Citations

PurposeTo quantify the effects of DCE acquisition and pharmacokinetic modeling processing methodologies on the absolute accuracy and precision of derived pharmacokinetic (PK) parameter values using a novel anthropomorphic phantom test device in which “ground truth” values were known a priori.MethodsGround truth arterial input function (AIF), tumor, and healthy tissue contrast agent concentration‐time curves (CTCs) were established within the phantom and repeatedly measured on a 3T MRI scanner with varying temporal resolution (Tres = 1.22–30.6 s). Ground truth CTCs, Ktrans, ve, and kep values were directly compared to measured values as a function of Tres, with and without the application of voxel‐wise flip‐angle corrections applied to the data and PK modeling performed using linear and nonlinear forms of the standard Tofts model.ResultsMeasurement of the AIF was strongly affected by the Tres used (AIF curve‐shape feature errors: 3%–222% for Tres: 1.22–30.6 s), which directly translated to errors in the derived Ktrans, ve, and kep values of 1%–24%, 2%–5%, and 1%–26% respectively across this Tres range (flip‐angle correction applied). Further appreciable improvements in accuracy and precision arising from the use of flip angle corrections and nonlinear least squares fitting were quantified and used to identify optimal acquisition and analysis methodologies for which measurement errors could be constrained below threshold levels.ConclusionThis quantitative study provides insight into how errors in AIF measurement propagate to errors in PK parameter outputs. Absolute quantification of the accuracy and precision of MR‐measured CTCs, and resultant PK parameter values, allowed for an optimal temporal resolution to be defined commensurate with maintaining Ktrans, ve, and kep measurement errors below 5% and 10% levels. An appreciable gain in PK parameter estimation accuracy at the analysis stage was also demonstrated using flip‐angle corrections and a linear approach to PK model fitting.

AbstractIntroductionFour less well‐studied but promising “emerging” cerebrospinal fluid (CSF) biomarkers are elevated in late‐onset Alzheimer disease (AD): neurogranin, synaptosomal‐associated protein‐25 (SNAP‐25), visinin‐like protein 1 (VILIP‐1), and chitinase‐3‐like protein 1 (YKL‐40).MethodsCSF neurogranin, SNAP‐25, VILIP‐1, and YKL‐40 were measured in families carrying autosomal‐dominant AD mutations.ResultsThe four emerging CSF biomarkers were significantly elevated in the mutation carriers (n = 235) versus noncarriers (n = 145). CSF SNAP‐25, VILIP‐1, and YKL‐40 were altered very early in the AD time course, approximately 15–19 years before estimated symptom onset. All CSF biomarkers predicted important AD‐related outcomes including performance on a cognitive composite, brain amyloid burden as measured by amyloid positron emission tomography, and the estimated years from symptom onset.DiscussionEarly abnormalities in CSF tTau, pTau, SNAP‐25, VILIP‐1, and YKL‐40 suggest that synaptic damage, neuronal injury, and neuroinflammation begin shortly after the commencement of brain amyloid accumulation.

