Discovery and disclosure of incidental findings in neuroimaging research

PURPOSE: To examine different protocols for handling incidental findings on brain research MRIs, and provide a platform for establishing formal discussions of related ethical and policy issues. MATERIALS AND METHODS: Corresponding authors identified from a database of peer-reviewed publications in 1991-2002 involving functional MRI (fMRI), alone or in combination with other imaging modalities, were invited to participate in this web-based survey. The survey asked questions regarding knowledge and handling of incidental findings, as well as characteristics of the scanning environment, training required, IRB protocol requirements, and neuroradiologist involvement. RESULTS: Seventy-four investigators who conduct MRI studies in the United States and abroad responded. Eighty-two percent (54/66) reported discovering incidental findings in their studies, such as arteriovenous malformations, brain tumors, and developmental abnormalities. Substantial variability was found in the procedures for handling and communicating findings to subjects, neuroradiologist involvement, personnel permitted to operate equipment, and training. CONCLUSION: Guidelines for minimum and optimum standards for detecting and communicating incidental findings on brain MRI research are needed.     

Subjects' expectations in neuroimaging research

PURPOSE: To explore subjects' attitudes and expectations concerning the detection and management of incidental findings in neuroimaging research. MATERIALS AND METHODS: Healthy control subjects (N = 105) who previously participated in neuroimaging studies in medical and nonmedical settings were surveyed about their expectations and attitudes toward unexpected clinical findings on their research brain scans. We hypothesized that even though the participants consented to a scanning procedure for research purposes alone, they would still expect pathology, if present, to be detected and reported to them. RESULTS: Fifty-four percent of participants reported that they expected research scans to detect abnormalities if they existed. Nearly all subjects (>90%) reported that they would want findings communicated to them, and many (59%) preferred this to be done by a physician affiliated with the research team. The participants responded in similar ways whether they were scanned in medical or nonmedical settings. CONCLUSION: Clarity about procedures for handling incidental findings when obtaining written and verbal informed consent is essential to ensure that the subjects' expectations are consistent with the purpose and scope of the research.     

The prevalence and clinical importance of incidental soft-tissue findings in cervical CT scans of trauma population

Objectives:

To define the age-related prevalence of incidental soft-tissue findings in cervical CT scans of a trauma population and to investigate their clinical importance.

Methods:

The original diagnostic radiology reports and the CT images of the 357 patients with cervical trauma were retrospectively evaluated. Incidental soft-tissue findings were investigated. All findings were grouped according to age. The findings were classified based on their clinical importance into three categories: Category 1: no clinical importance, Category 2: possible clinical importance requiring further investigation and Category 3: obvious clinical importance. In addition, the medical records of the patients were investigated. The follow-up ratio of the pathologies mentioned in the original radiology report was recorded.

Results:

The most frequently encountered findings in Categories 2 and 3 were carotid artery calcification (n = 89, 24.9%) and tonsillolith (n = 115, 32.2%), respectively. The reporting ratio in the original reports of Categories 1, 2 and 3 findings was 1.1% (n = 4), 9% (n = 27) and 34.5% (n = 64), respectively. No further investigations and follow-up was accomplished for Category 1 lesions, whereas 11.1% of Category 2 and 35.9% of Category 3 lesions were subjected to further investigations and follow-up.

Conclusions:

The cervical CT scans of trauma patients reveal many clinically important soft-tissue incidental findings. Cervical region incidental findings may be followed up on an outpatient basis, rarely being of life-threatening value. The ratio of reporting and follow-up of incidental findings increases parallel to the clinical importance of the lesions.     

The American College of Radiology strategy for managing incidental findings on abdominal computed tomography

There has been a dramatically increased awareness of the substantial clinical challenges posed by incidental findings found on cross-sectional imaging. In 2006, an Incidental Findings Committee was organized under the Body Imaging Commission in the American College of Radiology to create a consistent and rational approach to these findings. This article describes the formation, process of developing recommendations, and future tasks of this committee.     

