Relevance of 18F-DOPA visual and semi-quantitative PET metrics for the diagnostic of Parkinson disease in clinical practice: a machine learning-based inference study

Abstract

Purpose To decipher the relevance of visual and semi-quantitative 6-fluoro-(18F)-L-DOPA (18F-DOPA) interpretation methods for the diagnostic of idiopathic Parkinson disease (IPD) in hybrid positron emission tomography (PET) and magnetic resonance imaging. Material and methods A total of 110 consecutive patients (48 IPD and 62 controls) with 11 months of median clinical follow-up (reference standard) were included. A composite visual assessment from five independent nuclear imaging readers, together with striatal standard uptake value (SUV) to occipital SUV ratio, striatal gradients and putamen asymmetry-based semi-quantitative PET metrics automatically extracted used to train machine learning models to classify IPD versus controls. Using a ratio of 70/30 for training and testing sets, respectively, five classification models—k-NN, LogRegression, support vector machine, random forest and gradient boosting—were trained by using 100 times repeated nested cross-validation procedures. From the best model on average, the contribution of PET parameters was deciphered using the Shapley additive explanations method (SHAP). Cross-validated receiver operating characteristic curves (cv-ROC) of the most contributive PET parameters were finally estimated and compared. Results The best machine learning model (k-NN) provided final cv-ROC of 0.81. According to SHAP analyses, visual PET metric was the most important contributor to the model overall performance, followed by the minimum between left and right striatal to occipital SUV ratio. The 10-time cv-ROC curves of visual, min SUVr or both showed quite similar performance (mean area under the ROC of 0.81, 0.81 and 0.79, respectively, for visual, min SUVr or both). Conclusion Visual expert analysis remains the most relevant parameter to predict IPD diagnosis at 11 months of median clinical follow-up in 18F-FDOPA. The min SUV ratio appears interesting in the perspective of simple semi-automated diagnostic workflows.

Dopamine Synthesis in the Nigrostriatal Dopaminergic System in Patients at Risk of Developing Parkinson’s Disease at the Prodromal Stage

“…At the same time, the AI for the putamen was higher in 7 of 17 patients at risk of developing PD. In five of seven patients at risk of developing PD at the prodromal stage, the AI was even higher than that in patients with PD [51]. One of these at risk patients subsequently developed motor symptoms (see below).…”

“…These include the SBR, AI, and putamen/caudate nucleus ratio. The most informative indicator of the dopaminergic denervation of the striatum in PD patients is interhemispheric asymmetry in the accumulation of 18F-DOPA in this particular brain region [50,51]. In healthy people, the AI is significantly lower than that in patients with PD, being on average 0.95% for the caudate nucleus and 2% for the putamen [52].…”

Towards an Automated Approach to the Semi-Quantification of [18F]F-DOPA PET in Pediatric-Type Diffuse Gliomas

“…Approaches for analyzing [ 18 F]F-DOPA PET/CT images, either semi-automated or fully automated, have been developed for use in Parkinson's disease, where they can benefit from prior knowledge of the target and reference regions. A variety of techniques can be employed, including the extraction of radiomic features from the image, the application of classical machine learning methods, and the calculation of the striatal-to-occipital ratio [21,22]. Defining target and normalization regions in oncological PET imaging is a challenging task due to the inherent variability and the methodological drawbacks of common manual or threshold-based procedures (e.g., time consumption, low reproducibility, scanner type, reconstruction algorithm, and image noise [23]).…”

Manufacturing 6-[18F]Fluoro-L-DOPA via Flow Chemistry-Enhanced Photoredox Radiofluorination

“…6-[ 18 F]­FDOPA, an FDA-approved radiopharmaceutical agent, finds extensive use in PET imaging for visualizing and measuring dopaminergic neuron activity . Its application extends beyond managing neurologic disorders like Parkinson’s disease, , with ongoing research and clinical trials in oncology. − Given its advantageous diagnostic potential, since the 1980s, diverse methods have been developed for 6-[ 18 F]­FDOPA synthesis, each with unique advantages and limitations (Scheme S1). , However, the complexity of current methods, involving expensive automated modules and HPLC instruments, impedes the widespread adoption of 6-[ 18 F]­FDOPA.…”