BackgroundMR image intensity nonuniformity is often observed at 7T. Reference scans from the body coil used for uniformity correction at lower field strengths are typically not available at 7T.PurposeTo evaluate the efficacy of a novel algorithm, Uniform Combined Reconstruction (UNICORN), to correct receive coil‐induced nonuniformity in musculoskeletal 7T MRI without the use of a reference scan.Study TypeRetrospective image analysis study.SubjectsMRI data of 20 subjects was retrospectively processed offline.Field Strength/Sequence: Knees of 20 subjects were imaged at 7T with a single‐channel transmit, 28‐channel phased‐array receive knee coil. A turbo‐spin‐echo sequence was used to acquire 33 series of images.AssessmentThree fellowship‐trained musculoskeletal radiologists with cumulative experience of 42 years reviewed the images. The uniformity, contrast, signal‐to‐noise ratio (SNR), and overall image quality were evaluated for images with no postprocessing, images processed with N4 bias field correction algorithm, and the UNICORN algorithm.Statistical TestsIntraclass correlation coefficient (ICC) was used for measuring the interrater reliability. ICC and 95% confidence intervals (CIs) were calculated using the R statistical package employing a two‐way mixed‐effects model based on a mean rating (k = 3) for absolute agreement. The Wilcoxon signed‐rank test with continuity correction was used for analyzing the overall image quality scores.ResultsUNICORN was preferred among the three methods evaluated for uniformity in 97.9% of the pooled ratings, with excellent interrater agreement (ICC of 0.98, CI 0.97–0.99). UNICORN was also rated better than N4 for contrast and equivalent to N4 in SNR with ICCs of 0.80 (CI 0.72–0.86) and 0.67 (CI 0.54–0.77), respectively. The overall image quality scores for UNICORN were significantly higher than N4 (P < 6 × 10‐13), with good to excellent interrater agreement (ICC 0.90, CI 0.86–0.93).Data ConclusionWithout the use of a reference scan, UNICORN provides better image uniformity, contrast, and overall image quality at 7T compared with the N4 bias field‐correction algorithm.Level of Evidence: 4Technical Efficacy: Stage 1J. Magn. Reson. Imaging 2019;50:1534–1544.

Abstract Introduction Diversifying the workforce is an important strategy to reducing health disparities. Since 2007, the Society for Research on Nicotine and Tobacco (SRNT) Health Disparities Network has funded a travel scholarship to promote inclusion, professional development, and diversity among investigators interested in tobacco-related health disparities research. This study examined indicators of productivity among former scholarship recipients. Methods: Scholarship recipients between 2007 and 2014 were invited to complete a survey online. The survey assessed demographic characteristics, academic productivity, and perceived professional benefit resulting from the scholarship. Results: Of the 117 scholarships recipients, 89 (77%) responded. Respondents were 67% female and had a mean age of 37.8 years. Twenty eight percent were African American, 25% Asian American, and 17% Latino. Most respondents worked in academia (80%) and nearly three-quarters (74%) reported publishing manuscripts on tobacco-related disparities, with a mean of 3.8 (SD 4.4) disparities-related publications since receiving the scholarship. Respondents’ work focused on a wide range of health disparities topics and nearly all respondents reported that the scholarship removed barriers to attending the meeting and reported professional benefit from receiving the travel scholarship. Following receipt of the SRNT travel scholarship, a diverse group of scientists demonstrated scholarly productivity, professional development, and advancement of health disparities research. Similar efforts are encouraged in other professional societies. Implications This study examines the productivity of early career recipients of the SRNT Health Disparities Scholarship. Results suggest that the investment in annual travel scholarships by a professional organization is an important support system for emerging scientists from diverse backgrounds. This investment may help to advance the science of health disparities and engage researchers in an area where there are critical gaps in the research workforce.

AbstractObjectiveThe prognostic value of cerebrospinal fluid neurofilament light chain, total tau, phosphorylated tau181, and amyloid beta1‐42was examined in frontotemporal dementia subtypes.MethodsWe compared baseline biomarkers between 49 controls, 40 patients with behavioral variant frontotemporal dementia, 24 with semantic variant primary progressive aphasia, and 26 with nonfluent variant primary progressive aphasia. Linear mixed effect models were used to assess the value of baseline biomarkers in predicting clinical and radiographic change in patient cohorts over multiple yearly follow up visits.ResultsNeurofilament light chain concentrations were lowest in controls. Elevated baseline neurofilament light chain predicted faster worsening in clinical severity, frontotemporal volume and frontotemporal fractional anisotropy in patients with behavioral variant frontotemporal dementia and nonfluent variant primary progressive aphasia. High total tau similarly predicted faster progression in nonfluent variant primary progressive aphasia. In behavioral variant frontotemporal dementia, higher phosphorylated tau181predicted faster clinical progression whereas lower amyloid beta1‐42predicted faster volumetric and fractional anisotropy reduction. Neurofilament light chain and phosphorylated tau181were of greater predictive value in patients with tau pathology as compared toTDP‐43 pathology. Baseline neurofilament light chain correlated with baseline clinical severity and frontotemporal volume in behavioral variant frontotemporal dementia. Baseline total tau correlated with baseline clinical severity in semantic variant primary progressive aphasia.InterpretationHigh cerebrospinal fluid neurofilament light chain predicts more aggressive disease in behavioral variant frontotemporal dementia and nonfluent variant primary progressive aphasia. Total tau, phosphorylated tau181, and amyloid beta1‐42also predict some measures of disease aggressiveness in frontotemporal dementia.

