Abstract

Objective. To explore the viability of developing a computer-aided diagnostic system for Parkinsonian syndromes using dynamic [11C]raclopride positron emission tomography (PET) and T1-weighted magnetic resonance imaging (MRI) data. Approach. The biological heterogeneity of Parkinsonian syndromes renders their statistical classification a challenge. The unique combination of structural and molecular imaging data allowed different classifier designs to be tested. Datasets from dynamic [11C]raclopride PET and T1-weighted MRI scans were acquired from six groups of participants. There were healthy controls (CTRL n = 15), patients with Parkinson’s disease (PD n = 27), multiple system atrophy (MSA n = 8), corticobasal degeneration (CBD n = 6), and dementia with Lewy bodies (DLB n = 5). MSA, CBD, and DLB patients were classified into one category designated as atypical Parkinsonism (AP). The distribution volume ratio (DVR) kinetic parameters obtained from the PET data were used to quantify the reversible tracer binding to D2/D3 receptors in the subcortical regions of interest (ROI). The grey matter (GM) volumes obtained from the MRI data were used to quantify GM atrophy across cortical, subcortical, and cerebellar ROI. Results. The classifiers CTRL vs PD and CTRL vs AP achieved the highest balanced accuracy combining DVR and GM (DVR-GM) features (96.7%, 92.1%, respectively), followed by the classifiers designed with DVR features (93.3%, 88.8%, respectively), and GM features (69.6%, 86.1%, respectively). In contrast, the classifier PD vs AP showed the highest balanced accuracy (78.9%) using DVR features only. The integration of DVR-GM (77.9%) and GM features (72.7%) produced inferior performances. The classifier CTRL vs PD vs AP showed high weighted balanced accuracy when DVR (80.5%) or DVR-GM features (79.9%) were integrated. GM features revealed poorer performance (59.5%). Significance. This work was unique in its combination of structural and molecular imaging features in binary and triple category classifications. We were able to demonstrate improved binary classification of healthy/diseased status (concerning both PD and AP) and equate performance to DVR features in multiclass classifications.

Highlights

  • Parkinsonian syndromes are a group of movement disorders characterised by diverse primary motor and non-motor symptoms with variable expression [1]

  • Features’ extraction The distribution of the features’ values extracted from the magnetic resonance imaging (MRI) grey matter (GM) images and from the [11C]raclopride positron emission tomography (PET) images is represented in figure 1

  • The binary classifiers (CTRL vs Parkinson’s disease (PD), CTRL vs atypical Parkinsonism (AP)) achieved the highest balanced accuracy by integrating DVRGM features (96.7%, 92.1%, respectively), followed by the classifiers designed with distribution volume ratio (DVR) features (93.3%, 88.8%, respectively), and GM features (69.6%, 86.1%, respectively)

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Summary

Introduction

Parkinsonian syndromes are a group of movement disorders characterised by diverse primary motor (tremor at rest, postural instability, bradykinesia and rigidity) and non-motor symptoms with variable expression [1]. They include, among others, Parkinson’s disease (PD), dementia with Lewy bodies (DLB), multiple system atrophy (MSA) and corticobasal degeneration (CBD) [2]. DLB, CBD, and MSA are categorised as atypical Parkinsonism (AP) This designation is used to categorise disorders presenting with symptoms of progressive Parkinsonism together with additional symptoms atypical of idiopathic PD. Parkinsonian syndromes are understood to be consequence of degeneration and dysfunctions that lead to dopaminergic deficiency across multiple pathways. Voxel-based morphometry (VBM), diffusion tensor imaging (DTI), or single-photon emission computed tomography (SPECT) and positron emission tomography (PET) computational techniques (dynamic PET protocols, compartmental models and multipletime graphical analysis) have been applied to quantify syndrome-specific alterations in brain morphology and physiology [4, 5]

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