PET in Movement Disorders: Parkinson's and Atypical Parkinsonism

People who look up brain scans for Parkinson's disease almost always find the same name: DaTscan. Many then assume it is a PET scan, because it sits in the same family of nuclear medicine tests. It is not, and the difference matters if you are trying to understand a report, a referral or an article. This page sorts out SPECT versus PET, then looks at what PET tracers such as F-DOPA and FDG can contribute in Parkinson's disease and in the related conditions called atypical parkinsonism. Throughout, imaging is an aid to a neurologist's judgment. Protocols differ by centre, and your own movement-disorder team has the final word.

Parkinson's is still diagnosed at the bedside

The Michael J. Fox Foundation states that doctors diagnose Parkinson's from the symptoms people report and what they see on examination, a clinical diagnosis, and that there is not yet a test specifically to diagnose it. The American Parkinson Disease Association adds that once motor symptoms are present, even subtle ones, a neurologist can usually make the diagnosis on examination, and that conventional MRI appears normal in Parkinson's disease. Both organisations make the same practical point: for many people a dopamine scan adds little to what the examination has already shown, and it would not change treatment.

So when is imaging considered? Typically when the examination is not clear-cut, when symptoms do not fit neatly, or when there is a question that could change the plan. A movement-disorder specialist, meaning a neurologist with extra training in these conditions, normally makes that call.

SPECT and PET: what the difference is

Both are nuclear medicine scans. A small amount of a radioactive tracer is injected, it travels to the brain, and a scanner builds a three-dimensional map of where it has gone. The names describe the physics: single-photon emission computed tomography (SPECT) detects tracers that give off single gamma photons, while positron emission tomography (PET) detects tracers that give off positrons, whose annihilation produces a pair of photons. If you want that physics in detail, see the physics of positron emission and annihilation.

DaTscan is a SPECT test. According to the American Parkinson Disease Association, the tracer is ioflupane (123I), the US Food and Drug Administration approved it in 2011, and it attaches to the dopamine transporter, a molecule found on the endings of dopamine-producing nerve cells. People with Parkinson's disease typically show a smaller signal in the striatum, the part of the brain where those endings are meant to be. A review in the Turkish Journal of Medical Sciences says that SPECT is the modality used to assess this transporter in the striatum, that PET tracers for the dopamine transporter, such as fluorine-18 FP-CIT, exist, and that none of them were commercially available at the time of writing. So a dopamine transporter scan in practice usually means SPECT, even though PET versions exist.

What a dopamine transporter scan can and cannot separate

The Michael J. Fox Foundation says a DaTscan can help tell Parkinson's disease from conditions that do not damage dopamine cells, such as essential tremor or drug-induced parkinsonism. The American Parkinson Disease Association adds that the FDA indication is for distinguishing Parkinson's disease from essential tremor, a distinction that is often straightforward on examination but can be hard when tremor features are mixed.

The limit is just as important. The scan is abnormal in any illness that causes loss of dopamine nerve endings in the striatum. Multiple system atrophy, progressive supranuclear palsy and corticobasal degeneration, the main atypical parkinsonisms, typically give abnormal scans too, so a DaTscan cannot tell them apart from Parkinson's disease, or from each other. The Foundation also notes that a DaTscan cannot be used on its own to diagnose Parkinson's, and the American Parkinson Disease Association says the clinical version is not quantitative and is not used to follow progression. The Turkish review notes that symptoms of parkinsonism appear when an estimated 60 to 80 percent of presynaptic dopamine neurons have been lost, which helps explain why the scan can be abnormal before symptoms are obvious. Every test, the American Parkinson Disease Association points out, has false positives and false negatives, so results are read in the whole clinical context.

What PET tracers add

PET approaches the same questions with different tracers. F-DOPA (fluorodopa, labelled with fluorine-18) is a PET tracer used to look at the dopamine pathway from the nigra to the striatum. A systematic review of 77 studies in the European Journal of Nuclear Medicine and Molecular Imaging found F-DOPA uptake reduced in multiple system atrophy, progressive supranuclear palsy and corticobasal syndrome. In Parkinson's disease, the loss follows a front-to-back gradient in the putamen, whereas in progressive supranuclear palsy the caudate and the front of the putamen were reduced to the same level as the back. Still, the review reports that F-DOPA could reliably separate healthy people from people with parkinsonism, but that telling Parkinson's disease, multiple system atrophy and progressive supranuclear palsy apart from each other remained difficult.

FDG-PET asks a different question. Instead of looking at dopamine terminals, it maps glucose use across the brain, which reflects nerve cell activity (the tracer is explained in PET radiotracers explained). A review in the Journal of Nuclear Medicine describes characteristic patterns: Parkinson's disease with reduced metabolism toward the back of the cortex and relatively increased metabolism in the putamen, pallidum, thalamus, pons and cerebellum; multiple system atrophy with marked reduction in the putamen, pons and cerebellum; progressive supranuclear palsy with reduction in the medial frontal areas, midbrain, thalamus and caudate; and corticobasal degeneration with asymmetric reduction in the parietal and sensorimotor cortex and striatum. The systematic review above reports that disease-specific patterns of reduced glucose metabolism have shown higher accuracy than dopaminergic imaging techniques for distinguishing parkinsonian syndromes.

What the accuracy figures mean

The Journal of Nuclear Medicine authors made a preliminary pooled estimate that visual FDG-PET readings supported by voxel-based statistical analysis had about 91 percent sensitivity and 91 percent specificity for diagnosing atypical parkinsonian syndromes, and report that specificity for individual atypical conditions was consistently above 90 percent while sensitivity was more variable. These numbers come from research settings with expert readers and defined patient groups. The authors also note that isolated reduction in the cerebellum can occur in other causes of cerebellar degeneration, so a pattern is a clue and not a verdict. The review further notes that FDG-PET can help evaluate cognitive impairment in Parkinson's disease, a topic that overlaps with PET in dementia and memory evaluation.

It also helps to know the research context. Much of what is written about F-DOPA and newer tracers comes from specialist research centres, and the systematic review itself lists many other radioligands, for example for microglial activation or tau, that remain experimental in this setting.

An aid, not a stand-alone diagnosis

Imaging in movement disorders is best seen as one piece of evidence. MRI is often part of the work-up and, as the American Parkinson Disease Association notes, can show abnormalities in conditions such as vascular parkinsonism. A dopamine scan, SPECT or PET, can show whether a dopamine deficit exists. FDG-PET can suggest which pattern of network involvement fits. Response to levodopa, the course of illness over time and the neurologist's examination remain central. If a result seems to conflict with how you or a relative are doing, ask the treating neurologist how the pieces fit. Practical preparation, including whether any medicines need to be paused for a dopamine transporter scan, is given by the imaging department, as the Michael J. Fox Foundation notes; the general routine for a PET visit is in what to expect on scan day, and combined scanners are explained in PET-CT and PET-MRI.

The short version

DaTscan is a SPECT test of dopamine nerve endings, and it cannot separate Parkinson's disease from the atypical parkinsonisms. PET tracers such as F-DOPA and FDG add information about the dopamine pathway and about patterns of brain metabolism, which can help in uncertain cases. Parkinson's disease remains a clinical diagnosis, and imaging is an aid to the neurologist.