Considerable enthusiasm for the growing knowledge about human neurocognitive function available from neuroimaging is paralleled by growing empirical evidence about individual brain pathology that is unexpected and accidentally discovered during such studies. Incidental findings have implications for research participants and researchers alike. The data here suggest substantial procedural variability across research units for engaging participants, protecting participants in the research environment, and detecting and communicating abnormal findings to them. Moreover, the data point to the need for researchers to take such findings into account when designing studies and creating research teams.
This study has a number of limitations that must be recognized in interpreting the data. First, the 11% response rate limits the generalizability of the results to the larger MRI community. Second, the uniformity of sampling, and characteristics of the responding laboratories are unknown. Therefore, the impact that affiliation with or independence from a medical center or radiology department has on scanning protocols and procedures for consenting research participants, especially insofar as incidental findings are concerned, will require future study.
Nonetheless, a number of important results emerge from this study that, juxtaposed with other recent reports about incidental findings, are especially noteworthy. First, more than 80% of the respondents reported findings of unexpected pathology in their studies. Second, despite this large effect, only a fraction of research scans are reviewed professionally within a time frame of one week or less. This raises particular concerns in light of a recent study by Illes et al (4
) showing that while the number of abnormalities detected in college-age subjects (one of the largest cohorts used in MRI research today) is low, the majority of such findings are highly significant. These data complement clinical reports of incidental findings in the central nervous system (CNS) of asymptomatic choroid plexus cysts in the lateral ventricles on diffusion-weighted MRI (8
), non-functioning pituitary adenomas (9
), and abnormal MR signal intensity indicating a subclinical stage of primary progressive multiple sclerosis (11
Also, in a subset of the responders for whom neuroradiologist involvement is not an IRB requirement, almost 20% do not send scans out to be read at all. This may be a problem that is compounded by the fact that a substantial proportion of personnel who conduct research using imaging protocols such as MRI (including undergraduate and graduate students, post-docs, and many PIs) are not medically qualified to review scans for incidental findings. It is often the case that PIs and other senior researchers only view processed functional data presented on a standardized brain, and never view the original scans themselves. However, even senior researchers are often not M.D.s, let alone trained radiologists certified in image interpretation who, in nearly every other setting, would be the ones interpreting those same images. Third, given higher rates than expected of incidental findings, the presence of nonre-search personnel in the scanning environment during adult studies may be inadvisable given institutional and Health Insurance Portability and Accountability Act of 1996 (HIPPA) requirements for medical privacy.
We predict that although subjects sign consent forms acknowledging no clinical benefit and an understanding that the scans conducted are of research (not clinical) quality, they will nonetheless presume that if pathology exists, it will be detected and reported to them. We are currently testing this hypothesis in a study of subject expectations in both medical and nonmedical research settings.
On one hand, despite the high degree of variability observed, current procedures for handling incidental findings may be adequate. To our knowledge, neither the legal nor the medical literature has yet documented an adverse outcome due to a missed finding, and while brain MRI may represent an ideal modality for neurologic and neuroradiologic screening prior to subject enrollment, this would be difficult to implement in terms of both practicality and cost. Moreover, even though neuroimaging research may present an ideal opportunity for expanding collaborations among clinicians and researchers, and especially for providing hands-on research experience to clinical trainees in neuroradiology and other specialists who are familiar with reading brain MRIs (e.g., neurologists and certain psychiatrists), the sheer volume of scans requiring review would be daunting.
The counterpoint, on the other hand, bears on the potential imprudence of waiting for a catastrophic event or significant legal action before taking steps to recognize and manage any abnormalities that are discovered. The number of research participants scanned today is staggering—no doubt in the tens of thousands. The data reported here provide for the first time a perspective on incidental findings from the purview of the investigator, and further support our urgings in previous publications on this subject: before scientific progress is forestalled, and for the sake of both scientific integrity and public trust, we must revisit the relative trade-offs among all procedural alternatives and identify minimum and optimum standards of practice. We believe that the duty of disclosure is transparent to all professionals in the medical setting—clinical or research—regardless of professional degree (12
Ethics research, quite apart from ethical conduct, has not been a focus of the medical imaging community in the past. However, the new field of neuroethics has gained substantial visibility and credibility in imaging, neurosciences, and other areas (including law, public policy, and the humanities) over the past few years (14
). The study of neuroethics has shown that dialogue and methodologies drawn from multidisciplinary areas are not only desirable but are a powerful means of achieving scientific solutions to difficult research dilemmas. In the present case, we believe that processes formulated with the benefit of a wide range of disciplinary input will have greater acceptability and relevance, and will be easier to implement than those that may be imposed through a later regulatory process. Like other guidelines for research conduct that are embodied in our professional code of ethics, such as those for protecting the confidentiality of human subjects and authorship, guidelines regarding unexpected findings on brain scans are vital to our continuing research.