![]() Glaab, Enrico ![]() ![]() in Neurobiology of Disease (2019), 124(1), 555-562 The diagnosis of Parkinson's disease (PD) often remains a clinical challenge. Molecular neuroimaging can facilitate the diagnostic process. The diagnostic potential of metabolomic signatures has recently ... [more ▼] The diagnosis of Parkinson's disease (PD) often remains a clinical challenge. Molecular neuroimaging can facilitate the diagnostic process. The diagnostic potential of metabolomic signatures has recently been recognized. Methods: We investigated whether the joint data analysis of blood metabolomics and PET imaging by machine learning provides enhanced diagnostic discrimination and gives further pathophysiological insights. Blood plasma samples were collected from 60 PD patients and 15 age- and gender-matched healthy controls. We determined metabolomic profiles by gas chromatography coupled to mass spectrometry (GC-MS). In the same cohort and at the same time we performed FDOPA PET in 44 patients and 14 controls and FDG PET in 51 patients and 16 controls. 18 PD patients were available for a follow-up exam after one year. Both data sets were analysed by two machine learning approaches, applying either linear support vector machines or random forests within a leave-one-out cross-validation and computing receiver operating characteristic (ROC) curves. Results: In the metabolomics data, the baseline comparison between cases and controls as well as the followup assessment of patients pointed to metabolite changes associated with oxidative stress and inflammation. For the FDOPA and FDG PET data, the diagnostic predictive performance (DPP) in the ROC analyses was highest when combining imaging features with metabolomics data (ROC AUC for best FDOPA + metabolomics model: 0.98; AUC for best FDG + metabolomics model: 0.91). DPP was lower when using only PET attributes or only metabolomics signatures. Conclusion: Integrating blood metabolomics data combined with PET data considerably enhances the diagnostic discrimination power. Metabolomic signatures also indicate interesting disease-inherent changes in cellular processes, including oxidative stress response and inflammation. [less ▲] Detailed reference viewed: 193 (27 UL)![]() Glaab, Enrico ![]() ![]() Poster (2018, October 08) Objective: To investigate whether the integration of PET imaging and metabolomics data can provide improved machine learning models for PD diagnosis. Background: The reliable diagnosis of PD can remain ... [more ▼] Objective: To investigate whether the integration of PET imaging and metabolomics data can provide improved machine learning models for PD diagnosis. Background: The reliable diagnosis of PD can remain challenging, even at the motor stage. PET imaging can be used to confirm the clinical diagnosis. However, limitations in the robustness of predictive features extracted from the data and the costs associated with PET imaging restrict its application. Using blood metabolomics data as an additional information source may provide improved combined diagnostic models and/or an initial filter to decide on whether to apply PET imaging. Methods: Metabolomics profiling of blood plasma samples using gas chromatography coupled to mass spectrometry (GCMS) was conducted in 60 IPD patients and 15 healthy controls. After pre-processing, these data were compared to neuroimaging data for subsets of the same individuals using FDOPA PET (44 patients and 14 controls) and FDG PET (51 patients and 15 controls). Machine learning models using linear support vector machines were trained on 50% of the data and evaluated on a 50% holdout test set using Receiver Operating Characteristic (ROC) curves. Next, standardized FDOPA and FDG PET intensity measurements were combined with those from the metabolomics data to build and evaluate sample classification models in the same manner as for the individual datasets. Results: Both for the FDOPA and FDG PET data, the predictive performance given by the area under the ROC curve (AUC) was highest when combining imaging features with those from the metabolomics data (AUC for FDOPA + metabolomics: 0.98; AUC for FDG + metabolomics: 0.91). The performance was generally lower when using only the respective PET attributes (FDOPA: 0.94, FDG: 0.8) or only the metabolomics data (AUC: 0.66). [less ▲] Detailed reference viewed: 202 (25 UL) |
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