Susceptibility‐weighted imaging in pediatric neuroimaging

Susceptibility‐weighted imaging (SWI) has become a key MR sequence in pediatric neuroimaging. The usage of SWI has significantly expanded recently. The strength of SWI lies not just in its ability to identify hemorrhage, calcium or nonheme iron by virtue of its susceptibility artifact, but also more importantly, the blood oxygen level dependent venography principle whereby several diseases can be diagnosed earlier. We are continuing to harness the power of SWI in the field of pediatric neuroimaging. In this paper, we will make a comprehensive review and discuss the utility of SWI in pediatric neuroimaging in establishing the diagnosis, differential diagnosis, and also understanding the pathomechanism of various pediatric brain pathologies. J. Magn. Reson. Imaging 2014;40:530–544 . © 2013 Wiley Periodicals, Inc.     

The participation of minors in preventive HIV research trials in South Africa: legal and human rights considerations

The constitutional prohibition of experimentation/research without the individual subject's (own) consent is investigated. A distinction is drawn between therapeutic and non-therapeutic research. A minor of 14 is competent to consent independently to medical treatment (which would include therapeutic research), but not to non-therapeutic research. A minor must be at least 18 years to be able to do so. Proxy consent can be secured for the participation of minors under 18 in non-therapeutic research only if they assent, if their participation in the research is indispensable and the research carries no more than negligible risk. Since the risks inherent in HIV preventive vaccine trials may carry more than negligible risk, these trials may not be carried out on children under 18. The limitation of rights and the consideration of foreign and international law in the interpretation of the South African Bill of Rights are investigated.     

Effects of group sports on health‐related physical fitness of overweight youth: A systematic review and meta‐analysis

Group sports interventions have been developed to improve health‐related physical fitness of overweight/obese youth. However, its benefits are not systematically documented. This study synthesizes the evidence about the effects of group sports on health‐related physical fitness of overweight/obese youth. Pubmed, Web of Knowledge, Scopus, Medline, CINAHL, SportDiscus, and Academic Search Complete were searched in February 2016. Studies assessing the effects of group sports on body composition, cardiorespiratory endurance, muscle strength, flexibility, and neuromotor fitness of overweight/obese youth (aged <18 years) were included. Effect sizes (ES) were calculated with Cohen's d and its 95% confidence intervals (CI). Improvements were found in (i) body composition – percentage of fat body mass (pooled ES = 0.67; 95% CI = 0.24–1.10) and waist circumference (ES = 0.69; P = 0.004); (ii) cardiorespiratory endurance – peak oxygen consumption (pooled ES = 0.53; 95% CI = 0.13–0.92) and (iii) muscle strength – hand grip strength (ES = 0.72; P = 0.003). No significant effects were found for body mass index (pooled ES = 0.27; 95% CI = ?0.14 to 0.69), percentage of lean body mass (ES = 0.01; P > 0.05), maximal power output (ES from 0 to 0.06; P > 0.05), sit‐and‐reach test (pooled ES = 0.26; 95% CI = ?0.16 to 0.68) and agility test (ES = 0; P = 0.48). Group sports improve body composition, cardiorespiratory endurance, and hand grip strength of overweight/obese youth. Flexibility and neuromotor fitness do not seem to change following group sports.     

Neglectable benefit of searching for incidental findings in the Dutch--Belgian lung cancer screening trial (NELSON) using low-dose multidetector CT

