Incidental Findings from 16,400 Brain MRI

BACKGROUND AND PURPOSE: Incidental findings are discovered in neuroimaging research, ranging from trivial to life-threatening. We describe the prevalence and characteristics of incidental findings from 16,400 research brain MRIs, comparing spontaneous detection by nonradiology scanning staff versus formal neuroradiologist interpretation. MATERIALS AND METHODS:We prospectively collected 16,400 brain MRIs (7782 males, 8618 females; younger than 1 to 94 years of age; median age, 38 years) under an institutional review board directive intended to identify clinically relevant incidental findings. The study population included 13,150 presumed healthy volunteers and 3250 individuals with known neurologic diagnoses. Scanning staff were asked to flag concerning imaging findings seen during the scan session, and neuroradiologists produced structured reports after reviewing every scan. RESULTS: Neuroradiologists reported 13,593/16,400 (83%) scans as having normal findings, 2193/16,400 (13.3%) with abnormal findings without follow-up recommended, and 614/16,400 (3.7%) with “abnormal findings with follow-up recommended. ” The most common abnormalities prompting follow-up were vascular (263/614, 43%), neoplastic (130/614, 21%), and congenital (92/614, 15%). Volunteers older than 65 years of age were significantly more likely to have scans with abnormal findings (P, .001); however, among all volunteers with incidental findings, those younger than 65 years of age were more likely to be recommended for follow-up. Nonradiologists flagged ,1% of MRIs containing at least 1 abnormality reported by the neuroradiologists to be concerning enough to warrant further evaluation. CONCLUSIONS: Four percent of individuals who undergo research brain MRIs have an incidental, potentially clinically significant finding. Routine neuroradiologist review of all scans yields a much higher rate of significant lesion detection than selective referral from nonradiologists who perform the examinations. Workflow and scan review processes need to be carefully considered when designing research protocols. ABBREVIATIONS: CHS 1⁄4 Cardiovascular Health Studies; NPV 1⁄4 negative predictive value; PI 1⁄4 principal investigator; PPV 1⁄4 positive predictive value; SE 1⁄4 standard error Brain MRIs are performed for research and even commercial purposes. In addition to supporting primary research objectives, neuroimaging can uncover incidental findings. Incidental findings herein refer to previously unknown abnormalities of potential clinical significance discovered during MRIs that are both unrelated to the purpose of the research examination and distinct from the clinical history of the volunteer. It is estimated that incidental findings are found in approximately 4% of research brain MRIs; however, further examination is warranted, given that past studies have used small sample sizes, homogeneous Received December 16, 2022; accepted after revision February 20, 2023. From the University of Wisconsin School of Medicine and Public Health (P.A.R., L.B.E., A.S.F., R.J.D., S.C.J., S.A., V.P., B.B.B., B.R.P., H.H.G., C.M.C., M.A.B., N.H.K., L.E.W., H.A.R.), Departments of Radiology (P.A.R., LB.E., A.S.F., V.P., H.A.R.), Statistics (M.J.P.), and Psychology (R.J.D., B.R.P., H.H.G.), Wisconsin Alzheimer’s Disease Research Center (S.C.J., S.A., B.B.B., C.M.C.), and Departments of Medicine (S.C.J., S.A., N.A.C., B.B.B., C.M.C.), Orthopedics (M.A.B.), and Psychiatry (N.H.K., L.E.W.), University of Wisconsin–Madison, Madison, Wisconsin. This work was supported, in part, by the Grand Alliance Concussion Assessment, Research and Education Consortium, funded, in part, by the National Collegiate Athletic Association and the Department of Defense. The US Army Medical Research Acquisition Activity is the awarding and administering acquisition office. This work was also supported by the Office of the Assistant Secretary of Defense for Health Affairs through the Psychological Health and Traumatic Brain Injury Program under award No. W81XWH-14-2-0151 and by grants from the National Institute of Mental Health: R21MH092581 (N.H. Kalin), R01MH107563 (N.H. Kalin, L.E. Williams), and U01MH112913 (N.H. Kalin, L.E. Williams). Other funding sources include R01AG062285, R01AG037639, UF1AG051216, P30AG062715, R01MH064498. Opinions, interpretations, conclusions, and recommendations are those of the authors and are not necessarily endorsed by the Department of Defense (Defense Health Program funds). Please address correspondence to Paul Rowley, MD, University of Wisconsin School of Medicine and Public Health, Department of Radiology, 600 Highland Ave, Madison, WI 53792-3252; e-mail: prowley@wisc.edu Indicates open access to non-subscribers at www.ajnr. org Indicates article with online supplemental data. http://dx.doi. org/10.3174/ajnr.A7821 AJNR Am J Neuroradiol 44:417–23 Apr 2023 www.ajnr. org 417 population-based cohorts across narrow age ranges, and specialty MRI