Whole-Body Magnetic Resonance Imaging in the Large Population-Based German National Cohort Study: Predictive Capability of Automated Image Quality Assessment for Protocol Repetitions.

BACKGROUND: Reproducible image quality is of high relevance for large cohort studies and can be challenging for magnetic resonance imaging (MRI). Automated image quality assessment may contribute to conducting radiologic studies effectively. PURPOSE: The aims of this study were to assess protocol repetition frequency in population-based whole-body MRI along with its effect on examination time and to examine the applicability of automated image quality assessment for predicting decision-making regarding repeated acquisitions. MATERIALS AND METHODS: All participants enrolled in the prospective, multicenter German National Cohort (NAKO) study who underwent whole-body MRI at 1 of 5 sites from 2014 to 2016 were included in this analysis (n = 11,347). A standardized examination program of 12 protocols was used. Acquisitions were carried out by certified radiologic technologists, who were authorized to repeat protocols based on their visual perception of image quality. Eleven image quality parameters were derived fully automatically from the acquired images, and their discrimination ability regarding baseline acquisitions and repetitions was tested. RESULTS: At least 1 protocol was repeated in 12% (n = 1359) of participants, and more than 1 protocol in 1.6% (n = 181). The repetition frequency differed across protocols (P < 0.001), imaging sites (P < 0.001), and over the study period (P < 0.001). The mean total scan time was 62.6 minutes in participants without and 67.4 minutes in participants with protocol repetitions (mean difference, 4.8 minutes; 95% confidence interval, 4.5-5.2 minutes). Ten of the automatically derived image quality parameters were individually retrospectively predictive for the repetition of particular protocols; for instance, "signal-to-noise ratio" alone provided an area under the curve of 0.65 (P < 0.001) for repetition of the Cardio Cine SSFP SAX protocol. Combinations generally improved prediction ability, as exemplified by "image sharpness" plus "foreground ratio" yielding an area under the curve of 0.89 (P < 0.001) for repetition of the Neuro T1w 3D MPRAGE protocol, versus 0.85 (P < 0.001) and 0.68 (P < 0.001) as individual parameters. CONCLUSIONS: Magnetic resonance imaging protocol repetitions were necessary in approximately 12% of scans even in the highly standardized setting of a large cohort study. Automated image quality assessment shows predictive value for the technologists' decision to perform protocol repetitions and has the potential to improve imaging efficiency.

White matter hyperintensity volume in pre-diabetes, diabetes and normoglycemia.

INTRODUCTION: As white matter hyperintensities (WMHs) of the brain are associated with an increased risk of stroke, cognitive decline, and depression, elucidating the associated risk factors is important. In addition to age and hypertension, pre-diabetes and diabetes may play important roles in the development of WMHs. Previous studies have, however, shown conflicting results. We aimed to investigate the effect of diabetes status and quantitative markers of glucose metabolism on WMH volume in a population-based cohort without prior cardiovascular disease. RESEARCH DESIGN AND METHODS: 400 participants underwent 3 T MRI. WMHs were manually segmented on 3D fluid-attenuated inversion recovery images. An oral glucose tolerance test (OGTT) was administered to all participants not previously diagnosed with diabetes to assess 2-hour serum glucose concentrations. Fasting glucose concentrations and glycated hemoglobin (HbA1c) levels were measured. Zero-inflated negative binomial regression analyses of WMH volume and measures of glycemic status were performed while controlling for cardiovascular risk factors and multiple testing. RESULTS: The final study population comprised 388 participants (57% male; age 56.3±9.2 years; n=98 with pre-diabetes, n=51 with diabetes). Higher WMH volume was associated with pre-diabetes (p=0.001) and diabetes (p=0.026) compared with normoglycemic control participants after adjustment for cardiovascular risk factors. 2-hour serum glucose (p<0.001), but not fasting glucose (p=0.389) or HbA1c (p=0.050), showed a significant positive association with WMH volume after adjustment for cardiovascular risk factors. CONCLUSION: Our results indicate that high 2-hour serum glucose concentration in OGTT, but not fasting glucose levels, may be an independent risk factor for the development of WMHs, with the potential to inform intensified prevention strategies in individuals at risk of WMH-associated morbidity.

Associated factors of white matter hyperintensity volume: a machine-learning approach.