The purpose of this study was to prospectively determine the frequency and spectrum of incidental findings (IFs) and their clinical implications in a high risk population for lung cancer undergoing low-dose multidetector computed tomography (MDCT) screening for lung cancer. Scans of 1,929 participants were evaluated for lung lesions and IFs by two radiologists. IFs were categorised as not clinically relevant or possibly clinically relevant. Findings were considered possibly clinically relevant if they could require further evaluation or could have substantial clinical implications. All possibly clinically relevant IFs were reviewed by a third radiologist, who determined its clinical relevance. Of all 1,929 participants, 1,410 (73%) had not clinically relevant IFs and 163 (8%) had possibly clinically relevant IFs of which 129 (79%) were indeed considered clinically relevant. Additional imaging was performed mainly by ultrasound (112 of 118, 96%). All but one lesion were concluded to be benign, mostly cysts (n = 115, 80%). Only 21 (1%) participants had findings with clinical implications. In one participant a malignancy was found, yet without any clinical benefit since no curative treatment was possible. Based on our results, we advise against systematically searching for and reporting of IFs in lung cancer screening studies using low-dose MDCT. The NELSON study group consists of: H.J. de Koning (Dept. of Public Health, Erasmus Medical Centre Rotterdam), H.J.M. Groen (Dept. of Pulmonology, University Medical Centre Groningen), W.P.Th.M. Mali (Dept. of Radiology, University Medical Centre Utrecht), W.M. Prokop (Dept. of Radiology, University Medical Centre Utrecht), J-W.J. Lammers (Dept. of Pulmonology, University Medical Centre Utrecht), E.Th. Scholten (Dept. of Radiology, Kennemer Gasthuis Haarlem), C. Weenink (Dept. of Pulmonology, Kennemer Gasthuis Haarlem), E. Thunissen (Dept. of Pathology, Canisius-Wilhelmina Hospital Nijmegen), J. Verschakelen (Dept. of Radiology, University Hospital Gasthuisberg Leuven), K. Nackaerts (Dept. of Pulmonology, University Hospital Gasthuisberg Leuven)     

Comparison of fMRI data from passive listening and active‐response story processing tasks in children

Purpose

To use functional MRI (fMRI) methods to visualize a network of auditory and language‐processing brain regions associated with processing an aurally‐presented story. We compare a passive listening (PL) story paradigm to an active‐response (AR) version including online performance monitoring and a sparse acquisition technique.

Materials and Methods

Twenty children (ages 11–13 years) completed PL and AR story processing tasks. The PL version presented alternating 30‐second blocks of stories and tones; the AR version presented story segments, comprehension questions, and 5‐second tone sequences, with fMRI acquisitions between stimuli. fMRI data was analyzed using a general linear model approach and paired t‐test identifying significant group activation.

Results

Both tasks showed activation in the primary auditory cortex, superior temporal gyrus bilaterally, and left inferior frontal gyrus (IFG). The AR task demonstrated more extensive activation, including the dorsolateral prefrontal cortex and anterior/posterior cingulate cortex. Comparison of effect size in each paradigm showed a larger effect for the AR paradigm in a left inferior frontal region‐of‐interest (ROI).

Conclusion

Activation patterns for story processing in children are similar in PL and AR tasks. Increases in extent and magnitude of activation in the AR task are likely associated with memory and attention resources engaged across acquisition intervals. J. Magn. Reson. Imaging 2009;29:971–976. © 2009 Wiley‐Liss, Inc.     

Management of incidental findings during imaging research in "healthy" volunteers: current UK practice

Objectives

Incidental findings (IF) are becoming increasingly common due to the proliferation of imaging research. IFs can be life-changing for “healthy” volunteers. This study examined variation in IF management in UK research studies of healthy volunteers, including comparison with ethical and legal guidelines, thus providing baseline data and informing future practice.

Methods

Questionnaire of participant background [medical/non-medical; radiologist/non-radiologist; years as principal investigator (PI)], type of research (involving children or not), institutional policy, volunteer information, radiologist involvement in reporting scans and IF disclosure mechanisms. Investigator''s current and perceived “ideal” practice was examined. Participants were PIs performing imaging research of healthy volunteers approved by UK ethics committees (2006–2009).

Results

63/146 (43%) surveys completed. 54/61 (88.5%) had site-specific guidelines. Information commonly provided to volunteers should IF be found: personal data (51/62; 82%), contingency plans (54/62; 87%) and disclosure to general practitioner (GP)/treating physician (47/62; 76%). PIs used different strategies for image review. Commonest: radiologist reports research scans only when researcher suspicious of IF [15/57 (26%) compared with 5/28 (16%) in ideal practice]. Commonest ideal reporting strategy: routine reporting by specialist radiologists [9/28 (29%) compared with 8/57 (14%) in current practice]. 49/56 (87.5%) have a standardised disclosure contingency plan, usually involving GP. PIs most commonly disclosed IFs to volunteers when judged relevant (27/58; 47%), most commonly face to face (22/54; 41%), by volunteer''s GP (26/60; 43%). Background of PI influenced consent, reporting and disclosure practice.