Abstract Background: Pancreatic cancer (PC) ranks among the top causes of cancer mortality. Risk stratification is an important step toward prevention and early detection. Prior work has shown that ABO blood type (non-O) and first-degree family history of PC are associated with increased PC risk. Individuals with first-degree family history of PC have a 2- to 3-fold increased risk, but it is unclear if ABO blood type plays a role in the familial aggregation of PC. We investigated PC risk among first-degree relatives (FDRs) of PC probands based on the probands' serologic blood type (O vs non-O). Methods: A total of 702 probands sequentially enrolled in the Mayo Clinic Pancreas Research Registry from 2000-2016 with serologic ABO blood type provided information on family history of cancer for 5,178 FDRs. FDRs were grouped based on their related probands' blood type as type O (n=242; 1,768 FDRs) vs non-O (n=460; 3,410 FDRs). Standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated by comparing the number of PC cases observed among FDRs to those expected using data from the Surveillance, Epidemiology and End Results (SEER) Program as the reference population. SIRs for PC risk were calculated separately for FDRs of probands with type O vs FDRs of probands with non-O blood, and stratified by sex of FDRs and relationship to proband (parent, sibling, or offspring). Results: Compared to the SEER reference, PC risk was nearly 2-fold higher among FDRs of PC probands (SIR=1.76; 95%CI: 1.35-2.26). When stratified by probands' ABO type, risk for PC was higher among FDRs of probands with non-O blood (SIR=1.94; 95%CI: 1.41-2.60), compared to FDRs of probands with O blood (SIR=1.42; 95%CI: 0.83-2.28). Parents of probands with non-O blood had increased PC risk (SIR=3.28; 95%CI: 2.18-4.74, n=920), but not parents of probands with O blood (SIR=1.75; 95%CI: 0.75-3.45, n=484), p-value for between-group difference=0.10. Among FDRs of probands with O blood, female FDRs had increased PC risk (SIR=2.12; 95%CI: 1.06-3.79), but male FDRs did not (SIR=0.86; 95%CI: 0.31-1.88). Higher PC risk was observed among female FDRs of probands with non-O blood (SIR=2.28; 95%CI: 1.44-3.41) than male FDRs of probands with non-O blood (SIR=1.62; 95%CI: 1.00-2.48). Mothers of probands with O blood had increased PC risk (SIR=2.89; 95%CI: 1.05-6.28) compared to fathers (SIR=0.79; 95%CI: 0.09-2.84). Both mothers (SIR=3.60; 95%CI: 1.96-6.03) and fathers (SIR=2.95; 95%CI: 1.61-4.95) of probands with non-O blood had increased PC risk. No major findings were observed among probands' siblings or offspring. Conclusions: PC risk is greater among FDRs of PC probands with non-O blood than among FDRs of probands with type O. PC risk is higher among parents of probands with non-O blood, and female FDRs and mothers of probands with non-O blood. Possible clustering of non-O blood type in families may contribute to increased PC risk. Citation Format: Aarti Kolluri, Samuel O. Antwi, Sarah E. Fagan, Kari G. Chaffee, Brendan T. Broderick, William R. Bamlet, Ann L. Oberg, Robert R. McWilliams, Gloria M. Petersen. Risk of pancreatic cancer is increased among first-degree relatives of pancreatic cancer probands who have non-O ABO blood type [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1239.