Elsevier

The Lancet Neurology

Volume 10, Issue 11, November 2011, Pages 987-1001
The Lancet Neurology

Review
Advances in imaging in Parkinson's disease

https://doi.org/10.1016/S1474-4422(11)70214-9Get rights and content

Summary

Advances in imaging have made it possible to detect functional and, increasingly, structural changes in Parkinson's disease. Although imaging is not yet routinely used for diagnosis, such an application is becoming increasingly feasible. Of potentially greater interest, however, is the use of imaging as a biomarker to detect premotor disease and disease progression. Imaging also provides insights into complications of Parkinson's disease and its long-term treatment, and the role of dopamine in the normal brain. Furthermore, these techniques can be applied to animal models, to help validate these models and allow their use in the study of potential disease-modifying therapies.

Introduction

The past 25 years have seen extensive developments in imaging approaches to the study of CNS disorders. Although diagnosis of Parkinson's disease remains clinical, advances in functional and structural imaging have improved the capacity to differentiate between Parkinson's disease and essential tremor, and between different akinetic-rigid syndromes. Recent advances in our understanding of the pathogenesis of Parkinson's disease have stimulated greater interest in the development of potential disease-modifying therapies, and, therefore, a more urgent need to detect early disease and identify biomarkers to assess the results of interventions.

Here, we review applications of imaging as a biomarker for early disease detection and for the study of disease progression. Imaging studies of animal models provide important complementary information on pathogenesis and for assessment of novel therapies, but are currently in their infancy. Imaging can provide significant insights into the basis of motor and non-motor complications of Parkinson's disease and its therapy, and the role of dopamine in normal brain function. Novel markers might permit in-vivo assessment of processes contributing to disease pathogenesis, such as inflammation and abnormal protein deposition. Although much of the interest in imaging approaches in Parkinson's disease has focused on PET or SPECT imaging using radionuclide scanning or on functional MRI, novel magnetic resonance approaches, including anatomical studies of connectivity and shape analysis, and the ability to measure iron deposition in vivo are all potentially relevant to Parkinson's disease and are reviewed here. Novel technologies are emerging that can draw on the strengths of radionuclide imaging and MRI. Some approaches, such as transcranial sonography, have been previously reviewed1 and are not considered further here.

Section snippets

Human radionuclide studies

The most widely accepted application of PET and SPECT in Parkinson's disease is the assessment of dopamine function (figure 1). Presynaptic dopamine integrity can generally be assessed in one of three ways: 18F-fluoro-L-dopa (18F-FDOPA) is taken up by L-aromatic amino acid decarboxylase (AAAD), converted to 18F-fluorodopamine, and packaged in synaptic vesicles from which it ultimately leaves and is subject to enzymatic degradation; 11C-dihydrotetrabenazine or its 18F-labelled analogue2 labels

Magnetic resonance techniques

The role of MRI in the diagnosis and monitoring of parkinsonian syndromes has progressed from excluding conditions that result in parkinsonism to distinguishing idiopathic Parkinson's disease from atypical parkinsonian disorders such as PSP, MSA, and corticobasal syndrome.115 Advances in hardware allow, for example, direct visualisation of the substantia nigra at high field strengths,116 but most of the recent advances have been in quantitative analyses of the images.

Conclusions and future directions

Radionuclide imaging is exquisitely sensitive for the assessment of neurochemical function, including the synthesis, storage, release, and reuptake of neurotransmitters. Radionuclide imaging can also be used to assess altered metabolism and functional connectivity. These properties are beneficial for the study of conditions such as Parkinson's disease, in which functional changes are of greater magnitude than anatomical changes, which are somewhat limited and difficult to detect. Thus,

Search strategy and selection criteria

References for this Review were found through a search of PubMed using the terms “PET” or “SPECT” and “Parkinson*” from 1980 to August, 2011, and “MR spectroscopy”, “MR imaging”, “Parkinson's disease”, and “iron” from 1993 to August, 2011, and from a search of Google Scholar using the terms “MRI”, “shape analysis”, “segmentation”, and “Parkinson's disease” from 2008 to August, 2011. Only reports published in English were included. Additional searches were done as needed for specific topics.

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