To identify the most important parameters associated with cerebral white matter hyperintensities (WMH), in consideration of potential collinearity, we used a data-driven machine-learning approach. We analysed two independent cohorts (KORA and SHIP). WMH volumes were derived from cMRI-images (FLAIR). 90 (KORA) and 34 (SHIP) potential determinants of WMH including measures of diabetes, blood-pressure, medication-intake, sociodemographics, life-style factors, somatic/depressive-symptoms and sleep were collected. Elastic net regression was used to identify relevant predictor covariates associated with WMH volume. The ten most frequently selected variables in KORA were subsequently examined for robustness in SHIP. The final KORA sample consisted of 370 participants (58% male; age 55.7 ± 9.1 years), the SHIP sample comprised 854 participants (38% male; age 53.9 ± 9.3 years). The most often selected and highly replicable parameters associated with WMH volume were in descending order age, hypertension, components of the social environment (i.e. widowed, living alone) and prediabetes. A systematic machine-learning based analysis of two independent, population-based cohorts showed, that besides age and hypertension, prediabetes and components of the social environment might play important roles in the development of WMH. Our results enable personal risk assessment for the development of WMH and inform prevention strategies tailored to the individual patient.

Incidental findings in whole-body MR imaging of a population-based cohort study: Frequency, management and psychosocial consequences.

OBJECTIVES: Management of incidental findings (IF) remains controversial but highly relevant. Our aim was to assess the frequency, management and psychosocial consequences of IF reporting in a population-based cohort study undergoing whole-body MR imaging. METHODS: The study was nested in a prospective cohort from a longitudinal, population-based cohort (KORA-FF4) in southern Germany. All MR obtained on 3 T MR scanner were reviewed by board-certified radiologists regarding clinically relevant IF. A baseline and follow-up questionnaires including PHQ-9 were completed prior to and 6-month after to the scan. RESULTS: Of 400 participants (56.3 ±â€¯9.2years, 58 % male) undergoing whole-body MR, IF were found in 22 % of participants (n = 89); most frequently located in the abdominal sequences. In the pre-scan survey, most participants stated as the motivation that they wanted to "contribute to a scientific purpose" (91 %), while "knowing whether I'm healthy" was the most frequent motivation reported 6 months post-scan (88 %). The desire for IF reporting increased over time (pre- vs. 6-months-post-scan), also for clinically less important IF (72 % vs. 84 %, p = 0.001). Regarding psychosocial impact, a small portion (3.4 %) reported that awaiting the IF report added "definitely" or "very probably" additional stress burden. Of participants with reported IF, 56.8 % classified the results as "very helpful". In the post-scan survey moderate depression was observed in 3.3 % and severe depression in 1.2 %. This did not differ between participants with and without reported IF. CONCLUSION: In a cohort with whole-body MR imaging, the prevalence of IF was high. Participants considered reporting of IF highly important and added only minor psychological burden.

Machine-learning based exploration of determinants of gray matter volume in the KORA-MRI study.

To identify the most important factors that impact brain volume, while accounting for potential collinearity, we used a data-driven machine-learning approach. Gray Matter Volume (GMV) was derived from magnetic resonance imaging (3T, FLAIR) and adjusted for intracranial volume (ICV). 93 potential determinants of GMV from the categories sociodemographics, anthropometric measurements, cardio-metabolic variables, lifestyle factors, medication, sleep, and nutrition were obtained from 293 participants from a population-based cohort from Southern Germany. Elastic net regression was used to identify the most important determinants of ICV-adjusted GMV. The four variables age (selected in each of the 1000 splits), glomerular filtration rate (794 splits), diabetes (323 splits) and diabetes duration (122 splits) were identified to be most relevant predictors of GMV adjusted for intracranial volume. The elastic net model showed better performance compared to a constant linear regression (mean squared error = 1.10 vs. 1.59, p < 0.001). These findings are relevant for preventive and therapeutic considerations and for neuroimaging studies, as they suggest to take information on metabolic status and renal function into account as potential confounders.

How to report incidental findings from population whole-body MRI: view of participants of the German National Cohort.

