Dysfunctional homeostasis of transition metals is believed to play a role in the pathogenesis of Alzheimer’s disease (AD). Although questioned by some, brain copper, zinc, and particularly iron overload are widely accepted features of AD which have led to the hypothesis that oxidative stress generated from aberrant homeostasis of these transition metals might be a pathogenic mechanism behind AD. This meta-analysis compiled and critically assessed available quantitative data on brain iron, zinc and copper levels in AD patients compared to aged controls. The results were very heterogeneous. A series of heavily cited articles from one laboratory reported a large increase in iron in AD neocortex compared to age-matched controls (p<0.0001) while seven laboratories failed to reproduce these findings reporting no significant difference between the groups (p=0.76). A more than three-fold citation bias was found to favor outlier studies reporting increases in iron and this bias was particularly prominent among narrative review articles. Additionally, while zinc was not significantly changed in the neocortex (p=0.29), copper was significantly depleted in AD (p=0.0003). In light of these findings, it will be important to re-evaluate the hypothesis that transition metal overload accounts for oxidative injury noted in AD.

Early prediction of outcomes after traumatic brain injury (TBI) is often difficult. To improve prognostic accuracy soon after trauma, we compared different radiological modalities and anatomical injury distribution in a group of adult TBI patients. The four methods studied were computed tomography (CT), magnetic resonance imaging (MRI) with T2-weighted imaging (T2WI), fluid-attenuated inversion recovery (FLAIR) imaging, and susceptibility weighted imaging (SWI). The objective of this study was to identify which modality and anatomic model best predict outcome. The patient population consisted of 38 adults admitted between February 2001 and May 2003. Early CT, T2WI, FLAIR, and SWI were obtained for each patient as well as a Glasgow Outcome Score (GOS) between 0.1 and 22 months (mean 9.2 months) after injury. Using a semi-automated computer method, intraparenchymal lesions were traced, measured, and converted to lesion volumes based on slice thickness and pixel size. Lesions were assigned to zones and regions. Outcomes were dichotomized into good (GOS 4-5) and poor (GOS 1-3) outcome groups. Brain injury detected by imaging was analyzed by median total lesion volume, median volume per lesion, and median number of lesions per outcome group. T2WI and FLAIR imaging most consistently discriminated between good and poor outcomes by median total lesion volume, median volume per lesion, and median number of lesions. In addition, T2WI and FLAIR imaging most consistently discriminated between good and poor outcomes by zonal distribution. While SWI rarely discriminated by outcome, it was very sensitive to intraparenchymal injury and its optimal use in evaluating TBI is unclear. SWI and other new imaging modalities should be further studied to fully evaluate their prognostic utility in TBI evaluation.

Diffusion-weighted imaging (DWI) and consequent apparent diffusion coefficient (ADC) maps have been used for lesion detection and as a predictor of outcome in adults with traumatic brain injury (TBI), but few studies have been reported in children. We evaluated the role of DWI and ADC for outcome prediction after pediatric TBI (n=37 TBI; n=10 controls). Fifteen regions of interest (ROIs) were manually drawn on ADC maps that were grouped for analysis into peripheral gray matter, peripheral white matter, deep gray and white matter, and posterior fossa. All ROIs excluded areas that appeared abnormal on T2-weighted images (T2WI). Acute injury severity was measured using the Glasgow Coma Scale (GCS) score, and 6-12-month outcomes were assessed using the Pediatric Cerebral Performance Category Scale (PCPCS) score. Patients were categorized into five groups: (1) controls; (2) all TBI patients; (3) mild/moderate TBI with good outcomes; (4) severe TBI with good outcomes; and (5) severe TBI with poor outcomes. ADC values in the peripheral white matter were significantly reduced in children with severe TBI with poor outcomes (72.8+/-14.4x10(-3) mm2/sec) compared to those with severe TBI and good outcomes (82.5+/-3.8x10(-3) mm2/sec; p<0.05). We also found that the average total brain ADC value alone had the greatest ability to predict outcome and could correctly predict outcome in 84% of cases. Assessment of DWI and ADC values in pediatric TBI is useful in evaluating injury, particularly in brain regions that appear normal on conventional imaging. Early identification of children at high risk for poor outcome may assist in aggressive clinical management of pediatric TBI patients.

