Role of brain 2-[${}^{18}$F]fluoro-2-deoxy-D-glucose-positron-emission tomography as survival predictor in amyotrophic lateral sclerosis

The identification of prognostic tools in amyotrophic lateral sclerosis (ALS) would improve the design of clinical trials, the management of patients, and life planning. We aimed to evaluate the accuracy of brain 2-[${}^{18}$F]fluoro-2-deoxy-D-glucose-positron-emission tomography (2-[${}^{18}$F]FDG-PET) as an independent predictor of survival in ALS. A prospective cohort study enrolled 418 ALS patients, who underwent brain 2-[${}^{18}$F]FDG-PET at diagnosis and whose survival time was available. We discretized the survival time in a finite number of classes in a data-driven fashion by employing a k-means-like strategy. We identified "hot brain regions" with maximal power in discriminating survival classes, by evaluating the Laplacian scores in a class-aware fashion. We retained the top-m features for each class to train the classification systems (i.e., a support vector machine, SVM), using 10% of the ALS cohort as test set. Data were discretized in three survival profiles: 0-2 years, 2-5 years, and > 5 years. SVM resulted in an error rate < 20% for two out of three classes separately. As for class one, the discriminant clusters included left caudate body and anterior cingulate cortex. The most discriminant regions were bilateral cerebellar pyramid in class two, and right cerebellar dentate nucleus, and left cerebellar nodule in class three. Brain 2-[${}^{18}$F]FDG-PET along with artificial intelligence was able to predict with high accuracy the survival time range in our ALS cohort. Healthcare professionals can benefit from this prognostic tool for planning patients' management and follow-up. 2-[${}^{18}$F]FDG-PET represents a promising biomarker for individual patients' stratification in clinical trials. The lack of a multicentre external validation of the model warrants further studies to evaluate its generalization capability.