Cerebral Perfusion Imaging Predicts Levodopa-Induced Dyskinesia in Parkinsonian Rat Model

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Abstract Approximately half of Parkinson’s disease (PD) patients manifest motor complications related to treatment called levodopa-induced dyskinesia (LID). Preventing onset of LID is crucial to long-term management of PD, but the reasons why some patients develop LID are unclear, for instance, it is unknown if vascular or neuroinflammatory abnormalities exist prior to levodopa therapy or are a response to chronic exposure. The ability to prognosticate predisposition to LID would be valuable for the management of LID and for the investigation of strategies for its mitigation. Thirty rats received 6-hydroxydopamine to induce parkinsonism-like behaviors before treatment with levodopa (2 mg/kg) daily for 22 days. Fourteen developed LID-like behaviors. Fluorodeoxyglucose PET, T2-weighted MRI and cerebral perfusion imaging were collected before treatment. Support vector machines were trained to classify LID vs. non-LID animals. Volumetric perfusion imaging performed best overall with 86.16% area-under-curve, 86.67% accuracy, 92.86% sensitivity, 81.25% specificity for classifying animals with LID vs. non-LID from treatment-naïve baseline imaging in leave-one-out cross-validation. We have demonstrated proof-of-concept for imaging-based classification of a parkinsonian rat model. The ability to non-invasively identify a predisposition to LID would allow for more targeted investigations into the risk factors for LID and its prevention in the earliest stages.

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