Conclusion

There is wide variation in handling IFs in UK imaging research. Much of the current practice contravenes the vague existing legal and ethical guidelines, and is unlikely to be in the best interests of volunteers or researchers.The term “incidental finding” may give the impression that an unexpected finding is trivial, but an incidental finding (IF) can be life-changing [1]. One definition is “a finding that has potential health or reproductive importance which is discovered in the course of conducting research, but is beyond the aims of the study” [2]. The wider use of imaging in research is making incidental imaging findings more common, and recent academic and popular press editorials have highlighted the need for better management [3,4]. Advancing research practice is controversial and has led to recent debate [5] and deadlock [6] among imaging researchers in Europe and North America.IFs are common in research imaging. Their prevalence on brain MRI was 2.7% across 16 studies involving 19 559 participants [7] and may be as high as 12.8% on body MRI [8]. Extracolonic IFs at CT colonography require further investigation, medical or surgical intervention in 5–8% [9]. There are, therefore, important implications for informed consent, clinical review of images and mechanisms for notifying the subject. For the volunteers themselves, an IF may have serious implications for health, employment, medical or life insurance, and their state of mind. Furthermore, irrelevant imaging features incorrectly identified as pathological by non-radiologically trained researchers may cause unnecessary distress.We recently reviewed UK, European and other international legal and ethical guidance on management of IFs, and limited available information on volunteers'' expectations. Current recommendations are consistent with the principles that research volunteers should be informed of how their research images will be managed, that there should be measures for identifying and acting on IFs, and information should be disclosed to the subject and his or her responsible physician in a timely, sensitive and appropriate manner [10]. However, this guidance is hard to find and ambiguous, and does not distinguish management of imaging from other types of research sample. We suspected that management of IFs varies considerably between imaging research centres, but lacked reliable data on current practice. We have therefore surveyed UK imaging researchers to determine how IFs are currently managed to provide baseline data to inform future UK practice.     

Novel approach to improve molecular imaging research: Correlation between macroscopic and molecular pathological findings in patients

Purpose

Currently, clinical research approaches are sparse in molecular imaging studies. Moreover, possible links between imaging features and pathological laboratory parameters are unknown, so far. Therefore, the goal was to find a possible relationship between imaging features and peripheral blood cell apoptosis, and thereby to present a novel way to complement molecular imaging research.

Materials and methods

The investigation has been done in systemic lupus erythematosus (SLE), a prototype of an autoimmune disease characterized by multiorgan involvement, autoantibody production, and disturbed apoptosis. Retrospectively, radiological findings have been compared to both autoantibody findings and percentage apoptotic blood cells.

Results

Two SLE groups could be identified: patients with normal (annexin V binding < 20%), and with increased apoptosis (annexin V binding > 20%) of peripheral blood cells. The frequency of radiological examinations in SLE patients significantly correlated with an increased percentage of apoptotic cells (p < 0.005). In patients with characteristic imaging findings (e.g. lymph node swelling, pleural effusion) an elevated percentage of apoptotic cells was present. In contrast SLE-patients with normal imaging findings or uncharacteristic results of minimal severity had normal percentages of apoptotic blood cells.

Conclusion

This correlation between radiographic findings and percentage of apoptotic blood cells provides (1) further insight into pathological mechanisms of SLE, (2) will offer the possibility to introduce apoptotic biomarkers as molecular probes for clinical molecular imaging approaches in future to early diagnose organ complaints in patients with SLE, and (3) is a plea to complement molecular imaging research by this clinical approach.     

Unexpected findings at imaging: Predicting frequency in various types of studies

Objective

: The objective was to evaluate the prevalence and associated variables of unsuspected findings from imaging tests in clinical practice.

Material and Methods

: Cross-sectional study of patients referred for an imaging test in 2006. Two independent radiologists classified the imaging tests according to the presence or absence of an unexpected finding in relation with the causes that prompted the test (kappa = 0.95). A thorough chart review of these patients was carried out as a quality control.

