantitative synthesis of studies reporting technical failures and/or unreliable measurements of TE, pSWE, or 2D-SWE is presented. Meta-analytic pooling was conducted using the random effects model. Meta-regression analysis was conducted to explore potential causes of heterogeneity. RESULTS: Forty of 69 studies (58%) provided technical performance information. Technical failure data were reported in 3 TE, 6 pSWE, and 8 2D-SWE studies. Unreliable measurement data were provided in 21 TE, 4 pSWE, and 1 2D-SWE study. The pooled proportion of unreliable measurements of TE was 12.1%. Meta-regression analysis showed that the study population size and readers' blinding to pathologic results affected the study's heterogeneity. The pooled proportions of technical failure during pSWE and 2D-SWE were 4.1% and 2.2%, respectively, demonstrating no significant difference between the techniques. CONCLUSIONS: We reviewed the technical performance of SWE, especially the rate of unreliable measurements from TE studies and rates of technical failure from pSWE and 2D-SWE studies. Considering the importance of technical performance for clinical validation of SWE, numbers of and reasons for technical failure and unreliable measurements should be reported in future studies. Further efforts are necessary to standardize SWE reliability criteria. KEY POINTS: • Most TE studies reported rate of unreliable measurements, whereas pSWE and 2D-SWE studies were likely to report rates of technical failure. • The pooled proportion of unreliable measurements of TE was 12.1%. • The pooled proportions of technical failure during pSWE and 2D-SWE were 4.1% and 2.2%, respectively, demonstrating no significant difference between the techniques.

Perfusion CT for prediction of hemorrhagic transformation in acute ischemic stroke: a systematic review and meta-analysis.

OBJECTIVE: To investigate the diagnostic performance of perfusion CT for prediction of hemorrhagic transformation in acute ischemic stroke. METHODS: A computerized literature search of Ovid MEDLINE and EMBASE was conducted up to October 29, 2018. Search terms included acute ischemic stroke, hemorrhagic transformation, and perfusion CT. Studies assessing the diagnostic performance of perfusion CT for prediction of hemorrhagic transformation in acute ischemic stroke were included. Two reviewers independently evaluated the eligibility of the studies. A bivariate random effects model was used to calculate the pooled sensitivity and pooled specificity. Multiple subgroup analyses were performed. RESULTS: Fifteen original articles with a total of 1134 patients were included. High blood-brain barrier permeability and hypoperfusion status derived from perfusion CT are associated with hemorrhagic transformation. The pooled sensitivity and specificity were 84% (95% CI, 71-91%) and 74% (95% CI, 67-81%), respectively. The area under the hierarchical summary receiver operating characteristic curve was 0.84 (95% CI, 0.81-0.87). The Higgins I2 statistic demonstrated that heterogeneity was present in the sensitivity (I2 = 80.21%) and specificity (I2 = 85.94%). CONCLUSION: Although various perfusion CT parameters have been used across studies, the current evidence supports the use of perfusion CT to predict hemorrhagic transformation in acute ischemic stroke. KEY POINTS: • High blood-brain barrier permeability and hypoperfusion status derived from perfusion CT were associated with hemorrhagic transformation. • Perfusion CT has moderate diagnostic performance for the prediction of hemorrhagic transformation in acute ischemic stroke. • The pooled sensitivity was 84%, and the pooled specificity was 74%.

Amide proton transfer-weighted MRI can detect tissue acidosis and monitor recovery in a transient middle cerebral artery occlusion model compared with a permanent occlusion model in rats.