protocols limiting external validity and/or having problematic methods for identifying incidental findings. There is poor consensus on whether the baseline prevalence of clinically significant brain abnormalities in the general population justifies the routine use of neuroradiologists to review research MRIs. Standard practices for research MRI interpretation differ by institution and by country, but budgetary and workflow constraints have historically limited expert review solely to scans flagged by scanning technologists and research personnel. These nonradiologists have variable experience and, in most circumstances, lack formal training in diagnostic MR imaging reporting; nonetheless, they are tasked with screening and referring concerning findings for further review, leaving most scans without formal interpretation. In this prospective cross-sectional study, we describe the prevalence and characteristics of incidental findings and assess the detection rate of abnormalities of nonradiologists compared with neuroradiologists from a series of 16,400 consecutive research brain MRIs collected at a single institution across 18 years. MATERIALS AND METHODS All research activities performed and described were conducted in accordance with an institutional review board–approved protocol at the University of Wisconsin-Madison. Population Recruitment and Inclusion Brain MRIs were collected from 17,010 consecutive volunteers from research studies conducted at the University of WisconsinMadison from April 2002 to March 2020. The final study population included 16,400 scans (7782 males, 8618 females; younger than 1 year of age to 94 years; median age, 38 years) after excluding 610 whose participant intake forms lacked age and/or sex. The overall study data base compiled neuroimaging from volunteers in . 300 research protocols and 73 principal investigator (PI) groups. All volunteers or their guardians provided informed consent before participation. Participants were recruited by each individual PI on the basis of eligibility criteria for their respective studies. Most studies recruited healthy age-matched control volunteers, while a minority recruited individuals with pre-existing conditions such as stroke, MS, and dementia. Each scan was treated as a unique case, though some participants were scanned more than once. We are unable to quantify how many participants were serially scanned because of the research scan anonymization, a code that sometimes changed with time for the same individual. Typical workflow required that all scans be read unless a prior MRI in the same protocol had been read within the past year, in which case the PI was not required to submit the scan for radiologist interpretation. We encountered significant abnormalities on follow-up scans in some previously healthy subjects, justifying review of new studies. Most important, volunteers with known pre-existing medical conditions, including those with disease-related neuroimaging findings, were not excluded. Therefore, volunteers with known conditions were considered to have either normal or abnormal findings, or no follow-up was recommended unless other previously unknown brain abnormalities were discovered. If a volunteer had previously been informed of a clinically significant finding and this was seen again at follow-up, this duplicate was placed in the “abnormal, no follow-up” category unless there had been clear-cut interval worsening. Volunteers with normal anatomic variants and common incidental findings of doubtful significance were categorized as having normal findings. Brain MRI Acquisition and Analysis MRIs were performed on GE Healthcare MRI scanners at multiple research sites. Most scans were performed at 3T (15,888/ 16,400, 97%). Each PI chose pulse sequences on the basis of individual study needs, leading to a heterogeneous variety of scan protocols. Virtually all included T1-weighted images (mostly volumetric acquisitions) and additional sequences were included for most protocols, particularly in those older than 45 years of age for aging and dementia research. Examinations containing brain anatomy and already postprocessed parameter maps (eg, perfusion if available) were sent to the PACS for neuroradiologist interpretation. Advanced imaging techniques and raw data files including PET, 4D flow MRA, fMRI, and diffusion tensor maps were not interpreted. MRI Interpretation and Reporting Nonradiologists including scanning staff (MRI technologists and nurses) and research personnel (PhD scientists and neuropsychologists) were instructed to document concerns at the time of scanning using the same Web-based intake form they had used to upload cases to the reading queue of neuroradiologists. All scanning technicians were certified for MRI safety and technical proficiency, as verified by more senior technicians and ultimately the PI. The technicians in our neuroscience centers were specialty research personnel, most without a radiologic technologist degree, typically