Results

: Out of 3259 patients in the study, 488 revealed unsuspected findings (15.0%). The prevalence of abnormal findings varied according to age: from 20.4% (150/734) in the over 74-group to 9.0% (76/847) in the under 43-group. The largest prevalence was in the category of infectious diseases (14/49, 28.6%) and in CT (260/901, 28.9%) and ultrasound (138/668, 20.7%). Studies showing moderate clinical information on the referral form were less likely to show unexpected findings than those with null or minor information (OR 0.51; 95% CI 0.36-0.73).

Conclusion

: Clinicians should expect the frequency of diseases detectable by imaging to increase in the future. Further research with follow-up of these findings is needed to estimate the effect of imaging technologies on final health outcomes.     

Changes in physical activity and sedentary time in the Finnish Schools on the Move program: a quasi‐experimental study

The aim of the Finnish Schools on the Move program is to create a more active and pleasant school day through physical activity (PA). In this quasi‐experimental design, we compared changes in moderate‐to‐vigorous‐intensity physical activity (MVPA) and sedentary time (ST) during the school day and outside school hours for Grades 1–9 over two academic years in four program schools and two reference schools. Altogether 319 girls and boys aged 7–15 participated in the study between 2010 and 2012. MVPA and ST were measured four times over the 1.5‐year follow‐up period for seven consecutive days, using a hip‐worn ActiGraph accelerometer. Linear growth curve modeling was used to examine the effect of the program on MVPA and ST during follow‐up. School day MVPA increased (P = 0.010) and school day ST decreased (P = 0.008) in program primary schools (Grades 1–6) more compared with the reference schools. The effect sizes (Cohen's d) for the difference in change (from the first to the last measurement) were small (d = 0.18 and d = ?0.27, respectively). No differences in the changes of leisure‐time or whole‐day MVPA and ST between the program and reference schools were observed during follow‐up. In conclusion, the changes in school day MVPA and ST did not translate into positive effects across the whole day. More effective and longer promotion actions are needed for positive changes in PA and ST, especially in lower secondary schools and for all daily segments.     

Quantitative assessment of the effects of high‐permittivity pads in 7 Tesla MRI of the brain

The use of high‐permittivity materials has been shown to be an effective method for increasing transmit and receive sensitivity in areas of low‐signal intensity in the brain at high field. Results in this article show that the use of these materials does not increase the intercoil coupling for a phased array receive coil, does not have any detrimental effects on the B₀ homogeneity within the brain, and does not affect the specific absorption rate distribution within the head. Areas of the brain close to the pads exhibit significant increases (>100%) in transmit field efficiency, but areas further away show a less pronounced (～10%) decrease due to the homogenization of the transmit field and the loss introduced by the dielectric pads. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc.     

Ski and snowboard school programs: Injury surveillance and risk factors for grade‐specific injury

The objective of our study was to evaluate incidence rates and profile of school program ski and snowboard‐related injuries by school grade group using a historical cohort design. Injuries were identified via Accident Report Forms completed by ski patrollers. Severe injury was defined as those with ambulance evacuation or recommending patient transport to hospital. Poisson regression analysis was used to examine the school grade group‐specific injury rates adjusting for risk factors (sex, activity, ability, and socioeconomic status) and accounting for the effect of clustering by school. Forty of 107 (37%) injuries reported were severe. Adolescents (grades 7‐12) had higher crude injury rates (91 of 10 000 student‐days) than children (grades 1‐3: 25 of 10 000 student‐days; grades 4‐6: 65 of 10 000 student‐days). Those in grades 1‐3 had no severe injuries. Although the rate of injury was lower in grades 1‐3, there were no statistically significant grade group differences in adjusted analyses. Snowboarders had a higher rate of injury compared with skiers, while higher ability level was protective. Participants in grades 1‐3 had the lowest crude and adjusted injury rates. Students in grades 7‐12 had the highest rate of overall and severe injuries. These results will inform evidence‐based guidelines for school ski/snowboard program participation by school‐aged children.     

