The basics of PET molecular imaging in neurodegenerative disorders with dementia and/or parkinsonism

Abstract

Positron emission tomography (PET) imaging biomarkers have become crucial in understanding and diagnosing neurodegenerative disorders. PET imaging allows for the in vivo quantification of molecular targets with high sensitivity, aiding in the study of disease pathophysiology and progression from preclinical stages. By visualising specific molecular pathologies, PET biomarkers enable a shift from symptom-based to biology-based definitions of neurodegenerative diseases, allowing for earlier and more accurate detection and diagnosis. This has significant implications for developing and testing new therapies aimed at modifying disease course. In this review, we will go through the standards of PET imaging in the evaluation of neurodegenerative disorders. Specifically, we will review PET molecular imaging of amyloid-β plaques, tau pathology, as well as the effect of neurodegeneration on neuronal activity in different disorders. Moreover, we will revise PET tracers targeting neurotransmitter systems such as the dopaminergic system which can detect early functional changes in movement disorders. Issues related to methods, image interpretation, normal findings and mimics will be an important part of this review. KEY POINTS: Question A review of PET molecular imaging tools for assisting the clinical diagnosis of patients presenting with cognitive impairment or parkinsonism and suspected neurodegenerative disease. Findings PET molecular imaging tools vary widely in their image acquisition protocols and image interpretation, allowing us to study different features of neurodegenerative diseases. Clinical relevance The majority of PET molecular imaging tools are currently in use in our clinical practice. Despite the differences between them, standardised visual reading methods and specific semi-quantitative parameters have been established, allowing for their use.

Keywords: Brain diseases; Molecular imaging; Positron Emission Tomography; Single photon emission computed tomography.

Fig. 1

Axial PET images of [¹⁸F]florbetapir (A), [¹⁸F]flutemetamol (B), and [¹⁸F]florbetaben (C) in the colour scale recommended by the tracer manufacturer. Positive brain amyloid scans of Alzheimer’s patients in images 1 (A.1, B.1, and C.1) and negative brain amyloid scans in images 2 (A.2, B.2, C.2)

Fig. 2

Pitfalls and artefacts in amyloid PET imaging. A [18F]Florbetapir PET/CT scan of a patient with right frontal stroke and brain atrophy. The PET/CT fusion images clearly show no difference between white matter and grey matter (positive amyloid PET scan). B [18F]Florbetapir PET/CT scan of a patient with normal pressure hydrocephalus. In this case, the fusion images showed much higher activity in the white matter than in the grey matter (negative amyloid PET scan)

Fig. 3

[¹⁸F]FDG PET (A) and [¹⁸F]flortaucipir (B) in an AD patient. Images show temporoparietal and frontal hypometabolism (A), which correlates with AD-related tau deposits

Fig. 4

Stereotactic surface projection displaying local deviations of individual patients from an age-adjusted normal reference sample (3D surface z-maps)

Fig. 5

Pitfalls and artefacts in [¹⁸F]FDG PET imaging. A Scan of a patient with CNS drug interference showing cortical hypometabolism that could mimic an AD pattern, but with thalamic hypometabolism characteristic of this interference. B Scan of a patient with a right frontoparietal ischaemic antecedent (arrow), showing a diaschisis of the contralateral cerebellum (arrow) due to disruption of the corticospinal tract. C An example of a PET scan with motion artefacts

Fig. 6

A [¹⁸F]FDOPA PET image of a healthy patient (A.1) and a patient with PD (A.2). B Pitfalls and artefacts in presynaptic dopaminergic imaging. [¹⁸F]FDOPA PET scan (B.1) of a patient with suspected Parkinson’s disease showing a decrease in the right putamen. However, the fusion PET/MRI image (B.2) shows that the decreases are due to the artefact of spaces surrounding the walls of vessels within the brain parenchyma observed on MRI