OBJECTIVES: In the German National Cohort (GNC), 30,000 individuals are examined with whole-body MRI (wbMRI), of which about 3000 participants are expected to receive an incidental finding (IF) disclosure. In order to get feedback from participants and to evaluate the IF-management procedure of the wbMRI substudy, a follow-up questionnaire was developed. This single-center pilot trial was aimed to get a first impression on feasibility reproducibility and validity of such a survey in order to take necessary adjustments before initiating the survey among several thousand participants. METHODS: The questionnaires were sent out in test-retest manner to 86 participants who received a wbMRI examination in January-February 2016 at the imaging center in Neubrandenburg. The ratio of participants with and without IF notification was 1:1. Descriptive statistics was performed. RESULTS: A first response of 94% and completion proportion of 99% were achieved. Participants were satisfied with the examination procedure. Ninety-five percent of participants considered it very important to receive notification of IFs. Participants reported minimal stress levels while waiting for a possible IF notification letter, but high stress levels when an IF letter was received. Phrasing of the IF reports was rated in 97% as well understandable and in 55% as beneficial to health status. CONCLUSIONS: This questionnaire will serve researchers within the GNC as a fundamental instrument not only for quality management analyses but also for the investigation of still unacknowledged scientific and ethical questions contributing to evidence-based guidelines concerning the complex approach to IFs in future population-based imaging. KEY POINTS: • Evidence-based guidelines for reporting incidental findings in population whole-body MRI are lacking. • Pilot-testing of a questionnaire for the evaluation of practical and ethical aspects of the procedure to report incidental findings in the German National Cohort shows a high level of acceptance and high return rate by participants. • Participants reported minimal stress levels while waiting for a possible incidental finding notification letter, which increased significantly, when such a letter was received.

[Quality standards for epidemiologic cohort studies : An evaluated catalogue of requirements for the conduct and preparation of cohort studies]. / Qualitätsstandards für epidemiologische Kohortenstudien : Ein bewerteter Anforderungskatalog zur Studienvorbereitung und Studiendurchführung.

BACKGROUND: Cohort studies are a longitudinal observational study type. They are firmly established within epidemiology to assess the course of diseases and risk factors. Yet, standards to describe and evaluate quality characteristics of cohort studies need further development. OBJECTIVE: Within the TMF ("Technologie- und Methodenplattform für die vernetzte medizinische Forschung e. V.") project "Quality management standards in cohort studies", a catalogue of requirements was compiled and evaluated, focusing on the preparation and conduct of epidemiologic cohort studies. MATERIALS AND METHODS: The catalogue of requirements was established based on a consensus process between representatives of seven German epidemiologic cohort studies. For this purpose, a set of expert meetings (telephone, face-to-face, web-based) was conducted and the importance of each element of the catalogue was assessed as well as its implementation. RESULTS: A catalogue of requirements with 138 requirements was consented. It is structured into ten sections: 1. Study documentation; 2. Selection of instruments; 3. Study implementation, 4. Organizational structure; 5. Qualification and certification; 6. Participant recruitment; 7. Preparation, conduct and follow-up processing of examinations; 8. Study logistics and maintenance, 9. Data capture and data management; 10. Reporting and monitoring. In total, 41 elements were categorized as being essential, 91 as important, and 6 as less important. CONCLUSION: The catalogue of requirements provides a guideline to improve the preparation and operation of cohort studies. The evaluation of the importance and degree of implementation of requirements depended on the study design. With adaptations, the catalogue might be transferable to other study types.

Subclinical Disease Burden as Assessed by Whole-Body MRI in Subjects With Prediabetes, Subjects With Diabetes, and Normal Control Subjects From the General Population: The KORA-MRI Study.

Detailed pathophysiological manifestations of early disease in the context of prediabetes are poorly understood. This study aimed to evaluate the extent of early signs of metabolic and cardio-cerebrovascular complications affecting multiple organs in individuals with prediabetes. Subjects without a history of stroke, coronary artery disease, or peripheral artery disease were enrolled in a case-control study nested within the Cooperative Health Research in the Region of Augsburg (KORA) FF4 cohort and underwent comprehensive MRI assessment to characterize cerebral parameters (white matter lesions, microbleeds), cardiovascular parameters (carotid plaque, left ventricular function, and myocardial late gadolinium enhancement [LGE]), and metabolic parameters (hepatic proton-density fat fraction [PDFF] and subcutaneous and visceral abdominal fat). Among 400 subjects who underwent MRI, 103 subjects had prediabetes and 54 had established diabetes. Subjects with prediabetes had an increased risk for carotid plaque and adverse functional cardiac parameters, including reduced early diastolic filling rates as well as a higher prevalence of LGE compared with healthy control subjects. In addition, people with prediabetes had significantly elevated levels of PDFF and total and visceral fat. Thus, subjects with prediabetes show early signs of subclinical disease that include vascular, cardiac, and metabolic changes, as measured by whole-body MRI after adjusting for cardiometabolic risk factors.