OBJECTIVES: To assess whether increases in amide proton transfer (APT)-weighted signal reflect the effects of tissue recovery from acidosis using transient rat middle cerebral artery occlusion (MCAO) models, compared to permanent occlusion models. MATERIALS AND METHODS: Twenty-four rats with MCAO (17 transient and seven permanent occlusions) were prepared. APT-weighted signal (APTw), apparent diffusion coefficient (ADC), cerebral blood flow (CBF), and MR spectroscopy were evaluated at three stages in each group (occlusion, reperfusion/1 h post-occlusion, and 3 h post-reperfusion/4 h post-occlusion). Deficit areas showing 30% reduction to the contralateral side were measured. Temporal changes were compared with repeated measures of analysis of variance. Relationship between APTw and lactate concentration was calculated. RESULTS: Both APTw and CBF values increased and APTw deficit area reduced at reperfusion (largest p = .002) in transient occlusion models, but this was not demonstrated in permanent occlusion. No significant temporal change was demonstrated with ADC at reperfusion. APTw deficit area was between ADC and CBF deficit areas in transient occlusion model. APTw correlated with lactate concentration at occlusion (r = - 0.49, p = .04) and reperfusion (r = - 0.32, p = .02). CONCLUSIONS: APTw values increased after reperfusion and correlated with lactate content, which suggests that APT-weighted MRI could become a useful imaging technique to reflect tissue acidosis and its reversal. KEY POINTS: • APT-weighted signal increases in the tissue reperfusion, while remains stable in the permanent occlusion. • APTw deficit area was between ADC and CBF deficit areas in transient occlusion model, possibly demonstrating metabolic penumbra. • APTw correlated with lactate concentration during ischemia and reperfusion, indicating tissue acidosis.

Reliability of fast magnetic resonance imaging for acute ischemic stroke patients using a 1.5-T scanner.

OBJECTIVES: To determine whether fast scanned MRI using a 1.5-T scanner is a reliable method for the detection and characterization of acute ischemic stroke in comparison with conventional MRI. METHODS: From May 2015 to June 2016, 862 patients (FLAIR, n = 482; GRE, n = 380; MRA, n = 190) were prospectively enrolled in the study, with informed consent and under institutional review board approval. The patients underwent both fast (EPI-FLAIR, ETL-FLAIR, TR-FLAIR, EPI-GRE, parallel-GRE, fast CE-MRA) and conventional MRI (FLAIR, GRE, time-of-flight MRA, fast CE-MRA). Two neuroradiologists independently assessed agreements in acute and chronic ischemic hyperintensity, hyperintense vessels (FLAIR), microbleeds, susceptibility vessel signs, hemorrhagic transformation (GRE), stenosis (MRA), and image quality (all MRI), between fast and conventional MRI. Agreements between fast and conventional MRI were evaluated by generalized estimating equations. Z-scores were used for comparisons of the percentage agreement among fast FLAIR sequences and fast GRE sequences and between conventional and fast MRA. RESULTS: Agreements of more than 80% were achieved between fast and conventional MRI (ETL-FLAIR, 96%; TR-FLAIR, 97%; EPI-GRE, 96%; parallel-GRE, 98%; fast CE-MRA, 86%). ETL- and TR-FLAIR were significantly superior to EPI-FLAIR in the detection of acute ischemic hyperintensity and hyperintense vessels, while parallel-GRE was significantly superior to EPI-GRE in the detection of susceptibility vessel sign (p value < 0.05 for all). There were no significant differences in the other scores and image qualities (p value > 0.05). CONCLUSIONS: Fast MRI at 1.5 T is a reliable method for the detection and characterization of acute ischemic stroke in comparison with conventional MRI. KEY POINTS: • Fast MRI at 1.5 T may achieve a high intermethod reliability in the detection and characterization of acute ischemic stroke with a reduction in scan time in comparison with conventional MRI.

Amide proton transfer-weighted MRI in distinguishing high- and low-grade gliomas: a systematic review and meta-analysis.