Purpose: Prostate specific membrane antigen targeted radiotracers are promising agents for imaging patients with prostate cancer biochemical recurrence after definitive therapy. We report the results of a systematic review and metaanalysis of the detection of biochemical recurrence after definitive therapy for prostate cancer stratified by prostate specific antigen levels and using prostate specific membrane antigen targeted radiotracers. Materials and Methods: According to the Preferred Reporting Items for Systematic reviews and Meta-Analysis Diagnostic Test Accuracy guidelines, we searched for articles in PubMedÒ and EMBASEÒ databases in our systematic review from 2012 to July 2018. Studies evaluating men with prostate cancer biochemical recurrence after definitive therapy and without known metastatic disease who underwent prostate specific membrane antigen positron emission tomography/computerized tomography to detect recurrent disease were included in analysis. The risk of bias and applicability concerns were assessed by QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2). Statistical heterogeneity was assessed with the Cochrane Q and an I 2 estimate. The reference standard was pathology findings, followup imaging or a prostate specific antigen decline after salvage treatment. We calculated pooled estimates and the 95% CI around the prevalence of a positive examination in the study population using a random effects model. Results: A total of 5,113 patients in 43 studies were included in this systematic review. Of the studies 15 (34.8%) were prospective, 3 (6.9%) were multiinstitutional and the remainder were done at a single center. A total of 18 studies (41.8%) were done in subjects after radical prostatectomy, 2 (4.6%) were in subjects after radiotherapy and 23 (53.5%) were in subjects after radical prostatectomy and radiotherapy. Median prostate specific antigen was 1.6 ng/ml (IQR 0.7e4.4) and median subject age was 68 years (IQR 67e70). Of the 43 studies 33 (76.7%) evaluated 68 Ga prostate specific membrane antigen-11 (Ga-HBED-CC) positron emission tomography/computerized tomography. The pooled detection rate was 70.2% (95% CI 65.0e75.4) in the entire cohort. For prostate specific antigen less than 0.5, 0.5 to 0.9, 1 to 1.9 and 2 ng/ml or greater the pooled detection rate was 44.9% (95% CI 36.0e53.9), 61.3% (95% CI 52.3e70.3), 78.2% (95% CI 70.8e85.6) and 93.9% (95% CI 92.0e95.8), respectively. A reference standard was confirmed to be positive in 684 of the 715 patients (95.7%). There were significant study heterogeneity and publication biases (p <0.01).

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Purpose: To investigate whether longitudinal magnetic resonance proton spectroscopic imaging (MRSI) demonstrates regional metabolite abnormalities after traumatic brain injury (TBI) that predict long-term neurologic outcome. Materials and Methods:Two-dimensional-MRSI (point resolved spectroscopy sequence [PRESS]; TR/TE ϭ 3000/ 144 msec; 10 mm) was acquired prospectively in 42 adults with severe TBI through the level of the corpus callosum 7 Ϯ 4 days after injury. Measurements were repeated in 31 patients six to 12 months after injury. Regional and pooled (all regions combined) mean ratios were compared with control values and then used to predict long-term (six-to -12-month) neurologic outcome (good vs. poor) using a logistic regression model. Results:Initial pooled mean N-acetylaspartate (NAA) ratios were lower (P Ͻ 0.01) and choline (Cho)/creatine (Cr) ratios higher (P Ͻ 0.01) in all TBI patients compared to controls. Ratios from the corpus callosum region were affected most and predicted long-term dichotomized outcome with 83% accuracy. When repeated at six to 12 months after injury, pooled mean NAA/Cr remained lower (P ϭ 0.03) and Cho/Cr remained higher (P ϭ 0.01) in patients with poor outcomes. Conclusion:The NAA/Cr ratio from the corpus callosum was most useful for outcome prediction. Chronic alterations of metabolite ratios are likely due to neuronal loss and glial proliferation long after injury.

Background: National guidelines endorse fluorine 18 ( 18 F) fluciclovine PET/CT for the detection of prostate cancer (PCa) in men with biochemically recurrent PCa. The comparative performance between fluciclovine and gallium 68 or 18 F prostate-specific membrane antigen (PSMA) PET/CT, a newer examination, is unclear.Purpose: To compare the detection of biochemical recurrence using fluciclovine versus PSMA-targeted radiotracers in patients with a prostate-specific antigen (PSA) level less than 2 ng/mL. Materials and Methods:With use of the Preferred Reporting Items for a Systematic Review and Meta-Analysis of Diagnostic Test Accuracy, or PRISMA-DTA, guidelines, a systematic review of PubMed and EMBASE databases between 2012 and 2019 was performed. Studies of fluciclovine PET/CT or PSMA PET/CT in biochemical recurrence were identified. PSA levels, clinical data, and reference standards were obtained when available. A random-effects model was applied to pooled estimates and 95% confidence intervals (CIs) around the prevalence of a positive examination, stratified according to PSA tier.Results: Quantitative analysis included 482 patients (median age, 67 years; interquartile range, 67-67 years) in six fluciclovine studies and 3217 patients (median age, 68 years; interquartile range, 67-70 years) in 38 PSMA studies. Pooled detection rates for PSMA and fluciclovine were 45% (95% CI: 38%, 52%) and 37% (95% CI: 25%, 49%), respectively, for a PSA level less than 0.5 ng/mL (P = .46); 59% (95% CI: 52%, 66%) and 48% (95% CI: 34%, 61%) for a PSA level of 0.5-0.9 ng/mL (P = .19); and 80% (95% CI: 75%, 85%) and 62% (95% CI: 54%, 70%) for a PSA level of 1.0-1.9 ng/mL (P = .01). A reference standard was positive in 703 of 735 patients (96%) in the PSMA cohort and 247of 256 (97%) in the fluciclovine cohort. Conclusion:Patient-level detection rates for biochemically recurrent prostate cancer were greater for prostate-specific membrane antigen-targeted radiotracers than fluciclovine for prostate specific antigen levels of 1.0-1.9 ng/mL.