Automated, high accuracy classification of Parkinsonian disorders: a pattern recognition approach

Abstract

Progressive supranuclear palsy (PSP), multiple system atrophy (MSA) and idiopathic Parkinson's disease (IPD) can be clinically indistinguishable, especially in the early stages, despite distinct patterns of molecular pathology. Structural neuroimaging holds promise for providing objective biomarkers for discriminating these diseases at the single subject level but all studies to date have reported incomplete separation of disease groups. In this study, we employed multi-class pattern recognition to assess the value of anatomical patterns derived from a widely available structural neuroimaging sequence for automated classification of these disorders. To achieve this, 17 patients with PSP, 14 with IPD and 19 with MSA were scanned using structural MRI along with 19 healthy controls (HCs). An advanced probabilistic pattern recognition approach was employed to evaluate the diagnostic value of several pre-defined anatomical patterns for discriminating the disorders, including: (i) a subcortical motor network; (ii) each of its component regions and (iii) the whole brain. All disease groups could be discriminated simultaneously with high accuracy using the subcortical motor network. The region providing the most accurate predictions overall was the midbrain/brainstem, which discriminated all disease groups from one another and from HCs. The subcortical network also produced more accurate predictions than the whole brain and all of its constituent regions. PSP was accurately predicted from the midbrain/brainstem, cerebellum and all basal ganglia compartments; MSA from the midbrain/brainstem and cerebellum and IPD from the midbrain/brainstem only. This study demonstrates that automated analysis of structural MRI can accurately predict diagnosis in individual patients with Parkinsonian disorders, and identifies distinct patterns of regional atrophy particularly useful for this process.

Figure 1. Example confusion matrix for an m-class classification problem.

C_i,j denotes the number of predictions in row i, column j. The sensitivity and predictive value measure the performance of each class. The accuracy and overall predictive value are constructed by averaging the sensitivity and predictive value over all classes. Note that the accuracy and overall predictive value are balanced in that they avoid potential bias arising from variable numbers of samples in each class.

Figure 2. Sensitivity (Sens) and predictive value (PV) for each class within each diagnostic classifier based on the subcortical motor network features (classifiers I–IV in panels A-D respectively).

Bars denote the chance levels determined by the proportion of samples in the training set. * = p < 0.01, # = p < 0.05 + = p < 0.1.

Figure 3. Confusion matrices for each diagnostic decision (classifiers I–IV in panels A-D respectively).

Numbers in each cell describe the total number of predictions.

Figure 4. Sensitivity (Sens) and predictive value (PV) for each region in the subcortical motor network for the four-class classifier contrasting PSP, IPD, HC and MSA (Classifier II).

A: cerebellum; B: brainstem; C: caudate; D: putamen; E: pallidum; F: accumbens. Bars denote the chance levels determined by the proportion of samples in the training set. * = p < 0.01, # = p < 0.05 + = p < 0.1.