Pretherapeutic MRI for decision‐making regarding selective neoadjuvant radiochemotherapy for rectal carcinoma: Interim analysis of a multicentric prospective observational study

Purpose:

To study the accuracy of different cutoffs for an involved circumferential resection margin (CRM) compared with T and N categories measured by MRI as basis for selective application of neoadjuvant radiochemotherapy (nRCT) in rectal carcinoma.

Materials and Methods:

In a prospective multicenter observational study involving 153 primarily operated patients, the preoperative results of MRI with pathohistological findings of resected specimens were compared.

Results:

For a cutoff of ≤1 mm for involvement of the CRM, the accuracy of preoperative MRI was 90.9% (139/153). The negative predictive value was 98.5% (134/136). The four participating departments did not differ significantly. For a cutoff of >2 mm and >5 mm, the rates of false‐positive findings increased significantly from 5% to 12% and 35% with a decrease in accuracy to 82% and 62%, respectively. In contrast, the accuracy in predicting T (69.3%) and N categories (61.4%) was much lower.

Conclusion:

The indication for nRCT should be based on the determination of the minimal distance of the tumor from mesorectal fascia with a cutoff point of >1 mm as measured by MRI. J. Magn. Reson. Imaging 2013;37:1122–1128. © 2013 Wiley Periodicals, Inc.     

Pre‐ and postoperative MR brain imaging with automatic planning and scanning software in tumor patients: An intraindividual comparative study at 3 Tesla

Purpose

To evaluate the feasibility of automatic planning and scanning of brain MR imaging (MRI) protocols on a clinical 3 Tesla system in tumor patients before and after neurosurgical intervention.

Materials and Methods

Twenty‐nine patients with intra‐axial lesions were examined with automated planscan software pre‐ and postoperatively. MR section geometries were determined using intensity‐based three‐dimensional registration and an extraction of landmarks. The technique involved an active shape model to match the boundaries of anatomical structures and typical shape variations. Insufficient geometries were corrected manually by a trained operator.

Results

In 29/29 of the preoperative and 47/58 MRI sessions in total, no manual interaction was necessary. Predominantly minor corrections were necessary in 11/29 postoperative sessions, with critical corrections (≥ 3‐mm offcenter change or ≥ 5° in alignment of the stacks) in 3/58 sessions. Mean offcenter correction was 1.41 mm (range, 0–7.33 mm), mean angle change toward the midline or commissural line was 1.43° (range, 0–8.05°).

Conclusion

Automatic planning and scanning before and after brain surgery yields robust results in most of the patients with substantial shape deviations. The dimensions of necessary geometry corrections are predominantly small. These results are promising to minimize interscan variability in longitudinal studies. J. Magn. Reson. Imaging 2009;30:672–677. © 2009 Wiley‐Liss, Inc.     

Postmortem findings in COVID-19 fatalities: A systematic review of current evidence

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the ongoing pandemic of coronavirus disease 2019 (COVID-19). Almost 17 months after the first COVID-19 case was reported, the exact pathogenesis of the virus is still open to interpretation. Postmortem studies have been relatively scarce due to the high infectivity rate of the virus. We systematically reviewed the literature available for studies that reported gross, histological, microscopic, and immunohistochemical findings in COVID-19 fatalities with the aim of reporting any recurrent findings among different demographics. PubMed and Scopus were searched up till the second of May 2021 and 46 studies with a total of 793 patients were shortlisted after the application of inclusion and exclusion criteria. The selected studies reported gross, histological, microscopic, and immunohistochemical autopsy findings in the lungs, heart, liver, gallbladder, bowels, kidney, spleen, bone marrow, lymph nodes, CNS, pancreas, endocrine/exocrine glands, and a few other miscellaneous locations. The SARS-CoV-2 virus was detected in multiple organs and so was the presence of widespread microthrombi. This finding suggests that the pathogenesis of this highly infectious virus might be linked to some form of coagulopathy. Further studies should focus on analyzing postmortem findings in a larger number of patients from different demographics in order to obtain more generalizable results.