PURPOSE: Grading of brain gliomas is of clinical importance, and noninvasive molecular imaging may help differentiate low- and high-grade gliomas. We aimed to evaluate the diagnostic performance of amide proton transfer-weighted (APTw) MRI for differentiating low- and high-grade gliomas on 3-T scanners. METHODS: A systematic literature search of Ovid-MEDLINE and EMBASE was performed up to March 28, 2018. Original articles evaluating the diagnostic performance of APTw MRI for differentiating low- and high-grade gliomas were selected. The pooled sensitivity and specificity were calculated using a bivariate random-effects model. A coupled forest plot and a hierarchical summary receiver operating characteristic curve were obtained. Heterogeneity was investigated using Higgins inconsistency index (I2) test. Meta-regression was performed. RESULTS: Ten original articles with a total of 353 patients were included. High-grade gliomas showed significantly higher APT signal intensity than low-grade gliomas. The pooled sensitivity and specificity for the diagnostic performance of APTw MRI for differentiating low-grade and high-grade gliomas were 88% (95% CI, 77-94%) and 91% (95% CI, 82-96%), respectively. Higgins I2 statistic demonstrated heterogeneity in the sensitivity (I2 = 68.17%), whereas no heterogeneity was noted in the specificity (I2 = 44.84%). In meta-regression, RF saturation power was associated with study heterogeneity. Correlation coefficients between APT signal intensity and Ki-67 cellular proliferation index ranged from 0.430 to 0.597, indicating moderate correlation. All studies showed excellent interobserver agreement. CONCLUSIONS: Although heterogeneous protocols were used, APTw MRI demonstrated excellent diagnostic performance for differentiating low- and high-grade gliomas. APTw MRI could be a reliable technique for glioma grading in clinical practice.

Intracranial aneurysms in patients receiving kidney transplantation for autosomal dominant polycystic kidney disease.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease, leading to kidney failure. One of the most serious extrarenal complications of ADPKD is comorbid intracranial aneurysms. The aim of this study is to evaluate the prevalence, rupture rate, and treatment outcomes of intracranial aneurysms in ADPKD. METHODS: Adult patients with a documented diagnosis of ADPKD who received kidney transplantation at our center from January 1994 to December 2018 were included in the study. Medical history, physical examination, laboratory findings, imaging studies, and operation records were collected and analyzed from our database. RESULTS: Among 154 kidney transplant recipients with ADPKD, 113 (73.4%) patients were screened for intracranial aneurysms preoperatively. Twenty three patients (14.9%) had intracranial aneurysms with mean diameter size of 4.5 ± 2.7 mm. Nine patients (5.8%) experienced aneurysm rupture and the mean age at time of rupture was 34.9 ± 9.3 years. Twelve patients (52.2%) presented with multiple aneurysms. The most common aneurysm location was the bifurcation of the middle cerebral artery (34.9%). Clipping was the most common treatment in both ruptured and unruptured aneurysms. CONCLUSIONS: Intracranial aneurysms are more frequent in patients with ADPKD, and the average age of intracranial artery rupture in patients with ADPKD is earlier than in the general population. It is necessary to consider proper evaluation and management of intracranial aneurysms when counseling ADPKD patients who will undergo kidney transplantation.

Multiparametric MRI as a potential surrogate endpoint for decision-making in early treatment response following concurrent chemoradiotherapy in patients with newly diagnosed glioblastoma: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the value of multiparametric MRI for determination of early treatment response following concurrent chemoradiotherapy in patients with newly diagnosed glioblastoma. METHODS: A computerized search of Ovid-MEDLINE and EMBASE up to 1 October 2017 was performed to find studies on the diagnostic performance of multiparametric MRI for differentiating true progression from pseudoprogression. The beginning search date was not specified. Pooled estimates of sensitivity and specificity were obtained using hierarchical logistic regression modeling. We performed meta-regression and sensitivity analyses to explain the effects of the study heterogeneity. RESULTS: Nine studies including 456 patients were included. Pooled sensitivity and specificity were 84 % (95 % CI 74-91) and 95 % (95 % CI 83-99), respectively. Area under the hierarchical summary receiver operating characteristic curve was 0.95 (95 % CI 0.92-0.96). Meta-regression showed true progression in the study population, the mean age and the reference standard were significant factors affecting heterogeneity. CONCLUSION: Multiparametric MRI may be used as a potential surrogate endpoint for assessment of early treatment response, especially in the differentiation of true progression from pseudoprogression. However, based on the current evidence, monoparametric and multiparametric MRI perform equally in the clinical context. Further evaluation will be needed. KEY POINTS: • Multiparametric MRI shows high diagnostic performance for early treatment response in glioblastoma. • Multiparametric MRI could differentiate true progression from pseudoprogression in newly diagnosed glioblastoma. • The normalized rCBV derived from DSC was the most commonly used parameter.