Saturday, 22 January 2011

When "Healthy Brains" Aren't

There's a lot of talk, much of it rather speculative, about "neuroethics" nowadays.

But there's one all too real ethical dilemma, a direct consequence of modern neuroscience, that gets very little attention. This is the problem of incidental findings on MRI scans.

An "incidental finding" is when you scan someone's brain for research purposes, and, unexpectedly, notice that something looks wrong with it. This is surprisingly common: estimates range from 2–8% of the general population. It will happen to you if you regularly use MRI or fMRI for research purposes, and when it does, it's a shock. Especially when the brain in question belongs to someone you know. Friends, family and colleagues are often the first to be recruited for MRI studies.

This is why it's vital to have a system in place for dealing with incidental findings. Any responsible MRI scanning centre will have one, and as a researcher you ought to be familiar with it. But what system is best?

Broadly speaking there are two extreme positions:
  1. Research scans are not designed for diagnosis, and 99% of MRI researchers are not qualified to make a diagnosis. What looks "abnormal" to Joe Neuroscientist BSc or even Dr Bob Psychiatrist is rarely a sign of illness, and likewise they can easily miss real diseases. So, we should ignore incidental findings, pretend the scan never happened, because for all clinical purposes, it didn't.
  2. You have to do whatever you can with an incidental finding. You have the scans, like it or not, and if you ignore them, you're putting lives at risk. No, they're not clinical scans, they can still detect many diseases. So all scans should be examined by a qualified neuroradiologist, and any abnormalities which are possibly pathological should be followed-up.
Neither of these extremes is very satisfactory. Ignoring incidental findings sounds nice and easy, until you actually have to do it, especially if it's your girlfriend's brain. On the other hand, to get every single scan properly checked by a neuroradiologist would be expensive and time-consuming. Also, it would effectively turn your study into a disease screening program - yet we know that screening programs can cause more harm than good, so this is not necessarily a good idea.

Most places adopt a middle-of-the-road approach. Scans aren't routinely checked by an expert, but if a researcher spots something weird, they can refer the scan to a qualified clinician to follow up. Almost always, there's no underlying disease. Even large, OMG-he-has-a-golf-ball-in-his-brain findings can be benign. But not always.

This is fine but it doesn't always work smoothly. The details are everything. Who's the go-to expert for your study, and what are their professional obligations? Are they checking your scan "in a personal capacity", or is this a formal clinical referral? What's their e-mail address? What format should you send the file in? If they're on holiday, who's the backup? At what point should you inform the volunteer about what's happening?

Like fire escapes, these things are incredibly boring, until the day when they're suddenly not.

A new paper from the University of California Irvine describes a computerized system that made it easy for researchers to refer scans to a neuroradiologist. A secure website was set up and publicized in University neuroscience community.

Suspect scans could be uploaded, in one of two common formats. They were then anonymized and automatically forwarded to the Department of Radiology for an expert opinion. Email notifications kept everyone up to date with the progress of each scan.

This seems like a very good idea, partially because of the technical advantages, but also because of the "placebo effect" - the fact that there's an electronic system in place sends the message: we're serious about this, please use this system.

Out about 5,000 research scans over 5 years, there were 27 referrals. Most were deemed benign... except one which turned out to be potentially very serious - suspected hydrocephalus, increased fluid pressure in the brain, which prompted an urgent referral to hospital for further tests.

There's no ideal solution to the problem of incidental findings, because by their very nature, research scans are kind of clinical and kind of not. But this system seems as good as any.

ResearchBlogging.orgCramer SC, Wu J, Hanson JA, Nouri S, Karnani D, Chuang TM, & Le V (2011). A system for addressing incidental findings in neuroimaging research. NeuroImage PMID: 21224007

9 comments:

bradley.voytek@gmail.com said...

Whoa, I would have missed this paper. Glad you wrote about it. Sending it to my (f)MRI colleagues now.

Anonymous said...

A very difficult problem indeed. If a center chooses not to ignore such findings, what is the liability of the researchers? If they do not refer a scan to an expert, is there an implicit assumption that they deemed it "normal"? If you open the door to expert opinion on research scans, then perhaps centers should have all the scans checked, rather than rely on unqualified cognitive scientists.

N.M.Levesque said...

What's that large black space where there's supposed to be brain matter on that image?

Neuroskeptic said...

N.M.Levesque: According to the site I nicked it from it's an arachnoid cyst. It's not quite as serious as it looks.

Most incidental findings aren't that dramatic but you do get some extreme ones. I know of one centre which discovered that one of their volunteers had no corpus callosum. He had a diagnosis of autism, so it wasn't like he was a completely healthy control, but still, very unexpected.

petrossa said...

@neuro

You have a link to that CC missing story? I'm very interested

Neuroskeptic said...

petrossa: I read it in a paper from the group behind this work. I actually thought it was in that paper, but I just checked and it wasn't, must have been another one. But I'm 99% it was that group.

petrossa said...

tnx Neuro. At least i have an angle to follow up. Would fit in nicely with my theory on the origin of autism.

petrossa said...

@neuro

Seems your spamfilter isn't very hot :)
Found 100's of CC agenesis patients, most of them initially diagnosed with some form of autism.

The orginal rainman was one, never knew that.

Food for thought.

petrossa said...

Objective: The purpose of this study was to examine the size of subregions of the corpus
callosum in autistic individuals. Method: The areas of three subregions (anterior, body, and
posterior) of the corpus callosum were examined on midsagittal magnetic resonance images
of 35 autistic subjects whose mean age was 18 years and 36 healthy comparison subjects
matched on age and IQ. Results: After controlling for total brain volume, gender, and performance
IQ, the authors detected a significantly smaller size of the body and posterior subregions
of the corpus callosum in the autistic individuals. Conclusions: In the context of recent
reports of increased brain size in autism, several possible mechanisms are considered in exploring
the significance of a smaller relative size of the corpus callosum in autism.

http://ajp.psychiatryonline.org/cgi/reprint/154/8/1051

I rest my case.